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Textbook of

Oral Medicine, Oral Diagnosis


and Oral Radiology

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Textbook of

Oral Medicine, Oral Diagnosis


and Oral Radiology
Second Edition

Editors
Ravikiran Ongole BDS, MDS
Professor
Department of Oral Medicine and Radiology
Manipal College of Dental Sciences, Manipal University
Mangalore, India

Praveen BN BDS, MDS


Professor and Head
Department of Oral Medicine and Radiology
KLE Societys Institute of Dental Sciences
Bengaluru, India

ELSEVIER
A division of
Reed Elsevier India Private Limited

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Textbook of Oral Medicine, Oral Diagnosis and Oral Radiology, 2/e


Ongole and Praveen
ELSEVIER
A division of
Reed Elsevier India Private Limited
Mosby, Saunders, Churchill Livingstone, Butterworth Heinemann and
Hanley & Belfus are the Health Science imprints of Elsevier.
2013 Elsevier
First Edition 2010
Second Edition 2013
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any
means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the publisher.
ISBN: 978-81-312-3091-6
Medical knowledge is constantly changing. As new information becomes available, changes in treatment, procedures, equipment and
the use of drugs become necessary. The authors, editors, contributors and the publisher have, as far as it is possible, taken care to ensure
that the information given in this text is accurate and up-to-date. However, readers are strongly advised to confirm that information,
especially with regard to drug dose/usage, complies with current legislation and standards of practice. Please consult full prescribing
information before issuing prescriptions for any product mentioned in the publication.
Published by Elsevier, A division of Reed Elsevier India Private Limited.
Registered Office: 305, Rohit House, 3, Tolstoy Marg, New Delhi 110 001.
Corporate Office: 14th Floor, Building No. 10B, DLF Cyber City, Phase-II, Gurgaon, Haryana 122 002.
Publishing Manager: Ritu Sharma
Sr. Commissioning Editor: Nimisha Goswami
Managing Editor: Anand K Jha
CopyEditor: Saroj K Sahoo
PublishingOperations Manager: Sunil Kumar
Production Manager: NC Pant
Typeset by Olympus Premedia Pvt. Ltd. (formerly Olympus Infotech Pvt. Ltd.), Chennai, India.
www.olympus.co.in
Printed and bound at

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Dedicated to
My Wife, Parents and Brother
Ravikiran Ongole
My Parents, Wife and Daughter (Aadya)
Praveen BN

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Foreword I

The current academic scenario in our country has witnessed an abundance of postgraduate courses and postgraduate
teachers. An offshoot of this has been the burgeoning demand for reliable sources of knowledge for undergraduates,
postgraduates and the dental practitioners.
The mushrooming number of textbooks is a welcome sign of enterprise and effort on the part of our teachers. However
all are not of acceptable quality. One needs to separate the wheat from the chaff and restrict ones interest to the textbooks
with quality content.
Once such gem is the Textbook of Oral Medicine, Oral Diagnosis and Oral Radiology brought out by Dr Ravikiran Ongole
and Dr Praveen BN, committed academicians with a number of scientific publications and a previous textbook to their
credit; they have succeeded in creating a tome of oral medicine and radiology. It is a matter of great pride to me personally
since Dr Ravikiran is a faculty member and a gifted teacher in my institution.
Their task has been a Herculean one since they have not only contributed their own knowledge to this book; they have
also used the combined experience of other dental and medical professionals from diverse fields.
I am happy that the first edition of the book was received well and I am confident that the second edition of the book
with an additional section on dental radiology would help in imparting further knowledge to students in the field of
Oral Medicine and Radiology.
A brief overview of the book reveals the amount of effort put in by the editors and their contributors. I wish them all
the best in their endeavor to spread knowledge in Oral Diagnosis and Radiology and whole heartedly recommend this
book to all those who seek the same.
Prof (Dr) V Surendra Shetty
Pro Vice Chancellor
Manipal University, Mangalore

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Foreword II

Dentistry has always been an evolving science and every effort is to be made to keep up pace with the advancement. This
textbook has received wide recognition for its contribution to the practice of dentistry. I would like to congratulate the
editors in their continuing effort to present the second edition with attention to detail, written principally for a student
in an attempt to penetrate some depth towards newer research.
The edition has maintained its firm commitment in assuring a thorough and complete text. The examination of a case
confronts every clinician. I think this book gives a well-reasoned explanation of fundamental aspects, emphasized on
clinical scenario with illustrations, which are of value to a practicing dentist.
Launching a subsequent edition of a warmly received text is more of a challenge. I whole heartedly congratulate their
feat for their truly admirable skills and the contributors for this splendid work of knowledge.
Prof (Dr) Srivatsa G
Principal
KLE Societys Institute of Dental Sciences
Bengaluru

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List of Contributors

Carol M Stewart MS, DDS, MS


Professor, Oral Medicine
Department of Oral and Maxillofacial Surgery and
Diagnostic Sciences
University of Florida College of Dentistry
Gainesville, Florida, USA
Madhu K Nair BDS, DMD, MS, Lic Odont (Sweden), PhD
Associate Professor
Oral and Maxillofacial Radiology
Department of Oral and Maxillofacial Surgery and
Diagnostic Sciences
University of Florida College of Dentistry
Associate Professor, Radiology
UF College of Medicine
Gainesville, Florida, USA
Syed Vaseemuddin BDS, MDS
Formerly Assistant Professor
Department of Oral Medicine and Radiology
KLE Societys Institute of Dental Sciences
Bengaluru, India
Francisco Lopez Sanchez DDS, MDS
Professor
Periodontics and Oral Pathology
UMSNH College of Dentistry
Professor, Endodontic surgery, Endo-periodontology and
Ortho-periodontolgy
CUEPI Morelia
Michoacan, Mxico

Sadhana Shenoy S BDS, MDS


Reader
Dept of Oral Pathology
Oxford Dental College
Bengaluru, India
Karen Boaz BDS, MDS
Professor and Head
Department of Oral Pathology
Manipal College of Dental Sciences, Manipal University
Mangalore, India
Ajit Auluck MDS, PhD
Clinician Scientist
BC Cancer Agency
Simon Fraser University
Canada
Manuel Thomas BDS, MDS
Associate Professor
Department of Conservative Dentistry
Manipal College of Dental Sciences
Mangalore, India
Ajay G Nayak BDS, MDS
Reader
Department of Oral Medicine and Radiology
Mahatma Gandhi Vidyamandirs
Karmaveer Bhausaheb Hiray Dental College and Hospital
Nashik, India

Sara Carolina Rodriguez Pea DDS, MDS


Orthodontist, Military College of Dentistry
UNITEC, Mxico

Joanna Baptist BDS, MDS


Assistant Professor
Department of Oral and Maxillofacial Surgery
Manipal College of Dental Sciences
Manipal University, Mangalore, India

Nandita Shenoy BDS, MDS


Reader
Department of Oral Medicine and Radiology
Manipal College of Dental Sciences, Manipal University
Mangalore, India

Thomas Zachariah BDS, MDS


Reader
Department of Oral and Maxillofacial Surgery
Meenakshi Ammal Dental College and Hospital
Chennai, India

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List of Contributors

Ashok I Lingappa BDS, MDS


Professor and Head
Department of Oral Medicine and Radiology
Bapuji Dental College and Hospital
Davangere, India
Nagamani Narayana DMD, MS
Assistant Professor
Department of Oral Biology
College of Dentistry
University of Nebraska Medical Center
Lincoln, USA
Keerthilatha M Pai BDS, MDS
Associate Dean, Professor and Head
Department of Oral Medicine and Radiology
Manipal College of Dental Sciences
Manipal, India
Braz Campos Durso DDS, MSD
Professor of Oral Diagnostic and
Orofacial Pain Department
School of Dental Medicine
Porto Velho, RO
Brazil
K Srinivas BDS, MDS
Professor
Department of Oral Medicine and Radiology
AECS Maruti College of Dental Sciences and
Research Centre
Bengaluru, India
Sarita Dimri MD
Formely Assistant Professor
Department of Dermatology
Kasturba Medical College and Hospital
Mangalore, India
Shibu Thomas BDS, MDS
Reader
Department of Oral Medicine and Radiology
Indira Gandhi Institute of Dental Sciences
Nellikuzhi, Kothamangalam
Kerala, India
Indraneel Bhattacharyya DDS, MSD
Assistant Professor
Oral and Maxillofacial Pathology
Department of Oral and Maxillofacial Surgery
and Diagnostic Sciences
University of Florida College of Dentistry
Gainesville, Florida, USA

James C Pettigrew DMD


Associate Professor
Oral and Maxillofacial Radiology
Department of Oral and Maxillofacial Surgery and
Diagnostic Sciences
University of Florida College of Dentistry
Associate Professor, Radiology, UF College of Medicine
Gainesville, Florida, USA
Seunghee Cha DDS, PhD
Assistant Professor
Department of Oral and Maxillofacial Surgery
and Diagnostic Sciences
University of Florida College of Dentistry
Gainesville, Florida, USA
Joseph Katz DMD
Professor
Department of Oral and Maxillofacial Surgery and
Diagnostic Sciences
University of Florida College of Dentistry
Gainesville, Florida, USA
Sunanda C BDS, MDS
Professor
Department of Oral Medicine and Radiology
Dr Syamala Reddy Dental College and Hospital
Bengaluru, India
NVS Sekhar Reddy BDS, MDS
Professor
Department of Oral and Maxillofacial Surgery
Dr Syamala Reddy Dental College and Hospital
Bengaluru, India
Mala Kamboj BDS, MDS
Associate Professor
Department of Oral Pathology and Microbiology
Career Institute of Dental Sciences and Hospital
Lucknow, India
SV Kumaraswamy BDS, MDS
Formerly Professor and Head
Department of Oral and Maxillofacial Surgery
VS Dental College and Hospital
Bengaluru, India
Jeevan Prakash V BDS, MDS
Professor and Head
Department of Oral and Maxillofacial Surgery
Jodhpur Dental College and General Hospital
Jodhpur, Rajasthan, India
Vivekananda Pai BDS, MDS
Professor and Head
Department of Conservative Dentistry
Manipal College of Dental Sciences, Manipal University
Mangalore, India

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List of Contributors

Jeeth Rai BDS, MDS


Assistant Professor
Department of Periodontology
KLE Societys Institute of Dental Sciences
Bengaluru, India

Veena KM BDS, MDS


Professor
Department of Oral Medicine and Radiology
Yenepoya Dental College and Hospital
Mangalore, India

Sumati Nagappa Baddannavar BDS, MDS


Reader
Department of Oral Medicine and Radiology
KLE Societys Institute of Dental Sciences
Bengaluru, India

Manish Juneja BDS, MDS, DNB


Associate Professor
Department of Oral Pathology and Microbiology
PDM Dental College and Research Institute
Haryana, India

Syeda Arshiya Ara BDS, MDS


Professor
Department of Oral Medicine and Radiology
Al-badar Rural Gulbarga Dental College and Hospital
Gulbarga, India

Balaji Rao B BDS, MDS


Formerly Principal, Professor Emeritus
Department of Oral Medicine and Radiology
KLE Societys Institute of Dental Sciences
Bengaluru, India

Ceena Denny E BDS, MDS


Associate Professor
Department of Oral Medicine and Radiology
Manipal College of Dental Sciences, Manipal University
Mangalore, India

Sumanth KN BDS, MDS


Department of Oral Diagnosis, Oral Medicine and
Oral Pathology
Faculty of Dentistry, Melaka Manipal Medical College
Melaka, Malaysia

Gajendra Veeraraghavan BDS, MDS, MFDS RCPS


Reader
Department of Oral Medicine and Radiology
Sree Mookambika Institute of Dental Sciences
Kulasekharam, Tamil Nadu, India

Adel Kauzman DMD, MSc, FRCD(c)


Associate Professor, Department of Stomatology
Faculty of Dentistry
Universit de Montral, Quebec, Canada

Seema Patil BDS, MDS


Reader, Department of Oral Medicine and Radiology
DAPM RV Dental College
Bengaluru, India
Vishwananth R BDS, MDS
Professor and Head
Department of Oral Medicine and Radiology
Indira Gandhi Institute of Dental Sciences
Puducherry, India
Sarat Gummadapu BDS, MDS, MFDS RCPSG
Associate Professor
Department of Oral Medicine and Radiology
Drs Sudha and Nageswara Rao Siddhartha
Institute of Dental Sciences
Krishna (Dt), Andhra Pradesh, India
Srikant N BDS, MDS
Associate Professor
Department of Oral Pathology and Microbiology
Manipal College of Dental Sciences, Manipal University
Mangalore, India

Iona Leong BDS, MSc, FRCD(c)


Department of Oral Pathology and Oral Medicine
Faculty of Dentistry
University of Toronto, Ontario, Canada
Head, Department of Dentistry
Division of Oral Pathology and Oral Medicine
Mount Sinai Hospital
Nagaraj A BDS, MDS
Reader
Department of Oral Pathology
KLE Societys Institute of Dental Sciences
Bengaluru, India
Shubha Sairam BDS, MDS
Assistant Professor
Department of Oral Medicine and Radiology
KLE Societys Institute of Dental Sciences
Bengaluru, India
Ashith B Acharya BDS, GDFO
Associate Professor and Head of Forensic Odontology
SDM College of Dental Sciences and Hospital
Dharwad, India

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List of Contributors

Foluso J Owotade BChD, FWACS


Associate Professor and Head
Department of Oral and Maxillofacial Surgery and
Oral Pathology
College of Health Sciences
Obafemi Awolowo University
Ile-Ife, Nigeria
Eyitope O Ogunbodede BSc, BChD, MPH, DDPH, RCS
Head of the Department of Preventive Dentistry
Faculty of Dentistry, Obafemi Awolowo University
Ile-Ife, Nigeria
Ranganath D Rattehalli MBBS, MRCPsych, M Med Sc,
CCT(UK), DPM, PG Diploma (Cli Psy)

Consultant Psychiatrist, Leeds Partnerships NHS Trust,


Seacroft Hospital, Leeds, UK
Sandip Deshpande MBBS, MD, DPM, MRCPsych,
CCT (UK), PG Diploma (Sex and Reln. therapy)

Consultant Psychiatrist, Sexual and Relationship therapist


Manipal Northside Hospital, Bengaluru
Ex-consultant, NHS, Leeds, UK
Raghavendra Kini BDS, MDS
Professor
Department of Oral Medicine and Radiology
AJ Institute of Dental Sciences
Mangalore, India
Anshul Mehra BDS, MDS
Reader
Babu Banrasi Das College of Dental Sciences
Faizabad Road, Lucknow
Uttar Pradesh, India
Thomas George BDS, MDS
Faculty of Dentistry
University of Malaya, Kuala Lumpur, Malaysia
Shubhasini AR BDS, MDS
Reader, Department of Oral Medicine and Radiology,
KLE Societys Institute of Dental Sciences,
Bengaluru, India
Bhanushree R BDS, MDS
Lecturer, Department of Oral Medicine and Radiology,
KLE Societys Institute of Dental Sciences,
Bengaluru, India
Kvan Kamburolu DDS, MSc, PhD
Associate Professor
Department of Dentomaxillofacial Radiology
Faculty of Dentistry, Ankara University, Ankara, Turkey

Gail F Williamson RDH, MS


Faculty Fellow of Faculty Advancement Initiatives
Professor of Dental Diagnostic Sciences
Oral Pathology, Medicine and Radiology
Indiana University School of Dentistry
Indianapolis, USA
Muralidhar Mupparapu D MD
Director, Oral and Maxillofacial Radiology
University of Pennsylvania School of Dental Medicine
Philadelphia, USA
Suman Jai Sanghar BDS, MDS
Professor
Department of Oral Medicine and Radiology
KSR Institute of Dental Sciences and Research
Tiruchengode, Tamil Nadu, India
Jai Sanghar N BDS, MDS
Professor and Head
Department of Oral Medicine and Radiology
Rajah Muthiah Dental College and Hospital
Annamalai University, Chidambaram
Tamil Nadu, India
Medha Babshet BDS, MDS
Assistant Professor
Department of Oral Medicine and Radiology
Hasanamba Dental College and Hospital
Hassan, Karnataka, India
Rinky Nyachhyon BDS, MDS
Assistant Professor
Department of Oral Medicine and Radiology,
Peoples Dental College and Hospital
Kathmandu, Nepal
Apeksha Mainali BDS, MDS
Assistant Professor
Department of Oral Medicine and Radiology
Kantipur Dental College
kathmandu, Nepal
Praveen BN BDS, MDS
Professor and Head
Department of Oral Medicine and Radiology
KLE Societys Institute of Dental Sciences
Bengaluru, India
Ravikiran Ongole BDS, MDS
Professor
Department of Oral Medicine and Radiology
Manipal College of Dental Sciences
Mangalore, India

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Preface to the
Second Edition

The first edition of the book was published two years ago. Since then we have received very encouraging feedback from
students and faculty alike. It was also heartening to note that this book was included by various health universities in their
recommended list of textbooks for undergraduate and postgraduate students.
We also received suggestions for including a section on dental radiology with a special request to include chapters on
implant imaging and cone beam computed tomography. Taking these views into consideration, we included a section on
radiology that covers varied topics from radiation physics to specialized imaging techniques. The oral medicine section has
also been updated with the latest concepts in the diagnosis and medical management of various orofacial disorders.
We wish this comprehensive Textbook of Oral Medicine, Oral Diagnosis and Oral Radiology gains wider popularity
amongst the student community and the faculty and continues to cater to the needs of students pursuing the specialty of
Oral Medicine and Radiology.
Ravikiran Ongole
Praveen BN

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Preface to the
First Edition

Oral Medicine in India is still in its nascent stages of growth. Consequently, there is not much literature that is easily
available to the student community. While there are many excellent textbooks available outside the Indian shores, in the
editors opinion, there is not much emphasis on diseases that tend to occur in the Indian subcontinent. Further, content
prescribed by the Dental Council of India, which is very useful to undergraduate and postgraduate students of dentistry,
is rarely available.
Many popular textbooks that are available to students of dentistry in India are either exam-oriented (not sufficient
background material; not suitable for reference beyond a particular examination) or focus only on oral medicine or on
oral radiology.
Our goal was two-fold: publish content that would appeal to undergraduate students because the content corresponded
to DCI curriculum; to postgraduate students and practitioners to serve as reference for diseases that seem to occur very
frequently in India. We have tried our best to combine oral medicine, diagnosis and radiological aspects of various orofacial
diseases and oral manifestations of systemic disorders. Chapters such as maxillofacial trauma, Lab investigations, Mental
illness and Syndromes of the head and neck have been specially written for postgraduate students.
We have tried our best to provide up to date references. Another unique feature of this book is the contributions made
from more than 60 authors from various dental colleges all over India and from countries such as USA, England, Canada,
Mexico, Brazil and Nigeria. We have made a conscious effort to tap into the expertise of authors from various fields of
medicine such as plastic surgery, dermatology and psychiatry and from various dental specialties apart from oral medicine
such as oral pathology, oral surgery, conservative dentistry, orthodontics, prosthodontics and periodontics.
We sincerely hope that this textbook will stimulate minds and satiate the intellectual appetite of the students of oral
medicine, diagnosis and radiology.
Ravikiran Ongole
Praveen BN

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Acknowledgments

The editors would whole heartedly like to acknowledge contributions from various individuals, especially the authors to
this book.
We would like to acknowledge the encouragement, guidance and support rendered by Dr V Surendra Shetty, Pro Vice
Chancellor, Manipal University, Dr Dilip G. Nayak, Dean, Manipal College of Dental Sciences, Manipal University, Mangalore
and Dr Srivatsa G, Principal, KLE Societys Institute of Dental Sciences, Bengaluru. We would also like to thank them for
graciously permitting us to use photographs from the department archives.
We would like to thank the teaching faculty of the Departments of Oral Medicine and Radiology, MCODS (Mangalore)
and KLE Societys Institute of Dental Sciences (Bengaluru) for their help and suggestions provided during the preparation
of this book.
Our heartfelt thanks to Dr Saranya B, Dr Richa Gaba, Dr Bijina, Dr Sumsum P Sunny, Dr Sushma CN and Dr Pramila
Mendonca who helped us at every step during the preparation of the book.
Our sincere sense of gratitude go out to Mr Mark Dirlam, Supervisor and Graphic Artist and Mr Timothy Centers,
Photographer, Department of Illustrations, Indiana University School of Dentistry, Indianapolis, Indiana, USA and
Dr Jaideep Shekhar for helping us in preparing illustrations for the book.
We are extremely indebted to Dr John O Keefe, Editor, Journal of the Canadian Dental Association, Dr Foluso Owotade
and Dr Carol Stewart for their words of strength and encouragement and for lending us photographs.
We appreciate the support and constant encouragement received from the ever enthusiastic publishing team of Elsevier
India, especially Ms Ritu Sharma, Ms Nimisha Goswami and Mr Anand K Jha.
Our sincere appreciation and gratitude to our patients, some of who were terminally ill, for enduring pain and discomfort
in the hope of relief and cure. We hope that this textbook will in some small way alleviate their sufferings.
Above all our deepest gratitude to our families for their affection, unconditional support and encouragement.
We sincerely apologize to individuals whose names have been inadvertently not mentioned.

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Contents

Dedication
Foreword I
Foreword II
List of Contributors
Preface to the Second Edition
Preface to the First Edition
Acknowledgments

v
vii
ix
xi
xv
xvii
xix

Part IOral Medicine and Oral Diagnosis


SECTION I

INTRODUCTION AND APPROACH TO DIAGNOSIS

Chapter 1

History and Scope of Oral Medicine and Oral Radiology

History of Oral Medicine Oral and Maxillofacial Radiology Oral Medicine and Radiology in India

SECTION II

ORAL AND MAXILLOFACIAL DISTURBANCES

Chapter 2

Developmental Disturbances

11

Fordyces Granules (Fordyces Spots/Disease) Lingual Tonsils Leukoedema Retrocuspid Papillae Prominent Palatal
Rugae Circumvallate Papillae or Vallate Papillae Parotid Papilla Racial Pigmentation/Physiological Pigmentation
Mandibular and Maxillary Tori Developmental Disorders Affecting Tongue Developmental Disorders Affecting
the Lip Developmental Disorders Affecting Buccal Mucosa and Gingiva Developmental Disturbances of the Jaws
Developmental Disturbances Affecting Teeth
Chapter 3

Orofacial Pigmentation Disorders

61

Pigmented Lesions of Oral Mucosa Pigmentation of Teeth Dental Fluorosis


Chapter 4

Bacterial, Viral and Fungal Infections

82

Scarlet Fever Diphtheria Tularemia (Rabbit Fever, Deer-fly Fever, Francis Disease, Tick-Borne Disease, Oharas
Disease) Erysipelas Impetigo Melioidosis Tetanus Actinomycosis Noma (Cancrum Oris, Gangrenous or Necrotizing
Stomatitis) Botryomycosis (Bacterial Pseudomycosis) Rhinoscleroma (Respiratory Scleroma) Cat-scratch Disease
Infectious Mononucleosis (Monoglandular Fever, Kissing Disease) Acute Lymphonodular Pharyngitis Measles (Rubeola)
German Measles (Rubella) HIV and AIDS Acquired Immune Deficiency Syndrome Sinusitis Histoplasmosis
Blastomycosis (Gilchrist Disease) Mucormycosis (Zygomycosis, Phycomycosis) Aspergillosis Cryptococcosis (European
Blastomycosis, Torulosis, Busse-Buschke Disease)
Chapter 5

Orofacial Pain

111

Pain Physiology Classification of Orofacial Pain Clinical Assessment of Pain Pain from Orodental Structures
Barodontalgia Paranasal Sinus-related Pain Myofascial Pain Neuralgias Atypical Odontalgia Atypical Facial
Pain Burning Mouth Syndrome

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Contents

SECTION III MUCOCUTANEOUS DISORDERS


Chapter 6

Red and White Lesions

133

Description of Red and White Lesions Etiologic Classification of Red and White Lesions White Lesions of the Oral
Cavity Red Lesions of the Oral Cavity Red Lesions of the Tongue
Chapter 7

Vesiculobullous Disorders

174

Classification of Vesiculobullous Lesions Predominantly Vesicular Lesions Herpes Simplex Virus (HSV) Infections
Herpetic Whitlow and Herpes Gladiatorum Recurrent Herpes Infections Varicella Zoster Infections Hand, Foot and
Mouth Disease Herpangina Dermatitis Herpetiformis Predominantly Bullous Lesions Bullous Lichen Planus
Erythema Multiforme StevensJohnson Syndrome and Toxic Epidermal Necrolysis (Lyells Syndrome) Bullous
Impetigo Epidermolysis Bullosa
Chapter 8

Oral Ulcerative Diseases

196

Classification of Oral Ulcers Traumatic Ulcers Primary Herpetic Gingivostomatitis Recurrent Herpes Infection
Varicella Zoster Infection Acute Necrotizing Ulcerative Gingivitis (Trench Mouth, Vincents Disease, Vincents
Gingivostomatitis) Tuberculosis Syphilis Deep Fungal Infections Drug-induced Oral Ulcers Erythema Multiforme
Blood Disorders Causing Oral Ulcers Immunologic Disorders Dermatological Disorders Pemphigoid Gastrointestinal
Disorders Associated with Oral Ulcers Neoplastic Ulcers Ulcers of Unknown Etiology Syndromes Associated with
Oral Ulcers Diagnostic Protocol
Chapter 9

Dermatological Diseases

218

Lichen Planus Epidermolysis Bullosa Psoriasis Ectodermal Dysplasia EhlersDanlos Syndrome Pachyonychia
Congenita Dyskeratosis Congenita Pityriasis Rosea Xeroderma Pigmentosum Acanthosis Nigricans GoltzGorlin
Syndrome Acrodermatitis Enteropathica HaileyHailey Disease (Familial Benign Chronic Pemphigus) Dariers
Disease (Keratosis Follicularis) Reiters Syndrome Incontinentia Pigmenti (BlochSulzberger Syndrome) Kawasaki
Disease (Mucocutaneous Lymph Node Syndrome) Tuberous Sclerosis Complex (Epiloia, Bournevilles Disease)
Graft-versus-Host Disease

SECTION IV DISEASES OF SPECIFIC STRUCTURES


Chapter 10

Temporomandibular Disorders

239

Components of Temporomandibular Joint Clinical Evaluation of Temporomandibular Joint Clinical Evaluation of


Muscles of Mastication and Accessory/Cervical Muscles Disorders Associated with Deviation/Alteration in the Form of
Articular Surfaces Articular Disk Defects Inflammatory Joint Disorders Degenerative Joint Diseases TMJ Ankylosis
Masticatory Muscle Disorders Congenital, Developmental and Acquired Disorders of the TMJ Neoplasms Affecting
the TMJ Condylar Fractures
Chapter 11

Diseases of Salivary Glands

265

Developmental Disturbances Saliva, Xerostomia, Hyposalivation and Sialorrhea Inflammatory Conditions of Salivary
Glands Viral-induced Salivary Gland Pathology Non-inflammatory Conditions of Salivary Glands Salivary Gland
Tumors Benign Tumors Malignant Tumors

SECTION V

CYSTS AND TUMORS OF OROFACIAL REGION

Chapter 12

Cysts of Orofacial Region

303

Classification of Cysts of Orofacial Region Theories of Cyst Expansion Odontogenic Cysts Odontogenic Keratocyst
Gingival Cysts of Adults Calcifying Epithelial Odontogenic Cyst (Gorlin Cyst) Glandular Odontogenic Cyst Nonodontogenic Cysts Nasolabial Cyst Mid-palatal Raphe Cyst of Infants Cysts of Maxillary Antrum and Salivary
Glands Inflammatory Cysts Pseudocysts Cysts of Soft Tissues of Mouth, Face and Neck Nasopharyngeal Cysts
Thyroglossal Duct Cysts Lymphoepithelial Cysts (Branchial Cleft Cysts) Cystic Hygroma Dermoid, Epidermoid and
Teratoid Cysts Parasitic Cysts
Chapter 13

Tumors of Orofacial Region

331

Benign Odontogenic Tumors Odontogenic Carcinomas Odontogenic Sarcomas Epithelial Malignant Tumors
Connective Tissue Malignant Tumors
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Contents

Chapter 14

Oral Cancer

380

Incidence of Cancer of Head and Neck Etiology and Risk Factors for Oral and Maxillofacial Cancer Tobacco Alcohol
Systemic Health Molecular Basis of Cancer Clinical Signs of Cancer Clinical Examination of a Patient with
Suspected Malignancy TNM Staging Nodal Metastasis Diagnosis of Oral Cancer

SECTION VI TEETH AND PERIODONTIUM


Chapter 15

Dental Caries, Pulp and Periapical Lesions

405

Definition and Etiology Contributory Factors in Dental Caries Classification of Dental Caries Microbiology of
Dental Caries Fascial Space Infection Ludwigs Angina Osteomyelitis
Chapter 16

Gingival and Periodontal Diseases

440

Classification System in Periodontal Disease Gingival Diseases HostMicrobial Interaction Periodontal Diseases
Syndromes Sex Hormones Stress and Psychosomatic Factors Nutritional Factors Radiographic Evaluation of
Periodontal Diseases
Chapter 17

Regressive Alterations of Teeth

458

Classification of Regressive Alterations Affecting Teeth Tooth Surface Loss Attrition Abrasion Erosion (Corrosion)
Abfraction Classification of Tooth Wear Resorption of Teeth

SECTION VII
Chapter 18

SYSTEM REVIEW
Systemic Disorders and their Clinical Implications

473

Symptoms Suggestive of Cardiovascular Disease Common Cardiovascular Disorders and their Dental Considerations
Ischemic or Coronary Heart Disease Myocardial Infarction Congenital Heart Disease Rheumatic Fever Infective
(Bacterial) Endocarditis Heart Failure Red Blood Cell Disorders Polycythemia Anemia Thalassemia White Blood
Cell Disorders Qualitative Disorders Non-neoplastic Disorders Neoplastic Disorders Bleeding Disorders Vascular
Disorders (Vessel Wall) Platelet Disorders Thrombocytopathic Disorders Thrombocytopenic Disorders Disorders of
Coagulation Inherited Coagulation Disorders Acquired Coagulation Disorders Upper Respiratory Tract Infections
Lower Respiratory Tract Infections Granulomatous Diseases Malignant Disorders Other Respiratory Diseases
Renal Diseases Gastroesophageal Reflux Disease Inflammatory Bowel Disease Ulcerative Colitis Crohns Disease
Hiatal Hernia Peptic Ulcer Disease Eating Disorders Liver Diseases Bells Palsy Epilepsy Parkinsonism
Multiple Sclerosis Muscular Dystrophy Oromandibular Dystonia Myasthenia Gravis Growth Hormone Thyroid
Gland Parathyroid Glands HypothalamusPituitaryAdrenal Axis Pregnancy Saliva and Monitoring of Hormone
Levels Interesting Interface between Dentistry and Psychiatry Management of Psychiatric Disorders
Chapter 19

Bone Diseases and Fibro-osseous Lesions

568

Fibro-osseous Lesions Bone Diseases


Chapter 20

Autoimmune Disorders

590

Concepts of Immunity and Autoimmunity Pemphigus Epidermolysis Bullosa Acquisita Systemic Lupus Erythematosus
Autoimmune PolyendocrinopathyCandidiasisEctodermal Dystrophy Diabetes Mellitus Type I (IDDM) Systemic
Sclerosis Myasthenia Gravis
Chapter 21

Granulomatous Diseases

605

Tuberculosis Leprosy (Hansens Disease) Syphilis Deep Fungal Infections Foreign Body Granulomas Wegeners
Granulomatosis Sarcoidosis Orofacial Granulomatosis Crohns Disease (Regional Ileitis, Regional Enteritis)
Chapter 22

Sexually Transmitted Diseases

625

Fellatio Syndrome Traumatic Lesions of Lingual Frenum Syphilis or Lues Human Immunodeficiency Virus Infection
Intraoral Molluscum Contagiosum Condyloma Acuminatum Oropharyngeal Gonorrhea Oropharyngeal Chlamydial
Infection Oropharyngeal Trichomonal Infection
Chapter 23

Nutritional and Metabolic Disorders

633

Nutritional Requirements of Indians Carbohydrates Proteins Lipids Vitamins Metabolic Disorders Lipid
Reticuloendothelioses
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Contents

SECTION VIII
Chapter 24

FORENSIC DENTISTRY

Clinical and Radiological Perspective

653

Introduction, History and Relevance Dental Identification Challenges in Postmortem Examination Postmortem
Alterations to the Teeth and Oral Tissues Social Profiling Identifying the Edentulous Craniofacial Identification
Facial Approximation Age Estimation Methods Bite Mark Procedures Lip Print Investigation

Part IIOral Radiology


SECTION IX BASICS OF RADIOLOGY
Chapter 25

Basics of Radiation Physics

685

Pioneers in Dental Radiology Fundamentals of Radiation Physics Intraoral X-Ray Units Interaction of X-Rays with
Matter
Chapter 26

Radiation Biology

697

Effects on Living Systems Molecular and Cellular Radiobiology Deterministic and Stochastic Effects Sources of
Radiation Dose and Risk in Radiography Radiation Detection and Measurement Film Exposure and Processing

SECTION X

RADIOGRAPHIC METHODOLOGY

Chapter 27

Radiographic Films and Accessories

719

Intraoral Films Extraoral Films


Chapter 28

Radiographic Techniques

724

Conventional Imaging Intraoral Radiography Extraoral Radiography Posteroanterior Projection Standard


Occipitomental view 30 Occipitomental Parietoacanthial View (Waters View) Parietoacanthial View (Open Mouth
Waters View) Modified Parietoacanthial Projection (Modified Waters View) Acanthoparietal Projection (Reverse
Waters Method) Submentovertex View (Base or Full Axial Projection, Schuller Method) Lateral View Lateral
Cephalometry AP Axial Projection (Townes Method) Reverse Townes View Lateral Oblique View TMJ Radiography
Transcranial View Transpharyngeal View (Parma Projection, Macqueen-Dell Technique) Transorbital View
Lesser Known/Forgotten Extraoral Radiographic Techniques Panoramic Radiology Specialized Imaging Computed
Tomography Dentomaxillofacial Cone-Beam Computed Tomography Magnetic Resonance Imaging Nuclear Medicine
Ultrasonography Sialography Arthrography Thermography (Thermal Imaging or Infrared Imaging)

SECTION XI PROCESSING OF RADIOGRAPHS AND RADIOGRAPHIC INTERPRETATION


Chapter 29

Latent Image Formation

801

Formation of Latent Image


Chapter 30

Processing of Radiographic Films

803

Manual Processing of Films Automatic Processing


Chapter 31

Radiographic Faults

812

Errors in Film Storage and Handling Errors in Film Placement and Projection Technique Errors in Exposure Parameters
and Processing Technique Artifacts

SECTION XII
Chapter 32

RADIOGRAPHIC LANDMARKS
Intraoral Radiographic Anatomical Landmarks

825

Landmarks Common to both the Maxillary and Mandibular Radiographs Landmarks Unique to the Maxillary Intraoral
Periapical Radiograph Landmarks Unique to the Mandibular Intraoral Periapical Radiograph
Chapter 33

Extraoral Radiographic Landmarks

837

Chapter 34

Site Selection, Evaluation and Imaging for Dental Implants

842

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Contents

SECTION XIII

APPENDICES

Appendix 1

Terminologies

861

Appendix 2

Summary of Radiographic Pathology

867

Appendix 3

Characteristics of Ideal Radiograph

871

Appendix 4

Indications for Intraoral Radiography

872

Appendix 5

Patient Position for Extraoral Radiography

873

References

879

Index

885

Contents on Website (http://www.manthan.info)


I. A B C of Drugs Used in Dentistry

e1

II. Syndromes of the Head and Neck

e23

III. Laboratory Diagnostic Procedures

e78

IV. Halitosis

e147

V. Occupational Hazards in Dentistry

e154

References

e236

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PART

Oral Medicine and


Oral Diagnosis

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SECTION

Introduction
and Approach
to Diagnosis

History and Scope of Oral Medicine and Oral Radiology

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History and Scope of Oral


Medicine and Oral Radiology

CHAPTER

Carol Stewart, Madhu K Nair,


Syed Vaseemuddin, Ravikiran Ongole

History of Oral Medicine

Mission
Training and Scope of Practice
Future

Oral Medicine and Radiology in India


Course and Curriculum of Oral Medicine and Radiology
Undergraduate Student Competencies as per Dental
Council of India Regulations
Scope of Oral Medicine and Radiology in India

Oral and Maxillofacial Radiology

HISTORY OF ORAL MEDICINE


Carol Stewart
In the British literature, Sir Jonathan Hutchinson (1828
1900), a surgeon at the London Hospital, is regarded as the
Father of Oral Medicine. He described dental manifestations of congenital syphilis, intraoral pigmentation and
perioral pigmentation associated with intestinal polyposis,
later described by Peutz and Jegher. Much of the early
description of oral mucosal diseases was found in dermatology textbooks, as documented in the works of
Dr Erasmus Wilson.
Sir William Osler recognized the importance of the oral
cavity and believed that the tongue and oral mucosa acted
as mirrors reecting the state of health of a patient. He
studied medicine at McGill University and in 1884, moved
to Philadelphia and became the Chair of Clinical Medicine
at the University of Pennsylvania. Ultimately, he became
the Chief of Staff at Johns Hopkins University and Hospital.
The early inuence of Dr Kurt Thoma is internationally
recognized as well. Dr Thoma was a Swiss-born oral surgeon who produced signicant textbooks in the 1920s and
1930s on oral surgery and oral pathology. His work promoted these disciplines, oral diagnosis, oral medicine and
oral pathology, to have greater prominence in dental
schools.
The study of oral medicine in the United States has
a unique history among medical/dental specialties. In the
United States, the roots of considering oral medicine as
a distinct area of study began with Dr William Gies of
Columbia University. Dr Gies, a professor of biological
chemistry, became interested in dental research. In 1926,
the Carnegie Foundation sponsored Dr Gies work entitled

Report on Dental Education in the United States and


Canada. He believed that dental students education should
be more similar to that of medical students. He stressed
the importance of biomedical sciences and research in the
dental school curriculum. His report suggested that oral
medicine be included in a dental curriculum. Another pioneer of great intellect and vision was Dr Lester Burket,
professor of Oral Medicine at Pennsylvania School of Dental
Medicine. He also promoted the integration of medicine into
dental education and the role of oral health in reecting systemic health. He is considered by many as the Father of
Oral Medicine and published one of the rst denitive
textbooks devoted to oral medicine in 1946.
The American Academy of Oral Medicine (AAOM) was
organized in 1945 as the American Academy of Dental
Medicine, and its founder was Samuel Charles Miller,
Professor and Chairman of the Department of Periodontics
at New York University College of Dentistry. In 1966, the
name was changed to the American Academy of Oral Medicine. The academy was founded to broaden understanding
and knowledge of oral disease and to integrate dentistry
with medicine to provide more complete patient care. The
memberships include an internationally recognized group
of professionals.

Mission
The mission of the AAOM is stated in Box 1.
The AAOM is the heart and pulse of oral medicine in
the United States and is also internationally recognized
through the excellent educational training programs and
scientic symposia hosted, and the educational literature
and treatment guidelines published for medically complex
patients.
5

Section I Introduction and Approach to Diagnosis

Box 1

Mission of the American Academy of Oral Medicine

To foster excellence in education, research and patient care in the


field of oral medicine
To promote the study and dissemination of knowledge regarding
the medical aspects of dentistry while serving the best interests
of the public
To promote the highest standard of care in the diagnosis and
treatment of oral conditions that are not responsive to conventional
dental, oral or maxillofacial surgical procedures
To provide an avenue of referral for dental practitioners who have
patients with severe, life-threatening medical disorders or complex
diagnostic problems involving the oral and maxillofacial region that
require ongoing non-surgical management
To improve the quality of life in patients with medically-related oral
disease
To foster increased understanding and cooperation between the
medical and dental professions

and sexually transmitted diseases as well. Skills mastered


include completion of a comprehensive physical evaluation and medical risk assessment, selection of appropriate diagnostic and laboratory procedures including
blood studies, cytology, culture, biopsy techniques, and
delivery of appropriate care and assessment of treatment
outcomes. Critical to completing an oral medicine curriculum is the acquisition of skills necessary to communicate
effectively with patients regarding the nature, rationale,
advantages, disadvantages, risks and benets of a recommended treatment.
American Academy of Oral Medicine is a sponsor of the
American Board of Oral Medicine, the body responsible
for examining and certifying candidates who have received
approved post doctoral training. The board examination is
offered during September/October each year.

Future
Healthy collaborations have been developed between
AAOM and the European Academy of Oral Medicine
(EAOM). EAOM was founded in 1998 based on representation from European countries including Austria, Croatia,
Denmark, England, Estonia, Finland, France, Germany,
Greece, Hungary, Iceland, Ireland, Israel, Italy, Latvia,
Netherlands, Norway, Portugal, Romania, Scotland, Serbia,
Slovenia, Spain and Sweden.

Training and Scope of Practice


As defined on the website of the AAOM, oral medicine is
the specialty of dentistry concerned with the oral healthcare of medically complex patients and the diagnosis and
non-surgical management of medically related disorders
or conditions affecting the oral and maxillofacial regions.
These conditions include oral mucosal diseases, oral manifestations of systemic conditions and oral sequelae of
medical treatments. In addition, practitioners have special
expertise in the management of neuropathic pain conditions involving the head and neck area and in pharmacotherapy and drug interactions.
Currently, 10 certied 2-year programs are thriving
throughout the United States and Canada. The curriculum
consists of clinical sciences, biomedical sciences and clinical care interacting with all medical specialties. The material presented in the biomedical sciences provides the
scientic basis needed to understand and carry out the
diagnostic and therapeutic skills required by the clinical,
academic and research aspects of oral medicine. A distinct
curriculum in internal medicine allows the oral medicine
specialist to gain unique expertise in the management
of patients with endocrine, neuromuscular, hematopoietic,
immune and autoimmune, mucocutaneous, cardiovascular, renal, respiratory, musculoskeletal, gastrointestinal
6

Future research will move further into genetics and proteomics to define etiopathogenesis of these complex diseases as well as find targeted treatment approaches. The
potential for using saliva as a diagnostic tool is growing as
well. As the life span of patients continues to lengthen due
to polypharmacy, advancement in diagnostic technologies
and treatment strategies, the demand for the oral medicine
specialist, both as a primary provider and consultant, will
grow exponentially. Medicine and dentistry are coming
closer together as they gain an appreciation of what each
can provide to enhance patient care. The quality of patient
care will continue to improve in parallel with these synergistic interactions.

ORAL AND MAXILLOFACIAL RADIOLOGY


Madhu K Nair
Oral and Maxillofacial Radiology is the newest dental
specialty recognized by the American Dental Association.
The prospects of this discipline are excellent, especially in
light of the increased use of advanced imaging techniques
in dentistry. Two-dimensional imaging that was used in
clinical dentistry is being replaced by newer image acquisition modalities that can generate information in 3D.
Digital radiography is fast replacing film-based imaging,
bringing with it numerous advantages. These include among
others, the ability to reduce doses (in comparison with
older generation films and the use of round collimation),
faster image generation, the capability to post-process
images based on the diagnostic task and also carry out
specific image processing to enhance the signal-to-noise
ratio, as well as the ability to archive, transmit and retrieve
images using dedicated Picture Archiving and Communications System (PACS).

Chapter 1 History and Scope of Oral Medicine and Oral Radiology

In addition, the introduction and increased use of


advanced imaging modalities such as cone beam volumetric
computed tomography (CBVCT) and MRI in dentistry has
resulted in the need for these images to be interpreted by
a board certied maxillofacial radiologists to rule out the
presence of other incidental pathology, and patients
referred for specialized techniques including contrast imaging or functional studies in selected cases. Integration of
services with Neuroradiology/Head and Neck Imaging at
hospitals is thus essential for ensuring optimal patient care.
Most medical radiologists are not trained in the interpretation of oral and maxillofacial pathology, anatomic variations or anomalies and treatment modalities in dentistry to
the extent a maxillofacial radiologist is. The maxillofacial
radiologist understands the diagnostic needs of the dental
patient both from a dental and general maxillofacial perspective and can cater to the needs of the dental community more efciently based on a specic diagnostic task.
Most specialty areas within dentistry including Oral and
Maxillofacial Surgery, Orthodontics, Periodontics, Prosthodontics, Pedodontics, Endodontics, etc. use advanced imaging for a variety of diagnostic tasks and treatment planning,
as also for follow-up evaluations. Some instances include
trauma, facial and other developmental anomalies such
as isolated clefts or defects, syndromes, obstructive sleep
apnea, temporomandibular joint disorders, implant surgery,
localization of impacted teeth and root canals, image-guided
surgical applications, and orthodontic evaluation and treatment planning. When an advanced imaging study is done,
it is expected that the entire volume of data is interpreted
to prevent any incidental pathology from being missed.
Some examples include life-threatening arteriovenous or
lymphovenous malformations, malignancies, aggressive
benign tumors, intracranial lesions and cystic lesions of
jaws in patients imaged for dental purposes.
The future of Oral and Maxillofacial Radiology is bright.
Medical radiology went through the same phases of evolution in the 1990s as many hospitals transitioned to a lmless, paper-less environment and improved their workow
by incorporating digital imaging and PACS on an enterprisewide basis. Currently, radiology is one of the highly ranked
and ercely competitive residencies in medicine. The evolution of radiology informatics as a separate discipline
within radiology indicates the signicance of information
technology resources and computer applications in the
continued development and growth of radiology. Oral and
maxillofacial radiology is headed down the same path.
Medical radiology textbooks acknowledge the fact that
interpretation of oral and maxillofacial pathology on the
need for maxillofacial radiologists in optimizing patient
care. Currently, several post-doctoral and residency programs exist in the United States and Canada for dental
students to specialize in the discipline (http://www.aaomr.
org/adv_edu_prog.php). The American Board of Oral and
Maxillofacial Radiology grants Diplomate status to residents

once they successfully challenge a very rigorous written and


oral examination lasting several days, upon completion of
an accredited oral and maxillofacial radiology residency/
graduate program (http://www.aaomr.org/abomr_contact.
php). The Board comprises a Board of Directors elected by
the Diplomates.

ORAL MEDICINE AND RADIOLOGY


IN INDIA
Syed Vaseemuddin, Ravikiran Ongole
Oral Medicine was introduced in the curriculum and syllabus of the Bachelor of Dental Surgery (BDS) course in
India about 37 years ago. The Government Dental College,
Bangalore affiliated to Bangalore University was the
first dental school in India to teach Oral Medicine. Dental
radiology was only a minor subject being merged with
subjects like Conservative Dentistry, Periodontia and Oral
Surgery. However, its importance was appreciated in the
late 1950s and Master of Dental Surgery (MDS) in radiology, a 2-year program, was introduced by Bombay University in 1959. However, oral medicine was still not included
in the BDS curriculum.
Under the expert guidance of WHO advisors, Oral Medicine, Diagnosis and Radiology was introduced as a separate subject by Bangalore University in 1966. It was taught
during the third and nal year BDS course in Government
Dental College, Bangalore. However, without qualied and
trained teachers in this specialty, the training of BDS students remained inadequate. Government Dental College,
Bangalore was the rst institute to start MDS course with
2-year duration in Oral Medicine, Diagnosis and Radiology in 1970. As a part of the training program the rst
orthopantomograph X-ray unit, the rst in India was
installed and commissioned in Government Dental College
in 1970a gift from the WHO. The subject was introduced
in the southern universities in both BDS and MDS courses
a few years later. Bombay University followed, changing
the MDS course in Dental Radiology to MDS course in Oral
Medicine, Diagnosis and Radiology in the 1970s.
The growth and development of the subject oral medicine would have remained incomplete without an organization for the specialists to meet, discuss and propagate
the acquired knowledge. Hence, the specialists mostly of
Karnataka and a few from Andhra Pradesh and Tamil Nadu
met on 20th June 1985 in Bangalore and unanimously
resolved to form an organization called Indian Academy of
Oral Medicine. Dr BK Venkataraman and Dr Ramachandra
Reddy were the founder members of this academy. The
society was registered under Karnataka Societies Registration Act of 1960 at Bangalore. During the fth national
conference in Chennai, the Academy was renamed as
Indian Academy of Oral Medicine and Radiology.
7

Section I Introduction and Approach to Diagnosis

The Indian Academy of Oral Medicine and Radiology,


launched its ofcial publication Journal of Indian Academy
of Oral Medicine and Radiology in the year 1986. Presently,
the Academy has 800 members.

Course and Curriculum of Oral Medicine


and Radiology
In India, the specialty of Oral Medicine, Diagnosis and
Radiology is taught to undergraduate students in the third
and final year of the BDS program. Following the BDS
degree a student can pursue a 3-year program in the specialty that leads to an MDS degree in Oral Medicine, Diagnosis and Radiology. Admission to the MDS program is
gained through competitive exams.
The syllabus in Oral Medicine and Radiology is divided
into Diagnosis, Diagnostic Methods, Oral Medicine and
Oral Radiology.

Undergraduate Student Competencies as per


Dental Council of India Regulations
The student should be able to recognize various diseases
affecting the oral and paraoral structures and identify precancerous and cancerous lesions of the oral cavity and refer
the patient to the concerned specialist for necessary management. They should have adequate knowledge about
common laboratory investigations and interpretations of
their results.
The student should have adequate knowledge about
medical complications that can arise while treating systemically compromised patients and take prior precautions/
consent from the concerned medical specialist. He or she
should have adequate knowledge about radiation health
hazards, radiation safety and protection.
Students should be competent to take intraoral radiographs and interpret the radiographic ndings. They should
gain adequate knowledge of various extraoral radiographic procedures, TMJ radiography and sialography. The
student should be aware of the importance of intra- and
extraoral radiographs in forensic identication and age
estimation. They should be familiar with jurisprudence,
ethics and understand the signicance of dental records
with respect to law.

Scope and Future of Oral Medicine and


Radiology in India
Oral Medicine and Radiology specialists in India are usually full-time academicians in teaching hospitals. Some of
the specialists engage in specialty practice that includes
diagnosing orofacial diseases, recognizing the oral manifestations of systemic diseases and assessing oral health of
medically compromised patients and medically managing
these patients.
Oral medicine specialists can further pursue a PhD in the
area of their interest as a part-time program or a full-time
program.
In spite of remarkable progress made by the subject of
Oral Medicine and Radiology during the last two decades
many teachers and clinicians feel that there is plenty of scope
for improvement in teaching methodology and research.
Presently across all dental schools in India, the Department of Oral Medicine and Radiology functions more like a
source of patient referral to various dental specialties rather
than a specialty in itself. Following the registration formalities, patients are sent to the Oral Medicine Department,
wherein patients are interviewed, examined, diagnosed and
referred to various specialties for the necessary treatment.
The authors instead feel that the patients should be
directed from the reception/registration counter to the necessary department based on the patients need.
Those specialties in turn can refer patients for an expert
opinion and further management of specic problems such
as orofacial pain, temporomandibular disorders, oral precancers and cancers, salivary gland disorders, cysts and tumors
of the head and neck and syndromes or patients with various underlying systemic illnesses that may require modications in the treatment plan and maxillofacial imaging.
Another area that needs a lot of improvement is oral and
maxillofacial radiology. Although radiology is an integral
part of the course and curriculum of both the undergraduate
and postgraduate training in oral medicine and radiology,
it is mainly conned to extensive training in conventional
radiographic techniques.
Though specialized imaging techniques such as computed tomography, magnetic resonance imaging, ultrasonography, sialography and arthrography are theoretically
taught, the practical exposure to the technique and interpretation is far from adequate.

SECTION

II

Oral and
Maxillofacial
Disturbances

2
3
4
5

Developmental Disturbances
Orofacial Pigmentation Disorders
Bacterial, Viral and Fungal Infections
Orofacial Pain

11
61
82
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Developmental Disturbances

CHAPTER

Sadhana Shenoy, Karen Boaz, Sara Carolina


Rodriguez Pea, Francisco Lopez Sanchez,
Ravikiran Ongole

NORMAL ANATOMIC VARIATIONS

Lingual Varices
Lingual Thyroid

Fordyces Granules

Lingual Tonsils

Fissured Tongue

Leukoedema

Retrocuspid Papillae

Prominent Palatal Rugae

Lingual Varices

Circumvallate Papillae

Parotid Papilla

Physiological Pigmentation

Hard Tissue Disturbances (Jaws)

Hairy Tongue

Exostoses/Tori

Developmental Disorders of the Jaws


Agnathia, Micrognathia, Macrognathia
Hemifacial Hyperplasia, Atrophy
Condylar Aplasia, Hypoplasia, Hyperplasia
Bifid/Trifid Condyle
Coronoid Hyperplasia
Exostoses, Tori

Developmental Disorders Affecting Tongue

Identification of normal anatomical structures forms the


basis for diagnosis. The skill and knowledge to differentiate normal from abnormal plays a decisive role in effective management of the disease process. It is a known fact
that normal anatomic structures can have various clinical
presentations within the same species.
However, one should realize that even the slightest of
change in the appearance of the structure of organs and
tissues makes the recognition of pathological conditions
challenging. On the other hand, normal oral anatomic
structures can induce cancerophobia in many individuals.
These individuals have to be educated regarding the absolutely benign nature of these anatomical variations.

Developmental Disorders Affecting Buccal


Mucosa and Gingiva
Oral Melanotic Macule
Fordyces Granules
Fibromatosis Gingivae

Soft Tissue Disturbances


Aglossia
Microglossia/Hypoglossia
Macroglossia
Ankyloglossia
Cleft Tongue
Fissured Tongue
Geographic Tongue

Developmental Disorders Affecting the Lip


Paramedian Lip Pits/Commissural Pits
Double Lip
Cleft Lip and Palate

DEVELOPMENTAL DISTURBANCES

Developmental Disorders of the Teeth


Disturbances Affecting Size of Teeth
Disturbances Affecting Shape of the Teeth
Disturbances Affecting Number of Teeth
Disturbances Affecting Eruption of Teeth
Disturbances Affecting Structure of Teeth

FORDYCES GRANULES
(Fordyces Spots/Disease)
Fordyces granules are named after an American dermatologist, John Addison Fordyce. This is an ectopic/heterotopic collection of sebaceous glands seen in more than
80% of the normal population.
They are considered ectopic because sebaceous glands
are typically appendages of the skin. When they are present in the oral mucosa they seldom have hair follicles.
This condition is characterized by the presence of
multiple discrete minute yellow colored dots, spots or
granules involving various sites in the oral cavity such as
11

Section II Oral and Maxillofacial Disturbances

Figure 1

Figure 2

Duct
opening
into
epithelium

Sebaceous
glands

Multiple yellowish dots on the buccal mucosa suggestive of


Fordyces granules. Courtesy: Department of Oral Medicine
and Radiology, MCODS, Mangalore

the buccal mucosa (opposite the molar teeth), lips, oral


commissures, retromolar pad, faucial pillars and the palate
(Figure 1). Some authors have described the appearance as
rice-like, white or yellow white papules. The sebum produced by these sebaceous glands imparts the yellow color
to these spots. Each of these granules can vary in size from
1 to 3 mm. The condition is asymptomatic and usually
prominent in adults and generally persist throughout life.
Histopathologically acinar lobules are seen below the
surface epithelium. These acinar lobules usually communicate with the epithelial surface via a central duct (Figure 2).
The ducts may show keratin plugging. The sebaceous cells
are roughly polygonal in shape with a central nucleus. The
cells contain copious amounts of foamy cytoplasm.
Unless these granules are esthetically disturbing in an
individual, no surgical intervention is recommended.
Patient should be educated regarding the harmless and
persistent nature of the condition. Ocampo-Candiani et al
(2003) showed that CO2 superpulsed laser can be used as
an effective treatment modality for patients who desire
treatment for cosmetic reasons. Sebaceous gland adenoma
may occur at times.

LINGUAL TONSILS
Lingual tonsils are the lymphoid aggregates present in the
oral cavity that are part of the Waldeyers ring. It can occur
unilaterally or bilaterally on the posterolateral border of
the base of the tongue. Lymphoid follicles of the lingual
tonsil are irregular in shape and size and vary in number
from 30 to 100.
12

The acinar lobules of the sebaceous glands below


the epithelium with a central duct opening into the
epithelium. Courtesy: Department of Oral Pathology,
MCODS, Mangalore

Anatomically, the arterial supply to the lingual tonsils


is via the lingual branches of the external carotid arteries.
The venous drainage is through the lingual vein that
nally empties into the internal jugular vein. The lingual
tonsils are mainly innervated by the lingual branch of the
glossopharyngeal nerve and to some extent from the superior
laryngeal branch of the vagus nerve.
Lymphatic vessels of the lingual tonsil drain into the
superior deep cervical or jugular lymph nodes.
The lingual tonsil is generally not evident on routine
clinical examination. It may appear as solitary pink colored papule or nodule with a glossy yellowish-pink surface. However, it becomes clinically evident when inamed
and enlarged. Persistent inammation of these tonsils has
also been referred to as lingual tonsillitis. Lingual tonsillitis which is a painful condition characterized by the
symptoms of sore throat and cough. The tonsils are erythematous and spongy or soft on palpation, mimicking
lesions of erythroplakia or oral cancer. However, the bilateral presence of these nodules will help in differentiating
it from carcinoma.
Lingual tonsils do not require any active management.
The patient should be reassured and told to report any
change in size or presence of symptoms. Lingual tonsillitis can be managed with antibiotics. Extensive enlargement of the lymphoid aggregates can impede intubation.
Histopathological evaluation is advised when the lymphoid aggregate enlarges rapidly in size or exhibits surface ulceration.

Chapter 2 Developmental Disturbances

Figure 3
A

(A) Fissured tongue with central median groove. (B) Fissured tongue with multiple grooves in irregular fashion.
Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Fissured Tongue

Management

Fissured tongue has been described by various names in


literature such as scrotal tongue or lingua scrotalis, lingua
plicata, lingua fissurata, cerebriform tongue and furrowed
tongue. The tongue in this relatively common malformation exhibits multiple grooves or furrows of 26 mm depth
and varied pattern on the dorsal surface. Heredity, aging,
chronic trauma and vitamin deficiency have been proposed
as the causes for this condition.
The exact etiology for this condition is still unknown.
However, a polygenic mode of inheritance is suspected
because it is seen clustering in families who are affected.
Based on the geographic location and population studies,
the prevalence of ssured tongue ranges from about 2%
to 21%. Males are said to be slightly more predisposed to
exhibiting this condition.
The ssures are seen on the dorsal surface of the tongue
sometimes extending to the lateral margins. The ssures
can have various morphological patterns; a single prominent groove in the midline of the tongue, multiple horizontal groves radiating from the median groove and multiple
grooves in an irregular fashion (Figure 3A, B).
The tongue ssures can be seen in childhood. However,
the ssures are usually prominent with advancing age.
Fissured tongue is usually associated with other conditions
such as geographic tongue (see Figure 21), Melkersson
Rosenthal syndrome and Down syndrome.
The condition is generally asymptomatic. However, the
deep ssures provide an excellent site for lodgment of
food debris and candidal colonization. These patients may
complain of burning sensation in the tongue.

Patients should be counseled regarding the benign nature


of the condition. They should be motivated to follow optimum oral hygiene practices. They can be encouraged to
use a soft bristled toothbrush to cleanse the grooves of
food debris. In symptomatic patients, topical application
of clotrimazole is recommended.

LEUKOEDEMA
Leukoedema is a common alteration of the oral mucosa,
which appears as a diffuse grayish white opalescent area on
the oral mucosa. It is believed that the intercellular edema
of the superficial epithelial cells and the parakeratinized
epithelium produces the typical grayish white appearance
in this condition.
Axell et al (1981) studied the inuence of tobacco habits and leukoedema among 20,333 individuals in Sweden.
In his study 48.9% of the individuals exhibited leukoedema. Males were more commonly affected. Leukoedema
was more commonly found in the second and third decades
of life. The condition was signicantly more prevalent in
individuals with any form of tobacco habit (60%) and relatively less common in individuals without any tobacco
habit (36.3%).
Van Wyk (1985) studied the association between leukoedema and smoking. He examined 1996 high school students.
He concluded that smoking does not cause leukoedema
but may aggravate it. He also suggested that the etiology
for leukoedema is multifactorial.
13

Section II Oral and Maxillofacial Disturbances

Clinical features
Leukoedema presents as an asymptomatic, grayish white
diffuse opalescent region on the buccal mucosa and occasionally extending into the vestibule, floor of the mouth
and soft palate. The surface appears spongy and usually
comprises folds or grooves. It has been shown that it is
more common in blacks (almost 90%) compared to whites
(Figure 4).
Clinically, this condition can be differentiated from
other white lesions occurring in the oral cavity by stretching the mucosa. Grayish white areas of leukoedema usually disappear at least partially on stretching. Some authors
call this technique the stretch test.
Histopathology and ultrastructural features
Histopathological studies reveal increased epithelial thickness. Parakeratinized epithelium with broad and elongated
rete pegs are typically seen. Intracellular edema within the
spinous layer is a characteristic feature in leukoedema. The
edematous/vacuolated cells are large with a pyknotic nuclei.
Histopathologically it is believed to mimic lesions of white
sponge nevus.
Van Wyk and Ambrosio (1983) studied the ultrastructural and histochemical features of leukoedema in 12 individuals and compared it with normal buccal mucosa. They
concluded that the intracellular edema of the epithelial
cells in leukoedema is due to vacuolation in the cytoplasm
of cells. Toward the surface of the epithelium, the vacuolated cells collapsed into a compact layer of attened cells.
The outer cells of this layer abruptly swelled again to form
the characteristic supercial layer of ballooning cells of
leukoedema.

Figure 4

Opalescent grayish white hue on the buccal


mucosa characteristic of leukoedema.
Courtesy: Dr Ajit Auluck

14

They proposed that the vacuolation in the cell cytoplasm represents a reversible form of cellular degeneration
resulting from cell damage. They believed that the vacuolation was caused because of reduced mitochondrial
function. The supercial ballooning cells are degenerated
cells. They stated that the presence of a compact layer of
vacuolated cells, keratohyalin granules and keratohyalinlike structures in the supercial cells are features of an
aborted form of keratinization.
Treatment
No active treatment is necessary as it is considered as a
variation in the normal anatomy of the oral cavity. However, it is believed that the condition becomes less prominent with the cessation of tobacco habit.

RETROCUSPID PAPILLAE
The retrocuspid papilla is a normal variation in anatomy
characterized by the presence of pink colored, soft to
firm, generally sessile papule or nodule (Figure 5), located
on the gingiva on the lingual surface of the mandibular
canines (cuspid).
The size of the nodule may vary in size from 1 to 5 mm in
diameter. It is very commonly seen in children and believed
to regress with age.
DAoust et al (1991) studied the distribution of retrocuspid papillae among three groups (Ecuador, Honduras and
Nicaragua) of Latin American patients. He found that the
retrocuspid papilla was most prevalent in children below the
age of 5 years. He also found a signicantly higher female

Figure 5

Retrocuspid papilla. Courtesy: Department of


Oral Medicine and Radiology, MCODS, Mangalore

Chapter 2 Developmental Disturbances

predilection in the Honduras group of Latin Americans and


unilateral presentation was more common. Bilateral presence
of retrocuspid papillae was seen in the Nicaragua group.
Retrocuspid papilla was seen involving the attached gingiva
more frequently than the free marginal gingiva. Brannon
et al (2003) also showed that retrocuspid papillae are common in females and young children. In the 51 cases that were
evaluated, bilateral retrocuspid papillae was more common.
Histological features
Buchner et al (1990), histopathologically analyzed 30 specimens of retrocuspid papillae. They showed that almost 80%
of the specimens showed loosely arranged delicate fibrous
connective tissue with stellate and multinucleated fibroblasts.
They also showed that significant number of specimens
exhibited elongated rete ridges and/or increased vascularity.
These papillae do not require any form of treatment.
The need for treatment may arise only during the fabrication
of prosthetic appliances.

PROMINENT PALATAL RUGAE


Palatal rugae have also been referred to as rugae palatinae
and plicae palatinae transversae.
The word ruga (plural: rugae) is a Latin word meaning
ridge, wrinkle or fold. For descriptive purposes palatine
rugae are anatomical ridges, folds or wrinkles in the anterior part of the palatal mucosa. The rugae are present on
either side of the median palatal raphe behind the incisive
papilla. Approximately four to seven rugae are seen on
either side of the midpalatine raphe (Figure 6).
Based on the shape of the rugae they have been categorized as curved, wavy, straight and circular. Individual
studies have shown that males generally have slightly
Figure 6

more number of palatine rugae and the left side of the palate shows slightly more number of rugae in both males
and females. No bilateral symmetry is seen in the number
of rugae. As age advances, the length of the rugae and the
transverse palatal rugal region width increases.
Luke (1988) studied the development of palatal rugae in
mice. He showed that the rugae develop as localized regions
of epithelial proliferation and thickening prior to the elevation of the palatal shelves. Later on, the broblasts and
collagen bers accumulate within the connective tissue
beneath the thickened epithelium and then assume a characteristic orientation. The direction of the collagen bers
running across the base of the palatine rugae determines
their orientation.
In the human embryos the palatal rugae are usually
prominent and present throughout the length of the palatal
shelves at the time of their elevation. At about the 550 mm
stage of the embryo there are about ve to seven symmetrical ridges. The anterior ridges originate at the midpalatine
raphe. Other ridges are seen laterally.
However, toward the end of the intrauterine life, the
posterior ridges almost disappear completely and the anterior ridges become compressed and prominent.
It is believed that the role of rugae in humans is more or
less vestigial. However, in animals palatine rugae help in
suckling and feeding.

Classification of Palatine Rugae Based on Length


Kapali et al (1997) in their study to evaluate the palatal rugae
patterns in Australian Aborigines and Caucasians used the
following clinical classication:
1.
2.
3.

Primary rugae: (A5 to 10 mm; B10 mm or more)


Secondary rugae: 3 to 5 mm
Fragmentary rugae: Less than 3 mm.

On histological examination palatine rugae are stratified


squamous (predominantly parakeratinized) epithelium on a
connective tissue base, which is similar to the adjacent
palatal tissue.
Palatal rugae pattern analysis has been employed successfully in positive human identication. Coslet et al
(1980) reported that the palatal rugae returned back in
several months after its surgical removal.
Many studies have shown that although minor changes
in the morphology of the rugae occur due to orthodontic
tooth movement, extractions, aging and palatal expansion,
these do not signicantly alter the rugal morphology
enough to hamper identication.

Lingual Varices
Palatal rugae. Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

Lingual varices are characterized by the presence of tortuous dilated veins on the ventral surface of the tongue. It is
estimated that approximately 10% of the patients in the
15

Section II Oral and Maxillofacial Disturbances

4th decade and above exhibit lingual varicosities and the


extent of the varicosities increases with advancing age.
Lingual varices have been referred to by various other
names in literature such as phlebectasia linguae, caviar
lesions and linguae varicosities.

Figure 7

Etiopathogenesis
Various theories have been proposed to explain the occurrence of these varices. Ettinger et al (1974) showed that the
incidence of varicosities increases with age. Koscard et al
(1970) reported that the elastic support to capillaries significantly diminishes with advancing age. This reduction in
the elastic support of the connective tissue supporting the
blood vessels leads to dilation of capillaries and formation of
varicosities. It is also suggested that these are due to abnormally dilated and tortuous veins (varices), as they are not
protected by surrounding tissues against hydrostatic pressure.
Eddy et al (1977) studied the role of vitamin C in 22
elderly vegetarians. He showed that vegetarians had high
levels of ascorbic acid values in plasma (10.2 0.4 mg/l),
compared to other elderly individuals. He concluded that
there was a lower incidence of sublingual petechiae and
varicosities in the vegetarian group.

Sublingual varices. Courtesy: Department of Oral Medicine


and Radiology, MCODS, Mangalore

Clinical features
In this condition multiple, bluish-purple papular blebs are
seen on the ventral and lateral borders of the tongue and
occasionally seen on the lips and buccal mucosa. Ventral
surface of tongue reveals the presence of tortuous and
dilated veins (Figure 7). Susmita et al (2006) reported a
case with palatal varicosities. These are usually seen in the
elderly and are not symptomatic unless the varices are
thrombosed. Jassar et al (2000) reported a symptomatic
case of sublingual varices in a patient with portal hypertension secondary to liver cirrhosis.

Figure 8

Histopathologic features
Microscopically, dilated veins are seen with little smooth
muscle and elastic tissue. Thrombosis may be seen as
concentric zones of platelets and erythrocytes (lines of
Zahn). Older thrombi show dystrophic calcification and/or
phleboliths.
Management
Treatment is usually unnecessary. Surgical treatment is
indicated for cosmetic purposes or when there is thrombosis.

CIRCUMVALLATE PAPILLAE OR VALLATE


PAPILLAE
The word vallate is derived from the Latin word vallatus,
which means walled. Hence circumvallate papillae do not
16

Mushroom-shaped circumvallate papillae.


Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

project out onto the surface of the tongue. They are surrounded by a marginal groove. Each of the papillae are
attached to the tongue via their slender bases.
Roughly eight to 12 large (35 mm in diameter) mushroom shaped papillae are arranged all along the V-shaped
sulcus terminalis that divides the tongue into the body and
base (Figure 8). However, occasionally they tend to grow
in size when inamed.

Chapter 2 Developmental Disturbances

Figure 9

Figure 10
Keratinized
stratified
squamous
epithelium
Nonkeratinized
epithelium
Circular
trench
Taste bud
Von Ebner
gland

Circumvallate papillae. The picture reveals keratinized


stratified squamous epithelium, circular trough, taste bud on
the lateral surface of the papilla and von Ebner gland.
Courtesy: Department of Oral Pathology,
MCODS, Mangalore

Histologically, the surface of the vallate papillae exhibits


secondary papillae that are covered by stratied squamous
epithelium. The epithelium lining the lateral surface of the
papillae shows numerous taste buds (Figure 9). The minute
ducts of the von Ebners glands pours its serous secretions
into the base of the circular depression (trough). It is
believed that the secretions of the von Ebners glands is the
primary source of salivary lipase and it also cleanses the
trough so that the taste buds can respond to various stimuli
instantaneously.
Sbarbati et al (1999) suggest that the concept of
von Ebners gland described as ancillary to the taste buds
(washing the trough around the vallate papillae or in perireceptorial events) should be discarded. In their laboratory
studies they have found that the von Ebners gland and the
vallate papillae form a single functional unit. They suggest
this unit be termed circumvallate papilla/von Ebners gland
(CP/VEG) complex. They believe that the CP/VEG complex represented an important enzyme- and pheromoneproducing system composed of a sensitive (taste buds) and
an effectory (VEG) branch linked by feedback mechanisms
of control. They hypothesize that the taste buds located in
the distal portion of the VEG ductal system can be considered similar to the chemoreceptor cells located in other
parts of the digestive apparatus such as pancreatic and bile
ducts. Hence, they concluded that the CP/VEG complex
represented a rare example of chemoreceptor-secretory
organ.
Though, circumvallate papillae are usually not readily
evident on the surface of the tongue, some patients tend to
panic when they notice these mushroom-shaped papillae
while brushing their teeth. Patients need to be educated
about their normal presence.

A small nodule on the buccal mucosa corresponding to the


first and second molars characteristic of the parotid papilla.
Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

PAROTID PAPILLA
Stensens duct of the parotid salivary gland opens into the
oral cavity in the buccal mucosa opposite to the maxillary
first and second molars.
In many instances the orice is hardly noticeable.
However in some individuals a small, triangular raised
pink to red color papule or nodule is readily visible. This
ap of tissue covering the orice of the Stensens duct is
called parotid papilla (Figure 10). Parotid papillae are usually seen bilaterally. As a result of their anatomic location
adjacent to the occlusal plane, the parotid papillae are
common sites for formation of traumatic ulcers.

RACIAL PIGMENTATION/PHYSIOLOGICAL
PIGMENTATION
Pigmentation of the oral mucosa can occur due to a wide
variety of endogenous and exogenous agents. Most of these
are due to five basic pigments, namely, melanin, melanoid,
oxyhemoglobin, reduced hemoglobin and carotene.
Physiologic oral pigmentations are genetically determined. Various stimuli, such as trauma, hormonal changes,
medication and radiation may result in an increased production of melanin. An age-related increase of oral melanocytes has also been observed.
In dark-skinned people, oral pigmentation increases,
but there is no difference in the number of melanocytes
between fair-skinned and dark-skinned individuals.
17

Section II Oral and Maxillofacial Disturbances

Figure 11

Figure 12

Physiologic black colored pigmentation of the gingiva.


Courtesy: Dr Ajit Auluck
Physiologic black pigmentation of the dorsum of the tongue.
Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

The variation is related to the differences in the activity of


melanocytes.
Clinical features
Physiologic pigmentation, which is common in African,
Asian and Mediterranean populations is probably to the
greater melanocyte activity. Oral physiological pigmentation is present in all races and seen equally in males and
females. The pigmentation develops during the first
decade of life but the patient may not be aware of it. The
color depends on the amount of melanin produced and
the site where it is deposited, which may vary from brown
to black.
It is clinically manifested as multifocal or diffuse melanin pigmentation. The attached gingiva is the most common intraoral site of such pigmentation (Figure 11), where
it appears as a bilateral, well-demarcated, ribbon-like,
dark brown band that usually spares the marginal gingiva.
Other sites of involvement are the tongue (Figure 12), lips,
buccal and labial mucosa and perioral skin.
Pathophyisology
The pigmentation of the skin depends on the natural pigment produced in the body called melanin. Melanin is
formed by melanocytes, which are located at the stratum
basale of the epidermis. Head and neck region is the first
site of the body where melanocytes appear after approximately 10 weeks of gestation. These melanocytes produce
melanin from tyrosine by the action of tyrosinase. The
melanin that is formed is transported in the form of melanosomes to keratinocytes via the dendritic processes of the
melanocytes.
Melanosomes persist in dark complexioned individuals.
However in fair skinned individuals the cells in the skin
18

breakdown the melanosomes and the melanin. Albinic


individuals exhibit very minimal or no presence of
melanin. Though all human beings have almost similar
concentration of melanocytes, based on the race of the
individual, melanin producing genes stimulate the production of melanin. Melanin is normally found in the skin,
produced by melanocytes, its functions include absorption
of ultraviolet light and scavenging of some cytotoxic
compounds.
There are typically three forms of melanin; namely,
pheomelanin, eumelanin and neuromelanin. Eumelanin is
found in abundant quantities. It is present in the skin and
hair. It can produce colors ranging from black to gray
and brown to yellow. Pheomelanin is abundantly found in
women. It can produce colors ranging from pink to red.
Neuromelanin is responsible for the pigmentation of four
nuclei of the brain, namely, substantia nigra, locus ceruleus,
median raphe nucleus of pons and dorsal motor nucleus of
the vagus nerve.
Management
Physiological pigmentation is treated only when esthetics
is the concern. Dermabrasion, use of chemical bleach, free
gingival graft placement and cryosurgery are some of the
surgical techniques to lighten the pigmentation.

Hairy Tongue
This condition has also been referred to as black hairy
tongue. Etiology is unknown, however certain predisposing
factors include poor oral hygiene, frequent use of mouthwashes, smoking and alcohol consumption, radiation therapy

Chapter 2 Developmental Disturbances

Figure 13

MANDIBULAR AND MAXILLARY TORI


Exostoses
Exostoses or hyperostoses are non-pathologic, benign
bony growths projecting outward from the cortical plate.
Though exostoses are developmental disturbances they are
usually noticed only in adulthood and may enlarge with
age. They are asymptomatic and self-limiting. It is estimated that the prevalence rate of tori is approximately 27
in every 1,000 individuals. Eskimos, American Indians and
Asians and more specifically Koreans are said to have a
higher incidence of tori.
Etiopathogenesis

Yellowish-brown colored hairy tongue.


Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

for head and neck cancers, fungal infections, topical or


systemic antibiotics and corticosteroids and debilitating
systemic illness.
Clinical features
The condition is characterized by the hypertrophy of
the filiform papillae on the dorsum, producing a hairy
appearance. This condition results from inadequate desquamation or increased keratinization of the papillae. The
filiform papillae are usually about 1 mm in length. However in hairy tongue these papillae may elongate to about
10 mm.
Though the condition has historically been referred to
as black hairy tongue, the color can vary from yellow
to brown to black (Figure 13). The coloration depends on
the chromogenic bacteria, consumption of beverages like
tea and coffee and tobacco use. This condition is usually
asymptomatic. However some individuals complain of
altered taste sensation, halitosis and occasionally gagging
sensation.
Histologically hyperkeratosis of the liform papillae is
seen.
Patients should be advised to avoid excessive consumption of beverages like tea and coffee. They should also be
advised to discontinue the use of tobacco. They can be
motivated to use a medium bristled brush over the dorsal
surface of the tongue.

According to some authors, micro-damage and inflammation in periodontal tissue in genetically susceptible individuals causes exostoses. Abnormal loads during mastication
have also been implicated in inducing exostoses. Buccal
exostoses may result from lateral pressure of the adjacent
teeth.
Palatal tori may be a result of chronic periosteal ischemia due to nasal septum pressure. The torquing action of
the arch of the mandible during mandibular movements is
said to produce mandibular tori.
Clinical classification
Although a formal classification system does not exist,
based on the clinical occurrence, exostoses may be categorized as those that are commonly seen and the rarer forms.
Commonly occurring exostoses
Palatal torus
Mandibular torus
Rarer forms of exostoses
Buccal exostoses
Palatal exostoses
Subpontine exostoses

Torus/Tori
The word torus is derived from Latin, which means a
swelling or bulge. Although etiology is unknown, a hereditary basis is suspected. A torus located along the midline
of the hard palate is called a palatal torus, or torus palatinus, and a torus in the lingual aspect of the mandible is
called a mandibular torus, or torus mandibularis.
Clinical classification of tori based on
morphology
Flat torus: Occurs as a slightly convex bony protuberance with a smooth surface for mandibular tori. However
19

Section II Oral and Maxillofacial Disturbances

Figure 14

Palatal torus. Courtesy: Department of Oral Medicine and


Radiology, MCODS, Mangalore

Figure 15

Bilateral mandibular tori. Courtesy: Department of


Oral Medicine and Radiology, MCODS, Mangalore

in the palatal region it extends symmetrically on either


sides of the palate.
Lobular torus: Occurs as a pedunculated or a sessile lobular mass on either the mandible or palate. It arises from a
single base.

Figure 16

Nodular torus: These are seen as multiple bony protuberances each arising from individual bases. As they enlarge
these may coalesce forming grooves between them.
Spindle torus: Occurs along the length of the midpalatal
raphe region for palatal tori. Elongated tori are evident
bilaterally in the mandible.

Torus palatinus
This condition exhibits exostoses in the midline of the
hard palate. It may be inherited as an autosomal dominant
trait. In individual studies the incidence of palatal tori
among the population of United States has been reported
as high as 2035%. It is believed to be twice as prevalent
in females as in males.
The tori in the palatal vault may vary in size from a few
centimeters to larger sized lesions and are usually lobulated and dome shaped with a smooth surface (Figure 14).
These exostoses generally tend to enlarge with age. Histopathologically smaller lesions are composed of compact
bone. However larger tori may exhibit a central core of
cancellous bone covered by compact bone.

Buccal exostoses. Courtesy: Dr Evelyne Verweij

female predilection is reported. The mandibular tori usually


occur in a symmetric fashion on the lingual surface
of the mandible above the level of the mylohyoid ridge
(Figure 15). The tori are usually located near the canine
and premolar teeth. Occasionally the bilateral tori are so
extensive that they meet at the midline. These tori are
termed kissing tori.

Buccal exostoses
Torus mandibularis
Torus mandibularis is the term used to describe exostoses
occurring on the lingual surface of the mandible. It is
estimated that 710% of the population of United States
exhibit torus mandibularis. However no specific male or
20

Buccal exostoses are benign, broad-based surface masses


of the outer or facial aspect of the maxilla (Figure 16)
and less commonly, the mandible (5.1:1). They begin to
develop in early adulthood and may very slowly enlarge
over the years.

Chapter 2 Developmental Disturbances

Figure 17

Occlusal radiograph with palatal torus marked.


Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

Figure 18

Mandibular occlusal radiograph showing radiopaque


masses extending from the lingual cortical plate, bilaterally.
Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

Palatal Exostoses
They appear as bilateral bony nodular protuberances arising on the palatal cortical plate usually corresponding to
the maxillary tuberosities.

Reactive Subpontine Exostoses


It has also been referred to as subpontic osseous hyperplasia. It is a reactive exostoses arising from the crest of the
alveolar ridge beneath the pontic of a fixed partial denture
presenting as nodule or protruberance of crestal bone. It
was first reported in 1971 by Calman et al.
It may have a genetic origin similar to other exostoses.
However some authors believe that a chronic gingival irritation leads to the subpontic bone proliferation.
Radiographic findings
Exostoses and tori appear as well-defined radiopacities
superimposed on the roots of the teeth. Palatal tori may
not be appreciated in periapical radiographs.
However occlusal radiographs may show a faint radiopaque shadow over the midpalatal region (Figure 17).
Mandibular tori are readily visualized as radiopaque areas
projecting from the lingual cortical plate on mandibular
occlusal radiographs (Figure 18).
Histopathologic features
Exostoses show dense cortical plate with a laminated pattern. The laminar bone reveals scattered osteocytes. The
minute bone marrow spaces may show presence of a fatty
marrow or a loose fibrovascular stroma. Generally minimal osteoblastic activity is seen. However some lesions

show excessive periosteal activity. The bone may show


large lacunae with pyknotic osteocytes, indicative of bone
ischemia.
Clinical considerations
Exostoses may interfere with normal speech and other
functions. Occasionally these bony overgrowths may predispose to gingival and periodontal diseases by way of
forcing food toward the gingival margins during mastication. Large overgrowths may be covered by relatively thin
mucosa that ulcerates even by routine activities such as
mastication and brushing.
They also interfere with the preparation and insertion
of prosthetic appliances and lm placement in intraoral
radiography. Some authors have reported obstructive sleep
apnea in these patients. Difculty in endotracheal intubation was also reported in these patients.
Tori may be used for harvesting bone for alveolar ridge
augmentation and as source of autogenous cortical bone
in periodontal surgery.
Management and prognosis
Bony exostosis generally will not require any form of treatment. The indications for treatment include functional
disturbance (difficulty in mastication), inability to place
the denture or repeated history of traumatic ulcerations.
These bony outgrowths can be surgically contoured
or removed. Brunsvold et al (1995) reported recurrence
of mandibular tori after surgical removal. The author followed up one patient for 11 years and the other for
14 years.
21

Section II Oral and Maxillofacial Disturbances

SOFT TISSUE DISTURBANCES

Figure 19

DEVELOPMENTAL DISORDERS AFFECTING


TONGUE
Aglossia/Lingual Agenesis/Aglossia
Congenita
Failure in the embryogenesis of lateral lingual swellings
during intrauterine life leads to this rare and highly fatal
condition of absence of tongue. However literature review
reveals reports of individuals living a relatively normal
life. Khalil et al (1995) reported aglossia in a 30-year-old
man. It may occur alone or in association with other
deformities including micrognathia; microsomia; congenital absence of mandibular incisors; collapse of the mandibular arch; sagittal band between the floor of the mouth
and the palate; and situs inversus (also called situs
transversuscongenital condition where all major visceral
organs such as the heart, stomach, spleen, liver, etc. are
placed reversed or mirrored from their normal position).
Functional thyroid disorder may develop because of the
embryological association between development of tongue
and thyroid gland. The absence of the lingual muscular
stimulus generally affects the development of jaws and
results in malocclusion of teeth. These individuals have
impaired speech and difficulty in swallowing. Highasi
et al (1996) reported conductive deafness, esophageal atresia, hypoplastic epiglottis and ptosis of the eyelid in an
individual with aglossia.

Microglossia/Hypoglossia
This rare developmental condition is characterized by an
abnormally small tongue. It may occur as an isolated anomaly or, more commonly, as part of oromandibular limb hypogenesis syndrome (hypoglossia-hypodactylia syndrome) or
in association with micrognathia, hypodontia, situs inversus, asplenia, absence of lower incisors, or enamel hypoplasia. Prognosis depends on nature and severity of the
condition. Treatment is directed toward improvement of
oral function with an understanding of the changes in the
mechanisms of oral suction, mastication, swallowing, speech,
as well as dental occlusion.

Macroglossia
An abnormally enlarged tongue is one that protrudes beyond
the teeth or the alveolar ridge in the resting position
(Figure 19). Macroglossia can be broadly categorized as true
macroglossia and pseudo macroglossia (Table 1). In true
macroglossia enlarged tongue is associated with histological
abnormalities. In pseudo macroglossia (relative macroglossia)
the enlargement is apparent; though histology does not
provide a pathologic explanation (e.g. Downs syndrome).
22

Macroglossia. Courtesy: Dr Sumanth

Table 1

Classication of macroglossia

Pseudo macroglossia
Tongue posture
Habitual (tongue thrust)
Poor neuromuscular control
Edentulousness
Maxillofacial skeletal deficiencies
Shallow palatal vault
Deficient maxilla and mandible
Effects of surrounding structures
Enlarged adenoids
Cysts, tumors, space infections displacing the tongue
True macroglossia
Congenital causes
Muscular hypertrophy
Vascular malformations (hemangioma, lymphangioma)
Down syndrome
BeckwithWiedemann syndrome
Mucopolysaccharidoses I and II
Congenital hypothyroidism
Behmel syndrome
Transient neonatal diabetes mellitus
Trisomy 22
Laband syndrome
Lethal dwarfism of Blomstrand
Skeletal dysplasia of Urbach
Tollner syndrome
Ganglioside storage disease type I
Lipoid proteinosis
Acquired causes
Endocrinal disturbances
Acquired hypothyroidism
Acromegaly
Pituitary gigantism
Myxedema
(Contd...)

Chapter 2 Developmental Disturbances

Table 1

Continued

Infections
Tuberculosis
Actinomycosis
Traumatic injuries
Self-inflicted (self-harm, injury during epileptic seizure)
Presurgical (intubation)/surgical trauma/postsurgical (anesthesia/
hemorrhage)
Neoplasms
Lymphangioma
Hemangioma
Carcinoma
Sarcoma
Solitary plasmacytoma
Neurofibroma
Granular cell tumor
Nutritional and metabolic disorders
Amyloidosis
Scurvy
Pellagra
Autoimmune disorders
Sarcoidosis
Giant cell arteritis
Miscellaneous
Angioneurotic edema
Modified from Richard D Thrasher III (2007)

Figure 20

Ankyloglossia. Courtesy: Department of Oral Medicine


and Radiology, MCODS, Mangalore

tip (Figure 20). Messner (2000) reported that the incidence


of ankyloglossia ranged from 0.02% to 4.8% in newborns.
Classification of ankyloglossia
I. Based on anatomical appearance

Clinical features
Clinical features include, crenated lateral border of tongue,
open bite, mandibular prognathism and airway obstruction.
There may be ulceration, secondary infection and necrosis.
In infants it leads to lisping speech, noisy breathing, drooling and difficulty in eating. The tongue has a pebbly surface with multiple vesicle like blebs in lymphangioma; in
hypothyroidism there is diffuse smooth enlargement; the
tongue is multinodular in amyloidosis and neurofibromatosis, papillary appearance of the tongue is seen in MEN type
II and tongue is fissured in Downs syndrome. A unilateral
enlargement of tongue is seen in hemihyperplasia.
Management
Macroglossia, unless causing a functional disturbance
need not be corrected. It is treated with surgical techniques
chosen in accordance with the functional results that one
wants to achieve. It must be the most conservative technique to preserve the vascular nerve bundle. Speech therapy may be required in some cases. Tracheostomy is indicated
in cases of airway obstruction.

Ankyloglossia/Tongue-tie
Ankyloglossia or tongue-tie, is the result of a short, tight,
thick, lingual frenulum causing tethering of the tongue

Type 1: Frenulum attaches to tip of tongue in front of


alveolar ridge in low lip sulcus
Type 2: Attaches 24 mm behind tongue tip and attaches
on alveolar ridge
Type 3: Attaches to mid-tongue and middle of floor of
the mouth, usually tighter and less elastic. The
tip of the tongue may appear heart-shaped
Type 4: Attaches against base of tongue, is shiny, and
is very inelastic
II. Classification of ankyloglossia based on distance of the
insertion of the lingual frenum to the tip of the tongue
This classification was suggested by Kotlow (2004)
Normal:
16 mm
Class I (Mild):
1216 mm
Class II (Moderate):
812 mm
Class III (Severe):
48 mm
Class IV (Complete):
04 mm
Clinical significance
Ankyloglossia may lead to difficulties in breast feeding,
articulation problems, gingival recession, open bite and
abnormal facial development. Frenotomy and frenuloplasty
have been effective treatments for ankyloglossia.
23

Section II Oral and Maxillofacial Disturbances

Intraoral radiography may be difcult in some patients


owing to the limited space available to position the lm.

Cleft Tongue
Cleft tongue or bifid tongue is caused due to lack of merging of lateral lingual swellings of tongue. Partial cleft is
more common than the total cleft and is characterized by
a deep groove in the midline of the dorsal surface. It is often
found as one of the features of orofacial digital syndrome
with thick fibrous bands in the lower anterior mucobuccal
fold and clefting of hypoplastic mandibular alveolar process. Food and microorganisms may collect in the base of
the cleft and cause irritation.

Fissured Tongue
Described on page 13.

Geographic Tongue
Geographic tongue has also been referred to as benign migratory glossitis, wandering rash of the tongue, annulus migrans,
stomatitis areata migrans and erythema areata migrans. It
is a common benign condition that is seen in almost 3% of
the population. Geographic tongue is seen in males and
females equally. However, few articles in literature describe
a slightly higher female predilection (2:1). However, the
tongue changes are more prominent in adults compared to
children.
Etiopathogenesis and predisposing factors
The etiopathogenesis of the condition is still not understood.
Histologically it is said to be an inflammatory condition
associated with human leukocyte antigen (HLA)-DR5,
HLA-DRW6, and HLA-Cw6. Eidelman et al (1976) reported
that many of the parents and siblings of individuals with
geographic tongue also presented with the condition. This
substantiated the possibility of heredity being an etiological factor.
Guimaraes et al (2007) in their investigations found that
the polymorphism3954 interleukin (IL)-1B is associated
with an increased risk of developing geographic tongue.
Redman et al (1966) and Bnczy (1975) et al suggested
that emotional stress was associated with the occurrence
and severity of geographic tongue.
There are many studies with regard to the association
of geographic tongue and diabetes mellitus. Wysocky et al
(1987) reported a four-fold increase in the presence of
geographic tongue in diabetics. However, Guggenheimer
et al (2000) reported no signicant correlation between
geographic tongue and insulin-dependent diabetes mellitus.
Waltimo (1991) in his study on the severity of geographic tongue in a patient taking oral contraceptive pills
24

reported that the tongue changes were the severest on the


17th day of the menstrual cycle.
Marks and Simon (1979) showed a denitive association between geographic tongue and atopy.
Many authors postulate that psoriasis manifests orally
as geographic tongue. Gonzaga (1996) in his investigations showed a signicant association of Cw6 with both
psoriasis and benign migratory glossitis. This antigen was
found in 59.1% of the patients with psoriasis and 43.8%
of the patients with benign migratory glossitis. Zargari
(2006) in a study including 306 patients with psoriasis
concluded that geographic tongue is more common in
early onset psoriasis and may be an indicator of the severity of psoriasis.
Yarom et al (2004) found a strong correlation between
the occurrence of geographic tongue and ssured tongue.
Clinical features
Geographic tongue is commonly seen in the 2nd decade
of life.
The common sites of involvement are the tip of the
tongue, lateral margins and dorsum of the tongue. However some lesions tend to extend to the ventral surface.
The appearance of the lesion typically mimics geographic
outlines on a map, hence the name geographic tongue
(Figure 21). It appears as circinate irregular erythematous
patches which represent the atrophic liform papillae,
bound by keratotic white bands or lines which represent
the regenerating liform papillae (Figure 22).
These erythematous patches occur in multiple sites on
the tongue. Very rarely a single site of involvement may be
seen. In this condition the liform papillae regenerate in the
atrophic site in a few days and a new site begins to reveal
atrophy. Patients typically report this as migrating rash.
Many patients are unaware of the condition as it is
generally asymptomatic. However, some report of inability
to consume spicy food owing to burning sensation. Some
authors believe that the association of ssured tongue with
superimposed candidal infection causes the burning sensation. The condition is seldom painful.
Though this condition is typically seen involving the
tongue, it can occur on other sites in the oral mucosa.
Some authors use terms such as ectopic geographic tongue,
geographic stomatitis, erythema migrans, erythema areata
migrans, and stomatitis areata to refer to such a nding.
The common ectopic sites include the buccal mucosa, labial
mucosa (Figure 23), gingiva, oor of mouth and less commonly the soft palate and uvula.
Histopathologic features
Biopsy specimens should ideally be obtained from a site
which includes the keratotic serpiginous margin and the
atrophic area. On histopathological examination hyperkeratosis, acanthosis and slender, elongated rete pegs are seen.

Chapter 2 Developmental Disturbances

Figure 21

Figure 23

Geographic lip. Courtesy: Dr Foluso Owotade

Geographic tongue. Courtesy: Department of Oral Medicine


and Radiology, MCODS, Mangalore

Figure 22

Management
All patients of geographic tongue need to be reassured of the
harmless nature of the condition. In symptomatic patients
palliative therapy with topical or systemic antihistaminics
have proved beneficial due to their local anesthetic effect
(Sigal et al, 1992). Presence of associated fissured tongue
with superimposed candidal infection can be effectively
managed with topical clotrimazole. Benzydamine hydrochloride mouthrinse can be used to manage burning sensation. Gibson et al (1990) in their study showed that zinc
supplements proved effective for managing geographic
tongue.

Lingual Varices
Described on page 15.

Lingual Thyroid

Geographic tongue on the dorsum of the tongue.


Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

Neutrophil infiltrations are seen in the thick layer of keratin and to a lesser degree in other portions of the epithelium. These infiltrations produce microabscess (Munros
abscess) in the keratin and spinous layers.

Failure of the thyroid tissue to descend from its developmental origin at the foramen caecum to its normal pretracheal location leads to its presence in the tongue at the
foramen caecum. Van Der Gaag et al (1985) postulated
that maternal antithyroid immunoglobulins may arrest the
descent of the thyroid in some individuals.
Thyroid tissue may be deposited ectopically along this
early thyroglossal tract. Apart from tongue, ectopic thyroid tissue has also been reported at other midline locations of the neck such as below the level of hyoid bone,
larynx and trachea, mediastinum and esophagus.
It is estimated that the incidence of lingual thyroid varies
between 1:3,000 and 1:100,000 (Williams et al, 1989).
The lingual thyroid is seen as a nodular mass in the
midline about 23 cm in diameter with a smooth surface.
It appears erythematous when highly vascular. Depending
25

Section II Oral and Maxillofacial Disturbances

Figure 24

Lingual pits on the dorsum surface of the tongue.


Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

on the size, it may produce symptoms of pain, feeling of


fullness in the throat, dysphagia, dysphonia and dyspnea.
The diagnostic test is thyroid scan with iodine isotopes
or technetium-99m, CT scan or MRI helps in delineating the
size and extent of the lesion. Biopsy is avoided as there is
risk of hemorrhage and it could be the only thyroid tissue
(in about 70% cases). Histopathologically it resembles normal thyroid tissue. If it has to be excised, it should be done
after conrming the presence of a functioning thyroid in
the normal position. If it is not so, then the excised tissue
is transplanted in a muscle with adequate vascularity.

Tongue Pits
The authors report a case of lingual pits on the dorsal surface of the tongue in a 24-year-old male (Figure 24). The
patient was asymptomatic and reported that these pits
were present since childhood. Review of literature shows
no mention of this condition.

DEVELOPMENTAL DISORDERS AFFECTING


THE LIP
Paramedian Lip Pits (Congenital Lip Pits)
These congenital invaginations of the lower lip arise from
persistent lateral sulci on the embryonic mandibular arch.
They are seen as bilateral (occasionally unilateral), symmetrical pits on the vermillion border on either side of
the midline ranging from subtle depressions to prominent
humps. This trait may be transmitted genetically to the
offspring.
26

Figure 25

Commisural lip pit. Courtesy: Department of Oral Medicine


and Radiology, MCODS, Mangalore

These can extend to a depth of 1.5 cm. On squeezing they


may express salivary secretions. These lip pits may be a part
of Van der Woude syndrome or popliteal pterygium syndrome. Histopathologically, tracts lined by stratied squamous epithelium are seen; minor salivary glands may be seen
communicating with the sinus. Surrounding connective tissue
is often inltrated by chronic inammatory cells. Excision
of these pits may be performed for cosmetic reasons.

Commissural Lip Pits


These small mucosal invaginations occur at the corners
of the mouth on the vermillion border (unilaterally or
bilaterally), possibly due to failure of fusion of embryonal
maxillary and mandibular processes (Figure 25). Though
considered congenital, these often develop later in life
prevalence in children (0.20.7%) being much lower than
in adults (1220%). Males are more often affected than
females. An autosomal dominant pattern of transmission is
noted in some families. In most cases, they are asymptomatic and are discovered on routine examination; they may
express saliva on squeezing. The depth of these pits range
from 1 mm to 4 mm. Associated preauricular pits may be
seen in some. They are generally not associated with facial
or palatal clefts. Histopathologically they are similar to
paramedian lip pits.
No treatment is necessary. However excision is indicated if there is excessive salivary secretion or secondary
infection.

Double Lip
Here a mucosal fold appears on the mucosal side of the lip,
commonly the upper lip. The congenital form is due to

Chapter 2 Developmental Disturbances

Table 2 Syndromes associated with cleft lip

Figure 26

Achondroplasia
BeckwithWiedemann syndrome
DiGeorge syndrome
Fetal alcohol syndrome
Goldenhar syndrome
Gorlin syndrome
Treacher Collins syndrome
Van der Woude syndrome
Waardenburg syndrome

Table 3 Syndromes associated with cleft palate


Achondroplasia

Unilateral cleft lip extending into the floor of the nose.


Courtesy: Dr Foluso Owotade

BeckwithWiedemann syndrome
Cleidocranial dysplasia
Crouzon syndrome (craniofacial dysostosis)
EhlersDanlos syndrome
Fetal alcohol syndrome

Figure 27

Gorlin syndrome (basal cell nevus syndrome)


Marfan syndrome
Pierre Robin syndrome
RubinsteinTaybi syndrome
Treacher Collins syndrome (mandibulofacial dysostosis)
Van der Woude syndrome

persistence of sulcus between the pars glabrosa and pars


villosa of the lip. The acquired form may be due to trauma,
repeated sucking on the lip or as part of Aschers syndrome (double lip, blepharochalasis and non-toxic thyroid
enlargement). In most cases, it becomes visible only when
the lip is tense or while smiling. Histopathologically normal structures are seen with a slight abundance of minor
salivary glands. Excision is the treatment for esthetic
reasons.
Bilateral cleft lip. Courtesy: Department of Oral and
Maxillofacial Surgery, MCODS, Mangalore

Cleft Lip and Cleft Palate


Cleft lip results from failure of merging of epithelial groove
between the medial and lateral nasal process by penetration
of mesodermal cells. Cleft palate is the result of epithelial
breakdown with in growth failure of mesodermal tissue and
lack of lateral palatal segment fusion. Most cleft cases are
polygenic but the 5% of cleft cases associated with syndromes are said to be monogenic (Tables 2 and 3). Environmental factors like nutritional deficiencies, stress, infections,
alcohol, drugs, toxins and ischemia may cause clefts.
Veau system of classication is generally used where
the emphasis is on the extent to which the clefting is seen.
Submucosal clefts are not included here.

Cleft lip

Class I: Unilateral notching of vermillion border that


does not extend into the lip
Class II: Unilateral notching of the vermillion extending
into the lip but not involving the floor of the nose
Class III: Unilateral clefts of the vermillion border
extending through the lip into the floor of the nose
(Figure 26)
Class IV: Any bilateral cleft of the lip exhibiting incomplete notching or a complete cleft (Figure 27).
27

Section II Oral and Maxillofacial Disturbances

Figure 28

Figure 29

Orthopantomograph showing cleft alveolus on the right


maxillary lateral incisor region. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

Figure 30

Complete cleft palate in an adult.


Courtesy: Dr Prakash Chhajlani

Cleft palate (Figure 28)

Class I: Cleft limited to soft palate


Class II: Defects of both hard and soft palate. They
extend till the incisive foramen
Cleft palate can either be complete or incomplete.
Complete cleft includes cleft of soft and hard palate
to the incisive foramen.
Incomplete cleft involves the velum and a portion
of the hard palate.
Class III: These are complete unilateral clefts extending
from the uvula to the incisive foramen in the midline
and the alveolar process unilaterally (Figure 29).
Class IV: Complete bilateral clefts involving the soft
and hard palate and alveolar process on both sides of
premaxilla leaving it free and often mobile.
Rarely, a lateral cleft lip can be seen due to non-fusion
of the maxillary and mandibular process (Figure 30).
Cleft of soft palate including submucosal clefts are associated with eustachian tube dysfunction, recurrent otitis
media and hearing deficits.
Dental anomalies include congenitally missing lateral
incisor, supernumerary teeth, delayed tooth formation,
enamel hypoplasia, micro/macrodontia and fusion.

Prenatal Diagnosis of Clefts


The facial structures of the fetus are best imaged after the
15th week in utero using ultrasound (Figure 31). Though
28

Lateral cleft lip. Courtesy: Dr Prakash Chhajlani

the fusion of the midline structures is complete by the


8th week, the position of the head is not readily accessible
for adequate imaging. It is also believed that the head is
relatively smaller compared to the size of the transducer
in the first 15 weeks of gestation.
Classication of clefts based on ultrasound imaging
Type 1: Cleft lip
Type 2: Unilateral cleft lip and palate
Type 3: Bilateral cleft lip and palate
Type 4: Midline clefts
Type 5: Facial clefts associated with amniotic bands or
limb-body wall complex.
Treatment of clefts requires a multidisciplinary team including dental, medical and surgical specialists with assistance
of allied health professionals in social services, child development and hearing and speech therapy. Cleft lip repair is
done when the child weighs 10 pounds, has hemoglobin
level of 10 mg/dl and older than 10 weeks. Cheiloplasty is
required later in life. By 1 year, closure of soft palate with

Chapter 2 Developmental Disturbances

Figure 31

Figure 32

In utero diagnosis of bilateral cleft lip at 30 weeks pregnancy


using ultrasound. Courtesy: Dr Sudheer Gokhle,
Ultrasonologist, Indore, India

pharyngeal flaps is recommended to promote normal speech


development (Figure 32).
Palatal obturators are used when there are feeding
problems in cases of cleft palate (Figure 33).

Surgically closed cleft palate.


Courtesy: Dr Prakash Chhajlani

Figure 33

DEVELOPMENTAL DISORDERS AFFECTING


BUCCAL MUCOSA AND GINGIVA
Oral Melanotic Macule
Labial melanotic macule is an otherwise asymptomatic,
usually solitary, small (generally 5 mm), flat, brown to
brownish-black lesion found on the vermillion border of
the lower lip near the midline. It can occur at any age. Oral
melanotic macules usually occur on the gingiva, buccal
mucosa and soft palate. Histopathologically there is an
increased amount of melanin in the basal cells with a
dropout of melanin from these basal cells into the macrophages of connective tissue. This is called melanin incontinence. Unlike in actinic lentigo the rete ridges here are not
elongated. Excision biopsy is done to rule out melanoma
and other pigmented lesions. Excision of these macules may
be undertaken for esthetic reasons.

Fordyces Granules (Fordyces Disease/Spots)


Described on page 11.

Feeding palate for cleft lip and palate neonates.


Courtesy: Dr Prakash Chhajlani

Fibromatosis Gingivae
This is an autosomal dominant disorder affecting the
gingiva of one or both arches and characterized by noninflamed, non-painful smooth or nodular diffuse overgrowth (Figure 34). The overgrowth may prevent eruption
of teeth or may be seen covering a large portion of the
29

Section II Oral and Maxillofacial Disturbances

Figure 34

Figure 35

Diffuse non-inflammatory gingival enlargement in


fibromatosis gingivae. Courtesy: Department of Oral Medicine
and Radiology, MCODS, Mangalore
Micrognathia

crown in erupted teeth. It may be associated with hypertrichosis, corneal dystrophy, craniofacial deformities, nail
defects, deafness, epilepsy and mental retardation. Histopathologically dense non-inflamed collagenous connective
tissue with the overlying epithelium showing elongated
rete ridges are seen. Gingivectomy is the treatment of
choice. Recurrences may be seen but can be prevented by
extraction of teeth.

HARD TISSUE DISTURBANCES (JAWS)


DEVELOPMENTAL DISTURBANCES OF THE
JAWS
These include complete absence or diminished or excessive development of the jaws. Abnormally small and large
jaws are called micrognathia or macrognathia respectively.
Apparent under-development or over-development due
to skeletal malpositioning of the jaws (e.g. retrognathia
or prognathia) is called pseudo-micrognathia or pseudomacrognathia. Disorders of development of facial skeleton
may also affect the jaws. In hemifacial hyperplasia one
side of the facial skeleton is abnormally large and in hemifacial atrophy, it is under-developed.

(e.g. missing premaxilla) or mandible (e.g. missing ramus).


Partial absence of mandible is more common. When there
is unilateral absence of mandibular ramus, the ear too may
be deformed or absent.

Micrognathia
Congenital micrognathia is usually seen in association
with other congenital abnormalities like congenital heart
disease and Pierre Robin syndrome. Occasionally, they
may follow a hereditary pattern. Micrognathia of maxilla
is usually due to deficiency in the premaxillary area.
The middle third of face appears retracted. Associated
maldevelopment of nasal and nasopharyngeal structures
can predispose to mouth breathing. Mandibular micrognathia is commonly due to agenesis of the condyles.
Normal growth of mandible depends on the development
of condyles as well as muscle function. If there is ankylosis of the joint due to trauma, infection of mastoid, middle
ear or the joint, it causes acquired micrognathia of mandible. Clinically, severe retrusion of chin, a steep mandibular angle, and a deficient chin button are observed
(Figure 35). Table 4 lists few of the syndromes associated
with micrognathia.

Macrognathia
Agnathia
Though the term agnathia refers to absence of jaws,
usually there is incomplete development of either maxilla
30

Only the mandible, both maxilla and mandible or the entire


skeleton may be abnormally large. Mandibular macrognathia may be due to increased height of ramus (Figure 36),

Chapter 2 Developmental Disturbances

increased mandibular body length, increased gonial angle,


anterior positioning of glenoid fossa or prominent chin
button.
Both the jaws are affected in Pagets disease of bone,
acromegaly, leontiasis ossea (a form of brous dysplasia).
Pituitary gigantism leads to generalized increase in size of
entire skeleton. In addition to treating the underlying
cause, the length of the mandible may be reduced by
ostectomy.

Hemifacial Hyperplasia
Although this is known more commonly as hemifacial
hypertrophy, there is actually hyperplasia of the tissues.
Some degree of facial asymmetry is common. Hemifacial
hyperplasia refers to significant unilateral enlargement of
the face including eyes, ears, nose and intraoral tissues
(Figure 37). It is often noted at birth and sometimes at
puberty. The disproportionate growth continues until the
patients overall growth ceases, resulting in permanent
asymmetry.

Table 4

It may also be associated with malformation syndromes


like BeckwithWiedemann syndrome, McCuneAlbrights
syndrome and neurobromatosis.
Etiology and clinical features
Etiologic factors suggested include vascular or lymphatic
abnormalities, central nervous system disturbances, endocrine dysfunction, aberrant twinning mechanisms and
chromosomal anomalies.
Women are aficted twice as many as men. In them,
either side is equally affected, while in males, right side is
more commonly affected. About 1520% have enlargement of cerebrum and mental retardation. Malignancies of
adrenal cortex, liver and kidney (e.g. Wilms tumor) are
more common in them. On the affected side, the skin is
thick and coarse, hair is thick and abundant and sebaceous
and sweat gland secretions are excessive. Excessive pigmentation may also be evident.
Lee et al (2001) described three cases with hemifacial
hyperplasia of the muscles of facial expression with no
other organ system involvement. They proposed to name
this condition with unique characteristics as hemifacial
myohyperplasia.

Syndromes associated with micrognathia

Cohen syndrome

Intraoral findings

DiGeorge syndrome

Malocclusion is common. Unilateral macroglossia with


prominent papillae are characteristic.

Fetal alcohol syndrome


Pierre Robin syndrome
Potter syndrome

Radiographic features

RubinsteinTaybi syndrome

The facial skull bones (mandible, maxilla, zygomatic, temporal and frontal) are enlarged on the affected side (Figure 38).

Treacher Collins syndrome

Figure 36
A

(A) Lateral cephalogram showing mandibular macrognathia. (B) Orthopantomograph showing increased ramal length and
mandibular body in macrognathia

31

Section II Oral and Maxillofacial Disturbances

Figure 37
A

(A) A child with hemifacial hyperplasia affecting the right side. (B) Right side of the tongue showing enlargement.
(C) PA view showing enlargement of the mandible and soft tissues on the right side. (D) Enlarged body and
ramus of the mandible on the right side

Figure 38

The roots and crown of the teeth particularly the permanent teeth are often enlarged and may erupt prematurely.
Primary teeth are shed prematurely on the affected side.
The mandibular canal can appear enlarged.
Management
Functional and cosmetic improvements may be achieved
through orthodontic tooth alignment and serial staged
surgeries. Because enlargement is related to all tissue levels, perfect symmetry cannot be obtained.

Hemifacial Atrophy (Parry Romberg Syndrome,


Romberg Syndrome)
Photograph showing atrophic changes of the tissues in one
side of the face. Courtesy: Department of Oral Medicine and
Radiology, KLE Societys Institute of Dental Sciences, Bangalore

32

This condition is characterized by atrophic changes of


tissues on one side of the face including eyes, ears,
nose and intraoral tissues. Trophic malfunction of the
cervical sympathetic nervous system, viral or borrelia

Chapter 2 Developmental Disturbances

infection, trauma, genetic factors, peripheral trigeminal


neuritis, etc. have been speculated as the causes. Many
investigators believe that it represents a localized form of
scleroderma.
It commonly affects females in the rst two decades of
life. The condition begins as a localized area of atrophy of
skin and subcutaneous structures. This atrophy progresses
at a variable rate and affects the dermatome of one or more
branches of the trigeminal nerve. Osseous hypoplasia may
occur when the condition begins during the rst decade.
The overlying skin often exhibits dark pigments (Figure 38).
Some patients have a sharp line of demarcation resembling
a large linear scar between normal and abnormal skin near
the midline of the forehead known as coup de sabre (strike
of the sword). Atrophy of upper lip may expose the maxillary teeth. Unilateral posterior open bite develops as a result
of mandibular hypoplasia and delayed eruption of the teeth.
Teeth on affected side may show decient root development or root resorption. Atrophy progresses for several
years and then becomes stable. Cosmetic surgery and orthodontic therapy may help in correcting deformity and
malocclusion respectively.

injuries sustained during the growth and development of


the mandible, therapeutic radiation and arthritis. This condition is managed using grafts followed by orthognathic
surgery and orthodontic correction of malocclusion.

Condylar Hyperplasia
Condylar hyperplasia refers to a unilateral enlargement of
the mandibular condyle. Though the etiopathogenesis is
still unclear, various causes have been proposed such as
trauma, endocrinal disturbances and local deficiency of
circulation.
Clinical features

The complete failure of development of the mandibular


condyle either unilaterally or bilaterally is referred to as
condylar aplasia. It is estimated that the incidence of condylar aplasia is around 1 in 5,600 births.
The developmental defect is rarely seen in isolation.
It may usually be associated with hemifacial microsomia,
Goldenhaars syndrome and Treacher Collins syndrome.
Lesser known associations of condylar malformations
and agenesis are with Proteus syndrome, Morquio syndrome and auriculocondylar syndrome. Santos et al (2007)
reported a case of condylar aplasia without any syndrome
association.
In unilateral aplasia obvious facial asymmetry and shifting of the mandible to the affected side on mouth opening
are common ndings.

Condylar hyperplasia is usually encountered in the second


and third decades of life. Patients generally complain of progressive facial asymmetry. On clinical examination unusually large condylar head can give arise to a clinically evident
swelling in the temporomandibular joint region. The mandible is deflected to the normal side. Open bite on the
affected side is a characteristic feature.
The progressive facial asymmetry can be conrmed
by comparing photographs of the patient from childhood
through adolescence to adulthood.
Orthopantomograph (OPG) is a good scout radiograph
for comparing the relative increase in size of the condyle
with respect to the unaffected side. Other radiographic views
that could prove benecial are the open and closed TMJ
views, TMJ views (transcranial, transpharyngeal and transorbital), posteroanterior skull view, submentovertex base
of skull view and computed tomography.
Histopathologically the condition shows normal features after completion of the growth. However proliferation of the condylar cartilage is seen during the periods of
active growth.
The condition is generally self-limiting. However unusually large condyles causing functional and esthetic disturbances can be managed by surgical recontouring. In some
cases condylectomy may be required.

Condylar Hypoplasia

Bifid/Trifid Condyle

Condylar hypoplasia results from congenital or developmental disturbances or due to acquired causes. In this condition the condyle usually retains its shape but appears
smaller. Unilateral involvement of the condyles is more
common than bilateral involvement.
Most of these patients also present with a proportionately smaller ramus and body of the mandible. A prominent antigonial notch may be seen. The acquired causes
that result in hypoplasia of the condyle include traumatic

Hrdlicka in 1941, was the first to describe bifid condyles in


skull specimens. Schier in 1948 described bifid condyles in
a living person based on radiographic findings. Artvinli
et al (2003) and Cagirankaya et al (2005) reported trifid
mandibular condyle.
Most of the cases reported were involving individuals
over 20 years of age. Males and females are equally
affected. Literature reveals the left condyle being twice
more affected than the right side.

Condylar Aplasia

33

Section II Oral and Maxillofacial Disturbances

Figure 39

34

Figure 40

Cropped orthopantomograph showing bifid condyle.


Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

Cropped orthopantomograph showing trifid condyle.


Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

The etiology for the condition is unknown. Some


authors believe that the condylar cartilage, during the
early stages of its development, is divided by well-vascularized brous septa and the persistence of such a septum,
within the growing cartilage might give rise to the bid
condyle. It is also believed that the rupture of the septal
vessels secondary to trauma can give rise to the bid condyle. Various other factors that have been implicated are
exposure to teratogenic substances, endocrinal disturbances,
infections, exposure to therapeutic radiation and nutritional
deciencies.
It is believed that bid mandibular condyle resulting
from trauma will exhibit one glenoid fossa, whereas those
of developmental origin exhibit separate glenoid fossa for
each of the two parts of the bid condyle. It is also postulated that the anteroposterior (sagittal) form of bid condyle results from facial trauma during childhood, and the
mediolateral form (coronal) with persistence of the brous
septa at the condylar cartilage.
Bid or trid condyles (Figures 39 and 40) are usually
found incidentally on radiographic investigations. Though
commonly an orthopantomograph can reveal the possibility of a bid or trid condyle the best imaging modality to
visualize the condyle for this condition is coronal computed
tomography. Moreover, a 3D reconstruction helps in accurately assessing the morphology of the condyles.

No treatment is required for this condition as it is


asymptomatic.

Coronoid Hyperplasia
Hyperplasia of the coronoid process is an uncommon
developmental disturbance affecting the jaws. The hyperplasia of the coronoid process can either be unilateral or
bilateral.
This condition is characterized by a progressive limitation in mandibular movement, due to impingement of the
elongated coronoid processes on the posterior surface of
the zygomas. The shape of the coronoid process usually
does not change, however it only increases in size.
On clinical examination there is no apparent facial
asymmetry or pain. It usually begins at puberty. Males
are more commonly affected than females (5:1). Apart
from genetic inheritance other causes for coronoid hyperplasia to occur have been proposed such as trauma,
increased activity of the temporalis muscle and endocrinal
stimulus.
Waters view and orthopantomograph are usually sufcient to evaluate coronoid hyperplasia. It is believed
that the projection of the tips of the coronoid processes
at least 1 cm over the inferior rim of the zygomatic arch is
pathognomonic of coronoid hyperplasia. The impingement

Chapter 2 Developmental Disturbances

of the elongated coronoid process over the zygomas can


be best appreciated by an axial CT image with the mouth
open.
Literature reveals reports of coronoid hyperplasia in
syndromes such as trismus-pseudocamptodactyly syndrome
(Yamashita et al, 1979) and nevoid basal cell carcinoma
syndrome (Leonardi et al, 2001).
The condition can be managed by surgically contouring the coronoid process or by coronoidectomy followed
by a rigorous regimen of physiotherapy.

Figure 41

Exostoses/Tori
Described on page 19.

DEVELOPMENTAL DISTURBANCES
AFFECTING TEETH

Unusually elongated root in premolar.


Courtesy: Department of Oral Pathology,
MCODS, Mangalore

These include disorders of size, shape, number, structure


and eruption of teeth.
Figure 42

Developmental Disturbances Affecting


Size of Teeth
These include either decreased or increased size of the teeth.
Localized microdontia is fairly common, especially that
affecting maxillary lateral incisor (peg lateral) and the third
molar. When only the roots are long/elongated, the condition is called rhizomegaly or radiculomegaly (Figure 41).
Similarly, rhizomicry or root dwarfism is the term used to
refer to teeth with short roots (Figure 42).
Microdontia In this condition the teeth are smaller than
usual (microdonts). Apparently small teeth due to abnormally large jaws (pseudomicrodontia) are not included
here. Microdontia can either be localized or generalized
(Figure 43).
In generalized microdontia all the teeth are smaller than
normal. It may be seen in pituitary dwarsm and Down
syndrome (Figure 44A, B). Other conditions that are associated with microdontia are AxenfeldRieger syndrome
(ODwyer et al, 2005), Fanconi anemia (Tekcicek et al, 2007),
BardetBiedl syndrome (Drugowick et al, 2007) and oculodentodigital dysplasia (Vasconcellos et al, 2005). Remmers
et al (2005) reported microdontia as a late effect of chemotherapy on dental development in a patient treated for
neuroblastoma during the early years of life.
Localized microdontia is a rather common condition. It
affects most often the maxillary lateral incisor and third
molar. The common form which affects maxillary lateral
incisor is called peg lateral (Figure 45). Localized microdontia can be seen in hemihyperplasia.

Stunted root length in a maxillary central incisor.


Courtesy: Department of Oral Pathology,
MCODS, Mangalore

Macrodontia It refers to teeth that are larger than normal. However, the term macrodontia should not be applied
to teeth that appear large due to fusion or gemination.
Localized macrodontia is seen in hemihyperplasia. All the
teeth are larger than normal in generalized macrodontia.

35

Section II Oral and Maxillofacial Disturbances

Figure 43

Figure 45

Microdontic tooth specimen. Courtesy: Department of


Oral Pathology, MCODS, Mangalore
Peg-shaped maxillary lateral incisor. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

Figure 44
A

et al, 2006), EkmanWestborg and Julin syndrome (Nemes


et al, 2006), Cockaynes syndrome (ArenasSordo Mde et al,
2006), Dubowitz syndrome (Chan et al, 2005) and Schinzel
Giedion syndrome (Cooke et al, 2002).

Developmental Disturbances Affecting the


Shape of the Teeth (Gemination, Fusion and
Concrescence)

Generalized microdontia. Courtesy: Department of


Oral Medicine and Radiology, MCODS, Mangalore

It is associated with pituitary gigantism but is extremely


rare. Various other syndromes are associated with either
generalized or partial macrodontia such as BerardinelliSeip
syndrome (Solanki et al, 2008), KBG syndrome (Brancati
36

Gemination and fusion have been referred to by various


names in literature such as double teeth, double formations, joined teeth, fused teeth and dental twinning.
In gemination, a single tooth bud divides and results in
the formation of teeth with a bid crown and a common
root and root canal. The crown may be clearly bid or there
may just be a groove (Figures 46 and 47). It is seen commonly in the maxillary anterior regions.
Aquilo et al (1999) classied gemination into four types
based on the morphology.
Type I: Bid crown with a single root
Crown is larger than normal with a notch on the incisal
edge and a bid pulp chamber. The root and pulp chamber
are of normal size.
Type II: Large crown with a large root
Crown is larger than normal and has no groove or
notch. The pulp chamber is single and large. The root is
wider than normal and has one large root canal.
Type III: Two fused crowns with a single root
There are two crowns with a vertical groove. The cervical portion of both crowns may be joined. The pulp chamber may be separate. The root is conical shaped and larger
than normal.
Type IV: Two fused crowns with two fused roots

Chapter 2 Developmental Disturbances

Figure 46

Gemination of the lower anterior tooth exhibiting a subtle


groove on the incisal edge. Courtesy: Department of
Oral Medicine and Radiology, KLE Societys Institute of
Dental Sciences, Bangalore

Figure 48

Fusion of the central and lateral mandibular incisors.


Courtesy: Department of Oral Medicine and Radiology,
KLE Societys Institute of Dental Sciences, Bangalore

Figure 49

Figure 47

Fusion of the crown and roots. Courtesy: Department of


Oral Pathology, MCODS, Mangalore

Intraoral periapical radiograph showing a bifid crown with a


common root and root canal. Courtesy: Department of Oral
Medicine and Radiology, MCODS, Mangalore

There are two crowns with a vertical groove. The cervical portion of both crowns is joined along with the pulp
chambers.
Fusion occurs when there is union of two tooth buds
with the conuence of dentin, resulting in single tooth

with separate or fused root canals (Figures 4850). Fusion


may occur between normal tooth and a supernumerary
tooth like mesiodens or distomolar.
The most reliable method of distinguishing between
gemination and fusion is by counting the number of teeth
in the arch. In gemination, the count of teeth remains normal, whereas in fusion the tooth count will reveal a missing tooth.
Concrescence is the union of two adjacent teeth by
cementum alone without conuence of underlying dentin
(Figures 51 and 52). The common teeth that may show
concrescence are the maxillary molars, especially third
molar and a supernumerary tooth.
37

Section II Oral and Maxillofacial Disturbances

Figure 50

Tooth specimen showing fusion of the roots. Courtesy:


Department of Oral Pathology, MCODS, Mangalore

Figure 52

Radiograph showing concrescence. Courtesy: Department of


Oral Medicine and Radiology, MCODS, Mangalore

Figure 51
this may have to be resolved by radiography. Some authors
have reported abnormal patterns in concrescence such as
concrescence between an impacted third molar and an
erupted second molar (Romito, 2004), concrescence between
a third molar and a supernumerary fourth molar in the
mandible (Gunduz et al, 2006) and concrescence of the
crown of an impacted tooth and the roots of the erupted
tooth as a result of the deposition of acellular cementum
on the crown (Sugiyama et al, 2007).
Presence of geminated and fused teeth in deciduous
dentition can cause crowding, abnormal spacing, delayed
or ectopic eruption of underlying permanent teeth. Extraction may be necessary to prevent an abnormality in eruption. If the permanent teeth are affected, treatment of choice
is determined by patients needs. Surgical division followed
by endodontic treatment may be done. Selective shaping is
done with/without placement of full crowns. In some cases,
surgical removal of tooth with prosthetic replacement is
done.
Concrescence (fusion of the teeth via the cementum).
Courtesy: Department of Oral Pathology, MCODS, Mangalore

Unlike fusion and gemination, concrescence may be


post inammatory too (e.g. trauma, crowding with resorption of interdental bone, caries, etc.). In these conditions,
there is discrepancy in the number of teeth and roots, and
38

Dilaceration
It refers to a sharp bend or curve anywhere along the length
of the tooth, most commonly at the root (Figures 5355).
Literature review reveals interesting names that have
been used to describe dilaceration such as scorpion tooth
(Moreau, 1985) and hand of a traffic policeman (Stewart,
1978).

Chapter 2 Developmental Disturbances

Figure 53

Figure 55

Intraoral periapical radiograph reveals dilacerated root of


the mandibular third molar. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

Dilacerated roots of a molar. Courtesy: Department of


Oral Pathology, MCODS, Mangalore

Figure 54

Dilacerated root of a premolar. Courtesy: Department of


Oral Pathology, MCODS, Mangalore

Factors which affect the normal development of the


tooth, including trauma, cyst, tumor, etc., can cause this condition. Dilaceration most commonly affects the anteriors
and the teeth may be non-vital. Dilaceration of deciduous

teeth can cause delayed eruption of permanent teeth, and


may require extraction.
Malcic et al (2006) assessed the prevalence of dilaceration in Caucasian patients. Nine hundred and fty-three
periapical intraoral radiographs and 488 panoramic radiographs were evaluated. The results of the study showed
that dilacerations were found more commonly in the maxilla and posterior teeth were the highest affected. The
prevalence of the root dilacerations were mandibular third
molars (24.1%), maxillary rst molars (15.3%), maxillary
second molars (11.4%) and maxillary third molars (8.1%).
Hamasha et al (2002) studied the prevalence of dilaceration in Jordanian adults. 4,655 teeth from 814 dental
records were evaluated. The results of the study showed
that the mandibular third molar teeth were the most commonly affected teeth followed by the mandibular rst
molars. The maxillary anterior teeth and mandibular incisors were least affected. Almost two-thirds of the dilacerations were in the mandible and approximately 5% were in
anterior teeth.
Radiographically when the roots are dilacerated toward
the buccal or lingual directions, a round opaque area with
a dark shadow in its central region, cast by the apical foramen along with the root canal surrounded by a radiolucent
halo formed by the periodontal ligament space is typically
seen. This nding has been termed bulls eye appearance.
Extraction may be difcult and result in root fracture
on removal. Perforation of roots is a complication associated
with root canal treatment of the dilacerated teeth.

Talon Cusp
Mitchell in 1892 first described talon cusp as a prominent
accessory cusp on the lingual surface of a maxillary incisor.
39

Section II Oral and Maxillofacial Disturbances

Figure 56

Intraoral photograph showing talon cusp in relation to the


maxillary right lateral incisor. Courtesy: Department of
Oral Medicine and Radiology. MCODS, Mangalore

Talon cusp was later defined by Gorlin and Goldman as a


very high accessory cusp, which may meet the incisal edge
of the tooth to give rise to a T- or a Y-shaped configuration.
The name talon was used because this dental anomaly
resembled the claw of an eagle (Figure 56).
Talon cusp predominantly affects the permanent dentition. However there are reports of involvement of the
deciduous dentition. Almost 90% of the talon cusps occur
in the maxilla. The teeth commonly affected are the lateral
incisors, central incisors and rarely the canines. Some
authors have reported the presence of labial or facial talon
cusps and very few reports mention the presence of facial
and lingual talon cusp occurring on the same tooth. Males
and females are equally affected.
Etiopathogenesis
A polygenetic component along with various external
influences is proposed to be the cause for the formation of
the talon cusp.
It is believed that the compression of the lateral incisor
tooth germ between the central incisors and canine during
the morphodifferentiation stage will either produce infolding of the dental lamina (dens invaginatus) or an outfolding
(dens evaginatus/talon cusp).
Clinical classification of talon cusp
Hattab et al classified talon cusps as Type 1 talon, Type 2
semi talon and Type 3 trace talon. However this classification did not take into consideration the presence of the
talon cusp on the facial aspect of the tooth. Later on this
classification was modified by Stephen-Ying et al, as
major, minor and trace talon.
Type 1 (major talon): A morphologically well-delineated
additional cusp that prominently projects from the facial
40

or palatal/lingual surface of an anterior tooth and extends


at least half the distance from the cementoenamel junction
to the incisal edge.
Type 2 (minor talon): A morphologically well-dened
additional cusp that projects from the facial or palatal/
lingual surface of an anterior tooth and extends more than
one fourth, but less than half the distance from the cementoenamel junction to the incisal edge.
Type 3 (trace talon): Enlarged or prominent cingula and
their variations, which occupy less than one-fourth the
distance from the cementoenamel junction to the incisal
edge.
Talon cusp can either occur as an isolated dental
anomaly or found in association with other developmental
disturbances like supernumerary teeth, microdont and
macrodonts. Literature reveals the association of talon
cusp with Mohr syndrome (oral-facial-digital syndrome,
type II), incontinenta pigmentii achromians (Bloch
Sulzberger syndrome), RubinsteinTaybi syndrome, Ellis
van Creveld syndrome, SturgeWeber syndrome and
Alagilles syndrome.
Radiographically, the talon cusp is seen as a radiopaque
structure, in which the enamel, dentin and occasionally
the pulp can be seen. Typically the cusp resembles a
V-shaped structure superimposed over the normal image
of the crown.
The common problems associated with talon cusps are
increased susceptibility to caries, occlusal interferences and
esthetic concerns. Other associated problems are speech
disturbances, tongue irritation, accidental cuspal fracture
and periodontal problems due to excessive occlusal forces.
This accessory cusp can be removed via periodic selective
grinding, such that adequate time is allowed for deposition
of tertiary dentin and pulpal recession.

Dens Invaginatus
Dens invaginatus has also been referred to as dens in dente
and gestant odontome.
Dens invaginatus is an enamel-lined surface invagination of the crown or root. Based on the site the condition may be subdivided into coronal and radicular forms.
Cementum-lined invaginations of the root are considered
variations in the root morphology and are not a type of
invaginatus.
The coronal form is formed by the infolding of the
enamel organ into the dental papilla. The radicular form of
dens invaginatus is produced because of the invagination
of the Hertwigs epithelial root sheath.
The invagination can be of varying lengths. It may be
restricted to the coronal portion or it may extend into the
root. When it extends into the root, it may or may not communicate with the pulp. If the invagination is too extensive it gives the appearance of a tooth within a tooth (dens
in dente) (Figure 57). Some of the invaginations can get

Chapter 2 Developmental Disturbances

Figure 57

Figure 58
Coronal dens in dente

Type I

Type II

Type III

The three stages of dens in dente based on


Oehlers classification. Type I dens invaginatus,
Type II dens invaginatus, Type III dens invaginatus.
Courtesy: Dr Ravikiran Ongole

Intraoral radiograph showing dens in dente appearance.


Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

dilated, with dystrophic enamel at the base and these are


referred to as dilated odontomas. Such teeth usually show
abnormal crowns. Others may perforate the root and cause
inammatory lesions in spite of the vital pulp.
Oehlers in 1957 classied coronal dens invaginatus
into three types, depending on the depth of invagination
(Figure 58).
Type I: Invagination ends in a blind sac, limited to the
dental crown.
Type II: Invagination extends to the cementoenamel
junction, also ending in a blind sac.
Type III: Invagination extends to the interior of the root,
providing an opening to the periodontium, sometimes presenting another foramen in the apical region of the tooth.
The maxillary teeth are more commonly affected. Dens
invaginatus most commonly affects the maxillary lateral
incisor followed by the central incisors, premolars, canines
and the molars.
Radiographically dens invaginatus is evident as a looplike or pear-shaped defect lined by a radiopaque line with
density equal to that of enamel, resembling a tooth within
a tooth. In severe forms of invagination, the crown is malformed and an open apex is present.
The point of invagination is caries prone and as a preventive measure, restoration is recommended. If the tooth
is carious and the invagination is close to the pulp then
indirect pulp capping is done. However pulpally involved
invagination is best managed by endodontic treatment.

Dens Evaginatus
Dens evaginatus has also been referred to as occlusal
enamel pearl, Leongs premolar, tuberculated cusp, accessory tubercle, occlusal tuberculated premolar and evaginatus odontomas.
Dens evaginatus is a rare developmental anomaly characterized by the presence of an accessory cusp or enamel
pearl on the occlusal surface of the premolars occurring
between the cusps. The tubercle consists of enamel, dentin
and pulp. The condition occurs as a result of proliferation and
evagination of an area of the inner enamel epithelium and
the underlying dental papilla into the enamel organ during
early stages of tooth development.
It is believed that the prevalence of this condition
ranges between 1 and 4%. It occurs most commonly in the
Mongoloids, Chinese, Thai and Caucasians. The premolars
are most commonly affected followed by the molars,
canines and incisors. The mandibular teeth are ve times
more frequently affected than the maxillary teeth.
Presence of the occlusal tubercle can lead to occlusal
disharmony, attrition and tendency to fracture thereby
resulting in pulpal exposure. The involved tooth can turn
non-vital. Some authors have reported fascial space infections and osteomyelitis.
Grinding of the accessory cusp along with indirect pulp
capping is recommended. Non-vital teeth are best treated
endodontically.
Shovel-shaped incisors
Shovel-shaped incisors may be seen in association with dens
evaginatus. Marginal ridges of the incisors are prominent
41

Section II Oral and Maxillofacial Disturbances

and lingual surface is hollowed resulting in a shovel shape.


At the cingulum a deep pit or fissure or in some cases dens
invaginatus may be seen. These are caries-prone and hence
should be restored soon after eruption.

Figure 59

Taurodontism
Taurodontism originated from the Greek words tauros
meaning bull and odontos meaning tooth. Like the name
suggests the tooth resembles the tooth of a bull. The term
taurodontism was first used by Keith in 1913. He defined
taurodontism as a tendency for the body of the tooth to
enlarge at the expense of the roots. According to Witkop
taurodont teeth have pulp chambers in which the bifurcation or trifurcation is displaced apically, so that the chamber
has a greater apico-occlusal height than in cynodont teeth
and lacks a constriction at the level of the cementoenamel
junction. The distance from the bifurcation or trifurcation
of the roots to the cementoenamel junction is greater than
the occlusal-cervical distance.
In this condition the body of the tooth (usually the
molars) is enlarged and rectangular in shape at the expense
of the roots. The teeth thus resemble bulls teeth. The pulp
chamber is large, with a greater apico-occlusal height. It
also lacks the constriction at the cervix. Shaw in 1928 classied the affected tooth into three subtypes based on the
degree of apical displacement of the pulpal oor, namely
hypotaurodontism, mesotaurodontism and hypertaurodontism (Figure 59).
Taurodontism is more frequently seen in permanent
dentition compared to deciduous dentition (Figure 60). The
rst molar is the most frequently affected followed by the
second and the third molar (Figure 61). Premolars may
also be affected (Figure 62).
Taurodontism may be associated with multiple syndromes. A few of the syndrome associated with this condition have been listed in Table 5.
The condition needs no specic dental management.
However there is difculty in locating, instrumenting and
obturating pulp canals during endodontic treatment.

Shaws classification of the subtypes of taurodontism.


(A) Normal tooth. (B) Mild taurodontism (hypotaurodont).
(C) Moderate taurodontism (mesotaurodont).
(D) Severe taurodontism (hypertaurodont).
Courtesy: Dr Ravikiran Ongole

Figure 60

Orthopantomograph showing taurodontism in


deciduous dentition. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

Figure 61

Ectopic Enamel
It is a term used to describe the enamel present in unusual
locations like the root. Enamel pearls and cervical enamel
extensions are two types of ectopic enamel seen (Figure 63).

Enamel Pearl (Enameloma)


It is an ectopic mass of enamel which can occur anywhere
on the roots of teeth but is usually found at the furcation
area of roots. Maxillary molars are more frequently affected
than the mandibular molars. Premolars and incisors are
rarely affected. These radiopaque droplets may also contain
42

Intraoral periapical radiograph showing


taurodontic maxillary permanent first molar.
Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

Chapter 2 Developmental Disturbances

Figure 62

Figure 63

Types of ectopic enamel. (A) Normal cervical enamel.


(B) Extension of cervical enamel. (C) Enamel pearl in the
furcation area. Courtesy: Dr Ravikiran Ongole
Intraoral periapical radiograph showing taurodontic
mandibular permanent second premolar.
Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

Figure 64

Table 5 Taurodontism and syndrome association


Aarskog syndrome (Dayal et al, 1990)
Amelogenesis imperfecta, severe form (Pavlic et al, 2007)
Amelo onycho hypohidrotic syndrome (Herrerias et al, 1987)
Chondroectodermal dysplasia/Ellisvan Creveld syndrome
(Hunter et al, 1998)
Down syndrome (Moraes et al, 2007)
GoltzGorlin syndrome (McNamara et al, 1996)
Hypophosphatemic vitamin D rickets (Goodman et al, 1998)
Hypohidrotic ectodermal dysplasia (Glavina et al, 2001)
Klinefelters syndrome (Schulman et al, 2005)
Lowe syndrome (Tsai et al, 1997)
Microcephalic dwarfism (Sauk Jr, 1973)
Seckel syndrome (Seymen et al, 2002)

Intraoral periapical radiograph showing radiopaque


enamel pearl in the furcation area of the mandibular
first molar. Courtesy: Department of Oral Medicine
and Radiology, MCODS, Mangalore

SmithMagenis syndrome (Tomona et al, 2006)


Tricho-dento-osseous syndrome (Wright et al, 2008)
Trisomy 18 (Ribiero et al, 2006)
von Gierkes disease/glycogen storage disease type IA
(Avsar, 2007)

The complications associated with the presence of the ectopic enamel in deciduous teeth are delayed exfoliation of
the primary tooth and deviation in the eruption path of
the succedaneous tooth.

WolfHirschhorn syndrome (Johnston et al, 2006)


XXXXY syndrome (Hata et al, 2006)

small amounts of dentin and pulp (Figure 64). Removal of


the lesion may lead root caries, external resorption and pulpitis, as the pearl may contain vital pulp tissue. Hence they
are not generally treated; maintenance of good oral hygiene
is recommended. Literature review shows reports of enamel
pearls occurring in the furcation area of deciduous teeth.

Cervical Enamel Extensions


(Cervical Enamel Projections)
In this condition, enamel extends from the CEJ toward the
bifurcation of molars forming a triangular extension on
the buccal surface. Localized loss of periodontal attachment may be seen with furcation involvement. This may
lead to formation of buccal bifurcation cyst. Flattening or
removing the enamel in combination with an excisional
43

Section II Oral and Maxillofacial Disturbances

new attachment procedure and furcation plasty is done to


achieve a durable attachment.

Supernumerary Roots/Accessory Roots


This is characterized by an increase in the number of roots,
commonly in the third molars, mandibular canines and premolars (Figure 65). These supernumerary roots may occur
due to the disturbances of the Hertwigs epithelial root sheath
during root formation. During extraction it is important to
make sure that all the roots are removed. This condition
may also pose problems during endodontic procedures.

surface of the crown of the mandibular molar. The protostylid is usually seen on the rst or third permanent molars
or in deciduous lower second molars. It is seen in almost
40% of the population. The appearance can vary from a
simple pit in the buccal groove to a furrow or a prominent
cusp (Figure 69).
The Uto-Aztecan upper premolar is known to occur only
in native Americans, with its highest frequency in Arizona.
It occurs in the permanent upper rst premolar. In this
trait the buccal cusp may bulge out to the buccal aspect
with a marked fossa in its distal shoulder (Figure 70).

Figure 66

Supernumerary Cusps/Accessory Cusps


The common accessory cusps that are seen are talon cusp,
dens evaginatus, cusp of Carabelli and protostylid of lower
molars. Other rare alterations in morphology are the 6th cusp,
7th cusp, Uto-Aztecan upper premolar, deflecting wrinkle and
sinodonty. These alterations in tooth morphology are race
specific. Occasionally the accessory cusps can be located on
non-specific sites on the tooth surface (Figures 66 and 67).
The cusp of Carabelli was rst described in 1841 by Georg
Carabelli, who was a court dentist to the Austrian Emperor
Franz. It was also referred to as Carabellis tubercle and
tuberculus anomalus of Georg Carabelli.
This accessory cusp is located on the palatal aspect of
the mesiopalatal cusp of the maxillary molar. Though this
trait is commonly seen on the rst molar it may also be
seen involving the second and the third molar. Permanent
and deciduous dentitions may exhibit this trait (Figure 68).
Protostylid was rst described and extensively studied by
Dahlberg (1945). Protostylid is a feature on the mesiobuccal

Accessory cusp on the lingual surface of the mandibular molar.


Courtesy: Department of Oral Pathology, MCODS, Mangalore

Figure 67
Figure 65

Tooth specimen showing six roots in a mandibular molar.


Courtesy: Department of Oral Pathology, MCODS, Mangalore

44

Accessory cusps in relation to the buccal aspect of the


maxillary first molar. Courtesy: Department of Oral Medicine
and Radiology, KLE Societys Institute of Dental Sciences,
Bangalore

Chapter 2 Developmental Disturbances

Developmental Disturbances in Number of


Teeth
This includes total absence of teeth (anodontia), reduced
number of teeth (hypodontia and oligodontia), and increased
number of teeth (hyperdontia/supernumerary teeth).
Hypodontia and oligodontia
Hypodontia is lack of development of one or more teeth.
Oligodontia refers to lack of development of six or more
teeth. Anodontia is rare and most cases occur in the presence of ectodermal dysplasia.
Damage to dental lamina before tooth formation can
result in hypodontia. Causes of hypodontia include genetic
(autosomal dominant, recessive or sex-linked patterns),
trauma, endocrine disturbances, infection, radiation and
chemotherapeutic medications.
Hypodontia may also occur in hereditary syndromes such
as Crouzon syndrome, Downs syndrome, ectodermal dysplasia, Hurler syndrome and Turner syndrome (Figure 71).
Hypodontia is more common in females. It usually
affects permanent third molars, second premolars and lateral incisors in that order. Associated microdontia may be

observed. Hypodontia may cause abnormal spacing of teeth,


delayed tooth formation, delayed deciduous tooth exfoliation and late permanent tooth eruption. Prosthetic replacement of teeth may be needed.
Hyperdontia
Hyperdontia results from development of excess dental
lamina and additional tooth germ formation. This may
show a hereditary pattern (autosomal dominant) and may be
a part of Apert syndrome, cleidocranial dysplasia, Ehlers
Danlos syndrome, Gardner syndrome and SturgeWeber
syndrome. These teeth are referred to as supernumerary
teeth.
Supernumerary teeth are commonly unilateral. Macrodontia and male predominance are seen. Most develop during rst two decades of life. Single tooth hyperdontia is

Figure 70
Lingual

Figure 68
Mesial

Distal

Carabelli cusp
Distal

Buccal

Mesial

The location of cusp of Carabelli on the


maxillary permanent first molar.
Courtesy: Dr Ravikiran Ongole

The Uto-Aztecan feature in the maxillary first premolar.


Courtesy: Dr Ravikiran Ongole

Figure 71
Figure 69
Buccal

Mesial

Distal

Lingual

Location of protostylid on the mandibular first permanent


molar. Courtesy: Dr Ravikiran Ongole

Orthopantomograph of a patient suffering from ectodermal


dysplasia showing hypodontia. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

45

Section II Oral and Maxillofacial Disturbances

Figure 72

Double mesiodens in the maxillary incisor region.


Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

seen more in permanent dentition and approximately 90%


present in maxilla with a strong predilection for anterior
region. Most common sites are maxillary incisors, maxillary
fourth molars, mandibular fourth molars, premolars, canines
and lateral incisors in that order. Non-syndrome multiple
supernumerary teeth occur most frequently in mandible and
in premolar region. Supernumerary teeth may be seen in
gingiva, maxillary tuberosity, soft palate, maxillary sinus,
sphenomaxillary ssure, nasal cavity, and between the
orbit and brain.
Several terms have been used to describe supernumerary
teeth according to their location.
Mesiodens: Maxillary anterior incisor region (Figures 72
and 73).
Paramolar: Lingually or buccally to a molar tooth
(Figure 74).
Distomolar/distodens: Distal to third molar (Figure 75).
Supernumerary teeth may predispose the area to subacute
pericoronitis, gingivitis, periodontitis, abscess formation,
odontogenic cysts and tumors. Early removal of accessory
tooth is recommended.
Supplemental teeth are supernumerary teeth. However
they resemble the morphology of the tooth they are associated with (Figure 76).

Disturbances of Eruption of Teeth


Premature eruption
Deciduous or permanent teeth may erupt prematurely. This
may involve single tooth or the entire dentition. Prematurely erupted teeth were earlier known by various other
names such as congenital teeth, fetal teeth and dentitio
praecox.
Massler and Savara suggested the terms natal and neonatal teeth. According the new terminology deciduous
46

Figure 73

Mesiodens. Courtesy: Department of Oral Medicine and


Radiology, MCODS, Mangalore

Figure 74

A buccally placed paramolar. Courtesy: Department of


Oral Medicine and Radiology, MCODS, Mangalore

teeth found in infants at birth is called natal teeth and


those erupting within 30 days after birth called neonatal
teeth. Sponge and Feasby further subdivided these teeth
into mature or immature. It is believed that the incidence
of natal and neonatal teeth is approximately between 0.3%
and 0.5%.
These teeth generally erupt in the same position as that
of deciduous teeth in the arch. These teeth are commonly
seen in the mandibular incisor region. Based on the reports
of various authors, the site of eruption of natal and neonatal
teeth are: mandibular incisor region (85%), maxillary incisor
region (11%), mandibular canine region (3%) and maxillary
canine and molar regions (1%).

Chapter 2 Developmental Disturbances

Figure 75

Histopathological evaluation of ground sections show


hypomineralized enamel and loss of normal architecture
of the enamel rods. The normal architecture of dentinal
tubules is lost. The teeth have large pulpal chambers.
The presence of these prematurely erupted teeth in
infants can cause difculty in suckling. RigaFede disease
is a well-recognized lesion associated with natal and neonatal teeth. It is characterized by the presence of a traumatic ulcer on the lingual surface of the tongue or lingual
frenum. The ulcer is formed secondary to the trauma caused
by these teeth during suckling.
Delayed eruption

Intraoral radiograph showing a microdontic distomolar


placed paramolar. Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

Figure 76

Grossly delayed eruption of teeth may affect both deciduous


and permanent dentition and can be localized or generalized.
Local causes include retained deciduous tooth and gingival hyperplasia. Systemic causes include rickets, cretinism
and cleidocranial dysplasia. In most cases the cause may
be difficult to ascertain. One such factor may be the lack
of eruptive force. Treatment of local factors or primary
conditions would lead to eruption of the affected teeth.
Eruption sequestrum
When a molar erupts, the bone overlying the cusps is
resorbed earlier, leaving a tiny irregular spicule of bone,
or sometimes a complex odontoma in the central occlusal
fossa. This may be asymptomatic or cause slight soreness.
It appears as a tiny irregular radiopacity overlying the central occlusal fossa but separated from tooth itself. The bone
would ultimately disappear by sequestration during the
eruption. If it remains in the soft tissue it can be removed.

Supplemental teeth bilaterally on the lingual aspect of the


mandibular premolars. Courtesy: Dr Sumanth

Etiopathogenesis The etiology for the occurrence of


these teeth is still not known. Various theories have been
proposed to explain the occurrence of these teeth. Some
authors believe that excessive development during the initiation and proliferation stage will produce these teeth.
Another theory put forth suggests that there could be
hyperactivity of osteoblastic cells within the tooth germ. It
is also believed that a superficial positioning of tooth germs
during developmental period may cause premature eruption of these teeth.
Endocrine disturbances may also be an etiologic factor.
When the entire dentition is affected, hyperthyroidism
should be considered.
The prematurely erupted teeth are well-formed and normal in all respects, except that they may be somewhat
mobile.

Transposition of teeth
Peck et al described dental transposition as the positional
interchange of two adjacent teeth, or the development or
eruption of a tooth in a position normally occupied by a
non-adjacent tooth. The transposition can either be complete (crowns and the roots of the involved teeth exchange
positions in the dental arch) and incomplete (crowns are
transposed, but the roots remain in their original positions).
It is estimated that approximately 1% of the population
exhibit transposition of teeth. It can be seen in the maxillary or mandibular teeth. Transposition can either be unilateral or bilateral. The common teeth that show transposition
are canine-rst premolar in the maxilla (Figure 77) and
the mandibular canine-lateral incisor. Though literature
review reveals almost all cases of transpositions affecting
the permanent dentition, Duncan et al (1996) reported the
fusion and transposition of the maxillary right central and
lateral primary incisors.
Etiology Some authors believe that dental transposition
occurs because of interchange of developing tooth buds.
47

Section II Oral and Maxillofacial Disturbances

Figure 77

Orthopantomograph showing bilateral transposition of


caninefirst premolar in the maxillary arch.
Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

Several theories have been proposed to account for dental transposition, including the interchange of developing
tooth buds, inherited condition, altered eruption paths,
trauma and the presence of retained primary teeth. It is
also believed that root dilacerations of the adjacent teeth
may be a potential etiological factor of canine-premolar
transpositions.
Peck and Peck classied dental transpositions based on
the teeth involved as:

Maxillary canine-first premolar (Mx.C.P1)


Maxillary canine-lateral incisor (Mx.C.I2)
Maxillary canine to first molar site (Mx.C to M1)
Maxillary lateral incisor-central incisor (Mx.I2.I1)
Maxillary canine to central incisor site (Mx.C to I1)
Mandibular lateral incisor-canine (Mnd.I2.C).

Since they are asymptomatic no active management is


necessary.
Transmigration
The term transmigration is used to describe the preeruptive migration of a tooth across the midline of the jaw.
It is believed that transmigration is unique to the mandibular permanent canines. However Aras et al (2008) and
Aydin et al (2003) reported transmigration of maxillary
canines.
Various authors have proposed diagnostic criteria for
transmigration. Some believe that an impacted mandibular canine that has crossed the midline more than half of
its length should be considered as transmigrated. Others
suggest that the tendency of a canine to cross the mandibular midline is a more important consideration than the
distance of migration after crossing the midline.
Mupparapu (2002) proposed a classication system to
trace the pathway of transmigration. However, this classication system is presently being improved upon by many
authors to accommodate various patterns of transmigration.
48

Classification of transmigrated canines


Type 1: The canine is impacted mesioangularly across the
midline, labial, or lingual to the anterior teeth with
the crown portion of the tooth crossing the midline.
Type 2: The canine is horizontally impacted near the inferior border of the mandible below the apices of the
incisors.
Type 3: The canine has erupted either mesial or distal to
the opposite canine.
Type 4: The canine is horizontally impacted near the inferior border of the mandible below the apices of
either premolars or molars on the opposite side.
Type 5: The canine is positioned vertically in the midline
with the long axis of the tooth crossing the midline.
Over retained deciduous canines or missing permanent
canines in a patient can be radiographically evaluated to
assess for impacted or transmigrated teeth.

Impacted Teeth
Impaction of a tooth occurs when its eruption is impeded
by a physical barrier. Impaction of deciduous teeth is rare;
it generally involves the second molars, probably due to
ankylosis. In the permanent dentition, third molars are
impacted most frequently (mandibular commoner than
maxillary). This is followed by maxillary cuspids and
mandibular premolars. In permanent teeth, the causes for
impaction include insufficient maxillofacial development,
overlying cysts or tumors, trauma, thickened overlying
bone or soft tissue. Impacted teeth may erupt partially or
completely encased within the bone. The former may be
associated with pericoronitis and the latter may cause
resorption of roots of adjacent tooth, periodic pain or trismus; dentigerous cysts and adenomatoid odontogenic
tumors are common in these. Multiple impacted teeth may
be related to syndromes and metabolic disorders such as
cleidocranial dysostosis, Gardner syndrome, YunisVaron
syndrome, tricho-dento-osseous syndrome, GAPO [growth
retardation, alopecia, pseudoanodontia (failure of tooth
eruption) and progressive optic atrophy] syndrome and
mucopolysaccharidoses. However literature review also
shows reports of multiple impacted teeth in non-syndromic
individuals (Figure 78).
Impaction may be classied according to angulation of
tooth in relationship to the remaining dentition: mesioangular impaction (Figure 79), distoangular, vertical (Figure
80) and horizontal (Figure 81). There can be variation of
angulation in sagittal plane, the impacted third molars
may be deected buccally or lingually (Figure 82). When
the crown points toward the inferior border of mandible or
when it is completely within the ramus of mandible it is
referred to as inverted impaction (Figure 83). Occasionally
interesting patterns of impacted teeth are seen such as sleeping molars (Figure 84) and kissing molars (Figure 85).

Chapter 2 Developmental Disturbances

Figure 78

Figure 80

Orthopantomograph showing multiple impacted teeth in


a non-syndromic individual. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

Figure 79
Cropped orthopantomograph showing vertically impacted
mandibular third molar. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

Figure 81

Orthopantomograph showing mesioangularly impacted


mandibular third molars bilaterally. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

Impacted teeth are usually considered for removal when


they are symptomatic or causing resorption of adjacent and
undergoing a cystic degeneration.

Orthopantomograph showing horizontally impacted


mandibular third molars bilaterally. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

Ankylosed Deciduous Teeth (Submerged Teeth)


In this condition, there is fusion of cementum or dentin with
the alveolar bone preventing shedding of the deciduous
teeth. Proposed causes include changes in local metabolism,
trauma, infection and genetic influence. These are commonly
seen in mandibular first molars. The affected teeth lie well
below the occlusal plane; a sharp solid sound is heard on
percussion in contrast to the dull sound of the normal
teeth. Radiographically partial absence of periodontal ligament is observed. The adjacent teeth often incline toward
affected tooth, leading to occlusal and periodontal problems
(Figure 86). Supra-eruption of the opposing tooth may
also be seen. Impaction of underlying permanent tooth
may also occur. Since forceps extraction is not possible,
surgical removal is recommended.

Figure 82

Orthopantomograph showing buccoversion of an impacted


mandibular third molar. Courtesy: Department of Oral
Medicine and Radiology, MCODS, Mangalore

49

Section II Oral and Maxillofacial Disturbances

Figure 83

Developmental Disturbances in Structure of


Teeth
Developmental defects affecting the structure of
enamel
Overview of amelogenesis The development of enamel
occurs in two phases:
1.
2.

Orthopantomograph showing the crown of the third


molar directed toward the lower border of the mandible.
Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

The secretory phase


The maturation phase

In the first phase, ameloblasts secrete enamel matrix by


the secretion of enamel proteins like amelogenins and enamelins, and also aid in its immediate partial mineralization.
The second phase, the maturation of enamel takes place
by introduction of more mineral that is accommodated by
the removal of water and organic matter. The defects that
arise in the structure of enamel may be traced back to
occurring at any of these phases. Accordingly, most systems of classication of developmental defects of enamel
relied on this convenient yet simplistic view of enamel formation. The defects in enamel may thus be broadly classied
as follows:
1.

Figure 84
2.

Hypoplastic enamel, a quantitative defect of enamel


(as a result of defective/deficient enamel matrix formation), and
Hypomineralized enamel, a qualitative defect of enamel
(as a result of defective mineralization/maturation of
enamel).

The entire process of amelogenesis is influenced by a number of environmental influences and genetic mutations,
causing aberrant enamel formation. The further categorization of enamel hypoplasia is done on the basis of the
cause as follows:
Orthopantomograph showing bilateral sleeping molars.
Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

1.
2.

Hereditary enamel hypoplasia (amelogenesis imperfecta)


Environmental enamel hypoplasia.

Figure 86

Figure 85

Orthopantomograph showing kissing molars on the left side.


Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

50

Orthopantomograph showing submerged mandibular


right side first molar. The radiograph also shows adjacent
teeth tipping over the submerged tooth. Multiple impacted
teeth are also seen. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

Chapter 2 Developmental Disturbances

Genes associated with amelogenesis


Numerous genes are expressed in an orderly fashion during the various stages of the formation and maturation of
enamel. The protein products of these genes regulate gene
expression and ameloblast function. More than a thousand
genes may potentially be involved in odontogenesis with
hundreds involved in amelogenesis alone. With such a highly
regulated process orchestrated by so many genes, it is not
surprising that 2580% of the general population suffers
from enamel defects. Below are mentioned a few candidate
genes for the causation of structural defects in enamel.
AMELX: Tooth-specic gene expressed in preameloblasts, ameloblasts and in remnants of the epithelial root
sheath. Its product amelogenin forms the bulk of the protein in developing enamel and is crucial for the regulation
of the size and shape of enamel crystallites.
ENAM: Expressed predominantly by the enamel organ.
Its gene product is enamelin that may interact with amelogenin to determine the length of enamel crystallites.
KLK4: Kallikrein-4 codes for a calcium-independent
serine protease that is secreted during the maturative
phase of enamel development. Mutation of KLK-4 results
in poorly mineralized enamel.
MMP-20: A gene that codes for a calcium-dependent
proteinase that is a member of the MMP family. Its product,
enamelysin is a proteinase that cleaves amelogenin and
plays a major role in processing the enamel matrix proteins.
DLX3: A homeobox gene that is homologous to the
distal-less (Dll) gene of drosophila and is critical for craniofacial, tooth, brain, hair and neural development.
Ameloblastin (product of AMBN), Tuftelin (product of
TUFT1), Amelotin (product of AMELOTIN) and Dentin
Sialophosphoprotein (DSPP) are a few other gene products
that are involved in amelogenesis.

is the significant time when crowns of all permanent


teeth (except those of the third molars) develop. Hypoplasia of the primary teeth and the cusp tips of the
first molars would reflect ameloblast damage in utero.
Once teeth have fully calcified, they are immune to
these external factors, namely,
a. Ingestion of fluoride
b. Chemicals
c. Nutritional deficiencies
d. Exanthematous diseases/infections
e. Birth-related injuries
f. Metabolic disorders
g. Celiac disease.
Clinical features
While the appearance of the hypoplastic enamel varies
depending upon the specific etiology, mostly teeth affected
by enamel hypoplasia appear to have deficient thickness
of enamel. This may manifest as any/all of the following:
1.
2.
3.
4.

Affecting a single tooth, a group of teeth, or all of the


teeth.
Pits or grooves on the enamel surface (Figure 87).
An overall reduction in enamel thickness.
White in color and opaque (lacking the translucency
of normal enamel), later changing color after eruption
to yellowishbrown.

Local infection or trauma


Local trauma or infection (e.g. abscess formation) can
affect ameloblasts overlying a developing crown, resulting
in enamel hypoplasia or hypocalcification. The affected
permanent tooth is also known as Turners tooth and the
condition referred to as Turners hypoplasia.

Environmental Enamel Hypoplasia


Ameloblasts are sensitive to various forms of injury and
insults, either local or systemic, during the process of amelogenesis. The effect of the external factors (like metabolic and
genetic conditions) leaves a lasting impression on the formed
enamel that cannot be erased as enamel does not heal unlike
other tissues in the body. With knowledge of the chronology
of various stages in the formation of a tooth and a wellelicited history from the patient, a good clinician will be able
to trace the event that led to the hypoplasia of enamel.
The known environmental factors inuencing ameloblast
function during amelogenesis are:
1.

2.

Localized causes:
a. Local infection or trauma
b. Irradiation
Systemic causes: Systemic causes may have an effect
on permanent teeth if they occur between the time
soon after birth and before the age of 6 years, as this

Figure 87

Grooves and pitting defects in enamel hypoplasia.


Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

51

Section II Oral and Maxillofacial Disturbances

Most commonly seen to affect permanent maxillary


incisors or maxillary or mandibular premolars, as a result
of periapical infection of the deciduous predecessor or
trauma involving the deciduous tooth being forced into
the follicle of the underlying permanent tooth.
The affected tooth exhibits an irregular surface with
pits and most often has a smaller crown than normal. The
tooth may show a mild brownish discoloration.
The severity of the hypoplasia depends upon the severity of the infection and the stage of development of the
underlying permanent tooth.

Figure 88

Irradiation Radiation in the region of the developing


teeth and jaws results in discoloration of enamel besides
anodontia and microdontia.
Ingestion of fluoride The ingestion of excessive amounts
of fluoride (more than one part per million) results in a
characteristic form of enamel hypoplasia called as mottled enamel, first described by GV Black and Frederick
McKay in 1916.
Mottled enamel is mostly endemic in areas where the
drinking water contains excessive amounts of naturally
occurring uoride.
The severity of mottling however varies even in an endemic
area and may depend on the duration of exposure, timing
of exposure relative to enamel formation and the frequency
of exposure to high concentrations of uoride in water.
Mild-to-moderate uorosis manifests as occasional
white ecks or enamel spots to white opaque, lusterless
areas that cover larger areas of the crown. Enamel opacities are seen to occur symmetrically around the dental arch.
Severe uorosis manifests as pitted, irregular, brownstained teeth that may have a corroded appearance
(Figure 88).
Histologically, uorosed enamel shows a well-calcied
surface layer on subsurface areas of diffuse hypomineralization. The perichymata are accentuated.
Generally, the teeth affected by endemic uorosis are
relatively caries-resistant. The patients only concern is
likely to be esthetic.
Chemicals Certain therapeutic agents like anticancer
drugs, tetracycline, thalidomide, vitamin D as well as compounds like lead, mercury and fluorine are known to cause
enamel hypoplasia in addition to other defects like microdontia and hypodontia.
Nutritional deficiencies Rickets is the most common
known cause of enamel hypoplasia.
Generalized malnutrition and deciencies of vitamins
A, C and D are known to cause enamel hypoplasia. The
affected enamel appears pitted.
Exanthematous diseases/infections
These include measles, chicken pox, scarlet fever, CMV,
rubella, congenital syphilis, respiratory infections. The
52

Yellowish-brown intrinsic staining of teeth associated with


dental fluorosis. Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

occurrence of exanthematous diseases and nutritional


deficiencies tends to principally affect the permanent incisors, canines and first molars as they form within the first
18 months of life. Thus, the type of enamel hypoplasia
that they cause can also be termed chronological hypoplasias. The enamel appears pitted and may even show a
horizontal band of hypoplasia.
Congenital syphilis Dental abnormalities as a result of
congenital syphilis are fortunately rarely seen nowadays.
Hutchinsons incisor was the term used to denote a characteristic appearance of the anterior teeth in congenital
syphilis, where the crowns of the teeth tapered toward the
incisal edge, giving it a screw-driver appearance. The central
portion of the incisal edge was deficient as a result of
hypoplasia of the middle labial lobe of the incisor.
Mulberry molars is the term used to describe the molar
teeth affected by congenital syphilis that have smaller
than normal occlusal tables and a nodular occlusal surface
that resembles the surface of a mulberry. They have also
been referred to as Moons molars or Fourniers molars.
Birth-related injuries Hypoxia, premature birth, prolonged labor are some of the birth-related conditions that
may result in enamel hypoplasia.
It has been noted that the average width of the neonatal
line in primary tooth enamel is wider in children born after
difcult labor, and is narrower in children born through
cesarean section. (The neonatal line is a zone of hypocalcication that serves as a histologic landmark corresponding to the event of birth and denotes the transition from
intra-uterine to extra-uterine environment).
Metabolic disorders Enamel hypoplasia of varying severity is seen in general systemic conditions like hypocalcemia, hypothyroidism, maternal diabetes and toxemia of
pregnancy.

Chapter 2 Developmental Disturbances

Celiac disease A genetically influenced immune-mediated


disorder characterized by damage to the small bowel mucosa
as a result of contact with the protein gluten.
The cause of enamel defects seen in celiac disease is
not known, but it is postulated that the gluten-induced
immunological process that occurs between the age of
6 months and 7 years results in malabsorption with attendant hypocalcemia, and damage to the delicate enamel
organ. Aine has classied the specic enamel defects seen
in children with celiac disease and categorized them from
grades I to IV.

Figure 89

Amelogenesis Imperfecta
Amelogenesis imperfecta (AI) represents a group of inherited, congenital defects that primarily affect only enamel
formation and are not accompanied by morphologic or
metabolic defects in other body systems other than tooth
form or eruption.
Amelogenesis imperfecta has also been known as hereditary enamel dysplasia; hereditary brown enamel and
hereditary brown opalescent teeth.

Generalized yellowish-brown discoloration of


teeth in amelogenesis imperfecta.
Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

Figure 90

Etiology
The trait of AI can be transmitted by either an autosomal
dominant, autosomal recessive, or X-linked mode of
inheritance.
Mutations in the amelogenin gene (AMELX) and enamelin gene (ENAM) are believed to cause X-linked AI and
autosomal inherited forms of AI respectively.
Recent reports have mentioned the presence of mutations
in the KLK4, MMP-20 and DLX3 genes in the etiology
of AI.
Clinical features
The incidence varies between 1:718 (Sweden) and 1:14,000
(Michigan, USA); the data varies widely depending on the
geographical clustering of patients.
Affects both dentitions (deciduous and permanent);
sometimes only a part of the dentition may be affected.
Teeth exhibit a yellow to dark brown discoloration (Figure
89); the consistency varying from cheesy to hard. The
teeth exhibit pits and grooves and in some cases, enamel
may be entirely absent (Figure 90).
Classification
Amelogenesis imperfecta has been subjected to numerous
classifications but the one proposed by Witkop Jr (1989) is
the most popular and widely used classification to date.
It is based on the predominant clinical and radiographic
appearance of the defect and on the mode of inheritance
of the trait (Table 6).

Yellowish-brown intrinsic staining of teeth associated


with pitting defects in the enamel. Courtesy:
Department of Oral Medicine and Radiology,
MCODS, Mangalore

Revision of the concepts of inheritance/


genetics
In an autosomal recessive mode of inheritance, both parents carry a single mutated (defective) gene but are protected by the presence of a normal gene which is generally
sufficient for normal function. Two defective copies of the
gene are required to produce a disorder (i.e. both copies
of the gene in each cell are altered). Each child has a 50%
chance of being a carrier like both parents and a 25% risk
of inheriting the disorder.
In an autosomal dominant mode of inheritance, the
affected parent has a single mutated gene which dominates
53

Section II Oral and Maxillofacial Disturbances

Table 6

Amelogenesis imperfecta: classication

Type

Clinical appearance

Type I

Hypoplastic

Type IA
Type IB
Type IC
Type ID
Type IE
Type IF
Type IG

Hypoplastic, pitted
Hypoplastic, local
Hypoplastic, local
Hypoplastic, smooth
Hypoplastic, smooth
Hypoplastic, rough
Enamel agenesis

Type II

Hypomaturation

Type IIA
Type IIB
Type IIC
Type IID

Hypomaturation, pigmented
Hypomaturation
Snow-capped teeth
Snow-capped teeth

Type III

Hypocalcified

Type IIIA
Type IIIB

Hypocalcified
Hypocalcified

Type IV

Hypomaturation-hypoplastic
with taurodontism

Type IVA

Hypomaturation-hypoplastic with
taurodontism
Hypoplastic-hypomaturation with
taurodontism

Type IVB

Mode of inheritance
Autosomal dominant
Autosomal dominant
Autosomal recessive
Autosomal dominant
X-linked dominant
Autosomal dominant
Autosomal recessive

Autosomal recessive
X-linked recessive
X-linked
Autosomal dominant

Autosomal dominant
Autosomal recessive

Autosomal dominant
Autosomal dominant

its normal counterpart. Each child has a 50% risk of inheriting the faulty gene and the disorder. In other words, one
copy of the altered gene in each cell is able to cause the
disorder.
In an X-linked disorder, one normal copy of a gene on
the X chromosome is generally sufcient for normal function. Women who have a defective gene on one of their
two X chromosomes are protected by the normal copy of
the same gene on the second chromosome. This benet is
not available to men since they have one X and one Y
chromosome. Each male child of a mother who carries the
defect has a 50% risk of inheriting the faulty gene and the
disorder. Each female child has a 50% chance of being a
carrier like her mother. Males with an X-linked form of
disease are generally more severely affected than females
with similar mutations.
The Lyonization effect/Lyon hypothesis/X chromosome
inactivation Since the female has two X chromosomes,
a mechanism exists to ensure that only one of them
(even if both are normal) will remain active for functioning, and the other X chromosome gets switched-off or
inactivated.
A recessive disorder is thought to arise from a defect in
genes that code for enzymes, while a dominant disorder
results from mutation in a gene that codes for a structural
protein.
54

Other systems of classication applied to AI include:


1. Weinmann et al (1945); based on phenotype: hypoplastic and hypocalcified.
2. Darling (1956); five phenotypes based on clinical,
microradiographic and histopathological findings.
3. Witkop (1957); five types based on phenotype.
4. Schulze (1970); based on phenotype and mode of
inheritance.
5. Witkop and Rao (1971); based on phenotype and
mode of inheritance.
6. Winter and Brook (1975); based primarily on
phenotype with mode of inheritance as system for
subclassification.
7. Witkop and Sauk (1976); based on phenotype and
mode of inheritance.
8. Sundell and Koch (1985); based only on phenotype.
9. Witkop (1989); based on phenotype and mode of
inheritance; the most widely followed system of
classification of AI.
10. Aldred and Crawford (1995); based on molecular
defect, mode of inheritance, biochemical defect and
phenotype.
11. Hart et al (2002); subclassification based on the
molecular defect associated with AMELX.
12. Aldred et al (2003); based on mode of inheritance,
phenotype (clinical and radiographic), molecular
defect and biochemical result.

Type I/Hypoplastic AI
Clinical features There is a deciency of enamel matrix
with subsequent normal mineralization.
The enamel does not develop to normal thickness; at
places the enamel is so thin that crowns do not meet at
contact points. The decreased crown height leads to anterior open bite (in about 50% of cases).
Enamel matrix defects vary from pinpoint to pinhead
size pits arranged in rows or columns on labial or buccal
surfaces of permanent teeth. Sometimes pits and grooves
of hypoplastic enamel are seen in a horizontal fashion
across the middle-third of teeth.
In type IE, the carrier females have alternating bands
of normal thick and abnormal thin enamel (Lyonization
effect).
Enamel agenesis is seen in Type IG where the tooth has
a rough granular surface and has no contact with adjacent
teeth.
Radiographic features The enamel, although thin, shows
normal contrast from dentin. Square-shaped crowns.
Type II/Hypomaturation AI
Clinical features Enamel is of normal thickness but has
a mottled appearance. It is slightly softer than normal

Chapter 2 Developmental Disturbances

Figure 91

reveals a family history, presents with all teeth similarly


affected, reports a relevant medical history that resulted in
metabolic dysfunction at the time of enamel formation or
if the clinician can identify a chronological distribution to
the appearance of teeth.
Differential diagnosis

Orthopantomograph showing enamel having the same


radiodensity as that of dentin. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

enamel, and is easily penetrated by the point of a probe


and chips away from the crown.
Enamel appears clear to cloudy, mottled yellow to brown.
Enamel in Type II B has random alternating vertical bands
of either opaque white or opaque yellow enamel with
bands of translucent normal enamel.
The snow-capped teeth (Type II C) have opaque white
enamel on the incisal or occlusal thirds of the crowns of teeth.
Radiographic features The enamel has approximately the
same radio density as dentin (Figure 91).
Type III/Hypocalcified Type AI
Clinical features Enamel initially develops with normal
thickness, is orange yellow in color at the time of eruption.
It is friable and soft and consists of poorly calcied matrix
which is rapidly lost by attrition leaving cores of dentin.
The teeth are sensitive to temperature changes. Cervical
enamel is better calcied. Anterior open bite is frequently
seen.
Radiographic features Enamel is less radiopaque than dentin. Crowns have a moth-eaten appearance with a radiopaque
line representing calcied enamel in the cervical area.
Type IV This is a combination type wherein features of
the hypoplastic and hypomaturation types of AI are seen
in combination with taurodontism.
Histological features of AI Light microscopic studies of
enamel have their limitations and ground sections of teeth
affected by AI show a reduction in enamel thickness.
Ultrastructural study of enamel in hypoplastic AI shows
increased enamel porosity and changes in prism morphology and crystallite organization.
Diagnosis
Identification of AI is made primarily by clinical examination. A differential diagnosis may be made if the patient

Dentinogenesis imperfecta: Increasing attrition leads


to deposition of secondary dentin resulting in the
obliteration of the pulp chamber in AI. DI may be
excluded from the diagnosis as it exhibits bulbous
crowns, narrow roots, obliteration of pulp chambers in
the absence of attrition and normal radio density of
enamel.
Dental fluorosis: Type II C (snow-capped teeth) may be
mistaken for fluorosis but does not have the accentuated perichymata seen in fluorosis. If fluorosis is suspected, usually the premolars and second permanent
molars may be spared and the history will reveal
excessive fluoride intake.
Tricho-dento-osseous syndrome: Type IV A of AI is
differentiated from tricho-dento-osseous syndrome in
the absence of nail, hair and bone changes.
Widespread enamel defects similar to those seen in
AI may also be seen in conditions like epidermolysis
bullosa, tuberous sclerosis and oculo-dento-osseous
dysplasia.
Molar-incisor hypoplasia: This condition (also called
cheese molars) peculiarly affects the first permanent
molars and the permanent incisors, with no symmetrical affliction to strongly suggest a chronological disturbance. It has been suggested that the changes seen
are due to a combination of genetic predisposition and
environmental insult.

Management
The three principles of management of patients with AI
involve:
1.
2.
3.

Alleviation of pain and anxiety


Restoration and maintenance of the remaining dentition
with regard to esthetics
Maintenance/restoration of the occlusal vertical height.

The management of young patients with AI is preferably


done in three phases.
1.

The temporary phase, undertaken during the primary


or mixed dentition. Posterior teeth in the primary and
early mixed dentition are generally restored with stainless steel crowns, while anterior teeth in the primary
dentition may be restored with composites or polycarbonate crowns. (Since the enamel prisms in teeth
affected by AI are irregular, the affected enamel may
be pre-treated by sodium hypochlorite solution to
enhance bonding).
55

Section II Oral and Maxillofacial Disturbances

2.

3.

The transitional phase, when all permanent teeth have


erupted; this phase continues till adulthood. The anterior
teeth in adolescents may be restored using porcelain
veneers.
The permanent phase, which lasts through adulthood.
The anterior teeth may now be restored with porcelain
jacket crowns. The anterior open bite may at times
require surgical management.

The treatment of AI generally extends over many years


and requires the patients commitment to regular restorative
procedures and meticulous oral hygiene.
Frequent topical uoride applications and dietary control are needed to prevent caries. The roughened enamel
surfaces may retain plaque. The exposed dentin may be
sensitive.
Association of AI with syndromes/conditions
It is worth recalling the proposal made by Witkop (1989)
that the term amelogenesis imperfecta be limited to those
inherited, congenital defects that primarily affect only
enamel formation and are not accompanied by morphologic
or metabolic defects in other body systems other than tooth
form or eruption. Not withstanding the classification of AI
proposed by Witkop in 1989 based on this premise, there
are a number of conditions where enamel defects resembling AI do occur, but have no place in Witkops classification. Aldred et al (2003) have argued that the definition
of AI should be changed to incorporate the statement that
the enamel defects may be associated with morphologic or
biochemical changes elsewhere in the body.
The reported occurrence of autosomal recessive AI
(hypoplastic AI with delayed eruption/failure of eruption
of permanent teeth) in some cases of nephrocalcinosis
has raised the issue of AI being considered an indicator
for renal examination (ultrasound), as unrecognized and
untreated nephrocalcinosis is associated with signicant
morbidity.
Occurrences of hypoplastic/hypomineralized AI in association with cone rod dystrophy (autosomal recessive
inherited) have been reported. Most of the reported cases
are seen to have occurred in close-knit communities that
practice consanguineous relationships. The ocular symptoms include photophobia, nystagmus and reduced central
vision, with a gradual loss of night vision.
KohlschutterTonz syndrome is a CNS degenerative disease with convulsions, dementia, epilepsy, spasticity and
characteristic yellow teeth that are consistent with hypocalcied AI.
Usher syndrome is a genetically inherited disorder
characterized by progressive hearing loss and retinitis pigmentosa with progressive loss of vision. A few cases have
been reported of patients with Usher syndrome having
enamel defects (thin enamel in permanent teeth) that
resemble the hypoplastic AI.
56

Developmental Defects Affecting the


Structure of Dentin
An overview of dentinogenesis
At the late bell stage of tooth development, the cells of the
inner enamel epithelium induce the adjacent cells of the
dental papilla to differentiate into odontoblasts, which are
the cells responsible for the formation and mineralization
of the most abundant dental tissue, the dentin. The process
of dentinogenesis involves the deposition of predentin
that subsequently mineralizes to form dentin. The first
layer of predentin that is deposited acts as a signal to the
overlying inner enamel epithelial cells to differentiate into
ameloblasts and begin secreting the enamel matrix. Seventy
percent of dentin is mineralized, while the remainder is
made up of organic material and water (20% and 10% by
weight respectively). The organic component is made up by
collagen (mainly type I with small amounts of types III and
V) and non-collagenous matrix proteins (mainly dentin
phosphoprotein/phosphophoryn, dentin sialoprotein, dentin
matrix protein, osteonectin, osteocalcin, etc).
The process of dentinogenesis thus involves:
1.

2.
3.

The differentiation of odontoblasts from ectomesenchymal cells of the dental papilla following an organizing
influence of the inner enamel epithelium.
Formation of organic matrix
Mineralization of the formed matrix to the extent of
nearly 70%.

Dentinogenesis Imperfecta
Dentinogenesis imperfecta (DI) is a hereditary developmental defect of dentin formation resulting in the appearance of opalescent teeth and occurring in the absence
of any systemic disorder. It is the most common disorder
affecting the structure of dentin.
Dentinogenesis imperfecta has also been referred to as
Capdeponts teeth and hereditary opalescent dentin.
Etiopathogenesis

Hereditary (autosomal dominant trait) with variable


expressivity.
Mutations in the DSPP gene (that encodes for dentin
sialophosphoprotein, needed for normal dentin formation) mapped to chromosome 4q, resulting in abnormally soft dentin.
Mutations in the COL1A1 and COL1A2 genes that
regulate the structure of Type I collagen that is a component of several soft (skin, joint ligaments) and mineralized tissues (bone, dentin).
Classification
The original classification by Shields, Bixler and El-Kafrawy
(1973) proposed three types of DI which correlates with

Chapter 2 Developmental Disturbances

Table 7

Dentinogenesis imperfecta: classication

Classification by
Shields et al

Classification by Witkop

Gene mutation

DI type I

Dentinogenesis imperfecta

Mutation in
COL1A1 and
COL1A2 genes

DI type II

Classical hereditary opalescent


dentin

Mutation in DSPP
gene at 4q 21.3

DI type III

DI found in the Brandywine


tri-racial isolate in Maryland

Mutation in DSPP
gene

the classification given by Witkop (1979) as depicted in


Table 7.
[Subsequently, investigators were unable to satisfactorily
differentiate clinically and histologically between types II
and III when seen in adults. Many researchers now conclude that types II and III are essentially the same with the
latter being merely a variation of type II].
Shields type I was initially known as DI occurring in
association with osteogenesis imperfecta, but recently, the
term for dentinogenesis imperfecta is reserved for similar
cases seen in association with osteogenesis imperfecta. The
preferred term for only the dental defect in the absence of
systemic disease is hereditary opalescent dentin. However,
in the absence of a universal consensus and for reasons of
convenience, the terms hereditary opalescent dentin and
dentinogenesis imperfecta will be used synonymously.
Clinical features
Affects approximately 1 in 6,000 to 1 in 8,000 children,
with a predilection for occurrence in whites. Teeth exhibit
an unusual translucency and opalescence, and the color of
the affected teeth varies from yellowish brown to bluish
gray. Affected teeth have bulbous crowns with prominent
cervical constriction, and narrow roots. Deciduous teeth are
affected more severely, while the permanent second and
third molars that develop later are least affected in DI.
Enamel fractures easily or rapidly undergoes attrition
exposing the underlying dentin (this may be due to the dentinoenamel junction being straight instead of scalloped,
thus rendering it unable to withstand shearing forces).
Affected teeth are less susceptible to decay (as a result of
defective dentin providing fewer pathways for invasion of
dental caries).
Radiographic appearance
Short, blunt roots with partial or total obliteration of the
pulp chambers and root canals. Crowns of teeth appear
bulbous with cervical constriction (Figures 9294).
Shell teeth are a rare radiographic variant of DI rst
seen in the Brandywine tri-racial isolate in Maryland, USA.

Figure 92

Orthopantomograph showing bulbous crowns, short and


blunt roots Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

Figure 93

Intraoral periapical radiograph showing short and


blunt roots of maxillary posterior teeth. Courtesy:
Department of Oral Medicine and Radiology,
MCODS, Mangalore

Shell teeth are so called because they appear like thin shells
of dentin covering large pulps. The enamel may be of normal thickness. The deciency in thickness of dentin is due
to insufcient or defective dentin formation and it may
extend to involve even the crown.
Histological features
Other than a thin layer of mantle dentin, the rest of the dentin has fewer tubules, which are wide and irregular. Areas of
atubular dentin are also seen partly or totally obliterating
the pulp chamber and root canals. The dentinoenamel
junction is smooth instead of being scalloped. Vascular
inclusions are sometimes seen in the dentin (probably remnants of pulp tissue). Biochemical analysis of dentin shows
increased water content and a decreased mineral content
when compared to normal dentin. Following the loss of
enamel, the defective dentin rapidly wears away because
of the low micro hardness.
57

Section II Oral and Maxillofacial Disturbances

Figure 94

A defect in Hertwigs epithelial root sheath causes it to


fragment and these fragments get incorporated into the
dental papilla where they induce the formation of globules
of dysplastic dentin.
Clinical features
Type I/radicular dentin dysplasia The crowns of affected
teeth in both dentitions are normal in shape, size and
color. Premature exfoliation of erupted affected teeth (due
to their short roots). Affected teeth may be more resistant
to dental caries. Pattern of tooth eruption is normal.

Intraoral periapical radiograph of mandibular posterior


teeth showing bulbous crowns, short and blunt roots
with total obliteration of the pulp chambers and root canals.
Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

Management
The rapid loss of enamel and wearing away of dentin has
to be compensated in order to maintain vertical dimension
for function. However, like many other structural defects
in teeth, it is increasingly difficult to retain the affected
teeth. The risk of pulp exposure is high in such teeth, and the
cervical constriction renders it liable to cervical fracture
when teeth are covered by crowns or used as abutments.

Dentin Dysplasia
The term dentin dysplasia was given by Rushton to
describe a rare hereditary condition affecting dentin formation that was first described by Ballschmiede in 1920 as
rootless teeth. The enamel is normal, while the dentin is
atypical and there is abnormal pulpal morphology. It has
also been referred to as rootless teeth.
Dentin dysplasia is of two types; Type I/radicular dentin dysplasia (rootless teeth) is so called because the
crowns of the primary and permanent teeth seem normal
while the roots appear short/stunted. Type II/coronal dentin
dysplasia shows a defect in the crowns of primary teeth,
but the lengths of the roots seem normal.
Etiopathogenesis
Hereditary (autosomal dominant trait).
Mutations in the DSPP gene (that encodes for dentin
sialophosphoprotein) may be responsible for some cases of
type II dentin dysplasia. (This is similar to the mutation
seen in DI type II).
58

Type II/coronal dentin dysplasia Rarer than Type I. The


crowns of affected teeth in the primary dentition appear
opalescent yellow, brown or bluish, whereas the permanent teeth appear normal in color. Periapical lesions are
infrequent when compared to Type I.
Radiographic appearance
Type I/radicular dentin dysplasia The roots are extremely
short, blunt and tapering or may be absent in both
dentitions.
Primary teeth show total pulp obliteration, while the permanent teeth show pre-eruptive pulpal obliteration resulting
in crescent-shaped pulpal remnants (chevrons of pulp)
parallel to the cementoenamel junction.
Periapical radiolucencies (representing chronic granulomas, cysts or abscesses. These lesions may have developed as a result of microscopic communication between
the residual pulp and the oral cavity in the absence of
clinically apparent dental caries) may be associated with
teeth that appear to be vital.
Type II/coronal dentin dysplasia Root length is normal
in both dentitions.
The primary teeth show obliteration of pulp chambers.
Permanent teeth exhibit enlarged pulp chambers (thistletube shape in anterior teeth and premolars or ame-shaped
in molars) with multiple foci of radiopacity/pulp stones.
Histological features
Type I/radicular dentin dysplasia Enamel, mantle dentin
and most of the coronal dentin appear normal.
Deeper layers of dentin and all of the root dentin are
dysplastic and shows atypical, amorphous, tubular patterns. Numerous calcied, spherical bodies (denticles?) disrupt the tubular course of dentin formation with the result
that dentinal tubules are displaced giving rise to the classic
lava owing around boulders/water streaming around
boulders/cascading waterfall appearance.
Type II/coronal dentin dysplasia The primary teeth show
altered dentin, resembling the changes seen in DI.
The permanent teeth have normal enamel and coronal
dentin, while the roots exhibit atubular, amorphous dentin

Chapter 2 Developmental Disturbances

and large areas of interglobular dentin. (The atypical


dentin seen in coronal dentin dysplasia has a large amount
of Type III collagen).
Differential diagnosis
Teeth affected by DI may resemble those of dentin dysplasia. The differentiating features include:
Dentin dysplasia

Dentinogenesis
imperfecta

Color

Yellow to brown to
bluish

Yellow to brown to
bluish

Crown morphology

Normal, shape and


size of crown

Bulbous crown with


cervical constriction

Obliteration of pulp
chamber

Occurs 56 years
after eruption of the
tooth (type II)

Occurs before tooth


eruption

Thistle tube-shaped
pulp chamber

Mostly present

Absent

Root morphology

Normal appearing
roots (type II)
No roots (type I)

Short, narrow roots

Management
Meticulous maintenance of oral hygiene is the key to prolonged retention of teeth affected by dentin dysplasia,
although the presence of short roots and periapical lesions
may make it seem a daunting task for the dentist. Endodontic
and periodontal treatment is accomplished reasonably well
in teeth affected by coronal dentin dysplasia.

Making Sense of It All! Is it DGI? Or is it DD?


Or are they all the same?
This is no doubt puzzling as for more than 30 years, the
two entities were classied using clinical, radiographic,
and histopathologic features. This nosology seemed to
suit everyone ne, even though Shields et al (1973) made
a mention that the heritable dentin defects can be
viewed as a continuum. Recent research has focused on
the genetic mutations that underlie these non-syndromic
heritable defects of dentin. Mutations in the DSPP gene
(dentin sialophosphoprotein gene) cause varied defects
in dentin and the defects are seen to correlate with the
severity of the mutation. Accordingly, a new concept is
emerging of referring to DI and dentin dysplasia as
DSPP-associated dentin defects. Beattie et al (2006) recommend the setting-up of a gene-based classication
system that would group all of the DD-II, DGI-II, and
DGI-III cases that are associated with DSPP defects into
a single category, and then make distinctions based upon
severity. According to the same designations as are currently in use, the DD-II phenotype would be the least

severe, DGI-II intermediate, and the DGI-III phenotype


the most severe form of the disease. While not studied in
as much depth and interest as the DSPP, the DMP1 (dentin matrix acid phosphoprotein gene) is another candidate gene for these dentin defects. DI type I is the dental
phenotype associated with osteogenesis imperfecta and
people with this disorder may best be categorized as having osteogenesis imperfecta with DI.

Regional Odontodysplasia
Regional odontodysplasia is a rare, localized, developmental disorder of dental origin with affected teeth having
characteristic clinical and radiographic appearances. This
condition has been described under various names by different authors, but Zegarelli (1963) is credited with coining the term odontodysplasia to describe a peculiar dental
anomaly of unknown cause. Later, Pindborg (1970) preferred the term regional odontodysplasia to describe the
segmental and localized nature of this condition.
Regional odontodysplasia has also been termed as ghost
teeth, odontogenesis imperfecta, odontogenic dysplasia, unilateral dental malformation, AI non-hereditaria segmentalis
and localized hypoplasia (Turner teeth).
The term regional odontodysplasia best describes the
segmental and localized nature of this condition that is of
unknown etiology and affects enamel, dentin and pulp.
Etiology
The cause of this rare dental developmental disorder is not
precisely known, but a few theories have been proposed.
1.

2.

3.

A somatic mutation in early tooth development (probably in the developing dental lamina) that disrupts
odontogenesis. This may explain the involvement of
both deciduous and permanent dentitions.
A disturbance in vascular supply that creates local
ischemia, thereby affecting odontogenesis. Many cases
of odontodyplasia have been reported to be associated
with hemangiomas or vascular nevi adjacent to the
affected teeth. (Some researchers have even proposed
that the irregularities in the dental hard tissues are a
result of the blood overflow from vessels that affects
the local concentration of magnesium and sodium
around the crystals).
Activation of a latent viral infection of the tooth germ
during odontogenesis.

Other theories that have been proposed but are unsatisfactory to explain the occurrence of ghost teeth are a hereditary basis, medications taken during pregnancy, irradiation,
and failure of migration of neural crest cells, systemic
disorders, Rh incompatibility, nutritional and metabolic
disorders.
59

Section II Oral and Maxillofacial Disturbances

Clinical features
Age at presentation is variable (423 years); the condition
is often diagnosed at the time of eruption of primary and
permanent teeth. Affects both primary and permanent
dentitions.
Generally, the disturbance is localized to one arch, most
often the maxillary left quadrant (incisors and canines).
Females are affected more often than males (1.7:1); there
is no racial predilection observed.
Pulp or periapical pathology may be associated with
the affected teeth even in the absence of gross dental caries (the pathogens may gain access to the pulp through the
clefts in the defective enamel and dentin). Patient may
present with delayed/incomplete eruption of teeth and
unesthetic appearance of affected teeth.
Affected teeth appear hypoplastic and small, discolored
yellow to brown with the enamel surface having shallow
furrows to severe pits and grooves. The gingiva surrounding the affected teeth may be enlarged.

Figure 95

Orthopantomograph showing irregularly shaped


teeth with incomplete root formation in regional
odontodysplasia. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

Differential diagnosis

Radiographic appearance
The affected teeth have a ghost-like appearance because
of a decreased radiopacity and lack of distinction between
the enamel and dentin.
The teeth have an irregular shape with hypoplastic
crowns. Affected teeth have reduced thickness of dentin with
large pulp chambers, presence of pulp calcications, incomplete root formation and wide open apices (Figure 95).
Unerupted teeth may be surrounded by a pericoronal
radiolucency (representing an enlarged follicle) with abnormal foci of calcication interspersed. The trabeculae of the
alveolar bone adjacent to the affected teeth may show rarefaction. Periapical abscesses may be seen in relation to
the affected teeth.
Histological features
Undecalcified ground sections of the affected tooth have
thin, pitted enamel with disorganized/altered prismatic
structure. The dentin is thinner than normal, and contains
large areas of interglobular dentin, containing clefts that
may communicate with the pulp. Areas of amorphous dentin and cellular dentin may also be seen with occasional
capillaries. The dentin has fewer tubules than normal.
The predentin zone is very wide. The pulp chambers are
enlarged and contain pulp stones. Dental follicles are often
enlarged and contain epithelial rests and calcications.
Scanning electron microscopy reveals thin enamel with
irregular enamel prisms and irregular crystalline aggregates.

60

Regional odontodysplasia
(RO)

Dentinogenesis
imperfecta

Hereditary basis

Absent

Present

Enamel hypoplasia

Present

Absent

Involvement of
teeth

Isolated segment of the


arch in either dentition/
few teeth involved

All primary teeth


involved

The teeth affected by RO may also be mistaken for odontomes or as being involved by dental caries.
Management
Depending upon the vitality of the pulp, pulpotomy or
apexification may be performed to stimulate root formation. Affected primary teeth may be treated by pulpotomy
and restored with steel crowns.
However, most dentists prefer to extract the affected
teeth for esthetic reasons and rehabilitate the patient with
prosthesis. This seems a safer option as the longer the
affected teeth are retained; the higher is the risk of development of pathology. However, the clinician must weigh
the choice against the psychological effects of a youngster
having to remove teeth with a resultant decrease in alveolar bone height, potentially decreasing the ability to optimally restore/rehabilitate the affected area. The possibility
of the future use of implants may be discussed with the
patient.

CHAPTER

Orofacial Pigmentation
Disorders
Ajit Auluck, Manuel Thomas

Pigmented Lesions of Oral Mucosa

Molecular and Pathologic Correlation of Pigmentation


Metal Pigmentation
Diffuse and Multiple Pigmented Lesions
Focal/Localized Pigmented Lesions

PIGMENTED LESIONS OF ORAL MUCOSA


Oral mucosa can have a variety of discolorations like blue,
black, brown or yellow because of endogenous pigments
or exogenous materials. Recognition and diagnosis of pigmented lesions of the oral mucosa is an important aspect
of clinical dental practice because it may be suggestive of an
underlying systemic or metabolic disorder, or it can be an
initial stage of malignancy. Therefore, dentists must determine the cause of pigmentation, ask relevant questions in
the history to determine the cause and request appropriate
investigations for early diagnosis and prompt treatment.

Molecular and Pathologic Correlation of


Pigmentation
A pigment is any organic or inorganic coloring substance.
A pigmented lesion can be defined as an area of altered coloration of the oral mucosa either because of physiologic or
pathologic process because of deposition of endogenous or
exogenous pigments or embedded foreign material in the
tissues.
Exogenous substances cause oral mucosal pigmentation
because these substances are embedded in the oral tissues
either by direct trauma or iatrogenic implantation, amalgam
being the most common. Cavity preparation of a tooth with
an existing restoration (secondary caries) by a rotary bur can
forcefully entrap some ne amalgam particles into the oral
tissues. Amalgam can also enter oral tissues while removing
old or fractured restorations. It can also accidentally enter
into an extraction socket during extraction of a restored

Pigmentation of Teeth
Extrinsic Discoloration
Intrinsic Discoloration

tooth. Amalgam particles can be left behind in the oral tissues


after root canal treatment or retrograde amalgam lling. The
silver particles from the embedded amalgam restorations
slowly leach out and stain reticulum bers causing gray/
black discoloration of mucosa which is called as amalgam
tattoo.
Lead pencils contain graphite which is another source of
exogenous pigmentation which usually occurs in the palate.
Rarely when the graphite fragment gets embedded in the
palatal tissues following trauma, the mucosa covering this
fractured fragment gets discolored and appears as a bluish
black focal pigmented area.
In heavy metal poisoning also we can observe oral
mucosal pigmentation because of formation of metal suldes which get precipitated in inamed areas of gingiva
causing bluish black discoloration. Table 1 summarizes the
type of exogenous substances that can cause oral mucosal
pigmentation.
Oral mucosal pigmentation can also occur due to variety
of endogenous pigments. Each of these endogenous pigments
can result in a distinct oral discoloration suggestive of various disease processes which are described in Table 2. Blue,
bluish red and purple type of oral pigmentation generally
occur as a consequence of blood or vascular disorders. Black,
brown or gray discoloration of the oral mucosa is because
of melanin or hemosiderin pigments. Yellow discoloration
of oral mucosa is because of bilirubin deposition or ingestion of large amount of beta-carotene. The pigmented
lesions can either be localized or diffuse depending upon
their etiology or disease process which they manifest.
Blood pigments can cause red, bluish red or brown pigmentation of oral mucosa. These pigments are deposited into

61

Section II Oral and Maxillofacial Disturbances

the connective tissues after lysis of erythrocytes causing


extravasation of hemoglobin. The extravasation of blood
into soft tissues is attributed to trauma, capillary fragility,
platelet defects, or clotting disorders. This extravasated
hemoglobin is acted upon by the enzymes to form hemosiderin, which is further broken down into bilirubin and
biliverdin, all of which cause oral pigmentation. Therefore,
the same endogenous pigments may result in different
types of oral pigmentations over a period of time. An early
hematoma is bluish red in color while a late hematoma
becomes dark brown in color. Blood pigments are usually
cleared from the skin or mucosa within 2 weeks.
Melanin causes blue or blue black discoloration of oral
mucosa. Melanin is produced from an amino acid tyrosine
by the melanocytes within the membrane-bound organelles called as melanosomes. These melanocytes are found
in the basal layers of the oral epithelium. Melanin is also
produced by the nevus cells, which originate from the neural crest cells and are found in the skin and mucosa. Color
of pigmented lesions caused by melanin deposition may
be brown, blue, gray or black, depending on the amount of
melanin produced as well as on the location of melanin
within the tissues.
Oral lesions can occur either due to excessive production
of melanin pigment or due to proliferation of melanocytes.
Sometimes there is no increase in the number of melanocytes but there is only an increase in the synthesis or production of melanin pigment. Over a period of time the

Table 1

Type of exogenous foreign materials causing pigmentation of oral mucosa

Source

Color

Etiology

Silver, amalgam

Gray, black

Iatrogenic implantation,
trauma

Graphite

Gray, black

Tattoo, trauma

Lead, mercury,
bismuth

Gray

Ingestion of paints,
medicines, poisoning

Chromogenic
bacteria

Black, brown,
green

Superficial colonization

capacity of cells to store melanin pigment is exceeded and


then melanin spills into the underlying connective tissues
into the adjacent basilar keratinocytes. This process is called
as basilar melanosis and melanin incontinence.
In the oral cavity we can observe melanosis over the healed
areas which had an earlier injury. When the traumatized
oral epithelium regenerates, usually there is overproduction
of melanin by the melanocytes that repopulate this region
causing post inammatory pigmentation.
Certain hormones and drugs can also inuence production of melanin. The adrenal corticalhypothalamic axis is
affected by hypofunction of the adrenal cortex. As serum
corticosteroid levels decreases, adrenocorticotropic hormone
(ACTH) production by the posterior pituitary increases. ACTH
also has a melanocyte stimulatory function so melanin
production increases and it causes diffuse melanosis of the
oral tissues. Therefore oral mucosal pigmentation can also
occur in endocrine disorders. Certain drugs like minocycline can also increase the production of melanin within
the cells causing diffuse pigmentation of oral mucosa and
is called as drug-induced melanosis.
Oral pigmented lesions can also occur due to the proliferation of melanocytes as observed in the cases of nevi and
melanoma. Melanocytic nevi develop during childhood and
rarely arise in adult life. Most nevi originate from the melanocytes in the basal layer of epithelium and proliferate along
the junction with the connective tissue. These are called as
junctional nevi. Later these melanocytes drop off into the
connective tissue to form islands of cells and are called as
compound nevi. Later all these cells are completely
detached from basal epithelium and form clusters in the
dermis or submucosa and are called as intradermal nevi.
Rarely do we observe blue nevi in oral cavity and they are
comprised of spindle-shaped melanocytes which synthesize copious amounts of melanin pigment.
Occasionally, bluish discoloration of oral mucosa can be
due to optical phenomenon as a consequence of accumulation of uid within the epithelial layers. For example a ranula appears blue in color because the mucous absorbs most
of the visible wavelength except blue.
In albinism the gene for tyrosinase is mutated. In vitiligo,
depigmented patches are caused by diminished number of

Table 2 Type of endogenous pigments, the discoloration caused by them and disease process they indicate

62

Pigment

Color

Disease process

Hemoglobin

Blue, red, purple

Varix, hemangioma, Kaposi sarcoma, angiosarcoma, hereditary hemorrhagic telangiectasia

Hemosiderin

Brown

Ecchymosis, petechiae, thrombosed vein, hemorrhagic mucocele, hemochromatosis

Melanin

Brown/black/gray

Melanotic macule, nevus, melanoma, hormonal imbalance, drugs

Bilirubin

Yellow

Jaundice/liver disorder

Carotene

Yellow

Precursor of vitamin A

Chapter 3 Orofacial Pigmentation Disorders

melanocytes. However, these entities are rarely seen in the


oral cavity.

Metal Pigmentation
Pigmentation of the oral cavity caused by foreign materials or metals is called exogenous pigmentation. The importance of recognizing oral mucosal pigmentation caused by
heavy metals lies primarily in the identification and treatment of the cause to avoid severe systemic toxic effects.
Depending on the type of metal implicated, a number of
systemic signs and symptoms may be associated with
chronic exposure of metals.
Amalgam tattoo
Amalgam tattoo is the most common solitary focal pigmentation lesion of the oral mucosa. These lesions are generally less than 1 cm (rarely amalgam tattoos can be large)
and appear as flat, gray-black to blue-black color macules.
They are usually found in close approximation to a restoration. Majority of the lesions are located on the buccal
mucosa, gingiva and alveolar mucosa with mandibular
region being more affected as compared to the maxillary
region (Figure 1). All these lesions are asymptomatic and
are discovered during routine dental examination. If particles are large enough they can be viewed with help of a
radiograph (taken with reduced exposure parameters for soft
tissues). The amalgam granules and fragments are found
mainly in the lamina propria but were sometimes also seen

Figure 1

in the submucosa. Histopathologically, we may observe a


giant cell reaction surrounding these amalgam particles.
Mercury poisoning
Mercury poisoning can be because of acute or chronic
exposure of mercury vapors. Clinical features include gastric disturbances, diarrhea, excitability, headache and mental depression. Patients complain of gastric disturbances,
diarrhea, excitability, headaches and mental depression.
Patient may have tremors of lips and extremities, dermatitis and nephritis.
Oral manifestations include increased salivation (ptyalism) as mercury is excreted in saliva. Tongue may be
enlarged and painful (glossodynia). There may be hyperemia
and swelling of gingiva, ulcerative stomatitis, loosening and
exfoliation of teeth.
Acrodynia (Swift disease, Pink disease) is idiosyncratic
reaction to large doses of amalgam. It is an uncommon
mercurial toxicity reaction in which skin is also involved.
It usually occurs after ingestion of mercury from powder,
ammoniated mercury ointment, calomel lotion. It is mainly
seen in the children below the age of 56 years. Manifestations are widespread involving the hand, feet, nose and
cheeks which become red or pink in color, cold and
clammy like a raw beef. Skin may have maculopapular
rashes with pruritis. Patients may complain of irritability,
photophobia and muscular weakness. Children may be
able to remove their hair in patches.
Oral manifestations include profuse salivation, gingiva
is painful and ulcerated, teeth may become loose and exfoliate and bruxism is a common nding.
Arsenic
Arsenic in both organic and inorganic forms may produce
acute or chronic symptoms. Oral manifestations may include
increased salivation, gingivitis, and oral ulcerations. Exposure produces severe edema of the eyelids, gastrointestinal
irritation, and both central and peripheral neuropathies.
Arsenic levels can be assessed by complete blood
count, urine analysis and hair and nger nail clippings.
The condition can be managed by removing the offending
agent followed by gastric lavage and chelation therapy
with d-penicillamine.
Bismuth

Amalgam tattoo on the left buccal mucosa in close vicinity


to the restoration. The lesion also shows faint white
keratotic striae indicative of a lichenoid reaction.
Courtesy: Dr Ajit Auluck

Bismuth is used in treatment of syphilis and dermatological


disorders. Patients usually have systemic complaints and it
is characterized by bismuth grip, muscular cramps in the
abdomen.
Orally, we usually see bismuth line which is a bluish
black line in marginal gingiva conned to gingival papilla.
Bismuth may react with hydrogen sulde produced by

63

Section II Oral and Maxillofacial Disturbances

the bacteria to form bismuth sulde that gets precipitated


around periphery of an ulcer or erupting molar. Patient
may also complain of burning sensation and metallic taste
in the mouth.

Figure 2

Lead
Lead (plumbism) is an occupational hazard seen in plumbers due to acute or chronic exposure because of inhalation
of lead vapors or dust. It is also seen among the children who
chew wood painted with lead.
Clinical features include gastrointestinal symptoms like
nausea, vomiting and constipation. Patients may have encephalitis or peripheral neuritis characterized by wrist drop or foot
drop. Patients may have hypochromic anemia with basophilic stippling in red blood cells.
Oral manifestations include linear bluish black discoloration seen in the gingival margin called Burtonian line.
Gingivitis, ulcerative stomatitis, excessive salivation, metallic taste, or rarely bismuth may get deposited in the deciduous teeth too.

Grayish black pigmentation of the oral mucosa characteristic


of physiologic pigmentation. Courtesy: Department of Oral
Medicine and Radiology, MCODS, Mangalore

Silver
Argyria (silver poisoning) is caused due to chronic exposure
due to occupational hazard by silver nitrate. It can result
in pigmentation of both the skin as well as the mucous
membrane. Exposure to silver causes a violet marginal line,
often is accompanied by a diffuse bluish-gray discoloration
throughout the oral mucosa. It can also be associated with
neurologic and hearing damage. Histologically we can
observe silver particles staining the reticular fibers.

Diffuse and Multiple Pigmented Lesions


Racial/physiologic pigmentation
Physiologic pigmentation of the oral tissues is clinically
manifested as multifocal or diffuse melanin pigmentation
with variable prevalence in different ethnic groups. Gingiva
appears darker in color among Africans, Asians, Caucasians
and Hispanics and other dark skinned people. The variability in the color of the oral tissues is not due to the difference in the number of melanocytes is same but this color
difference is due to the difference in the activity of the
melanocytes. In dark skinned people melanocytes are
more active as compared to the fair skinned people.
Physiologic pigmentation is seen as diffuse macular pigmentations that may be brown, gray or black in color and
can appear anywhere in the mouth with buccal surface and
gingiva being most commonly involved. On the gingiva it
appears as well-demarcated, ribbon-like, dark brown continuous band that does not extend to involve the marginal
gingiva. Occasionally pigmentation may also be seen on the
tongue, lips and lingual gingiva as diffuse brown patches with
ill-dened or diffuse borders (Figure 2).
64

Racial pigmentation mainly occurs in the childhood.


However during early years it may not attract patients
attention and may be observed after puberty. Racial pigmentation is asymptomatic and does not require any
treatment.
Drug-induced pigmentation
Many medications when taken over a long period of time can
cause oral mucosal pigmentation. Drug-induced pigmentation can be due to increased synthesis and accumulation of
melanin pigments, deposition of the drug or its metabolites
into the oral tissues or deposition of iron after damage to
the dermal vessels (Table 3).
Chloroquine and other quinine derivatives which are
usually used in the treatment of malaria and cardiac arrhythmia can cause pigmentation of oral tissues due to a direct
stimulating effect on the melanocytes (Figure 3). According
to some of the studies these drugs usually cause pigmentation of the palatal tissues.
Minocycline is another drug causing pigmentation of
oral tissues. It is a synthetic tetracycline that is commonly
used in the treatment of acne vulgaris. Tetracycline causes
pigmentation of only the bones and teeth but minocycline
can also cause pigmentation of soft tissues. It usually causes
diffuse brownish discoloration of the hard palate, gingiva,
mucous membranes and tongue.
Oral pigmentation can also be due to intake of birth control pills. Chloasma is the term which is used to describe
perioral and periorbital pigmentation in such patients
(Figure 4). The pigmentation usually occurs as a diffuse
brown macular pigmentation which is asymptomatic and
lesions resolve upon cessation of drug intake. These lesions

Chapter 3 Orofacial Pigmentation Disorders

Table 3 List of drugs that can induce oral pigmentation

Figure 4

Bleomycin
Busulphan
Clofazimine
Chloroquine
Chlorpromazine
Cyclophosphamide
Doxorubicin
Estrogen
5-Fluorouracil
Gold
Hydroxychloroquine
Ketoconazole
Minocycline
Tetracycline
Quinacrine hydrochloride

Perioral and periorbital pigmentation. Courtesy: Department


of Oral Medicine and Radiology, KLE Societys Institute of
Dental Sciences, Bangalore

Zidovudine

Figure 5
Figure 3

Smokers melanosis of the buccal mucosa associated with


leukoplakia. Courtesy: Dr Ajit Auluck
Brownish-black pigmentation of the lips and buccal mucosa
caused by chloroquine. Courtesy: Dr Ajit Auluck

usually occur due to the hormonal changes which inuence melanocyte stimulation.
Smokers melanosis
Tobacco smokers have more intense pigmentation of oral
mucosa as compared to non-smokers. Smokers melanosis
is more common in females. Women are more commonly
affected than men because of synergistic effect between
the female sex hormones and smoking. Smoking may
cause oral pigmentation in light-skinned individuals and

accentuate the pigmentation in dark-skinned patients.


Clinically, there may be multiple diffuse brown pigmented
macules of less than 1 cm in diameter. These lesions can
occur anywhere in the mouth but may be usually localized
on the attached labial anterior gingiva and the interdental
papillae of the mandible. These lesions are completely
asymptomatic and benign in nature (Figure 5).
Microscopically there is evidence of basilar melanosis
but there is no melanocyte proliferation. The increased
melanin production may be a biologic defense mechanism
against the noxious agents present in the tobacco smoke.
The intensity of the oral pigmentation is directly related to
the duration and amount of smoking. Smokers melanosis
65

Section II Oral and Maxillofacial Disturbances

Figure 6

Figure 7

Diffuse pigmentation of palate in a patient with Addisons


disease. Courtesy: Dr Ajit Auluck
Perioral pigmentation of the lip in PeutzJeghers syndrome.
Courtesy: Dr Ajit Auluck

usually disappears within 3 years of smoking cessation.


Biopsy must be advised whenever there is a surface elevation or increase in the pigment intensity or rapid increase
in the size of the lesion.
Endocrine disorders
Adrenal cortical insufficiency can occur secondary to
pathologic processes such as neoplasms that may cause
damage to the adrenal glands. Due to the deficiency of the
adrenocortical hormones in the blood there is an increased
production of ACTH by the anterior pituitary gland. But
ACTH stimulates the production of melanocyte-stimulating
hormone which results in diffuse pigmentation of all the
tissues. As a consequence the skin darkens and becomes
bronzed. Also multifocal diffuse pigmentations appear in
the mucous membranes of the oral cavity, conjunctiva, and
genital regions.
In the oral cavity pigmentation may appear as diffuse
brown patches on the gingiva, buccal mucosa, palate and
tongue (Figure 6). This may resemble physiologic pigmentation. Physiologic pigmentation can be differentiated from
pigmentation caused by Addisons disease as the later
develops and progresses during adult life and not present
since birth. It is also accompanied by systemic manifestations like weakness, nausea and vomiting, abdominal
pain, constipation or diarrhea, weight loss and hypotension.
Oral pigmentation may be the rst sign of Addisons disease. Therefore complete examination must be done for
patients with diffuse pigmentation of oral cavity and associated with systemic signs and symptoms. Patients presenting
with such features should be sent for medical evaluation
and laboratory tests to assess levels of ACTH, plasma cortisol and serum electrolytes.
A biopsy of these oral lesions shows acanthosis with silverpositive granules in the cells of the stratum germinativum.
66

Melanin pigment can be seen in the basal layer of the epithelium. Management involves treatment of the underlying cause and corticosteroid replacement therapy.
A tumor of the posterior pituitary or certain small cell
carcinomas can also secrete excessive amounts of ACTH
which can cause pigmentation of oral tissues. In ACTH
secreting tumors (paraneoplastic syndromes) the patient
manifests features of the Cushings syndrome. In both these
conditions there occurs diffuse pigmentation of oral tissues
along with associated systemic features.
Caf au lait pigmentation
It manifests as bronze or tan diffuse multifocal macular
pigmentations that appear on the skin as well as the oral
mucosa. These pale brown macules may vary considerably
in size. They have widespread distribution and can occur on
the face, neck or the oral cavity. Because of the pale brown
color these lesions are called as caf au lait spots. It is usually associated with neurofibromatosis (von Recklinghausens
syndrome), Albrights syndrome (polyostotic fibrous dysplasia) and PeutzJeghers syndrome.
Caf au lait pigmentations in neurobromatosis have
smooth borders and are associated with axillary freckling.
It is an autosomal dominant inherited disease with multiple skin nodules.
In PeutzJeghers syndrome patients have intestinal polyposis along with oral macular pigmentations that appear
around the mouth (Figure 7) and on the ngers. When
such lesions are observed, a detailed history of the patient
should be taken about gastrointestinal complaints as well
as the family history for intestinal polyps. These pigmented melanotic spots do not require any treatment and
are not associated with any risk for malignant transformation. However, the patient should be monitored for the

Chapter 3 Orofacial Pigmentation Disorders

Figure 8

Figure 9

Post inflammatory pigmentation of tongue with lichen planus.


Courtesy: Dr Ajit Auluck

Diffuse pigmentation of tongue in HIV patient.


Courtesy: Dr Ajit Auluck

Figure 10

development of internal malignancies especially of gastrointestinal tract.


Similar pigmented spots are also associated with McCune
Albrights syndrome that is characterized by polyostotic
brous dysplasia and precocious puberty. Caf au lait
spots associated with it have regular borders in contrast to
neurobromatosis.
HIV infection
In patients infected with human immunodeficiency virus
(HIV), progressive hyperpigmentation of the skin, oral
mucosa, fingernails, and toenails is reported. Such pigmentation is related to primary adrenocortical deficiency and
to antiretroviral therapy like zidovudine (azidothymidine)
therapy. Clinically, oral pigmentation appears as irregular
macules with brown or dark brown color. The tongue,
buccal mucosa, and palate are the most commonly affected
sites (Figure 8).

of oral cavity can be involved but the buccal mucosa and


the attached gingiva are the most frequently involved sites.

Hemochromatosis

Post inflammatory pigmentation

Hemochromatosis is also called bronze diabetes. It is a


chronic disease characterized by the deposition of excess
iron (ferritin and hemosiderin) in the body tissues. Deposition of these can result in fibrosis and functional insufficiency of the involved organs. Hyperpigmentation may
appear both in the skin as well as of the mucous membranes of oral cavity and conjunctiva. The oral mucosa
shows diffuse homogeneous pigmentation which may vary
from gray-brown to deep brown in color. Although any part

Long-standing inflammatory mucosal diseases like lichen


planus can cause diffuse pigmentation of the oral cavity
(Figure 9). Most commonly post inflammatory pigmentation
is seen more frequently among the dark-skinned individuals. Clinically, multiple brown-black pigmented areas are
observed adjacent to the reticular or erosive lesions of
lichen planus. Post inflammatory pigmentation can also
occur following periodontal surgery and biopsy (Figure 10).
Histologically, there is increased production of melanin by

Post inflammatory pigmentation of buccal mucosa following


traumatic ulceration. Courtesy: Dr Ajit Auluck

67

Section II Oral and Maxillofacial Disturbances

Figure 11

Figure 12

Yellowish discoloration of sclera in a patient with jaundice.


Courtesy: Dr Ajit Auluck

Figure 13
Yellowish discoloration of palate in a patient with jaundice.
Courtesy: Dr Ajit Auluck

the melanocytes and accumulation of melanin laden macrophages in the superficial connective tissue.
Cyanosis
Rarely generalized discoloration of oral mucosa can also
be associated with cyanosis in which entire oral mucosa may
become blue black in color when reduced hemoglobin level
reaches above the critical value of 5 g/100 ml.
Beta carotene
Yellowish discoloration of oral mucosa can also be due to
consumption of large amounts of beta carotene in patients
having metabolic disorders that impairs conversion of
beta carotene to vitamin A.
Liver disease
Yellowish discoloration of oral mucosa can also be due to
liver diseases (jaundice) when bilirubin level increases
more than 23 mg/dl (Figure 11). To distinguish between
the two conditions we must examine the sclera of the eyes.
In jaundice sclera will also be yellow in color as bilirubin
pigments stain the reticular fibers of sclera whereas betacarotene will not stain the sclera (Figure 12).

Focal/Localized Pigmented Lesions


Hemangioma and vascular malformations
Hemangiomas occur due to proliferation of cells lining the
blood vessels and are tumor like hamartomas which usually
occur in children. Vascular malformations occur due to
structural defects in the vessels without the proliferation
of endothelial cells. Both hemangioma as well as vascular
68

Hemangioma of the tongue. Courtesy: Dr Ajit Auluck

malformation starts at birth but hemangioma resolves with


age while vascular malformation does not resolve with age.
If hemangiomas are associated with seizures then skull
radiographs should be advised which may reveal tram line
calcications suggestive of SturgeWeber syndrome.
Hemangiomas may appear as at or slightly raised. The
color can range from red to bluish purple depending on the
type of vessels involved (capillaries, veins or arteries) and
also the depth of the lesion in the tissues (Figure 13). If the
lesions are supercial to the overlying epithelium they are
reddish blue in color and if they are deep then they are
blue in color.
Hemangiomas can be diagnosed with diascopy test
which they usually blanch on pressure. Diascopy test is
performed by pressing glass side gently on the lesion. A
positive diascopy result is indicated by blanching and suggests that blood is present within vascular spaces and is
displaced out of the lesion by application of pressure.
However, lack of blanching does not exclude the possibility
of a vascular lesion as some cutaneous hemangiomas may
not respond positively to diascopy test.

Chapter 3 Orofacial Pigmentation Disorders

Figure 14

Figure 15

Ecchymosis of the palate. Courtesy: Dr Ajit Auluck

Traumatic hematoma of the buccal mucosa.


Courtesy: Dr Ajit Auluck

Lingual varices are usually seen in adults on the ventral


surface of the tongue. These are pathologic dilatations of
veins and venules. They become more pronounced with age.
These are painless and can rupture leading to uncontrolled
hemorrhage/bleeding. Varices resemble hemangiomas but
can be easily distinguished as hemangiomas resolve with age
while varices become more pronounced with age. Varix has
nite growth potential while hemangiomas may grow
larger in size. Hemangiomas on palpation may have bruit
and thrill which is absent in varices.
Hematomas can also cause various types of discoloration
of oral mucosa. Early hematoma is supercial and can cause
bluish swelling of mucosa. They are slightly elevated, often
uctuant and rubbery in consistency. Blood cannot be
evacuated from hematomas with digital pressure. But late
hematomas are blue-black in color as hemoglobin breaks
down to form hemosiderin (Figure 14). Eruption hematoma
is a dome-shaped blue swelling that appears around a developing tooth. None of these hematomas have pain or any
other associated complaints.
Petechiae are minute pin point macules that occur due
to erythrocyte extravasation, lysis of RBCs and subsequent
breakdown of pigments. When these areas of discoloration
are larger than 2 cm then they are called ecchymosis (Figure
15). Usually petechiae and ecchymosis are seen at the
junction of soft and hard palate. In normal patients we do
not see them but they are seen in patients with bleeding
disorders (hemophilia), clotting disorders, vessel wall
defects, platelet disorders, vomiting, coughing or fellatio.

Dilated vessels are also seen in hereditary hemorrhagic


telangiectasia (RenduOslerWeber syndrome) which is
genetically transmitted as an autosomal dominant disease
and cause microaneurysms due to weakening of the
adventitial coat of blood vessels.
Rarely, there may be vascular neoplasms that may
appear as pigmented lesions or masses in the oral mucosa.
Angiosarcoma is a malignant vascular neoplasm that
presents as nodular tumor and arises from the pericytes of
the blood vessels.
Kaposis sarcoma is also a tumor of vascular origin
mainly seen in HIV patients. Presence of Kaposis sarcoma
in HIV patients is diagnostic of AIDS. It is a malignancy
which never metastasizes. A human herpesvirus (HHV-8,
also called Kaposis sarcoma-associated herpesvirus) has
been implicated in its etiology. Kaposis sarcoma is usually
seen on the palate, gingiva or tongue. Initially lesions will
appear as at or slightly elevated brown to purple lesions
while later lesions may become dark red or purple that
may ulcerate, bleed or undergo necrosis. Therefore for
establishing a denitive diagnosis we must advice a biopsy
which may show proliferation of spindle-shaped cells surrounding poorly formed vascular spaces with numerous
extravasated red blood cells.
Graphite
Graphite is commonly introduced into the oral mucosa following an accidental injury with a graphite pencil. The
lesion appears as an irregular gray to black macule mainly
seen in the anterior palatal region of children. A history of
injury confirms the diagnosis.
Melanotic macule
They appear as an asymptomatic macule on the vermillion
border of the lower lip. However, they can also occur on the
69

Section II Oral and Maxillofacial Disturbances

Figure 16

Table 4

Warning signs in a mole suggestive of early melanoma

AAsymmetry: One half of the lesion does not match the other half
BBorder irregularity: The edges are ragged, notched, or blurred
CColor variegation: Pigmentation is not uniform and may display
shades of tan, brown, or black; white, reddish, or blue discoloration is
of particular concern
DDiameter: A diameter greater than 6 mm is characteristic, although
some melanomas may have smaller diameters; any growth in a nevus
warrants an evaluation
EEvolving: Changes in the lesion over time are characteristic; this
factor is critical for nodular or amelanotic (non-pigmented) melanoma,
which may not exhibit the classic criteria above

Melanotic macule of the buccal mucosa.


Courtesy: Dr Ajit Auluck

Histologically, only increased melanin pigmentation is


seen in the basal cell layer without an increase in the number
of melanocytes.
Pigmented nevi

Figure 17

Melanotic macules on the gingiva. Courtesy: Dr Ajit Auluck

gingiva, buccal mucosa and the palate (Figures 16 and 17).


The color may be gray, brown, blue, black or a combination
of all these. Oral melanotic macules are formed due to focal
increase in the melanin production. There is no increase
in the number of melanocytes but there is only increase in
the amount of melanin production.
Oral melanotic macules are usually smaller than 1 cm in
size. Usually they occur as solitary lesions, which are homogenous in color and have smooth borders. They are benign
in nature and do not transform into malignancy. If there is
a sudden increase in size of the lesion, change in color or
size increases more than 1 cm, a biopsy must be advised to
exclude possibility of melanoma (Table 4).
70

These are relatively uncommon cause of oral mucosal pigmentation and may appear as blue or black focal pigmented
areas. Histologically, there is increase in the number of
nevus cells in the epithelium, connective tissue or both.
Accordingly, nevi are classified as junctional nevi, intradermal nevi or intramucosal or compound nevi.
Usually melanocytic nevi develop during childhood.
Most nevi originate from the basal layer of melanocytes and
proliferate in the epithelium along the junction with the
connective tissue and are called as junctional nevi. Later,
these melanocytes drop off into the connective tissue to
form islands or cluster of melanocytes and are called as
compound nevi. Eventually all the cells leave the surface
epithelium and reside in the dermis or submucosa so called
as intradermal or intramucosal nevi.
Blue nevi arise from dermal or mucosal melanocytes that
persist in the connective tissue during embryonic neural
crest migration and therefore do not arise from junctional
activity at the epithelium and connective tissue interface
(Figure 18). In blue nevi there are spindle-shaped melanocytes which synthesize huge amounts of melanin pigment.
Blue nevi can also occur along with ocular pigmentation
along the distribution of trigeminal nerve and is called
nevus of Ota (Figure 19).
Malignant melanoma
Described in Chapter 13 on page 368.
Clinical evaluation of pigmented lesions
When a patient presents with a pigmented oral lesion a
detailed medical and dental history must be recorded.
A complete extraoral and intraoral examination should be
done and relevant laboratory tests must be advised.

Chapter 3 Orofacial Pigmentation Disorders

Figure 18

Extensive blue nevus of the buccal mucosa.


Courtesy: Dr Ajit Auluck

carefully recorded as they may help to ascertain the nature


of the lesion.
Usually benign pigmented lesions are small, symmetric,
uniform in color and show regular borders. Occasionally
benign lesions can be slightly elevated. But if the lesions
have irregular borders, color variation or surface ulceration
then it is most likely to be a malignancy and biopsy must
be advised in such cases. Surface characteristics and morphological appearance of the lesions may not point toward
the true nature of the lesion so if there is any pigmented lesion
seen in oral cavity whose etiology cannot be ascertained, we
must advice a biopsy.
Clinical tests such as diascopy or appropriate laboratory
investigations such as blood tests or radiographs may be
advised to conrm a clinical impression and reach a denitive diagnosis.
Flowcharts 1 and 2 summarize the approach to the diagnosis and differential diagnosis of pigmented oral lesions.

PIGMENTATION OF TEETH
Figure 19

Extraoral photograph showing oculodermal


pigmentation. Courtesy: Dr Ajit Auluck

The history should include details like the onset and


duration of the lesion, the presence of associated skin
lesions, associated systemic signs and symptoms, history of
intake of medications and habits. During extraoral examination record the pigmented lesions on the face, perioral
skin as well as the lips. A complete intraoral examination
of oral cavity should be done. The number, distribution,
size, shape and color of all pigmented lesions should be

Discoloration of the tooth is one of the most frequent reasons why a patient seeks dental care. Tooth discolorations
are usually esthetically displeasing and psychologically
traumatizing. There are many factors that could steal the
sparkle from a smile. An understanding of the etiology
of tooth discoloration is important to a dentist in order to
come to the correct diagnosis, which allows the dental
practitioner to explain to the patient the exact nature of
the condition. In some instances, the mechanism of staining may have an effect on the outcome of treatment and
influence the treatment options the dentist will be able to
offer to patients.
The causes for tooth discoloration can be classied
according to the location of the stains, either as extrinsic
or intrinsic. Extrinsic discoloration lies on the tooth surface or in the acquired pellicle. The intrinsic discoloration
occurs when the chromogens are deposited within the bulk
of the tooth, which may be of local or systemic origin.
The coronal aspect of the tooth consists of enamel, dentin and pulp. Any change to these structures during odontogenesis or post eruption can cause an alteration in the
outward appearance of the tooth because of the change in
the light transmitting and reecting properties.

Extrinsic Discoloration
Extrinsic discolorations are defined as discolorations located
on the outer surface of the tooth structure and caused by
topical or extrinsic agents. This can be divided into two
groups; direct staining by the compounds incorporated into
the pellicle layer and producing the stain as a result of the
basic color of the chromogen, and indirect staining were
71

Section II Oral and Maxillofacial Disturbances

Flowchart 1
Any discoloration of the oral mucosa

Heavy metal poisoning


Amalgam/graphite tattoo

Exclude extrinsic causes of pigmentation

Drugs like minocycline, oral contraceptives


Stains due to chromogenic bacteria

Observe the lesion and note the


color and other clinical characteristics

Tobacco and food stains

Blue/black melanin
pigmentation

Blue red/brown pigmentation


due to blood pigments or iron

Blanch on
pressure

Do not blanch
on pressure

Tumor masses

Diffuse
pigmentation

Focal
pigmentation

Hemangioma
Varices
Early hematoma
Telangiectasia
Kaposis sarcoma

Petechiae
Ecchymosis
Hemochromatosis

Neuroectodermal
tumor of infancy
Malignant
melanoma

Physiologic
pigmentation
Endocrine disorders
Smokers melanosis
Drug-induced
pigmentation
Post inflammatory
pigmentation
HIV infection

Melanotic macule
Nevi
Amalgam tattoo

Clinical approach for diagnosis of pigmented lesions in the oral cavity

there is chemical interaction at the tooth surface with


another compound that produces the stain.
Direct staining has multifactorial etiology with chromogens derived from dietary sources or habitually placed in the
mouth. It is the polyphenolic compounds found in the food
that are thought to give rise to the color of the stains.
Indirect extrinsic tooth staining is associated with
cationic antiseptics and metal salts. The agent is without
color or a different color from the stain produced on the
tooth surface.
Traditionally, extrinsic tooth discoloration has been
classied according to its origin, whether metallic or
non-metallic.
Table 5 summarizes the extrinsic causes of tooth
discoloration.

Classification of Extrinsic Stains


Nathoo (1997) proposed the Nathoo classification system
of extrinsic dental stains. According to this classification
system three categories of extrinsic stains are described.
72

Nathoo type 1: The chromogen binds to the tooth surface. The color of the chromogen is similar to that of dental stains caused by tea, coffee, bacteria, and metals.
Nathoo type 2: The colored material changes color after
binding to the tooth. The stains actually are Nathoo type 1
food stains that darken with time.
Nathoo type 3: The colorless material or prechromogen
binds to the tooth and undergoes a chemical reaction to
cause a stain. These stains are caused by carbohydrate-rich
foods, stannous uoride, and chlorhexidine.
Factors responsible for extrinsic discoloration
Diet factors Deposition of tannins found in tea, coffee,
and other beverages cause brown stains on the surface
of the teeth. Commercially available soft drinks and food
products containing permitted synthetic food colors (red
color: Ponceau 4R, carmoisine, erythrosine, yellow color:
tartrazine pyrazolone, sunset yellow FCF, blue color:
indigo carmine, brilliant blue FCF, green color: fast green
FCF) and additives can temporarily cause discoloration of
the teeth and the oral mucosa (Figure 20).

Chapter 3 Orofacial Pigmentation Disorders

Flowchart 2
Bluish/black discoloration of oral mucosa
Usually due to metals/melanin pigment

Localized pigmentation

Exclude pigmentation due to metals


like amalgam, graphite, lead etc.
In oral cavity, usually amalgam tattoos
are seen in close vicinity of restorations

Diffuse pigmentation

Physiological pigmentation
Present since birth
Smokers melanosis

Melanotic macule
Small size, mostly on lips, increase
in melanin synthesis

History of smoking
Endocrine disorders like Addisons
disease/Cushings syndrome

Nevi

Look for systemic signs and symptoms

Increased proliferation of
melanocytes, usually from birth

HIV associated melanosis


Advice ELISA for HIV

Malignant melanoma
Dark, irregular borders, asymmetric
and rapid growth

Associated with syndromes like


Albrights syndrome, PeutzJeghers
syndrome

Post inflammatory pigmentation due to


healing of lesions like lichen planus

General examination to find


other associated features

Algorithm for differential diagnosis of pigmented lesions in the mouth with characteristic features which help in diagnosis
*Biopsy must be advised if there is increase in size, change in color or any proliferative changes associated in
pigmented lesions

Oral hygiene related factors Accumulations of dental


plaque, calculus and food particles cause brown or black
stains. Chromogenic bacteria have been suggested as an
etiologic factor in the production of stains typically at the
gingival margin of the tooth (Figure 21). The most common is a black stain caused by Actinomyces species. The
stain is composed of ferric sulfide and is formed by the
reaction between hydrogen sulfide produced by bacterial
action and iron in the saliva and gingival exudates (Figure
22). Green stains are attributed to fluorescent bacteria and
fungi such as Penicillium and Aspergillus species. Orange
stain is less common than green or brown stains and is
caused by chromogenic bacteria such as Serratia marcescens and Flavobacterium lutescens.
Habit related Tobacco from cigarettes, cigars, pipes, and
chewing tobacco causes tenacious dark brown and black
stains that cover the cervical one-third to midway on the
tooth toward the gingival margin (Figure 23).

Chewing of pan (a combination of betel nut of the areca


palm, betel leaf, and lime) results in the production of red
colored substance that causes red-black stain on the teeth,
gingiva, and oral mucosal surfaces (Figure 24).
Drug related Cationic antiseptics such as chlorhexidine,
cetylpyridinium chloride and other mouth washes (the
essential oil/phenolic mouthrinse Listerine, delmopinol
mouthrinses) can cause staining after prolonged use.
Chlorhexidine, for example, produces brown to black discoloration (Figure 25). Most evidence indicates that the
likely cause of staining is the precipitation of anionic
dietary chromogens onto the adsorbed cations.
Some systemic medications (e.g. minocycline, doxycycline, co-amoxiclav, linezolid) have also shown to cause
extrinsic staining.
Metallic compounds are also implicated in dental discolorations because of the interaction of the metals with
dental plaque to produce surface stains. Iron-containing
73

Section II Oral and Maxillofacial Disturbances

Table 5

Extrinsic causes for tooth discoloration

Classification

Factors responsible

Examples

Color

Non-metallic stains
Direct stains

Diet

Tea, coffee and other foods

Brown to black

Oral hygiene

Dental plaque, calculus and food particles


Chromogenic bacteria

Yellow/brown
Brown/black/green, orange

Habits

Tobacco smoking/chewing
Pan chewing

Dark brown/black
Red-black

Non-metallic stains
Indirect stains

Medications

Cationic antiseptics (e.g. chlorhexidine)


Essential oils/phenolic mouthrinse
Systemic antibiotics (e.g. minocycline)

Yellow brown
Yellow
Green-gray

Metallic stains
Indirect stains

Medications

Iron containing oral solutions


Copper salts in mouthrinse
Potassium permanganate in mouthrinse
Stannous fluoride
Silver nitrate

Black
Green
Violet to black
Golden brown
Gray

Occupation

Exposure to iron, manganese, silver


Exposure to mercury and lead dust
Copper and nickel
Chromic acid fumes

Black
Blue green
Green
Deep orange

Figure 20

Figure 21

Accumulation of calculus and food particles at the cervical


margin of the tooth causing yellowish brown stains.
Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

oral solutions used for treatment of iron deciency anemia


cause black stains (Figure 26). Green discoloration can
result from the use of mouthrinses containing copper salts.
Potassium permanganate mouthwash (violet-black stain),
silver nitrate (black stain), and stannous uoride (brown
stain) also can induce dental discolorations.
Ice cream candy color staining of the oral mucosa.
Courtesy: Dr Prem Prakash Kar, Dr Snehal Thatte,
Dr Shomshukla Bhowmick

74

Occupation related Industrial exposure to iron, manganese, and silver may stain the teeth black. Mercury and
lead dust can cause a blue-green stain; copper and nickel,

Chapter 3 Orofacial Pigmentation Disorders

Figure 22

Figure 24

Black stains caused by chromogenic bacteria.


Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

Figure 23

Brown and black staining of teeth and orange-red staining of


the buccal mucosa in a patient with a habit of chewing pan.
Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

Figure 25

Tenacious brown stains on the cervical margin of the teeth in


a tobacco chewer. Courtesy: Department of Oral Medicine
and Radiology, MCODS, Mangalore

Extrinsic stains due to prolonged use of chlorhexidine


mouthrinse

green-to-blue-green stain and chromic acid fumes may


cause deep orange stain.
Predisposing factors
Factors that predispose children and adults to extrinsic
stains include enamel defects, salivary dysfunction, and
poor oral hygiene.
Microscopic pits, ssures, and defects on the outer surface of the enamel are susceptible to the accumulation of
stain-producing food, beverages, tobacco, and other topical
agents.

Since saliva plays a major role in the physical removal


of food debris and dental plaque from the outer and interproximal tooth surfaces, diminished salivary secretion can
lead to extrinsic discoloration. Decreased output may be
caused by local disease (e.g. salivary obstructions and
infections), systemic disease (e.g. Sjgren syndrome), head
and neck radiation therapy for cancer, chemotherapy, and
multiple medications (e.g. anticholinergics, antihypertensives, antipsychotics, antihistamines).
75

Section II Oral and Maxillofacial Disturbances

Intrinsic Discoloration
There are several causes of intrinsic tooth discolorations
which have either an endogenous or exogenous origin.
These changes may occur during or after odontogenesis.
During odontogenesis, teeth may become discolored from
the changes in the quality or quantity of enamel or dentin,
or from the incorporation of discoloring agent into the
hard tissues. Post-eruption discolorations occur when the
discoloring agent enter the hard tissues. They may originate from the pulp cavity or the tooth space.
Pre-eruptive causes of intrinsic
discoloration (Table 6)
Metabolic causes The diseases that have the potential
to cause neonatal hyperbilirubinemia may cause the
Figure 26

Black colored extrinsic stains due to use of iron tonic.


Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

Table 6

76

incorporation of bilirubin into developing teeth, producing jaundice like yellow-green tint within the dental hard
tissue known as chlorodontia. These diseases include sickle
cell anemia; thalassemia; hemolytic disease of the newborn due to Rhesus factor, ABO, or other erythrocyte antigen incompatibility (erythroblastosis fetalis/icterus gravis
neonatorum); biliary atresia; bile duct obstruction; biliary
hypoplasia; and cholestasis associated with sepsis.
Congenital erythropoietic porphyria (Gnthers disease) is
a rare, autosomal recessive disorder of porphyrin metabolism,
resulting in an increase in the formation and excretion or
porphyrins. The porphyrin pigments have an afnity for calcium phosphate and are incorporated into teeth during dental formation and this causes a characteristic reddish-brown
discoloration of the teeth, called erythrodontia. The affected
tooth shows a red uorescence under ultraviolet light.
Alkaptonuria, also known as phenylketonuria or ochronosis is an inborn error of metabolism of tyrosin and phenylalanine causing a build-up of homogentisic acid. This
results in a brown discoloration of the permanent dentition.
Disturbance during development of a tooth Enamel hypoplasia may result due to the disturbance of the developing
tooth germ following trauma, infection or nutritional deficiency giving rise to localized or generalized enamel defects
(Figure 27).
Periapical odontogenic infections of the primary teeth
can disrupt normal amelogenesis of the underlying permanent successors and can cause localized enamel hypoplasia. Trauma to developing, yet unerupted, teeth can also disturb
amelogenesis and may result in enamel hypoplasia, which
is visualized as a localized opacity on the erupted tooth.
Such teeth commonly are referred to as Turners teeth.

Intrinsic causes for tooth discoloration (pre-eruptive)

Classification

Factors responsible

Examples

Color

Pre-eruptive

Metabolic disorders

Hyperbilirubinemia
Porphyria
Alkaptonuria

Yellow-green
Reddish brown
Brown

Disturbance of tooth germ

Localized
Turner tooth
Generalized
Infection (maternal or childhood)
Nutritional deficiency
Molar incisor hypomineralization (MIH)

White to
yellow to
brownish

Genetic disorder

Amelogenesis imperfecta
Dentinogenesis imperfecta
Dentin dysplasia
Systemic syndrome
e.g. epidermolysis bullosa

Yellow brown
Blue brown
Yellow
Yellow

Medication

Tetracycline
Minocycline
Ciprofloxacin
Fluoride

Yellow, brown, blue or greenish


Blue-green
Greenish
Chalky white to brown/black

Chapter 3 Orofacial Pigmentation Disorders

Figure 27

Generalized chalky white opacifications of the teeth in enamel


hypoplasia. Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

Crown formation begins in utero; therefore, the potential for extensive intrinsic discoloration of the primary
dentition may be present throughout pregnancy. Although
rare, maternal rubella or cytomegalovirus infection, maternal vitamin D deciency, drug intake during pregnancy
and toxemia of pregnancy can lead to tooth discoloration,
which generally manifests as a focal opaque band of
enamel hypoplasia. Such defects will be chronologically
laid down in the teeth depending on the state of development at the time of interference and the effect is directly
related to the degree of systemic upset. There may be pitting or grooving which predisposes to extrinsic staining of
the enamel in the region of tooth disturbed, often then
becoming internalized.
Crown formation of the permanent dentition occurs until
the child is aged approximately 8 years. Systemic postnatal
infections (e.g. measles, chicken pox, streptococcal infections,
scarlet fever) can also cause enamel hypoplasia. The band
like discolorations on the tooth are visualized where the
enamel layer has variable thickness and becomes extrinsically stained after tooth eruption.
Vitamins C and D, calcium, and phosphate are required for
healthy tooth formation. Deciencies can result in exposurerelated or dose-related enamel hypoplasia.
Molar-incisor hypomineralization (MIH) is an idiopathic condition characterized by severe hypomineralized
enamel affecting incisors and permanent rst molars.
The enamel defects can vary from white to yellow to
brownish areas but they always show a sharp demarcation
between sound and affected enamel. The nature of the
enamel is porous and brittle, breaking down shortly after
eruption under masticatory forces, often resembling
enamel hypoplasia, but distinguished by having irregular

Figure 28

Generalized yellowish discoloration of teeth in amelogenesis


imperfecta. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

borders with normal enamel as opposed to smooth borders


with hypoplastic lesions. The suggestions as to the possible etiologies, including environmental changes during
the limited time period, infections during the early childhood, dioxin in breast milk and genetic factors, have yet
to be eliminated from the possible causes.
Genetic defects and hereditary diseases
Genetic defects in enamel or dentin formation include
amelogenesis imperfecta (AI), dentinogenesis imperfecta
(DI), and dentinal dysplasia (DD). These hereditary diseases
can be associated with intrinsic tooth discoloration.
Amelogenesis imperfecta is a hereditary disorder which
affects the enamel formation in both primary and permanent
dentition. Type I is hypoplastic AI. The teeth typically
have an abnormally thin enamel layer that reveals the yellow color of dentin beneath the enamel (Figure 28).
Hypoplastic teeth with rough or pitted enamel surfaces are
also at a greater risk for extrinsic staining. Type II is hypocalcied AI. The enamel in the hypocalcied type is yellow
to orange, soft, and lost soon after eruption. Therefore,
hypocalcied teeth develop dark stains and are at high
risk for dental caries. Type III is hypomaturation AI. Teeth
with hypomaturation have soft enamel with a mottled
opaque white, yellow, or brown discoloration. Type IV AI
involves hypomaturation or hypoplastic dentition with
taurodontism.
Dentinogenesis imperfecta, an inherited disorder, is
classied into three types. DI type I is associated with
osteogenesis imperfecta and is characterized by opalescent
primary teeth. DI type II (hereditary opalescent dentin)
affects both the dentition. The pulp chambers often become
obliterated and the dentin undergoes rapid wear once the
77

Section II Oral and Maxillofacial Disturbances

enamel has chipped away. The teeth have a typical amberlike translucency or opalescence against reected light,
and there color varies from different shades of yellow to
bluish-brown. DI type III (brandywine isolate hereditary
opalescent dentin) is a very rare autosomal dominant disorder which occurs in a racial segregate in Maryland,
United States. It is similar in appearance to type I and II
but with radiographic appearance of shell teeth with multiple pulpal exposure in the primary dentition.
Dentin dysplasia occurs in two types. In type I DD the
primary and permanent dentition are of normal shape and
form but may have an amber translucency. Teeth with
type II DD are characterized by thistle shaped pulp chamber and pulp stones with brown tooth discoloration.
Defects in enamel formation may also occur in a number of systemically involved clinical syndromes such as
vitamin D dependent rickets, epidermolysis bullosa, Ehlers
Danlos syndrome and pseudohypoparathyroidism. Patients
with epidermolysis bullosa may have enamel hypoplasia
and pitting, which produce a yellowish tint and the
patients are at risk for caries.

Figure 29

Yellowish discoloration of teeth due to use of tetracycline

Figure 30

Medications
Tetracycline, a broad spectrum antibiotic, is known to
cause intrinsic discoloration when prescribed during tooth
development. Tetracycline staining results from systemic
administration of the drug, which chelates with the calcium ions on the surface of the hydroxyapatite crystals as
a stable orthophosphate complex. Dentin has been shown
to be more heavily stained than enamel. The severity of
the discoloration produced depends on the type of tetracycline used, the dosage and the period of time it was taken
for, as well as the age at the time of administration.
Tetracycline should be avoided from 29 weeks in utero
until full term, in breast feeding mothers and in children
up to the age of 12 years to avoid discoloration of the
developing teeth. It has been shown that the discoloration
occurs with the greatest frequency in the developing dentition when total administration is over 3 g, or the treatment exceeds 10 days. The various analogs of tetracycline
produce different color changes, for instance, chlortetracycline produces a slate gray color and oxytetracycline
causes a creamy discoloration.
Teeth affected by tetracycline have a yellowish or browngray appearance which is worse on eruption and diminishes with time (Figure 29). The affected teeth also uoresce
under ultraviolet light, giving off a bright yellow color.
Exposure to the sunlight can change the color to brown; the
anterior teeth are particularly susceptible to this photooxidation induced color change. In severe cases of tetracycline involvement enamel hypoplasia may result.
Tetracycline discoloration has been classied according
to the extent, degree and the location of the tetracycline
involvement (Jordan and Boksman).
78

Bluish discoloration of teeth due to minocycline.


Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

Degree I: There is minimal expression of tetracycline


stain uniformly conned to the incisal three-quarters of
the crown and is light yellow in color.
Degree II: There is more variability of staining ranging
from a highly uniform deep yellow to gray banded discoloration in which a distinctive difference in discoloration is
noted between the cervical region and the incisal fourfths of the crown.
Degree III: There is very dark blue or gray uniform
discoloration.
Minocycline is a semi-synthetic derivative of tetracycline.
It is commonly used to treat acne vulgaris. The ingestion of
minocycline can lead to a green-gray or blue-gray intrinsic
staining of teeth (Figure 30). Unlike with other tetracyclines,

Chapter 3 Orofacial Pigmentation Disorders

staining occurs during and after the complete formation


and eruption of teeth. Staining of the adult dentition appears
to occur in 36% of patients taking long-term minocycline
at more than 100 mg daily. The staining caused by minocycline is different from that caused by tetracycline. The
onset of discoloration can occur any time from 1 month to
many years after the initiation of the treatment.
Four theories have been put forward to explain the
possible mechanism by which minocycline causes tooth
discoloration. The rst is the extrinsic theory, where it is
thought that minocycline attaches to the glycoprotein in
acquired pellicle. It oxidizes on exposure to air or as a result
of bacterial activity, and so causes degradation of the aromatic ring forming insoluble black complex. The pigmentation may be incorporated into the dentin and is possibly
a demineralization/remineralization phenomenon related
to the high local levels of the drug. The second is the
intrinsic theory, where the minocycline bound to the
plasma proteins is deposited in collagen-rich tissues, such
as the teeth. This then oxidizes slowly over time with exposure to light. The third possibility is that the drug chelates
with iron to form an insoluble complex. The fourth suggestion is that minocycline could be deposited in dentin
during dentinogenesis, and the process of secondary dentinogenesis can be accelerated in bruxists.
Doxycycline has recently been reported to cause extrinsic staining of teeth, possibly by binding to glycoproteins
in the dental pellicle in patients with poor oral hygiene in
whom oxidation occurs (e.g. sunlight exposure, bacterial)
or via mechanisms similar to those for minocycline.
Ciprooxacin, a quinolone given intravenously to infants
at dosages of 10 to 40 mg/kg/day to treat infections with
Klebsiella, has been associated with greenish discoloration
of the teeth when they erupted.

DENTAL FLUOROSIS
Dental fluorosis is characterized by enamel discoloration
resulting from subsurface hypomineralization due to the
excessive ingestion of fluoride during the early maturation
stage of enamel formation. Fluoride sources are numerous
and include naturally or artificially fluoridated drinking
water, commercially available beverages, foods prepared
in fluoridated water, chewable vitamins, oral healthcare
products (e.g. toothpastes, mouthrinses, oral fluoride supplements), and professional fluoride products prescribed
by dentists. The severity is related to age and dose, with
the primary and permanent dentitions both being affected
by endemic fluorosis. The enamel is often affected and may
vary from areas of flecking to diffuse opaque mottling
superimposed on to chalky white or dark brown/black
appearance (Figure 31). The dark discoloration thought to
be post-eruptive by a process of internalization of the
extrinsic stains into the porous enamel.

Figure 31

Yellowish brown intrinsic staining of teeth in fluorosis.


Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

Post-eruptive Causes (Table 7)


Dental conditions and caries
Tooth wear is the progressive loss of enamel and dentin
due to attrition, abrasion and erosion. As the enamel thins
the teeth become darker as the color of the dentin becomes
more apparent. Once the dentin is exposed the potential of
chromogens to enter the body of the tooth increases.
The various stages of carious process can be recognized
by the change in color as the disease progresses. The
pathogenesis of dental caries begins with an incipient
lesion conned to the enamel layer. Incipient carious
lesions are associated with plaque accumulation and manifest as chalky white areas of discoloration secondary to
hypocalcication. As caries progresses into the dentin, the
overlying translucent enamel reveals the color of the
underlying caries and appears yellowish brown. Extensive
caries that involve destruction of both enamel and dentin
produce a color that ranges from light brown, to dark
brown or almost black (Figure 32). The brown color is
attributed to the formation of Maillard pigments (reaction
between proteins and small aldehydes produced by cariogenic bacteria), melanins, lipofuscins, and uptake of various food colors and bacterial pigments. In some patients,
the caries process can self-arrest, and remineralization
may occur; however, the brown discolorations usually
remain.
The natural darkening and the yellowing of the teeth and
the change in their light transmission properties with age
are due to the combination of the factors involving both
enamel and dentin. The enamel undergoes both thinning
and textural change, while the deposition of secondary
and tertiary dentin and pulp stones all contribute to the
darkening process of aging.
79

Section II Oral and Maxillofacial Disturbances

Table 7

Intrinsic causes for tooth discoloration (post-eruptive)

Classification

Factors responsible

Examples

Color

Post-eruptive

Dental conditions

Dental caries
Incipient
Active
Arrested
Tooth wear
Aging

Chalky white
Yellowish brown
Dark brown to black
Yellowish
Yellowish

Pulpal causes

Pulpal trauma with hemorrhage


Calcific metamorphosis
Internal resorption

Gray-brown
Yellowish to yellowish brown
Pinkish

Dental materials

Amalgam
Composite glass ionomer cement (GIC)
Intracanal medicaments (e.g. iodoform, ledermix)
Obturating materials and sealers

Blue-gray
Yellowish brown
Brownish gray
Grayish

Figure 32

Grayish black discoloration in the proximal aspect of the


tooth indicative of dental caries. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

Pulpal causes
Bacterial, mechanical, or chemical irritation to the pulp may
result in tissue necrosis and the release of disintegration
by-products that might penetrate the tubules and discolor
the surrounding dentin. Trauma that occurs to erupted teeth
also causes discoloration. After acute trauma, intrapulpal hemorrhage will give the tooth a reddish tinge. Occasionally, in
younger patients, the color may return to normal as the
inammation subsides. More often, the discoloration changes
to gray-brown in a matter of days as the pulp becomes
necrotic. Hemolysis of the red blood cells would follow and
release the heme group to combine with the putrefying
pulpal tissue to form black iron sulde. In vitro studies
have recently shown that the major cause of discoloration of
80

Figure 33

Discolored upper central incisors following trauma.


Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

non-infected traumatized teeth is the accumulation of the


hemoglobin molecule or other hematin molecules. In the
absence of infection, the release of iron from the protoporphyrin ring is unlikely.
Excessive formation of irregular dentin in the pulp
chamber and along the canal walls may occur following
certain traumatic injuries. This is known as calcic metamorphosis. As a result of this, the translucency of the
crown gradually decreases, giving rise to yellowish or yellowish brown discoloration (Figure 33).
Root resorption following trauma often presents as a
pink spot lesion at the cementoenamel junction in an
otherwise symptomless tooth, known as the pink tooth of
Mummery. The resorption may be internal, being of pulpal
origin or external of periodontal origin.

Chapter 3 Orofacial Pigmentation Disorders

Dental Materials

Clinical examination

Dental restorations most commonly cause intrinsic discoloration. Amalgam restorations can generate corrosion
products, leaving a blue-gray color in the tooth, especially
in large cavity preparations with undermined enamel
known as amalgam blue.
Metal pins and prefabricated posts are sometimes used
to reinforce composite restoration on the anterior dentition.
Discoloration from inappropriately placed pins and posts
is caused by the metal seen through the composite or the
tooth structure.
Microleakage around composite or glass ionomer restoration causes staining. Open margins may allow chemicals
to enter between the restoration and the tooth structure
and discolor the underlying dentin.
Several intracanal medicaments are liable to cause
internal staining of the dentin. Phenols or iodoform based
medicaments sealed in the root canal and the chamber
are in direct contact with dentin, allowing penetration and
oxidation. These compounds discolor dentin gradually.
Tetracyclines (e.g. ledermix-triamcinolone acetonide and
demethylchlortetracycline) used within the tooth for endodontic therapy may also cause dark gray-brown discoloration.
Obturating materials are frequent cause for single tooth
discoloration. Incomplete removal of obturating material
and sealer remnants in the pulp chamber, mainly those
containing metallic components, often result in dark
discoloration.

The scratch test is usually used to distinguish between


extrinsic and intrinsic discoloration. Discolored tooth
surfaces are scratched with care by using a dental explorer,
scaler, or similar sharp instrument to assess surface texture. Light scratching with a dental instrument removes
weakly adherent plaque that causes extrinsic discoloration. If the discoloration requires removal with a sharp
dental scaler, the discoloration is considered to be tenacious. Intrinsic discoloration cannot be removed by using
the scratch test.
Extrinsic staining of a single tooth is unusual. The distribution is usually generalized. The stains are usually found
on surfaces with poor toothbrush accessibility. Whereas in
case of intrinsic discoloration distribution is either generalized to all teeth or localized to certain teeth or tooth
surfaces. An intrinsic etiology usually exists when a single
tooth is discolored.
Regarding other physical ndings, teeth with extrinsic
tooth discoloration usually demonstrate no signs of pulpal
disease. Teeth with intrinsic discoloration may demonstrate
signs of pulpal disease. A single discolored tooth with a
history of trauma will usually be non-vital. Radiographs
may reveal periapical pathology.
Under ultraviolet light, teeth with tetracycline staining
and congenital porphyria may uoresce yellow or red,
respectively.

Diagnosis
History The patients history of tooth discoloration provides useful information regarding the etiology. The history includes the following:

Dental history: Previous dental treatment, oral hygiene


practices, use of mouthwash, amount and scheduling
of fluoride intake, history of dental trauma.
Medical history: History of maternal or childhood diseases, use of medications.
Family history: Genetic disorders.
Diet history: Nutritional deficiencies, diet that can
cause staining of the teeth.
Social history and personal history: Occupational
exposure to metals and use of tobacco.

Management
The treatment of tooth discoloration consists of identifying the etiology and implementing the required therapy.
Scaling and polishing of the teeth remove many extrinsic
stains. For more stubborn extrinsic discoloration and
intrinsic stain, various bleaching techniques may be
attempted. Tooth bleaching can be performed externally,
termed night guard bleaching or vital tooth bleaching, or
intracoronally in root-filled teeth, called non-vital tooth
bleaching.
Teeth discolored by dental caries or dental materials
require the removal of the caries or restorative materials,
followed by proper restoration of the tooth. Partial (e.g.
laminate veneers) or full-coverage dental restorations may
be used to treat generalized intrinsic tooth discoloration in
which bleaching is not indicated or in which the esthetic
results of bleaching fail to meet the patients expectations.

81

CHAPTER

Bacterial, Viral and Fungal


Infections
Ravikiran Ongole, Praveen BN

Bacterial Infections

Viral Infections

Scarlet Fever

Infectious Mononucleosis

Diphtheria

Acute Lymphonodular Pharyngitis

Tularemia

Measles (Rubeola)

Erysipelas

German Measles (Rubella)

Impetigo

HIV and AIDS

Melioidosis

Sinusitis

Tetanus

Fungal Infections and Protozoal Diseases

Actinomycosis

Histoplasmosis

Noma

Blastomycosis

Botryomycosis

Mucormycosis

Rhinoscleroma

Aspergillosis

Cat-scratch Disease

Cryptococcosis

Many of the systemic diseases are caused by a wide range of


bacteria, viruses and fungal organisms. Some of these microbial diseases can exhibit oral manifestations. However, some
of the microbial diseases such as dental caries and periodontal diseases are localized to the oral cavity. Systemic microbial diseases with oral manifestations are discussed in this
chapter.

BACTERIAL INFECTIONS
SCARLET FEVER
Scarlet fever is also known by the names scarlatina, scarlatinella and scarlatiniform rash. It is caused by an infection
with a pyogenic exotoxin-producing group A -hemolytic
streptococci. The upper respiratory tract is the usual portal
of entry. Most cases occur between 1 and 10 years of age
and may occasionally be seen in adults.
The organism expresses an erythrogenic toxin that acts
on the blood vessels to produce the typical skin rash.
Clinical features
The incubation period of the bacteria ranges from 1 day
up to a week. Patients will present with fever and skin rashes
82

within the first 2 days of the infection. The fever and rash
usually resolve in about 7 days. Other associated clinical
features include headache, tonsillitis, pharyngitis and
lymphadenopathy.
The scarlet fever rash appears bright red and mimics a
sunburn appearance. Normal pin head-sized areas of the skin
may project through the rash giving rise to a sandpaper
like surface texture, which is popularly referred to as sandpaper rash or sunburn with goose bumps or goose pimples.
The skin rashes are commonly seen over the trunk,
extremities, neck, groin and specically along Pastias lines
(darkening of the normal skin fold/creases, such as the
axillary crease, anticubital crease).
Once the rash resolves, a 38 months phase of desquamation begins, which is characterized by peeling away of
the skin in large akes.
Oral manifestations
Patients may present with circumoral pallor. The soft palate, pharynx, tonsillar region and the tongue are commonly
affected. The oral cavity appears extensively erythematous
and edematous (stomatitis scarlatina). Occasionally a yellowish-white exudate may be seen in the tonsillar crypts.
During the rst 2 days of the infection the dorsal surface
of the tongue exhibits a white coat through which the

Chapter 4 Bacterial, Viral and Fungal Infections

fungiform papillae are visible. Such an appearance is


referred to as white strawberry tongue. After about 4 days
the white coat on the tongue desquamates to reveal an
erythematous dorsal surface with hyperplastic fungiform
papillae, which is referred to as red strawberry tongue.
The complications of untreated scarlet fever may occur
either due to streptococcal toxin (myocarditis), or bacterial
invasion (septic arthritis, meningitis, osteomyelitis) or by
an allergic reaction (rheumatic fever, glomerulonephritis).
The diagnosis can be made based on the characteristic
clinical presentations, culture of the secretions from the
pharynx or tonsillar regions and detection of antigens specic for group A -hemolytic streptococci.

dead cells, leukocytes and bacteria) initially forms on the


tonsils and subsequently spreads to involve the larynx,
pharynx, uvula, soft palate and occasionally the gingiva.
Removal of this mildly adherent membrane leaves a raw
bleeding surface. Some patients may exhibit transient
paralysis of the soft palate.
Extensive involvement of the respiratory tract may lead
to respiratory obstruction. The other serious complications
include effects of the toxin on the cardiovascular system,
nervous system and renal system to cause myocarditis,
polyneuritis and acute interstitial nephritis.

Management

Immunization of the infants with DPT vaccine (weakened


form of diphtheria toxin) along with booster doses every
10 years, throughout life will effectively prevent the occurrence of diphtheria.
Diphtheria is treated with antitoxin along with antibiotics such as intravenous penicillin or erythromycin.

A single episode of scarlet fever will usually confer permanent antitoxin immunity. However, recurrences are not
unusual. This is due to the fact that toxin produced by other
strains is not neutralized and the bacterial immunity is
temporary.
Penicillin is the drug of choice. Erythromycin may be used
in patients who are allergic to penicillin. Acetaminophen
or ibuprofen may be used to alleviate pain and manage
fever. Analgesic mouthrinses (benzydamine hydrochloride) may be used for stomatitis.

DIPHTHERIA
Diphtheria is an acute infectious disease caused by toxinproducing Corynebacterium diphtheriae or Klebs-Lffler
bacillus (after Klebs who discovered the bacillus and Lffler
who isolated the bacillus in pure culture).
The bacteria reside in the upper respiratory tract of the
infected individual and cause local infection of the upper
respiratory tract and occasionally the skin and the heart,
kidneys, and peripheral nerves.
It spreads through droplet infection and direct contact.
The incubation period lasts for a few days, following
which the bacterium expresses an exotoxin that causes
tissue necrosis that subsequently spreads peripherally.
General clinical and oral manifestations
Tonsillitis is usually the first clinical finding. Patients
present with fever, malaise, headache, sore throat, foul
taste/breath and cervical lymphadenopathy. The exotoxin
causes necrosis of the soft tissues producing a thick, grayish white membrane. As the infection progresses patients
may complain of difficulty in speech, swallowing and
breathing.
Diphtheria involving the skin causes excoriation of the
skin of the nasal and perinasal regions.
The grayish pseudo membrane (diphtheritic membrane
covers necrotic ulcerated areas of the mucosa and contains

Prevention and management

TULAREMIA (Rabbit Fever, Deer-fly Fever,


Francis Disease, Tick-Borne Disease,
Oharas Disease)
Tularemia is caused by gram-negative pleomorphic bacterium, Francisella tularensis (named after the extensive
work on tularemia done by Dr Edward Francis).
It is transmitted to men from animals (chiey rabbits
and also by muskrats and squirrels) by contact with diseased or dead animals, by the bites of deer ies, eas, and
ticks; by contact with contaminated animals or their products; by ingestion of contaminated food or water or by
inhalation of aerosolized bacteria. Young and middle-aged
individuals who are actively involved in outdoor activities
are more susceptible to the disease.
Clinical manifestations
The incubation period of tularemia usually varies from 3 to
4 days. The initial symptoms include fever, chills, myalgias
and malaise. Disseminated form of the disease can cause
tularemic meningitis, pericarditis, peritonitis, endocarditis
and osteomyelitis. Occasionally a severe form of tularemia, typhoidal tularemia may be seen.
Based on the type of the tularemia, specic clinical manifestations are seen (Table 1).
Oral manifestations
In the initial stages solitary nodular masses may be appreciated which may eventually form abscesses or ulcerate.
Generalized stomatitis along with extremely painful necrotic
ulcers may be seen affecting any part of the oropharynx.
Regional lymphadenopathy is usually a prominent feature.
83

Section II Oral and Maxillofacial Disturbances

Table 1

Clinical manifestations and types of tularemia

Type of tularemia

Mode of transmission

Clinical features

Ulceroglandular tularemia

Bite of infected insects and animals (ticks, rabbits)

Ulcers at the site of inoculation (fingers, hands, feet)


Inflammation of the regional glands. Tender nodes

Glandular tularemia

Similar features as that of the ulceroglandular variety except


that there is no evidence of ulcer

Pneumonic tularemia

Inhaling of airborne bacteria from soil or inhalation


of the bacteria by healthcare workers

Pneumonia is the characteristic feature. Other symptoms


include dry cough, dyspnea, and pleuritic chest pain

Oropharyngeal tularemia

Eating undercooked meat of an infected animal or


drinking contaminated water

Vomiting, diarrhea and other digestive problems

Oculo-glandular form

Occurs following exposure of the conjunctiva to


infected blood

The affected eye is tender and erythematous. Occasionally


purulent exudate may be seen along with inflamed regional
glands

Management
Tularemia responds well to antibiotics. The drugs of choice
include aminoglycosides (gentamicin, streptomycin) fluoroquinolones (ciprofloxacin, gatifloxacin) and chloramphenicol.

ERYSIPELAS
Erysipelas is an acute inflammation of the skin, with marked
involvement of cutaneous lymphatic vessels. It is usually
caused by -hemolytic Streptococcus pyogenes of group A.
Erysipelas has to a lesser extent been caused by group B, C, or
G streptococci, and occasionally by Staphylococcus aureus.
It has also been referred to as St. Anthonys re after
the name of the Egyptian monk who is believed to have had
the powers to cure this disease.
Clinical features
The typical lesion of erysipelas is evident as an erythematous, well defined area that may be warm to touch. Occasionally a butterfly rash mimicking lupus erythematosus
may be seen when the bridge of the nose is involved. Fever
of sudden onset is a typical feature. Erysipelas is usually
seen in young or old patients and in systemically compromised patients.
The typical rash of erysipelas can affect skin on any
part of the body. However previous sites of trauma are the
most commonly affected. The common sites affected
include the legs, cheeks, eyelids and bridge of the nose.
The infection causes destruction of the cutaneous lymphatic vessels. This in turn increases the susceptibility for
future recurrences (30% recurrence rate).
Management
Long-term antibiotic therapy with narrow spectrum penicillins (benzylpenicillin) or macrolides may help in preventing recurrent erysipelas infection.
84

IMPETIGO
Impetigo is a highly contagious superficial skin infection
caused by -hemolytic streptococci and Staphylococcus
aureus. Impetigo is considered as the most common bacterial
dermal infection in children. It is more common in children receiving dialysis.
Clinical features
Impetigo usually affects children in the age group of 26
years. It spreads via direct skin contact. The incidence of
impetigo is greatest in the summer months, and the infection most often occurs in areas with poor hygiene and in
crowded living conditions.
There are two types of impetigo: non-bullous (impetigo
contagiosa) and bullous.
The host response to the infection results in the nonbullous type of impetigo. On the other hand, the bullous
form is not dependent on the host response but results
from the direct action of the staphylococcal toxin.
Non-bullous impetigo The skin of the face and the
hands and legs are commonly affected sites. The infection
begins as a solitary red macule or papule that almost
immediately turns into a vesicle. The vesicle ruptures to
form an erosion, and the contents dry to form characteristic honey-colored crusts that may be pruritic. These lesions
may spread to surrounding areas by autoinoculation.
Bullous impetigo Bullous impetigo is described in detail
in Chapter 7 on Vesiculobullous Disorders.

MELIOIDOSIS
Meliodosis is a potentially fatal bacterial infection caused
by exposure to soil or water contaminated with the bacterial species Burkholderia pseudomallei. The causative

Chapter 4 Bacterial, Viral and Fungal Infections

organism, Burkholderia pseudomallei, was thought to be a


member of the Pseudomonas genus and was previously
known as Pseudomonas pseudomallei.
Alfred Whitmore, a pathologist and his assistant
CS Krishnaswami in 1911, rst described melioidosis as a
glanders-like disease among morphia addicts in Rangoon,
Myanmar (formerly Burma).
Stanton and Fletcher in 1932 renamed this disease as
meliodosis, which is a derivative from the Greek words
melis (distemper of asses) and eidos (resemblance).
Melioidosis is regarded as endemic to southeast Asia
and northern Australia. In the Indian subcontinent a survey
conducted by Kang et al (1996) revealed a seroprevalence of
7% in a rural rice-growing area near Vellore.
Risk factors
Diabetes, thalassemia, excessive consumption of alcohol,
renal disease, and frequent history of occupational or recreational exposure to mud or pooled surface water are
common risk factors resulting in melioidosis.
Clinical features
Melioidosis can present in an acute or chronic form.
The average incubation period of acute melioidosis is
about 9 days. However patients can exhibit a period of
latency. Such patients do not present any clinical symptoms. Literature review reveals that the longest duration
between presumed exposure and clinical presentation was
62 years. Such prolonged periods of incubation were recognized in American soldiers involved in the Vietnam
War, and was referred to as the Vietnamese time-bomb.
The typical clinical presentations of acute melioidosis
usually include pain and fever. Other clinical ndings are
cough or pleuritic chest pain suggestive of pneumonia,
bone or joint pain suggestive of osteomyelitis or septic
arthritis, or cellulitis, thyroid, lymph node and scrotal
abscess and ocular infection. Parotid abscess has been
reported specically in Thai children.
The chronic form of melioidosis is seen in about 10% of
the patients. A chronic form is characterized by the presence
of symptoms for longer than 2 months. Patients may present with chronic pneumonia, ulcers on the skin surface and
chronic dermal infections. Since the chronic form closely
resembles tuberculosis, some authors term chronic melioidosis as Vietnamese tuberculosis.
Diagnosis and management
The bacterium can be cultured from the tissue fluid from
the abscesses and the patients blood and sputum. The
drugs of choice include antibiotics such as trimethoprim
sulfamethoxazole and ceftazidime orally. However serious
infections are best managed with intravenous tetracycline,
chloramphenicol, and trimethoprim-sulfamethoxazole.

TETANUS
The word tetanus comes from the Greek tetanos, which is
derived from the term teinein, meaning to stretch. Tetanus,
commonly called lockjaw, is an acute neurologic disease
that results from wound contamination with Clostridium
tetani, an anaerobic, gram-positive, motile, spore-forming
rod characterized by generalized muscle rigidity and spasm,
sometimes associated with autonomic dysfunction.
Pathophysiology
It is believed that although most wounds may be contaminated with the spores of Clostridium tetani, the germination and toxin production occurs only in wounds with
low oxidation reduction potential, such as those with devitalized tissue, foreign bodies, or active infection. The bacteria produce two exotoxins: tetanolysin (role still unclear)
and tetanospasmin. Tetanospasmin is the neurotoxin responsible for the clinical manifestations of the disease. The toxin
spreads hematogenously to the peripheral nerves and travels in a retrograde fashion along the nerve fibers to reach
the central nervous system where it blocks the release of
gamma-aminobutyric acid (GABA) from presynaptic
inhibitory neurons. This loss of inhibitory impulses results
in the cardinal clinical manifestations of reflex irritability
and autonomic hyperactivity.
Clinical features
Tetanus is usually seen in young adults who are prone to
traumatic injuries. Four types of tetanus are recognized
based on the clinical presentation: localized, generalized,
cephalic and neonatal.
The localized form of tetanus is characterized by a limited area of muscular spasm that is conned to the area of
the entry of the bacilli.
The cephalic subtype of tetanus is characterized by cranial nerve palsies that often precede trismus. Patients present with cranial nerve palsy (usually facial nerve is
affected). Approximately two thirds of cases progress to
generalized tetanus. The incidence of cephalic tetanus
ranges from 0.9 to 3.0%. The cephalic form results from
injuries sustained to the head and neck region, tooth
extraction or chronic tympanitis. Some patients may present with incomplete Bells palsy.
Generalized tetanus is the most common form of the
disease and carries the highest mortality. Incubation periods for the generalized form range from a few hours to
greater than 1 month.
Trismus or lockjaw is the initial presentation in 75% of
cases. Facial muscle spasm may cause the classic sneering
grin of risus sardonicus. Motor ndings progress to involve
the neck, trunk and extremities, eventually leading to abdominal rigidity and opisthotonus. The muscle spasms may be
sustained or paroxysmal. In severe cases the spasm of
85

Section II Oral and Maxillofacial Disturbances

intercostal, diaphragmatic and pharyngeal muscles leads


to breathing difculties which may eventually lead to death.
Neonatal tetanus is a fatal yet preventable disease that
accounts for 14% of annual neonatal deaths worldwide. The
neonatal form of tetanus has a high mortality rate. It results
from unhygienic delivery practices, application of harmful
substances on the umbilical cord, and lack of maternal TT
immunization. Risk for contamination and subsequent occurrence of neonatal tetanus remains high for several days after
delivery until the babys cord wound heals. The incubation
period varies from 3 to 10 days. Neonates failure to suckle
is often the rst sign of infection in the neonate, and typically occurs between the 3rd and 10th day of life. In spite
of efforts by the infant, spasms of the masseter muscle impede
feeding. The newborn becomes irritable and cries constantly. Exhaustion may subsequently bring about cessation of audible crying. Sometimes the lips are pursed as if
to whistle. Variable degree of muscle spasm develops leading to asphyxia.
Differential diagnosis
Fascial space infections causing trismus, dystonic reactions induced by such drugs as phenothiazines and metoclorpropramide, hypocalcemia, meningitis, encephalitis,
rabies and strychnine poisoning can be considered in the
differential diagnosis for tetanus.
Diagnosis
A simple bed side test may be used effectively to diagnose
tetanus. The spatula test is said to have a sensitivity of 94%
and specificity of 100%. The posterior pharyngeal wall is
touched with a spatula. The test is considered positive if
there is a reflex spasm of masseter and negative if there is
a normal gag reflex.
Enzyme immunoassays for antitoxin levels can also be
used. A level of 0.01 IU/ml or greater is considered protective, making the diagnosis of tetanus less likely.
Prevention and management
The first step should include rapid-sequence intubation
with midazolam and succinylcholine. Passive immunization with human tetanus immune globulin (5,000 IU) will
help to neutralize free tetanospasmin. It should be given
after airway control and before wound debridement.
Finally the source wound should be thoroughly debrided,
with removal of all foreign bodies and devitalized tissue.
Metronidazole, 500 mg IV every 6 hours, is recommended
as the rst-line antibiotic.
As a part of the supportive measures, sympathetic overactivity can be managed with a labetalol infusion at 0.25
1 mg/min. Diazepam may be used to sedate the patient.
The WHO recommends that an individual should receive
3 doses of DTP in infancy, followed by a TT-containing
86

booster at school-entry age (47 years), in adolescence


(1215 years), and in early adulthood.

ACTINOMYCOSIS
Actinomycosis is subacute to chronic, suppurative granulomatous disease that tends to produce draining sinus tracts.
It is caused by anaeroboic gram-positive, non-acid fast
bacilli. The common isolates in humans include Actinomyces
naeslundii, A. israelii, A. meyeri, A. viscosus and rarely
A. odontolyticus. Kalfas et al (2001) identified a new species, Actinomyces radicidentis that was isolated from apical
periodontitis.
Von Langenbeck noted the rst case of human actinomycosis in 1845. Bollinger and Harz in 1877, named the
genus Actinomyces when they described the etiologic
agent of bovine actinomycosis (lumpy jaw) and called it
Actinomyces bovis.
Clinical features
Actinomycosis is mostly found in young adults. Women
are less frequently affected than men. Based on the site of
involvement, actinomycosis can be grouped into the cervicofacial (55%), pulmonary (15%), abdominal and pelvic
(25%) and cutaneous and genitourinary actinomycosis
(5%). Cutaneous actinomycosis is extremely rare and these
are said to arise from wounds contaminated with saliva or
as a consequence of hematogenous dissemination following a dental procedure. However primary cutaneous actinomycosis have also been reported. The genitourinary
form has been reported in patients using intrauterine contraceptive devices.
The presenting symptoms of pulmonary actinomycosis
are fever, cough, thoracic pain and dyspnea. The sputum is
mucopurulent or even sanguineous. With the appearance
of stulae, the disease spreads to the mediastinum, the pericardium, and nally to the skin of the chest.
Actinomycosis is believed to be acquired by endogenous implantation into deep tissues where anaerobic conditions prevail. Actinomyces israelii is an anaerobic normal
inhabitant of the mouth, especially in the teeth and tonsils.
In the cervicofacial region, puncture wounds, dental
extractions, or compound fractures are some of the routes
of infection. The cervicofacial variant is characterized by
the appearance of solid sub- or supramandibular nodules
or swellings and the overlying skin becoming purple to
violet.
Clinical presentation of cervicofacial actinomycosis is
characterized by the presence of suppurative or wooden
indurated mass with discharging sinuses. Pus from the discharging sinuses contains tiny yellow sulfur granules.
Common initial symptoms of infection including pain,
fever, erythema, edema, and suppuration may be absent.

Chapter 4 Bacterial, Viral and Fungal Infections

Actinomycosis often involves lymphatic nodes but by


the direct extension of a primary lesion. Occasionally, the
masticatory muscles and tongue may be involved resulting in trismus and dysphagia.

Noma is considered to represent the face of poverty


because many of the risk factors that are associated
with poverty. The World Health Organization (1998) has
reported an estimated worldwide incidence of 140,000
cases per year.

Radiographic features
Actinomycotic osteomyelitis affecting the maxilla and
mandible have been reported. Radiographs reveal ill-defined
radiolucencies with a radiopaque periphery.
Periapical actinomycosis is believed to be a non-resolving periapical lesion associated with actinomycotic infection and has been suggested as a contributing factor in the
perpetuation of periapical radiolucencies after root canal
treatment. A diagnosis is usually made by identifying the
typical actinomycotic colonies in a surgical specimen.
Occasionally, the periapical actinomycotic lesion may
appear radiopaque mimicking condensing osteitis.
Investigations
Sinus tracts may reveal the presence of yellowish granules
(16 mm in diameter) referred to as sulfur granules. On
histological examination, the sulfur granules consist of a
central tangled mass of gram-positive mycelia surrounded
at the periphery by gram-negative, club-shaped rods.
The hematoxylin and eosin stained specimen shows the
ray phenomenon. The periphery of the granule shows laments that are radially oriented and embedded in eosinophilic material.

Clinical features
Noma is usually seen in children between the age of 3 and
12 years mainly in the developing countries especially
sub-Saharan Africa. Children at risk for noma have been
seen to have low plasma concentrations of zinc, retinol,
ascorbate, and essential amino acids with increased plasma
and saliva levels of free cortisol.
Many authors believe that noma, occurs secondary to
the extension of necrotizing ulcerative gingivitis.
In the initial stages ulcerative areas from the gingiva
extend to involve the adjacent soft tissues. Subsequently
the necrotic areas spread both into deeper tissue planes
and supercially. The overlying skin turns deep blue to
black and eventually sloughs away. Extensive necrosis can
lead to exposure of bone and osteomyelitis. Patient may
present with pain, fever, malaise, foul odor and regional
lymphadenopathy. The differential diagnosis for noma
must include mucocutaneous leishmaniasis, lupus erythematosus, leprosy, agranulocytic ulcerations, injuries associated with physical trauma (including burns), syphilis,
oral cancer and yaws.
Other variants of Noma

The sinus tracts have to surgically excised and abscess


drainage should be facilitated. Long-term antibiotic therapy with penicillin or tetracycline is recommended.

Noma neonatorum is characterized by gangrenous process


of the nose, oral cavity, eyelids, and perineum usually seen
in premature infants at births or within the first month of
life. The causative organism for noma neonatorum is usually Pseudomonas.
Noma pudendi is the term used for noma affecting the
anogenital area and causing necrosis of the genitalia.

NOMA (Cancrum Oris, Gangrenous or


Necrotizing Stomatitis)

Complications and management

The word noma is derived from the Greek word nomein


that means to devour. It is rapidly progressive opportunistic infection which is caused primarily by Fusobacterium
necrophorum, Fusobacterium nucleatum and Prevotella
intermedia. Other reported organisms isolated from the
Noma lesions include -hemolytic Streptococci, Actinomyces
spp., Peptostreptococcus micros, Veillonella parvula, Staphylococcus aureus, Corynebacterium pyogenes, Bacteroides
fragilis, Bacillus cereus and Pseudomonas species.
The predisposing and/or risk factors for noma include
poverty, malnutrition, immunosuppression (including HIV
infection), poor oral hygiene, unsanitary environment,
leukemia, and infectious diseases caused by measles and
herpesviridae.

Extensive necrosis can cause premature loss of deciduous


teeth, damage to the permanent tooth buds, sequestration
of the jaws, trismus, and bony or fibrous ankylosis of the
temporomandibular joint. Occasionally, infection from the
oral cavity can extend to other parts of the body causing
systemic complications such as toxemia, dehydration and
bronchopneumonia. Untimely intervention can lead to
death.
Local wound care along with restoration of the hydration, nutritional and electrolyte imbalance should be given
adequate importance.
Penicillin along with metronidazole are the antibiotics of
choice in the management of noma. However, clindamycin
and gentamicin are the drugs of choice in the management
of neonatal noma.

Management

87

Section II Oral and Maxillofacial Disturbances

BOTRYOMYCOSIS (Bacterial
Pseudomycosis)
Botryomycosis arises from chronic infections produced by
low-virulence organisms in an altered host environment.
Staphylococci have been the most common organisms
implicated, but various other bacteria have also been identified in lesions of human botryomycosis.
The disease, later referred to as botryomycosis, was rst
described involving the lung of a horse by Bollinger in
1870. Sebastiano Rivolta in 1884 coined the term botryomycosis (botryos from Greek for bunch of grapes) after
he found globular granules in a tumor from the cut spermatic cord of a horse.
Clinical types and features
Winslow (1959) categorized botryomycosis into two types
based on their site of involvement: integumental and
visceral.
The integumental botryomycosis affects the exposed
body surfaces such as the hands, feet or the head. It occurs
in the site of a contaminated wound, foreign body or
trauma and manifests as a localized granulomatous infection. Occasionally it causes osteomyelitis.
The visceral form is relatively rare. It is usually seen in
immunocompromised individuals. It affects the lung, liver,
kidney, spleen, brain, prostate, bowel and the lymphatic
tissues (tonsil, lymph node).
The typical botryomycotic lesions are indurated brotic
masses that may form draining sinuses and stulas.
Literature review reveals a few reports of botryomycosis
affecting the orofacial region. Small and Kobernick (1967)
reported a patient with botryomycosis of the tongue. Rawal
and Rawal reported a patient with gingival botryomycosis
and Alavandar (1979) reported botryomycosis affecting
the mandible.
Histopathologic features
Hematoxylin and eosin stained specimens show chronic
suppurative and granulomatous inflammation with giant
cells, epithelioid macrophages and scattered microabscesses.
Within the areas of the purulent inammation, Bollingers
granules are seen. These are relatively small, but frequently microscopically visible, pale yellow or yellow-white
granules consisting of irregular aggregates or colonizations
of gram-positive cocci, usually staphylococci.
Bollingers granules are surrounded by an amorphous,
eosinophilic, refringent matrix called the Splendore-Hoeppli
phenomenon (this phenomenon is also seen around colonies of certain bacteria, fungi, helminthes, actinomyces,
mycetoma, nasofacial and subcutaneous phycomycosis and
around silk sutures).
88

Management
Surgical resection along with antibiotic therapy is the treatment of choice.

RHINOSCLEROMA (Respiratory
Scleroma)
Rhinoscleroma is an endemic, chronic, slowly progressive
granulomatous disease caused by Klebsiella rhinoscleromatis (a gram-negative rod-shaped bacteria, 2.5 m in
length).
In 1882, von Frisch identied K. rhinoscleromatis as
the etiologic agent. In 1870 Ferdinando Von Hebra, a dermatologist described the disease for the rst time. It was
later named respiratory scleroma. The word skleroma in
Greek meaning hard tumefaction, was adopted in 1932 at
the International Clinical Otorhinolaryngology Conference
(in Madrid), emphasizing involvement of upper and lower
airways.
Rhinoscleroma is contracted by direct inhalation of
droplets or contaminated material.
Clinical stages
Humans are the only identified host of K. rhinoscleromatis.
It usually affects individuals in the 2nd to 4th decades of
life. It affects people living in crowded conditions with poor
hygienic and nutritional conditions (including iron deficiency
anemia). Rhinoscleroma affects women more commonly
than men (13:1).
The nose is the most common site of infection, although
the nasopharynx, paranasal sinuses, and pharynx may also
be involved. Other affected organs include the paranasal
sinuses, eustachian tubes, middle ear, orbital tissues and
the brain.
Rhinoscleroma occurs in three overlapping stages:
catarrhal-atrophic (sometimes called ozaena), granulomatous (proliferative or nodular) and sclerotic (cicatricial or
brotic).
In the catarrhal stage, patient may complain of foul
smelling purulent nasal discharge and nasal obstruction. On
clinical examination atrophy and crusting of the nasal
mucosa or hyperemia and exudates in the respiratory tract
mucosa are evident.
In the granulomatous stage, epistaxis, nasal deformity
and destruction of the nasal cartilage (Hebra nose), hoarseness of voice, anosmia and anesthesia of the soft palate
are common signs and symptoms. Clinical examination
may reveal a bluish red and rubbery granulomatous lesion.
These lesions over a period of time turn into a pale hard
granulomatous mass.
In the sclerotic stage, clinical examination shows granulomatous lesions surrounded by dense brotic tissue.

Chapter 4 Bacterial, Viral and Fungal Infections

Diagnosis
The diagnosis of rhinoscleroma is made by the bacterial
isolation by culture on blood or MacConkey agar. Histopathological specimens can be stained with periodic acidSchiff, Giemsa and WarthinStarry stain. The presence of
Mikulicz cells (clear cytoplasm vacuolated histiocytes
containing the bacillus) and degenerated plasmocytes in
Russel bodies are diagnostic of rhinoscleroma.
The hypertrophic stage of rhinoscleroma has characteristic mild to marked high signal intensity on both T1- and
T2-weighted MR images.
Management
Nasal or pharyngeal obstruction is best managed surgically along with antibiotic therapy. Many authors recommend the use of cephalosporins and clindamycin. Shaer
et al (1981) have shown that the topical application of
2% acriflavine solution is an effective and safe treatment
option for rhinoscleroma. Tracheostomy may be required
if laryngeal scarring causes airway obstruction.

CAT-SCRATCH DISEASE

couple of months. The lymph nodes can enlarge to a size


of about 10 cm.
Other systemic manifestations include parotitis, osteomyelitis, hepatosplenomegaly, neurological conditions (seizures, altered behavior or consciousness, peripheral facial
nerve paresis, myeloradiculitis) and hematological conditions (hemolytic anemia, thrombocytopenia and eosinophilia).
When a pets saliva contaminated (as the cat constantly
licks its fur) fur is groomed, organisms from the fur are
transferred to the individuals hand. Such contaminated
ngers, when used to rub the eyes might cause self-inoculation of the organisms to the conjunctiva. Conjunctival
involvement will result in preauricular lymphadenopathy.
This association of conjunctival involvement and preauricular lymphadenopathy in cat-scratch fever is referred to
as Parinaud oculoglandular syndrome.
Several skin reactions have been reported, including
erythema nodosum, erythema marginatum and erythema
multiforme.
B. henselae and B. quinata are implicated in the causation of bacillary angiomatosis and peliosis in immunocompromised hosts such as in AIDS. Orally these lesions
mimic Kaposis sarcoma and appear as vascular lesions
and within bone may cause alveolar bone loss.
Diagnosis

Cat-scratch disease arises from the inoculation of the


gram-negative bacillus Bartonella henselae following a
cats scratch, lick or bite. It is estimated that almost 40%
of the domestic cats may have an asymptomatic B. henselae infection accompanied by bacteremia, which can persist for more than a year. It is believed that domestic cats
tend to rapidly develop antibodies and therefore appear
healthy in spite of the bacteremia.
The rst description in the literature of cat-scratch
disease is credited to Henri Parinaud in 1889. Dr Robert
Debr in 1931 described a case of a boy with a cat-scratch
on his hand associated with a suppurative epitrochlear
lymph node. He is credited with recognizing the cat as
the vector of this illness and coined the term catscratch disease. Regnery and coworkers (1992) identied
B. henselae as the causative organism for cat-scratch
disease.
Cat-scratch disease is considered as a self-limiting
granulomatous condition characterized by suppurative
regional lymphadenitis.
Clinical features
The incubation period varies from 7 to 15 days. It usually
affects individuals in the second decade of life. Patients
may present with mild fever, fatigue and malaise. The initial lesion occurs as a pustule or papule seen at the site of
the trauma (cat-scratch or bite). These initial lesions are
followed by regional lymphadenopathy that lasts for a

Neville and coworkers enumerated certain criteria for the


diagnosis of cat-scratch fever. Evidence of at least three of
the following four criteria is considered to be positive for
cat-scratch disease:
1.
2.

Contact with a cat, presence of a scratch or a primary


dermal or ocular lesion.
Positive HangarRose skin test (cat-scratch disease
skin test).

This skin test was first developed by Hanger and Rose


in 1946. Aspirated material from a lymph node of a
patient with known cat-scratch disease is pasteurized,
standardized, and tested for sterility. It is then injected
subdermally and skin reaction is noted.
3.
4.

Unidentifiable cause for lymphadenopathy.


Presence of pleomorphic bacilli with WarthinStarry
method or BrownHopps method.

However, serological test (ELISA for IgM antibodies to


B. henselae) is the gold standard for the diagnosis of
cat-scratch disease. Elevated serum titers are seen 13 weeks
after the onset of the disease process.
Management
The condition is self-limiting and usually resolves in about
6 months duration. Suppurative nodes may be aspirated to
evacuate the pus. The recommended surgical procedure to
evacuate the pus is to introduce the needle into the skin
89

Section II Oral and Maxillofacial Disturbances

1 to 2 cm away from the swelling and then burrow beneath


the surface of the skin to reach the affected node. The technique helps to hasten the healing and prevent formation of
a persistent sinus.
Antibiotics such as gentamicin, penicillin, ciprooxacin and rifampin may be used when systemic involvement
is apparent.
Other bacterial infections with oral manifestations such
as tuberculosis, syphilis, leprosy and gonorrhea have been
described in Chapters 8, 21 and 22.

VIRAL INFECTIONS
INFECTIOUS MONONUCLEOSIS
(Monoglandular Fever, Kissing Disease)
Infectious mononucleosis (IM) is a clinical syndrome caused
by EpsteinBarr virus-4 (EBV, human herpes virus-4).
EBV replicates primarily in beta-lymphocytes but also
may replicate in the epithelial cells of the pharynx and
parotid duct.
Children and young adults are usually affected. The virus
is transmitted via intimate contact. Children may acquire
the virus through sharing of saliva contaminated ngers,
toys and serving spoons. Direct transfer of contaminated
saliva may occur in adults following kissing (hence the
name kissing disease) or sharing of straws. The incubation
period is 48 weeks.
Clinical features
The characteristic clinical features of IM include, malaise,
fatigue and anorexia. These symptoms are immediately
followed by high fever (about 104F) which lasts for almost
2 weeks.
The most striking feature of IM is the presence of
lymphadenopathy. Any or all lymphatic chains may be
enlarged. Lymphadenopathy is always bilateral and symmetrical in all patients. Bilateral posterior and anterior
cervical lymphadenopathy is highly suggestive of EBV
infectious mononucleosis.
Other clinical features include the presence of tonsillar
enlargement, hepatosplenomegaly, jaundice, rhinitis and
pharyngitis.
Hoaglands criteria (1975) for the diagnosis of IM
include: at least 50% lymphocytes and at least 10% atypical lymphocytes in the presence of fever, pharyngitis, and
adenopathy, and conrmed by a positive serologic test.
Oral manifestations include hard and soft palate
petechiae, necrotizing ulcerative mucositis, necrotizing
ulcerative gingivitis and pericoronitis. Occasionally, the
parotid gland may be affected along with facial nerve
palsy.
90

Warwick et al (2003) reported a patient with IM, ruptured spleen and Cullens sign (periumblical ecchymosis).
They also suggest that the presence of abdominal pain is an
uncommon symptom in infectious mononucleosis and its
occurrence is therefore a danger sign that may forewarn a
potentially life threatening complication of ruptured spleen.
The complications of IM include myocarditis and cardiac conduction abnormalities, neurologic abnormalities,
meningitis, encephalitis, cranial nerve palsies, retrobulbar
neuritis, acute interstitial nephritis, hemolytic anemia,
thrombocytopenia and upper airway obstruction.
Syndrome association
Chronic fatigue syndrome and Lemierres syndrome have
been reportedly associated with IM. The association of IM
and chronic fatigue syndrome is still very questionable
and debatable.
Diagnosis
The Paul-Bunnell test is a serological test that detects heterophile antibodies by agglutination of sheep or horse red
blood cells. However, in the 1st week of infection, the falsenegative rate is as high as 25%.
VCA-IgG and VCA-IgM tests are useful in diagnosing
patients who have highly suggestive clinical features but
negative heterophile antibody test results.
Antibody to EpsteinBarr nuclear antigen (EBNA),
while typically not detectable until 68 weeks after the
onset of symptoms, can help distinguish between acute
and previous infections.
Elevated hepatic transaminase levels may be seen in
about 50% of the IM patients.
Management
Infectious mononucleosis usually resolves in about 6 weeks.
IM is best managed with extensive palliative and supportive
healthcare. Patient should be adequately hydrated. Fever
and malaise may be managed with acetaminophen and
NSAIDs. Though steroids have been used frequently, they
are best used only in an emergency to relieve the patient
of respiratory compromise secondary to pharyngeal edema.
Antibiotics like penicillins are best avoided as these
patients have a higher risk of developing a morbilliform
skin rash.

ACUTE LYMPHONODULAR PHARYNGITIS


Acute lymphonodular pharyngitis is caused by Coxsackie
virus A10. It is characterized by prodromal fever, anorexia,
headache and sore throat. Like most viral infections, the
condition is self-limiting and generally resolves in about
2 weeks.

Chapter 4 Bacterial, Viral and Fungal Infections

Clinical features
Acute lymphonodular pharyngitis is usually seen in children and young adults. Clinically, the hyperplastic lymphoid aggregates are evident as discrete yellow to dark
pink colored nodules or white to yellow papules surrounded
by an erythematous ring, generally 15 in number. These
lesions are typically found on the tonsillar pillars, uvula,
soft palate and oropharynx.
Histopathological evaluation of these nodules may reveal
epithelial necrosis and inclusion bodies (intranuclear or
cytoplasmic) and multinucleated cells.
Management
The condition is self-limiting and the management is
aimed at supportive care. Non-aspirin containing analgesics are beneficial.

MEASLES (Rubeola)
Measles is caused by an RNA virus, paramyxovirus.
Measles is an acute and highly communicable disease and
infection confers lifelong immunity. The disease process
is marked by the presence of prodromal fever, cough, conjunctivitis and coryza (profuse discharge from the nasal
mucous membrane).
Measles may often occur as an epidemic. The virus is
transmitted via direct contact or by droplet infection and
the respiratory tract forms the portal of entry.
Measles is usually considered as a serious disease in
malnourished, immunocompromised or vitamin decient
individuals.
Clinical features
Following a 14-day incubation period skin rashes begin to
appear. About 23 days before the typical skin rash
appears the patient may exhibit prodromal upper respiratory symptoms and conjunctivitis along with lymphadenopathy. The skin rash fades away in about 7 days. Pale
skinned individuals may exhibit areas of altered pigmentation following resolution of the skin rash.
During this stage of the infection the pathognomonic
Kopliks spots begin to appear on the buccal mucosa. Kopliks
spots are small, irregular, red spots with a minute bluish
white speck in the center of each seen on the buccal
mucosa and lingual mucosa. They are named after Henry
Koplik (18581927), an American pediatrician who rst
described them in 1896.
Patients are usually irritable and photophobic at this
stage. These spots represent sites of virus replication and
sites of inammation of the mucous glands.
As the disease progresses, bacterial superinfection
may lead to diarrhea, bacterial pneumonia, cancrum oris,

convulsions and subacute sclerosing panencephalitis may


develop.
Diagnosis
Measles can be diagnosed based on the characteristic skin
rash and the Kopliks spots. The diagnosis can be confirmed by the measles virus sandwich-capture immunoglobulin M (IgM) antibody assay.
Prevention and management
Infants below 1 year of age are protected by the maternal
antibodies. Live attenuated measles vaccination given to a
child older than 1 year provides immunity.
The measles-mumps-rubella (MMR) vaccine is given in
two doses. The rst dose is given to children at the age of
1 year. The second dose is given usually between 4 and
6 years of age.
Supplementation by vitamin A during an acute attack,
minimizes the morbidity and mortality risks.

GERMAN MEASLES (Rubella)


Rubella is caused by Rubivirus, an RNA virus of the
Togaviridae family. Rubella runs a milder course and it
affects the skin, lymphatic system and the joints. However,
infection of the mother during pregnancy may lead to
serious complications for the developing infant.
The disease spreads via the respiratory route and mainly
by droplet infection and to a lesser extent by direct contact with contaminated throat or nasal secretions.
Clinical features
The incubation period lasts for approximately 18 days. It
typically affects children and to some extent young adults.
The initial prodromal symptom period is followed by
lymphadenopathy. Suboccipital and posterior auricular
nodes are typically enlarged. The other clinical findings
include skin rashes and pharyngitis. The most important
complication of rubella is the congenital rubella syndrome. The maculopapular rash appears pink and appears
first on the face and then spreads rapidly downwards to
involve the trunk and the extremities. These eruptions are
generally transitory and persist only for about 3 days, thus
accounting for the famous synonym 3-day measles.
Oral manifestations
The common oral manifestation is the presence of minute
red macules and petechiae on the soft palate and uvula
(Forchheimer spots: non-specific for rubella) of pinpoint
red macules and petechiae can be seen over the soft palate
and the uvula just before or with the exanthem.
91

Section II Oral and Maxillofacial Disturbances

Mothers suffering from rubella during the rst trimester are likely to have children who exhibit pitting and
enamel hypoplasia and rarely complete aplasia. Eruption
of teeth may be retarded. Some authors have reported cleft
lip and palate in some of these children.
Prevention and management
Rubella is best prevented by mumps-measles and rubella
vaccination. The disease is self-limiting. As individuals are
highly contagious in the first 1 week, following appearance of the skin rash, they should ideally abstain from
group activities during this period. Maintenance of hydration and bed rest is generally sufficient. Non-aspirin containing NSAIDs may be given for managing the prodromal
symptoms.

HIV AND AIDS


Human immunodeficiency virus (HIV) is a lentivirus (a
member of the retrovirus family) that can lead to acquired
immunodeficiency syndrome (AIDS). HIV infects cells of
the human immune system and destroys them or prevents
them from functioning. Such individuals whose immune
system is defective are much more vulnerable to opportunistic infections.
Retroviruses have an inherent advantage of both mutation (typical of RNA viruses) and latency (typical of DNA
viruses).

Discovery of HIV
Disease syndromes similar to the clinical manifestation of
AIDS have been described in the ancient Ayurvedic literature. Sushrutha in 800 BC and later Charaka and Vagbhatta
describes a conditions with loss of muscle mass, fever, skin
eruptions and ulcers, complexion changes, neurological
disorders, exhaustion, coma and death, and stated that in
irremediable stages treatment should be given up.
In 1981, homosexual men with symptoms of a disease
that now are considered typical of the acquired immunodeciency syndrome (AIDS) were rst described in Los
Angeles and New York. The men had an unusual type of
lung infection (pneumonia) called Pneumocystis carinii
(now known as Pneumocystis jiroveci) pneumonia (PCP)
and rare skin tumors called Kaposis sarcoma. The patients
were noted to have a severe reduction in CD4 cells. These cells,
often referred to as T cells, help the body ght infections.
Shortly thereafter, this disease was recognized throughout
the United States, western Europe, and Africa. In 1983,
researchers in the United States and France described the
virus that causes AIDS, now known as the human immunodeciency virus (HIV) and belonging to the group of viruses
called retroviruses. In 1985, a blood test became available
92

that measures antibodies to HIV that are the bodys immune


response to the HIV. This blood test remains the best
method for diagnosing HIV infection. American researcher
Robert Gallo and French scientist Luc Montagnier are both
credited for discovering HIV.
In the later parts of 1986 in India, rst cases of HIV
were diagnosed among sex workers in Chennai, Tamil Nadu.
It was noted that contact with foreign visitors had played
a role in initial infections among sex workers.
In 1987 a National AIDS Control Program was launched
to co-ordinate national responses. Its activities covered
surveillance, blood screening, and health education. By
the end of 1987, out of 52,907 who had been tested, around
135 people were found to be HIV positive and 14 had
AIDS. Most of these initial cases had occurred through
heterosexual sex, but at the end of the 1980s a rapid
spread of HIV was observed among injecting drug users in
the three north-eastern states of India, namely Manipur,
Mizoram and Nagaland. In 1992 the government set up
NACO (the National AIDS Control Organization), to oversee the formulation of policies, prevention work and control programs relating to HIV and AIDS.
In 1982, AIDS was originally dened by US Center for
Disease Control as the disease, at least moderately predictive of a defect in a cell mediated immunity occurring in a
person with no known cause for diminished resistance to
that disease.
HIV infection in children was rst recognized in 1983.
Pediatric AIDS can be dened as disease occurring in children less than 13 years of age.
The etiologic agents of AIDS and HIV infections belong
to the family of human retroviruses and the subfamily of
lentiviruses.
The four recognized human retroviruses belong to two
distinct groups:
i.
ii.

The human T lymphotropic viruses [HTLV-1 and 2]


The human immunodeficiency virus [HIV-1 and 2]

The most common cause of HIV disease throughout the


world is HIV-1, which was identified in May 1983, and
HIV-2 was first identified in 1986 in west African patients
and was originally confined to west Africa. The major difference in the genomes of HIV-1 and 2 is that the HIV-2
lacks the vpu gene. HIV is more closely related to an SIV
(simian immunodeficiency virus) isolated from chimpanzees in 1990. HIV-2 is much more closely related phylogenetically to the simian immunodeficiency virus found in
sooty mangabees.

Structure of the HIV-1 Virion


HIV-1 virion is spherical in shape and contains an electron
dense core surrounded by a lipid envelope derived from
the host cell membrane during budding of the virus from
the infected cell.

Chapter 4 Bacterial, Viral and Fungal Infections

The virus core contains several core proteins, two


strands of genomic RNA, and the enzyme reverse transcriptase that is characteristic of all retroviruses.
The viral envelope is studded with two viral glycoproteins, gp120 and gp41. The gp41 projects outward and is
important for the fusion of the virus to its target cells and
gp120 helps in binding of host cell CD4 receptor.
The virion is approximately 10 kb in length, and it contains the gag, pol and env genes, that code for the core
protein, reverse transcriptase and envelope proteins
respectively.
Each structural region comprises three structural proteins/
antigens. Env gene makes gp160, gp120 and gp41 glycoproteins. Gag gene is responsible for p55, p24, and p17
antigens and pol for p31, p51, p66 antigens.

Subtypes HIV-1 Virus


The strains of HIV-1 can be classified into three groups:
the major group M, the outlier group O and the new
group N. These three groups may represent three separate
introductions of simian immunodeficiency virus into
humans.
More than 90% of HIV-1 infections belong to HIV-1
group M. Group O is believed to be restricted to westcentral Africa and group N (discovered in 1998) is seen in
Cameroon is extremely rare.
Within group M there are known to be at least nine
genetically distinct subtypes (or clades) of HIV-1. These
are subtypes A, B, C, D, F, G, H, J and K (Table 2).
Occasionally, two viruses of different subtypes can
meet in the cell of an infected person and mix together
their genetic material to create a new hybrid virus (a process similar to sexual reproduction, and sometimes called
viral sex).
Many of these new strains do not survive for long, but
those that infect more than one person are known as circulating recombinant forms or CRFs. For example, CRF
A/B which is a mixture of subtypes A and B.
Lentivirus
HIV-1

HIV-2

Group M

Group N

Table 2

Predominant types of HIV-1 in various parts of the


world

Region

Predominant type

Other subtypes

South America

Australia

C, F

Western Europe

A, C, D

Eastern Europe

B, C, G, D

Africa

A, B, D, C, E, F, G, H, O

Uganda

A, B, C, D, G

Zaire

A, D, H

Kenya

Nigeria, Gabon

G, H

Cameroon

A, B, E, G, H, F

Central Africa

A, C, D, E

Zambia, Malawi
(Southeast Africa)

China

Bb

Southeast Thailand,
Myanmar

Bb, E

Indonesia

India

A, B, F

nucleic acids in the reverse direction, i.e. DNA from RNA


and hence termed reverse transcriptase and the virus as
retroviruses.

Basic Genetics of HIV


HIV contains nine genes made of 9,749 base pairs.
Gag (codes for internal structural proteins and capsid proteins using about 2,000 base pairs), pol (codes for the three
enzymes necessary for replication using about 2,900 bp) and
env (codes for the surface proteins gp120 and gp41 that
protrude from the lipid envelope and attach to cellular
receptors using about 1,800 bp).
Other genes are tat (transactivator protein), rev (regulator of expression of virus protein), vif (virus infectivity
factor), nef (misnamed negative regulator factor, but really
an enhancing factor), vpr (virus protein R), and vpu (virus
protein U).

Group O

Stages of Infection (Figures 117)


Clades A, B, C, D, F, F2, G, H, J, K

The hallmark of the life cycle of HIV infection is the reverse


transcription of genomic RNA to DNA by the enzyme reverse
transcriptase. Crispian Scully (1997) stated that HIV is an
RNA virus containing an enzyme, which can transcribe

Step 1: Entry of the HIV virion into the host T-cell, is triggered by the binding of membrane proteins to receptors
on the T-cell surface.
Step 2: The membrane proteins on the virus are units
called gp120. These gp120 unit binds to the receptors
called CD4 on the T-cell. The union of gp120 and CD4
initiates another event.
93

Section II Oral and Maxillofacial Disturbances

Figure 1

Figure 3
gag p17
gag p24

HIV

RNA

4
CD
gp 40
gp 120

Envelopment of
virus into host cell

T-cell

Co-receptor CCR5 combines with CD4

Figure 4
Binding of HIV virion into host T cell

Figure 2
HIV

Endocytosis

T-cell

CD

Complete envelopment of virus

T-cell

5
CR

Figure 5

Capsid

gp120 unit binding to CD4 receptor


HIV

Step 3: CD4 changes its shape so that another membrane


protein of the T-cell called CCR5 fits. CCR5 is a co-receptor that is essential in enabling the virus to enter the cell.
Patients with defective co-receptors do not show signs of
HIV infection in spite of repeat exposures.
Step 4: These events lead to the envelopment of the virus
into its host cell.
Step 5: This process is known as endocytosis.
Step 6: Once inside the host cell capsid begins to shed its
coat.
94

T-cell

Capsid within host cell

Step 7: Shedding of the capsid is necessary for the exposure


of viral RNA and enzymes. In HIV, the viral genome is in
the form of RNA. There are two strands of RNA connected
at one end. The capsid also contains important enzymes for
the events leading to infection of the host cell.

Chapter 4 Bacterial, Viral and Fungal Infections

Figure 6

Figure 8

Enzymes
Double stranded
viral DNA
RNA
Capsid (shedding the capsid)

Shedding of capsid

Formation of double stranded DNA

Figure 7

Figure 9
Viral RNA

Viral DNA

Reverse
transcriptase
Viral DNA
Host cell nuclear
envelope

Reverse transcription
Host DNA

Step 8: The first event is called reverse transcription. From


a strand of RNA, the enzyme reverse transcriptase catalyzes the formation of viral DNA.
Step 9: Reverse transcriptase also helps in the formation
of the second strand of viral DNA.
Step 10: The viral genetic material is ready to enter the
host cell nucleus and become integrated into the host DNA.
Step 11: The viral DNA is integrated with the help of
another enzyme called retroviral integrase. The integrated
DNA is now called a provirus.
Step 12: The provirus serves as a template for the synthesis of viral RNA. Upon completion, the newly formed viral
RNA moves out into the cytoplasm.
Step 13: The viral RNA carries information that codes for
viral proteins and enzymes. Therefore, it is also called
messenger RNA. The codes on the viral RNA are translated
into proteins and enzymes in the form of a long chain
called a polypeptide chain.
Step 14: The polypeptide chain includes important proteins for the envelope, capsid, enzymes, and other parts of

Viral DNA entering host cell nucleus

Figure 10

Viral DNA

Host DNA

Retroviral integrase
[PROVIRUS]

Viral DNA integrating with host DNA

95

Section II Oral and Maxillofacial Disturbances

Figure 11

Figure 13

Ribosome
Viral RNA

Synthesis of viral RNA


Protease breaking polypeptide chain

Figure 12
Figure 14
Viral RNA

Host cell

T-cell nucleus

Capsid begins to form


Polypeptide chain

Early stages of capsid formation


Formation of polypeptide chain

Figure 15

the new virus to be formed. The enzyme protease helps to


cut this chain into individual components.
Step 15: With all the components ready to leave the host
cell the capsid forms to envelop these pieces.
Step 16: Assembly of the capsid initiates the insertion of
membrane proteins on the host cells plasma membrane.
Step 17: As the new virus leaves or buds from the surface
of the host cell, it forms an envelope with the inserted
membrane proteins.
Step 18: Numerous new viruses can be formed from one
T-cell and move on to infect other T-cells in various parts
of the body.
96

Membrane proteins

Host cell

Formation of membrane proteins on host cell

Chapter 4 Bacterial, Viral and Fungal Infections

Figure 16
Plasma membrane

Budding
Host cell

Newly formed virion leaving host cell

Figure 17

New HIV molecule


Host cell

Newly formed HIV molecule

Step 19: The T-cells are eventually destroyed, leaving the


body with a compromised immune system and susceptible
to attack by foreign bodies.

Transmission
Transmission of HIV-1 occurs mainly through one or more
of three routes:
1.
2.
3.

Sexual contact
Passage of the virus from infected mothers to the
newborn
Through blood and parenteral inoculation.

Sexual contact
It is the predominant mode of transmission. The rate of
infection is increased with the number of sexual partners

and with the frequency of anal receptive intercourse,


which predisposes to rectal trauma in the receptive partner. It is believed that the virus is carried in lymphocytes
present in the semen and enters the recipients body
through abrasions in rectal mucosa. HIV-1 has been found
in vaginal and cervical secretions and in monocytes and
endothelial cells within the submucosa of the uterine cervix of infected individuals through which the transmission
to the male partners takes place.
Zagury D Bernard and Leibwitch et al (1984) stated that
HIV spreads to women from men through the semen and
from cervical secretions of infected woman to men. This
was based on the isolation of HIV from semen and cervical
secretions, which makes it biologically possible for HIV to
spread heterosexually from men to women and women
to men.
Faltz, Mc Clure and Doughaty et al (1986) stated that
infection can occur without trauma to the vagina. This
was substantiated by experimental vaginal HIV infection
of a chimpanzee and from the case reports of infection
through articial insemination of the virus.
Pandian et al (1987) reported a relatively higher risk for
those engaged in anal intercourse than those having only
vaginal intercourse but emphasized that anal intercourse
was not always necessary for transmission.
Greenblatt et al (1987) stated that a factor that may
inuence transmission is genital ulceration. He stated that
an African study found an increased risk of being infected
on those with a history of genital ulceration.
Mayer and De Glottal (1987) stated that anecdotal cases
of HIV transmission by oral sexual activity have been
reported but has never been convincingly demonstrated.
Nobut Gilmole (1992) reported that among the sexual modes of HIV transmission, intercourse is the most
predominant factor, as more than 60% of HIV transmission worldwide were attributed to vaginal intercourse. He
also stated that everybody is susceptible to HIV infection
although some people have been reportedly exposed to
the virus and inexplicably they have not been infected.
He stated that susceptibility to HIV may need to be facilitated by mucosal injury caused by trauma, sexually transmitted diseases or genital ulcers.
Anne M Johnson (1988) stated that there is some evidence that the risk of transmission increase both with the
duration of the sexual relationship and the frequency of
sexual contact.
WHO (1997) stated that individuals vary on their susceptibility to infection for reasons that are not known.
Through sexual intercourse some may get infected by a
single exposure from infected partners while others may
not become infected even after repeated exposures. The
receptive partner is at greater risk than the insertive partner
in both vaginal and anal intercourse. Male to female
transmission was higher than transmission from female to
males. This was substantiated on 5-year follow-up study
97

Section II Oral and Maxillofacial Disturbances

at San Francisco where 20% of female partners of HIV


positive men got infected whereas only one case of female
to male transmission was observed. As per their observation they stated that anal sex was more hazardous than
vaginal sex because there was greater degree of trauma in
anal intercourse as anal mucosa is thin and vascular. So
the highest risk is for person who is passive or receptive
partner in anal intercourse. They also opined that oral sex,
deep kissing may carry a risk of infection and risk of
acquiring infection is much higher in those suffering from
sexually transmitted disease especially so in the presence
of ulcerative lesions of the genitalia.
Passage of the virus from infected mothers
to the newborns
Carrew, Jaffe, Hardy A Metal (1988) stated that the proportion of HIV-infected pregnant women whose infants are
subsequently found to be infected ranges from 16 to 33%,
but the specific determining perinatal infection remains
unexplained.
Oxdely (1988) stated that a rare case of transmission
through breast milk has been documented. Philiop A
Piczzo and Karina M Balter (1991) stated that the exact
time during pregnancy or delivery when HIV transmission
occurs is not well established. Although the presence of
virus had been documented in fetal tissues after 815
weeks gestation, HIV was found predominantly during
intrapartum period. This might occur because of ingested
maternal blood or because of maternal-fetal transmission
during labor and delivery.
Goryle, Selik and Chersov (1990) stated that the most
common means of transmission of HIV to a child from an
infected mother is either during pregnancy or at birth.
They stated that although the vertical transmission of HIV
from an infected mother to an infant is unique, few cases
may represent a blood borne transmission.
In 1996, Indian Council of Medical Research stated
about the selected factors associated with mother to child
transmission of HIV-1. It was classied into:
1.

2.

98

Proved or possible modes of transmission


Maternal immune deficiency
Chorioamnionitis
Breast feeding
Vaginal delivery
Low maternal serum vitamin A concentration
Instrumental injury during labor and/or delivery
(episiotomy, forceps, etc.)
Premature rupture of membranes
Prematurity
Prolonged labor
Controversies
Maternal immune response against HIV
Viral strain characteristics

Ramos-Gomez (1997) stated that HIV can be transmitted


perinatally from mother to newborn infant in three
ways:
1.
2.
3.

Transplacentally during pregnancy


During delivery as the infant passes through the birth
canal
Postnatally during breast feeding

An estimated 94% of pediatric HIV infection is acquired


perinatally and around half of these reported perinatal
infection occurred when the infant through the birth
canal.
WHO and NACO (1997) in their publication stated that
most of the children acquire HIV from their mothers through
the three possible routes: transplacentally, intrapartum
and breast feeding.
The other routes like blood transfusion and role of
contaminated syringes also contributed in a small way.
They stated that transplacental is a major source of infection and parental transmission accounting for 80% of
all AIDS cases. Frequency of transmission from mother
to child was around 25% and transmission was more in
mothers with HIV symptomatic group than asymptomatic
group. They stated that intrapartum transmission was due
to contact of child with maternal blood during delivery.
They also stated that the transmission can occur through
breast feeding, as the virus has been isolated in breast
milk.
The mother to child transmission can be now prevented by the recent use of antiretroviral drugs. These are
said to prevent the virus transmission from mother to
child if the virus status of the mother is detected in early
stages of pregnancy and prompt use of antiretroviral
therapy.
Through blood and parenteral inoculation
Volken Wah, Hans H Kramer and Thomas et al (1986)
reported a case of HIV infection that appeared to have
occurred through horizontal transmission with two siblings. They stated even minor bites by HIV infected children may carry the risk of transmitting the virus. They
cautioned the parents and teachers and other people
responsible for HIV infected children should be aware of
this possibility and try to prevent spread of virus by this
route.
Fashy, Schmith and Sash et al (1989) stated that risk of
HIV transmission to healthcare workers by accidental parenteral exposure to infected blood has been estimated to
be 0.36% and 0.41% of such injuries.
Gershon, Valhov and Nelson (1990) stated that in a
study of more than 1,300 dental healthcare workers 94%
had sustained an accidental inoculation type injury with a
median number of three parenteral injuries per year.

Chapter 4 Bacterial, Viral and Fungal Infections

However the risk of HIV infection in this study was


only 0.08%.
Desjarlair and Friedman (1995) stated that transmission
by parenteral exposure to infected blood such as through
the sharing of uncleaned injection equipment during
injecting drug appeared to be the most efcient means of
HIV transmission. They also stated that the prevalence of
HIV infection has risen rapidly among equipment sharing
during drug abuse in many countries, emphasizing the
spread by the HIV by this mode. Mast and Grebreding
(1995) stated that volume of blood involved in percutaneous exposure may prove an important determinant of risk.
The type of gauge of needle used, the depth of penetration
and glove use, effect the amount of blood transferred during needle prick injuries. They also stated that the titer of
virus in the contaminant is hypothesized to be an important variable affecting the infection. They stated that mean
circulating viral titer in patients with AIDS was 1001,000
times higher than in patients with HIV infection who are
asymptomatic and exposure of blood from patients with
AIDS was associated with higher risk of transmission.

HIV and Saliva


Malamad et al (1997) in their review article Inhibition of
HIV infectivity by saliva stated that viral inhibitory factors are present in a variety of human saliva. They
proposed that the inhibitory factors are produced within
the salivary glands probably in greater concentration in
submandibular saliva and may indicate the presence of
multiple factors. They concluded from their study that
saliva does not lyse HIV.
Shugars and Wahi (1998) in their article How oral cavity resists transmission of HIV stated that the thick epithelial layer of intact oral mucosa is a barrier to infection.
They stated that saliva lubricates the mucosa, dilutes the
microbial burden and also washes microbes into the gastrointestinal tract where they are destroyed. When trauma
or disease ruptures the physical barrier of the mucosa, HIV
can potentially enter susceptible cells. They stated that
rare cases of transmission have been reported through
blood, blood contaminated oral mucosa or saliva. Further
they stated that saliva inhibits HIV by several endogenous
inhibitors and oral secretion can neutralize HIV via virus
specic antibody response. Various salivary components
like lactoferrin, lysosome, lactoperoxidase exert antimicrobial effects. Mucins and thrombospondin can entrap
viruses. DefensinsSLP-I and thrombospondin work to
inhibit HIV from entering susceptible cells. They conclude
that mouth is made resistant to HIV transmission by
the combination of a thick epithelial layer, low number of
CD4 bearing target cells and variety of endogenous inhibitors antiviral antibodies. They also stated that these
inhibitory mechanisms may fail when mucosal surface is
not intact.

ACQUIRED IMMUNE DEFICIENCY SYNDROME


Centers for Disease Control and Prevention (CDC) in 1993
had defined acquired immunodeficiency syndrome (AIDS)
as the occurrence of one or more group of life-threatening
opportunistic infections, malignancies, neurologic diseases, and other specific illnesses in patients with HIV
infection and/or with CD4 counts less than 200/mm3. CDC
stated that this definition was a surveillance definition that
was established to track the incidence of this disease and
the relative occurrence of diseases that are likely to occur
in severely immunosuppressed individuals. It is stated that
in that part of the world where CD4 enumeration is not as
readily available, clinical diagnoses, in conjunction with
serologic tests for HIV, could be used to define patients
with AIDS and to track the spread of this epidemic.

Revised Classification System of HIV Disease


(CDC, 1993)
The CDC disease staging system assesses the severity of
HIV disease by CD4 cell counts and by the presence of
specific HIV-related conditions.
The denition of AIDS includes all HIV-infected individuals with CD4 counts of  200 cells/l (or CD4 percentage 14%) as well as those with certain HIV-related
conditions and symptoms.
CD4 (mm3)

 500

A1

B1

C1

200 to 400

A2

B2

C2

 200

A3

B3

C3

Category A

Asymptomatic HIV infection


Persistent generalized lymphadenopathy
Acute retroviral syndrome

Category B

Bacillary angiomatosis
Candidiasis
Cervical dysplasia
Constitutional symptoms (fever, diarrhea  1 month)
Oral hairy leukoplakia
Herpes zoster
Idiopathic thrombocytopenic purpura
Listeriosis
Pelvic inflammatory disease
Peripheral neuropathy

Category C (AIDS defining conditions)

CD4 count less than 200 cells/l


Candidiasis (pulmonary, esophageal)
99

Section II Oral and Maxillofacial Disturbances

Cervical cancer
Coccidiodomycosis
Cryptosporidiosis
Cytomegalovrius
Encephalopathy
Herpes simplex (chronic, esophageal)
Histoplasmosis
Isosporiasis
Kaposis sarcoma
Lymphoma
Mycobacterium avium/Mycobacterium kansasii
Pneumocystis carinii
Recurrent pneumonia
Progressive multifocal leukemia.

WHO (1997) suggested the criteria for HIV infection. This


criterion was based on the clinical diseases and was classified into cardinal findings, characteristic findings and
associated findings.
Cardinal findings
Adults

Children

Kaposis sarcoma

Kaposis sarcoma (rare in


children)
Pneumocystis carinii
pneumonia
Lymphoid interstitial
pneumonitis
Esophageal candidasis

Pneumocystis carinii
pneumonia
Toxoplasma encephalitis
Esophageal candidiasis
Cytomegalovirus retinitis

Diarrhea (continuous or
intermittent more than
1 month)
Generalized extrainguinal
lymphadenopathy
Skin infection (severe or
recurrent)
Cough for more than
1 month dermatitis

Stages

CD4 count range

Oral thrush

Severe prurigo (itching


without lesion)
Non-Hodgkins lymphoma
Recurrent bacterial/viral
infections
Herpes zoster, past or
present
Progressive neurological
disease
Herpes zoster:
multidermatomal

Oral hairy leukoplakia


Miliary, extrapulmonary or
Non-cavity pulmonary
tuberculosis
Cryptococcal meningitis
Non-cavity pulmonary
tuberculosis

Acute infection

1,000750
750200

215 weeks

Early symptomatic

500100

15 years

Late symptomatic

50200

14 years

Advanced disease

500

02 years

Weight loss more than 10%

CD4 Strata

Complication

500/mm

Persistent generalized lymphadenopathy


Candida vaginitis
GuillainBarre syndrome
Polymyositis
Aseptic meningitis
Pneumococcal pneumonia
Pulmonary tuberculosis
Thrush
Zoster
Cryptosporidiosis, self-limited
Cervical intraepithelial neoplasia
Kaposis sarcoma
B cell lymphoma
Anemia
Idiopathic thrombocytopenic purpura
Mononeuritis multiplex
Oral hairy leukoplakia
P. carinii pneumonia
Disseminated or chronic herpes simplex
Miliary/extrapulmonary
Tuberculosis
Candida esophagitis
CNS lymphoma
Wasting
HIV-associated dementia
Peripheral neuropathy
Cryptococcosis
Disseminated histoplasmosis and
microsporidiosis
Disseminated/chronic herpes simplex
Disseminated M. avium
CMV retinitis

200/m3
(usually
100/m3)

Fever (continuous or
intermittent more
than 1 month)
100

Children
Neurologic findings
(dementia)
Focal motor deficits

14 weeks

Correlation of CD4 cell count and AIDS


complications

Associated findings
Adults

Duration

Asymptomatic

Characteristic findings
Children

Drug reactions (previously


not seen)
Failure to thrive fever
(continuous/intermittent
than 1 month)
Generalized
lymphadenopathy

Stages in HIV disease

200500/mm3

Adults

Progressive headache

50/mm3

Chapter 4 Bacterial, Viral and Fungal Infections

Tuberculosis and HIV


It is suggested that the clinical presentation of tuberculosis
is dependent on the degree of immune suppression and
those patients with CD4 cell counts above 200/mm3 more
likely to have classical upper lobe disease and cavitary
changes characteristic of reactivation disease. Extrapulmonary tuberculosis frequently occurs with HIV infection
and usually seen in 70% of patients with CD4 cell count
less than 100/mm3. WHO (1997) stated that in India, 60%
of AIDS patients have tuberculosis infection.

5.

6.

Oral manifestations
In 1986 the European community took the initiative to
establish a classification system for oral manifestations
in HIV infection. The classification was presented by
Pindborg. He classified the oral manifestations into six
categories based on associated agents like fungal, bacteria,
viral, neoplasm, neurological and unknown cause.
1.

2.

3.

4.

Fungal infection
a. Candidiasis
i. Pseudomembranous
ii. Erythematous
iii. Hyperplastic
iv. Angular cheilitis
b. Histoplasmosis
c. Cryptococcosis
d. Geotrichosis
Bacterial infection
a. HIV Necrotizing gingivitis
b. HIV Gingivitis
c. HIVPeriodontitis
Caused by: Mycobacterium avium intercellulare,
Klebsiella pneumoniae, Enterobacterium cloacae,
Escherichia coli
d. Actinomycosis
e. Cat-scratch disease
f. Sinusitis
g. Exacerbation of apical periodontitis
h. Submandibular cellulitis
Viral infection
a. Herpes simplex
b. Cytomegalovirus
c. EpsteinBarr
Hairy leukoplakia
d. Varicella zoster
i. Herpes zoster
ii. Varicella
e. Human papilloma virus
i. Verruca vulgaris
ii. Condyloma acuminatum
iii. Focal epithelial hyperplasia
Neoplasms
a. Kaposis sarcoma

b. Squamous cell carcinoma


c. Non-Hodgkins lymphoma
Neurologic disturbances
a. Trigeminal neuropathy
b. Facial palsy
Unknown cause
a. Recurrent aphthous ulceration
b. Progressive necrotizing ulceration
c. Toxic epidermolysis
d. Delayed wound healing
e. Idiopathic thrombocytopenia
f. Salivary gland enlargement
g. Xerostomia
h. Melanotic hyperpigmentation

Diagnostic criteria
In 1989, WHO Collaboration Center for Oral Manifestation
of the HIV under WHO Global Program on AIDS and
European Clearing House of Oral Problems related to HIV
defined the diagnostic criteria for oral manifestations.
These diagnostic criteria were proposed for epidemiological surveys. The diagnostic criteria were given for the most
common oral manifestations. Following are the diagnostic
criteria suggested.
1. Candidiasis
i.

Pseudomembranous: The pseudomembranous is presented as a white or yellow removable plaque leaving


a red surface. Pseudomembranous may be located in
all parts of the oral cavity.
ii. Erythematous: It is defined as red area without
removable plaques often located on palate, dorsum
of the tongue and buccal mucosa. Smears from red
area must be positive for candida hyphae on PAS
staining.
iii. Angular: Fiery and commissures. Smears from red area
must be positive for candida on PAS staining.
2. Periodontal disease
a.

b.

c.

Gingivitis: They defined gingivitis as the disease characterized by fiery red edematous attached gingiva and
may affect the alveolar mucosa. No ulceration must be
present.
Necrotizing gingivitis: This is characterized by gingival pain, swelling, ulcerations, necrosis or as distribution of interdental papillae covered with a fibrous
slough. The patient suffers from fever and halitosis
may be present.
Periodontitis: This is characterized by aggressive
irregular bone destruction. Any infection that gives
the impression of affecting periodontal structure other
than gingiva.
101

Section II Oral and Maxillofacial Disturbances

3. Hairy leukoplakia

Focal epithelial hyperplasia


Verruca vulgaris
Varicella zoster virus
Herpes zoster
Varicella

Hairy leukoplakia presents as a white, non-removable


lesion on margin of the tongue. The surface is corrugated,
but might be non-corrugated if it is seen on the inferior
surface of the tongue or on the buccal mucosa. To establish a reliable diagnosis, a biopsy must be performed.
Biopsy from hairy leukoplakia shows hair-like projections,
hyperparakeratosis, koilocytic like cells and no inflammation. The surface layer of the epithelium shows numerous
hyphae of candida.

Group 3: Lesions seen in HIV infection

4. Oral Kaposis sarcoma

A characteristic macroscopic appearance of either erythematous or violaceous plaque-like lesions, or a bulky tumor
predominantly seen in palate or on the gingiva.

Revised classification by the European Community


Clearing House (1992)
European Community Clearing House in 1992 revised the
classification of oral lesions associated with HIV infection.
The manifestations were divided into three main groups:
i. Lesions strongly associated with HIV infection
ii. Lesions less commonly associated with HIV infection
iii. Lesions seen in HIV infection
Group 1: Lesions strongly associated with HIV infection

Candidiasis: Erythematous
Pseudomembranous
Hairy leukoplakia
Kaposis sarcoma
Non-Hodgkins lymphoma
Periodontal disease
Linear gingival erythema
Necrotizing (ulcerative) gingivitis
Necrotizing (ulcerative) periodontitis

Group 2: Lesions less commonly associated with HIV


infection

102

Bacterial infections
Mycobacterium avium intercellulare
Mycobacterium tuberculosis
Melanotic hyperpigmentation
Necrotizing (ulcerative) stomatitis
Salivary gland disease
Dry mouth due to decreased salivary flow rate, unilateral or bilateral swelling of the major salivary
glands
Thrombocytopenic purpura
Ulceration NOS (not otherwise specified)
Viral infections
Herpes simplex virus
Human papilloma virus (warty-like lesions)
Condyloma acuminatum

Bacterial infections
Actinomyces israelii
Escherichia coli
Klebsiella pneumoniae
Cat-scratch disease
Drug reactions (ulcerative, erythema multiforme, lichenoid, toxic epidermolysis)
Epithelioid (bacillary) angiomatosis
Fungal infections other than candidiasis
Cryptococcus neoformans
Geotrichum candidum
Histoplasma capsulatum
Mucoraceae (mucormycosis/zygomycosis)
Aspergillus flavus
Neurologic disturbances
Facial palsy
Trigeminal neuralgia
Recurrent aphthous stomatitis
Viral infections
Cytomegalovirus
Molluscum contagiosum

Laboratory diagnosis
There are two main approaches for the diagnosis of HIV
infection, the direct and the indirect.
The direct method seeks information on the presence of
virus itself by classical isolation method and identifying the
presence of virus specic genes by molecular biology techniques. George Babu in his review states that the classical
method of isolation for HIV is time consuming, expensive,
requires special containment laboratory and highly trained
personnel.
He also states that molecular biology technique such as
polymerase chain reaction (PCR) is expensive and should
be done by highly trained personnel but it is less expensive than classical virus isolation and less time consuming. He further states that PCR nds application under
special circumstances such as the presence of early stages
of infection.
The indirect methods are based upon the observation
that infected persons make antibody eventually. In most
cases, the IgG class of antibody can be detected on the
serum 68 weeks after infection.
ELISA Test
1. The first system to have been introduced is ELISA
(enzyme linked immunosorbent assay) for screening
and western blot test for confirmation of HIV antibody.

Chapter 4 Bacterial, Viral and Fungal Infections

2.

3.

ELISA is done in a 96-well polystyrene microtiter


plates, the plates being coated with HIV specific antigen and allowed to react with patients serum.
The other rapid tests include DOT tests (e.g. tridot insti,
HIVcheck and agglutination tests (e.g. Combaids,
Immunocomb).
Western blot test is used to detect the presence of
nine antibodies to the nine HIV specific antigens.
In asymptomatic stage, the presence of one antibody
(gp160, gp120 or gp41) one from core region (p17,
p24 or p55) and one from polymerase region (p31, p51
or p66) is required. In a symptomatic person, the presence of gp41 with one band from any of the two
regions is adequate.

Management
The management of HIV disease is two pronged: one aimed
at managing the conditions arising out of the immunosuppression and opportunistic infections and the other targeted at the virus itself.
I. Management of the viral infection
Antiviral therapy is instituted in patients with AIDS
regardless of the CD4 count and in patients who are
asymptomatic but with CD4 count less than 200 cells/
mm3 (Table 3).
Four groups of drugs can be used to combat the virus.
A combination of these drugs may be used in the management of HIV infection. These regimens are referred to
as highly active antiretroviral therapy (HAART).
The commonly employed regimens used include:

HAART may be associated with adverse side effects such


as IRIS (immune reconstitution inammatory syndrome,
which is characterized by worsening of the already existing opportunistic infection, appearance of new opportunistic infections and autoimmune disorders.
Other side effects of HAART include: bone marrow
suppression, bleeding disorders, liver and renal toxicity,
hypersensitivity reactions and severe forms of erythema
multiforme.
Charles Barr (1995) recommended the following therapy for oral disease associated with HIV/AIDS.
I. Fungal disease
Candida albicans
1. Nystatin vaginal tablets: 100,000 IU/tablet to dissolve
one tablet in the mouth 3 times daily for 12 weeks.
2. Mycostatin pastilles: (Nystatin) 200,000 IU/pastille.
One pastille dissolved in mouth to 5 times daily for
12 weeks.
3. Mycelex troches (Clotrimazole): 10 mg troche one troche
dissolved in the mouth 5 times daily for at least 14 days.
4. Nizoral (Ketaconazole): 2,000 mg/tablet one tablet
daily with food until lesions disappear if response is
poor2 tablets daily.
1.

2.

a. 1 NNRTI  2 NRTI
b. 1 or 2 PI  2 NRTI
c. Triple NRTI.
3.
Table 3 Antiviral therapy for management of HIV infection
Drug

Examples

Mechanism of action

Fusion inhibitors

Enfuvirtide

It is an anti-HIV peptide
that inhibits entry of the
virus into host cells

Nucleoside reverse
transcriptase
inhibitors (NRTIs)

Abacavir
Didanosine
Lamivudine
Stavudine
Zalcitabine
Zidovudine

They terminate the


elongation of the
growing DNA chain and
reduce or prevent
replication of HIV in
infected cells

Non-nucleoside
reverse transcriptase
inhibitors (NNRTIs)

Nevirapine
Efavirenz
Delavirdine

They inhibit a vital step in


the transcription of RNA
genome into double
stranded viral DNA

Protease inhibitors
(PIs)

Indinavir
Ritonavir
Atazanavir

They inhibit the cleavage


of viral proteins

Zovirax (acyclovir)200 mg tablets. Two tablets 45


times daily. Recurrence is frequently noted after therapy is discontinued.
Podophyllin resin25% solution. Dab solution on
lesions with cotton applicator 23 times daily. To
rinse mouth with plain water for 3060 seconds following last application last application. Allow 1 week
for beneficial effect. Second application may be necessary depending on thickness of lesion.
Retin A (tretinoin)topical retinoid solution 0.05%
apply to involved area for 12 minutes daily for several days.

Herpes simplex virus-1 Zovirax (acyclovir) 200 mg


tablets 2 tablets 45 times daily until healing occurs.
Varicella zoster virus Zovirax (acyclovir) 200 mg tablet
or 800 mg tablets: to take 4 g/day.
Cytomegalovirus Cytovene (ganciclovir sodium), intravenous 7.515 mg/kg/day for 1014 days.
Human papilloma virus Surgical excision by scalpel.
Cryotherapy, CO2 base, or electrocoagulation.
II. Bacterial disease
A. Linear erythematous banding
1. Irrigation with 10% povidone iodine solution
2. Prophylaxis
3. Antifungal therapy (if suspect candiasis)
103

Section II Oral and Maxillofacial Disturbances

4. 125 chlorhexidine gluconate


5. Frequent systemic follow-up.
B.

Necrotizing (ulcerative) gingivitis and periodontitis


1. Irrigation with 1% povidone iodine solution
2. Debridement of necrotic gingival tissue, scaling,
root planing
3. Antibiotic therapy
4. Hydrogen peroxidewater rinses
5. 12% chlorhexidine gluconate rinse
6. Frequent systemic follow-up of the case.

Sterilization
Steam: Autoclave instruments at a temperature of 121C,
at 15 lb/sq in pressure for 1520 minutes on specially
modified cooker.
Flame: Heating with ame until red-hot to sterilize instruments such as knives and other skin piercing instruments.
Disinfection
a.

III. Neoplasia
Kaposis sarcoma
1. Chemotherapy: Wet Velban (Vinblastine sulfate) 0.1 ml
of a 0.2 mg/ml solution for each 0.5 cm lesion. Drug is
injected 0.2 intralesionally after local anesthesia.
2. Localized radiation therapy: Fractionated radiotherapy of approximately 800 to 1,500 cGy
3. Intro A (Interferon): 35 million IU injected into lesion
3 times per week
4. Sotradecol (sodium tetradecyl sulfate): Intralesional
injection of a 3% solution at 0.2 cc/cm
5. CO2 laser.
VI. Aphthous ulcers
1.
2.

3.
4.
5.
6.

Lidex (Fluocinonide) ointment 0.05% or clobetasol


ointment. Apply to lesion
Dexamethasone 0.5 mg/5 ml swish 12 teaspoonful
around mouth for at least 1 minute and expectorate,
4 times daily until lesion disappears
Prednisone10 mg tablets. One tablet up to 6 times
daily for 1 week depending on healing
Thalidomide 200 mg every 12 hours for 5 days
Tetracycline oral suspension125 mg/5 ml swish and
expectorate
Levamisol: 50 mg every 8 hours for 3 years.

b.

WHO also recommends that the needle, syringe should not


be recapped, bent or broken by hand to avoid needle prick
injuries or skin puncture. They suggested that it should be
collected in a container with bleach solution and destroyed.
For reusable syringe and needles, they suggested that these
should be decontaminated by soaking in 0.1% sodium
hypochloride solution for 2030 minutes. They also stated
that when autoclaving is not possible, sterilization can
be achieved by specially modified cooker at 15 Ibs/sq inch
pressure at 121C temperature for 1520 minutes or by
boiling in water for 20 minutes.
Diana Shin Flemming and John C Fahley (1996) have
mentioned about CDC classication of dental instruments
into three categories on their risk of transmitting infection:
1.

Universal precautions
WHO (1997) recommended Universal Safety Precautions
for preventing the spread of HIV infection. They stated
that Universal Safety Precaution means that all body fluids and blood of patients should be considered as infections and all precautions should be taken since it is not
known who is infected with HIV.
The universal precaution starts with:

104

Hand washing.
Creating appropriate barrier by use of gloves, masks,
gowns, eye protectors.
Careful handling of sharp objects.
Proper sterilization and disinfection.
Disposal of instruments after use/decontamination of
instruments including syringes, needles and equipment.
Proper disposal of infected waste.

Boiling: Completely immerse instruments in water, for


about 20 minutes, WHO states that boiling is sufficient to inactivate (destroy) HIV.
Chemical: HIV is highly fragile and easily inactivated
by the following chemicals:
1. Ethanol70%
2. Glutaraldehyde2%
3. Household bleach1% solution
4. Formaldehyde8% (dilute formalin 1:5)
5. Chlorine sodium10% solution
6. Isopropyl alcohol3.5% solution

2.

3.

Critical: These are surgical and other instruments


used to penetrate soft tissue or bone which should be
sterilized after each use. These devices include forceps, scalpels, bone chisels, scalers and burs.
Semicritical: These instruments are those which do
no penetrate soft tissue or bone but contact oral tissues
which should be sterilized after each use; if not feasible
it should receive high level disinfection (e.g. Mouth
Mirrors, Amalgam condensers).
Non-critical: These are the instruments or medical
services such as external components of X-ray heads
that come contact only with skin; these could be disinfected by detergent or washing depending upon the
nature and degree of contamination.

SINUSITIS
Inflammation of the paranasal sinus mucosal lining is
referred to as sinusitis. When all the paranasal sinuses

Chapter 4 Bacterial, Viral and Fungal Infections

(frontal, maxillary, sphenoid and ethmoid) are inflamed


the term pansinusitis may be used. Based on the duration
of the clinical presentation sinus diseases can be categorized into:

Acute: defined as disease lasting less than 1 month.


Subacute: presence of disease for 1 to 3 months.
Chronic: is longer than 3 months duration.

Acute Sinusitis
Sinusitis occurs when the mucous membranes of the upper
respiratory tract namely the nares, pharynx, sinuses and
larynx become inflamed. The swelling obstructs the sinus
openings and prevents mucus from draining normally.
This creates a moist environment which aids in harboring
infection.
The most common cause for sinusitis is a viral infection. However sinusitis can also occur as a result of a bacterial or fungal (secondary to aspergillosis, mucormycosis,
candidiasis, histoplasmosis and coccidiomycosis) infection. When the upper respiratory tract infection persists
for longer than 2 weeks, a bacterial etiology is more likely.
Other causes for sinusitis include allergies, deviated nasal
septum, nasal polyps, antroliths (Figure 18) and as complications of systemic conditions such as cystic brosis, gastroesophageal reux or immunodeciency diseases. The
severity of sinusitis may exacerbate when exposed to polluted air or when an individual smokes.
Clinical features
Patients suffering from sinusitis include facial pain (especially in the periorbital region, maxillary sinus region and
forehead), fever, fatigue, nausea, nasal congestion, erythema over the sinus region (owing to increased blood
Figure 18

flow), referred tooth pain, halitosis and reduced smell and


taste.
Usually acute sinusitis when untreated will result in a
medically irreversible chronic phase of sinusitis. In rare
instances, acute sinusitis can trigger an asthmatic attack,
may spread to the brain to cause meningitis and can cause
visual disturbances.

Chronic Sinusitis
Chronic maxillary sinusitis is defined as sinusitis lasting
longer than 12 weeks. Patients may report of chronic
facial pressure in the maxillary region, headache, rhinorrhea, postnasal drip, light headedness, decreased sense of
smell, or toothache.
In children, the symptoms of sinusitis are less specic
than in adults. Symptoms include persistent nasal congestion and cough lasting for more than 10 days, high fever
and purulent nasal discharge. Children are less likely to
present with facial pain or headache.
Clinical and radiographic diagnosis
Apart from history, clinical examination of the sinuses
will help in diagnosing sinusitis. In many individuals the
sinuses are tender in palpation. Another simple chair side
test that can be employed is transillumination to assess the
maxillary and frontal sinuses. The paranasal sinuses can
be assessed using plain radiographs such as Waters view
(facilitates viewing of the maxillary, frontal sinuses and
sphenoid sinuses), Caldwell view (visualization of the
frontal and ethmoid sinuses), lateral view (to visualize the
sphenoid sinus and the posterior frontal sinus wall) and
the submentovertex view (sphenoid sinuses are visualized).
The typical radiographic ndings in a paranasal
sinus view include: localized thickening of the mucosal
lining at the base of the sinus, generalized thickening of
the mucosal lining (Figure 19), partial lling of the sinus
(uid level appearance) and a complete cloudy or hazy
sinus (Figure 20).
CT of the osteomeatal complex has been used to assess
pansinusitis. It has been frequently reported that sinus CT
scanning has a high sensitivity but a low specicity for
demonstrating acute sinusitis. CT scanning may be used to
assess signicant mucosal thickening, air-uid levels
(Figure 21), osteomeatal complex obstruction, polyposis
(Figure 22), or calcication suggestive of fungal sinusitis.
Management

Intraoral periapical radiograph showing antrolith.


Courtesy: Department of Oral Medicine and Radiology,
Manipal College of Dental Sciences, Mangalore

Acute sinusitis is best managed medically using nasal


decongestants and systemic antihistamines. Patients
should be instructed to use steam inhalation. In most
infections amoxicillin is sufficient to neutralize pathogens
such as S. pneumoniae, H. influenzae and M. catarrhalis.
However when the infection does not subside in a weeks
105

Section II Oral and Maxillofacial Disturbances

time, following culture, the antibiotic coverage can be


widened to include clavulanic acid.
In extreme cases when the medical line of management
fails to provide adequate drainage of the sinus, surgical
drainage may be undertaken. Surgical treatment includes
antral lavage, middle meatal antrostomy and endoscopic
enlargement of the osteomeatal complex.
Herpes simplex virus infections, varicella zoster infections, herpangina, herpangina, hand, foot and mouth disease, mumps, condyloma acuminatum and molluscum
contagiosum are described in Chapters 7, 8, 11 and 22.

FUNGAL INFECTIONS AND


PROTOZOAL DISEASES
HISTOPLASMOSIS
Histoplasmosis was first described by an American physician, Samuel Darling in 1906. Histoplasmosis is caused by
the dimorphic fungus (present as yeast at body temperature and as mold in the natural environment) Histoplasma
capsulatum.
The mold typically inhabits soil in humid areas containing bat or bird excrement. When humans inhale these

Figure 19
Figure 21

CT scan showing thickening of the mucosal lining of the


ethmoid sinus

CT scan showing fluid level appearance in the right


maxillary sinus

Figure 20
Figure 22

Paranasal sinus view showing complete haziness of the


left maxillary sinus

106

CT scan showing a large polyp in the right maxillary sinus

Chapter 4 Bacterial, Viral and Fungal Infections

air borne spores, they travel to the lungs. It is primarily a


lung disease. There are two varieties of H. capsulatum that
are pathogenic to humans, H. capsulatum var capsulatum
and H. capsulatum var duboisii. Histoplasmosis is an
endemic infection in most of the United States.
Pathogenesis
Following deposition of the spores in the alveoli at the
normal body temperature the spores germinate into the
yeast form. The yeast form of the organism is promptly
ingested by pulmonary macrophages. The yeasts become
parasitic, multiply within these cells, and migrate to hilar
and mediastinal lymph nodes. They subsequently gain
access to the blood circulation and eventually disseminate
to various organs.
Macrophages throughout the reticuloendothelial system
ingest and sequester the organism.
In an immunocompetent host, in about 2 weeks after
exposure, cellular immunity develops, and the macrophages become fungicidal and eliminate the infection. The
sites infected (such as the lung, liver, spleen, bone marrow
and lymph nodes) show evidence of necrosis, leading to
caseation, brous encapsulation, calcium deposition and
within a few years of the initial exposure, calcied granulomas are formed.
However, in an immunocompromised host due to defect
in the cellular immunity, a lethal progressive disseminated
form of infection is seen.
Clinical features
There are three clinical forms of histoplasmosis: acute pulmonary, chronic pulmonary and disseminated form.
Most of the infected individuals are either asymptomatic or present very mild illness. Only less than 1% of the
individuals exhibit symptoms.

Acute Pulmonary Histoplasmosis


Patients may present with malaise, fever, headache, chills,
weight loss, myalgias, sweating, non-productive cough
and pleuritic chest pain.
However, when large number of spores are inhaled
patients may present with dyspnea and hypoxia. Occasionally, hepatosplenomegaly, adenopathy, erythema nodosum, and erythema multiforme may be seen.
Acute pulmonary infection may lead to mediastinal
granuloma, pericarditis and arthritis (symmetrical and multiple joints are involved).
Chest radiographs may reveal solitary or multiple patches
of air space, especially in the lower zones of the lung. Severe
infections may reveal presence of hilar and mediastinal
adenopathy and small diffuse pulmonary nodules.
The symptoms of the acute form of the disease resolve
spontaneously.

Chronic Pulmonary Histoplasmosis


It is usually seen in elderly white males who have a preexisting lung disease such as emphysema. Patients present
with malaise, productive cough, fever, and night sweats
mimicking the clinical features of tuberculosis. The form
of histoplasmosis causes necrosis and loss of lung tissue.
Chest radiograph may reveal cavitation and inltration
in the upper lobe of the lungs.
Progressive thickening of cavity walls and retraction of
adjacent lung tissue occur over time. Radiographs typically reveal the absence of adenopathy.

Disseminated Histoplasmosis
The disseminated form of histoplasmosis is a rare disease
and occurs primarily in immunocompromised persons
(patients with HIV infection, lymphoreticular neoplasms,
corticosteroid therapy, cytotoxic therapy and immunosuppressive agents).
The spectrum of illness in disseminated disease ranges
from a chronic, intermittent course in immunocompetent persons to an acute and rapidly fatal infection that usually occurs
in infants and severely immunosuppressed persons. Fever
is the most common symptom; however, headache, anorexia,
cough, weight loss, and malaise are frequent complaints.
Hepatosplenomegaly, lymphadenopathy and oropharyngeal ulcerations are typically encountered.
The buccal mucosa, tongue and palate are the most
common sites affected. Solitary painful ulcers are seen.
These erythematous ulcers exhibit rm rolled-out margins
that resemble malignant ulcers. The disseminated form of
the disease also affects the nervous system, gastrointestinal system and the renal system.
Diagnosis
Histoplasmosis can be diagnosed by culture, fungal stains,
serologic tests for antibodies, and antigen detection.
In order to demonstrate the yeast of H. capsulatum special stains such as PAS and Grocott-Gomori methenamine
silver have to be used.
Prognosis and management
Histoplasmosis is a self-limiting disease. However the
untreated disseminated form may result in death in almost
90% of the individuals. Analgesics and antipyretics may be
used to manage fever and myalgias. Intravenous amphotericin B is used as the drug of choice. Other drugs that have been
used with good results are ketoconazole and itraconazole.

BLASTOMYCOSIS (Gilchrist Disease)


Blastomycosis was first described in America by the
American dermatologist, Thomas Caspar Gilchrist in 1894.
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Section II Oral and Maxillofacial Disturbances

It is caused by Blastomyces dermatitidis, a dimorphic fungus. It is believed to thrive in organic matter and soil
which have high moisture content.
Following inhalation of the spores, three forms of the
disease are manifested: acute, chronic and a disseminated
form.
Clinical manifestations
Blastomycosis is typically seen in men engaged in outdoor
activities usually in the 3rd and 4th decades of life. The
acute form of blastomycosis is characterized by fever,
malaise, myalgias, weight loss, cough, and pleuritic chest
pain.
The chronic form is much more commonly seen than
the acute form. It is characterized by symptoms mimicking
those of tuberculosis such as night sweats, low-grade fever,
productive cough and weight loss.
Rarely, dissemination to other body sites such as the
skin, bone, CNS, genitourinary system and oral cavity may
be seen. Cutaneous lesions may appear as erythematous
nodules that subsequently ulcerate.
Oral features
Intraoral lesions of blastomycosis appear as irregular pink
or white areas. The ulcers may be painful and appear
irregular with rolled borders.
Histologic findings
On histological section blastomyces can be easily discernible with PAS stan, H and E stain, PAP and methenamine
silver stains. It can be cultured using Sabourauds agar.
Management
For mild cases itraconazole and ketoconazole can be used
effectively. Patients who are refractory to ketoconazole
can be treated with amphotericin B.

MUCORMYCOSIS (Zygomycosis,
Phycomycosis)
Mucormycosis is an opportunistic deep fungal infection
caused by bread mold fungi of the genera Mucor, Absidia,
Rhizopus and Cunninghamella, also collectively known as
Phycomycetes.
Zygomycosis was rst described by Platauf in 1885 as
Mycosis mucorina. The class Zygomycetes is subdivided
into two orders, which contain the agents of human
Zygomycosis, the Mucorales and the Entomophthorales.
Among the Mucorales, Rhizopus (most common), Mucor,
Absidia, Rhizomucor, Cunninghamella, Saksenaea, Cokeromyces and Apophysomyces have been implicated in
causing human disease.
108

The hallmarks of disease with these organisms are


angioinvasion, thrombosis, infarction and necrosis of the
involved tissue.
Predisposing factors
The predisposing factors for mucormycosis include diabetes,
hematological malignancies (leukemia, lymphoma), bone
marrow or organ transplant, prolonged use of steroids,
patients on deferoxamine therapy (Rhizopus species thrive
well in iron rich environment), severe and prolonged neutropenia, deficient T cell immunity and low birth weight.
Diabetes with ketoacidosis is a very potent predisposing
factor. Mucormycosis thrives very well in acid pH and glucose rich medium. Hyperglycemia enhances fungal growth
and impairs neutrophil chemotaxis, while lactic acidosis
decreases phagocytosis.
Clinical features
Mucormycosis may manifest as a rhinomaxillary form or
a more severe rhinocerebral form. It also manifests as pulmonary, gastrointestinal, cutaneous or a disseminated form.
In the early stages of the disease, patients exhibit facial
cellulitis, anesthesia, nasal discharge, epistaxis, fever, headache and lethargy.
Involved tissues become red, then violaceous and
nally black as vessels are thrombosed and tissues undergo
necrosis. Extension into the orbital region can lead to periorbital edema, proptosis, tearing and ocular or optic nerve
involvement spreading along the cribriform plate can
result in intracranial involvement.
Oral manifestations and radiographic features
The most common oral sign of mucormycosis is ulceration
of the palate, which results from necrosis due to invasion of
a palatal vessel. It characteristically causes denudation of
underlying bone, occasionally forming an oroantral fistula. Ulcers have also been reported on the lip, gingiva and
alveolar ridge. Gingiva has a peculiar erythematous hyperplasia and is termed strawberry gingivitis.
Paranasal sinus radiographs may reveal thickening of the
sinus mucosal lining and occasionally air-uid levels. In
severe forms of the disease bone destruction may be seen.
Diagnosis
Special stains like calcofluor white stain; Gomori methenamine silver stain, periodic acid Schiff and Papanicolau
stains are required. Cytological specimens may show ribbon like, wide, aseptate hyphal elements exhibiting angioinvasion and necrotic debris.
Management
Underlying predisposing factors should be corrected.
The necrotic lesions have to be surgically debrided.
Amphotericin B is the first line drug of choice for most

Chapter 4 Bacterial, Viral and Fungal Infections

cases of zygomycosis. Some authors suggest the use of


hyperbaric oxygen therapy as it may aid in inhibiting the
growth of fungal spores.

ASPERGILLOSIS
Aspergillosis was first described in 1729 by a priest botanist, Micheli. In 1893, Morrel Mackenzie published the
first case of aspergillosis affecting the maxillary sinus. It is
a saprophyte that belongs to the class of myocetes.
Aspergillus avus, A. niger and A. fumigatus are
pathogenic to humans. It is believed that aspergillosis is
the second most common opportunistic infection to affect
immunocompromised individuals.
Aspergillus is usually present in decaying matter, soil
and water. It is contracted via inhalation. Aspergillus may
cause hypersensitivity reactions and in some individuals it
exhibits direct angioinvasion. Aspergillus primarily affects
the lungs resulting in allergic bronchopulmonary aspergillosis, chronic necrotizing Aspergillus pneumoniae, aspergilloma (fungus ball/mycetoma) and invasive aspergillosis.
However, in immunocompromised host the fungi is no
longer restricted to the lung. This disseminated form causes
endophthalmitis, endocarditis, and abscesses in the myocardium, kidney, liver, spleen, soft tissue, and bone and
oral involvement.
Oral findings
Involvement of the oral cavity may be seen in the disseminated form of the disease. The tongue, soft and hard palate
and an occasional report of pulp and periodontal tissue
involvement have been described in literature. Involvement
of the maxillary sinus may result in an extension to the
adjacent structures and the palate to form a very painful
ulcer surrounded by a zone of necrotic black tissue.
Diagnosis
Aspergillus may be identified in branched septate hyphae
about 4 m in diameter in potassium hydroxide preparations. Aspergillus may be cultured in Sabourauds agar
media. The hyphae demonstrate a tendency to invade
adjacent blood vessels.
Management
The ulcerated lesion should be debrided, systemic amphotericin B therapy is the drug of choice.

CRYPTOCOCCOSIS (European Blastomycosis,


Torulosis, Busse-Buschke Disease)
Cryptococcosis is an opportunistic fungal infection caused
by Cryptococcus neoformans. It is usually present in bird

droppings, rotting wood and soil. Otto Busse, a pathologist,


in 1894, isolated C. neoformans from the tibia of a 31-yearold woman. Abraham Buschke also isolated C. neoformans
from the same patient, thus giving rise to the Busse
Buschke disease in recognition for their discovery.
Cryptococcosis is an acute, subacute, or chronic infection by C. neoformans, chiey affecting the central nervous system, causing a pulmonary, disseminated, or
meningeal mycosis.
The risk factors for developing serious forms of cryptococcosis include patients with AIDS, post organ transplantation,
reticuloendothelial malignancy, long-term corticosteroid
treatment and individuals suffering from sarcoidosis.
Cryptococcus neoformans is the second most common
cause of opportunistic fungal infection in patients with
AIDS. It is considered as a sentinel infection that signals
the perturbation of the hosts immune status.

Types
There are two varieties of C. neoformans: C. neoformans
var neoformans consisting of serotypes A and D (causes
disease in immunocompromised hosts) and C. neoformans
var gatti consisting of serotypes B and C (causes disease in
normal hosts).
The yeast is typically found in pigeon feces. Some of
these organisms are restricted to tropical and subtropical
areas, and are isolated from certain species of eucalyptus
trees and the air beneath them. Infections occur through
inhalation of yeast like organisms which enter smaller respiratory passages and then remain dormant depending on the
host reaction. Organisms are then reactivated from such
previous dormant infections in the lung or lymph node.
Clinical features
Cryptococcosis is seen more commonly in men due to
their occupational exposure or a lack of estrogens. The
infection usually affects the respiratory system and the
nervous system. However a wide dissemination into multiple body sites may also occur.
It is estimated that 4085% of the patients present
with involvement of the brain parenchyma. Patients may
initially complain of headache, fever and nuchal pain suggesting meningeal irritation. As the disease progresses,
stupor, coma and dementia may be seen. Papilloedema may
be seen. Complications of CNS involvement include internal hydrocephalus, focal motor decits, and symptoms of
raised intracranial pressure.
When the lung is involved, a primary pulmonary
complex, similar to TB may be seen. Symptoms of acute
pneumonia with cough, fever, and lobar pulmonary inltrates affecting alveoli may be seen. Pleural effusion without parenchymal lesions are rare.
Cutaneous involvement results in the formation of papules, abscesses, cellulitis, acneiform lesions, draining sinuses,
109

Section II Oral and Maxillofacial Disturbances

or subcutaneous swellings. Ocular involvement is seen as


choroidal infection and endophthalmitis. Direct traumatic
inoculation into the bone may result in osteomyelitis and
arthritis.
Oral features
Oral lesions of cryptococcosis appear as nodular or granulomatous lesions which subsequently ulcerate. These
ulcers typically reveal indurated borders and rolled-out
edges. The common sites that are affected include the hard
and soft palate, tongue, gingiva and the tonsillar pillars.
Cryptococcus infection has also been reported involving
extraction sockets.
Diagnosis
The organism can be isolated in culture, recognized histopathologically and its polysaccharide capsular antigen can

110

be detected in cerebrospinal fluid. The organism grows in


blood and chocolate agar within 35 days.
Histopathological examination requires the uses of Pap
stain, India ink preparation, alcian blue, Mayer mucicarmine
stain and Masson-Fontana silver stain. These stains help
in the detection of the polysaccharide capsule of the yeast.
India ink preparation is useful when greater than 10 colony
forming units (CFU)/ml of yeasts are present.
Alternatively, cryptococcal antigen in cerebrospinal uid
can be detected by latex agglutination.
Management
Amphotericin B is the drug of choice. However other drugs
that have fewer side effects compared to amphotericin such
as flucytosine, fluconazole and itraconazole can be used.
Oral candidiasis and paracoccidiodomycosis are described
in Chapters 6 and 8.

CHAPTER

Orofacial Pain
Joanna Baptist, Ajay Nayak, Ravikiran Ongole

Pain Physiology

Common Terminologies Associated with Pain


Properties of Pain
Pain Pathways
Gate Control Theory

Myofascial Pain

Neuralgias
Trigeminal Neuralgia
Glossopharyngeal Neuralgia
Postherpetic Neuralgia
Geniculate Neuralgia
Occipital Neuralgia

Classification of Orofacial Pain

Clinical Assessment of Pain

Pain from Orodental Structures

Atypical Odontalgia

Barodontalgia

Atypical Facial Pain

Paranasal Sinus-related Pain

Burning Mouth Syndrome

PAIN PHYSIOLOGY

2.

The International Association for Study of Pain (IASP) in


1994 defined pain as the subjects conscious perception of
modulated nociceptive impulses that generate an unpleasant sensory and emotional experience associated with actual
damage or described in terms of such damage.
The experience of pain is usually a protective mechanism
of the body. On a short-term basis, pain warns the individual that he or she is in danger so that one can alter the
situation. For example when a person accidentally touches
something hot he or she will alter the situation by spontaneously withdrawing from the source of injury. Long-term
pain will result in immobilization of the affected part such
that the individual can recover from the injury faster (for
example, muscle spasm).
Pain at times can be non-benecial, such as pain associated with cancer, psychogenic pains and neuralgias which
only adds to the misery of the patient. However, interestingly
these pains help the physician in diagnosis.

3.

Common Terminologies Associated with Pain


1.

Nociceptors: These are receptors that are sensitive to


painful stimulus and are responsible for initiating the
generation of pain.

4.
5.
6.
7.
8.

Nociception: It is defined as a noxious stimulus or has


potential to turn noxious over a period of time.
Allodynia: Pain that is produced by a stimulus that is
not normally painful.
Hyperalgesia: Increased sensitivity to painful stimuli.
Hypoesthesia: Reduced sensation in response to
stimulus.
Anesthesia: Absence of sensation in response to a
stimulus.
Causalgia: Persistent burning pain caused by deafferentation of sensory innervation.
Neuralgia: It is the pain that is experienced in the
tissues along the distribution of the nerve.

Properties of Pain
Weber and Fechners law
Weber and Fechner proposed that gradation of stimulus
strength is discriminated approximately in proportion to
the logarithm of stimulus strength.
This law can be mathematically expressed as
R log S
where R intensity of the reaction (i.e. the pain perceived),
constant and
S the intensity of the stimulus.
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Section II Oral and Maxillofacial Disturbances

According to this law, exponential increase in the


intensity of stimulus does not cause exponential increase
in pain perceived. Though the pain perceived increases
with increase in stimulus; the pain experienced is only in
terms of log of the intensity of the stimulus.
For example, if a pin prick (1 unit of tissue damage) of
1 unit of intensity of stimulus results in 1 unit of pain perception; a musculocutaneous laceration (100 units of tissue
damage) causing 100 units of intensity of stimulus results in
2 units of pain perception and not 100 units. Similarly, a
crushing injury (1,000 units of tissue damage) causing
1,000 units of intensity of stimulus results in 3 units of
pain perception and not 1,000 units.
This law ensures that an individual would perceive pain
of all intensities but at the same time will not cause signicant morbidity due to pain.
Adaptation
As long as nociceptors (pain receptors) are stimulated, pain
continues to be perceived as these receptors have very little
or no property of adaptation. It is interesting to note that
the inability to adapt to pain is beneficial in terms that a person is appraised of the injurious stimulus that causes pain as
long as it persists.
For example, olfactory receptors get adapted to a
particular smell when stimulated for a long period of time
thereby the smell is not perceived any longer.
Though pain is not adaptable, the brain itself along with
the spinal cord can suppress the input of pain signals to the
nervous system by activating a pain control system called
analgesia system.
Pain localization
Pain is poorly localized. It is said that superficial somatic
pain is more localized than deep visceral pain. However
this is not exactly true as the superficial injury not only
excites the nociceptors but also the tactile receptors, thus
helping in localizing the pain.
If the supercial nociceptors were alone to be stimulated,
it would still cause quite poorly localized pain.

Nociceptors
Pain receptors are called nociceptors (from Latin, nocereto
hurt). All nociceptors are free nerve endings (however
other cutaneous receptors when stimulated excessively
can result in pain). Either present in skin or any other tissues. They are more concentrated in superficial layers of
skin, periosteum, arterial walls, joint surfaces, the falx and
the tentorium of the cranial vault. Deep tissues are sparsely
supplied with nociceptors.
Two general types of nociceptors are characterized by the
neurons associated with them.
112

1.
2.

A fibers (wrapped in Schwann cells)


C fibers

A fiber

C fiber

16 m diameter

1.5 m diameter

Myelinated

Non-myelinated

530 m/s conduction velocity

0.52 m/s conduction velocity

Carries the first pain that is


experiencedsharp

Carries steady dull pain

Stimulation of nociceptors
Mechanical, chemical and thermal stimuli excite pain
receptors. Fast pain is conducted by A fibers which is
elicited by the mechanical and thermal stimuli. The slow
dull pain is conducted by the C fibers which are elicited by
all three types of stimuli. It is almost always caused by
release of chemicals liberated by the injured tissue. These
are endogenous chemicals called algogenic (pain producing) substances. Algogenic substances stimulate nociceptors to produce pain.
These chemicals are pain producing peptides, bradykinins, serotonin (5 HT), potassium ions, prostaglandins,
acetylcholine and proteolytic enzymes.
It is interesting to note that commonly used NSAIDs suppresses pain by inhibiting prostaglandin synthesis. These
prostaglandins by themselves cannot excite the nociceptors,
i.e. prostaglandins are not algogenic but they enhance the
sensitivity of the nociceptors toward the algogenic power of
bradykinins and other chemical mediators of pain.

Sequelae of Pain
Apart from nociception there are various other sequelae of
pain that alter other systems of the body. Pain affects an
individual psychologically as well as physically.
Psychological sequelae
An uninhibited individual would react to acute pain by
mourning and crying as seen in young children and animals. However, most individuals develop frustration, mental irritation or depression in response to long standing
pain. A patient with long standing atypical facial pain will
most often come to the physician with a frowning face
and would often get irritated with prolonged history taking.
Thus such patients should be treated both by medicines
and psychological counseling.
Muscular sequelae
Injury or disease causing pain results in spasm of skeletal
muscle in the vicinity of the affected region. This is protective as it immobilizes the affected region and thereby puts
it to forcible rest which is most essential for rapid healing.

Chapter 5 Orofacial Pain

But this spasm also causes ischemia of the muscles which


aggravates muscular pain.
Patients with internal derangement of temporomandibular
joint (TMJ) usually exhibit spasm of the masticatory muscles of the affected side thereby preventing further damage
to the affected TMJ. In such conditions apart from treating
the affected site of injury, muscular spasms should be managed with physiotherapy, muscle relaxants, massage, etc.
Autonomic nervous system sequelae
Patients with somatic pain generally present with increased
blood pressure, pupillary dilatation and tachycardia which
are all the signs of sympathetic over activity. However visceral pain is associated with fall in blood pressure and
vomiting.

Figure 1

Thalamus
Neospinothalamic
tract

Hypothalamus
Reticular
formation

Paleospinothalamic
tract
Gasserian ganglion
Motor nucleus (v)

Reflex
Withdrawal from painful stimuli is the reflex action exhibited by the individual. It is an important sequela of pain
that protects the individual from further injury.
For example, biting on a stone during mastication
would immediately initiate a reex action to keep the
mouth open until an individual realizes the presence of the
injurious agent (stone). Such reex action would protect
further injury to the periodontium.

Dual Pain Pathways


Peripheral pain fibers are of two types, the fast conducting
(A fibers) and slow (C fibers) conducting. The fast pain is
felt within 0.1 second of the application of the noxious stimulus. But it takes 1 second or more for slow pain to begin.
Occasionally slow pain may take over a few minutes to
begin after application of the noxious stimulus.
Though both fast and slow conducting bers have free
nerve endings as their receptors, they travel via two distinct
pathways for transmitting pain signals to the central nervous
system. Because of this dual pain pathway a single painful
stimulus would often give a rst sharp electrical pain that is
generally followed by a slow dull pain. This double pain sensation initially would cause an individual to react immediately to safeguard himself/herself. Whereas the slow pain
tends to become increasingly painful over a period of time.
Once these bers (A and C) enter the spinal cord, the
pain signals take two pathways to the brain. They are the
neospinothalamic tract and the paleospinothalamic tract
(Figure 1).
Neospinothalamic tract (for fast pain)
Sensations of mechanical and acute thermal pain are
brought to the spinal cord by the first order neurons. They
terminate in the lamina I (lamina marginalis) in the dorsal
horns where they synapse to excite the second order neurons

Sensory nucleus (v)


Spinal tract nucleus
(v)

Illustration showing the pain pathway

of the neospinothalamic tract. These fibers cross immediately to the opposite side through the anterior commissure
and then travel upward in the anterolateral column of the
spinal cord.
Few of these second order neurons terminate in the
reticular areas of the brain stem (the reticular areas when
stimulated causes excessive alertness and increases an
individuals sense perception), while most of the others
travel up to the thalamus terminating in the ventrobasal
complex along with the dorsal columnmedial lemniscal
tract. The remaining second order neurons terminate in
the posterior nuclear group of the thalamus.
From these areas third order neurons relay signals to other
basal areas of the brain and to the somatic sensory cortex.
Paleospinothalamic tract (for slow pain)
This pathway transmits pain, which is carried via the
peripheral slow conducting C pain fibers (it also transmits
very few A fibers). These peripheral fibers terminate in
the laminas I and II (together called substantia gelatinosa)
of the dorsal horns. Most of the signals then pass through
one or more additional short fiber neurons within the dorsal
horns themselves before entering laminas V through VIII,
also in the dorsal horn.
The next series of neurons gives rise to long axons that
mostly join the bers from the neospinothalamic tract,
passing rst through the anterior commissure to the opposite side of the spinal cord and then upward to the brain in
the same pathway.
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Section II Oral and Maxillofacial Disturbances

Analgesia system or pain inhibitory pathway

Figure 2

The analgesia system comprises three major components,


namely,
1.
2.
3.

The periaqueductal gray and periventricular areas of


the mesencephalon and upper pons
Raphe magnus nucleus and nucleus reticularis paragigantocellularis
Pain inhibitory complex located in the dorsal horns of
spinal cord

The electrical stimulation in the periaqueductal gray area or


in the raphe magnus nucleus can almost completely suppress
many strong pain signals entering the dorsal spinal roots.
Stimulation of areas at still higher levels in the brain that in
turn excite the periaqueductal gray can also suppress pain.
The nerve bers originating from periaqueductal gray
and periventricular nuclei secrete enkephalin at their terminals. These bers synapse with the bers originating from
the raphe magnus nucleus.
The bers originating from the raphe magnus nucleus
secrete serotonin at their nerve terminals. Finally these bers
terminate at the dorsal horns of the spinal cord. Serotonin
(secreted by the bers originating from the raphe magnus
nucleus) causes the cord neurons to secrete enkephalins.
Enkephalin causes presynaptic inhibition and post synaptic inhibition of A and C pain bers at the site of synapse
of the dorsal horns. This inhibition is caused by the blocking
of calcium channels of nerve membrane at their terminals.

Gate Control Theory


This theory explaining pain modulation was proposed by
Ronald Melzack and Patrick David Wall in 1965.
They hypothesized that pain perception was not just solely
due to activation of nociceptors but due to interaction between
pain conducting and non-pain conducting neurons. Nonpain conducting nerve bers interfere with the pain conduction thus altering pain perception.
There have been various modications of the original
gate control theory. A revised version of the gate control
hypothesis proposes that the projection neuron of the spinothalamic pathway when activated results in sensation
of pain (Figure 2).
The projection neuron synapses with both non-nociceptive
mechanoreceptors (A and A bers) and the nociceptive
C bers, hence activated by both. The interneuron is spontaneously active and this activation of interneuron causes
inhibition of projection neuron; thus inhibiting pain perception.
In turn, the interneuron synapses with the projection neuron, C bers, A and A bers. When the non-nociceptive
mechanoreceptors (myelinated and fast conducting A and
A bers) are stimulated they cause two effects: (i) activation
of interneuron and (ii) activation of projection neuron.
114

Dorsal horn
Spinal
cord
A or A fiber
(Non-nociceptive)
C fiber
(nociceptive)

+
+
+

Interneuron
Projection
neuron

To spinothalamic tract

Illustration showing gate control theory

Though it activates the projection neuron simultaneous


activation of interneuron causes inhibition of projection neuron thus resulting in lack of pain sensation.
When C bers are activated they again cause two effects:
(i) inhibition of interneuron and (ii) activation of projection
neuron, therefore resulting in pain perception.
When both non-nociceptive mechanoreceptors and
nociceptors are simultaneously activated, the mechanoreceptors being myelinated fast conducting bers, the signals from these bers reach interneuron and projection
neuron rst before C bers can conduct signals. In these
instances the A and A bers stimulate the interneuron
before C bers can inhibit the same. Thus the net effect is
no pain.
This would explain the benets of physiotherapy and massage in the effective management of painful conditions.
It is interesting to note that free nerve endings of unmyelinated nerve bers when relatively mildly stimulated produce
itch and tickle.
Unlike pain, itching occurs in supercial tissues and not in
deep structures like viscera.
It is common knowledge that scratching relieves itching
as the fast conducting mechanoceptive bers activated by
scratching suppress the itching sensation.
Studies indicate that the C ber system responsible for
itching may not be the same responsible for pain. Surprisingly tickling sensation in general is regarded as pleasurable whereas itching and pain are regarded as unpleasant
sensations.

Concept of Referred Pain


Referred pain is a spontaneous heterotopic pain that is felt
in an area innervated by a different nerve from the one that
mediates the primary pain.

Chapter 5 Orofacial Pain

Characteristics of referred pain


1.

Referred pain usually occurs within a single nerve root,


passing from one branch to the other.
Referred pain in the trigeminal area rarely crosses the
midline unless it originates at the midline.
Usually if the referred pain is felt outside the nerve that
mediates the pain, it is generally felt cephalad to the
nerve (upward and toward the head) and not caudally.
However in severe pain the excitatory effects are felt
caudal to the site of initiating input.

2.
3.

CLASSIFICATION OF OROFACIAL PAIN

Bell (1989) has classified orofacial pain as follows:


Axis I (Physical conditions)
1.

2.

The American Academy of Orofacial Pain has classified


orofacial pain as follows:
1.

2.

3.

4.

5.

Intracranial structures
Neoplasm
Aneurysm
Hematoma
Hemorrhage
Abscess
Edema
Extracranial structures
Teeth
Ears
Eyes
Nose
Throat
Sinuses
Tongue
Glands
Musculoskeletal disorders
TMJ disorders
Masticatory muscle disorders
Fibromyalgia
Cervical disorders
Generalized polyarthritides
Neurovascular disorders
Migraine headaches
Cluster headaches
Tension type headaches
Cranial arteritis
Neurologic disorders
Paroxysmal neuralgias
Trigeminal neuralgia
Glossopharyngeal neuralgia
Continuous neuralgias
Atypical odontalgia
Traumatic neuroma
Neuritis
Postherpetic neuralgia

Somatic pain
Superficial somatic pain (cutaneous, mucogingival)
Deep somatic pain
Musculoskeletal pain (muscle, TMJ, osseous and
periosteal, soft connective tissue, periodontal)
Visceral pain (pulpal, vascular, neurovascular,
visceral mucosal, glandular, ocular and auricular)
Neuropathic pain
Episodic (trigeminal, glossopharyngeal, geniculate, nervous intermedius neuralgias and neurovascular pains)
Continuous (neuritis, deafferentation pain and
sympathetically maintained pain)

Axis II (Psychologic conditions)


1.
2.
3.
4.

Mood disorders
Anxiety disorders
Somatoform disorders
Other conditions

Types of Pain
Acute pain
It is generally a physiologic response to an injury. It persists as long as the noxious stimulus is present. Acute pain
almost always subsides within the time period required for
the process of normal healing.
Chronic pain
Merskey and Bogduk (1994) described chronic pain as a
persistent pain that is not amenable, as a rule, to treatments
based on specific remedies, or to the routine methods of pain
control such as non-narcotic analgesics.
In common parlance chronic pain is regarded as pain
that persists way beyond the normal time required for the
process of normal healing. Pain is said to be chronic in nature
when it lasts over 3 months. It is generally associated/
inuenced by psychological, emotional, social and cultural
factors.

CLINICAL ASSESSMENT OF PAIN


The diagnosis and management of orofacial pain begins
with a comprehensive patient history. The most expeditious way to obtain such a history is via a detailed patient
questionnaire and detailed patientphysician interview.
115

Section II Oral and Maxillofacial Disturbances

Figure 3

Figure 4
None
(0)

Mild
(1)

Moderate
(2)

Severe
(3)

Throbbing
Shooting
Stabbing
Sharp
Cramping
Gnawing
Hotburning
Aching
Heavy
Tender
Splitting
Tiringexhausting
Sickening
Punishingcruel

McGill pain questionnaire (short version)


Illustration showing the pain diagram. Patient is
encouraged to mark areas on the picture that
represent the painful sites in the patient

Figure 5
The interview is followed by a complete oral and head
and neck examination, appropriate chair side investigations,
radiographic imaging and lab studies.
Assessment of pain can be achieved by certain subjective
and objective methods. Some widely accepted subjective
methods include the use of McGill Pain Questionnaire (long/
short), visual analog pain scale (VAS), brief pain inventory.
The faces pain scale and the pain diagram.
During the patient interview the clinician should obtain
the following data: mode of onset, duration, location of the
pain, quality or character of the pain, intensity of the pain,
frequency of the painful episodes, aggravating and relieving factors if any, radiation or referral patterns, any other
associated symptoms and history of any medical consultations/use of medications for the same.
The location of pain and referral patterns can be identied
by the patient using a pain diagram (Figure 3).
The pain quality or character can be expressed using
the widely accepted McGill Pain Questionnaire (Figure 4).
This questionnaire will help the patient to describe how
exactly he/she feels about the pain by selecting an appropriate adjective from a list in the questionnaire.
The intensity of pain can be quantied using the visual
analog scale (VAS). The VAS is a 10 cm long line with 0
marked on one end (represents no pain) and 10 at the other
end (represents worst possible pain). The linear scale has
markings from 0 to 10 at 1 cm intervals. The patient is
encouraged to mark a point along this scale that correlates
with the intensity of pain experienced. For convenience pain
116

10

No
pain

Worst
possible
pain

Visual analog scale

intensity can be categorized as mild (score 13), moderate


(score 46) and severe for scores 710 (Figure 5).
However the Faces Pain Scale can be used in child patients
for assessing the intensity of pain (Figure 6).
Following the history, physical examination should be
undertaken. A thorough physical examination of the head
and neck, including the TMJ, maxillary sinus, masticatory
muscles along with the accessory muscles, salivary glands
and the oral cavity should be performed.
Intraoral examination should include the evaluation of
teeth, periodontium and the oral mucosa.

PAIN FROM ORODENTAL STRUCTURES


Pulpal Pain
Dental pain is the single-most common cause why a patient
visits a dental clinician, a fact that will be vouched for by any
practicing clinician. Pulpal pain forms a major component of

Chapter 5 Orofacial Pain

Figure 6

10

Faces pain scale. Score the chosen face 0, 2, 4, 6, 8 or 10, counting left to right, so 0 = no pain and 10 = very much pain.
Do not use words like happy and sad. This scale is intended to measure how children feel inside, not how their face looks.
From PAIN, 2001, 93, 173183 The Faces Pain ScaleRevised: toward a Common Metric in Pediatric Pain Measurement,
by CL Hicks, CL von Baeyer, PA Spafford, I van Korlaar and B Goodenough. Reprinted with permission
of the International Association for the study of Pain.

this dental pain and needs to be comprehensively understood


for making accurate diagnosis and according the right
treatment options. Pulpal pain is classified as a visceral
type of pain and manifests features characteristic to such
a type of pain. The pulp responds to any form of noxious
stimuli by way of inflammation. Pulpal pain can be
brought about by a variety of causes, the most common
being, dental caries, trauma, chemical irritants and even
rarely, anachoresis.
Clinical features
The patient manifesting pulpal pain describes it as an aching
sensation that is not localizable to the patient. The patient
will point out to a region of the jaw and mention about the
pain, but when asked to specifically point out the tooth, will
be unable to do so. The absence of proprioception in the
pulp leads to such a scenario. On examination of the
region, some clinical finding of deep caries, pulpal involvement by caries or fracture of tooth, or deep cervical abrasion may be seen. The underlying inflammation of the pulp
shows typical sign of pain on movement of the part, especially since the pulp is tightly enclosed in a chamber of
dentin. This is evidenced by the history of postural changes
in pain that may be reported by the patient. The pain is
usually intermittent and aggravated by contact of the
tooth with sweets, cold and/or hot food stuff. The sweets
cause a change in the fluid dynamics within dentin due to
their hygroscopic nature and the thermal changes get
mediated via the A and C nerve fibers, leading to a crossing beyond the pain threshold of the pulpal receptors.
Reversible pulpitis gives a typical finding of pain occurrence on application of the noxious stimuli that characteristically disappears immediately on withdrawal of the
stimulus. Irreversible pulpitis, on the other hand, shows
persistence of pain for some time, even after removal of the
noxious stimulus. This differentiation is quite necessary as
the treatment options for both vary considerably, as the pulp
and/or the tooth need to be sacrificed in the irreversible

situation, while the pulp can be salvaged in the reversible


type. As the inflammation is totally confined within the pulp
space, no tenderness is elicited on percussion of the tooth.
Pulpal pain rarely remains unchanged for long periods of
time. It either resolves by itself, a rare scenario, or progresses
to chronicity and/or pulpal necrosis. Once the pulp undergoes necrosis, no painful stimuli are transmitted and leads
to relief from all symptoms. This may give rise to a false
feeling of cure to the patient and leads to neglect. During
the process of pulpal necrosis, thermal stimuli may evoke
differences in response. Pain may be aggravated by both
heat and cold when both the A and C nerve fibers are
intact. As the condition progresses, heat will cause the
pain to occur while cold may actually relieve it.
Diagnosis
Pulpal pain is of prime suspect when there is poor localization of the pain by the patient. At times, the patient
may not even be able to differentiate if the origin is maxillary or mandibular jaw. Definite clinical lesions like dental caries, faulty restorations, fractured teeth or others may
point to the source. Thermal, mechanical, chemical and
electric stimulation of a suspected tooth may provide the
noxious stimulation and induce the pain that the patient
can then identify. Vitality tests are not always reliable,
because they indicate the nervous response rather than the
intactness of the vascular supply and the presence of healthy
pulp in one root canal and necrotic pulp in another can
provide conflicting interpretations. Sequential analgesic
blocking can usually definitively identify the source tooth.
However if the pain is found to occur in a particular region
of the jaw, but exact localization is not possible clinically,
then waiting for the natural pain localization to occur by
extension into the periodontal ligament may be another
option. In rare situations, a direct exploration of the tooth
may be justified in severely painful conditions wherein
the patient is unwilling to wait for natural localization of
the pain. This would seem better than a radical option of
117

Section II Oral and Maxillofacial Disturbances

extracting the tooth. Radiographic examination will not


yield any direct characteristic signs of pulpal inflammation. However extension of any pathology into the pulp,
such as caries, restorations, etc. may be seen as a possible
causative agent and help in diagnosis.

Periodontal Pain
Pulpal pathology leading to necrosis of the pulp after a while
spills into the periodontium via the apical foramen and/or
the accessory foramina. The discussion here pertains to the
apical portion of the periodontium via the pulp being
affected rather than the progressive effects of the gingival
or periodontal diseases. The periodontal ligament behaves
and responds to noxious stimulation in a manner similar
to other ligaments of the body. Therefore periodontal pain
is felt as a deep somatic pain of the musculoskeletal type.
The receptors of the periodontal ligament can precisely locate
stimulus due to the property of proprioception. The causes
of pain originating in the periodontal ligament are as varied
for pulpal pain. Inflammatory reaction, trauma, endodontic
procedures, improperly contoured restorations, faulty occlusal contacts, orthodontic appliances and surgical procedures are the most common. Parafunctional oral habits
may also be a contributing factor.
Clinical features
The periodontal ligament pain is described by patients as
sharp jabs or pricking type of pain. The pain is usually
intermittent in nature and occurs whenever there is loading of the ligament, such as during chewing. The functional action causes movement of the tooth that compresses
the ligament, leading to displacement of the edema fluid
and irritation of the free nerve endings causing pain. This
feature can be observed clinically by percussing the suspect tooth, which simulates the functional action. Any
tenderness if present during percussion indicates periodontal ligament involvement. The patient will usually
precisely identify the tooth and mention it to be sore or a
feeling of elongation being present. Clinically the tooth
may be seen to be slightly out of occlusion. There may be
associated tenderness in the vestibule and at times a frank
swelling may be present in the gingival region or in the
vestibule.
Diagnosis
The exact location being pointed out by the patient is the
first clue in suspecting periodontal ligament involvement.
Clinical test of percussion along with presence of any of the
contributing factors further helps in diagnosis. Vitality testing can be of help if the cause is related to pulpal pathology,
because a necrotic or dead pulp definitely favors a diagnosis
of apical periodontal pathology of some degree. Radiographic
findings of a widening of the periodontal space with or
118

without a breach of lamina dura and altered trabecular pattern are a definitive indication of periodontal pathology.
Dental pain

Dental hypersensitivity

Caused due to noxious


stimulation of the nerve endings

Caused by normal physiologic


stimulation of nerve endings

May be intermittent or
continuous, depending upon the
stage of pathology

Usually always transient

May manifest at any age from


youngsters to elderly

Usually seen in the elderly


population

Not associated with any particular


habits

Parafunctional oral habits play a


role in its occurrence

May or may not respond to cold


test

Always occurs in response to a


cold test

BARODONTALGIA
Barodontalgia is the pain or injury associated with teeth as a
result of alteration in the pressure gradients. Historically, the
term aerodontalgia was used to describe pain experienced by
air crew in flight. Over a period of time it was noticed that
deep sea divers also suffered tooth pain due to pressure
changes, prompting the use of the term barodontalgia.
Barodontalgia can be explained by Boyles law, which
states that at a given temperature, the volume of a gas is
inversely proportional to the ambient pressure. As an individual descends deeper and deeper below the water surface,
pressure exerted by water on the diver increases and
reduces the volume of gases in enclosed spaces such as
teeth and the paranasal sinuses.
Similarly during a high altitude ight the atmospheric
pressure outside the aircraft decreases thereby permitting the
volume of gases to increase. These changes in pressure affect
air crew and passengers of a non-pressurized aircraft.
Barodontalgia arises when gases that are conned within
closed spaces are unable to contract to adjust the internal
pressure to correspond to the outside pressure. The phenomenon begins to occur at an altitude of approximately
3,000 m and at a water depth of 10 m where the ambient
pressures are 0.75 and 1 atm, respectively.
Individuals may experience a simple sharp or squeezing
tooth pain. Occasionally the pressure change may cause the
rupture of the alveolar mucosa.
Strohaver (1972) categorized barodontalgia into direct
and indirect types. In the direct type, reduced atmospheric
pressure contributes to a direct effect on a given tooth.
However in the indirect type, dental pain is secondary to
stimulation of the superior alveolar nerves by a maxillary
barosinusitis.
Direct barodontalgia is generally manifested by moderate to severe pain, which usually develops during ascent, is
well localized, and the patient can frequently identify the

Chapter 5 Orofacial Pain

involved tooth; indirect barodontalgia is a dull, poorly dened


pain that generally involves the posterior maxillary teeth and
develops during descent.

procedures such as pulpectomy and capping of an exposed


pulp. In these individuals endodontic treatment is recommended.

Etiology
Kollmann (1933) proposed three hypotheses to explain the
occurrence of barodontalgia: expansion of trapped air
bubbles under a root filling or against dentin that activates
nociceptors; stimulation of nociceptors in the maxillary
sinuses, with pain referred to the teeth; and stimulation of
nerve endings in a chronically inflamed pulp.
In most cases of barodontalgia the individuals tooth is
already affected by some sort of pathology such as acute or
chronic periapical infection, caries, deep restorations, residual dental cysts, sinusitis and a history of recent surgery.
The term barosinusitis has been used in literature to
describe pain in the tooth caused by congestion of the
maxillary sinus and most often the pain is experienced
during descent. Whereas barodontalgia is usually experienced during ascent and the tooth is affected usually by
periapical pathology.

Underwater Diving
During underwater diving the air from the pressurized tanks
may be forced into the tooth via the carious lesions or defective margins of restorations. With the fall in atmospheric
pressure during ascent, trapped gases may expand and enter
dentin tubules, thereby stimulating nociceptors in the pulp
or causing the movement of pulp chamber contents through
the apex of the tooth, resulting in pain.
Calder and Ramsey (1983) suggest that the physical
properties of the gas mixture used during deep sea diving
may contribute to barodontalgia. In scuba tanks, oxygens
natural diluent gas, nitrogen, is replaced by helium, resulting in a gas of lower viscosity. This gas can enter tissues,
including teeth, and can sometimes become trapped in
closed spaces, such as the pulp chamber and root canal.
There are two mechanisms by which gases can be trapped
in spaces: if there is a space between a tooth and its restoration, gas may be forced into it during an increase in
pressure; and dissolved gas may diffuse from tissues into
spaces as pressure decreases.
Occasionally, the trapped gas will expand and the resulting stress may cause tooth fracture. This process has been
called odontecrexis (Greek word meaning tooth explosion).
The Fdration Dentaire Internationale (FDI) recommends an annual check-up for divers and pilots, with oral
hygiene instructions. Also it recommends that the patients
should not dive or y in non-pressurized cabins within
24 hours of a dental treatment requiring anesthetic or for
a week following a surgical treatment.
Some authors suggest that when treating people who
are subjected to large pressure changes it is best to avoid

PARANASAL SINUS-RELATED PAIN


The paranasal sinuses are placed in close proximity to the
oral cavity, especially the maxillary sinus and have some
common innervations. This can cause pathologies in and
about the sinus to be referred to the dental structures and vice
versa. Therefore a careful consideration of their close relationship must be made in chronic painful conditions. Primary
pain that occurs at the opening of the sinuses into the
nasal cavity has secondary reference zones in the maxillary
posterior teeth of the same side and some areas of the face.
It should however be noted that the sinus lining mucosa is
actually insensitive to pain, but the junction of the sinus
lining with the nasal mucosa is richly innervated and when
stimulated causes intense pain. Hence any exudate present
within the sinus causes a feeling of fullness or pressure in
that sinus rather than pain or headache. When the patient
bends forward, the exudates can wash over the sensitive
ostium causing pain that may radiate to the maxillary teeth.
Many a times, sepsis from the maxillary teeth may in itself
be a cause for the sinus inflammation. If the teeth are secondarily involved by extension of prior sinus disease, the
dental pain will be of the periodontal type due to the effect
on the periodontal ligament with almost no features of
pulpal pain.
Pain of maxillary sinus origin will be usually felt as a
constant, dull non-pulsatile ache in the maxillary teeth of
the affected side and sometimes on the face. There may be
accompanying ear pain, malaise, nasal congestion and nasal
discharge. Inammation of the sinus will usually cause
radiographic ndings of haziness or cloudiness of the sinus
and/or hyperplasia of the sinus lining.

MYOFASCIAL PAIN
Pains of muscular origin are one of the frequent sources of
chronic pain anywhere in the body and the head and neck
region is not bereft from it. The pain originating from the
skeletal muscles, tendons and fascia surrounding these constitute the term myofascial pain (MFP). The intimate relation of the muscles in and around the oral cavity, both
anatomically and functionally accords the orofacial musculature an important consideration in the differential diagnosis of chronic orofacial pain. Pathology originating in the
dental structures can cause effects manifested in the musculature. The group of muscles involved, their number and their
relative location determine the severity of pain felt by the
patient. According to Bell (1989), it is a good rule to follow
119

Section II Oral and Maxillofacial Disturbances

in diagnosing pains about the face and mouth is initially to


assume that the pain is dental until proven otherwise, then
muscular until proven otherwise.
Myofascial pain is a regional muscle pain disorder that
manifests characteristic local areas of hypersensitive
bands of muscle tissue known as trigger points. The exact
nature of a trigger point is not known, but it has been
hypothesized that certain pain inducing events sensitize
the free nerve endings in the muscles that cause the occurrence of the hypersensitive areas. Some investigators
believe that the individual muscle spindles manifesting the
trigger point are innervated by the sympathetic nervous
system which may be the cause of muscle pain in emotional situations. The trigger point has an ability to cause
referred pain in a denite anatomical area when stimulated.
Each trigger point is thought to be less than 12 mm in
diameter. The complete range of etiologic factors for MFP
is difcult to determine, but both local and systemic causes
have been consistently identied in most patients, such as
trauma, emotional stress, fatigue, hypovitaminosis and
infections especially of the upper respiratory tract.
Clinical features
A patient manifesting MFP will complain of increased
fatigue, stiffness and pain in a particular group of muscles.
The patient may describe a feeling of subjective weakness
and restriction in the normal range of muscle motion. The
pain typically increases as the day progresses and is particularly more following a stressful day. The clinical presence of the characteristic trigger point is the hallmark of
this condition. When such a trigger point is detected and
palpated the patient gives a typical behavioral reaction,
acknowledging the tenderness felt in the area of pain reference, known as the jump sign. When the painful muscle
is stretched it is found to be restricted in motion and the
patient may adopt a faulty posture to obtain relief from
the pain. In some situations, multiple trigger points may
induce referred pain in the same region or a single trigger
point may cause radiating pain in two or more muscles. If
the muscle soreness persists for a long time, a cyclic painspasm-pain pattern may form. Therefore accurately locating the source of pain, the trigger point, and the zone of
reference is equally important. There may be accompanying
tingling or numbness of the associated area. Patient may
complain of pain in the TMJ region, the ear, scalp or the
neck. Rarely in some patients, autonomic changes may
be present, such as pallor, sweating, flushing, lacrimation,
nasal congestion, increased salivation and nausea.

stretching exercises and analgesic injection into the trigger


points are most commonly employed. The details of all
modalities used in management of MFP are beyond of the
scope of discussion of this book.

NEURALGIAS
Neuralgia is a clinical condition involving a pain of a severe
intensity, with a throbbing or stabbing character in the course
or distribution of a specific nerve.

Trigeminal Neuralgia
Trigeminal neuralgia (TN) is frequently encountered neuropathy in dental practice affecting the fifth cranial nerve.
Though it has been known by various names in the literature such as tic douloureux, trifacial neuralgia, Fothergills
disease, the currently accepted terminology is trigeminal
neuralgia. It is a well-recognized disorder characterized by
a severe, paroxysmal burst of pain in one or more branches of
the trigeminal nerve often induced by touching trigger points,
in or about the oral cavity. TN is diagnosed primarily on
the basis of the history of characteristically unilateral pain
attacks that are consistent with specific clinical criteria for
the diagnosis. However the typical sequence of events that
occur in a patient manifesting TN begins with the initial
symptoms of pain that may be misdiagnosed as pain of
odontogenic origin. A careful history-taking is of paramount
importance stressing upon the onset (whether insidious or
sudden), the duration and frequency of painful episodes, and
other associated symptoms.
The exact cause of TN pain attacks is not known in
spite of accurate description of the condition over the
years by several researchers. However, an interesting nding, that some benign tumors in the brain and/or vascular
anomalies leading to compression and possible demyelination of the trigeminal nerve root at the entry into the
pons, produce symptoms clinically characteristic of classic
TN. This nding strongly implies that injury to the nerve
root may be an important initiating factor. When such a
pathologic component is present, it is known as symptomatic TN, but in the absence of any such causative factor,
the condition is known as idiopathic TN. Oral causes, such
as periodontal lesions and traumatic lesions have been
long discarded.
Clinical features

Management
Management of MFP depends upon the identification of
the trigger point and the referred zone. Conservative
methods based upon physiotherapy principles should be
applied that can be supplemented with drugs. Basic muscle
120

Trigeminal neuralgia has most often a sudden onset and


progresses to become a chronic condition. Although no
mortality is associated with the condition, the quality of
life of the sufferer is severely affected. TN does not show
any specific racial predilection and is known to occur

Chapter 5 Orofacial Pain

throughout the world in more or less the same frequency


ranges irrespective of the ethnicity, geographic location or
climatic conditions. It manifests in both males and females,
with a slight female preponderance (2:3 males to females).
The condition usually occurs above the age of 50 years,
mostly in the 6070 years range. When this condition
manifests in adolescents or young adults, a demyelinating
lesion in the pons should be ruled out as that is one of the
most common occurrences.
The patient gives a typical history of paroxysms of lancinating painful episodes involving the face that are strikingly unilateral. The pain may be described like being
stabbed by a knife or an electric shock-like kind of pain.
The patient is usually able to precisely point out the area
affected by the pain and charts out an area supplied by the
branches of the trigeminal nerve on the face. The most
commonly affected divisions are the maxillary and mandibular divisions, either singly or in combination. The ophthalmic division may also be involved, though with less
frequency. There has been an unexplained nding of predominant right side involvement in most studies. The
attacks in each patient occur with same intensity and same
areas of the face, brought about by routine activities such
as chewing, smiling, talking, etc. The patient may point
out to an exact location on the skin, called as trigger point,
the stimulation of which causes the occurrence of an attack.
These trigger points are located most commonly around the
mouth, ala of the nose and periorbital or molar regions.
Majority of the patients complain of lancinating pain
shooting from the corner of the mouth to the angle of the
jaw. There may also be a history of jolts of pain from the
upper lip or canine teeth to the eye and eyebrow, without
actual involvement of the orbit itself. The painful episode
is usually brief lasting from a few seconds up to 2 minutes.
Though the episode may be brief, some patients can experience volleys of multiple attacks within a short span of
time. When an attack might get precipitated in the dental
ofce, the patient is seen clutching the face, especially the
region affected and show an expression of deathly pain
(indicates the severity). Several patients, in the past, have
been reported to have suicidal tendencies to rid themselves
of the pain. The severe pain as it fades away may give rise
to a burning ache that may last for a prolonged time after
the attack.
White and Sweet (1955) described a set of criteria for
diagnosing TN popularly known as Sweet criteria and
currently accepted by the International Association for the
Study of Pain (IASP) and the International Headache
Society (IHS):
1.
2.
3.
4.

The pain is paroxysmal and sudden in nature.


Light touch to the face on the trigger zones provokes
the pain.
The pain is confined to the trigeminal nerve distribution.
The pain is unilateral in manifestation.

5.

The clinical neurologic (sensory) examination is


normal.

The IHS has defined classic TN as a unilateral disorder characterized by brief electric shock-like pains, abrupt in onset
and termination, limited to the distribution of one or more
divisions of the trigeminal nerve. Pain is commonly evoked
by trivial stimuli including washing, shaving, smoking,
talking and/or brushing the teeth (trigger factors) and frequently occurs spontaneously. Small areas in the nasolabial fold and/or chin may be particularly susceptible to the
precipitation of pain (trigger areas). The pains usually remit
for variable periods. This definition covers most essential
clinical presentations of TN.
Differential diagnosis
There are few other conditions that can mimic such a characteristic condition. However, in some cases, especially in
the initial stages, may need other conditions to be ruled out.
Chief among these are odontogenic causes, TMJ-related disorders, atypical facial pain, glossopharyngeal neuralgia,
multiple sclerosis.
The specic age group and sex distribution usually helps
differentiate TN from other causes like atypical facial pain
and TMDs that usually begin at a much younger age. A valuable clue to the diagnosis of TN is the occurrence of the
pain attack with certain activities, such as rubbing the face
or shaving a trigger area, whereas in other facial pain syndromes, they massage the face or apply heat or ice, which
is strikingly missing out in the history reported by TN
patients.
Investigations
Usually all laboratory values are seen to be within normal
limits. Any kind of electrophysiological testing in the
affected area of the face also usually does not reveal any
profound abnormalities. However some clinicians insist
on an elective MRI scan of the brain to detect any missed
out clues, intracranially, and only then proceed with the
treatment.
Treatment
Given the older age manifestation of TN, medical therapy
is usually better tolerated than any form of surgical intervention, which can be attempted only if and when the pharmacologic therapy fails.
Two broad groups of pharmacologic agents, anticonvulsants and skeletal muscle relaxants, are usually employed
in the management of TN. Among the anticonvulsants,
carbamazepine is the drug of choice for TN. A 100-mg
tablet usually accords substantial relief within 2 hours, and
therefore it is used as a rst choice agent. So predictable
and powerful is the relief that if the patient does not respond
at least partially to carbamazepine, it should lead to a
121

Section II Oral and Maxillofacial Disturbances

reconsideration for the diagnosis of idiopathic TN. If the


initial dosage does not relieve the discomfort adequately,
administer a higher dose by increments of 100 mg (200 mg/
day) up to a maximum dosage of 1,200 mg/day. This drug
may cause bone marrow depression, drowsiness, dizziness,
blurred vision, vertigo, subjective feeling of dryness in the
mouth as a spectrum of its side effects. Therefore monitoring the bone marrow activity by obtaining a complete
blood count prior to initiating therapy and routinely
thereafter is indicated. The main disadvantage of this drug
is that, though very effective, it does not address the etiology of the neuralgia and needs to be prescribed on a longterm basis for symptomatic relief. Baclofen is the skeletal
muscle relaxant employed in treating TN based upon the
CNS depressant properties. Baclofen is most often used
after therapy with carbamazepine has been initiated as the
effects are synergistic with those of carbamazepine permitting a reduction in the dosing of carbamazepine, thereby
reducing any of its adverse effects. Baclofen is introduced
as 5 mg t.i.d. for 3 days, followed by increase to 10 and
20 mg/day every 3 days, up to a maximum dosage of
80 mg/day. Several other drugs have been tried in the
management of refractory TN, but their role has been
unclear and not supported by strong enough evidence to
be routinely employed. Another drug, pimozide has also
been used in the doses of 212 mg/day in managing TN.
This drug is however recommended only for very severe
and intractable cases given the higher rate of adverse side
effects. Drugs like gabapentin, lamotrigine, topiramate
have been used with some success in few clinical trials,
but their usefulness remains yet to be ascertained at this
point in time.
Over time, the drugs used for the treatment of TN often
lose effectiveness as patients experience pain in spite of the
routine medications. For such patients, in whom medical
therapy has failed, surgery is a viable and effective option.
There are various surgical options that may be explored as
options by the neurosurgeon, the description of which is
beyond the scope of this book (Flowchart 1).
Prognosis
Trigeminal neuralgia is not a life-threatening condition.
The disease manifests typically as clusters of attacks that
wax and wane in frequency. Exacerbations most commonly occur in fall and spring seasons. After an initial
attack, the disorder may remit for months or even years.
Thereafter the attacks may become more frequent, more
easily triggered, disabling, and may require long-term
medication.

Glossopharyngeal Neuralgia
Glossopharyngeal neuralgia (GPN) is a neuropathy similar
to TN, but occurs due to affliction in the distribution of the
122

ninth cranial nerve. Harris (1926) coined the term glossopharyngeal neuralgia. This condition though less frequently
seen in comparison to TN, is nonetheless equally painful
and causes a great deal of deterioration in the quality of
life in affected persons. The exact cause of this condition
is unknown as yet, with some reports of nerve compression
leading to the condition. However, this still remains to be
ascertained as the definitive cause of GPN.
Clinical features
Glossopharyngeal neuralgia characteristically manifests in
the older age group usually beyond 60 years of age. It does
not exhibit any specific gender predilection. A patient suffering from GPN will give a history of severe shooting
pain occurring in episodes. The attacks have no specific
pattern and may vary in frequency from a few per day to
rarely once in few months. The severity too can oscillate
from between intolerable to relatively milder attacks. The
pain is usually localized to areas around the posterior
parts of the oral cavity and the pharynx in a typical unilateral manifestation. The pain attacks may be initiated by
some specific functions like speech, swallowing, yawning
or coughing (associated with tongue movements).
Clinical examination usually yields no specic information, but careful probing may reveal certain sensitive areas
or trigger points, that are usually located in the oropharyngeal walls or the peritonsillar area (including the soft palate). Thus palpation of the lateral aspect of the throat can
easily provoke an attack conrming the diagnosis. Rarely,
the pain from GPN may be felt in the ear region only, caused
due to involvement of the tympanic plexus of the ninth
cranial nerve. The close proximity of the glossopharyngeal
nerve to the vagus nerve may cause accompanying vagal
manifestations like syncope, arrhythmia and at times,
even cardiac arrest.
Differential diagnosis
Since the trigger zones of GPN lie around areas of jaw
usage, the clinician may easily confuse it with odontogenic
causes, TMJ-related problems or masticatory muscle disorders. Masticatory pain may be easily differentiated by
avoiding movements of the mandible and allowing free
movements of the tongue. GPN will not be prevented as
tongue movements would precipitate the attack. Another
definitive method is to apply a topical anesthetic on to the
pharyngeal mucosa that would completely stop the pain
impulses arising from the stimulation of trigger zones. Any
relief by this method would certainly point to a diagnosis
of GPN.
Eagles syndrome, associated with an elongated styloid
process compressing the glossopharyngeal nerve may produce symptoms similar to those of GPN. A radiographic
examination of the neck can help rule out calcic enlargement of the styloid process. Also pain on rotation of the head

Chapter 5 Orofacial Pain

Flowchart 1
Trigeminal neuralgia

New case

Refractory cases

Resistance
Carbamazepine
(Mazetol, Tegretol)
100 mg b.i.d.

Increase the dose of


carbamazepine up to
600 mg b.i.d./day

Phenytoin sodium
(Eptoin, Dilantin)
100 mg

1. Percutaneous radiofrequency
thermocoagulation
2. Microvascular decompression

Sustained release
carbamazepine
(Mazetol SR, C-Lep SR)
400 mg b.i.d./day

Second line of drugs


(no established efficacy cochrane)
1. Lamotrigine 50 mg/day (Lyzin)
2. Pimozide 2 mg b.i.d./day
(Mozep, Pimojet)
3. Baclofen 25 mg b.i.d./day
(Spinofen, Lioresal)

1. Combination therapy carbamazepine


(half the last dose) + phenytoin sodium 100 mg
2. Oxycarbazepine 300 mg (Oxep, Oxetol) b.i.d./day
up to 1,200 mg/day
3. Gabapentin 300 mg (Gabantin, Gabapin) 1st day
300 mg, 2nd day 300 mg b.i.d., 3rd day 300 mg t.i.d.
and then maintain the dosage. Can be given up to
2,400 mg/day

Note: All available medications have been enlisted. however, the physician should
choose the appropriate mode of treatment/drug based on the clinical situations

Management of trigeminal neuralgia

to one side (causing impingement of the nerve) is a feature


more suggestive of Eagles syndrome rather than GPN.
Another situation that may compound the diagnosis of
GPN is its rare but simultaneous occurrence with TN. This
situation may necessitate ruling out any brain lesions
causing these conditions. Again topically anesthetizing the
pharyngeal mucosa will cause partial relief and the patient
will point out to the persistent pain in the areas of the trigeminal nerve distribution.
When GPN manifests exclusively in the tympanic
plexus, the excruciating ear pain may be confused with
geniculate neuralgia, ear-related or TMJ-related disorders.
Investigations
Laboratory tests do not exhibit any abnormality. In case of
concurrent GPN and TN, an elective MRI scan of the brain

may be performed to detect any intracranial or extracranial


tumors or any vascular anomalies.
A panoramic radiograph may be obtained to check for
the status of the styloid process calcication.
Treatment
The medical management of GPN is similar to that of TN. The
anticonvulsant, carbamazepine, is the drug of choice,
according relief to most of the affected persons. Baclofen
also aids in the management by providing a synergistic
action along with carbamazepine. The dosage schedules
used in managing TN are the same when applied to GPN.
Failure of medical therapy necessitates considering surgical options that have been known to provide relief, but
come with associated risks accompanying any surgical
intervention modality.
123

Section II Oral and Maxillofacial Disturbances

The occurrence of severe pain during swallowing may


lead to the avoidance of any food and drinks by the patient.
This can adversely impact the general health of the patient
due to a signicant lack of nutrition. Also the older age
manifestation may predispose to more severe effects of malnutrition in GPN patients. Therefore adequate dietary adjustments need to be made and counseling must be provided
regarding proper diet schedules.
Prognosis
Glossopharyngeal neuralgia is not a life-threatening condition. The disease produces episodic pain attacks that vary in
frequency. Some patients may suffer only few attacks with
natural remissions for prolonged periods. However frequent
pain in most cases requires long-term medication.

Postherpetic Neuralgia
The virus herpes virus varicellae or human herpes virus-3
(HHV-3) causes the infections varicella and herpes zoster
in man. The primary infection with this virus leads to the
clinical manifestation of varicella or chicken pox. Once
the primary infection resolves, the virus enters into the
sensory nervous system and can remain latent there for
many years. In the head and neck, the trigeminal ganglion
is the preferred site that harbors the virus during its
latency. Due to some reason, activation of such latent viral
particles causes the secondary infection called herpes
zoster.
Spontaneous pain, pain provoked by trivial stimuli, and
altered sensation accompany herpes zoster and which may
continue long after its characteristic rash has healed is
known as postherpetic neuralgia (PHN). Herpes zoster infection by itself is a painful condition and the pain continues
up to a month in most patients. But when the lesions have
clinically healed and the pain still persists beyond a period
of 3 months, the diagnosis points to PHN. The exact cause
of PHN is not known, as it does not occur in every patient
who manifests zoster infection. The sensory alterations
and pain that occur in PHN have been thought to occur as
a result of both peripheral and central disturbances in the
nervous pathways. Many risk factors have been noted in
clinical studies that predispose for development of PHN,
such as advancing age, the site of zoster rashes (a particularly higher risk for trigeminal manifestation), a severe
prodromal pain before the zoster manifestation and a very
severe degree of rashes.
Clinical features
Postherpetic neuralgia usually affects the elderly group of
patients over 60 years. As the age advances, the risk for
developing PHN increases. The general debilitation of the
health and/or any accompanying immunocompromised
124

states leads to manifestation of zoster and consequently


PHN. Generally it is not seen in patients below 40 years
and the incidence between 40 and 60 years is quite less as
compared to in those patients above 60 years. No specific
gender predilection is noted and it manifests in both male
and female patients. The patient provides a typical history of
unilateral pain or burning sensation that affects a region in
a dermatomal pattern. Clinical examination will reveal either
healing or already healed lesions of zoster infection. In rare
instances, subclinical reactivation of herpes zoster can occur
(without clinical manifestation of the rashes) known as zoster sine herpete. If PHN occurs in conjunction with such a
situation, the diagnosis may be slightly confusing.
Management
The condition is never fatal, but patients may experience
significant pain for a prolonged period of time thereby
decreasing their quality of life. The main goal of therapy is
to achieve relief from the constant gnawing pain the
patient experiences. Though most of the times complete
resolution is not achieved, some degree of reduction can be
hoped for, sufficient enough for the patient to bear while
performing routine daily activities.
The various drugs that have been employed in managing PHN are: the tricyclic antidepressants (amitriptyline,
nortriptyline), corticosteroids (dexamethasone, prednisone,
and methylprednisolone), and anticonvulsants (gabapentin). The antiviral drugs (famciclovir) that are used to treat
the zoster infection have shown to decrease the incidence of
PHN as compared to patients who have not received antiviral therapy. Topical therapy with capsaicin and lignocaine
has been effective in few patients.
Those patients who do not respond to the medications
within the rst year are unlikely to have any relief from the
pain and are labeled as refractory. These patients need to
be educated and counseled about the condition.

Nervus Intermedius (Geniculate) Neuralgia


Nervus intermedius is the sensory branch of the VII cranial
(facial) nerve that supplies the external auditory meatus,
ear auricle and regions around it. The neuralgia occurring
in this nerve is referred to as nervus intermedius neuralgia
or geniculate neuralgia or VII nerve neuralgia. This condition is very rare as compared with the other neuralgias in
the head and neck region. It may be associated with herpes
zoster infection of the geniculate ganglion (Ramsay Hunt
syndrome).
The patient describes paroxysmal pain occurring in the
external auditory meatus or the walls of auditory canal.
Rarely the pain may be felt only in the tympanic membrane or within the middle ear. The patient may describe
a feeling of a hot stick inserted within the ear. Rarely the
pain may be felt in the soft palate, tongue or even within

Chapter 5 Orofacial Pain

the facial musculature. However careful examination will


reveal that the pain occurs when the ear auricle is stimulated and cause radiation of pain to the structures mentioned before.
Management of the condition is similar to trigeminal neuralgia with the use of anticonvulsants like carbamazepine
in doses of up to 1,200 mg/day. In Ramsay Hunt syndrome
a short course (23 weeks) of high-dose steroid therapy has
been found to be particularly useful.

Occipital Neuralgia
Paroxysmal sharp pain occurring in the region supplied by
the greater and lesser occipital nerves constitutes occipital
neuralgia. The pain is felt in the posterior region of the skull
up to the vertex. Rarely the patient may manifest temporal
or at times even retro-orbital pain. Usually this condition
arises due to the compression of the nerves, following trauma,
infection or neoplasms. Given the frequency of musculoskeletal pains occurring in the same region the clinician needs
to carefully differentiate these from each other. The presence
of trigger points in the cervical region causing radiating
pain up to the occipital region favors a musculoskeletal disorder. Local anesthetic blocking of the taut trigger points
helps in easy differentiation. No satisfactory management
strategies have been outlined in literature due to the paucity of true occipital neuralgia cases.

ATYPICAL ODONTALGIA
Atypical odontalgia (AO) is a clinical condition that poses
quite a challenge to the dental clinician. As the name suggests it is toothache that cannot be attributed to any cause
that are usually suspected. It is therefore also known as
phantom pain. Various other terminologies have been
applied to this condition in the past, such as, atypical
facial neuralgia, migrainous neuralgia, idiopathic toothache, etc. that have only added to confusion rather than
clear many of the impending doubts regarding this condition. Therefore the use of these alternative terminologies is
best avoided. AO is a frequently encountered condition in
clinical practice. Patients usually end up getting various
dental treatment procedures performed for the problem
and often seek exacting therapy from the clinician. The
multiple procedures performed previously may at times
mislead the dentist into assuming the diagnosis provided
by the previous clinician. It is still a poorly understood
phenomenon with unclear pathophysiology and as a consequence diagnostic confirmation is achieved by excluding other known causes or those with a somatic etiology.
Some authors have suggested a deafferentation pain model
for explaining the clinical behavior, however till date,
this has not been conclusively proven. Another school of

thought, that too has not been validated, has believed that
some form of trauma has to be involved that may lead to
some unexplained changes in either transmission or recognition of the pain impulse. The association of AO with
psychological disorders has led to some belief that the pain
may be a component of the spectrum of the psychosomatic
disorders.
Clinical features
Atypical odontalgia is a very frequently encountered clinical situation and patients present with symptoms of
toothache. The patient is usually a middle aged lady in her
early forties but may manifest in significantly older
women too. The exact reason for this age and gender predilection has not been understood. The patient usually
points out specifically to a single tooth or very rarely a
group of adjacent teeth. The teeth most commonly affected
are the premolars and molars of the maxillary jaw, AO is
very rarely reported in the mandibular teeth. On examination, there is no abnormality detected in the complaint
tooth. Many a times, the tooth may have been treated endodontically, but does not otherwise show up any cause for
concern. The tooth may have been extracted and then in
such cases, the patients insist that the procedure has not
alleviated the pain and the pain still persists, as if the tooth
is still present, giving rise to the term, phantom pain of the
tooth. The pain described is of a dull, aching, throbbing or
burning and persistent type. The patient will usually
describe a feeling of unpleasant sensation being present
throughout the day that does not increase during functions
such as eating or swallowing. AO does not cause any disturbance in sleep and patients report of occurrence of pain
immediately after awakening. The presence of the pain is
usually not altered by local provocation such as during
pulp testing, percussion, etc. Very rarely the pain may
spread to the adjoining structures within the oral cavity,
such as jaw bones and even rarely may involve the broader
facial region.
Graff-Radford and Solberg have outlined the following
criteria that may help in identifying AO:
1.
2.
3.
4.
5.

Pain in a tooth or tooth site


Continuous or almost continuous pain
Pain persisting for more than 4 months
No sign of local or referred pain
Inconsistent results of a somatic nerve block

All investigative modalities such as laboratory or radiographic tests turn up with negative results. The patient usually undergoes a lot of attempted therapies without having
accorded a definitive diagnosis.
Differential diagnosis
Other pathologies manifesting similar symptoms need
to be ruled out before arriving at a diagnosis of AO, as
125

Section II Oral and Maxillofacial Disturbances

the diagnosis is primarily based upon exclusion. Common


pathologies are commoner than thought to be, while rare
ones are rarer than thought to be. This statement applies
accurately in disorders of the oral cavity too and therefore
it is necessary for the clinician to emphatically rule out the
common causes of toothache such as pain of pulpal, periodontal or myofascial origin and pain referred from contiguous structures.
Atypical odontalgia can be differentiated from pulpal
pain by the following features: patient cannot usually
point out to a specic tooth with pulpal pain because of the
absence of propioceptive ability of the pulp. Pulpal pain
tends to worsen over a period of time, while AO is more or
less persistent and of the same intensity. Local provocation
of heat, cold or electricity will give altered results from the
corresponding or opposing teeth in pulpal-related pain,
but not so in AO. Anesthetic blocks cause instantaneous
relief from pulpal pain. Finally the attempted dental therapies should have alleviated pulpal pathology, but AO manifests with persistence of the pain. Similarly periodontal pain
will show up clinical ndings of periodontal disease and
also some radiographic evidence of periodontal destruction.
Anesthesia usually relieves periodontal pain but not AO.
Myofascial pain usually involves the broader orofacial
region with the major component being involvement of
the musculature as opposed to the single tooth or tooth
site of AO. The presence of trigger points leading to either
spontaneous pain or pain on palpation is not a feature of
AO and movements of the musculoskeletal system such as
during talking, chewing, smiling cause exacerbation of
myofascial pain, again not encountered in AO.
Pain referred from the maxillary sinus may be mistaken
for AO, therefore needs careful consideration. Sinus pain
usually involves the whole of the maxillary jaw or at least
a quadrant on one side. Application of pressure below the
eyes and over the sinus region, and lowering or bending
down the head lead to an increase in pain of sinus origin, AO
however usually does not demonstrate any change in the
intensity of pain. Imaging studies can usually point out the
sinusitis leading to the pain, but AO will not show up any
imaging ndings.
In the rare instances, when AO may involve a region
more than a single tooth, trigeminal neuralgia (TN) may
need to be ruled out. TN occurs as lancinating pain in bursts
of paroxysms, while AO is a dull ache that is continuous in
nature. No specic trigger zones exist for AO unlike TN and
TN usually manifests in a much older age group.
Treatment
Management of deafferentation pains is usually not easily
accomplished and AO is no exception. The pharmacologic
therapy is usually the best suited strategy and all dental
procedures must be completely avoided once a diagnosis of
AO has been made, because any somatic treatment would
126

be of no value in causing any pain relief. The patients usually agree to this after having suffered through numerous
procedures not having provided relief. Any psychologic
association if suspected should be dealt with in conjunction with a psychologist.
Atypical odontalgia does not respond to opioid as well
as non-opioid analgesics. The tricyclic antidepressants are
the most favored drug employed in managing AO. The
exact mode of action of these medications is not known,
but it has been suggested that the analgesic properties of
these drugs are more likely acting than their antidepressant
effects. Amitriptyline is prescribed in doses ranging from
25 to 75 mg per day initially and if needed may be used up
to 200 mg per day. The benecial effect of the drug needs
to be carefully titrated against the risk of adverse effects
such as dizziness, drowsiness, headache, xerostomia, constipation, appetite and weight changes, nausea, weakness,
hypotension. But patients not achieving relief with high
doses are unlikely to have any satisfactory remission of the
condition. In those cases that do achieve relief, complete
elimination of pain is rare and therapy needs to be continued for a prolonged duration, a minimum of 3 months.
Other tricyclic antidepressants such as imipramine, nortriptyline, and dothiepin have also been used. However,
their effects are not very different from amitriptyline.
Phenothiazines have also been used with some success in
some clinical trials, however, their role is more supplementary to the tricyclic drugs. Tardive dyskinesia is a major
potential side effect of phenothiazines that has not allowed
for a major role of these drugs in AO. Once pain control of
a desirable degree is achieved, all these drugs should be
tapered off gently and then discontinued.

ATYPICAL FACIAL PAIN


This condition has been the cause of much confusion and
has led to many contradictions in the literature. The term
atypical facial pain (AFP) suggests that it is a painful condition not satisfying certain typical manifestations of
well-known conditions. In the current scenario, AFP has
been completely rejected as a diagnostic terminology by
the International Association for the Study of Pain (IASP),
for the simple reason that it does not describe any definitive condition and has been used injudiciously in the literature to signify conditions that were not understood or
correctly diagnosed. AFP has been as a wastebasket for
dumping any painful condition that has not conformed to
the set of criteria for other orofacial pain conditions and
thus is a diagnosis of exclusion rather than inclusion. AFP
has thus been encompassing a wide group of facial pain
problems.
Although rarely as severe as trigeminal neuralgia, facial
pain is continuous for AFP patients. Recent studies propose

Chapter 5 Orofacial Pain

that AFP is an early form of trigeminal neuralgia. Indeed,


some patients have components of both AFP and TN symptoms. Earlier literature has linked AFP to psychological
pathology. Recent studies however have shown no such
link exists.
Clinical features
The causes for AFP may be varied but they lead to strikingly similar symptoms. Facial pain, typically manifests in
middle-aged women who often describe some kind of a
vague, intractable, burning, aching or cramping, occurs
on one side of the face, often in the region of the trigeminal nerve that may extend into the upper neck or back of
the scalp. The pain is usually of a diffuse pattern and presents as a continuous manifestation with few, if any periods
of remission. On examination, however, no frank noticeable pathology is detected. The discomfort leads to a definite decrease in the quality of life. Invariably the patient
will have visited a number of clinicians and undergone
numerous dental procedures, in hopes of getting a cure.
Many clinical and laboratory tests would have been performed and most of them would have yielded negative
results. Though a psychological basis has been often attributed to this condition by various authors, the findings of
various studies have been conflicting and the occurrence
of psychogenic findings is not different from that of the
general population.
Diagnosis
Diagnosing AFP is a challenging task. As mentioned earlier, the diagnostic path for AFP is usually based upon a
process of elimination. When a patient complains of above
described symptoms the clinician must first rule out any
other conditions. The conditions needing careful considerations are oral (dental), paranasal sinus-related, myofascial and neurologic causes. Tests to be performed include
radiographs of the skull, advanced imaging modalities,
especially including the brain and the skull base. A careful
otolaryngologic evaluation and a neurological consultation should be comprehensively obtained. AFP patients are
considered complex and end up with a partial or incomplete diagnosis, the reason being that the patients are not
completely evaluated, but only examined by a given specialist, and what implies in the application of only that
specific field of treatment. Thus a multidisciplinary systematic evaluation for patients with suspicion of AFP is an
absolute must.
Management
Treatment of AFP can be difficult and perplexing for both
the doctor and patient. Pharmacotherapy is usually the first
resorted treatment that may be complemented by surgical
procedures. Drugs like amitriptyline and gabapentin have

been used with some degree of success. Other alternative


modalities that have been employed include hot and cold
compresses and acupressure and/or acupuncture. These
have been able to provide some degree of relief to majority
of the patients. Usually there are no associated long-term
consequences due to this condition other than altered quality of life, but the patients usually get used to the pain and
continue with routine activities.

BURNING MOUTH SYNDROME


Burning mouth syndrome (BMS) is not a very common
condition, yet can be encountered occasionally by the dental clinician. BMS is a poorly understood phenomenon that
may present with a dilemma to the attending clinician in
both diagnosing and managing such patients. BMS is a
chronic intraoral painful condition that is not characteristically associated with any clinical lesions. It is known by
various other synonyms, like burning tongue syndrome,
glossodynia, glossopyrosis, stomatodynia, and stomatopyrosis. However it would be incorrect to label the condition as glossodynia or glossopyrosis when the entire oral
mucosa is involved and in such a scenario BMS would be
the appropriate term. The IASP defines BMS as a burning
pain in the oral mucosa and glossodynia as a burning pain
in the tongue only.
The exact etiologic or precipitating cause of BMS is not
yet known in spite of various proposed hypotheses on the
matter. Over the years, local, systemic and psychologic
factors have been the broadly suggested causes. Local
causes include candidal infection, denture wear, decreased
salivary output, and parafunctional oral habits. Systemic
factors that have been suspected are various nutritional
deciency disorders (iron deciency anemia, vitamin deciencies), hormonal changes like menopause, diabetes,
thyroid and parathyroid disorders and drugs. Patients with
BMS have been described to have higher levels of anxiety,
depression, cancerophobia and mood disorders as compared to control groups. Eli Eliav et al (2007) conducted
a study to assess the role of chorda tympani in patients
with BMS. The striking feature of their study was the
presence of chorda tympani nerve dysfunction in patients
with BMS.
They concluded that BMS is a form of neuropathic pain,
which may be related to chorda tympani nerve dysfunction.
They proposed that the evidence of elevated taste detection threshold levels (via electrogustatory testing) and raised
taste/tingling detection thresholds ratio may help clinicians diagnose BMS.
Clinical features
The typical BMS patient will describe the problem as a
burning, scalding or a tingling feeling in the oral mucosa.
127

Section II Oral and Maxillofacial Disturbances

There may be accompanying persistent bad or altered taste


sensations. BMS usually affects the elderly, above the age
of 50 years and with a strong predilection for women. The
condition seems to occur between 3 and 12 years of reaching menopause and presence of other systemic diseases
just adds to the increased risk of developing the condition.
Evaluation of a suspected BMS patient should include
details regarding the onset, location, and character of the
pain. Any related oral symptoms of salivary changes should
also be noted. The pain and/or burning sensations typically start upon awakening and increase in intensity with
the progression of the day and the condition rarely interferes with sleep. The patient describes the typical sensation
as if the mouth or the tongue were scalded or on fire. The
burning sensation may be aggravated by hot and/or spicy
foods but is not specifically caused by them. In some
patients the symptoms begin in a particular oral location
and then gradually spread to cover the entire mucosa. The
tip of the tongue and the inner surface of the lips are the
most common starting locations. Functions such as eating
and drinking can bring about temporary relief. However in
majority of cases, no such clinical lesions will be detected.
The patient may give details of systemic symptoms that
might correlate the oral condition with hot flushes of menopause. The patients social and psychologic history should
also be taken into account and noted if any particular event
relates to the onset of the symptoms. Queries related to

cancer arising from the condition need to be resolved. BMS


patients often end up visiting many clinicians for getting
the problem resolved and often sound dejected. Whether
there is an underlying psychologic cause for the pain or
if the psychologic component is a consequence of the painful condition has not been accurately ascertained.
Petruzzi et al (2007) described ve patients who had
burning mouth syndrome along with vulvodynia. They
termed this condition vulvostomatodynia. The condition
is characterized by burning sensation in the tongue, lips,
vestibule and other mucosal sites in menopausal and post
menopausal women.
Differential diagnosis
Oral lesions such as local oral infections, oral lichen planus and the like should be ruled out. The oral mucosa
should, therefore, be thoroughly examined for any mucosal lesions that may be a cause for the symptoms. The
presence of the burning sensation may be an initial sign of
the neuralgias; however these will be typically unilateral
in manifestation. The combined occurrence of burning
sensation and decreased salivation should lead the clinician to investigate any underlying salivary gland pathology. Common systemic diseases causing burning sensations
in the oral mucosa such as diabetes and anemia must be
assessed by appropriate laboratory evaluation.

Flowchart 2
Burning mouth syndrome

Initial visit

Chronic cases

Topical:
A. Capsaicin gel 0.025% (Capsain-p)
B. Alpha-lipoic acid as mouthrinse
b.i.d./12 months (ALA-100, Aladin
100 mg)

Systemic:
A. Multivitamins B12, methyl
cobalamin and folic acid (MCBM-69,
Neurokind-G and Nuvolt-G t.i.d.;
Nurokind plus, Nuvolt: o.d.)

Systemic:
A. Amitriptyline 25 mg b.i.d. (Amitone, Amitryn, Amitrol,
Tadamit) for 15 days, o.d. for 15 days
B. Gabapentin 300 mg (Gabantin, Gabapin) 1st day 300 mg,
2nd day 300 mg b.i.d., 3rd day 300 mg t.i.d. and then maintain
the dosage. It can be given to a maximum of 2400 mg/day
C. Alprazolam 0.25 mg b.i.d. (Restyl, Alcalm, Anxit SR-0.5 mg)
for a week and slowly withdraw the drug
D. Clonazepam 2 mg o.d. at bed time for 15 days (Clozep,
Lonazep MD, Melzap)
E. Nortriptyline 25 mg o.d. for not more than 3 months (trip)

Note: All available medications have been enlisted. However, the physician should choose
the appropriate mode of treatment/drug based on the clinical situations

Management of burning mouth syndrome

128

Chapter 5 Orofacial Pain

Management
Any treatable cause of the burning sensations in the oral
mucosa should be identified and treated comprehensively
before labeling any patient to be suffering from BMS.
However, once all such conditions have been ruled out
and a diagnosis of BMS has been arrived at, the situation
should be explained to the patient and counseling regarding the benign nature of the condition should be offered.
The decrease in the quality of life should be explained as
in some patients the conditions undergoes spontaneous
remission while in the majority of cases it persists as a
chronic condition. Due to an unclear etiopathogenesis,
definitive pharmacologic therapy is not available for the
condition and all modalities are essentially palliative in
nature. Topical, systemic and psychologic therapies have
been used with varying degrees of success. Topical therapies with anesthetic products such as lignocaine and benzydamine hydrochloride seem to be effective in a handful

of cases and even in these rapidly lose effectiveness.


Topical clonazepam when used in doses of 1 mg used for
3 minutes thrice daily has imparted relief to some patients,
yet its routine use has not been validated. Systemic therapies with alpha-lipoic acid, capsaicin, amisulpride and
antidepressants have been tried with inconsistent results.
Gabapentin that has been effective in other chronic pain
disorders has demonstrated little or no effect on BMS
patients. Cognitive behavioral therapy (to replace patterns
of negative emotions and thoughts with more realistic
and positive ones) has helped few patients who have had
underlying psychological causes. However, labeling all cases
as psychologically based often leads to inefficient management of BMS patients by both dental and medical clinicians. Therefore, no single or sure-shot treatment strategy
has been evolved for this enigmatic condition and it would
be wrong to label each case of BMS to suffering from the
same causative mechanism, for therein lies the pitfall of
successfully managing BMS (Flowchart 2).

Trigeminal Pain Pathway


Trigeminal nerve is the primary sensory nerve of the maxillofacial region. Pain is conducted along the afferent fibers
of the branches of the trigeminal nerve into the semilunar or gasserian ganglion. The impulses from the ganglion are
carried to the sensory root of the nerve into the pons. The sensory root either ends directly in the main sensory nucleus
or branches out into the ascending fibers (carry general tactile sensation) and descending fibers (transmit pain and
temperature). Pain impulse, therefore descends from pons, through the medulla down to the level of second cervical
segment and terminates.
The secondary neurons emerge from the spinal nucleus, after which the axons cross the midline and ascend to join
the bers of mesencephalic nucleus to form spinothalamic tract of the fth nerve.
These axons continue to ascend and terminate in the posteroventral nucleus of the thalamus. Few of these second
order neurons activate the reticular area of the brain stem causing excessive alertness, increase the individuals sense
of perception and reaction to pain.
The third order neurons project from the posteroventral nucleus carrying pain impulse to the posterocentral convolutions of the cerebral cortex.

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SECTION

III

Mucocutaneous
Disorders

6
7
8
9

Red and White Lesions


Vesiculobullous Disorders
Oral Ulcerative Diseases
Dermatological Diseases

133
174
196
218

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CHAPTER

Red and White Lesions


Ashok L

Color of Oral Mucosa

Hereditary Benign Intraepithelial Dyskeratosis


(Witkops Disease)
Focal Epithelial Hyperplasia (Hecks Disease)
Dyskeratosis Congenita
White Sponge Nevus

Description of Red and White Lesions


White Lesion
Red Lesion

Etiologic Classification of Red and


White Lesions

Red Lesions of the Oral Cavity

White Lesions of the Oral Cavity

Red Lesions of the Tongue


Migratory Glossitis
Median Rhomboid Glossitis
Deficiency States
Foliate Papillitis
Erythroplakia
Discoid Lupus Erythematosus

Frictional Keratosis/Traumatic Keratosis


Chemical Burns and Thermal Burns
Leukoplakia
Lichen Planus
Candidiasis
Oral Submucous Fibrosis
Psoriasis

In day-to-day clinical practice oral physicians often encounter a wide spectrum of oromucosal lesions. These lesions
range from harmless mucosal alterations like change in
the color and texture of the oral mucosa, needing simple
therapeutic remedies and patient counseling to lesions of
a life-threatening nature. Red and white colored alterations
of the oral mucosa are commonly seen in dental practice.
Recognizing and differentiating these mucosal alterations
from normal anatomic variations is imperative for the
effective management of these lesions.

Color of Oral Mucosa


As the oral mucosa is translucent, it reflects the contents
of the underlying connective tissues. Normal color of the
oral mucosa is pink, the intensity being varied in different
parts of the oral cavity and depends upon various factors
like,

Thickness of the oral mucosa


Degree of keratinization
Amount of vascularity and fibrous content in the connective tissue

Formation of pseudomembranes
Pigmentation producing cells like melanocytes.

DESCRIPTION OF RED AND WHITE


LESIONS
White Lesion
White lesion is a non-specific term used to describe any
abnormal area of the oral mucosa that on clinical examination appears whiter than the surrounding tissue. It is
usually slightly raised, roughened or of different texture
from the adjacent normal mucosa (e.g. linea alba buccalis,
frictional keratosis, leukoplakia, chronic hyperplastic candidiasis etc).
This normal color of the mucosa may turn into white due
to the increased thickness of the epithelium with increased
production of keratin (hyperkeratosis) and production of
abnormal keratins and imbibition of uid by the upper layers of the mucosa. In situations like coagulation of tissue
surface (occurs in burns), results in the formation of white
pseudomembrane, which remains attached to the mucosa
but can be scraped off easily. Generally white lesions result
133

Section III Mucocutaneous Disorders

from various factors like, trauma, infections, immunologic injury to the mucosa or other genetically determined
factors.

5.

Red Lesion
Red lesion refers to an area of reddened mucosa that may
appear smooth and atrophic or exhibits a granular, velvety
texture (e.g. erythroplakia, median rhomboid glossitis,
erythematous candidiasis, etc). These lesions may occur
alone or in combination with a white lesion. Such lesions
may be termed as a mixed lesion or a red and white lesion
(e.g. speckled leukoplakia, erosive lichen planus, etc).
Individual variations in the color of the oral mucosa are
probably an expression of one or more genetically controlled factors.
Healthy masticatory mucosa (gingiva, palate, dorsal
surface of the tongue) is light pink in color. The lining
mucosa (mucosa over the vestibule, cheeks, lips, oor of
the mouth, and ventral surface of the tongue) is reddish
pink in color. Palatoglossal arch region is dusky red in
color due to increased vascularity and often misdiagnosed
as sore throat.
The histological reason behind the appearance of a red
lesion may be due to dilated blood vessels, inux of new
blood vessels, hemorrhage under the epithelium or a relatively thin outer epithelium.

ETIOLOGIC CLASSIFICATION OF RED


AND WHITE LESIONS
1.

2.

3.

4.

134

Normal mucosal variations


Leukoedema
Fordyce granule
Linea alba buccalis
Genetically linked white keratotic lesions
Oral genodermatoses
White sponge nevus
Hereditary benign intraepithelial dyskeratosis
Pachyonychia congenita
Post inflammatory white lesions
Traumatic keratosis
Mechanical trauma
Thermal burn
Chemical burn (aspirin burn, uremic stomatitis)
Radiation mucositis
Reactive mucosal hyperplasias (stomatitis nicotina
palati)
White and red lesions due to infections
Syphilis
Measles (Kopliks spots)
Candidiasis
Bacterial stomatitis

6.

7.

Premalignant lesions
Leukoplakia
Lichen planus
Lichenoid reactionsdrug induced, graft-versushost disease
Erythroplakia
Actinic keratoses
Discoid lupus erythematosus
Chronic hyperplastic candidiasis
Premalignant conditions
Oral submucous fibrosis
Oral psoriasiform lesion
Dyskeratosis congenita
Syderopenic dysphagia
Syphilitic glossitis
Miscellaneous
Intraoral skin grafts (people of Afro-Asian origin) will
not generally exhibit a white coloration of the skin
graft. The graft will appear black or brown depending
on the extent of melanin pigmentation (Figure 1).

WHITE LESIONS OF THE ORAL CAVITY


White lesions of the oral cavity can be categorized clinically
as keratotic (non-scrapable) or non-keratotic (scrapable)
lesions. Table 1 gives a list of scrapable and non-scrapable
lesions.

Frictional Keratosis/Traumatic Keratosis


Frictional keratosis is defined a white patch with a rough
surface which is clearly related to a source of mechanical
irritation and that will disappear over a period of time
with the removal of the stimuli. Lesions belonging to this
category include linea alba buccalis, and cheek, lip or
tongue biting or chewing.
Linea alba buccalis is a non-scrapable white line that is
present on the buccal mucosa usually along the plane of
occlusion (Figure 2). It may either be seen unilaterally or
bilaterally. Linea alba occurs due to the constant friction or
irritation of the buccal mucosa by the facial surfaces of teeth.
It is more pronounced with respect to the posterior teeth
and may have a scalloped architecture. It is asymptomatic
and usually does not require any form of management.
Chronic cheek, lip, tongue chewing usually presents
as thickened and shredded whitish areas. Habitual oral
mucosa chewing can sometimes lead to areas of localized
erosion and ulceration. The lesions may present bilaterally
or unilaterally.
Individuals with chronic cheek biting (morsicatio buccarum) have either a habit of sucking the cheeks frequently

Chapter 6 Red and White Lesions

Figure 1

Figure 2

Linea alba on the buccal mucosa. Courtesy: Department of


Oral Medicine and Radiology, MCODS, Mangalore
Skin graft. Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

Table 1

Non-scrapable and scrapable lesions

Keratotic lesions
(non-scrapable)

Non-keratotic lesions
(scrapable)

Linea alba buccalis


Frictional/traumatic keratosis
Homogeneous leukoplakia
Reticular lichen planus
Chronic hyperplastic candidiasis
Dyskeratosis congenita
White sponge nevus

Chemical burn/thermal burn


Pseudomembranous candidiasis
Syphilitic mucous patch
Diphtheritic patch

or push the cheek in between teeth with their nger.


Similarly individuals with chronic lip chewing habit
(morsicatio labiorum) and chronic tongue nibbling habit
(morsicatio linguarum) present with macerated appearance of the labial mucosa and lateral surface of the tongue
respectively. The lower labial mucosa is usually affected in
lip chewers (Figure 3A, B).
Habitual chewing may be associated with individuals
under stress. However most of the individuals are unaware
of the parafunctional habit. The management of these
conditions should be targeted at educating the patient
regarding the ill-effects of the parafunctional habit.
Frictional keratosis is also caused by the rough ange
of denture, sharp cusp of a tooth or sharp edge of broken
teeth (Figure 4).
Histologically traumatic keratotic lesions will show
varying degree of hyperkeratosis and acanthosis.

Management
Removal of the etiologic agent will generally result in complete resolution of the lesion within 2 weeks. Biopsy may
be considered in lesions that persist for a longer duration,
to rule out any dysplastic changes.

Chemical Burns and Thermal Burns


Chemical trauma to the oral mucosa may be due to
improper use of medicaments or the use of harsh chemical
substances such as strong acid or alkali.
Chemical burn usually results from the patient applying
analgesics like aspirin or acetaminophen or home remedies such as clove oil to the mucosa adjacent to a decayed
tooth to alleviate pain. Chemical substances like phenol,
silver nitrate, concentrated hydrogen peroxide, root canal
medicaments can also produce an area of necrosis.
Thermal burns are generally caused due to the accidental intake of hot food or beverages. These mucosal burns
are characteristically seen on the anterior one third of the
tongue and palate.
The clinical appearance of these burns in most cases
depends upon the severity of the tissue damage. Chronic
mild burn usually produces keratotic white lesion whereas
intermediate burn causes localized mucositis and the more
severe burns coagulates the surface of the tissue and produces a diffuse white lesion. In such cases the tissue can be
scraped off, leaving a raw bleeding painful surface (Figure 5).
Differential diagnosis
Acute pseudomembranous candidiasis and gangrenous
stomatitis can be considered in the differential diagnosis
for chemical and thermal burns.
135

Section III Mucocutaneous Disorders

Figure 3
A

(A) Whitish macerated appearance of the upper labial mucosa. (B) Whitish thickened and shredded area on the lower labial
mucosa. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 4

Frictional keratosis caused by the sharp cusp of the


adjacent molar. Courtesy: Dr Praveen, KLE Institute of
Dental Sciences, Bangalore

Figure 5

A chemical burn on the buccal mucosa that is characterized


by the presence of a white pseudomembrane that reveals
an underlying erythematous area when scraped off.
Courtesy: Dr Ashok

Management
1.

2.
3.

Topical application of anesthetic agent like benzocaine/


lignocaine gel (choline salicylate 8.7%, benzylkonium
0.01% and lignocaine hydrochloride 2%).
Topical application of steroids like triamcinolone acetonide (triamcinolone acetonide oral paste 0.1%).
In case of severe pain analgesics can be used.

Nicotine Stomatitis
(Stomatitis Nicotine Palatinus, Smokers Palate)
Thoma in 1941 was the first to use the term stomatitis nicotine because he noticed this lesion to almost exclusively
136

occur in individuals who had the habit of smoking tobacco.


This lesion is a reactive hyperplasia to the heat generated
by the tobacco smoke that acts as a chronic irritating
agent. These mucosal changes are mostly seen in reverse
cigarette/chutta and pipe smokers and relatively lesser in
cigar, cigarette and beedi smokers.
Clinical features
Smokers palate is usually seen in males. However, in the
Indian subcontinent women who have the habit of reverse
chutta smoking also exhibit these mucosal changes. It is

Chapter 6 Red and White Lesions

Figure 6
A

(A) Diffuse grayish white pigmentation of the palate with red pinpoint areas characteristic of smokers palate.
(B) Multiple papules on the palate with red pinpoint areas in smokers palate. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

generally asymptomatic. The palatal mucosa appears as a


diffuse grayish white surface or flat topped nodules may
be seen with red pinpoint areas situated in the center of
each nodule (Figure 6A, B). These red pinpoint areas correspond to the inflamed orifice of the minor salivary gland
ducts.
Differential diagnosis

Palatal papillary hyperplasia


Focal epithelial hyperplasia (Hecks disease)
Dariers disease (follicular keratosis)

Leukoplakia
Oral leukoplakia (OL) is the most common precancerous
lesion of the oral mucosa. The term leukoplakia was first
used by Schwimmer in 1877 to describe a white lesion on
the dorsum of the tongue, which probably represented
syphilitic glossitis. He proposed the term leukoplakia for
a diffuse patch on the dorsum of tongue. Since then it has
evolved as a clinicopathologic concept over many years;
sometimes representing an innocent hyperkeratosis and
sometimes dysplastic features.
Definition
The requirement for a clear definition for oral white
lesions has long been recognized. Similar requirements
also apply to red lesions or the red component of preponderantly white lesions. The definition of leukoplakia has
often been confusing and controversial. Currently the WHO
definition and definition given by Axell are widely used.

Auluck et al conducted a survey in 10 different dental colleges in India among 153 specialists including oral surgeons,
oral physicians and oral pathologists to check the prevalence of confusion regarding the definition of leukoplakia
and its application. It was found that 33.33% of the specialists preferred to follow WHO definition (1978), while 65.35%
preferred to follow Axell (1984) definition. The authors
described the current ambiguity regarding the accepted
definition of oral leukoplakia and emphasized the need for
an international collaboration to reach a consensus on the
use of the term leukoplakia.
WHO definition of leukoplakia (1978) Leukoplakia is a
white patch or plaque that cannot be characterized clinically
or pathologically as any other disease. The definition indicates that the term leukoplakia does not carry a histologic
connotation and should be used only in descriptive clinical
context.
Axell et al definition of leukoplakia (1984) Leukoplakia
is a white patch or plaque that cannot be characterized
clinically or pathologically as any other disease and not
associated with any physical or chemical causative agent
except the use of tobacco.
Axell et al definition of leukoplakia (1996) Leukoplakia
as a predominantly white lesion of the oral mucosa that
cannot be characterized as any other definable lesion;
some oral leukoplakia will transform into cancer. This definition is most widely accepted in the western world.
Pindborg et al definition of leukoplakia (1997) A predominantly white lesion of the oral mucosa that cannot be
characterized as any other definable lesion.
137

Section III Mucocutaneous Disorders

Epidemiology
The frequency of leukoplakia is highly variable among
geographical areas and demographic groups. The prevalence in the general population varies from less than 1 to
more than 5%. The prevalence of leukoplakia increases to
8% in men over the age of 70 and the prevalence in women
past the age of 70 is approximately 2%.
Mehta et al (1961) reported the prevalence of 3.5% in
4,734 Indian population. Manghi et al (1965) reported a
prevalence of 6.5% among 2,004 persons. Smith et al (1975)
reported a prevalence of 11.7% among 57,518 persons.
Yang et al (2001) reported the prevalence of leukoplakia
as 24.4% among the aborigines in southern Taiwan. Chang
et al (2005) reported the prevalence of 7.44%. In a 10-year
follow-up study, a random sample of 30,000 villagers in
three areas in India, the annual incidence rates varied
from 1.1 to 2.4 per 1,000 men and 0.03 to 1.3 per 1,000
women.
In India the prevalence of oral leukoplakia among betel
quid chewers with tobacco ranged from 0.4 to 1.8% and
among betel quid chewers without tobacco ranged from
0.3 to 0.7%.
Table 2 gives the overall impression of the prevalence of
oral leukoplakia with a geographic emphasis.
Classification and staging system for
oral leukoplakia
Van der Waal (2000) designed and proposed the classification and staging system. The present classification and
staging system is primarily designed for the purpose of
uniform reporting of treatment or management results and
requires the availability of a biopsy report. It also could
serve as means for epidemiological studies.
L (size of the leukoplakia)
L1 Size of single or multiple leukoplakia together  2 cm
L2 Size of single or multiple leukoplakias together 24 cm
L3 Size of single or multiple leukoplakias together  4 cm
Lx Size not specied

Table 2

138

P (pathology)
P0 No epithelial dysplasia (includes no or perhaps mild
epithelial dysplasia)
P1 Distinct epithelial dysplasia (includes mild to moderate and moderate to possibly severe epithelial dysplasia)
Px Absence or presence of epithelial dysplasia not
specied in the pathology report.
OLEP (Oral leukoplakia) staging system
Stage I
L1P0
Stage II
L2P0
Stage III
L3P0 or L1L2P1
Stage IV
L3P1
General guidelines for oral leukoplakia
staging system
1.

2.

3.

If there is doubt concerning the correct L or P category


to which a particular case should be allotted, then the
lower (i.e. less advanced) category should be chosen.
This will also be reflected in the stage grouping.
In case of multiple biopsies of single leukoplakia or biopsies taken from multiple leukoplakias the highest pathological score of the various biopsies should be used.
For reporting purposes the oral subsite according to
the ICD-DA should be mentioned.

The letter E in the OLEP abbreviation has been used to


prevent confusion with the often used abbreviation for oral
lichen planus.
Some leukoplakias have a white verrucous texture being
referred to as verrucous leukoplakia. In the majority of these
cases no epithelial dysplasia is present. Yet, such lesions
may easily recur (proliferative verrucous leukoplakia) after
conservative treatment and may nally lead to the development of a squamous cell carcinoma.
Etiopathogenesis
1. Tobacco (smoke/smokeless form) Use of tobacco in the
form of factory-made cigarettes, beedi, cigars and cheroots

Prevalence of leukoplakia

Author and year of study

Country

Number of persons examined

Prevalence (%)

Pindborg et al (19651966)

India

30,000

Gangadharan and Paymaster (1971)

India

2,03,249

0.7

Mehta et al (1972)

India

1,01,761

0.7

Axel (1976)

Sweden

20,333

3.6

Bouquet and Gorlin (1986)

USA

23,616

2.9

Hogewind and Van der Waal (1988)

Netherlands

1,000

1.4

Banoczy and Rigo (1991)

Hungary

7,820

1.3

Ikeda et al (1991)

Japan

3,131

2.5

Schepman et al (1996)

Netherlands

1,000

0.6

1.53.3

Chapter 6 Red and White Lesions

and powdered tobacco in pipes or rolled into hand-made


cigarettes, are the main etiological agents in the causation
of leukoplakia.
Much of the tobacco in the world is consumed in the form
of smokeless tobacco and it is placed in contact with the
mucous membrane. In south-east Asian countries tobacco
is mostly consumed mixed with other ingredients like
areca nut, betel leaf, slaked lime, catechu and condiments.
Smokeless tobacco use is practiced in many forms.
Chewing of tobacco containing products or snuff dipping
habits vary greatly from one part of the world to another.
It is of great importance to quantify the degree of exposure.
Over 300 carcinogens have been identied in tobacco
smoke or in its water-soluble components which can be
expected to leach into saliva. The major and most studied
among them include aromatic hydrocarbons, benzopyrene
and the tobacco specic nitrosamines, N-nitrosonornicotine
(NNN), nitrosopyrrolidine (NYPR), nitrosodimethylamine
(NDMA) and 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone (NNK). Benzopyrene is a powerful carcinogen and is
found in amounts of 2040 mg per cigarette. The mainstream smokes of a cigarette contain 310 mg of NNN and
150 ng of NNK. These agents act locally on keratinocytes,
stem cells, and are absorbed and act in many other tissues
in the body.
Cigarettes can be classied as low or medium, if the tar
yield is below 22 mg and as high if tar yield above 22 mg
compared with non-smokers the risk of oral cancer and OL
for smokers using low to medium tar cigarettes is 8.5%.
A case control study from Brazil also found an increased
risk among cigarette or pipe smokers with a strong doseresponse relationship between the number of years smoked
and oral cancer risk (Franco et al, 1989).
Snuff involves placing moistened, powdered tobacco,
treated with natron (sodium sesquicarbonate) in the lower
labial, buccal sulcus or the oor of the mouth against the
lingual side of the mandible. Snuff has been shown to
contain carcinogens such as N-nitrosamines which are
derived from tobacco.
Many studies have demonstrated that tobacco in any
form can predispose to OL (Pindborg et al, 1972; Salonen
et al, 1990; Christian et al, 1992).
2. Alcohol Alcohol has also been emerged as a significant risk factor for OL. In Germany, Wilsch et al (1978)
found that alcohol consumption was greater among people with leukoplakia as compared to control. In India
Gupta et al (1984) studied alcohol habits of over 7,000
individuals with tobacco habits and found that 31% consumed alcohol regularly, 25% occasionally and 44% did not
consume alcohol at all. The prevalence of OL was higher
among regular and occasional (3.9%) alcohol drinkers than
among non-drinkers (2.9%).
Although alcohol by itself not an important risk factor
for leukoplakia, it might produce synergetic effects when
combined with the habit of chewing tobacco or smoking.

Alcohol causes dehydration of the oral mucosa and increases


the ambient temperature of the oral cavity thereby making
the oral mucosa more vulnerable to the carcinogenic
effects of tobacco. Alcohol by itself contains known carcinogens such as hydrocarbons and nitrosamines. It also
causes liver induced cellular changes in target tissues
(increased acetaldehyde content).
3. Viral infection The possible implication of human
papilloma virus in the etiology and potential for malignant
transformation of oral premalignant lesion has been studied extensively and it was reported that the likelihood of
detecting HPV was 23 times higher in precancerous oral
mucosa and 45 times higher in oral squamous cell carcinoma than in normal oral epithelium.
The possible viral etiology of OL had been rst suggested by light microscopic demonstration of HPV suggestive changes (Fejerskov, 1977).
The rst evidence of HPV etiology of oral leukoplakia
had been provided by Loning (1985), Syrjanen (1986) and
Naghashfar (1985).
In a follow-up study of 20 leukoplakias, Lind (1987)
established a signicant correlation between the presence
of HPV antigen and the degree of dysplasia and malignant
transformation.
High prevalence of HPV in PVL had been found by
Maitland et al (1987) who found an overall rate of 42%
using probes specic for HPV 16. The differences in detection of HPV may be accounted for different sensitiveness
of methods used. Dcosta et al (1998) in their study detected
HPV 16 in 34% of the potentially malignant lesions and
Mao et al (1996) in 36% of precancerous lesions. In oral
cavity HPV 16 has been demonstrated in both homogeneous leukoplakia and in verrucous leukoplakia (Loning,
1985; De Villers, 1986; Milde, 1986; Syrjanen, 1988 and
Kashima et al, 1990).
Studies by Nielsen et al (1996) in the prevalence of HPV
in oral premalignant lesions found an overall rate of HPV
positive lesions to be 40.8% of which ve of them were
HPV 16. Elamin et al (1998) suggested that the prevalence
of HPV infection is higher in oral lesions from India. The
high prevalence of HPV infection in oral premalignant
cases indicates that HPV infection would be an early event
in the process of malignant transformation of oral epithelial
cells.
4. Leukoplakia and diabetes A few studies in the literature have found a significant association between diabetes
mellitus and OL prevalence (Albert et al, 1992; Ujpal et al,
2002).
Albert et al (1992) reported an OL prevalence of 6.2%
among diabetics as compared to 2.2% in a control group.
However the analysis did not adjust for age and gender.
Diabetes mellitus leads to a number of metabolic and immunologic changes that affect the oral mucosa and it is associated with a variety of oral conditions (Ponte et al, 2001).
139

Section III Mucocutaneous Disorders

Thomas et al (2004) have found a signicant association


between diabetes mellitus and OL prevalence.
According to weighted model, diabetics were three times
more likely to have OL than non-diabetics. However no
association between diabetes and the incidence of oral
squamous cell carcinoma has been described previously.
Therefore the signicance of the apparent association
between diabetes and OL is unclear.

Figure 7

5. Candidiasis and leukoplakia There is a longstanding


discussion whether Candida infection is a cause of leukoplakia or if it is a superimposed infection in a pre-existing
lesion. It has been shown that, upon treatment, nonhomogeneous Candida-infected leukoplakias convert into
a homogeneous lesion, and some lesions even regressed.
6. Dietary factors Ramaswamy et al (1996) have shown
that serum vitamins A, B12, C, E, beta-carotene and foliate
were decreased in leukoplakic patients as compared to controls. Many other studies supporting the protective effects
of carotinoids and vitamin A, C and E have been reviewed
by Enwon et al (1995) and Garewell et al (1999).
Only a very few studies have reported a positive association between estrogens and oral leukoplakia. Hashibe
et al (2000) reported an inverse relationship between body
mass index (BMI) and OL prevalence in a large population
in India. The authors hypothesize that higher estrogen levels in people with higher BMI may explain this relationship. Kushlinskill et al (1988) have demonstrated estrogen
receptors in oral squamous cell carcinoma and OL. Thomas
et al (2004) recently have demonstrated a strong protective
effect of estrogen use on OL prevalence in women. In their
study there was no case of OL among women who were
using estrogen.

Commissural leukoplakia. Courtesy: Department of Oral


Medicine and Radiology, MCODS, Mangalore

Figure 8

Clinical features
1.

2.
3.

140

Leukoplakia is seen most frequently in middle-aged


and older individuals. Sex distribution is also variable. Men are more affected in some countries, while
this is not the case in the western world. Less than 1%
of men below the age of 30 have leukoplakia. The
male-to-female ratio is reported to be about 3:1 to 6:1.
Leukoplakia can be either solitary or multiple.
Leukoplakia may appear on any site of the oral cavity,
the most common sites being: buccal mucosa, alveolar mucosa, floor of the mouth, lateral border of tongue,
lips and palate, however the lesions in the floor of the
mouth, lateral border of the tongue and lower lip are
most likely to show dysplastic or malignant changes.
By far the most affected oral sites are the commissures
(Figure 7) and the buccal mucosa (Figure 8) showing
6090% of the leukoplakia. Next are the lip (3.7%),
the alveolar ridge (3.0%) (Figure 9), the tongue (1.4%),
floor of the mouth (1.3%), vestibular mucosa (1.1%)
(Figure 10) and the palate (0.9%).

Homogeneous leukoplakia on the buccal mucosa.


Courtesy: Dr Ashok

4.

Early or thin leukoplakia appears as a slightly elevated grayish-white plaque that may be either well
defined or may gradually blend into the surrounding
normal mucosa (Figure 11). As the lesion progresses, it
becomes thicker and whiter, sometimes developing a
leathery appearance with surface fissures. Some leukoplakias develop surface irregularities and are referred
to as granular or nodular leukoplakias. Other lesions
develop a papillary surface and are known as verrucous or verruciform leukoplakia.

Clinical forms of leukoplakia


Classically two clinical types of leukoplakia are recognized:
homogeneous and non-homogeneous, which can co-exist.

Chapter 6 Red and White Lesions

Figure 9

Homogeneous leukoplakia on the alveolar ridge and


buccal mucosa. Courtesy: Dr Ashok

Figure 11

Early or thin leukoplakia on the buccal mucosa.


Courtesy: Dr Ashok

Figure 10
Figure 12

Keratotic white patch in the labial vestibule due to


placement of tobacco (tobacco pouch keratosis).
Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

Homogeneous leukoplakia is dened as a predominantly


white lesion of uniform at and thin appearance that may
exhibit shallow cracks and that has a smooth, wrinkled or
corrugated surface with a consistent texture throughout
(Figure 12). This type is usually asymptomatic.
Non-homogeneous leukoplakia has been dened as a
predominant white or white-and-red lesion (erythroleukoplakia) (Figure 13) that may be either irregularly at,
nodular (speckled leukoplakia) or exophytic (exophytic
or verrucous leukoplakia). These types of leukoplakia are
often associated with mild complaints of localized pain

Homogeneous leukoplakia on the dorsum of the tongue.


Courtesy: Dr Sumanth

or discomfort. Proliferative verrucous leukoplakia is an


aggressive type of leukoplakia that almost invariably
develops into malignancy. This type is characterized by
widespread and multifocal appearance, often in patients
without known risk factors. In general, non-homogeneous
leukoplakia has a higher malignant transformation risk,
but oral carcinoma can develop from any leukoplakia.
141

Section III Mucocutaneous Disorders

Figure 13

Erythroleukoplakia on the buccal mucosa.


Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

Malignant transformation
White lesion in the oral cavity were thought to be precancerous as early as 1870 by Paget, who gave them such appellations as ichthyosis, smokers patch and leukokeratosis.
Leukoplakia is an example for precancerous lesion.
The frequency of dysplastic or malignant alterations in
oral leukoplakia has ranged from 15.6 to 39.2% in several
studies. Although leukoplakia is more common in men
than women, several studies have shown that women with
leukoplakia have a higher risk of developing carcinoma.
A wide range of rates for the malignant transformation
of leukoplakia has been reported from 0.13 to 19.8% but it
is estimated that the annual transformation rate should
not exceed 1%. Up to 10% of leukoplakia may be malignant at the time of initial examination. The potential for
malignancy appears higher in certain risk sites like oor of
the mouth and ventral surface of the tongue, where the
lesion is associated with Candida species, or where the lesion
is verrucous or mixed with red lesions (erythroleukoplakia
or speckled leukoplakia).
Cawson (1966), Einhorn and Wersall (1967) and Banoczy
(1977) inferred that certain features of leukoplakia have
been reported to be associated with an increased risk of
malignant transformation. These are:

142

Gender, particularly women seems to be at risk


Long duration of the leukoplakia
Leukoplakia in non-smokers (idiopathic leukoplakia)
Location in the floor of the mouth and or on the tongue

Non-homogeneous type of OL
Presence of Candida albicans
Presence of epithelial dysplasia.

Longitudinal studies of the rate of malignant transformation in leukoplakia were first reported by Sugar and Banoczy
(1959) in Hungary.
In a study conducted by Gupta et al, 12,212 tobacco
users were followed up annually to assess the malignant
potential of precancerous lesions in Ernakulam district in
Kerala, India. They observed that out of a total of 19 new
oral cancers over period of 8 years, 15 (79%) originated
from leukoplakia.
The location of oral leukoplakia has a signicant correlation with the frequency of nding dysplastic or malignant changes at biopsy. In the study by Waldron and
Shafer (1975), the oor of the mouth was the highest risk
site, with 42.9% of leukoplakias showing some degree of
epithelial dysplasia, carcinoma in situ, or unsuspected invasive squamous cell carcinoma. The tongue and lips were also
identied as high risk sites, with dysplasia or carcinoma
present in 24.2% and 24% respectively.
The study by Silverman and colleagues (1984) showed
an overall malignant transformation of 17.5%. In their
study only 6.5% of homogeneous leukoplakia underwent
malignant change, however, 23.4% of speckled leukoplakia and 36.4% of leukoplakias with microscopic evidence
of dysplastic changes transferred into cancer.
Among the different clinical varieties of leukoplakias,
proliferative verrucous leukoplakia has got highest risk of
malignancy. In a follow-up study of 54 cases of proliferative
verrucous leukoplakia, Silverman and Gorsky found that
70.3% of the patients subsequently developed squamous
cell carcinoma.
Holmstrup and Besserman (1983) and Silverman (1990)
inferred that proper use of antifungal therapy might result
in a shift from high risk nodular or speckled leukoplakia to
low risk homogeneous leukoplakia. Hernandez et al (2003)
have suggested that in patients who display oral premalignant conditions like leukoplakia, immunosuppression must
be considered as an important risk factor for oral cancer.
Investigations
Although an experienced oral physician may be able to
diagnose and manage majority of the leukoplakias, it is
always prudent to follow a systematic investigative protocol to diagnose leukoplakia. The investigative procedures
includes the following:

Toluidine blue staining: Toluidine blue clinically stains


malignant lesions, but not normal mucosa. In vivo, the
dye may be taken up by the nuclei of malignant cells
manifesting increased DNA synthesis. Toluidine blue
also serves as a guide to biopsy by localizing tumor
cells within the area of the lesion. Toluidine blue

Chapter 6 Red and White Lesions

Figure 14

Figure 15

Hyperorthokeratosis and basal cell hyperplasia in leukoplakia.


Courtesy: Department of Oral Pathology, MCODS, Mangalore
Toluidine blue stained leukoplakic lesion on the gingiva and
buccal vestibule. Courtesy: Dr Ashok

staining uses a 1% aqueous solution of the dye that is


decolorized with 1% acetic acid. The dye binds to dysplastic and malignant epithelial cells with a high
degree of accuracy (Figure 14).
Cytobrush technique: This technique is more accurate
than any other cytologic technique used in the oral
cavity. The cytobrush technique uses a brush with firm
bristles that obtains individual cells from the full thickness of the epithelium.
These two techniques are adjuncts and not substitutes for
an incisional biopsy.

Biopsy: When a suspicious lesion is identified, an incisional biopsy using a scalpel or a biopsy forceps is
recommended. When the lesion is very small excisional
biopsy is performed as an investigative procedure and
as a treatment modality.
In homogeneous leukoplakia, the value of histological
examination to some extent is questioned. The occurrence of epithelial dysplasia is rather low in this type
as is the risk of future malignant transformation. However, even the experienced clinician will occasionally
be surprised by the histopathological findings of a
clinically innocent looking homogeneous leukoplakia.
Therefore a biopsy should be performed in homogeneous leukoplakia. In non-homogeneous leukoplakia,
i.e. usually symptomatic, epithelial dysplasia or even
carcinoma in situ or early squamous cell carcinoma is
rather common. The biopsy should be taken at the site
of symptoms, if present, and or a site of redness or
induration. Biopsies of exophytic, verrucous or papillary lesions should be taken deep enough to include a
sufficient amount of underlying connective tissue, and
preferably from the margins.

This lesion represents various degrees of epithelial dysplasias. Some lesions exhibit carcinoma in situ with top
to bottom basilar hyperplasia, loss of polarity, increased
mitosis, hyperchromatism, dyskaryosis and alteration
in nuclear cytoplasmic ratio without any evidence of
thickening of epithelial layer or without any evidence
of disturbance of keratinization process (Figure 15).
The frequency of epithelial dysplasia in leukoplakia
varies between less than 1% and more than 30%. The
presence of epithelial dysplasia is generally accepted
as one of the most important predictors of malignant
development in premalignant lesions.
Markers of proliferation in leukoplakia: There are
markers for determining future cancer development in
oral premalignant lesions. These markers are divided
into genomic markers and differentiation markers.
The genomic markers include DNA aneuploidy, loss of
heterozygosity and changes in expression of oncogenes and tumor suppressor genes (p53), whereas the
proliferative markers include keratins and carbohydrate
antigens.

Differential diagnosis
The keratotic lesions that could be considered in the differential diagnosis of homogeneous leukoplakia includes:

Chronic hyperplastic candidiasis


Reticular lichen planus
White sponge nevus.

Treatment (Flowchart 1)
General considerations As a standard rule all possible
agents leading to white keratotic lesions should be eliminated
such as sharp teeth, candidal infection, etc. so as to rule out
other definable lesions. In persisting lesions or in the absence
of possible causative factors, a biopsy should be taken to
143

Section III Mucocutaneous Disorders

Flowchart 1
Leukoplakia
Topical antifungal agents
Candid cream (clotrimazole),
thrice/day for a week

No response

Reduction in size

Less than 1 cm

More
Morethan
thanor
or
equal
equal to
to 11cm
cm

Excisional biopsy

Incisional biopsy

Dysplasia present

Total
Totalexcision
excisionof
ofthe
the
lesion
lesionwith
withgraft
graft

Follow
Followup
uponce
oncein
in
66months
monthsfor
for33years
years

Continue
Continuethe
thetopical
topical
antifungal
antifungalagent
agentfor
for
11month
month

Dysplasia absent

IfIfexcision
excisionisisnot
notpossible
possible
A.
Capsules of
of lycopene
lycopene 44 mg
A. Capsules
mg b.i.d.
bid or
8 mg
3 months
8ormg
ODo.d.
for for
3 months
B.
Capsules antioxidants
of antioxidants
with
B. Capsules
with
selenium bid
b.i.d.
6 months
selenium
forfor
6 months
C.
Topical bleomycin
bleomycin 1%
1% w/v
w/v thrice
thrice
C. Topical
a day
days
day
forfor
1515
days

Retinol
A
RetinolA
(VitaminAAanalogue)
analog)
(Vitamin
ointment
ointmentapplication
application
b.i.d./1
b.i.d./1month
month

Note: All available medications have been enlisted. However, the physician should choose
the appropriate mode of treatment/drug based on the clinical situation

Management of leukoplakia

exclude histologically the presence of a definable lesion and


to establish the degree of epithelial dysplasia, if present or
even the presence of carcinoma or carcinoma in situ.
Up to 60% of leukoplakias regress or totally disappear
if tobacco use is stopped. OL induced by smokeless tobacco
may resolve if the habit is stopped. Some candidal leukoplakias respond, at least partially to antifungal drugs (smoking should also be stopped) and dysplasia may regress.
Medical management of oral leukoplakia
Chemoprevention Chemoprevention is the interventional
use of chemical agents such as minor dietary constituents and pharmaceuticals to halt or slow the carcinogenic
process before invasion. These include natural or synthetic
compounds, micronutrients or non-nutrients.
1. Carotinoids and retinoids (-carotine, Vitamin E,
selenium, canthaxanthin, astaxanthin, phytoene and
spirulina-dunaliella)
144

Some carotinoids have antioxidant or anticarcinogenic


activities and can block genotoxic activity of oral carcinogens. Retinoids are the synthetic and natural analogs of
vitamin A. There are naturally occurring retinoid, including retinol, retinal, retinoic acid and their metabolites.
Beta-carotene is a natural precursor of vitamin A. More
recently etretinate 13-cis retinoic acid and other retinoid
have been successfully used for the treatment of oral
leukoplakia. Exactly how retinoids may act to inhibit
carcinogenesis is unclear, although some retinoids may
enhance anti-tumor immune responses. Retinoids have a
pronounced and essential effect on cell differentiation.
Retinoids may have an effect by their interaction with
growth control mechanisms such as transforming growth
factors and also possibly by acting on tumor suppressors
either directly or via an interaction with transforming
growth factors. Retinoids may inhibit the transformation
mediated by papillomaviruses. Oral leukoplakias have

Chapter 6 Red and White Lesions

been treated with a range of retinoids and carotinoids.


Leukoplakias have been successfully treated with systemic
13-cis retinoic acid.
Mulay and Urbach (1958) was the rst to use vitamin A
therapy for topical therapy of oral leukoplakia. Smith
(1962) administered 75,000300,000 IU of vitamin A daily
for a period of 318 months. Seventy two percent of
hyperkeratosis lesions, 25% of massively keratotic and
ulcerative forms of leukoplakia improved but the dyskeratotic forms were unresponsive. However signs of hypervitaminosis were not observed. Silverman et al (1965)
reported that short-term large dose treatment with vitamin A
(300,000900,000 IU daily) leads to the improvement of
leukoplakia.
2. 13-cis retinoic acid 13-cis retinoic acid (CRA) at
1.5 mg/kg per day for 3 months followed by 0.5 mg/kg
daily for 9 months resulted in an initial 55% beneficial
response followed by maintenance of effect in 92% of
cases. Kaugars and Silverman (1995) in a study of 10
patients with leukoplakia using 50 mg of 13-CRA per day
for 3 months showed a 50% reduction in the clinical size
of the lesions in three patients. Treatment of three patients
was discontinued because of elevated serum triglyceride
levels or headache.
3. Beta-carotene Many authors have proposed that
beta-carotene supplementation can be used for the treatment of leukoplakia with minimal side effects. Beta-carotene
alone in a dose of 30 mg daily for 36 months also produced a 71% response rate in 24 patients with oral leukoplakias, with no significant toxicity (Garewall et al, 1991).
The same workers have used beta-carotene 60 mg daily for
6 months and report similar benefit (Garewall et al, 1992).
Others have found beta-carotene 90 mg daily to produce
benefit in 44% after three cycles of use of 3 months each.
4. Fenretinide (n-4-hydroxy phenyl retinamide)
Fenretinide (synthetic retinoid) 200 mg daily used for 1
year reduced the relapses and appearance of new oral leukoplakias, compared with controls, with few adverse
effects in 39 patients having previously had leukoplakias
surgically excised.
5. Vitamin E Vitamin E has synergistic inhibitory activity against carcinogenesis in animal models and may have
some beneficial effect in man. Many studies, using vitamin E in oral leukoplakias showed a beneficial clinical
response in 46% of 43 patients by 24 weeks, and a histological response with no serious adverse effects. Another
study showed a significant decrease in oral leukoplakia
after combined treatment with vitamin E, retinol and
-carotene (Zaridze et al, 1993). Vitamin E therefore shows
promise in the control of leukoplakias.
Photodynamic therapy of oral leukoplakia A combined
parenteral and locally applied treatment modality in the

form of photodynamic therapy (PDT) using hematoporphyrins has been found to be effective in animal models
and has been used to treat head and neck cancers and
premalignant lesions in man. PDT was first used in 1990,
when acridine and light were combined to kill paramecia
and the first oncologic use of PDT was in 1903, when
eosin and light were employed in the treatment of skin
cancer. PDT involves using specific wavelength of laser
light to activate a photosensitizing drug which is administered systemically and is retained selectively in the lesion
and this triggers a cold photochemical reaction resulting
in the generation of reactive products such as singlet oxygen that damages tissue. Advantages of this type of treatment as reported by Sciubba (1995) includes inactivation
of clinically subtle or undetectable alteration, sparing of
normal tissue, minimal morbidity and its use as an adjunctive tool to more traditional modalities. However it was
pointed out that the major disadvantage of PDT is the
cutaneous photosensitivity which can persist for several
months after administration of the photosensitizer which
can be a major problem in the Indian subcontinent, where
oral cancer is most common.
Topical chemotherapy of oral leukoplakia Topical treatment of leukoplakia with podophyllin solution (Kovacs
et al, 1962) or bleomycin (Hammersley et al, 1985;
Malmstrom, 1988; Wong et al, 1989) has induced some
regression or even total resolution of dysplasia and of
clinical lesions. Hayasaki et al (1977) described the use of
bleomycin with iontophoresis in the treatment of cancer,
leukoplakia and papillomas of the head and neck region.
Their results showed that this method of application was
not effective for malignant lesions but was effective at
removing leukoplakia of the oral mucosa.
Newer treatments
Gene therapy Patients with head and neck cancer including oral cancer are more susceptible to chromosome damage when their cells are exposed to mutagens (Schantz et al,
1990) and there are a number of genetic changes now
described in oral carcinoma (Scully et al, 1993). Synthetic
antisense oligonucleotides complementary to the start
codons of human papilloma virus (HPV) type 18 E6 and E7
genes can significantly inhibit growth in vitro of oral carcinoma cell lines (Steele et al, 1992, 1993).
Even though laboratory and animal data for the use of
gene therapy is very incomplete, many investigators have
begun clinical trials in human patients. Tests of several
types of gene therapy have begun in various types of cancer, and for oral cancer; the trials include the testing of
recombinant p53, the expression of suicide genes and the
use of conditionally competent adenoviruses. Since the
scientic basis for these trials is rather weak, it can hardly
be expected that impressive results are imminent. There
are as yet no trials in oral potentially malignant lesions
145

Section III Mucocutaneous Disorders

aimed at correcting genetic changes or enhancing the


immune response by gene therapy; indeed the whole eld
of gene therapy has been publicly criticized for its rush
to clinical experiments, when the basic studies are still
incomplete.
Other alternative modalities of treatment
Green tea Tea, the dried leaves of the plant Camellia
sinensis is a popular beverage consumed worldwide. The
pharmacological actions of green tea includes; antiinflammatory action, antioxidant action and anticancer
action. Tea acts as an inhibitor of initiation of carcinogenesis in the following ways:

Tea polyphenols are effective in reducing the accumulation of free radicals by inducing the production of
superoxide dismutase (SOD), a free radical scavenger
(Das et al, 2002).
Tea inhibits formation of mutagens in a dose dependaet manner (Weisburger et al, 2002) and reduces lipid
peroxidation (Fadhel et al, 2002).
In UV induced responses, epigallocatechin gallate
(EGCG) prevents the formation of UVB induced cyclobutane pyrimidine dimers (Katiyar et al, 1999).
EGCG is also a strong inducer of the detoxifying
enzyme glutathione-s-transferase.
These reports strongly point toward antimutagenic activity of green tea. The gallated flavonoids (especially gallated EGCG and the aflavins) act Khafif et al (1998)
reported that green tea extract has been shown to have a
chemopreventive or inhibitory role in the treatment of oral
leukoplakia. Li et al (1999) conducted a double blind, placebo-controlled trial in 59 patients with oral leukoplakia,
and found that oral and topical administration with a
black and green tea mixture resulted in a partial regression
of the lesion in 37.9% of the treated patients compared to
placebo control. The treatment reduced cell proliferation
and the rate of chromosome aberration in peripheral blood
lymphocytes. Weisburger et al (1999) have proposed that
catechins, in particular EGCG are believed to be responsible for the chemopreventive effects of green tea, which act
by antioxidant and free radical scavenging activity.
Oral lycopene Oral lycopene in the dose of 8 mg/day is
beneficial in the treatment of oral leukoplakia.
Surgical line of treatment If the lesion is very small, it
should be excised as a part of investigation and as a treatment option.
Any leukoplakia could transform into a carcinoma,
even those which did not show epithelial dysplasia initially (or in which dysplasia happened to be absent from
the biopsy taken). The main problem is that the malignant
transformation cannot be reliably predicted yet. Regular
check-up of these patients is essential both in treated and
untreated patients.
146

Lichen Planus
The word lichen planus is derived from the Greek literature; lichen meaning tree moss and planus refers to flat.
In 1869 Erasmus Wilson, a dermatologist first reported the
condition. Oral lesions of lichen planus were first described
by Thiebergie. Wickham (1895) described the characteristic appearance of whitish striae and punctuations that
develop atop the flat-surfaced papules.
Definitions
Oral lichen planus (OLP) is a common chronic immunological inflammatory mucocutaneous disorder that varies
in appearance from keratotic (reticular or plaque like) to
erythematous and ulcerative.
Eisen (2005) dened OLP as a relatively common chronic
inammatory disorder affecting the stratied squamous
epithelia. It is a skin disease common with in the oral cavity, where it appears as either white reticular, plaque, or
erosive lesions with a prominent T-lymphocyte response
in the immediate underlying connective tissue.
Etiopathogenesis
In spite of extensive research, exact etiology is still unknown.
The most accepted and current data suggest that OLP is
T cell mediated disorder in which there is production of
cytokines which leads to apoptosis. Autocytotoxic CD8 and
T cells trigger apoptosis of oral epithelial cells (Eversole,
1997; Porter et al, 1997). The immune system is triggered
due to the interactions among genetic, environmental, and
lifestyle factors.
Other possible theories include the genetic background,
where the weak association between HLA antigen and
lichen planus was found by Powell et al (1986) and
Roston (1994). Dental materials and infectious agents like
Gram negative aerobic bacillus, spirochetes and increased
prevalence of Candida species were suggested by Simon
and Hornstein (1980). Vincent et al (1990), Soto Araya
et al (2004) reported the strong association of psychological factors like higher level of anxiety, greater depression,
and psychic disorders in patients with erosive lichen
planus.
Clinical features
Lichen planus commonly affects 12% of the general population, prevalence rate being 0.14%. Forty percent lesions
occur on both oral and cutaneous surfaces, 35% occur on
cutaneous surfaces alone, and 25% occur on oral mucosa
alone.
Lichen planus commonly affects the adults. However
it has also been observed in children as recently reported
by Sharma (1999). The age range usually varies from 40 to
70 years.

Chapter 6 Red and White Lesions

Figure 16
A

Violaceous papular lesions of cutaneous lichen planus on the upper and lower extremity. Courtesy: Dr Ashok

There is denite female predilection with ratio of 2:1.


The characteristic manifestation of oral lichen planus is the
appearance of white papules that usually coalesce forming
a network of lines that may intersect or crisscross each
other forming various patterns. Louis Frederic Wickham
described the presense of ne, white or gray lines or dots
seen on the top of the pruritic papular rash on the skin
in lichen planus. These striae are popularly referred to as
Wickhams striae.
Skin involvement in lichen planus
Skin lesions are characteristically itchy and violaceous to
brown papules, very frequently distributed over the flexor
aspect of the wrist or ankles, extensor aspect of the
lower legs, skin of the lower central back and natal clefts
(Figure 16A, B).
Scalp involvement results in loss of hair (alopecia)
which is referred to as lichen planopilaris. Longitudinal
ridging and grooves are seen over the nail (onychorrhexis).
Other changes seen in the nail includes distal splitting
(onychoschizia), separation of the nail plate from nail bed
(oncycholysis), permanent damaged nail matrix (pterygium) and nally permanent nail loss (anonychia).
Koebners phenomenon is the appearance of the lesions
at the site of micro trauma and is well demonstrated in
case of skin involvement as well demonstrated in the oral
lesions. Hence any mechanical trauma or irritation such as
sharp lling margins or rough surfaces or ill-tting dentures should be evaluated and eliminated.
Oral manifestations
The basic lesion of OLP is papule arranged in the linear or
annular forms and crisscrossing each other forming various patterns like annular and reticular forms.

Andreasen (1968) divided OLP into six types, namely,


reticular, papular, plaque like, erosive, atrophic and bullous type. Oral lesions may manifest in one of the following basic clinical forms; hypertrophic (plaque like, papular,
reticular), erythematous (atrophic, erosive) and bullous.
Reticular form is the most common type. It appears as
a series of ne, radiant, white striae known as Wickham
striae which may be surrounded by a discrete erythematous
border. The most common site of involvement is the posterior buccal mucosa, tongue and gingiva (Figure 17AD).
Plaque-like lesions resemble leukoplakia and occur as
homogeneous white patches.
In 1892 Kaposi rst described a distinctive clinical
variant of the disease with blisters, which was termed
lichen ruber pemphigoides or bullous lichen planus. This
form is rarer than other forms of oral lichen planus. It
appears as a small bullae or vesicle that tends to rupture
easily. The bulla or vesicle range from few millimeter to
several centimeters in size.
Erosive lichen planus is the second most common type
(Figure 18). Erosions are often extensive, irregular and
affect the lingual and buccal mucosa and are often associated with white lesions. Gingival involvement in erosive
lichen planus produces desquamative gingivitis (Figure 19),
which has greater potential for malignant transformation.
Occasionally diffuse melanosis may be seen along with erosive type of lichen planus, which is referred to as pigmented
lichen planus. The lesion presents as reticular white lesions
(may or may not be associated with erosive areas) surrounded by brownish to grayish black pigmentation (Figure
20A, B). It is believed that the T lymphocytes inltrate into
the basal layers and cause basal cell degeneration thereby
stimulating melanogenesis. Histopathological evaluation
of pigmented lichen planus shows basilar melanosis and
melanin incontinence.
147

Section III Mucocutaneous Disorders

Figure 17
A

(A) Reticular lichen planus on the buccal mucosa. (B) Reticular lichen planus on the buccal mucosa.
(C) Lichen planus on the palate. (D) Reticular lichen planus on the labial mucosa of the upper lip.
Courtesy: Dr Ashok

Atrophic lichen planus presents as diffuse red patches


usually surrounded by white striae. Such striae that radiate
peripherally are usually evident at the margins of atrophic
zones of the lesion (Figure 21A, B).
Reticular forms are usually asymptomatic and rarely
require treatment whereas erosive and atrophic forms are
frequently associated with severe discomfort and burning
sensation. It is an absolute necessity to evaluate periodically for malignant transformation.

Figure 18

Association of oral lichen planus with systemic


illness
Carrozzo et al (2003), Arrieta et al (2000) and Jubert et al
(1994) found the frequent association of hepatitis C virus
and OLP, and suggested that HCV occasionally replicates
in OLP tissue contributing to the pathogenesis of mucosal
damage. Lichen planus is often associated with immune
mediated diseases like alopecia areata, dermatomyositis,
148

Erosive lichen planus affecting the tongue.


Courtesy: Dr Sumanth

Chapter 6 Red and White Lesions

Figure 19

Figure 20
A

Desquamative gingivitis in erosive lichen planus.


Courtesy: Dr Ashok

lichen sclerosis et atrophicus, morphea, myasthenia gravis,


ulcerative colitis and primary biliary sclerosis.
Syndromes associated with OLP
Grinspan syndrome is the association of OLP with diabetes
mellitus and hypertension. Graham-Little syndrome and
vulvovaginogingival syndrome are other syndromes associated with OLP, in which there is mucosal involvement of
gingival and genital region, usually of erosive type.
Differential diagnosis
Differential diagnosis of reticular/annular type of OLP
includes lichenoid drug reaction, electrogalvanic white
lesions and frictional keratosis and leukoplakia. Keratotic
forms of lichen planus can be differentiated from leukoplakic plaque as the former is usually associated with
burning sensation and association with etiologic factors
in the latter. Hypertrophic form also resembles hyperplastic candidiasis. Erosive lichen planus resembles lupus
erythematosus.
Oral lichenoid reactions are identical clinically and
histologically with OLP but have an identiable etiology
like drugs and dental restorative materials including
amalgams, composite resins, cobalt and gold have been
implicated as the causes of lichenoid reactions. Even
avoring agents and plastics can be important in the
pathogenesis and management with oral lichenoid reaction. Patch test may be of help but lacks sensitivity and
specicity.
Erosive lichen planus has to be differentiated from
lichenoid reaction, graft-versus-host disease, discoid lupus
erythematosus and speckled leukoplakia. Desquamative
gingivitis of gingival erosive lichen planus should be

(A) Brown colored pigmentation on the buccal mucosa in


pigmented lichen planus. Courtesy: Dr Ashok. (B) Grayish
black pigmentation on the buccal mucosa bounded by
reticular lichen planus. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

differentiated from other forms like pemphigus, pemphigoid and linear IgA disease.
Erythematous lesions of OLP can be excluded from
atrophic candidiasis by the presence of whitish striations
at the periphery.
Investigations
Diagnosis is generally achieved by the characteristic clinical presentation and the complete history and the extraoral
manifestations. Sometimes biopsy may be complementary.
Gingival lichen planus is often difficult to diagnose and
149

Section III Mucocutaneous Disorders

Figure 21
A

(A) Diffuse red patches surrounded by white striae in atrophic lichen planus involving the buccal mucosa.
(B) Diffuse erythematous areas in atrophic lichen planus involving the tongue. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

Figure 22

(Max-Joseph space) and, rarely, clinical blistering of the


oral mucosa (bullous lichen planus). Immunouorescence
of perilesional mucosa shows the brin and shaggy brinogen in a linear pattern at the basement membrane zone
and cytoids in the absence of deposition of brinogen.
Malignant potential of OLP
First report of a gingival cancer diagnosed in patient with
OLP was in 1910 by Hallapeau. The most important complication of OLP is the development of oral squamous cell
carcinoma from the non-keratotic forms. The reported frequency of malignant transformation varies greatly, between
0.4 and over 5%, over periods of observation from 0.5 to
over 20 years.

Saw tooth rete pegs and subepithelial band of chronic


inflammatory cells, characteristic of lichen planus. Courtesy:
Department of Oral Pathology. MCODS, Mangalore

direct immunofluorescent studies are confirmatory as they


demonstrate presence of autoantibodies.
Histopathological features include the essential features
like supercial band-like inltrate of T lymphocytes,
basal cell liquefaction, degeneration and epithelial maturation pattern being normal (Figure 22). Additional features include jagged (saw-tooth) and spindly rete ridges,
colloid (Civatte, hyaline, cytoid) bodies, and separation of
epithelium from the lamina propria. Degeneration of basal
keratinocytes and disruption of the epithelial basement
membrane and basal keratinocyte anchoring elements in
OLP produce weaknesses at the epithelial-connective tissue
interface which may result in histological cleft formation
150

Prognosis
Cutaneous lesions are self-limiting and pigmentation may
fade after few years or remain permanent. Complete remission
occurs in 70% of cases after 1 year. Oral lesions are chronic,
rarely undergo spontaneous remission, furthermore, erosive
oral lesions are difficult to palliate. The spontaneous remission of OLP is much less than 5% of patients over 7.5 years
follow up. The reticular form of LP has best prognosis because
spontaneous remission occurs in 40% of cases. The erosive
form of the lesion can persist for 1520 years.
Management (Flowchart 2)
Treatment should be considered after the evaluation of
clinical type, associated symptoms, and age. Reticular
lesions are asymptomatic and require no therapy but only

Chapter 6 Red and White Lesions

Flowchart 2
Oral lichen planus

Symptomatic

Topical antifungal therapy


with clotrimazole 1% (Candid)
cream t.i.d./day for a week

Relief in
symptoms
Asymptomatic

No relief in
symptoms

Regular follow-up
once in 3 months

New cases

Recalcitrant cases

Intralesional steroids:
Injection triamcinolone 0.5 ml
(Amcort) with once/week
for 4 weeks

Topical corticosteroids (increasing order of potency)


1. Triamcinolone acetonide 0.1% (Tess gel, Ledercort
ointment) t.i.d./day until symptoms improve
(maximum of 1 month)
2. Fluocinolone acetonide 0.025% (Fluzone cream)
t.i.d./day for 2 months with tapering dose
3. Clobetasone propionate 0.05% (Clobetol cream,
Cosvate gel) b.i.d./day for 2 months
4. Clobetasone 17-butyrate (Eumosone) 0.05% b.i.d./day
for 1st month, o.d. for 2nd month
5. Mometasone furoate 0.1% (Mosone cream)

Immunomodulation:
chloroquine (Lariago, Laquin)
250 mg b.i.d. for 3 months

Immunosuppression:
Azathioprine (Imuzat, Azoran)
1 mg/kg/day (50 100 mg) for
one month. Dosage can be
increased up to 2 mg/kg/day
and should not be given
more than 3 months

No relief in
symptoms
Combination therapy (systemic + topical)
1. Tab prednisolone 10 mg (Wysolone, Emsolone)
t.i.d. for 2 weeks; 10 mg b.i.d. for 1 week; 10 mg o.d.
for 1 week; 5 mg o.d. for 1 week & 5 mg once in
2 days (thrice)
2. Topical triamcinolone acetonide 0.1% (Tess gel)
t.i.d./day till symptoms improve or cyclosporine
solution (Sandimmune) as mouthrinse twice/day
for 15 days

PUVA therapy
(Psoralen ultraviolet A rays)

Newer drugs like mycophenolite


mofetil 500 mg (Cellmune),
tacrolimus, sirolimus,
pimecrolimus can be tried (longterm side effects not studied)

Note: All available medications have been enlisted. however, the physician should
choose the appropriate mode of treatment/drug based on the clinical situations

Management of oral lichen planus

observation for changes. In general, all treatment should


be aimed at eliminating atrophic and ulcerative lesions,
associated symptoms, and minimize the risk of malignant
transformation.
All precipitating factors like mechanical irritants (sharp
llings, metallic restorations, ill-tting dentures) should

be eliminated. As gingival lesions may exacerbate with the


local factors due to Koebners phenomenon, an optimal
atraumatic oral hygiene program should be instituted.
The most commonly employed and useful agents are
topical corticosteroids and lack of their adherence to mucosa
has made preferable to use rinses.
151

Section III Mucocutaneous Disorders

Topical corticosteroids reduce pain and inammation.


Triamcinolone acetonide 0.1% in Orabase, oral suspension
of triamcinolone, high potency steroid mouthwashes like
betamethasone valerate 0.1%, uocinolone acetonide 0.1%,
clobetasol propionate 0.05% have been used effectively.
Systemic corticosteroids should be reserved for recalcitrant erosive or erythematous lichen planus, where the topical approaches have failed or wide spread involvement of
skin, genital, esophageal or scalp involvement.
Daily dosages of 4080 mg of prednisolone can be used
for brief period of time, i.e. 57 days and stopping abruptly
or the dosage should be reduced by 510 mg per day gradually over a 24 week period. When using most potent
steroids, the medication is not indicated for more than
15 days. For intractable erosive lesions intralesional injections of triamcinolone acetonide (1020 mg/ml per vial)
for every 24 weeks has been found effective, but results
in severe pain. Hydrocortisone, methylprednisolone and
dexamethasone can also be tried.
One third of OLP patients who are treated with topical
steroids develop secondary candidiasis, which necessitates
treatment with antifungals.
Immunosuppressive and immunomodulating
agents
Many immunosuppressive agents like cyclosporine 100 mg/ml
may be used as mouthrinse or finger rub application using
very low doses of cyclosporine 48 mg/day in adhesive base
was found to be effective in suppressing T cell cytokine
production.
Treatment of OLP with immunomodulators like levamisole 150 mg per day for 3 days along with prednisolone
has shown excellent response and long-term remission.
Tacrolimus, a steroid free topical immunosuppressive agent
approved for the treatment of atopic dermatitis is 10100
times effective than cyclosporine. Topical tacrolimus 0.1%
has shown resolution of erosive lesion in 14% of patients
as observed by an independent study, but causes side
effect of burning sensation. The US Food and Drug
Administration recently issued a health advisory to inform
healthcare providers and patients about a potential cancer
risk from the use of tacrolimus.
Topical retinoids like isotretinoin gel 0.1% that act by
down regulation of broblast function has been found to
be of little use when compared with topical steroids.
Other treatment modalities
Psoralens and long wave ultraviolet A (PUVA) therapy with
8-methoxy psoralen and photochemotherapy have shown
excellent results. To avoid PUVA side effects photosensitizer
with topical 0.01% trioxsalen can be used.
But the side effects of therapy include oncogenic
potential, nausea, vomiting, dizziness and headache. The
psychological factor should also be considered. In highly
152

anxious and depressed patients psychotherapy should be


considered.
Surgery
Excision, C02 laser, cryosurgery and photochemotherapy
have been effective for persistent or dysplastic lesions.
However surgery may lead to worsening OLP presumably
via a Koebner phenomenon and reportedly causes a high
rate of recurrence.
Miscellaneous treatments
Antibiotics like 2% aureomycin mouthwash, antimalarials
like hydroxychloroquine sulfate, azathioprine, dapsone,
interferons in the form of topical (human fibroblast interferon beta and human fibroblast interferon alpha) and systemic (IFN310 million for 3 weeks) have been found
effective but lack enough clinical trials. Thalidomide in the
dosage of 100150 mg per day has shown to be effective
in resolution but not preferred due to serious side effects.
As no therapy is curative and the goal for symptomatic
patients is palliation. Relief can be achieved in the majority of patients with topical steroid alone or in combination
with other immunomodulatory topical agents. Atrophic/
erosive forms of OLP have to be systematically and periodically reviewed for malignant transformation.
Lichenoid drug reaction
Lichenoid drug reactions and lichen planus exhibit similar
clinical and histologic findings. Clinically they demonstrate erythematous erosions and ulcerations with focal
areas of radiating lines.
The lichenoid reactions are distinguished from lichen
planus by two factors; the association with the administration of a drug, contact with a metal or foodstuff, or systemic disease, and their resolution when the offending
agent is eliminated (Figure 23A, B). The increased prevalence of oral lichenoid drug reactions are perhaps because
of increased use of newly introduced drugs and appearance of lesions similar to OLP and spontaneous remission
after the withdrawal of the drug.
Diagnosis depends upon establishing the relationship
between the onset and the use of offending agent and resolution of the symptoms upon withdrawal of the offending agent A careful drug history is complementary to the
diagnosis. Histology may be benecial as lichenoid lesions
may have a more diffuse lymphocytic inltrate and contain
eosinophils and plasma cells, and there may be more colloid bodies than in classical LP.
Agents causing lichenoid reactions
The most commonly used drugs that are implicated in
lichenoid reactions include antiarthritics, antihypertensives,
antimicrobials, antiparasitics, anxiolytics, non-steroidal

Chapter 6 Red and White Lesions

Figure 23
A

(A) Erythematous area on the buccal mucosa in relation to an amalgam restoration. (B) Lichenoid reaction on the buccal
mucosa in relation to a tooth that was previously restored with silver amalgam restoration. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

anti-inflammatory drugs, oral hypoglycemic agents, uricosuric agents. Lichenoid reaction may develop after months
or even years after taking the drug.
Dental materials like amalgam compounds, cobalt,
gold, acrylic and casting alloys have been known to cause
lichenoid reaction.
Some authors report that a low frequency of sensitization to mercury and no benecial effects from the removal
of silver amalgam llings, whereas others suggest that
sensitization to mercury is an important cause. In cases
where patch test negative patients improve with amalgam,
mercury may be acting as an irritant in the pathogenesis
of oral lichenoid reaction. Patch testing and biopsies however cannot accurately predict the response to removal of
amalgam llings with those of other material.
Betel quid lichenoid lesion
A quid-induced lichenoid oral lesion has been reported
among betel quid users. It resembles OLP but there are
specific differences. It is characterized by the presence of
fine, white, wavy parallel lines that do not overlap or crisscross, are non-elevated, and in some instances radiate from
a central erythematous area. The lesion generally occurs at
the site of placement of the quid. These lesions may regress
with decrease in frequency, duration, or change in site of
placement of the quid. There may be complete regression
of the lesion when the habit is given up.

Candidiasis
Candidiasis is a disease caused by infection with a yeast
like fungus, Candida (Monilia) albicans, although other

species may also be involved, such as C. tropicalis, C.


parapsilosis, C. stellatoidea, C. krusei, C. glabrata, C. pseutropicalis and C. guilliermondii. Candida albicans is a relatively common inhabitant of the oral cavity, gastrointestinal
tract and vagina. Candidiasis is the most common opportunistic infection in the world. Up to 60% of healthy, nonhospitalized individuals may harbor this pathogen in the
oropharyngeal region. The advent of HIV infection and
AIDS has resulted in a resurgence of oral candida infections that are usually seen in very young, the very old, and
the very sick. Its occurrence has increased remarkably since
the prevalent use of antibiotics, which destroy the normal
inhibitory bacterial flora, and immunosuppressive drugs,
particularly corticosteroids and cytotoxic drugs. Oral candidiasis or thrush usually remain as a localized disease, but
on occasion it may show extension to the pharynx or even
to the lungs.
The genus Candida is a collection of some 150 asporogenous yeast species. Because of their inability to form
asexual stage, they are most often classied among the
fungi imperfect in the class Deuteromycetes. C. albicans is
a dimorphic fungus existing both in the blastospore phase
and the hyphal or mycelial phase. C. albicans is the most
dominant species, followed by C. tropicalis, C. glabrata,
C. parapsilosis and C. krusei. Other Candida species and
genera are rare and transient.
Epidemiology
Candida is commensal organism and part of the normal oral
flora in about 3050% of the population, and is capable of
producing opportunistic infections within the oral cavity
when appropriate predisposing factors exist.
153

Section III Mucocutaneous Disorders

Etiology and pathogenesis


Candida is predominantly an opportunistic infectious agent,
the role of candida as opportunistic invader versus etiologic agent in the patients with oral white lesions has not
clearly been established. However the demonstration of
the catalytic role of some candida strains in endogenous
cellular nitrosamine production, the statistically significant association of certain strains with dysplastic red and
white lesions, and the hyperplastic effects on epithelium of
candida in vitro, indicate that candida may be a carcinogen or a promoting agent.
The pathogenesis of different biotypes and strains of
C. albicans varies. Candida albicans produces an enzyme
called phospholipase; this enzyme is concentrated at the
tips of the fungal hyphae and localized in the vicinity of
host cellular compartments where active invasion is occurring. A relationship has been suggested between the adherence of C. albicans to surfaces and its ability to colonize
and cause the disease. The adhesion of C. albicans to oral
mucosal cells might be due to interaction involving divalent cations. The adsorption of macromolecules onto epithelial cells onto epithelial cells is believed to occur via
electrostatic interactions involving calcium ions and other
ionic groups. The extent and strength of the adhesion
depends on the initial surface properties of both the organisms and substratum involved and can be inuenced by
several factors.
Neville et al have identied three general factors that
may lead to clinically evident oral candidiasis. These factors
are: (i) the immune status of the host, (ii) the oral mucosal
environment, and (iii) the particular strain of C. albicans
(the hyphal form is usually associated with pathogenic
infection). Oral candidiasis has been considered as the disease of the diseased.
The following is a list of specic conditions that may
predispose a patient to develop oral candidiasis:

Factors that alter the immune status of the host


Blood dyscrasias or advanced malignancy
Old age/infancy
Radiation therapy/chemotherapy
HIV infection or other immunodeficiency disorders
Endocrine abnormalities
Diabetes mellitus
Hypothyroidism or hypoparathyroidism
Pregnancy
Corticosteroid therapy/hypoadrenalism

Factors that alter the oral mucosal environment

154

Xerostomia
Antibiotic therapy
Poor oral or denture hygiene
Malnutrition/gastrointestinal malabsorption
Iron, folic acid, or vitamin deficiencies
Acidic saliva/carbohydrate-rich diets

Heavy smoking
Oral epithelial dysplasia

Classification of Candidiasis (Greenberg and Glick, 2003)


Pseudomembranous type
Atrophic (erythematous)antibiotic stomatitis
Atrophic
Denture sore mouth
Angular cheilitis
Median rhomboid glossitis
Hypertrophic/hyperplastic
Candida leukoplakia
Papillary hyperplasia of palate
Median rhomboid glossitis (nodular)
Multifocal
Syndrome associated
Familial endocrine neoplasia syndrome
Myositis (thymoma associated)
Localized
Generalized

Clinical presentation
Acute pseudomembranous candidiasis Pseudomembranous candidiasis is the most common form of oral candidiasis. The most common sites include buccal mucosa,
dorsal tongue and palate. It usually follows antibiotic
therapy or immunosuppression. A burning sensation usually precedes the appearance of as soft, creamy white to
yellow, elevated plaques, that are easily wiped off from the
affected oral tissues and leave an erythematous, eroded, or
ulcerated surface which may be tender (Figure 24). Thrush
may be seen in neonates and among terminally ill patients,
particularly in association with serious underlying conditions such as leukemia and other malignancies and in HIV
disease. A possible complication of oropharyngeal thrush
is the involvement of the adjacent mucosa, particularly
those of the upper respiratory tract and the esophagus. The
combination of oral and esophageal candidiasis is particularly prevalent in HIV infected patients.
Any mucosal surface may be involved and erythematous
or white areas often develop beneath the partial or complete
dentures. The lesions may involve the entire oral mucosa
or may relatively localized areas where normal cleansing is
poor. A prodromal symptom of rapid onset of a bad taste
and the loss of taste discrimination is described in adults.
Differential diagnosis Differential diagnosis of thrush
include food debris, habitual cheek biting, burns and
rarely, a genetically determined epithelial abnormality like
white sponge nevus.
Chronic hyperplastic candidiasis (candida leukoplakia)
Hyperplastic candidiasis is seen as chronic, discrete raised

Chapter 6 Red and White Lesions

Figure 24

White elevated plaques on the buccal mucosa and


erythematous areas where the white patches were
scraped off. Courtesy: Dr Ashok

Figure 25

Keratotic white plaques on the dorsum of the tongue in


chronic hyperplastic candidiasis. Courtesy: Dr Ashok

lesions that vary from small, palpable translucent whitish


areas to large, dense, opaque plaques, hard and rough to
touch (Figure 25).
The most common sites are the anterior buccal mucosa
along the occlusal line, and laterodorsal surfaces of the
tongue. The most common appearance is that of asymptomatic white plaques or papules (sometimes against an
erythematous background) that are adherent and do not
scrape off.
Chronic atrophic (erythematous) candidiasis The most
common site is the hard palate under a denture (Figure 26),
but atrophic candidiasis may also be found on the dorsal

Figure 26

Erythematous velvety area on the palate in a denture


wearer suggestive of atrophic candidiasis.
Courtesy: Dr Ashok

tongue and other mucosal surfaces. The most common etiology is poor denture hygiene, and/or continuous denture
insertion, but it may also be caused by immunosuppression, xerostomia, or antibiotic therapy.
The most common appearance is that of a red patch or
velvet textured plaque. When atrophic candidiasis occurs on
the hard palate in association with a denture, it is frequently
associated with papillary hyperplasia. Patient may complain
of a burning sensation associated with this type of candidiasis; 1565% of cases are usually associated with angular cheilitis. And lesions of chronic atrophic candidiasis
have also been frequently reported in HIV-positive and
AIDS patients. Three progressive clinical stages of denture
sore mouth have been described in the literature.
Median rhomboid glossitis Median rhomboid glossitis is
a form of chronic atrophic candidiasis characterized by an
asymptomatic, elongated, erythematous patch of atrophic
mucosa of the posterior mid-dorsal surface of the tongue
due to a chronic Candida infection (Figure 27). In the past,
median rhomboid glossitis was thought to be a developmental defect resulting from a failure of the tuberculum
impart to retract before fusion of the lateral processes of
the tongue.
A concurrent kissing lesion of the palate is sometimes
noted (Figure 28). Specic predisposing etiologic factor(s)
for median rhomboid glossitis have not been clearly
established.
Angular cheilitis (perleche) Clinical appearance is that
of red, eroded, fissured lesions which occur bilaterally in
the commissures of the lips and are frequently irritating
and painful (Figure 29). The most common etiology is loss of
vertical occlusal dimension, but it may also be associated
with immunosuppression.
155

Section III Mucocutaneous Disorders

Figure 27

A well defined erythematous area on the mid-dorsum of the


tongue roughly rhomboidal in shape suggestive of median
rhomboid glossitis. Courtesy: Dr Ashok

Figure 28

Figure 29

Erythematous fissures in the corners of the mouth bilaterally


as seen in angular cheilitis. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

immune defects, in which there is persistent mucocutaneous candidiasis that responds poorly to topical antifungal
therapy. The main types of this rare disorders include
familial CMC, diffuse CMC, candidiasis endocrinopathy
syndrome, candidiasis thymoma syndrome.
Role of candida in oral carcinogenesis

Erythematous areas on the palate in an individual with


candidal lesion on the dorsum of the tongue. Commonly
referred to as kissing lesion. Courtesy: Dr Ashok

Chronic multifocal oral candidiasis This term has been


given to chronic candidal infection that may be seen in
multiple oral sites, with various combinations, including
angular stomatitis, median rhomboid glossitis and palatal
lesions. All these lesions will be having 1 month duration
with no history of predisposing factors like systemic diseases, or patients receiving any drugs, or radiotherapy.
These lesions are most commonly seen in chronic smokers
in their 5th or 6th decade of life.
Chronic mucocutaneous candidiasis (CMC) It is the term
given to the group of rare syndromes, with a definable
156

Candidal leukoplakias may develop into carcinoma. It is


unclear whether the yeast are involved in the development
or transformation of leukoplakia. The Candida organisms
present in the candidal leukoplakia have higher nitrosation potential than others, which might indicate a possible
role of specific types in the transformation of some leukoplakias. The Candida species may be involved in carcinogenesis by elaborating nitrosamine compounds, which act
either directly on the oral mucosa or interact with other
chemical carcinogens to activate specified protooncogenes
and thereby initiate oral carcinoma.
Investigations for candidiasis
The diagnosis of oral candidiasis is most frequently made
on the basis of clinical appearance along with exfoliative
cytology examination.
Smear examination This involves the histologic examination of intraoral scrapings which have been smeared on
microscope glass slides. A 1020% potassium hydroxide
preparation (KOH prep) can be used for immediate microscopic identification of yeast cell forms. Alternatively, the
slide containing the cytologic smear can be sprayed with
a cytologic fixative and stained using PAS (periodic acidSchiff) stain and other slide with Grams stain prior to
microscopic examination. Yeast cell appears dark blue after
Gram staining and red or purple in PAS staining.

Chapter 6 Red and White Lesions

Hematologic investigations Since oral candidiasis is


associated frequently with predisposing factors such as
nutritional deficiencies, blood dyscrasias or HIV infections,
estimation of hemoglobin lymphocyte and white cell counts,
blood sugar and serum ferritin are important.
Biopsy A biopsy of affected tissue may be indicated,
especially when candidiasis is suspected in conjunction
with some concurrent pathology, such as candidal leukoplakia, epithelial dysplasia, squamous cell carcinoma, or
lichen planus. The sections should be stained with PAS or
Gridleys or Gomori methenamine silver (GMS), because
Candida species stain poorly by hematoxylin and eosin.
Microbiology It is also possible to culture Candida using
a Sabourauds dextrose agar, which is used as a primary
culture medium to aid in the definitive identification of
the fungal organism. To permit the distinction between
different yeast species Pagano-Levin medium is useful.
Imprint culture technique This technique uses a sterile
plastic foam pad of known size (2.52.5 cm) dipped in
Sabourauds broth and placed on the suspect mucosal surface for 60 seconds. Then the plastic foam is placed directly
on Sabourauds or Pagano-Levin agar. Candida density at
each site is determined by a Gallenkamp colony counter
and expressed as colony-forming units (CFU) per mm2.
Colony counts in excess of 30 CFU cm2 of mucosa in the
dentate and 49 CFU cm2 in denture wearers suggested a
candidal infection.
Salivary culture technique This involves patients 2 ml of
mixed unstimulated saliva into a sterile, universal container. The number of Candida expressed as CFU per mm
of saliva is estimated by counting the resultant growth on
Sabourauds agar.
Oral rinse technique Here the patient is asked to rinse
the mouth for 60 seconds with 10 ml of sterile phosphate
buffered saline or sterile water. The oral rinse is centrifuged at 1,700 g for 10 minutes and the deposit resuspended
in 1 ml of sterile PBS. The concentrated oral rinse is now
inoculated on appropriate media to assess CFU per mm of
rinse sample using a spiral plater prior to incubation. This
technique has advantages over the imprint technique
because it is simple to perform and it can be used for the
quantitation of other organisms such as coliforms.
Immunologic tests Immunity in oral candidiasis is predominantly cell mediated. Cell-mediated immunity to
C. albicans antigens can be demonstrated in most human
subjects both by the appearance of delayed skin hypersensitivity to candida antigens and by in vitro tests of cellular
immunity such as inhibition of leukocyte migration or
stimulation of lymphocyte transformation to candida antigens. As test of humoral immunity, the candida agglutinin
test, the candida complement fixation test, the candida
precipitin test, immunofluorescence, and ELISA test have

been used. Among these tests, ELISA is the standard and


ideal test, which uses the purified cytoplasmic protein of
C. albicans as antigen. The ELISA has been proven to be a
sensitive, cheap, and quick method for the quantification of
antibody titers and would undoubtedly be the laboratory
method of choice.
Rationale for treatment
Topical versus systemic drugs Topical antifungals are usually the drug of choice for uncomplicated, localized candidiasis in patients with normal immune function. Systemic
antifungals are usually indicated in cases of disseminated
disease and/or in immunocompromised patients.
Medication should be continued for at least 48 hours
after the disappearance of clinical signs of candidiasis along
with complete healing and the absence of mucosal erythema. Some sources recommend drug therapy should be
continued for 1014 days regardless of the disappearance
of clinical signs of candidiasis.
Suggested medications for the treatment of candidiasis
(Flowchart 3)
Topical antifungal medications Nystatin is the first specific antifungal agent effective in the treatment of candidiasis.
Nystatin taken systemically may lead to occasional GI
side effects such as nausea, vomiting and diarrhea. It can
be used in rinse form, oral and vaginal tablets or creams.
Nystatin oral suspension 100,000 units/ml; 300 ml: rinse
with one teaspoonful (5 ml) for 2 minutes, use q.i.d. (after
meals, and at bedtime) and spit out.
Patient can be directed to rinse and swallow if there is
pharyngeal involvement.
Amphotericin B is produced by Streptomyces nidus.
It has a broad spectrum of activity in humans and remains
a cornerstone of therapy for systemic fungal infections.
It is available as cream, lotion and ointment and as an
intravenous solution. It is usually fungistatic but fungicidal in higher concentrations.
Clotrimazole is the most potent topical agent in azole
group of antifungals. It has got GI and neurological toxicity
clotrimazole troches, 10 mg 70 troches; one troche dissolves in mouth ve times per day for 14 days.
Systemic antifungal medications include ketoconazole
tablets, 200 mg 1 tab q.i.d. with a meal or orange juice for
14 days. Ketoconazole is the drug being used in the treatment of chronic mucocutaneous candidiasis and candidiasis
in immunocompromised patients.
Fluconazole tablets, 100 mg, 15 tablets; 2 tablets to start,
then 1 tablet q.i.d. for 14 days, oral absorption of uconazole is rapid and nearly complete within 2 hours.
Itraconazole tablets, 100 mg, 1 tablet b.i.d. with a meal
or orange juice for 14 days. This drug has a long half-life
and fewer side effects than ketoconazole but is expensive.
Its use is contraindicated in liver diseases.
157

Section III Mucocutaneous Disorders

Flowchart 3
Oral candidiasis

If such rectification is not


possible (AIDS, diabetes)

Systemic candidiasis

Rectify the underlying


systemic/local cause

Physician opinion
sought

Topical route (denture stomatitis, angular


cheilitis, median rhomboid glossitis)

Parenteral route

1. Clotrimazole 1% cream (Candid, Canesten) five


times/day for 2 weeks
2. Clotrimazole 2% gel (Candid V) five times/day
for 2 weeks
3. Clotrimazole 1% solution (Canesten) five
times/day for 2 weeks
4. Nystatin 5 lakh unit tablets (Mycostatin) four
times/day for 14 days crush & mix with water &
use as mouthrinse & swallow
5. Hamycin 2 lakh unit/ml (Hamycin suspension)
23 times/day as mouthrinse for 710 days
6. Fluconazole dispersible tablet (Nuforce) with
water to use as mouthrinse 3 times/day for
14 days

Oral route (pseudomembranous,


hyperplastic, acute atrophic)

1. Fluconazole 150 mg (Flucole, Candizole)


b.i.d. for 14 days
2. Fluconazole 200 mg (Nuforce, Onecan)
b.i.d. for 14 days
3. Ketoconazole 200 mg (Ketozole, Fungicide)
o.d. for 14 weeks
4. Itraconazole 100 mg (Candistat)
o.d. for 14 days

Amphotericin B IV infusions 0.3 mg/kg


(Fungisome 10 mg, 25 mg, 50 mg)
can be infused over 48 hrs

Note: All available medications have been enlisted. However, the physician should
choose the appropriate mode of treatment/drug based on the clinical situations

Management of candidiasis

158

All the azole group of drugs are fungistatic, and not


fungicidal. This is an important consideration when treating the chronically immunosuppressed, such as those with
HIV and patients with candidal meningitis.

Nystatintriamcinolone acetonide ointment or clotrimazole cream 1% or miconazole cream 2% or ketoconazole


cream 2% can be applied to affected areas q.i.d. (after
meals, and at bedtime) for 14 days.

Treatment for chronic atropic candidiasis Application


of a thin coat of medicines like nystatin ointment or
clotrimazole cream 1% or miconazole cream 2%, ketoconazole cream 2% to entire inner surface of denture after
each meal for 14 days usually results in remission.
Instruct the patient to leave dentures out at night and
to soak denture in a 1% sodium hypochlorite solution for
15 minutes with thorough rinsing under running water for
at least 2 minutes, before bedtime.

Complementary and alternative medicine Garlic capsules. Garlic may have antifungal and antibacterial properties. One study found that ajoene, a compound obtained
from garlic, was as effective in treating the fungus that
causes athletes foot.
Caprylic acid capsules. This fatty acid, derived from
coconut oil, has been shown to have antifungal properties.
These are generally safe, but should not be used in patients
with ulcerative colitis.

Chapter 6 Red and White Lesions

Oral Submucous Fibrosis


Oral submucous fibrosis (OSMF) is an insidious, chronic disease affecting any part of the oral cavity, and sometimes
the pharynx. Occasionally it is preceded and/or associated
with vesicle formation and always associated with a juxtaepithelial inflammatory reaction followed by progressive
hyalinization of the lamina propria. The later subepithelial
and submucosal myofibrosis leads to the stiffness of the
oral mucosa and deeper tissues with progressive limitation
in opening of the mouth and protrusion of the tongue.
Oral submucous brosis is one of the most prevalent
premalignant condition in India which is easy to diagnose
but difcult to manage. At present it is considered as irreversible and incurable.
According to Pindborg and Sirsat (1966), OSMF is an
insidious chronic disease affecting any part of the oral
cavity and sometimes the pharynx. Although occasionally
preceded by and/or associated with vesicle formation, it is
always associated with juxta-epithelial inammatory reaction followed by a broelastic change of the lamina propria with epithelial atrophy leading to stiffness of mucosa
and causing trismus and inability to eat.
Epidemiology
The disease occurs mainly in Indians. It affects between
0.21.2% of urban population attending dental clinics in
India. The disease should be a cause of concern in countries with large migrant populations from south-east Asia.
Worldwide estimates in 1996 indicate that 2.5 million people are affected by the disease.
In ancient medicine Shushrutha described a condition,
Vidari under mouth and throat diseases. Schwartz (1952),
for the rst time reported a case of atropia idiopathica
tropica mucosae oris occurring in Indians in east Africa.
Lal and Joshi (1953) rst described this condition in India
and termed it as OSMF.
Etiopathogenesis
Pathogenesis of the disease is still not clear, and it is
believed to be multifactorial. The exact role of any of the
etiologic factor in the development, severity and progress
of the disease is not clear as the disease may still progress
even if none of these are present. The chewing of betel nut
has been recognized as one of the most important etiological factor for the causation of OSMF.
The chewing of areca nut in various forms and mixtures is deeply embedded in the social and cultural history
of India and other south-east Asian countries. Its use
appears in ancient Sanskrit literature. Areca nut contains
potent cholinergic muscarinic alkaloids, notably arecoline
and guavacoline, with a wide range of parasympatheticomimetic effects, they promote salivation and the passage
of wind through the gut, they rise blood pressure and

pulse rate and they elicit a degree of euphoria by virtue of


their GABA receptor inhibitory properties which contribute
to dependence and habituation. There are also bronchoconstrictor effects, and evidence for a role in precipitating
and exacerbating asthma and diabetes. This arecoline
plays a major role in the pathogenesis of OSMF by causing
an abnormal increase in the collagen production.
In genetically predisposed people, betel nut and pan
chewing render the oral mucosa susceptible to chronic
inammatory changes with decreased T-lymphocyte count
and higher null cell count. Areca nut, chilli and misi are
the chief local factors in the production of OSMF.
The role of chilli ingestion in the pathogenesis of OSMF
is controversial. A hypersensitivity reaction to chilies is
believed to contribute to the occurrence of OSMF, explained
by some authors as allergen induced eosinophilia due to
capsaicin.
Misi, a black colored powder containing the substances
like soda, borax, powdered alum, charcoal of myrobalan and
llers earth in varying proportion is predominantly used
by females in Uttar Pradesh is known to induce OSMF.
The avonoid catechin and tannins from betel nut stabilizes the collagen bers and makes them resistant to
degradation by collagenase.
Nutritional deciency: Malnutrition is more prevalent
in OSMF. Several investigators have reported anemia,
vitamin, iron and protein deciencies among OSMF
patients. Iron metabolism seems to be the primary factor
and deciency in folic acid, pyridoxine, and vitamin B12
deciencies are secondary.
The genetic factors like increased factors like HLA DR 10,
DR3 and DR7 have been reported. Immunological studies
have shown raised immunoglobulin like A, E and D.
Autoantibodies to gastric and parietal cells, as well as
thyroid microsomal, antinuclear, reticulin, and antismooth
muscle antibodies have been found in 65% of patients
with the disease.
Increased levels of proinammatory cytokines and
reduced antibrotic interferon gamma (IFN-) in patients
with OSMF, which may be central to the pathogenesis of
OSMF, has been demonstrated.
Matrix metalloprotein: The genomic studies have shown
the 5A genotype of MMP3 promoter was associated.
Studies have shown that six collagen related genes including COL1A1, COL1A2, COLase, LYOXase, TGF-1, and CST3
are found to be located on different chromosomes in OSMF
patients.
Role of saliva: Trivedi suggested the involvement of
trace metal copper in the molecular pathogenesis of OSMF
as they found the high levels of copper expression in
saliva could act as initiating factor and stimulation of
brogenesis by up regulation of lysyl peroxide.
According to the study conducted by Chaturvedi (1991),
saliva was found to contain alkaloids, tannins, nitrates,
thiocyanins, nitrosamines and have carcinogenic activity.
159

Section III Mucocutaneous Disorders

They found that chewing betel nut releases copper into the
saliva that stimulates lysyl oxidase enzyme lead to brosis.

b.
c.

Molecular pathogenesis of OSMF


(Rajalalitha and Vali, 2005)

d.

Collagen is the major structural component of the connective tissues and its composition within each tissue needs to
be maintained for proper tissue integrity. The synthesis of
collagen is influenced by a variety of mediators, including
growth factor, hormones, cytokines and lymphokines. A
prominent mediator is transforming growth factor-beta
(TGF-). The growth factor has also been implicated in the
development of many fibrotic diseases. It causes the deposition of extracellular matrix by increasing the synthesis
of matrix proteins like collagen and decreasing its degradation by stimulating various inhibitory mechanisms. So
transforming growth factor beta signaling pathway might
be critical for pathogenesis of OSMF.

No restriction in mouth opening


No restriction in tongue protrusion up to mesioincisal
angle of upper central incisor when maximally extended
with mouth wide open.
Burning sensation only on taking spicy food or hot
liquids.

Figure 30

Clinical features
Oral submucous fibrosis is very commonly seen among
the Indians. Indians who have settled in other countries
and to lesser extent in other Asiatic people. Several
Europeans in Europe, India and Africa have also been
mentioned as victims of the disease. Epidemiological surveys of Indian population have revealed that incidence
varied in the range of 0.040.4% and in urban population
0.181.2%. Overall prevalence of up to 0.4% in Kerala. The
common age of occurrence varies from 1262 years with
the mean age being 40 years but there are reports of OSMF
even in as younger as 4-year old. There is female predilection, with the ratio being 3:2.
First and the foremost feature of OSMF is burning sensation and pallor or blanching of oral mucosa. Intraoral
sites of involvement include the buccal mucosa (Figure 30),
retromolar area, followed by soft palate, palatal fauces,
uvula, tongue (Figure 31) and labial mucosa (Figure 32A, B).
There may be stiff and small tongue, blanched and leathery oor of the mouth (Figure 33), brotic and depigmented gingiva, rubbery soft palate with decreased
mobility and blanched and atrophic tonsils, and shrunken
bud like uvula. Mouth opening may become progressively
reduced (Figure 34).
Other symptoms include increased salivation, change of
gustatory sensation, hearing loss due to stenosis of the
Eustachian tubes, dryness of the mouth, nasal tonality to
the voice. Dysphagia to solids (if the esophagus is involved),
impaired mouth movements (e.g. eating, whistling, blowing, sucking) (Figure 35).

Pallor or marble-like appearance of the oral mucosa in OSMF.


Courtesy: Dr Ashok

Figure 31

Staging of OSMF
Stage 1: Early OSMF
a.
160

Mild blanching

Depapillation and pallor associated with the tongue in OSMF.


Courtesy: Dr Ashok

Chapter 6 Red and White Lesions

Figure 32
B

Pallor of the upper and lower labial mucosa in OSMF. Courtesy: Dr Ashok

Figure 33

Figure 34

Pallor of the ventral surface of tongue and floor of mouth in


OSMF. Courtesy: Dr Ashok

Difficulty in mouth opening due to the presence of


circumoral fibrous bands in OSMF. Courtesy: Dr Ashok

Stage 2: Moderate OSMF


a.
b.
c.
d.
e.
f.

Moderate to severe blanching


Mouth opening reduced by 33%, tongue protrusion
reduced by 33% and reduced flexibility
Burning sensation even in the absence of stimuli
Presence of palpable bands
Lymphadenopathy either unilateral or bilateral
Demonstrable anemia on hematological examination.

Stage 3: Severe OSMF


a.
b.

c.

Burning sensation very severe


More than 66% reduction in the mouth opening, cheek
flexibility and tongue protrusion. In much tongue
may appear fixed
Ulcers over the buccal mucosa

d.
e.

Thick palpable bands


Bilateral lymphadenopathy, definite nutritional compromise can be established in B complex (angular
cheilitis) and iron deficiency group.

Khanna and Andrade (1995) grouped OSMF into different


stages:
Group 1: Very early
Mouth opening is normal
Burning sensation
Excessive salivation
Acute ulceration and recurrent stomatitis.
161

Section III Mucocutaneous Disorders

Figure 35

Lips circular band felt around the entire mouth


Difficult intraoral examination

Group 5: Advance cases with premalignant and malignant


changes
OSMF and leukoplakia
OSMF, squamous cell carcinoma
Haider (2000) staged OSMF clinically and functionally as
follows:
Clinical Staging
Stage 1: Faucial bands only
Stage 2: Faucial and buccal bands
Stage 3: Faucial and labial bands
Functional Staging
Stage A: Mouth opening 1320 mm
Stage B: Mouth opening 1012 mm
Stage C: Mouth opening less than 10 mm.
Inability of the patient to blow his cheeks demonstrating
inelasticity of the oral mucosa in OSMF.
Courtesy: Dr Ashok

Group 2: Early cases


Mouth opening: 2635 mm (interincisal opening)
Soft palate and faucial pillars were the areas primarily
affected
Buccal mucosa appeared mottled and marble like
where dense pale, depigmented fibrosed areas alternated with pink normal mucosa
Red erythematous patches
Widespread sheets of fibrosis.

Group 3: Moderately advanced


Mouth opening 1525 mm (interincisal opening)
Trismus
Vertical fibrous bands could be palpated and firmly
attached to underlying tissue
Unable to blow out their cheeks and whistle
Soft palatethe fibrous bands were seen to radiate
from the pterygomandibular raphe
Or the anterior faucial pillars in a scar like appearance
Lipsatrophy of vermillion border

Unilateral posterior cheek involvement with only ipsilateral involvement of the faucial pillars and soft palate and
opening reduced to 1518 mm.
Group 4: Advanced cases
Stiffness/inelasticity of oral mucosa
Trismus
Mouth opening 215 mm (interincisal opening)
Fauces thickened, shortened and firm on palpation
Uvula was seen to be involved, shrunken, small, and
fibrous band
Tongue movement restricted
Papillary atrophy (diffuse)

162

Malignant potential and oral submucous fibrosis


Various authors in the past have suggested OSMF as a
precancerous condition. According to Pindborg, atrophy
of the epithelium increases the vulnerability of the action
of carcinogens. Due to irritation by exogenous factors, the
atrophic epithelium undergoes hyperkeratinization, there
is intercellular edema in the prickle cell layers and the
basal cells undergo hyperplasia. After this carcinoma can
develop at any stage. Congestion of the blood vessels due
to excessive fibrosis in the connective tissue compromises
the blood supply. Some have demonstrated abnormal
expression of P-53 tumor suppressor gene as detected by
immunohistochemistry in the epithelium of OSMF.
Other diseases associated with OSMF
There are reports of concomitant occurrence of oral lichen
planus, leukoplakia, pemphigus and squamous cell carcinoma in the literature.
Histopathologic changes
Epithelial changes Increase in the clinical severity of the
disease may be accompanied by epithelial hyperplasia or
atrophy (Figure 36), which is associated with an increased
tendency for keratinizing metaplasia. Deep invagination
of epithelial pegs into underlying lamina propria, liquefaction degeneration of basal cells have been reported.
Connective tissue changes The connective tissue changes
include hyalinization, with moderate number of chronic
inflammatory cells.
The most striking feature of connective tissue is the
presence of dense collagen bundles, randomly oriented
and extending into the underlying striated muscles.
Inammatory cell inltration includes lymphocytes,
monocytes, plasma cells, and occasionally macrophages.

Chapter 6 Red and White Lesions

Figure 36

melanocytes, a feature which explains the clinically observable loss of pigment. Absence of fibroblasts within the
hyalinized zones, total loss of epithelial rete pegs, and
extensive degeneration of muscle fibers.
Investigations

Studies have reported thickened basement membrane


with marked reduction in the vascularity in the connective
tissue which was inversely proportional to increased density
of collagen which appeared hyalinized.

Diagnosis of the disease is by clinical findings and confirmed by incisional biopsy. Many investigations have been
suggested by various authors, that include hematological,
serological, immunological and biochemical factors. Other
laboratory ndings include a raised ESR, slight eosinophilia, microcytosis and hyperchromic indicative of anemia.
Cytologic smears may be performed.
A neural network-based oral precancer stage detection
method has been proposed. This new technique uses wavelet coefcients from transmission electron micrography
images of subepithelial brillar collagen in normal oral
submucosa and in OSF tissues. These wavelet coefcients
are used to choose the feature vector, which, in turn, can be
used to train an articial neural network. This trained network is able to classify normal and oral precancer stages
(less advanced and advanced) after obtaining the image as
an input. It may be used as an adjunct to hematoxylin and
eosin histologic evaluations in the near future.

Histological staging of OSMF

Differential diagnosis

Khanna and Andrade (1995) have classified the histological findings of OSMF into four groups.

Oral manifestations of scleroderma: Scleroderma can be


distinguished by other cutaneous, systemic, and characteristic radiographic and laboratory findings.
Anemia: Pale oral mucosa can mimic atrophy and
brosis.
Amyloidosis: Hyalinized stroma can be distinguished
from amyloid inltration by using Congo red and thioavine T staining under polarized and immunouorescent
light.
Generalized bromatosis: Although soft tissue masses
are not produced in the usual sense, the brosis of OSMF
may be confused with generalized bromatosis.

Atrophic epithelium and the hyalinization and


homogenization of collagen fibers. Courtesy:
Department of Oral Pathology, MCODS, Mangalore

Group 1: A fine fibrillar collagen network with marked


edema, blood vessels dilated and congested. Large aggregate of plump, young fibroblasts containing abundant
cytoplasm. The inflammatory cells consist of PMNLs with
few eosinophils, normal epithelium with some hyperplastic
epithelium.
Group 2: The juxta-epithelial area shows early hyalinization. Collagen still appears as separate bundles and
thickened. Plump young fibroblasts are present in moderate numbers. The blood vessels are dilated and congested.
The inflammatory cells are mononuclear lymphocytes,
eosinophils and occasional plasma cells; flattening and
shortening of the epithelial rete pegs with varying degree
of keratinization.
Group 3: Juxta-epithelial hyalinization. Thickened collagen bundles are fairly describable, separated by edema.
Blood vessels constriction, fibrocytes with scanty cytoplasm and spindle-shaped nuclei and atrophic epithelium
with total loss of rete pegs. Muscle fibers seem to be interspersed with thickened and dense collagen fibers. The
degeneration of muscle fibers begin.
Group 4: Hyalinization of collagen bundles as smooth
sheet, obliteration of blood vessels and decreased/loss of

Treatment (Flowchart 4)
Since the exact etiology is unknown, various treatment
modalities have been tried from time to time. The treatments of the condition include avoidance of habits but
there is no reversal of fibrosis.
Management includes the following medications:
Corticosteroids These agents can be used in pharmacologic doses for their anti-inflammatory and immunosuppressant properties and their effects on blood and lymphatic
systems in the palliative treatment. In patients with moderate OSMF, weekly submucosal intralesional injections or
topical application of steroids may help prevent further
damage.
163

Section III Mucocutaneous Disorders

Dexamethasone (Decadron): Adult dose 4 mg IV/IM.


Decreases inammation by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability.
Placental extracts The rationale for using placental
extract in patients with OSMF derives from its proposed
anti-inflammatory effect, hence, preventing or inhibiting
mucosal damage. Cessation of areca nut chewing and submucosal administration of aqueous extract of healthy
human PE (Placentrex) showed marked improvement of
the condition.
Hyaluronidase The use of topical hyaluronidase has
been shown to have quicker improvement in symptoms
compared with steroids alone. The combination of steroids

and topical hyaluronidase shows better long-term results


than either agent used alone.
Interferon-gamma This plays a role in the treatment of
patients with OSMF because of its immunoregulatory effect.
IFN- is a known antifibrotic cytokine. Patients treated with
an intralesional injection of IFN- experienced improvement of symptoms. IFN-, through its effect of altering collagen synthesis, appears to be a key factor to the treatment
of patients with OSMF, and intralesional injections of the
cytokine may have a significant therapeutic effect on OSMF.
Surgical care: Surgical treatment is indicated in patients
with severe trismus and/or biopsy results revealing dysplastic or neoplastic changes. Surgical modalities that have
been used include the following:

Flowchart 4
OSMF

Stage I

Stage II & III

Stage IV

Systemic:
1. Iron supplements (Dexorange Syrup, Haemup Syrup/Capsules)
2. Antioxidant capsules b.i.d. for 3 months (Antoxid, Altomin Xl, Lynet, Revup, Oxyace, Oxidix)

Topical:
1. Benzydamine 0.15% mouth
rinse (Tantum)
2. Triamcinolone gel (Tess) or
crushed dexamethasone
tablets in 20 ml of water &
use as mouthrinse
Immunomodulators:
Levamisole 150 mg o.d. for
3 days twice in a month
for 3 months (Vermisol,
Levazole)

Intralesional injections:
1. Dexamethasone +
Hyaluronidase 1,500 IU
(Hylase) + Lignocaine
2 ml; multiple site
injections once/week
for 6 weeks
2. Betamethasone +
Hyaluronidase 1,500 IU +
Lignocaine + Placentrex
= 3 ml multiple site
injections once/week
for 6 weeks

Newer drugs:
1. Pentoxifylline 400 mg b.i.d. for 15 days
(Flexital, Flowpent)
2. Interferon gamma injections

No medicinal treatment
can be given
1. Surgical relieving of
fibrous bands with
buccal pad of fat
covering the wound
2. Laser surgery

Physiotherapy:
1. Mouth opening exercises
2. Mouth opening appliance
3. Ice cream stick
4. Ultrasound

Note: All available medications have been enlisted. However, the physician should
choose the appropriate mode of treatment/drug based on the clinical situations

Management of oral submucous fibrosis

164

Chapter 6 Red and White Lesions

Simple excision of the brous bands: Excision can result


in contracture of the tissue exacerbating the condition.
Split-thickness skin grafting following bilateral temporalis myotomy or coronoidectomy: Trismus associated
with OSMF may be due to changes in the temporalis tendon secondary to OSMF; therefore, skin grafts may relieve
symptoms. Nasolabial aps and lingual pedicle aps:
Surgery to create aps is performed only in patients with
OSF in whom the tongue is not involved. The use of vitamin supplements, balanced diet and stretching exercises
are aimed at increasing the mouth opening. Regular physical examinations, biopsy specimen analysis, and cytologic smear testing should be scheduled to detect oral
dysplasia or carcinoma, especially in patients with severe
OSMF. Patients with surface leukoplakia require close follow-up monitoring and repeat biopsies. Patients with dysplasia and carcinomas should receive routine treatment
for these entities.
Complications Oral dysplasia and squamous cell carcinomas are complications of OSMF. In patients with OSMF,
the risk of developing oral carcinoma is 714% over a
10-year period.
If the palatal and paratubal muscles are involved in
patients with OSMF, conductive hearing loss may occur
because of functional stenosis of the Eustachian tube.
Prognosis
No treatment is effective in patients with oral submucous
fibrosis, and the condition is irreversible. Recent reports
claim improvement of the condition if the habit is discontinued following diagnosis at an early stage.

Focal Epithelial Hyperplasia (Hecks Disease)


Hecks disease is considered among the most contagious
of the papillary lesions affecting the oral cavity. Presently
the etiology for this condition is said to be a subtype of the
human papillomavirus, HPV-13, and possibly HPV-32. It
is very commonly seen in Eskimos and American Indians
and less commonly in white Europeans. The predisposing
factors associated with this condition are poor hygiene,
poverty and communal lifestyle. Presence of this condition among close communities and family members suggests an infectious pathogenesis.
Dos Santos et al (2004) in their article state the prevalence
of this condition affecting the oral mucosa was highest in
Waimiri-Atroari Indians, reaching 21% with no differences between the sexes or among different age groups.
Patients of a younger age group presented with multiple
lesions, which were predominantly nodular, whereas older
patients had few or even single lesions, which tended to be
at and papular.
Clinical features
It is usually seen in children and adults. The condition is
characterized by multiple soft, circumscribed, sessile nodules of whitish color or a color mimicking the adjacent
oral mucosa (Figure 37). The common sites of involvement
are the lips, buccal mucosa and the lateral borders of the
tongue (Figure 38).

Figure 37

Psoriasis
Description is given in Chapter 9 (Dermatological
Diseases).

Hereditary Benign Intraepithelial Dyskeratosis


(Witkops Disease)
Witkop-von Sallmann disease It is a rare genetic disorder characterized by the oral lesions and bilateral conjunctival plaques. The oral lesions are similar to white
sponge nevus. They appear as thick corrugated asymptomatic white plaque involving the buccal and labial mucosa.
Other intraoral sites include oor of the mouth, lateral
tongue, gingiva and palate. The signicant feature of this
disease is the formation of corneal plaques that may lead
to blindness.
Differential diagnosis
White sponge nevus and pachyonychia congenita can be
considered in the differential diagnosis.

Well circumscribed, sessile nodules mimicking the color of


the adjacent oral mucosa in Hecks Disease. Courtesy:
Prof Braz Campos Durso, Brazil

165

Section III Mucocutaneous Disorders

Figure 38

Well circumscribed, papular lesions on the labial mucosa in


Hecks disease. Courtesy: Prof Braz Campos Durso, Brazil

The diagnosis of Hecks disease can be made by clinical


examination. However histological evaluation may show
features of viral infection. The condition is said to be associated with HIV infection. However the association between
these two conditions is yet to be substantiated. Suppression
of the immune system leaves the patient vulnerable to
opportunistic infections, including HPV infections.
Management
No treatment is necessary as it is self-limiting and regresses
completely. However some treatment modalities that have
been used include surgical or cryosurgical procedures,
electrocoagulation or treatment with carbon dioxide laser.
Steinhoff et al (2001) have used interferon- for successfully managing the condition. However, its efcacy in
the treatment of oral lesions has yet to be adequately
tested.

White sponge nevus involving the buccal mucosa.


Courtesy: Thomas S Pilak, Marquette University, USA

White sponge nevus is also known by other names


which include white folded gingivostomatitis, familial white
folded hypertrophy of the mucous membrane, leukokeratosis oris, hereditary leukokeratosis, leukoderma exofoliativum
mucosae oris and naevus spongiosus albus mucosae.
Etiopathogenesis
The basic defect lies in the epithelial cell maturation and desquamation. Atypical abundance and aggregation of tonofilaments and increased intracellular attachment cause piling
up of surface cells and keratin. There is also a decreased
shedding of keratin which leads to white sponge nevus.
Genetic basis
There are mutations in genes controlling keratins, i.e. K4
and K13 on chromosomes 12q13 and 17q2122. There is
also a K4-3bp deletion. Mutations are also seen in K14 and K19
controlling genes. Rugg et al described mutation in genes
N-60 and Richard et al reported mutations in gene L119P.

Dyskeratosis Congenita

Clinical features

Description is given in Chapter 9 (Dermatological


Diseases).

Usually presents itself at birth or early childhood. There is


no sex predilection. Lesions are seen involving the oral
mucosa and other mucosal sites such as the nasal cavity,
esophagus, larynx, vagina and rectum. The common sites
that are affected include buccal mucosa (Figure 39) followed by labial mucosa, alveolar ridge and floor of mouth.
Gingiva and tongue are rarely affected. Usually it presents
itself as an asymptomatic gray white folded or corrugated
spongy mucosal lesions that often have symmetrical
weavy pattern (Figure 40). They have soft or spongy texture and white opalescent hue. Size of the lesion can vary
from few millimeters to several centimeters. They present
usually as a symmetrically bilateral lesion.

White Sponge Nevus


White sponge nevus is a hereditary dyskeratotic hyperplasia of the mucous membranes that shows an autosomal
dominant inheritance pattern with irregular penetrance. It
is characterized by variable and some times severe leukokeratosis of the oral mucosa.
Hyde in 1909 gave the rst description of this condition.
Subsequently in 1935, Cannon named it white sponge nevus.
166

Figure 39

Chapter 6 Red and White Lesions

Figure 40

White corrugated spongy mucosal lesions on the labial


mucosa in white sponge nevus. Courtesy: Thomas S Pilak,
Marquette University, USA

It is usually asymptomatic. However it may become


symptomatic by the irritating stimuli like bacterial or yeast
infection. Patients can complain of pruritus, burning sensation or pain.
Differential diagnosis
Various conditions can be considered in the differential diagnosis such as leukoedema, leukoplakia, traumatic keratosis, chemical burn, candidiasis, lichen planus, pachyonychia
congenita, Dariers disease and dyskeratosis congenita.
Histopathologic features
Histopathological sections reveal epithelial thickening
showing both acanthosis and hyperkeratosis. The basal
layer is intact and the spinous cell layer is continuous till
the surface and shows intracellular edema and pyknotic
nuclei are seen. Parakeratin plugging runs deep into the
spinous layer. Mild inflammatory cell infiltrate is seen in
the submucosa (Figure 41).
Treatment
Since it is a benign lesion and usually asymptomatic, no
treatment is required. However in symptomatic cases tetracycline mouthrinse and penicillins have shown some
good results.

RED LESIONS OF THE ORAL CAVITY


Individual variations in the color of the oral mucosa are
probably an expression of one or more genetically controlled
factors.

Figure 41

White sponge nevus. Courtesy: Thomas S Pilak,


Marquette University, USA

The color of the oral mucosa depends on the thickness


of the oral epithelium, underlying connective tissue contents like brous tissue, vascularity, and the functional
adaptations of the mucosa toward forces of mastication
and the inammatory process.
Healthy masticatory mucosa (gingival, palate, dorsal
surface of the tongue) is light pink in color. The lining
mucosa (mucosa over the vestibule, cheeks, lips, oor of
the mouth, and ventral surface of the tongue) is reddish
pink in color. Palatoglossal arch region is dusky red in
color due to increased vascularity and often misdiagnosed
as sore throat.
Classification of red lesionscongenital and
acquired
Congenital red lesions Vascular malformations like
hemangiomas, AV shunts.
Acquired red lesions
Erythroplakia
Extravasations of blood (trauma or hemostatic disease)
Atrophy or erosion of the mucosa
Inflammation secondary to vascular dilatation
Infections like (cellulitis, secondary syphilis, candidiasis)
Inflammatory hyperplasias
Allergic and autoimmune diseases
Increase in the hemoglobin pigmentation
Traumatic erythematous macules Mechanical trauma to
the oral mucosa can produce a variety of clinical lesions
depending on the nature and severity and the host response.
These may be in the form of erythematic macules, hemorrhagic nodules, echymoses, erosions and ulcers in the order
of severity. Common causes include self-inflicted injury
like cheek bite or some deleterious habits, sharp margins
of the teeth or restorations and ill-fitting prostheses.
167

Section III Mucocutaneous Disorders

The most common site of occurrence of the erythematous macules are on the anterior and lateral borders of
the tongue, oor of the mouth, posterior palate, buccal
mucosa, and the mucosal surface of lips. Clinical congurations of these depend on the offending agent. This could
be either elicited by the history or by clinical examination.
The caustic drugs (aspirin) or hot foods or beverages
result in the coagulation necrosis of the supercial tissue
and appear as whitish scrapable membrane over an erythematous base.
Erythematous macules at the junction of hard and soft
palate should be differentiated from the purpuric macule
of oral sex, palatal bruising because of severe cough or
severe vomiting, allergic manifestations, macular hemangioma, atrophic candidiasis, infectious mononucleosis and
herpangina.
The lesions usually regress after the removal of the
causative factors. In case of multiple numbers, investigations are needed to rule out the underlying hemostatic
disorders.
Reddish ulcers or ulcers with red halo Ulcerative conditions like recurrent herpes and recurrent aphthous stomatitis are first manifested as erythematous macules.

RED LESIONS OF THE TONGUE


Migratory Glossitis
Description is given in Chapter 2 (Developmental
Disturbances).

Median Rhomboid Glossitis


Description is given in Chapter 2 (Developmental
Disturbances).

Deficiency States

Soft tissue odontogenic infection (cellulitis) Odontogenic infections may originate in canals and periapex of
the teeth, gingival and periodontal pockets, and the gingival operculum over an erupting tooth and may spread to
the surrounding soft tissues like oral mucosa appear red,
swollen and tender to palpate.

Certain deficiency states can produce a glossitis of a completely bald or patchy bald tongue. These include iron
deficiency anemias, pernicious anemia, Plummer-Vinson
syndrome; sprue and vitamin B complex deficiencies, especially those of thiamine, riboflavin, nicotinic acid, pyridoxine, pantothenic acid, and vitamin B12.

Mucositis secondary to systemic diseases Mucosa may


have reddish appearance in case of severe esophagitis and
other gastrointestinal disorders, uremic stomatitis in case
of end stage renal diseases.

Clinical features

Macular hemangiomas and telangiectasias Red macular hemangiomas occur as both syndromic and non-syndromes associated are readily differentiated from
erythemas by the history of long duration, non-tenderness, absence of inflammatory components, characteristic
emptying of the lesions.
Polycythemia Polycythemia also called erythremia is a
chronic and sustained elevation of erythrocytes and level
of hemoglobin. Primary polycythemia is a neoplastic condition of the hematopoietic system. Secondary polycythemia
results from stimulation of bone marrow at high altitudes
or by chronic pulmonary diseases like emphysema. In this
condition the entire oral mucosa appears deep red and
gingival and soft tissues easily bleed and seen as multiple
petechiae over the palate. Laboratory investigations
including elevated levels of erythrocyte count, raised hemoglobin concentration, hematocrit values quickly establish
the diagnosis.
168

Lupus erythematosus Lupus erythematosus is a connective tissue disease of unknown cause in which antibodies
to nuclear constituents are produced to result in the involvement of various organs. Two forms of the disease include
discoid and systemic lupus erythematosus. In Schiodts
study of 32 patients of lupus erythematosus with oral lesions,
early lesions were characterized by erythema without the
striae.

Tongue may be intensely red and then becomes smooth as


the filiform or both the types of papillae atrophy. Symptoms
vary from tender to burning tongue to extreme glossodynia.

Foliate Papillitis
Sometimes enlarged foliate papillae appear red in color
due to inflammatory enlargement of the lymphoid tissue
or due to upper respiratory tract infections or mechanical
irritation and may be mistaken for erythroplakic lesions
on the tongue.

Erythroplakia
Erythroplakia is a precancerous lesion occurring in the
oral cavity, The term erythroplakia (erythroplasia) was
coined to describe red lesions of the oral mucosa in contrast to oral leukoplakia.
The term erythroplasia was originally used by Queyrat
to describe a red, precancerous lesion of the penis. The term
erythroplakia is used for a clinically and histopathologically

Chapter 6 Red and White Lesions

similar process that occurs on the oral mucosa. Erythroplakia


is a clinical term that refers to a red patch that cannot be
dened clinically or pathologically as any other condition.
This denition excludes inammatory conditions that
may result in a red clinical appearance.
Definitions
Over the years several definitions for erythroplakia have
been suggested.
Mehta et al, diagnosed erythroplakia when the oral
mucosa was the seat of a well-demarcated, red, often ery
red patch, which could not be attributed to other causes.
According to Shafer and Waldron, Erythroplakia of the
oral cavity is a specic disease entity which must be differentiated from other specic or non-specic inammatory oral lesions, although this can only be done in most
cases by biopsy. WHO in 1978 dened erythroplakia as
any lesion of the oral mucosa that presents as bright red
velvety plaques which cannot be characterized clinically
or pathologically as any other recognizable condition.
This denition was conrmed during an international
seminar on oral leukoplakia and associated lesions related
to tobacco habits in 1983. In 1994, at another symposium
on oral white lesions with special reference to precancerous and tobacco-related lesions the denition of OE was
changed: The term erythroplakia is used analogously to
leukoplakia to designate lesions of the oral mucosa that
present as red areas and cannot be diagnosed as any other
denable lesion.
An updated denition for erythroplakia was proposed
by Bouquot as a chronic red mucosal macule which cannot be given another specic diagnostic name and cannot
be attributed to traumatic, vascular, or inammatory
causes.
Erythroplakia is dened as a ery red patch that cannot be characterized clinically or pathologically as any
other denable lesion. This denition is now widely
accepted, although it is based on the principle of diagnosis
per exclusion.
Incidence/prevalence
It is generally accepted that the erythroplakia is much less
common than oral leukoplakia and most of the prevalence
figures were derived from studies in South and South-East
Asia and no such figures have been published from other
geographic areas.
In a survey of 50,915 Indian individuals, Mehta et al
found only nine cases of erythroplakia (0.02%).
In 1975 Shafer and Waldron described 58 cases thought
to be representative of oral erythroplakia among 64,345
biopsies, representing 0.09%.
Two epidemiological surveys of oral mucosal lesions
from Malaysia revealed a prevalence of 0.02% for both
studies.

In a house-to-house survey in Burma among 6,000 villagers over the age of 15 years, ve cases of oral erythroplakia were diagnosed, with a prevalence of 0.83%.
Feller et al from South Africa studied 138 cases of oral
precancerous lesions, of which eight were oral erythroplakia.
A recently published case-control study from Kerala,
India, included 100 cases of erythroplakia among 47,773
controls, with a prevalence of 0.2%.
With these few data available it was observed that presently erythroplakia has a range of prevalence between
0.02% and 0.83%.
Classification
Shear suggested a classification of erythroplakia in 1972. He
differentiated between clinical and microscopic variations
and neoplastic from inflammatory changes.
Clinical variations
Homogeneous erythroplakia
Erythroplakia interspersed with patches of leukoplakia
Granular or speckled erythroplakia (embracing the
lesion described as speckled leukoplakia)
Microscopic variations
Neoplastic
Squamous carcinoma
Carcinoma in situ (intraepithelial carcinoma) and
less severe forms of epithelial atypia
Inflammatory
Candida albicans infections (including denture stomatitis)
Tuberculosis
Histoplasmosis
Miscellaneous specific, non-specific and nondiagnosable lesions
Etiopathogenesis
While erythroplakia does not seem to have a known geographic incidence, studies from India have shown that
erythroplakia may be associated with tobacco smoking
and chewing habits and that the risk to develop erythroplakia was strongly associated with these.
Etiology and pathogenesis of erythroplakia are poorly
understood. Predisposing factors are widely unknown, but
it was suggested that tobacco and alcohol use are probably
involved in most cases.
Reports of large case-control study in Kerala, India,
shed more light on some of the factors involved in the
etiology of erythroplakia. One of these studies evaluated
the risk of erythroplakia in relation to chewing tobacco,
smoking, alcohol drinking, body mass index (BMI), and
vegetable, fruit, and vitamin/iron intake. It was concluded
that tobacco chewing and alcohol drinking are strong risk
factors for erythroplakia in the Indian population.
169

Section III Mucocutaneous Disorders

Figure 42

and velvety surface; they may also be seen with other


morphological characteristics, like an irregular, red granular
surface interspersed with white or yellow foci, which may
be described as granular erythroplakia. Erythroplakia is soft
to palpation and does not become indurated or hard until
an invasive carcinoma develops in it.
Erythroplakia is often asymptomatic, although some
patients may complain of a sore or burning sensation.
Malignant transformation
Erythroplakia has the highest risk of malignant transformation compared to all other oral mucosal premalignant
lesions. The malignant transformation rate for erythroplakia
varies from 14 to 50%.
Differential diagnosis
Erythematous candidiasis, atrophic oral lichen planus and
denture-induced stomatitis can be considered in the differential diagnosis of erythroplakia.

A red velvety lesion involving the left buccal mucosa


suggestive of erythroplakia. Courtesy: Department of Oral
Medicine and Radiology, MCODS, Mangalore

In another study designed to study the risk factors for


multiple oral premalignant lesions, suggested that tobacco
chewing was the most important risk factor for multiple
oral premalignant lesions and therefore may be a major
source of eld cancerization on the oral epithelium in an
Indian population.
Clinical features
Oral erythroplakia occurs most frequently in middle age
and elderly and appears as a red macule or plaque with a
soft, velvety texture (Figure 42).
Among 58 cases reported by Shafer and Waldron 37 cases
(67.8%) occurred in the sixth and seventh decades (19 men,
18 women). It occurs most commonly in men. The soft palate, the oor of the mouth and the buccal mucosa are the
most commonly affected site; the tongue is rarely affected.
Shafer and Waldron, however, observed some differences
of location between women and men. The most common
site of occurrence of oral erythroplakia in men was the
oor of the mouth, but in women the combined mandibular alveolar mucosa, mandibular gingiva, and mandibular
sulcus was most commonly affected. In men this combined
site was the least common site of occurrence. The retromolar area in both men and women and the oor of the mouth
in women was the next most common site of involvement.
The typical lesion of oral erythroplakia is less than 1.5 cm
in diameter and half are less than 1 cm, but lesions larger
than 4 cm have also been observed. Some erythroplakias are
smooth and some are granular or nodular. Often there is a
well-dened margin adjacent to mucosa of normal appearance, although the erythroplakia lesions may have a smooth
170

Treatment and recurrence rate


Erythroplakia is a premalignant lesion, which shows highest risk for malignant transformation; therefore early treatment of such lesion is mandatory. Alcohol and tobacco
habits should be avoided as a preliminary measure. Regular
follow-up examination is recommended for the lesion
which shows no or moderate epithelial dysplasia. Surgical
excision of the lesion is recommended for those lesions
which show severe epithelial dysplasia or carcinoma in
situ histologically. Amagasa et al (1985) recorded a recurrence of erythroplakia in 5 of 7 cases.

Discoid Lupus Erythematosus


Discoid lupus erythematosus (DLE) is a chronic inflammatory condition of the skin, connective tissue and specific
internal organs that has associated circulating autoantibodies to DNA and other nuclear and RNA proteins; circular whitish buccomucosal lesions and erythematous rashes
of the sun-exposed skin.
Lupus erythematosus is a syndrome whose manifestations range from a localized skin lesion to a destructive
systemic disorder without any cutaneous changes.
Classification
Gilliam classification of skin lesions associated with LE
I. LE-Specific skin disease
A. Acute cutaneous LE
1. Localized ACLE
2. Generalized ACLE
B. Subacute cutaneous LE
1. Annular SCLE
2. Papulosquamous SCLE

Chapter 6 Red and White Lesions

C.

II.
A.

B.
C.
D.
E.
F.
G.
H.

Chronic cutaneous LE
1. Classic discoid LE
a. Localized DLE
b. Generalized DLE
2. Hypertropic/verrucous DLE
3. Lupus profundus
4. Mucosal DLE
a. Oral DLE
b. Conjunctival DLE
5. Chilblain DLE
6. Lichenoid DLE
LENon-specific skin disease
Cutaneous vascular disease
1. Vasculitis
2. Vasculopathy
3. Livedo reticularis
4. Thrombophlebitis
5. Raynauds phenomenon
Non-scarring alopecia
Sclerodactyly
Rheumatoid nodules
Calcinosis cutis
Urticaria
Erythema multiforme
Lichen planus

Alternatively DLE can be classified as:

Systemic lupus erythematosus


Bullous form of lupus erythematosus
Neonatal form of LE
Chronic cutaneous form of LE (CCLE)
Subacute cutaneous form (SCLE)
Drug-related lupus

Discoid lupus erythematosus (DLE) is named so because


the lesions are disc or coin shaped. DLE is also known by
the name cutaneous lupus erythematosus and chronic discoid lupus erythematosus.
The WHO Collaborating Reference Centre for Oral
Precancerous Lesions describes DLE as a benign disorder
of the skin, most frequently involving the face, and characterized by well-dened red scaly patches of variable
sizes, which heal with atrophy, scarring and pigmentary
changes. Discoid lupus erythematosus can present as a
localized or generalized form. In the localized form, head
and neck are most commonly involved, whereas in the
disseminated form the lesions may occur in a wide spread
pattern on the trunk and limbs, or may be localized to
other body sites.
Etiopathogenesis
Genetic factors Genetic deficiencies of the complement
components including C2, C3, C4, and C5 as well as the C1

esterase inhibitor are associated with DLE. Significant


increases of HLA B7, B8, DR3 and DQA0102 and a significant decrease in HLA A2 have been reported for patients
with DLE. It also occurs with increased frequency in female
carriers of X-linked chronic granulomatous disease.
Role of UV light Ultraviolet light is probably the most
important environmental factor in the induction phase of
LE specific skin disease. Early studies demonstrated that
cutaneous LE lesions could be provoked in the clinically
normal skin of the patients with both SLE and cutaneous
LE by repeated delivery of high doses of UVB radiation to
the same test site. More recent studies argue that UVA
radiation can also induce cutaneous LE lesions.
Environmental factors The onset of lesions may be precipitated by a variety of factors. At a study in Leeds,
lesions started with trauma in 11%, with mental stress in
12%, sunburn in 5%, infection in 3%, exposure to cold in
2% and pregnancy in 1%. Drugs like antibiotics (penicillin,
streptomycin, sulfonamides, tetracycline), antituberculous
drugs (isoniazid, paraaminosalicylate), antihypertensive
drugs (hydralazine and methyldopa), antifungal (griseofulvin) and antiarthritic (gold) have known to precipitate
lesions of DLE.
Clinical features
It is usually seen in the 3rd and 4th decades of life. The peak
age of onset is 30 years in females and 40 years in males.
It is predominantly seen in females in the ratio 3:1. Blacks
are reportedly more severely affected. The common sites of
involvement include the face, scalp, nose, ears, V area of the
neck and extensor aspect of the arms. Any area of the face
including the eyebrows, eyelids, nose and lips can be affected.
Skin lesions
Early lesions The lesion start as patches of erythema,
occasionally with an urticarial component; later they become
papulosquamous and eventuate in elevated reddish edematous plaques covered with adherent graying scales. The
lesions tend to enlarge peripherally and may coalesce to
produce bizarre patterns.
Chronic lesions Chronic lesions are well defined and circular, oval or irregular in shape. Often they have an elevated
erythematous border. The center of the lesion is usually
depressed. Dilated follicular openings plugged with horny
epithelial plugs are seen. Large areas may be involved.
Some of the patches may resolve, but residual scarring is
more common. The scars are smooth, atrophic, flat and
white. Telangiectasia may be present at the edges of the
scars so called telangiectatic lupus erythematosus is merely
the morphological form in which telangiectasia predominates. Post inflammatory hyperpigmentation also may occur.
Depigmentation may also be seen. Follicular involvement
171

Section III Mucocutaneous Disorders

is a prominent feature. Keratotic plugs accumulate in dilated


follicles that soon become devoid of hair. When the adherent scale is lifted from more advanced lesions, keratotic
spikes similar in appearance to carpet tacks can be seen to
project from the undersurface of the scale (carpet tack sign
or tin tact sign).
Color: Active lesionsred whereas burnt out or scarred
lesions are pink or white.
Shape is usually round, oval, annular, polycyclic with
irregular borders.
Distributionscattered discrete lesions.
Malar rash or the buttery rash is occasionally seen
in DLE.
Mucosal or oral lesions Lesions of the mucous membranes may be limited to these areas, but usually coexist
with skin lesions of DLE. Mucous membrane lesions more
commonly occur during acute systemic episodes of lupus
erythematosus. They typically consist of gingivitis, mucosal
hemorrhage, erosion and shallow ulcerations.

Early lesionsmucosal hemorrhage, erosion, superficial erythematous patches with dilated blood vessels
on the borders. The center is depressed or superficially
ulcerated.
Chronic lesionscentral atrophic areas with small white
dots, surrounded by a keratinized border composed of
radiating white striae.
Different types of DLE

Verrucous DLE: If hyperkeratosis is marked, a warty


lesion with a red slightly raised edge results.
Tumid DLE: The tissues are swollen, brawny, warm and
tense. The surface shows a reddish, mottled appearance due to scarring.
Chilblain lupus: Variant of DLE characterized by
purplish-blue, tender chilblain-like (chilblains are ulcers
affecting extremities that occur due to exposure to
cold and humidity) nodules.
LE profundus: In this cutaneous infiltrate occurs primarily in the deeper portions of the dermis and gives
rise to firm, rubbery, sharply defined nodules varying
in size from one to several cm in diameter.
LE and EM like syndrome (Rowells syndrome).
LE and LP overlap syndrome.
Rosacea like syndrome.

Discoid lupus erythematosus has negative response for


LE cell inclusion test usually patients with SLE typically
develop LE cells. This cell or phenomenon consists of a
rosette of neutrophils surrounding a pale nuclear mass
apparently derived from a lymphocyte. Only rare occasion
is the LE cell found in cases of DLE.
Immunofluorescence studies
Immunofluorescence studies reveal a granular or shaggy
pattern of IgG, IgM, IgA, C3 in the basement membrane or
in the dermal-epidermal junction. In comparison to IgM,
granular deposits of IgG are extensive at the dermoepidermal junction. Such a finding is referred to as lupus
band. Lupus band test (LBT) is positive in 90% of active
lesions that have not been recently treated with topical
corticosteroids. However the test is negative in burnt-out
or scarred lesions and in the normal skin (either sunexposed/non-sun-exposed).
Histological features
Hyperkeratosis with follicular or keratotic plugging, atrophy of the rete pegs, liquefaction degeneration of the basal
layer of cells, perivascular inltration of lymphocytes and
their collection about dermal appendages, and basophilic
degeneration of collagen and elastic bers with hyalinization, edema and brinoid change, particularly prominent
immediately beneath the epithelium.
Differential diagnosis
1.

2.

3.

4.

Laboratory findings
The laboratory findings for DLE are not specific. Patients
can present with anemia, leukopenia, thrombocytopenia,
elevated ESR levels, elevated serum globulin levels, high
IgG levels, presence of antithyroid antibodies and reduced
T-cell counts.
Urine examination and blood urea nitrogen has to be
done to rule out SLE and to know patients renal function.
Antinuclear antibodies are rarely present.
172

5.

Systemic lupus erythematosus (SLE): Systemic manifestations are present, LE cells are seen and antinuclear antibodies are present.
Polymorphous light eruption (PLE): Absence of antinuclear factor from the serum and of dermal-epidermal
immunoglobulin deposits.
Lupus vulgaris: Lesions usually occur at an early age,
and are rarely symmetrical, may be ulcerated and
usually show characteristic apple jelly nodules.
Lichen planus: The presence of concentrations of
lymphocytes in the immediate underlying lamina propria, deep focal accumulations of lymphocytes with
germinal centers and perivascular infiltrates of lymphocytes is helpful in differentiating lesions of LE and
those of LP. In more chronic lesions the presence of
hyperorthokeratosis and surface depressions containing keratin (keratin plugging) suggests LE than LP.
Seborrheic dermatitis, actinic keratosis and drug
eruptions.

The differential diagnosis for oral lesions include lichen


planus and leukoplakia. The classic oral discoid lesion has
three outstanding features according to Schiodt which can
be differentiated from other lesions; they are: a central
atrophic area with small white dots, a slightly elevated
border zone of irradiating white striae and telangiectasia.

Chapter 6 Red and White Lesions

Prognosis
The untreated skin lesions tend to be persistent, usually
heals with scarring. Less than 5% of the cases may convert
into SLE. Squamous cell and less commonly basal cell carcinomas occasionally occur in scars of DLE, particularly
on the scalp, ears, lips and nose.
Management
General measures Patient can be advised against excessive exposure to sunlight, UV light and heat. They can
be instructed to use umbrellas or broad brimmed hats.
Sunscreen creams or lotions can be used regularly.
Topical therapy 0.025% fluocinolone cream or 0.1% triamcinolone acetonide cream has shown to be effective.
Intralesional corticosteroid injections (triamcinolone acetonide 510 mg/ml) at 6 weekly interval are helpful in
resistant cases.
Oral therapy Oral prednisolone 0.5 mg/kg rapidly tapered
over 6 weeks or hydroxychloroquine, initially 200 mg
twice daily, reducing to 200 mg/day after response.
Alternatively chloroquine sulfate 200 mg twice daily
can be used. Other drugs that have been used include

aureomycin 69 mg/day, isotretinoin 2080 mg/day and


dapsone 100 mg/day.
When all of the above have failed in patients with
severe and persistent disease, then the following drugs can
be given.
Pulsed methylprednisolone 5001,000 mg/day for 23
days or cyclophosphamide 50200 mg/day or intravenous
pulses of above drugs at 10 mg/kg, at 34 weekly intervals.
Note: For a long time the terms precancerous lesions
and conditions have been used extensively in literature.
However, many authors believed that the use of the
prefix pre- implied that all the lesions and conditions
eventually turned into cancer, which is not true. In
order to simplify this understanding and avoid the confusion between lesions and conditions, the World
Health Organization in 2005 suggested the use of the
term potentially malignant disorders (PMDs).
As per this recommendation, PMDs are the disorders
in which the risk of malignancy is present in a lesion or
condition either at the time of initial diagnosis or at a
later stage.
Examples of high-risk PMDs are erythroplakia, leukoplakia, oral submucous fibrosis and erosive lichen planus.

173

CHAPTER

Vesiculobullous Disorders
Nagamani Narayana, Ravikiran Ongole

Classification of Vesiculobullous Lesions

Pemphigus Vulgaris
Paraneoplastic Pemphigus (Paraneoplastic
Autoimmune Multiorgan Syndrome)
Bullous Pemphigoid
Mucous Membrane Pemphigoid or Cicatricial
Pemphigoid

Predominantly Vesicular Lesions


Herpes Viruses

Herpes Simplex Virus (HSV) infections

Herpetic Whitlow and Herpes Gladiatorum

Recurrent Herpes Infections


Herpetic Labialis

Varicella Zoster Infections

Bullous Lichen Planus

Erythema Multiforme
Recurrent Erythema Multiforme

Complications Associated with Herpes Zoster

StevensJohnson Syndrome and Toxic


Epidermal Necrolysis (Lyells Syndrome)

Dermatitis Herpetiformis

Bullous Impetigo

Predominantly Bullous Lesions

Epidermolysis Bullosa

Pemphigus

Linear IgA Disease

Hand, Foot and Mouth Disease

Herpangina

There are a variety of oral lesions which clinically present


as vesiculobullous (VB) lesions. Although the lesions start
as vesicles or bullae they rupture early and appear as ulcerated or erosive areas. As a result they are better called ulcerovesiculobullous diseases. In this chapter common oral VB
lesions will be discussed.
A vesicle is dened as a uid-lled elevated lesion, less
than 1 cm in diameter. A bulla is a uid-lled elevated
lesion greater than 1 cm in diameter.

CLASSIFICATION OF VESICULOBULLOUS
LESIONS
I. Acute and chronic vesiculobullous lesions
(Table 1)
II. Based on the clinical presentation
1.

174

Predominantly vesicular
HSV infection
Varicella infection
Hand, foot and mouth disease

2.

Herpangina
Dermatitis herpetiformis
Predominantly bullous
Pemphigus vulgaris
Bullous pemphigoid
Benign mucous membrane pemphigoid
Bullous lichen planus
Erythema multiforme
StevensJohnson syndrome
Bullous impetigo
Epidermolysis bullosa
Linear IgA disease

III. Histopathological classification


Intraepithelial vesiculobullous lesions
HSV infection
Varicella infection
Herpangina
Hand, foot and mouth disease
Pemphigus
Familial benign chronic pemphigus

Chapter 7 Vesiculobullous Disorders

Table 1 Comparison between acute and chronic vesiculobullous lesions

Table 2

Site of latency of viruses

Name of virus

AcuteVB lesions

ChronicVB lesions

Duration

Short

Long

Age

Young

Middle agedolder

Etiology

Allergy, burns, viruses

Autoimmune

Examples

Herpes simplex infections

Pemphigus

Chicken pox

Bullous pemphigoid

Herpes zoster

Cicatricial pemphigoid

Herpangina

Bullous lichen planus

Hand, foot and mouth disease

Chronic herpes simplex

Erythema multiforme

Linear IgA disease

Site of latency

HSV 1 & 2, VZV

Sensory nerve ganglia

CMV

Lymphocytes, salivary gland tissue (rarely)

EBV

B lymphocytes and salivary gland tissue

HHV-6, HHV-7

CD4 lymphocytes

HHV-8

Still unknown but believed to be associated with B


lymphocytes circulating in hematopoietic system

Epidermolysis bullosa
Mucosal erythema multiforme
Subepithelial vesiculobullous lesions
Bullous pemphigoid
Cicatricial pemphigoid
Epidermolysis Bullosa
Dermal Erythema multiforme
Dermatitis herpetiformis
Linear IgA disease

It is estimated that out of the 80 known herpes viruses,


at least eight are known to infect human beings. The herpes viruses that are known to cause infection in humans
are herpes simplex virus (HSV 1 and 2), varicella zoster
virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus
(EBV), human herpes virus 6 (HHV-6), human herpes virus 7
(HHV-7) and human herpes virus 8 (HHV-8). These viruses
are usually transmitted from host to host by direct contact
or through saliva and genital secretions. Herpes viruses
are shed in the saliva of asymptomatic hosts.
When an individual comes in contact with the virus, primary infection is seen. Subsequently these viruses establish latency in the host. The site of latency for each form
of herpes virus is different (Table 2).

IV. Based on whether the lesions are infectious


or non-infectious

HERPES SIMPLEX VIRUS (HSV) INFECTIONS

Infectious VB lesions
Herpes simplex infections
Varicella infections
Herpangina
Hand, foot and mouth disease
Non-infectious VB lesions
Pemphigus
Paraneoplastic pemphigus
Bullous pemphigoid
Cicatricial pemphigoid
Erythema multiforme
Dermatitis herpetiformis
Epidermolysis bullosa acquisita
Linear IgA disease

PREDOMINANTLY VESICULAR LESIONS


Herpes Viruses
The word herpes is derived from the Greek word herpein
which literally means to creep. The word signifies the
creeping or spreading nature of the skin lesions caused by
many of the herpes viruses.

Etiology and pathogenesis


Herpes simplex virus infection is caused by two types of DNA
viruses namely HSV 1 and HSV 2. Characteristically, HSV 1
is responsible for infections involving the oropharyngeal
regions, dermatitis and meningoencephalitis (infections
above the waist) and HSV 2 is responsible for anogenital
infections (infections below the waist). However, changing
sexual practices have shown that these viruses may not
necessarily be responsible for infections of specific sites.
In contrast to other viruses HSV needs physical contact
to transfer infection. The incubation period ranges from
2 days to 3 weeks. After the primary infection the virus
hides within the trigeminal ganglia and becomes activated
when the environment is conducive for viral replication.
Approximately 90% of USA population is seropositive for
antibodies to HSV. Of this group only 1% exhibit primary
herpetic infections and 3040% demonstrate recurrent
infections. Primary HSV infections are usually seen after
6 months of age and peak at about 23 years of age.
Other specic HSV infections include herpetic whitlow,
herpetic gladiatorum, herpetic meningoencephalitis, herpetic
conjunctivitis, herpetic eczema (Kaposis varicelliform eruption) and disseminated herpes simplex of newborn.
175

Section III Mucocutaneous Disorders

Clinical features
Primary HSV infection Only 1% of the population in
USA exhibit all signs and symptoms of primary infection.
It usually affects young children and adolescents, and occasionally young adults. The primary HSV infection seldom
occurs in the first 6 months of life as the infant is protected
by the maternal antibodies that are still circulating in the
newborn.
Primary herpetic gingivostomatitis is characterized by
fever, malaise, anorexia, irritability and regional lymphadenopathy (especially, submandibular and supercial cervical group of nodes are involved). Subsequently the mouth
becomes sore and the individual may complain of burning
sensation in the mouth and difculty in swallowing. Apart
from the gingiva, the buccal mucosa, palate, tongue, tonsillar and pharyngeal region may be affected.
The gingiva is erythematous, boggy and bleeds spontaneously or on the slightest of provocation. As the disease
advances multiple tiny to moderately large (few mm to
almost a centimeter in size) yellow colored vesicles develop
that rupture to form shallow painful ulcers that are usually
covered by a grayish colored membrane. These ulcers are
bound by an erythematous halo.
Generally in about 2 weeks the lesion heals without
scarring. Immediately after the resolution of the primary
lesion, the virus travels along the nerve pathway and lies
dormant in the nerve ganglia regional to the site of the
primary infection. Within the regional ganglion the virus
incorporates its DNA into the hosts DNA thereby establishing the beginning of a life-long afiction. The trigeminal ganglion is usually the site for dormancy for HSV-1
and HSV-2.

HERPETIC WHITLOW AND HERPES


GLADIATORUM
Herpetic whitlow is an intense painful infection affecting
the fingers or toes of children, adults and healthcare workers. It typically involves the terminal phalanx of the index
and thumb fingers of children and healthcare workers. It is
believed that HSV-1 is responsible for 60% of the known
cases of herpetic whitlow and 40% are caused by HSV-2.
In children, most cases can be attributed to autoinoculation
of HSV-1 (infants suffering from acute herpetic gingivostomatitis who engage in thumb/finger sucking). In young
adults and elderly, herpetic whitlow is caused by autoinoculation of HSV-2, usually due to digital-genital contact.
Literature review reveals few reports describing herpetic
whitlow affecting the toe. Ozawa et al (2004) reported an
elderly patient who exhibited herpetic whitlow of the toe.
The lesions of herpetic whitlow are usually preceded by
prodromal symptoms of burning or tingling sensation and
pruritus of the affected digit and sometimes the whole limb.
176

As the lesion progresses, the involved digit reveals multiple


tiny vesicles which are extremely tender. The surrounding
area appears edematous and erythematous. The lesion may
rupture to form shallow ulcers and subsequently heal in
about 10 days time.
Similar vesicular lesions seen on the bodies of sportsmen (especially contact sports) and wrestlers is referred to
as herpes gladiatorum.
Investigations
Typical clinical features will usually suffice to make a clinical diagnosis. However for definitive diagnosis cytological
smears, antibody titers and viral isolation can be used.
Cytological smear requires deroong a fresh vesicle,
followed by scraping of the base of the lesion and the
smear made should be stained with Papanicolaous, Wrights
or Giemsas stain.
The characteristic ndings include the presence of multinucleated giant cells and intranuclear viral inclusion bodies such as Lipschtz bodies or Cowdry Type A (ovoid,
amorphous, eosinophilic bodies that exhibit peri inclusion
halo that is caused by the peripheral displacement of the
nucleolus and the nuclear chromatin). The cells exhibit
ballooning degeneration of the nucleus.
On biopsy the microscopic features include an ulcerated
epithelium with large keratinocytes showing glassy giant
marginated nuclei (Tzanck cells) (Figures 1 and 2).
Alternatively viral isolation can be done. It is one of the
most denitive methods of identifying HSV.
Serological tests can be used to detect antibodies in
patient suffering from primary HSV. For the test, blood
sample should be taken in the initial 3 days of an acute
infection. Alternatively a convalescent blood sample can
be obtained 4 weeks after the primary infection. It is
believed that the antibody titer should increase by four
times in convalescent serum sample for the diagnosis of
the primary infection.

RECURRENT HERPES INFECTIONS


Almost 3040% of the individuals exposed to HSV infection will exhibit at least one episode of recurrent herpes
infections. Recurrent infections can present either as
recurrent herpes labialis or recurrent intraoral herpes.
Various factors have been known to trigger these recurrent attacks such as stress, trauma, exposure to sunlight
and menstruation. These recurrent infections usually have
a milder course.

Herpetic Labialis
This is the most common secondary herpetic lesion,
usually following exposure to UV light or extreme cold.

Chapter 7 Vesiculobullous Disorders

Figure 1

Figure 3

Clusters of vesicles in a 26-year-old female, characteristic


of herpes labialis. Courtesy: Dr Nagamani Narayana,
Nebraska, USA

Photomicrograph of herpetic ulcer. H&E stain (10).


Arrow points to acantholytic cells and Tzanck cells.
Courtesy: Dr Nagamani Narayana, Nebraska, USA

Figure 2

treatment. These are also present with prodromal symptoms


such as paresthesia, swelling, burning and tingling.
Secondary herpetic lesions recur, and the recurrence
rate is 6 times/year. Secondary intraoral herpetic lesions
are seen in patients who are immunocompromised from
HIV/AIDS, pre-transplant and post-transplantation surgery
or post-chemotherapy. Intraorally ulcerations occur on
bound and mobile mucosa.
Yeo et al (2002) reported the presence of herpes labialis
in musicians who play woodwind instruments and brass
instruments such as the ute, saxophone, trumpet and horn.
They suggest that the herpetic lesions are precipitated by
mechanical trauma of the lips and stress suffered by the
musicians preparing for a performance. It is commonly
seen that the woodwind players tend to have lesions on
the lower lip and brass instrument players have herpetic
lesions on the upper lip.
Differential diagnosis

Photomicrograph (40). Arrow points to a Tzanck cell with


large molded nucleus. Courtesy: Dr Nagamani Narayana,
Nebraska, USA

Groups of vesicles appear at the vermillion border, and


rupture may result in crusty lesions. The lesions are tingly
and painful, normally healing within 2 weeks. The lesions
are highly contagious at the weeping stage.
Intraoral herpetic lesions are evident as clusters of vesicles (Figure 3). These vesicles rupture, leaving ulcerations
on bound mucosa, usually within 3 days of recent dental

Acute herpetic infections Streptococcal pharyngitis,


erythema multiforme and acute necrotizing ulcerative
gingivostomatitis (ANUG) have to be considered. All these
lesions will demonstrate systemic signs and symptoms.
Erythema multiforme lesions occur commonly on the lip
and less often on the gingiva. Lip lesions are bleeding
and crusty. In ANUG the gingival lesions demonstrate
punched-out interdental papilla with accompanying
bleeding and halitosis.
Secondary herpetic infections Consider aphthous ulcers
in the differential diagnosis of intraoral recurrent lesions.
Aphthous ulcers are found on mobile mucosa and do not
go through a vesicular phase. The ulcers are painful and
are difficult to differentiate from herpes simplex lesions.
177

Section III Mucocutaneous Disorders

Table 3

Treatment regimen for different kinds of HSV infection


Immunocompetent

Immunosuppressed

Primary herpetic gingivostomatitis


children

Symptomaticno aspirin or NSAIDs

Acyclovir capsules 200 mg or valacyclovir


caplets 500 mg

Primary herpetic gingivostomatitis


adult

Symptomatic, aspirin and NSAIDs, magic mouthwash

Acyclovir capsules 200 mg, 5 times daily


for 10 days or valacyclovir caplets 500 mg,
2 caplets twice daily for 5 days

Recurrent herpetic labialis

Abreva, Denavir 5%, valacyclovir 1,500 mg, single dose


or valacyclovir 750 mg, twice daily for 1 day started within
1 hour of onset of prodromal signs

Valacyclovir caplets 500 mg, 4 caplets taken


at prodromal symptoms and 4 caplets
12 hours later

Recurrent intraoral herpes

Acyclovir 200 mg 5 times a day for 10 days

Treatment
The aims of managing HSV infections are to inhibit autoinoculation and transmission. The management is targeted
at symptomatic relief. Topical and systemic antivirals like
acyclovir can be used (Table 3).
To be effective all treatment should be started within
72 hours of initial disease presentation. Patient compliance is shown to be better with fewer and shorter doses
(Whitley, 2006).
Prognosis
The main question arises should you treat these patients
when they have recurrent lesions. Universal precautions
including use of gloves enable us to do proceed with treatment. If the lesions are oozing and will transfer virus to
other sites and patient has no emergency it is advisable to
postpone treatment. If in an emergency application of
rubber dam may help in decreasing transmission of virus
to other sites.
Herpes simplex virus infections are described in detail
in Chapter 4 on Bacterial, Viral and Fungal Infections.

VARICELLA ZOSTER INFECTIONS


The primary and secondary infections are caused by VZV
belonging to Herpedes family. Chicken pox is the primary
infection and herpes zoster is caused by reactivation of the
VZV. This infection occurs due to inhalation and primary
infection occurs in children. Reactivation occurs when the
patient is stressed or immunosuppressed. It usually affects
dermatomes in the trunk, head or neck.
Clinical features
Primary infection (chicken pox) Primary varicella infection occurring in children is characterized by fever, chills,
malaise and headache with a quick rash. The rash is pruritic
178

and may get secondarily infected. The common sites of


involvement are the trunk, face and extremities. Intraorally,
the buccal mucosa, tongue, palate, gingiva and pharyngeal
mucosa are affected. Oral mucous membrane may show
multiple shallow ulcers preceded by thin walled vesicles,
which are usually not very painful.
In adults varicella may result in complications like
pneumonitis, encephalitis, and fetal abnormalities when
seen in pregnancy.
Secondary infection (herpes zoster) Herpes zoster is the
reactivated form of the VZV. It is also referred to as shingles. The word shingles is reportedly derived from the Latin
word cingulum which means girdle. The term girdle is
apt to describe the lesion of herpes zoster as it presents as
a unilateral rash that can wrap around the waist or torso
like a girdle. The word zoster is Greek word that refers to
a belt like object that is used by warriors to hold the armor
in place at the waist.
Secondary varicella zoster infection occurs in adults
with altered immune status or under stress and is unilateral. The main distinguishing feature of VZV is unilateral
and involves one of the branches of the trigeminal nerve.
Clinically tingling and vesiculation similar to herpes simplex are seen. Clinical appearance of these lesions is very
similar to herpes simplex except for the unilateral location
(Figures 4 and 5). Patients may complain of mild to severe
pain that may exacerbate on the slightest of touch. The
dermal lesions usually resolve in about a week forming
a scab.

Complications Associated with Herpes Zoster


The most common complication associated with HZ is the
development of postherpetic neuralgia. In this condition
the pain continues to persist even after the herpetic lesions
have resolved. The pain is typically presented as sharp or
burning pain. Postherpetic neuralgia is usually seen in
individuals over the 5th decade of life.

Chapter 7 Vesiculobullous Disorders

Figure 4

present with painful inammatory condition of the eye


along with impaired vision or transient blindness.
Some individuals exhibit only the prodromal symptoms
of pain and paresthesia without the development of visible
cutaneous rash. This phenomenon is referred to as zoster
sine herpete.
Ramsay Hunt syndrome is one of the rare manifestations
of HZV infection where geniculate ganglion is involved.
The facial and auditory nerves can be involved. The condition is characterized by facial paralysis, pain and vesicles
in the external auditory canal and pinna of the ear and the
oral cavity. Other associated ndings are tinnitus, vertigo
and ipsilateral hearing loss.
Investigations
Cytological smears derived from the vesicles reveal multinucleated giant cells along with intranuclear inclusion bodies. PCR and direct immunofluorescence assay are more
effective in diagnosing HZV infections.

Herpes zoster seen in a 70-year-old male with papular lesions


on the left half of his face. Courtesy: Dr Nagamani Narayana,
Nebraska, USA

Figure 5

Differential diagnosis
Recurrent herpetic lesions and aphthous ulcers should be
considered in the differential diagnosis of intraoral lesions.
Treatment and prognosis
In healthy patients if the diagnosis occurs within 72 hours
of initiation of the disease a course of acyclovir or valacyclovir can be administered. If the patient is seen later during the course of the disease symptomatic relief in the form
of magic mouthwash can be prescribed. In immunosuppressed patients a prescription of acyclovir or valacyclovir
can be administered. It is some belief that a prescription for
antiviral and corticosteroid therapy prevents postherpetic
neuralgia.

HAND, FOOT AND MOUTH DISEASE

Herpes zoster seen in a 70-year-old male with ulcerations in


the palate, characteristically involving one half of the palate.
Courtesy: Dr Nagamani Narayana, Nebraska, USA

The term hand, foot and mouth (HFM) disease was used for
the first time in 1960 following an outbreak of a relatively
mild febrile condition associated with papular and vesicular
lesions on the dermis and the oral cavity in Birmingham,
England.
Etiology

Herpes zoster is generally unilateral. However in immunocompromised individuals or an associated malignancy,


herpes zoster can exhibit a generalized involvement. Other
relatively uncommon complications involve encephalitis,
peripheral nerve palsies and myelitis.
Zoster ophthalmicus is seen when herpes zoster involves
the ophthalmic ganglion of the trigeminal nerve. Patients

Enteroviruses are known to cause HFM disease. The


enteroviruses that have been implicated are Coxsackie virus
serotype A 16, Coxsackie virus serotype A 4 to 7, 9, 10 and
Coxsackie virus serotype B 1 to 3 and 5. Asia Pacific region
including regions like Singapore, Japan, Indonesia, Malaysia
and Taiwan in the 1970s reported severe forms of HFM disease resulting in a widespread epidemic. The cause for this
179

Section III Mucocutaneous Disorders

epidemic was Enterovirus-71 A, B, C (EV 71). The EV-71


apart from causing HFM disease can also cause flaccid
paralysis, myocarditis, pulmonary hemorrhage, encephalitis and meningitis.
Deshpande et al (2003) isolated a strain of EV-71 from
the stool of a child suffering from acute accid paralysis
following administration of oral polio vaccine. They
termed this isolated strain as EV 71 D genotype.
Sasidharan et al (2005) studied 81 children (age group
of 7 months to 8 years) who presented with papulovesicular exanthems in Calicut, India. In their study 19 children
showed a signicant rise in the titers of IgM antibody
against EV-71.
Infection usually occurs by the fecal-oral route, leading
to viremia and invasion of the skin and mucosa. The incubation period is approximately 37 days.
Clinical features
Patients usually present with prodromal symptoms such
as low-grade fever, malaise, anorexia, myalgia, headache,
cough, rhinorrhea and sore throat. The skin of the hands
and feet along with the oral mucosa are involved. The oral
mucosa and the hand are almost always affected.
The skin lesions are characterized by the presence of
numerous erythematous macules in the initial stage. As
the disease progresses vesicles begin to appear in the macules which subsequently heal without crusts in about 10 to
14 days.
The common sites of involvement are the palms and
ngers of the hand, and soles and toes of the feet. Other
sites that are less commonly affected are the trunk, external genitalia and the buttocks.
Oral manifestations
The oral lesions usually occur before the skin lesions.
Multiple vesicles and ulcers may be seen affecting any
part of the oral mucosa. However the common sites that
are involved include the tongue, buccal mucosa and hard
palate. Patients usually complain of pain, sore throat and
dysphagia. Oral lesions usually heal without complications in about 7 days time.
The oral manifestations of HFM disease mimic lesions
of herpangina, acute herpetic gingivostomatitis, recurrent
herpetiform and minor aphthous ulcerations and erythema
multiforme.
Management
The disease is self-limiting and needs to be symptomatically managed. Systemic antipyretics (paracetamol suspension or tablet), topical analgesic mouthrinse (benzydamine
hydrochloride) and topical anesthetic agents (2% lignocaine gel) are effective in the management of fever and
sore mouth.
180

HERPANGINA
Herpangina was first described by John Zahorsky in 1920.
Herpangina is primarily caused by coxsackie virus A 1-10,
16, or 22. Other viruses that may cause herpangina are
coxsackie virus B 1-5, enterovirus 71 and echovirus 3, 6,
9, 11, 16, 17, 22, 25, and 30. Herpangina occurs in epidemics and usually occurs in the summer months. It usually
affects young children and adolescents. The mode of spread
is the fecal-oral route. The incubation period varies from
1 to 10 days and usually lasts 4 days.
Clinical features
Compared to hand, foot and mouth disease the disease
process is usually mild and patients may not exhibit overt
prodromal symptoms. Patients may present with mild rise
in temperature, malaise, anorexia, abdominal pain, sore
throat and cervical lymphadenopathy.
Oral manifestations
Oral manifestations are very typical of this condition.
Multiple minute vesicles and ulcers roughly measuring
12 mm in diameter are seen. The ulcers are surrounded by
an erythematous halo. These lesions are typically confined
to the posterior part of the oral cavity such as the faucial
pillars, tonsillar region, posterior pharyngeal region, soft
palate and uvula. Very rarely the posterior parts of the
buccal mucosa and tongue are involved. Patients may
complain of sore throat and difficulty in swallowing.
Management
Herpangina is a self-limiting disease. The fever associated
with this condition usually subsides within 34 days. The
oral ulcers heal within a week. The condition can be managed symptomatically with antipyretics and analgesic/
anesthetic mouthrinses.

DERMATITIS HERPETIFORMIS
Dermatitis herpetiformis (DH) is a rare, chronic, pruritic
immunobullous disorder of the skin that is associated with
gluten hypersensitivity. The condition is characterized by
the subepidermal deposition of IgA antibody against the
tissue transglutaminase. Antibody deposition leads to the
formation of dense neutrophilic abscesses, subepidermal
vesicles and bullae. Spurkland et al (1997) described the
genetic basis for DH. They showed that DH and celiac
disease are associated with class II HLA alleles A1*0501
and B1*02, which encode the HLA-DQ2 heterodimer.
Salmela et al (2001) showed that there was an upregulation of metalloelastase in both intestinal and lesional
skin.

Chapter 7 Vesiculobullous Disorders

Clinical features
Dermatitis herpetiformis usually affects individuals in the
2nd and 3rd decade of life. Dermal lesions are characterized by blisters over an erythematous or urticarial base.
The lesions are pruritic.
The common sites of involvement include the knees,
elbows, scalp, back and buttocks. It is believed that about
10% of the patients present with symptoms of celiac disease. DH is believed to be associated with some of the
autoimmune and connective tissue diseases such as Type I
diabetes mellitus, pernicious anemia, autoimmune thyroiditis, Sjgrens syndrome, lupus erythematosus, sarcoidosis,
scleroderma and psoriasis. DH has also been frequently associated with hypopigmentation.
Oral manifestations
Dermatitis herpetiformis can involve any part of the oral
mucosa. It manifests as multiple vesicles are bullae. These
fragile vesicles rupture immediately to form shallow painful ulcers.
Investigations
Histopathologically, presence of microabscesses in the
dermal papillae and subepithelial blister formation are
some of the findings associated with DH. The characteristic finding in DH is the presence of eosinophilia.
Direct immunouorescence test reveals the presence of
antibodies IgA, IgM and IgG at the junction of the dermis
and epidermis.
Dietrich et al (1999) demonstrated that the level of
immunoglobulin A autoantibodies to endomysium in patients
with DH was signicantly elevated.
Patients exhibit sensitivity to halogens.
Management
Dermatitis herpetiformis usually runs a prolonged course
and sometimes persists for life. Patients are advised to
avoid gluten in the diet. Dapsone is usually the drug of
choice. In the initial stages 50 mg/day is given and later
increased to about 300 mg/day as per the requirement.

PREDOMINANTLY BULLOUS LESIONS

Table 4

Antigens targeted by autoantibodies and corresponding forms of pemphigus

Antigens

Forms of pemphigus

Desmoglein 3

Predominantly mucosal
pemphigus vulgaris

Desmoglein 3, desmoglein 1 and


probably desmoglein 4

Mucocutaneous pemphigus
vulgaris

Desmoglein 1

Pemphigus foliaceous

Desmoglein 3, Desmoglein 1 and


plakin proteins

Paraneoplastic pemphigus

Adapted from Ettlin DA, Dent Clin North Am 2005;49:110.

short lived and easily break down resulting in ulcerations.


The term pemphigus is derived from the Greek word
pemphix which literally means a blister or bubble.
Chidgey (2002) in his update on desmosomes and disease
described pemphigus as an autoimmune disorder that
manifests with damage to the desmosomes of epithelial cells
induced by the activity of antibodies against transmembrane desmosomal glycoproteins belonging to the cadherin
supergene family of desmogleins (Dsg), resulting in intraepithelial immuno-deposits and breaking of intercellular
bridges. Table 4 summarizes the antigens targeted by autoantibodies in various forms of pemphigus.
Types of pemphigus
The three basic types of pemphigus depending upon the
extent of epithelial involvement and clinical presentation
include:
1.

2.

3.

Pemphigus vulgaris
Pemphigus vegetansvariant of pemphigus vulgaris
characterized by excessive granulation and crusting
Pemphigus foliaceous
Idiopathic pemphigus foliaceous
Drug induced pemphigus foliaceous
Pemphigus erythematosus
Endemic pemphigus foliaceous/fogo selvagem
Paraneoplastic pemphigus-associated with neoplasms
Pemphigus vulgaris and vegetanspemphigus foliaceous
and erythematosus
Affects entire epithelium
Involves oral mucosaaffects upper prickle/spinous
layer of epithelium of skin

Pemphigus
Pemphigus is an autoimmune disease characterized by
intraepithelial blister formation due to a breakdown in intercellular adhesion. This breakdown process is referred to as
primary acantholysis. Prior to the advent of steroids, pemphigus was fatal due to fluid loss and electrolyte imbalance and bacterial infection. Pemphigus presents itself as
clinically characterized vesicles and bullae. The lesions are

Pemphigus Vulgaris
Epidemiology
Pemphigus vulgaris occurs equally in both sexes during the
4th and 5th decades. Studies have shown a slight increased
incidence in Ashkenazi Jews and individuals with HLA-DR,
HLA-A10, HLA-DRB1 phenotypes. Other autoimmune
181

Section III Mucocutaneous Disorders

diseases such as myasthenia gravis, lupus eythematosus,


rheumatoid arthritis, Sjgrens syndrome and Hashimotos
thyroiditis also may be present.
Etiopathogenesis
The underlying mechanism causing the characteristic intraepithelial lesion of pemphigus vulgaris is the binding of
specific IgG antibodies to an antigen on the epithelial cell
membrane.
The stimulus that triggers the abnormal IgG production
is unknown. However certain exogenous factors such as
medications, dietary components and unknown environmental factors can induce or perpetuate pemphigus in a
genetically predisposed individual.
There is evidence that the binding of IgG antibody to
the pemphigus antigen leads to epithelial cell separation
by triggering either complement activity or the plasminogenplasmin system. IgG autoantibodies are said to target two
structural proteins of the desmosomes namely desmoglein 1
and desmoglein 3. Recently a new pemphigus antigen desmoglein 4 has been discovered and implicated in the
pathogenesis of pemphigus vulgaris.
Immunogenetic aspects of etiology
The increased incidence of pemphigus in Jews leads to the
proposition that there is a genetic predisposition to the
disease and initial studies examined the frequency of MHC
class I antigens in affected individuals. The first evidence
for genetically determined susceptibility was the demonstration by Krain et al (1973) of an increased frequency of
HLA-A10 in Caucasian patients with pemphigus vulgaris,
especially in those who were Jewish. A strong association
with HLA-A10 was also noted in Japanese patients by
Hashimoto et al (1977). Katz et al (1973) have reported an
association between HLA-A13 and pemphigus vulgaris,
but this has not been confirmed by others.
Subsequent studies have shown that almost all pemphigus
vulgaris patients have either HLA-DR4 or DRW6 haptotypes. Also the disease susceptibility has been linked to an
HLA-DQB gene.

Oral manifestations

Oral lesions usually appear first in this disease. Almost


8090% of the patients with pemphigus vulgaris develop
oral lesions sometime during the course of the disease
and in 60% of the cases oral lesions occur first.
The typical oral lesion begins as a bulla on a noninflamed base, which almost immediately ruptures to
produce shallow ulcer. The margins of the ulcer show
evidence of tissue tags.
The commonly involved sites are the buccal mucosa
(sites of trauma along the occlusal plane), gingiva and
palate (Figure 6A, B).
The edges of the shallow ulcers extend peripherally
over a period of weeks until they involve large portions of the oral mucosa.
Distal extension from the oral cavity causes involvement of the esophagus, pharynx and larynx, which
causes hoarseness of voice and dysphagia.

Clinical features

Differential diagnosis

Various bullous diseases that pemphigus vulgaris must be


differentiated are epidermolysis bullosa, erythema multiforme, bullous pemphigoid, cicatricial pemphigoid, bullous drug eruptions and other forms of pemphigus.
The histological presence of suprabasal intraepidermal
bulla with acantholysis is characteristic of pemphigus and
usually differentiates it from other similar diseases.

182

nail folds may be involved first, together with the oral


lesions.
Dermal lesions are characterized by bullae over the skin.
Fluid in the bullae appears clear at first but later it may
become hemorrhagic or even seropurulent. Initially
the bullae are tense, but soon become flaccid and rupture to form erosions which ooze and bleed easily. The
denuded areas sometimes are partially covered with
crusts with little or no tendency to heal and enlarge by
confluence. The healed lesions usually leave hyperpigmented patches. However in some instances these
solitary erosive areas may coalesce and involve extensive areas of the skin.
Nikolskys sign (first described by Pyotr Vasiliyevich
Nikolsky in 1896) is positive. The Nikolskys sign is positive if slight pressure or rubbing of the skin produces
lateral movement of the upper layers of the epidermis.
The Asboe-Hansen sign, or bulla spread phenomenon,
is positive in pemphigus. Gentle pressure on an intact
bulla will force the fluid to spread under the skin away
from the site of pressure.

Occurs in the 5th and 6th decade of life. Rarely affects


younger individuals.
Men and women are equally affected.
It most commonly occurs in Jews, Greeks, east Indians
and individuals from the orient.
Pemphigus vulgaris affects the mucosa and skin,
resulting in superficial blisters and chronic ulceration.
Various mucosal surfaces may be involved such as the
oral, ocular, nasal, pharyngeal, laryngeal, upper respiratory and anogenital mucous membranes.
The common sites of involvement are the groin,
scalp, face, neck, axillae and genitals. However the

Investigations
Cytology Smears taken from freshly opened vesicles are
usually preferred. Tzanck cells can be seen. These are epithelial cells that are free in the vesicular space and are

Chapter 7 Vesiculobullous Disorders

Figure 6
A

(A) Shallow ulcers on the buccal mucosa in a patient with pemphigus vulgaris.
(B) Shallow ulcers on the palate in a patient with pemphigus vulgaris. Courtesy: Dr Sumanth

characterized particularly by degenerative changes which


include swelling of the nuclei and hyperchromatic staining. This is also referred to as Tzanck test.
Shklar in 1971 reported that there is a marked increase
in RNA in the cytoplasm of these acantholytic cells as well
as in the epithelial cells at the oor of the vesicles.
Histopathology Tissue specimen for biopsies is obtained
from the active border of a denuded area, as intact blisters
are rarely seen.
The characteristic histological nding is an intraepidermal
bulla resulting from a loss of cell-cell adhesion of keratinocytes. Although the basal cells lose lateral desmosomal
contact with the adjacent cells, hemidesmosomes are intact.
Therefore, attachment to the basement membrane is maintained, giving the appearance of a row of tombstones.
Other pathologic changes seen are acantholysis, cleft
and blister formation in the interdermal areas just above
the basal cell layer and acantholytic cells. The separation
of cells in the layers of the stratum spinosum is known as
acantholysis. The loss of contact between the malphigian
cells begins with the detachment of tonolaments from
the desmosomes, loss of intercellular cement substances
and cellular degeneration with formation of the interepidermal cleft or bulla (Figure 7).
Immunofluorescent studies In pemphigus vulgaris the
antibody will bind the immunoglobulin deposits in the
intercellular substance and exhibits a positive fluorescence under the fluorescent microscope. This is termed
fish-net pattern of binding.
Management
Pemphigus was traditionally considered a potentially fatal
disease. Before the advent of effective therapies, mortality

Figure 7

Photomicrograph of the histological section of pemphigus


vulgaris. Courtesy: Department of Oral Pathology,
MCODS, Mangalore

approached 90%. However in the recent times the mortality rate is said to be approximately 10%.
Topical therapy
Eroded and crusted, painful skin lesions and the associated foul odor can be effectively managed by bathing
the area with 0.01% potassium permanganate solution
or 0.5% silver nitrate solution.
Alternatively the raw surfaces can be sprayed with
corticosteroids or 2% procaine hydrochloride.
Chlorhexidine mouthrinses can be used to alleviate
discomfort and malodor.
183

Section III Mucocutaneous Disorders

Painful oral ulcerations can be managed by topical application of viscous xylocaine especially before food intake.

Systemic therapy
Corticosteroids: Systemic administration of corticosteroids comprises three phases:
Control phase: Characterized by an initial high dose
corticosteroid administration to the point of obvious clinical improvement. Therapy is initiated by
giving 60160 mg of prednisone daily. If there is no
response even after a week, the dosage is doubled.
When new lesions cease to form and old lesions
heal, the dosage is decreased slowly. Lever (1977)
suggests 180360 mg of prednisone daily for
610 weeks.
Consolidation phase: In this phase the dosage of
prednisone is reduced over a period of several
weeks. According to Arnold, once the control over
the disease is achieved, an attempt to decrease the
steroid dose by transferring the patient to intramuscular injections of triamcinolone acetonide is
highly advisable.
Maintenance phase: The corticosteroids are gradually tapered down to alternate day dose and ultimately stopped. However this reduction in dosage
is made possible by replacing steroids with immunosuppressive drugs. The dosage of immunosuppressive drugs is reduced to zero in several months.
Immunosuppressive agents: Azathioprine 100200 mg
per day in conjunction with prednisone 150200 mg
daily can be used. Fellner et al reported good results
by combining 200 mg of prednisone with 100200 mg
cyclophosphamide.
Other agents that have been used with mixed
results are dapsone, gold sodium thiomalate and
aurothioglucose.
Plasmapheresis: It is particularly useful in patients who
are refractory to corticosteroids. It involves removal of
the circulating antibodies.
Photopheresis: This modality of treatment was described
by Rook et al. It involves administration of 8-methoxypsoralen followed by exposure of peripheral blood to
ultraviolet radiation, causing photoinactivation of WBC.
Immunomodulators: Chaffins et al in 1993 reported
that drugs like levamisole (100 mg/week), combination
of nicotinamide and tetracycline and oral prostaglandins
are effective in the treatment of pemphigus.

ulcerations and polymorphous skin lesions that progressed


to blisters on the trunk and extremities. It was found that
the autoantibodies from these patients reacted with an antigen complex composed of desmoplakin I and the 230-kd
antigen of bullous pemphigoid.
Paraneoplastic pemphigus is characterized by extensive
mucocutaneous erosions associated with a neoplasm such
as leukemia, lymphoma, sarcomas, thymomas, Castlemans
disease, Waldenstrms macroglobulinemia (high levels of
macroglobulin [IgM], increased serum viscosity, and lymphoplasmacytic inltrate in the bone marrow) pancreatic
carcinoma, bronchogenic squamous cell carcinoma or intraductal breast carcinoma.
It is believed that almost 80% of the patients suffer
from either non-Hodgkins lymphoma, chronic lymphocytic leukemia or Castlemans disease.
Clinical features
The predominant feature of paraneoplastic pemphigus is
painful mucous membrane erosions, of which oral erosions are the first sign of disease in 22.2% of cases. The most
common sites involved are the lips and oral mucosa, with
multiple, severe, persistent erosions. Symptoms of oropharyngeal involvement may include sore throat and dysphagia. Bilateral conjunctival involvement has been noted in
up to 72.2% of cases.
The skin lesions vary in shape and size, with a conuent erythema of the trunk, on which blisters and erosions
form. Erythematous maculopapular lesions with dusky centers or central vesicles may arise on the extremities, mimicking target lesions seen in erythema multiforme. Occasionally,
the lesions may be pruritic. Paraneoplastic pemphigus is an
extremely rare entity that has an onset at 60 years or older
and is more common in women than men.
Diagnostic criteria
Anhalt in 2004 proposed a four-point minimal criteria for
diagnosing paraneoplastic pemphigus:
1.

2.
3.
4.

Paraneoplastic Pemphigus
(Paraneoplastic Autoimmune Multiorgan Syndrome)
Anhalt and coworkers in 1990 were the first to suggest the
term paraneoplastic pemphigus for a clinically and immunologically distinct condition. They reported five patients
with underlying neoplasms associated with painful mucosal
184

Painful and progressive stomatitis which preferentially


involves the tongue. This criterion is the most characteristic of this condition.
Histologic findings of acantholysis or lichenoid or
interface dermatitis.
Demonstration of antiplakin autoantibodies, which are
the key serological markers for this condition.
Demonstration of an underlying lymphoproliferative
neoplasm.

Histopathologic features and immunological


studies
On histopathologic examination, paraneoplastic pemphigus appears to be a combination of pemphigus vulgaris and
erythema multiforme. There is suprabasilar acantholysis as

Chapter 7 Vesiculobullous Disorders

seen in pemphigus vulgaris, as well as basal cell vacuolation, lymphocytic exocytosis, and dyskeratotic keratinocytes typical of erythema multiforme.
Paraneoplastic pemphigus is distinguished from the
other forms of pemphigus as direct immunouorescence
reveals not only IgG and C3 deposits within the intercellular spaces but also along the basement membrane zone.
In the classic forms of pemphigus, indirect immunouorescence is positive only on stratied squamous epithelial substrates. However, in paraneoplastic pemphigus,
there is staining of other tissues, including the bladder, heart,
and liver. IgG autoantibodies are directed against desmoplakins I and II (components of the cytoplasmic plaque),
which are present in stratied squamous epithelium and
these other tissues.
Management and prognosis
There is little to offer in the treatment of paraneoplastic
pemphigus. If a benign tumor is resected, some patients
may go into remission. Unfortunately, the prognosis is
generally poor, and treatment is usually unsuccessful.
Immunosuppressive treatment and plasmapheresis have
not been effective; however, immunophoresis may be a
promising alternative.
Paraneoplastic pemphigus is a rapidly progressive bullous disease that is invariably fatal when associated with a
malignant tumor. When paraneoplastic pemphigus occurs
in the context of a benign neoplasm, the mucocutaneous
erosions will usually show gradual resolution after excision
of the tumor. It is important to remember that paraneoplastic pemphigus may precede the clinical appearance of
a neoplasm; therefore, it is mandatory that these patients
receive screening for neoplasms and regular follow-up care.
Other forms of pemphigus are described in Chapter 20,
Autoimmune Disorders.

Bullous Pemphigoid
Bullous pemphigoid (BP) was first described as a distinct
clinical entity by Lever in 1953. It is an autoimmune condition characterized by subepidermal blistering resulting
in large, tense bullae involving the skin and rarely the mucous
membrane. Autoantibodies are targeted at the components
of the basement membrane.
Pathophysiology
Kasperkiewicz et al (2007) reviewed the pathophysiology of
BP. They described that the autoimmune response in BP is
directed against two hemidesmosomal proteins within the
dermal-epidermal junction, namely BP180 and BP230 (also
known as BPAG1).
BP230 localizes intracellularly and associates with the
hemidesmosomal plaque. BP180 is a transmembrane
glycoprotein with an extracellular domain. Most of the

patients have autoantibodies binding to an immunodominant region of BP180, the non-collagenous 16A domain
(NC16A), which is located extracellularly close to the
transmembrane domain of the protein. Autoreactive T and
B cell responses to BP180 have also been found in patients
with BP.
Wohl and others (2008) studied the expression of vinculin in autoimmune cutaneous diseases. Vinculin is a cytoskeletal protein associated with cell to cell and cell to
matrix junctions, where it is thought to function as one of
several interacting proteins involved in anchoring F-actin
to the membrane.
On semiquantitative immunohistochemistry investigations they found that the expression and distribution of
vinculin are accentuated in patients with various skin
autoimmune diseases and appear to be stronger in diseases
involving the basement membrane.
Clinical features
Three distinct clinical types BP have been reported: the
commonly known adult form of BP and the relatively rare
forms of BP occurring at infancy and childhood.
The adult form of BP typically occurs between the 6th
and 8th decades of life. Males and females can be equally
affected. BP shows no ethnic or racial predilection. Dermal
lesions of BP are polymorphous in nature. Literature is
replete with reports of non-bullous forms of BP. They can
present as urticarial papules, plaques, vegetating forms,
nodular lesions, hyperkeratotic areas and erythematous and
eczematous lesions.
Initial lesions can usually present as urticarial eruptions that progress to bullae over weeks or months. The
bullae are pruritic, large and tense. However they generally persist longer due to their thick wall. Over a few days
the bullae rupture to form large and tender eroded regions.
These bullae can occur in any part of the body such as the
axillae, abdomen, legs, forearms and groin.
The bullae may contain clear uid or at occasions contain hemorrhagic content. The erosions heal without scar
formation.
Involvement of the mucous membrane is relatively
uncommon in BP compared to pemphigus vulgaris. The
oral cavity and genital and anal mucosa can be affected.
Oral bullae tend to rupture and form erosions or ulcers due
to the frequent micro trauma sustained during mastication.
Childhood BP though rare, is the most common IgG
mediated subepidermal bullous disease in children. It typically affects children below the age of 18 years and involves
the skin. The mucous membrane involvement is relatively
more common than the adult from of BP. The histopathologic
picture is similar to the adult form consisting of subepidermal bullae with variable amount of eosinophils and direct
immunouorescent studies show linear deposition of IgG
and/or C3 at the basement membrane zone.
185

Section III Mucocutaneous Disorders

The infantile form of BP is seen in infants in the rst


year of life. The mucous membrane involvement is slightly
more common than the adult form of BP. However the
characteristic feature is the involvement of hand and feet.
Maria Isabel Martinez-De Pablo and others (2007) suggest
that the IgA mediated autoimmune response predominates
in children in contrast to the IgG response that is predominant in adults, due to immunological immaturity or frequent exposure to infectious agents and/or vaccines.
Waisbourd-Zinman and others (2008) compared the
features of infantile BP with childhood BP. They found
that the number of infantile BP individuals is steadily increasing. The predisposition for acral (extremities like the hands
and legs) involvement is signicantly higher in infants.
However the genital involvement is very rare in infantile
BP compared to childhood BP. The deposition of IgM at
the basement membrane zone was higher in the childhood
variety of BP.
Oral manifestations
Bullous pemphigoid may or not affect the oral mucosa.
The incidence of oral involvement varies from 8 to 45%.
Some reports suggest that the oral lesions precede the skin
lesions.

Oral lesions are characterized by small bullae, which


form slowly and are less painful than those seen in
pemphigus vulgaris.
Buccal mucosal gingiva are relatively more commonly
involved.
Gingival lesions consist of generalized edema, inflammation and desquamation with localized area of
vesicle formation.
Oral lesions of bullous pemphigoid are clearly indistinguishable from oral lesions of cicatricial pemphigoid,
but remission of bullous pemphigoid is more common.
Bullous pemphigoid may coexist with lichen planus
and referred to as lichen planus pemphigoides.

Histopathological and immunofluorescent studies


Biopsy specimen from the perilesional area will show subepithelial separation. The epithelium is separated from the
connective tissue at the level of the basement membrane.
The typical nding in BP is the presence of eosinophils
within the content of the bullae. Other inammatory cells
such as lymphocytes and histiocytes are seen.
Electron microscopy reveals presence of the bullae within
the lamina lucida of the basement membrane resulting in
destruction of the anchoring laments and desmosomes.
Generally direct immunouorescence will be sufcient
to diagnose BP. However, some patients demonstrate circulating autoantibodies in the serum. Direct and indirect
immunouorescence reveals deposition of IgG and C3,
along the basement membrane zone in a linear fashion.
186

Management and prognosis


The clinical course of BP is limited, usually lasting from a
few months to years. It is seldom fatal. Almost 50% of the
patients exhibit remission in about 6 year duration.
Mild cases of BP can effectively be managed with topical corticosteroids. Systemic steroids such as prednisolone
is used for managing BP. Steroids can be tapered off with
improvement of the condition. Steroids can be used in
combination with immunomodulatory drugs such as dapsone, azathioprine and methotrexate.

Mucous Membrane Pemphigoid or Cicatricial


Pemphigoid
Mucous membrane pemphigoid is an autoimmune chronic
inflammatory disorder characterized by subepithelial blistering. It affects the skin, oral mucosa and ocular mucosa.
The name cicatricial pemphigoid is attributed to scarring
of the conjunctival mucosa.
Etiology and pathogenesis
The etiology of mucous membrane pemphigoid is unknown.
The pathogenesis is believed to be caused by the reaction
of IgG antibody with BP protein 180 and laminin 5 which
are present in lamina lucida of the basement membrane
complex resulting in breakdown of the attachment between
epithelium and connective tissue. The molecular players
responsible for the pathogenesis in blister formation are
still unknown.
Clinical features
Cicatricial pemphigoid is characterized by the presence of
vesicles which heal by scarring. These vesicles generally
tend to occur on the mucous membranes of the oral cavity
and conjunctiva. It has been reported that 90% of the
patients have oral involvement, 66% have conjunctival
lesions and approximately 25% have skin involvement.
Erosions and scarring may involve other mucous membranes, including those of the nasopharynx, oropharynx,
esophagus, larynx, vagina, penis and rectum. Esophageal
involvement can cause dysphagia secondary to brous
adhesions and scarring. Laryngeal erosions, edema and
scarring can be life threatening.
Oral lesions

Oral lesions can have two clinical presentationserosions on the non-keratinized mucosa/keratinized gingiva or desquamative gingivitis.
The common sites of involvement are the facial gingiva (64%), buccal mucosa (58%), palate (26%), edentulous alveolar ridge, especially under a prosthetic
appliance (16%), tongue (15%) and lower lip (15%).

Chapter 7 Vesiculobullous Disorders

Figure 8

Figure 10

Oral erosions with distinct margins on the palate in cicatricial


pemphigoid. Courtesy: Dr Sumanth

Figure 9

Symblepharon formation in cicatricial pemphigoid.


Courtesy: Dr Sumanth, Department of Oral Medicine and
Radiology, MCODS, Mangalore

Ocular findings

Subconjunctival scarring leading to blindness in about


15% of the patients.
Initial lesions may be limited to the upper tarsal conjunctiva, where they escape detection if the eyelid is
not everted.
Fibrous tracts fuse the scleral and palpebral conjunctiva resulting in symblepharon formation (Figure 10).
Histopathology

Desquamative gingivitis in cicatricial pemphigoid,


Courtesy: Dr Sumanth

Intact vesicles are rarely seen. However according to


Martin (1998), it is much more likely to see an intact
vesicle in cicatricial pemphigoid than in pemphigus as
the lesions are thicker walled and they are subepithelial.
The oral ulcers or erosions have a distinct margin. These
ulcers generally may become secondarily infected and
eventually heal in 34 weeks accompanied by scarring
and fibrosis (Figure 8).
Desquamative gingivitis can present as varying degree
of erythematous gingiva either localized or generalized.
Areas of erosion and denudation of the gingival surface
may be noticed (Figure 9).
Nikolskys sign is positive.
Spontaneous gingival bleeding may be seen.

The classic histological feature of mucous membrane pemphigoid is separation of the epithelium from the underlying connective tissue due to subepithelial separation.
A mixed inflammatory infiltrate is present in the underlying submucosa (Figure 11). Direct immunofluorescence
demonstrates linear deposition of IgG and C3 at the basement membrane (Figures 12 and 13).
Differential diagnosis
Mucous membrane pemphigoid must be differentiated
from pemphigus vulgaris, BP, lupus erythematosus, lichen
planus and paraneoplastic pemphigus. Bullous pemphigoid
is similar to mucous membrane pemphigoid, but BP is commonly seen in older women with circulating antibodies to
BP protein 230 in addition to BP antigen 180.
Treatment and prognosis
There is no single treatment for mucous membrane pemphigoid, as it must be tailored to the individual patient similar to pemphigus vulgaris. If extensive lesions involving
the oral cavity are present, systemic prednisone may be
187

Section III Mucocutaneous Disorders

Figure 11

Figure 13

Direct immunofluorescence pattern of benign mucous


membrane pemphigoid with C3 deposited against the
basement membrane. Courtesy: Dr Carol Stewart,
Florida, USA
Intact basal cells and sub-basal separation is seen in benign
mucous membrane pemphigoid. H&E stained section (20).
Courtesy: Dr Nagamani Narayana, Nebraska, USA

Figure 12

If lesions are extensive, immunosuppressive medications


such as azathioprine, mycophenolate and cyclophosphamide
may be necessary to manage symptoms. Also, a combination of tetracycline and niacinamide (niacin flush free),
500 mg taken three or four times a day for 6 months with
slow tapering, may be helpful in controlling the disease.
This latter combination has no known serious side effects
and is tolerated well by patients. It is important to educate
patients about the disease process and inform them that
treatment does not cure the condition, but only helps to
control the disease. The disease may cycle through periods
of exacerbations and remission over time. These patients
should be instructed to undergo an annual eye examination to avoid complications such as blindness.

BULLOUS LICHEN PLANUS

Direct immunofluorescence pattern of benign mucous


membrane pemphigoid with the autoantibody IgG-1
deposited against the basement membrane.
Courtesy: Dr Carol Stewart, Florida, USA

indicated. Normally a short course of prednisone is prescribed (40 mg per day for 7 days without tapering). Topical
steroids may be prescribed either alone or in addition
to systemic steroids, as ointments or oral rinse solutions.
188

Hebra used the term leichen ruber to describe lichen planus. However in 1869, Erasmus Wilson introduced the
term lichen planus (LP). It is believed that almost 0.5 to 1%
of the population is affected by lichen planus. Typically
lichen planus affecting the skin presents as violaceous,
polygonal flat topped papules, usually associated with
white striae on their surface.
Andreasen classied oral lichen planus into six types
namely reticular, plaque-like, erosive, papular, atrophic
and bullous lichen planus. It is believed that almost 25%
of the individuals present with oral manifestations alone
and about 50% of the patients with skin lesions have oral

Chapter 7 Vesiculobullous Disorders

lesions. Oral lesions are usually seen in women between


the 4th and 7th decades of life.
Bullous form of lichen planus is the rarest form of the
various varieties of oral lichen planus. Bullous oral lichen
planus manifests as small vesicles or bullae that rupture
easily to form shallow erosions. The lesions of bullous oral
lichen planus vary in size from few millimeters to several
centimeters in diameter. Patients usually complain of burning sensation and pain when the bullae rupture to form
erosive areas. These erosions mimic the clinical presentation of erosive lichen planus.
Bullous lichen planus commonly affects the buccal
mucosa (frequently seen adjacent to the second and third
molar teeth) and lateral margins of tongue. The less commonly affected sites include the gingiva and labial mucosa.
The exact etiology of bullous lichen planus is still unclear.
However it has been suggested that there is an immunologically induced degeneration of the basal cell layer of
the oral mucosa.
Histopathological findings
Histopathologic evaluation is required for identifying bullous lichen planus. The histopathologic features of dermal
lichen planus and bullous lichen planus are the same such
as hyperkeratosis and basal cell degeneration, a band of
inflammatory cells at the epithelial connective tissue interface, and Civatte bodies may be seen in the epidermal or
within the upper dermal cell layers.
Gawkrodger et al (1989) stated that the characteristic
feature of bullous lichen planus is the subepidermal clefting
leading to separation of the epithelium from the basement
membrane zone. However direct or indirect immunouorescence labeling is negative.
Lichen planus pemphigoides, bullous pemphigus and
pemphigus vulgaris have to be differentiated from bullous
lichen planus.
Management
Topical or systemic steroids, azathioprine, dapsone, cyclosporine, mycophenolate (Nousari et al, 1999) and retinoids
have all been used to manage bullous lichen planus. AnneMoon van Tuyll van Serooskerken et al (2007) successfully
treated bullous lichen planus on the lip with a combination of tretinoin 0.025% and triamcinolone 0.1%.

morphological appearances such as macule, papule, bullae


and crust, hence the name multiforme.
Previously, EM consisted of a disease spectrum that
ranged from a mild or minor form, severe or major EM,
StevensJohnson syndrome (SJS) and the most severe form
of the disease, toxic epidermal necrosis (TEN) or Lyells
syndrome.
The present understanding of the disease process, groups
EM minor and major into the EM spectrum and SJS and
TEN into another group. EM shows very minimal mucosal
involvement and less than 10% epidermal detachment.
Etiopathogenesis
It is estimated that almost 70 to 80% of the cases of EM are
triggered by HSV 1 and 2 infections. Besides HSV other
bacterial, viral and fungal infections have been reported to
trigger EM attacks. Viruses such as CMV, VZV and HIV
have been less frequently associated with EM. In children
Mycoplasma pneumoniae is reportedly a common etiological agent.
Other popular predisposing factors include drugs, chemicals and food coloring and avoring agents. Medications
that have been implicated in triggering EM include nonsteroidal anti-inammatory drugs, penicillins, phenothiazines, sulfonamides, barbiturates, hydantoins, ciprooxacin
and metformin. EM has also been reported to occur after
hepatitis B, smallpox and diphtheria-pertussis-tetanus
(DPT) vaccinations.
Aurelian et al (2003) and Kokuba et al (1999) studied the
association of EM with HSV and drug intake respectively.
They reported that the pathogenesis of herpes-associated
erythema multiforme is akin to a delayed type hypersensitivity reaction.
The disease begins with the transport of viral DNA
fragments to distant skin sites by peripheral blood mononuclear cells. HSV genes within DNA fragments are
expressed on keratinocytes, leading to the recruitment of
HSV-specic CD4 Th1 cells (helper T cells involved in
cell-mediated immunity). The CD4 cells respond to viral
antigens with production of interferon-gamma, initiating
an inammatory cascade.
However the drug-associated erythema multiforme lesions
exhibit positivity for tumor necrosis factor-alpha and not
interferon-gamma as in herpes-associated erythema multiforme lesions.

ERYTHEMA MULTIFORME

Clinical features

Erythema multiforme (EM) is an acute, reactive, self-limiting


and recurring mucocutaneous disorder that causes blistering and ulceration of the skin and mucous membranes.
Hebra in 1866 described EM as a benign condition characterized by skin lesions with concentric color changes,
which were distributed symmetrically. EM has various

Erythema multiforme may affect individuals of any age.


However, it is more common in young adults. Males and
females are equally affected. EM lesions seldom present
with prodromal symptoms. However mild and non-specific
symptoms are reported by some patients such as low-grade
fever, malaise, myalgia and diarrhea. The lesions of EM
usually appear within 23 days of onset of the disease.
189

Section III Mucocutaneous Disorders

Figure 14

Photograph showing the characteristic target lesion on the


patients back. Courtesy: Department of Oral Medicine and
Radiology, KLE Societys Institute of Dental Sciences,
Bangalore

The lesions of EM seldom involve more than 10% of the


surface area of the body.
Though the lesions of EM may involve any part of the
body, they are common in the sites of sun exposure, irritation or trauma. The face, oral mucosa, dorsal surface of the
hands, feet, elbows and knees are the sites that are commonly affected. The lesions of EM are usually restricted to
the oral mucosa unlike StevensJohnson syndrome.
The typical dermal lesions of EM are target, iris or bulls
eye lesion. These are asymptomatic, discrete, erythematous macules or papules set in a concentric ring pattern
usually comprising a central bulla. The iris lesion has three
concentric zones: a central dusky or darker red area (central bulla or area of necrosis), a paler pink or edematous
zone, and a peripheral erythematous zone (Figure 14).
The size of the iris lesion varies from a few mm to about
2 cm in diameter. These lesions usually resolve in about
3 to 5 weeks. However recurrence is generally reported
in EM.

Recurrent Erythema Multiforme


Schofield et al (1993) studied 65 patients who had recurrent EM. They observed that the mean number of recurrences was 6 per year and the mean duration of the
disease was 9.5 years.
Sen and Chua (2004) described that the HSV associated EM, mycoplasma associated EM and drug associated EM (repeated readministration) usually present
as recurrent EM. They state that infectious agents,
commonly viruses (due to reactivation), are likely to be
chiey associated with recurrent EM. It is estimated that
about 70% of cases have disease precipitated by HSV.

190

Some authors propose that though HSV infection may


not be readily apparent, subclinical attacks of HSV may
play an important role in the pathogenesis of the disease. Aurelian and others (1998) suggest that most cases
of recurrent EM may be herpes-related.
Sen and Chua (2004) reported that the recurrent
attack usually occurs even before the lesions from the
previous attack have completely resolved. They suggest
that the individuals suffering from recurrent EM report
two or more attacks of erythema multiforme per year,
with each episode lasting for about 2 weeks.
However one should not use the diagnostic term of
recurrent erythema multiforme for individuals with persistent skin lesions lasting weeks to months or a chronic
non-episodic course of the disease. One should not consider recurrent erythema multiforme when an individual
exhibits only acute mucosal inammation without skin
lesions.
The presence of the typical skin lesion is indispensable
for the diagnosis of the recurrent form of erythema multiforme.
Oral manifestations
Mucosal lesions of erythema multiforme are usually
restricted to the oral mucosa. However in the major form
of the condition mucosa of the eye and genitalia are frequently affected. It is estimated that approximately 40 to
60% of the individuals suffering from erythema multiforme major have oral manifestations. Lips and anterior
parts of the oral cavity are frequently affected. The oral
lesions of erythema multiforme are manifested as bullae,
erosions or ulcers, which may or may not be covered by
a pseudomembrane. Target lesions when seen are usually restricted to the lips. The vermillion border of the
lip exhibits a characteristic bloody crusted appearance
(Figure 15). These lesions generally heal without scarring. Gingiva is typically uninvolved.
Diagnosis
The diagnosis of EM is usually by the typical clinical
features. Histopathological features are not specific and
hence not diagnostic.
Perivascular inltrate of CD4 and CD8 lymphocytes
surrounding swollen blood vessels in the upper dermis
with papillary dermal edema is seen.
Vacuolar degeneration of the basal layer, subdermal
blister formation and epidermal necrosis of keratinocytes can be appreciated. The severity of the keratinocyte necrosis increases with the advancing lesion. The
individual necrotic keratinocytes are surrounded by CD8
cells termed satellite cell necrosis. An overproduction
of interferon-gamma by CD4 T helper-1 cells is seen in
the epidermis.

Chapter 7 Vesiculobullous Disorders

Figure 15

STEVENSJOHNSON SYNDROME AND


TOXIC EPIDERMAL NECROLYSIS
(Lyells Syndrome)
StevensJohnson syndrome (SJS) and toxic epidermal
necrolysis (TEN) are presently considered as a spectrum of
the same disease process. They can be distinguished from
erythema multiforme, varying only in the area of involvement of skin surface. The acute life-threatening conditions
are characterized by epidermal sloughing and mucositis
secondary to extensive keratinocyte apoptosis.
Etiopathogenesis

Bloody crusted appearance of the lips in a patient with


erythema multiforme. Courtesy: Department of Oral Medicine
and Radiology, MCODS, Mangalore

Ng and others (2003) used nested PCR to detect HSVDNA in skin biopsies with histologically proven EM.
Their ndings showed that PCR was positive in 60% of
the patients with HSV-related recurrent EM and PCR
was positive in 50% of the patients with idiopathic
recurrent EM.
Differential diagnosis
Dermal lesions may mimic lesions of hypersensitivity
reactions, drug eruptions and urticarial lesions. Intraoral lesions may resemble recurrent aphthous stomatitis, contact stomatitis and ANUG when the gingiva is
involved. Other conditions that can be considered are
pemphigus and varicella infections.
Management
Patients with mild EM usually do not require any form
of treatment as the condition is self-limiting. Since EM
is usually associated with HSV, oral acyclovir will minimize the duration of the condition. Topical steroids will
provide symptomatic relief.
The incidence of recurrent EM drastically falls down
following treatment with valacyclovir (5001,000 mg/
day) or famciclovir (125250 mg/day).
Severe recurrent EM can be managed with immunosuppressive agents. Dapsone or antimalarials (hydroxychloroquine) are the primary drugs in the treatment of
recurrent EM. Azathioprine also helps in suppressing the
condition, however it has many side effects. Davis et al
(2002) showed that mycophenolate mofetil can be used
as an effective drug in managing recurrent EM.

Murata and Abe (2007) reported that the keratinocyte apoptosis is brought about by the interaction of the fas receptor
and fas ligand. They also emphasize the need to evaluate
other genetic factors that may predispose to TEN and SJS.
Lerner et al (2000) used reverse transcriptase-PCR and
immuniperoxidase staining to study the role of inducible
form of nitric oxide synthetase in generating large amounts
of nitric oxide. They proposed that a large burst of nitric
oxide in TEN and SJS may cause the epidermal apoptosis
and necrosis.
In their study, inducible nitric oxide synthase was detected
by reverse transcription polymerase chain reaction. Strong
staining for inducible nitric oxide synthase was observed
in inammatory cells in the lower epidermis and upper
dermis.
Drugs are considered to be the most common cause of
SJS/TEN. The drugs that commonly cause SJS/TEN are anticonvulsants, sulfonamides, non-steroidal anti-inammatory
drugs and antibiotics.
SJS/TEN is considered as a cytotoxic immune reaction
causing destruction of keratinocytes expressing drug-related
antigens. TNF-alpha derived from macrophages and keratinocytes may play an important role in the pathogenesis
by inducing apoptosis of epidermal cells or by attracting
cytotoxic effector cells, or both. Drug metabolites such as
hydroxylamines and arene oxides derived from sulfonamides and aromatic anticonvulsants respectively, bind to
cell constituents if they are not rapidly detoxied by epoxide hydrolase. These metabolites act as haptens and render
the keratinocytes antigenic by binding to them. A defect
in the detoxication system may be the cause of the drug
eruption.
Clinical features
Toxic epidermal necrolysis and StevensJohnson syndrome
are usually seen in adults. Both the conditions occur as a
single episode and associated with drug exposure.
Literature review reveals various age groups being
involved. The involvement of men and women also shows
inconsistency.
191

Section III Mucocutaneous Disorders

Devi et al (2005) conducted a retrospective study of


41 patients diagnosed as SJS or TEN in India. The youngest patient in their study was 12 years old and the oldest
was 72. Majority of the patients were in the 2nd to 5th
decade of life.
Kaur et al (1990) evaluated 30 patients with drug
induced TEN in India. Their study revealed that the
peak incidence of TEN was in the 4th to 6th decades
of life.
It is believed that the increased incidence in the elderly
is due to their increased medicine intake and altered drug
metabolism with advancing age.
Kaur et al reported that males were slightly more commonly affected. Devi et al showed that males and females
were equally affected.
Most of the lesions of SJS or TEN are usually seen
within 2 months of drug intake.
However the recurrent lesions tend to appear within a
week of a repeat episode of drug intake. The striking feature of SJS and TEN are that they do not recur if the
offending drug is not taken, unlike in EM.
Prodromal symptoms such as fever, nausea, vomiting,
malaise, sore throat and rhinitis may been seen. This prodromal phase is followed by the appearance of macular
rashes affecting almost all regions of the body. It is
believed that TEN may be considered if the rash involves
more than 30% of the surface area of the body.
Severe sloughing of the skin and mucous membrane is
evident. Some authors describe this nding as scalded
appearance. Nikolskys sign and target lesions may be evident in some individuals. The oral, ocular and genital
mucosae are affected in SJS.
The ocular lesions present as corneal ulcerations, conjunctival scarring, uveitis and blindness. Genital lesions
are characterized by genital ulcers and phimosis. Extensive
sloughing may lead to secondary skin infection, sepsis,
renal failure and death.
Histopathological and laboratory studies
Extensive epidermal necrosis is appreciated. Markedly
lowered number of lymphocytes are seen around vessels.
Macrophages and dendrocytes are typically found in
large numbers in TEN. There is an elevated production of
tumor necrosis factor-alpha in the epidermis, unlike EM
(interferon-gamma is elevated in EM).
Inammatory cells are hardly found in TEN.
Acute phases of TEN may show a temporary phase of
reduced number of CD4 T-lymphocytes. Erythrocyte sedimentation rate may be elevated.
Management
The offending drug should be immediately identified and
discontinued. The following treatment guidelines followed
by University of Florida can be practiced effectively.
192

University of Florida management guidelines for


TEN and SJS
1.
2.
3.
4.

5.
6.

7.

8.
9.

10.

11.

12.
13.
14.
15.

16.
17.
18.
19.

Admit patient directly to the burn intensive care unit


(BICU) or an intensive care setting
Discontinue corticosteroids if they are being used to
treat the eruption
Discontinue unnecessary medications and suspect
medications
Obtain baseline laboratory tests, such as complete blood
count, liver function tests, metabolic panel, chest radiographs, and any other appropriate imaging or serologic
tests, including an immediate (stat) immunoglobulin
A (IgA) serum level
Look carefully for evidence of infection
Obtain punch biopsies of skin for diagnosis confirmation. An alternative for rapid diagnosis is removal of
a bulla roof for immediate frozen sections to differentiate between TEN and staphylococcal scalded skin
syndrome (SSSS)
Culture skin, blood, body orifices (as appropriate), and
urine daily to monitor for early infection, and keep
abreast of changing antibiotic sensitivities
Use systemic antibiotics only for documented infections or signs of sepsis
Place large-bore intravenous lines or a central venous
line in an area of uninvolved skin to ensure adequate
intravenous access
If within 4872 hours of bulla onset, use intravenous
immunoglobulin (IVIG), sucrose depleted, 1 g/kg/day for
3 days infused over 4 hours. If 72 hours have passed,
but the patient is still actively progressing with new
lesions, IVIG may still be useful
Monitor fluid and electrolytes closely and begin total
parenteral nutrition (TPN) in patients unable to take
nourishment. Fluid replacement need not be as
aggressive as for burns of same extent
Debridement of necrotic and desquamating areas may
be performed
Consult ophthalmologist to assess ocular involvement
Consult otorhinolaryngologist to evaluate extent of
upper respiratory tract involvement
Further consultations driven by patient condition (i.e.
internal medicine to manage comorbidities, pulmonary medicine for airway involvement, gastroenterology for alimentary involvement, and gynecology or
urology for genitourinary involvement)
Physical therapy daily to preserve limb mobility
Pain relief measures, such as patient-controlled analgesia (PCA) pump
Hydrotherapy (whirlpool) if needed
Non-stick dressings to denuded areas, saturated with
0.5% silver nitrate impregnated every 38 hour as
needed. Pre-impregnated dressings with silver nitrate
are an alternative

Chapter 7 Vesiculobullous Disorders

20. Avoid sulfa-containing topical or systemic preparations


21. Oral care with chlorhexidine rinses and white petrolatum to lips
22. Air-fluidized bed to minimize shearing force
23. Keep room warm to prevent hypothermia
24. Foley catheter and nasogastric tube placement only
when necessary
25. Avoid unnecessary manipulation of skin. Adhesive tape
should not be applied directly to involved skin when
possible
26. Baby shampoo for cleansing hairy areas daily
27. Mineral oil or petrolatum for dry skin
28. Skin substitute grafting (porcine xenografts or artificial skin) based on BICU protocol.

BULLOUS IMPETIGO
Impetigo is a bacterial infection that affects the superficial
areas of the skin. It commonly affects infants and young
children in the age group of 25 years. However it has
known to affect individuals of various age groups. It is
believed that impetigo is the most common skin disease to
affect children.
Donovan et al (1992) in their study to evaluate whether
bullous impetigo in homosexual men is a risk marker for
HIV-1 infection, concluded that bullous impetigo if seen
in an adult, it could prove to be a clinical indication that
a person is either infected with HIV-1 or is in close (possibly sexual) contact with a person with HIV-1 infection.
It is a highly contagious infection caused primarily by
Staphylococcus aureus. However some cases have been
reportedly caused by group A beta-hemolytic streptococcus (Streptococcus pyogenes) alone or in tandem with
Staphylococcus aureus. The mode of transmission is generally by direct contact.
Types
There are two forms of impetigo, namely, bullous impetigo
and non-bullous impetigo (impetigo contagiosa). The basic
difference between the two is that the non-bullous variety
represents the host response to the staphylococcal infection,
whereas in bullous impetigo the staphylococcal toxin is
responsible for the condition and not the host response.
Clinical features
Bullous impetigo is usually seen in infants. But it is seen
to affect children and adults likewise. Unlike the nonbullous form which may be caused by a combination of
staphylococcus and streptococcus. Bullous forms is always
caused by the toxins produced by Staphylococcus aureus.
Staphylococcus aureus, phage group II type 71 is the predominant causative organism. This strain of bacteria produces an exfoliatin toxin that causes subcorneal epidermal

cleavage. The exotoxin produced by staphylococci is


directed against epidermal desmoglein 1. Itzhak Brook
(1980) reported a case of bullous impetigo caused by
Streptococcus salivarius.
Bullous impetigo usually occurs in crowded places and
unhygienic surroundings. Presence of large families in clusters will help the disease spread through direct contact.
When the condition disseminates to affect various parts
of the body, it is referred to as staphylococcal scalded skin
syndrome. This is usually seen in immunocompromised
patients. The toxin may disseminate hematogenously and
lead to generalized staphylococcal scalded skin syndrome.
Bullous impetigo can affect any part of the skin and mucosa.
Literature review reveals few reports of buccal mucosa
involvement.
The initial lesion appears as small to large, supercial,
fragile bullae. These bullae usually occur on the extremities,
axille and the trunk. Some patients report history of trauma
or infections. These bullae are generally painless. However
some patients experience burning or itching sensation.
The bullae measure about 2 to 5 cm in size and usually do
not rupture easily. They contain a serous clear yellow uid
that subsequently turns cloudy and dark yellow. In about
34 days time the bullae rupture and produce a thin, light
brown, varnish-like or honey like crust. A characteristic nding in bullous impetigo is a collarette of scale surrounding the blister roof at the periphery of ruptured lesions.
Management and prognosis
Impetigo is a self-limiting condition and it usually resolves
spontaneously in about 2 weeks without scar formation.
The topical antibiotics mupirocin and fusidic acid are
effective. Orally administered systemic antibiotics can be
used in severe forms of the condition.

EPIDERMOLYSIS BULLOSA
Epidermolysis bullosa (EB) comprises a group of inherited
mucocutaneous disorders characterized by blister formation due to a defect in collagen metabolism. These blisters
may arise spontaneously or as a result of mild trauma.
These inherited forms of epidermolysis bullosa should be
differentiated from epidermolysis bullosa acquisita which is
an autoimmune disorder. Some authors prefer to use the term
hereditary epidermolysis bullosa to refer to the forms that are
generally inherited. EB is a genodermatosis. The pattern of
inheritance may either be dominant or recessive. The recessive forms of EB are relatively more severe and aggressive.
Types of EB based on ultrastructural features
Jo-David Fine et al (2008) The classification of inherited
EB: Report of the Third International Consensus Meeting
on Diagnosis and Classification of EB
193

Section III Mucocutaneous Disorders

Epidermolysis bullosa simplexintraepidermal cleavage is seen (epidermolytic)


Junctional epidermolysis bullosaintralamina lucida
cleavage (lamina lucidolytic)
Dystrophic epidermolysis bullosasublamina densa
cleavage (dermolytic)
Kindler syndromemixed
Epidermolysis bullosa simplex
There are two basic types of EB simplex
Suprabasal EB simplex
Lethal acantholytic
Plakophilin deficiency
EBS superficialis
Basal EB simplex
Localized (previously called EBS, Weber-Cockayne)
EBS, Dowling-Meara
EBS, other generalized (the earlier term EBS,
Koebner is no more used and presently included in
generalized EBS)
EBS with mottled pigmentation
EBS with muscular dystrophy
EBS with pyloric atresia
EBS, autosomal recessive
EBS, Ogna
EBS, migratory circinate
Junctional epidermolysis bullosa
There are two basic types in JEB
JEB, Herlitz
no subtypes
JEB, other
JEB, non-Herlitz, generalized (was previously generalized atrophic benign EB)
JEB, non-Herlitz, localized
JEB with pyloric atresia
JEB, inversa
JEB, late onset (was previously known as EB
progressiva)
Laryngo-onycho-cutaneous (LOC) syndrome
Dystrophic epidermolysis bullosa
There are two subtypes
Dominant dystrophic epidermolysis bullosa
DDEB, generalized
DDEB, acral
DDEB, pretibial
DDEB, pruriginosa
DDEB, nails only
DDEB, bullous dermolysis of the newborn
Recessive dystrophic epidermolysis bullosa
RDEB, severe generalized
RDEB, generalized other
RDEB, inversa

194

RDEB, pretibial
RDEB, pruriginosa
RDEB, centripetalis
RDEB, bullous dermolysis of the newborn
General clinical features and oral manifestations
Epidermolysis bullosa simplex The condition is characterized by the presence of the presence of multiple vesicles
or bullae at birth or some time after birth.
The common sites that are involved are the hand and
feet. Oral mucosa is seldom affected.
The condition is self-limiting. The vesicles heal in about
a week to 10 days time without the formation of scars.
Most of the children are free of this condition at puberty.
Junctional epidermolysis bullosa The junctional variety
of epidermolysis bullosa is a severe form that occurs at
birth and usually death ensues in the first 3 months of life.
In very severe forms the skin tends to shed increasing the
risk for superinfection and septicemia.
Children may present with hoarse cry, cough and breathing difculty. Apart from the skin, oral, ocular, pharyngeal
and genitor urinary mucosa may be affected.
The oral lesions manifest as bullae and erosions affecting
almost any part of the oral cavity. Infants may have difculty in feeding.
Dystrophic epidermolysis bullosa The dominant variety
usually occurs at birth and occasionally at adolescence. At
young age the condition has a generalized involvement.
As the age advances the condition tends to be confined to
a particular region.
Bullae are seen on the feet, ankles, knees and elbows.
Nails are typically dystrophic. Other features that may be
seen are palmoplantar hyperkeratosis and hypertrichosis.
The bullae rupture and heal with extensive scarring.
Milia (tiny keratin lled cysts) may be seen on the face.
Compared to the recessive form of the condition, the oral
involvement is limited. Occasionally bullae may be seen in
the oral cavity. Teeth are seldom affected.
The recessive form of the condition is usually seen at
birth or in neonates. Bullae are seen in the sites predisposed
to pressure or mild trauma such as the buttocks, knees,
elbows, feet and ngers. The bullae subsequently rupture to
reveal raw erosive areas. These heal by extensive scarring.
Scarring of the ngers may result in club like sts.
Like the dystrophic variety, nail may be absent altogether
or may be defective. Oral manifestations are commonly
seen. Bullae may be seen affecting any part of the oral
mucosa. With the rupture of the bullae, painful erosions are
seen which heal by scarring. Extensive scarring of the oropharyngeal and esophageal tissues may lead to hoarseness
of voice and difculty in feeding and swallowing. Dental
tissues are usually affected. Congenitally missing teeth,
malformed or hypoplastic teeth are usually seen.

Chapter 7 Vesiculobullous Disorders

Linear IgA Disease


Linear IgA disease has also been referred to as linear IgA
bullous dermatosis (LABD) and linear immunoglobulin A
dermatosis. It was considered to be a variant of DH or BP.
However, it is presently considered as a separate disease
entity.
LABD is a chronic subepidermal bullous disease associated with linear deposition of IgA along the basement
membrane. The disease can be idiopathic or drug-induced.
Other provoking factors for LABD are viral infections,
immunological disorders and malignancies.
LABD affects both children and adults and the disease
process is similar in both. However, when the disease occurs
in children it has been referred to as chronic bullous dermatosis of childhood.
Patients suffering from Linear IgA disease produce IgA
antibodies against the BP-180 glycoprotein (type VII collagen) which is a component of the hemidesmosomes.
Antibody deposition leads to complement activation and
neutrophil chemotaxis, which results in loss of adhesion at
the dermal-epidermal junction, thereby forming a bulla.
Marinkovich et al (1996) reported that LAD-1 (a basement
membrane component) is one of the targets of autoantibodies in patients with LABD.
Clinical features
Dermal lesions mimic lesions of DH or BP. Vesiculobullous
rash may be appreciated over a normal or erythematous
dermis. The bullae may contain serous sero-hemorrhagic
content. The common sites of involvement include the
extensor surfaces of the hand and feet, lower trunk, perioral region, genital region and buttocks. In adults, the
trunk and the limbs are usually affected. Lesions may not
be symmetric. The bullae may arrange in a herpetiform
manner or clusters of discrete bullae, which has been popularly termed as jewels sign. Another characteristic finding is the presence of vesicles or bullae bordering the
annular lesion which is termed string of beads sign.
Dermal lesions usually heal without scarring.
Mucosal manifestations
It is estimated that approximately 80% of patients suffering from LABD exhibit mucosa involvement. Oral, nasal,
ocular and/or genital mucosa can be involved. Mucosal
lesions heal with significant scarring. About 60% of these
patients show involvement of the oral mucosa.
Any part of the oral mucosa can be affected. Gingival
involvement can present as desquamative gingivitis. Oral

lesions are typically bullae which rupture to form tender


erosions or ulcers.
Patients complain of burning sensation and discharge
from the eye when the ocular mucosa is affected. Common
ophthalmic ndings are subconjunctival brosis, symblepharon formation and cicatricial entropion with trichiasis.
Drug-induced LABD
The clinical and histological picture is the same as the idiopathic form of LABD. However, like the name suggests LABD
develops after drug administration. Literature review reveals
various drugs that have known to produce LABD, such as
vancomycin, diclofenac, lithium, captopril, cyclosporine
glibenclamide, interferon-gamma, iodine contrast agent,
phenytoin sodium, somatostatin and sulfamethoxazole/
trimethoprim.
Disease associations
LABD has been reportedly associated with infections, malignancies and other autoimmune disorders. However many
of the associations may simply be coincidental in nature.
Few of the commonly associated infections with LABD
are typhoid, tuberculosis, varicella, herpes zoster, and
upper respiratory tract infections.
It has been reported that almost 5% of the patients with
LABD may have an associated malignancy such as Hodgkins
disease and non-Hodgkin lymphoma, chronic lymphocytic
leukemia, plasmacytoma, multiple myeloma and squamous
cell carcinomas.
LABD has also known to occur along with other autoimmune disorders such as Crohns disease, ulcerative colitis, multiple sclerosis, systemic lupus erythematosus and
rheumatoid arthritis.
Management and prognosis
The lesions of LABD generally follow a chronic course with
periods of acute exacerbations. Spontaneous remission
may be seen in some patients. However almost all patients
exhibit recurrence. Dermal lesions are managed with dapsone or sulfapyridine. However mucosal lesions are usually refractory to dapsone. Prednisolone along with dapsone
will usually help in controlling the condition. Lewis et al
(2007) successfully treated a patient suffering from LABD
with oral mucosal involvement using mycophenolate, an
antiproliferative immunosuppressive agent. They reported
that mycophenolate can be used as a useful adjunct to manage oral lesions of LABD, when other immunosuppressants
are contraindicated.

195

CHAPTER

Oral Ulcerative Diseases


Keerthilatha M Pai, Braz Campos Durso

Classification of Oral Ulcers

Stomatitis Medicamentosa
Stomatitis Venenata

Traumatic Ulcers

Ulcers Associated with Infections

Herpes Simplex Infection

Erythema Multiforme

Varicella Zoster Infection

Blood Disorders Causing Oral Ulcers


RBC Disorders
WBC Disorders

Chicken Pox
Herpes Zoster

Coxsackie Virus Infection

Herpangina
Hand, Foot and Mouth Disease

Acute Necrotizing Ulcerative Gingivitis

Tuberculosis

Syphilis

Deep Fungal Infections


Aspergillosis
Histoplasmosis
Mucormycosis
Cryptococcosis
North American Blastomycosis
South American Blastomycosis

Immunologic Disorders
Aphthous Ulcers

Dermatological Disorders
Pemphigus
Bullous Pemphigoid
Cicatricial Pemphigoid

Gastrointestinal Disorders Associated with


Oral Ulcers
Gastroesophageal Reflux Disease
Crohns Disease
Ulcerative Colitis
Celiac Disease

Neoplastic Ulcers

An ulcer may be described as breach in the continuity of


the surface epithelium of the skin or mucous membrane to
involve the underlying connective tissue as a result of micro
molecular cell death of the surface epithelium or its traumatic removal.

CLASSIFICATION OF ORAL ULCERS

Classification based on mode of onset


and clinical presentation

Ulcerative lesions affecting the oral cavity can be categorized based on the etiology or based on the mode of onset
and clinical presentation.

Classification based on etiology

196

Drug-induced Oral Ulcers

Traumatic
Infectious (bacterial, viral and fungal infections)
Drug induced

Ulcers associated with blood dyscrasias


Immune mediated
Oral ulcers associated with dermatological disorders
Oral ulcers associated with GI disorders
Neoplastic oral ulcers
Ulcers of uncertain etiology.

Single ulcers
Traumatic ulcer
Tuberculous ulcer
Syphilitic ulcer
Histoplasmosis
Blastomycosis
Mucormycosis
Neoplastic ulcers

Chapter 8 Oral Ulcerative Diseases

Multiple ulcers
Acute multiple ulcers
Herpes virus infections
Primary herpes simplex virus infections
Coxsackievirus infections
Varicella zoster virus infection
Erythema multiforme
Contact allergic stomatitis
Oral ulcers secondary to cancer chemotherapy
and/or radiotherapy
Acute necrotizing ulcerative gingivitis
Chronic multiple ulcers
Pemphigus
Subepithelial bullous dermatoses
Herpes simplex virus infection in immunosuppressed patients
Recurring oral ulcers
Recurrent aphthous stomatitis
Behets syndrome
Recurrent herpes simplex virus infection
Cyclic neutropenia
Chronic idiopathic neutropenia.
Flowcharts 1 and 2 summarize acute ulcers that are recurring in nature and those that occur as an isolated episode.

TRAUMATIC ULCERS
Traumatic injuries involving the oral cavity may lead to
the formation of surface ulcerations. Although the exact
incidence of these ulcerations is not known they are one
of the most common ulcers seen affecting the oral cavity.

Types of Trauma

Mechanical (sharp tooth, overextended denture, orthodontic brackets, toothbrush, ill-fitting dental prosthesis, etc.)
Chemical (aspirin, concentrated clove oil, sodium hypochlorite, hydrogen peroxide, root canal medicaments,
chemotherapy, etc.)
Thermal (extremely hot or cold insults such as hot
cheese, hot beverages, popsicle) (Figure 1)
Radiation (used in treatment of head and neck cancer)
Self-inflicted (self-harm)
Iatrogenic (injuries caused by high speed rotary instruments, cotton rolls, etc.)

The oral cavity is prone to injuries from events such


as accidentally biting oneself while talking, sleeping, mastication or as a result of an epileptic seizure. Fractured,
malposed, or malformed teeth, as well as the premature
eruption of teeth, can contribute to the formation of surface ulceration.

Flowchart 1
Recurrent episodes

Systemic symptoms

Absent

Trauma

Present
IBD
Location

Keratinized

Cyclic neutropenia

Nonkeratinized

Sprue
Behcets

RAS

Culture
+
HSV

Atypical RAS
HIV
Cyclic neutropenia

HIV
FAPA
Magic

Algorithm to evaluate acute oral ulcers that are recurrent


in nature. (Reprinted with minor modifications from
Bruce AJ (2003), Acute oral ulcers, Dermatologic Clinics,
Vol. 21, p. 2, with permission from Elsevier)

Nocturnal parafunctional habits, such as bruxism may be


associated with the development of traumatic ulcers of the
buccal mucosa, the labial mucosa and the lateral borders of
the tongue. Ulcerations may be the result of voluntary, selfinduced, and deliberate acts by patients with physical or
psychological symptoms who suffer from attention seeking
behavior. These ulcers are characteristically present over
visible surfaces such as the lips, corner of mouth and facial
aspects of gingiva (ulcers caused by gingival picking).
Bulimic individuals may present with nail marks or minute
pinpoint red spots and/or ulcerations over the palate
which is brought about by the frequent efforts to vomit.
Newborns and infants may present with sublingual
ulcerations (RigaFede disease). These ulcers may occur as
a result of chronic mucosal trauma due to adjacent anterior
natal or neonatal teeth. The trauma is often associated with
breast feeding. The lingual frenum may be ulcerated by
repeated trauma because of the frenum rubbing against the
mandibular incisors teeth in cunnilingus and in recurrent
coughing episodes.
Young children are commonly susceptible to electrical
and/or thermal burns of the lips and commissure areas.
197

Section III Mucocutaneous Disorders

Flowchart 2
Single episodes

Infection

Drugs

Iatrogenic

Trauma
Radiation

Bacterial

Viral
Chemotherapy
ANUG

HSV

Syphilis

VZV

Gonorrhea

Coxsackie

Tuberculosis

Rubeola

Rhinoscleroma

EBV

Algorithm to evaluate acute oral ulcers that occur as an isolated episode. (Reprinted with minor modifications from
Bruce AJ (2003), Acute oral ulcers, Dermatologic Clinics, Vol. 21, p. 2, with permission from Elsevier)

Figure 1

A thermal burn on the hard palate secondary to intake of


a hot bread sandwich. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

Extensive ulcerations with necrosis may develop. Children


in this age group have a tendency to chew their lips
immediately after surgical removal of teeth under the
inuence of local anesthesia.

associated with areas of erythema. The ulcer may reveal the


presence of a central yellowish purulent exudate. Occasionally the border of the ulcer is indurated.
Ulcerations can occur throughout the oral cavity. Ulcers
associated with mechanical trauma are often found on the
buccal mucosa, the labial mucosa of the upper and lower
lips, and the lateral border of the tongue (Figure 2). The
mucobuccal folds, gingiva, and palatal mucosa may also
be involved. Most lesions associated with electrical burns
occur in children and involve the lips and commissural
areas. Ulcers formed due to thermal injuries are generally
seen to occur on the posterior regions of the buccal mucosa
and the palate.
Caustic chemical agents can damage any area of the
oral mucous membrane. However, they are commonly seen
on the gingival margins and buccal vestibular regions of
the oral cavity. Very frequently these ulcers are covered by
a whitish pseudomembrane which when peeled leaves
behind a raw ulcerated surface (Figure 3). Some patients in
the Indian subcontinent use cloves and topical pain balms
meant for extraoral application over the gingiva to relieve
tooth pain. Hence, most of the chemical burns are generally seen adjacent to carious teeth.
Diagnosis

Clinical features
In most cases, the source of the injury is identified. The
patients usual complaint is pain or a painful ulceration.
Individual lesions usually appear as shallow or deep ulcers
198

The diagnosis of traumatic ulcerations is based on the history of trauma or insult (hot/cold or radiation therapy) prior
to onset of ulcer. Mechanical trauma induced ulcers often
have linear configuration. The depth of ulcer depends on

Chapter 8 Oral Ulcerative Diseases

Figure 2

Histologic features
Histopathologically an area of surface ulceration covered
by a fibrinopurulent membrane consisting of acute inflammatory cells intermixed with fibrin is seen. The stratified
squamous epithelium from the adjacent surface may be
hyperplastic and exhibit areas of reactive squamous atypia.
The ulcer bed is composed of a proliferation of granulation
tissue with areas of edema and an infiltrate of acute and
chronic inflammatory cells.
Management

A traumatic ulcer on the left lateral aspect of the tongue due


to sharp teeth. Courtesy: Department of Oral Medicine and
Radiology, KLEDC, Bangalore

Figure 3

A chemical burn on the right buccal mucosa extending


into the vestibule in patient who had the habit of applying
pain balm in the vestibule to manage periodontal pain.
Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

Consumption of a soft and bland diet.


Removal of traumatic factor (extraction of root stumps,
supraerupted teeth and malposed third molars, sharp
cuspal edges of teeth may be grounded, irritating dentures may be corrected, restoration of fractured teeth
and orthodontic correction of malposed teeth) will cause
the resolution of the ulcer in 1014 days.
Patient may be advised to rinse his/her mouth with
warm saline.
Topical application of antiseptic and analgesic/anesthetic
medication (choline salicylate 8.7%, benzylkonium
0.01% and lignocaine hydrochloride 2%patient can
be asked to apply the agent over the ulcers 10 minutes
prior to food intake, 34 times a day).
In case of multiple ulcersanalgesic/antiseptic mouthwash (chlorhexidine gluconate 0.2% or benzydamine
hydrochloride 0.15% mouthrinseone teaspoon of the
agent can be dissolved into 50 ml of water. This prepared solution is swished in the mouth for 1 minute.
The patient is advised to rinse the mouth 3 times a day,
30 minutes after food intake).
Application of topical corticosteroids (triamcinolone
acetonide oral paste 0.1%). Patient can be advised to
apply the paste 30 minutes prior to food intake, 3 times
a day for 2 weeks.
For extremely large and deep seated ulcers, penicillin
may be administered (Capsule Amoxicillin, 500 mg,
3 times a day for 5 days) to prevent secondary
infections.
Patients presenting with ulcers secondary to selfinflicted injuries may be referred to a psychiatrist or
psychologist after symptomatically managing the ulcer.

Complications
nature of trauma. Generally the area surrounding the ulcer
is inflamed. A traumatic factor will often be evident in the
vicinity of the ulcer (e.g. sharp edge of tooth).

Most traumatic ulcers resolve with the removal of the


etiological agent. However, some ulcers may be secondarily infected and subsequently heal with extensive scar
formation.

Differential diagnosis
Carcinomatous ulcer, recurrent aphthous ulcerations, ulcers
associated with deep fungal infections can be considered
in the differential diagnosis of traumatic ulcers.

Prognosis
The outcome of traumatic ulcerations is excellent, provided
the etiological factor is eliminated. Healing of the ulcerated
199

Section III Mucocutaneous Disorders

Table 1

Ulcers associated with infections


Bacterial

Viral
Specific

Non-specific

Herpes simplex virus


Primary herpetic gingivostomatitis
Recurrent herpes labialis
Recurrent intraoral herpes

Borrelia vincenti and Fusobaterium


ANUG
Cancrum oris/noma

Infected traumatic ulcer


Ruptured odontogenic abscess
presenting as ulcer

Varicella zoster virus


Chicken pox
Herpes zoster

Mycobacterium tuberculosis
Tuberculous ulcer
Tuberculosis cutis orificialis

Coxsackie virus
Herpangina
Hand, foot and mouth disease

Treponema pallidum
Chancre
Snail track ulcer
Gumma

EpsteinBarr virus
Infectious mononucleosis

Gonococci
Gonococcal stomatitis

Fungal

Histoplasmosis
Mucormycosis
Blastomycosis
Cryptococcosis
Coccidiodomycosis

Human immunodeficiency virus


AIDS

mucosa is usually delayed when the lesions overlie the


maxillary or mandibular alveolar process, hard palate and
tip of the tongue.
If the ulcer does not resolve within 2 weeks of removal
of the etiological agent, biopsy of the ulcer may be considered to rule out malignancy.

Ulcers associated with infections


(bacterial, viral and fungal infections)

Table 1 summarizes ulcers associated with infections.

PRIMARY HERPETIC GINGIVOSTOMATITIS

Prodromal systemic symptoms (fever, malaise, myalgia) precede oral lesions by 23 days.
The skin, mucous membranes, eyes and central nervous system are the most commonly affected sites.
Multiple oral ulcers affecting all parts of the mouth.
Generalized erythema of gingiva usually associated
with multiple vesicles or ulcers (Figure 4).
Cervical lymphadenopathy occurs as a rule.
Food intake becomes difficult and dehydration may
ensue.
Self-limiting condition in normal children. However,
it may become disseminated in immunocompromised
children or adults.

Diagnosis
Primary herpetic gingivostomatitis is caused by herpes simplex virus (double-stranded DNA virus which is a member
of the human herpes virus family). Most orofacial and ocular infections are caused by HSV-1. Infections involving the
genitalia and the skin surface of the lower part of the body
are caused by HSV-2. It has been reported that HSV-2 has a
greater virulence. Almost 95% of the cases have a subclinical infection, only about 5% manifest symptoms. The infection confers resistance against another primary infection
for lifetime.

Primary herpetic gingivostomatitis can be identified based


on history and clinical findings. Cytological (PAP/Tzanck)
smears of intact or recently broken vesicles may demonstrate
epithelial giant cells containing intranuclear eosinophilic
viral inclusions, that are typical of herpes viral infections.
Differential diagnosis
Leukemia, erythema multiforme and stomatitis medicamentosa can cause lesions that resemble primary herpetic
gingivostomatitis.

Clinical features

Primary herpetic gingivostomatitis has an acute onset.


Typically affects children (generally below 6 years of
age), but this infection also occurs in adults (immunocompromised).
Males and females are equally affected.
200

Treatment
Symptomatic management Ensure that the patient is
adequately hydrated and electrolyte balance is maintained.
Antipyretic and analgesic medication like acetaminophen, 500 mg given thrice daily is effective (3 times a day).

Chapter 8 Oral Ulcerative Diseases

Figure 4

2.

Herpes labialis (occurs along external vermillion border


of lips).

Precipitating Factors

Exposure to UV light (sunlight)


Menstruation
Fever
Stress
Decreased immunity
Traveling and change in climatic conditions.

Clinical presentation

Gingival erythema, multiple small ulcers and vesicles in the


attached gingiva in a 36-year-old man suffering from acute
herpetic gingivostomatitis. Reproduced with permission from
editor, JCDA. Ajar AH and Chauvin PJ. Acute herpetic
gingivostomatitis in adults: a review of 13 cases, including
diagnosis and management. J Can Dent Assoc
2002;68(4):24751

Soothening oral rinses (anesthetic mouthwashes like


dyclonine hydrochloride 0.5%, about 10 ml can be used
4 times a day as an oral rinse).
Specific management Antiviral therapy can be instituted
in children and adults. These medications will decrease the
fever, pain, severity of the lesions and minimize viral
shedding.
In children antiviral medications like acyclovir can be
given within rst 72 hours in a dosage of 200 mg 5 times
a day for 10 days. Acyclovir helps to decrease fever, pain,
lesions and viral shedding.
Newer drugs like valacyclovir (1 g orally times a day for
7 days) and famciclovir (500 mg times a day for 7 days) are
more effective.
Prognosis
The outcome of primary herpetic gingivostomatitis is good
in otherwise healthy individuals. Complications may occur
in immunocompromised individuals. The virus remains dormant in nerve ganglion and may get reactivated later in
life causing secondary infection.

Patients present with cluster of tiny fluid filled vesicles (Figure 5AC) which rupture to form pinpoint
ulcers. These ulcers may coalesce to form larger areas
of ulceration.
Lesions may be preceded by burning, itching, tingling
sensation or pain in the region.
The lesions last for 57 days and subside and subsequently recur. Now the frequency of recurrence may
be varied.
Occasionally associated with fever and pharyngitis.
As a consequence to healing an area of pigmentation
is noticed at the site of the lesion (however this pigmented area is readily visualized only in fair skinned
individuals).

Diagnosis
Recurrent herpes infection can be identified by their typical location and clinical presentation. In addition, biopsy
and Tzanck smear can be performed.
Treatment
The management of recurrent lesions is generally symptomatic. Patients can be advised to stay indoors to minimize exposure to sunlight. Sunscreen lotion can be used
when venturing out. However in individuals where there is
an increased frequency of recurrence, acyclovir therapy
can be instituted as a prophylactic measure (400 mg twice
a day for 10 days).

VARICELLA ZOSTER INFECTION

RECURRENT HERPES INFECTION

Varicella zoster virus causes two distinct clinical entities.


The primary infection by varicella zoster causes chicken
pox, while the reactivated virus causes a secondary infection termed herpes zoster or shingles.

Recurrent infections of herpes can manifest in two forms:

Chicken Pox

1.

The primary infection by varicella zoster virus usually


affects children. It is characterized by the sudden onset of

Intraoral herpes (occurs on highly keratinized mucosa


of hard palate/gingiva)

201

Section III Mucocutaneous Disorders

Figure 5

Figure 6

B
Vesicular lesions involving the face and neck in
chicken pox. Courtesy: Dr Ceena Denny

generalized pruritic vesicular rashes affecting the skin. The


incubation period of the virus varies from 10 to 21 days.
Approximately 50% of the affected children present with
prodromal symptoms of fever, malaise, headache, and
abdominal pain, which last for about 12 days before the
appearance of the dermal lesions.
Dermal lesions
C

Typical lesions of chicken pox, clinically exhibit four


phases. The maculopapular phase (erythematous macules
are evident), vesicular phase (minute fluid filled vesicles
are seen), ulcerative phase (commonly seen on mucous
membranes of oropharynx, vagina and conjunctiva)
and the phase of healing (Figure 6).
In the maculopapular phase erythematous macules are
seen. In some patients, vesicles develop within the
maculopapular rash giving rise to dewdrop on a rose
petal appearance.
The commonly involved sites are the scalp, face and
trunk.
The lesions are often pruritic.

(A) Vesicles on the upper lip in a patient with


recurrent herpes labialis. (B) Ulcers formed
subsequent to vesicle rupture in a patient with
recurrent herpes labialis. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore.
(C) Healing lesions of herpes labialis. Courtesy:
Department of Oral Medicine and Radiology,
KLEDC, Bangalore

202

On an average 100300 new lesions are found at any


given point of time. Lesions heal generally without scarring. Occasionally crusting of the lesions may be seen.
However, an area of hypopigmentation may be appreciated at the site of the healed lesion. These hypopigmented
areas fade away with time.
Oral lesions
The common intraoral sites affected are the hard and soft
palate, labial and buccal mucosa. Oral lesions of chicken

Chapter 8 Oral Ulcerative Diseases

pox are seen as small vesicles that subsequently rupture to


form shallow round ulcers surrounded by an erythematous
halo.

Figure 7

Management
Vaccination against varicella zoster should be given to
infants between 12th and 18th months of life. The management of the disease is mainly symptomatic. Acyclovir can
be administered in the early phases of the disease.

Herpes Zoster
Herpes zoster is caused by reactivation of varicella zoster
virus that is inactive in dorsal root or cranial nerve ganglion, after primary infection.
It is estimated that only in about 0.30.5% of the
population, the virus is reactivated after the primary
infection.
Clinical features

The clinical features depend on the dermatome


involved.
The nerves that are commonly affected are C-3, T-5,
L-1 and L-2.
Manifests in middle age.
When the trigeminal nerve is involved, the ophthalmic
division of the nerve is most commonly involved. About
1520% of the affected individuals show involvement
of the maxillary or mandibular division.
Painful vesicles and/or ulcers seen both inside and outside the oral cavity, which stop abruptly at the midline
(i.e. lesions do not cross midline) (Figure 7).
Bilateral lesions may indicate severely immunocompromised state. Literature review reveals reports of
necrosis of alveolar bone exfoliation of teeth in immunocompromised individuals.
Occasionally pain may be present along the course of
the affected nerve in the absence of vesicles. Such a
manifestation is termed zoster sine herpete or zoster
sine eruption.
Ramsay Hunt syndrome is a symptom complex associated with herpes zoster. It is characterized by varicella
zoster infection affecting the geniculate ganglion of
the facial nerve, unilateral facial paralysis and unilateral vesicular eruptions involving the oral mucosa and
external ear.

Post-herpetic neuralgia is one of the relatively common


sequelae of varicella zoster infection that results from
scarring of the involved nerve.
Management
Antiviral drugs like acyclovir, valacyclovir and famciclovir have been used successfully in shortening the course

Healed lesions of herpes zoster with scab formation.


Characteristically, the lesions do not cross the midline and
this patient had involvement of the ophthalmic, maxillary
and mandibular divisions of the trigeminal nerve.
Courtesy: Dr Sumanth

and healing time of the infection and reducing the pain


associated with the disease.
Acyclovir (800 mg) is given 5 times a day for a week or
valacyclovir (1,000 mg) or famciclovir (500 mg) can be
given 3 times a day for a week.

Herpangina
Herpangina is caused by coxsackie virus (A 1-10, 16, or 22).
It occurs generally in epidemics. It predominantly affects
posterior parts of oral cavity.
Clinical findings

In the early stages erythematous macules are seen.


As the disease progresses, vesicles with a central ulceration develop, which exhibit an erythematous halo.
Generally around 210 lesions are seen which measure
less than 5 mm in diameter.
The common sites involved are the posterior pharyngeal region, uvula, anterior faucial pillars, tonsils and
soft uvula. On occasions ulcers may be present on the
tongue and buccal mucosa corresponding to the posterior regions of the oral cavity.
The lesions are usually associated with mild fever which
subsides within a week.
203

Section III Mucocutaneous Disorders

It is a self-limiting condition and generally subsides


within a week.
Marginal gingiva is characteristically unaffected.

Hand, Foot and Mouth Disease


Hand, foot and mouth disease is a viral disease caused by
coxsackie viruses (members of the Picornaviridae family).
It is characterized by oral lesions associated with lesions
involving the extremities.
Infections can occur in a sporadic form (coxsackie virus
types A4A7, A9, A10, B1B3, and B5) or as epidemics
(coxsackie virus A16 or enterovirus 71). The incubation
period ranges from 3 to 6 days. Though the disease runs a
mild course and is self-limiting, a severe form of the condition is seen in infants and children. Enteroviral infections
may cause myocarditis, pneumonia, meningoencephalitis
and even death. Infection occurring during the rst trimester in pregnant women can result in spontaneous abortion
and retarded development of the fetus.
Clinical features
Hand, foot and mouth disease typically affects young children below 10 years of age. Males and females are equally
affected. Prodromal symptoms like low-grade fever,
anorexia, malaise, abdominal pain, sore mouth and cough
are evident which lasts for 1236 hours. The condition is
self-limiting. Mucosal and cutaneous lesions resolve spontaneously in 57 days.
Literature review reveals that almost 22% of the patients
may present with cervical or submandibular lymphadenopathy.
Skin lesions

Approximately 65% of the patients demonstrate skin


involvement.
The commonly affected sites are the hands (dorsal
aspect of the hands and sides of the fingers are very
commonly affected), feet and the buttocks.
The characteristic skin lesion is seen as asymptomatic,
erythematous macule characterized by a central grayish
vesicle. The macule varies in size from 2 to 10 mm.
These macules are elliptical with their long axis aligned
parallel to the skin lines.
The lesions subside in about a weeks time.

Oral lesions

In the early stages, oral lesions begin as erythematous


macules that evolve into 23 mm vesicles on an
erythematous base. However, intact vesicles are rarely
seen as they ulcerate instantaneously.
The ulcers are painful and interfere with chewing and
swallowing.
204

Approximately five to ten ulcers are seen.


Tongue may be involved in about 45% of the patients.
Tongue may become swollen and tender.
The other sites of involvement are the palate, buccal
mucosa and gingiva.
Management

Topical application of anesthetics like viscous lidocaine and diphenhydramine may be used to manage
painful oral ulcers. Sucralfate suspension can also be
effectively used.
Fever and arthralgias can be treated using antipyretics
and analgesics.
Literature review reveals that there is a reported quicker
resolution of symptoms with the use of oral acyclovir.
A low intensity laser ablation of the oral ulcers is said
to shorten the duration of painful oral ulcers.
Prognosis
The prognosis of the condition is generally excellent
owing to the self limiting nature of the disease. However,
complications like meningoencephalitis, myocarditis, pulmonary edema, and death have been reported.

ACUTE NECROTIZING ULCERATIVE


GINGIVITIS
(Trench Mouth, Vincents Disease,
Vincents Gingivostomatitis)
Acute necrotizing ulcerative gingivitis (ANUG) is an acute
bacterial infection affecting the gingiva. As per the 1999
American Academy of Periodontics classification system,
ANUG is presently classified as necrotizing periodontal
disease that is characterized by rapidly progressive ulceration typically starting at the crest of the interdental
papilla, spreading along the marginal gingival and subsequently causing rapid and extensive destruction of the
periodontal tissue.
The anaerobic organisms that are said to cause ANUG
are Fusobacterium necrophorum, Prevotella intermedia,
Fusobacterium nucleatum, Porphyromonas gingivalis and
Treponema species.
Predisposing factors
Suppressed immunity, malnutrition, stress, poor oral hygiene,
smoking and local trauma predisposes to the development
of ANUG. Literature review reveals that the prevalence of
ANUG among HIV patients ranged from 4 to 16%.
Clinical findings

ANUG is generally seen in young and middle-aged


adults. However, in the Indian subcontinent and

Chapter 8 Oral Ulcerative Diseases

Figure 8

Necrosis of the interdental papillae in acute necrotizing


ulcerative gingivitis. Reproduced with permission from editor,
JCDA. Mirbod SM, Ahing SI. Tobacco-associated lesions
of the oral cavity: part I. Non-malignant lesions.
J Can Dent Assoc 2000;66:2526

Africa, it occurs almost exclusively in children of age


group between 3 and 10 years. These children characteristically belonged to the low socioeconomic groups.
Hospital-based studies in Nigeria showed a prevalence
rate of about 23% in children less than 10 years of age.
Gingiva tends to bleed spontaneously or with the
slightest of provocation.
Marginal and interdental gingiva is erythematous and
edematous.
Crest of the interdental papillae is blunted.
Minute punched-out crater like ulcers are seen in the
interdental papillae. These ulcers are covered by a grayish white pseudomembrane. The ulcers are extremely
painful (Figure 8).
Foul odor.
Patients may present with fever, malaise and regional
lymphadenopathy.

Table 2 compares features of acute necrotizing ulcerative


gingivitis and acute herpetic gingivostomatitis.
Management of ANUG

Manage underlying factors.


Well balanced diet and regular meals.
Gently remove necrotic material with swab.
3% hydrogen peroxide diluted with equal amount of
water used to rinse mouth every 2 hours on first day;
34 times/day for next 4 days.
Penicillin V (oral): 400,000 units/day for 5 days/amoxicillin 250500 mg t.i.d. for 57 days.
Metronidazole 400 mg t.i.d. for 5 days.
Oral prophylaxis can be undertaken after acute symptoms subside.

Table 2

Comparison of acute necrotizing ulcerative gingivitis


and acute herpetic gingivostomatitis

Acute necrotizing ulcerative


gingivitis

Acute herpetic
gingivostomatitis

Complex bacterial etiology

Viral etiology

Ulcers confined to gingiva

Ulcers all over mouth

Indefinite clinical course and duration

Self-limiting lasts for 710 days

Non-contagious

Contagious in those with


depressed immunity

No viral antibodies

Convalescent sera shows viral


antibodies

Treatment with antibacterial agent

No role for antibacterial agents

TUBERCULOSIS
Tuberculosis is a chronic infectious granulomatous bacterial disease generally acquired by inhaling droplets contaminated by Mycobacterium tuberculosis. However, it can
also be acquired by consuming unpasteurized cows milk
that is infected by Mycobacterium bovis or by other atypical
mycobacteria.
Oral manifestations
It is hypothesized that tubercle bacilli enter the oral
mucosa through a break in the mucosal surface. Abbot
et al in an independent study were able to isolate tubercle
bacilli from the mouthwashings of 44.9% of the individuals suffering from pulmonary tuberculosis. This study
underlines the importance of intact mucosal lining in providing protection against tuberculosis affecting the oral
cavity.
The oral manifestations of tuberculosis are rare. It is
estimated that approximately 1.4% of the patients suffering
from tuberculosis exhibit oral manifestations. The tuberculous lesions may present as ulcer, ssure, tuberculoma
or as a generalized enlargement of the tongue. In the initial
stages the lesion can be in the form of a nodule or opalescent vesicle which progresses to form an ulcer. The most
common oral manifestation is ulcer (Figure 9). Oral tuberculous lesions typically present with severe, unremitting
and progressive pain.
Sites
Soft tissues are more frequently affected than hard tissues.
The sites of involvement include the tongue, soft palate,
hard palate, gingiva, lips, floor of the mouth, vestibular
and retromolar regions and recent tooth extraction sockets. Maxilla and the mandible have also been affected and
referred to as tuberculous ostemyelitis. Mandible is more
commonly involved. Tuberculous osteomyelitis generally
205

Section III Mucocutaneous Disorders

Figure 9

A solitary crateriform ulcer with slightly elevated


and indurated borders on the lateral margin of the
tongue in a patient with tuberculosis. Courtesy:
Dr Velia Ramrez Amador, Universidad Autnoma
Metropolitana-Xochimilco, Mexico

Figure 10

Caseation necrosis of a tubercular lymph node.


Courtesy: Department of Oral Pathology, MCODS,
Mangalore

Oral manifestations
occurs due to a hematogeneous spread of the bacilli or
through a direct extension through a fresh extraction
socket.
Typical lesion
The ulcer is irregular with ragged, undermined edges, minimal induration and yellowish granular base. The ulcer is
surrounded by sentinel tubercles. Primary oral tuberculous
lesions are usually associated with caseation of the regional
draining group of lymph nodes (Figure 10).
Differential diagnosis
Infected traumatic ulcer, major aphthous ulcer, syphilitic
ulcer, sarcoidosis, lymphogranuloma venereum, foreign
body granuloma, histoplasmosis and malignant ulcer can
be considered as differential diagnosis for tuberculous
ulcer.
Management
The pain associated with the ulcer can be treated symptomatically. Antitubercular therapy for 18 to 24 months
should be instituted.

SYPHILIS
Syphilis is a sexually transmitted disease that is caused by
Treponema pallidum.
206

All stages of acquired syphilis can present as oral ulcers


(chancre, mucous patch and gumma). Usually chancre
and mucous patch are self-limiting and pass on to the
next stage.
Chancre The occurrence of primary syphilis in the oral
cavity is extremely rare. Almost all chancres are seen in
the genital region. However with the change in the sexual
practices the oral cavity can also be a site for the presence
of chancre.
The lips, tongue, tonsillar regions and the palate are the
common sites that are involved. In the initial stages a papule may be seen which subsequently erodes. The typical
syphilitic ulcer is punched out, non-tender, indurated and
associated with a yellowish serous discharge. The associated nodes are generally rm and non-tender on palpation.
Chancres are self-limiting and last for a period of 2 weeks.
They heal with minimal scar formation.
Mucous patches Generally secondary syphilis appears
after a latency period of 6 months after the primary lesions
are noticed. Patients complain of fever, headache, bodyache and sore throat. Cutaneous maculopapular rashes
associated with lymphadenopathy are seen.
Oral lesions are characterized by the appearance of oval
red macules (usually seen on the palate) or papules (usually
seen on the buccal mucosa and commissures) and mucous
patches. The oral commissures demonstrate split papules.
Mucous patches are seen as raised erosive areas covered by
a grayish white pseudomembrane and surrounded by an
erythematous halo. They usually measure about 1 cm in

Chapter 8 Oral Ulcerative Diseases

diameter and seen bilaterally on the movable surfaces in the


oral cavity. These small lesions can join together to give
rise to snail track ulcers (serpiginous pattern).
A severe and generalized form of secondary syphilis can
result in lues maligna, which is also termed ulceronodular
disease. The oral mucosa reveals shallow crater like ulcers.
The common sites involved are the palate, buccal mucosa,
tongue, lower lip and gingiva.

Oral findings

Gumma Gumma is a highly destructive lesion that is


typically seen in tertiary stage of acquired syphilis. The
gummatous lesion may sometimes occur 810 years after
the initial infection. The hard palate and tongue are common sites of involvement. However, literature review
reveals sites like the parotid salivary gland, soft palate and
the lower alveolar ridge being affected.
Gumma of the hard palate will result in perforation,
thereby producing an oronasal communication.

Histoplasmosis

Diagnosis and management

Mucormycosis

Sensitive tests like VDRL and specific tests like FTA-ABS


test/TPI assay/ELISA can be used to diagnose syphilis.
According to the 1993 Centers for Disease Control and
Prevention (CDC) treatment guidelines for sexually transmitted diseases, parenteral penicillin G is the drug of choice
for managing syphilis. Patients allergic to penicillin can be
treated with doxycycline, tetracycline or erythromycin.

It is an opportunistic infection caused by a saprophytic


fungus that is found in the soil, bread mold, animal manure
and rotting vegetation. Mucoraceae are fungi that are commonly found in soil or in rotting vegetation. Rhizopus can
be found in moldy bread. Mucormycosis can assume various clinical forms based on the site of involvement such as
rhinocerebral form (spores deposited in nasal turbinates),
pulmonary form (spores lodged in the lungs by inhalation), cutaneous form (spores introduced through wounds
and cuts on the skin surface), gastrointestinal form (spores
ingested) and a disseminated form.
The rhinocerebral form of mucormycosis characteristically involves the paranasal sinuses. An extension of the
disease process can result in ulceration of the palate. The
typical lesion is seen as a large, painful ulcer of the palate
lled with blackish necrotic slough. Ulcers have also been
reported to occur on the gingiva, lip and alveolar ridge.

DEEP FUNGAL INFECTIONS


Deep fungal infections are relatively uncommon in the
oral cavity. These deep seated infections generally have
systemic manifestations and rarely involve the oral cavity.
The deep fungal infections that produce ulcerative lesions
in the oral cavity include mucormycosis, blastomycosis,
histoplasmosis, aspergillosis, cryptococcosis and paracoccidiodomycosis. Characteristically, these infections are seen
in immunocompromised individuals suffering from HIV,
AIDS or systemically debilitating conditions such as diabetes mellitus, malignancies and individuals on long-term
immunosuppressive therapy.

Aspergillosis
Aspergillosis is reportedly the second most commonly seen
fungal infection affecting the oral cavity after Candida.
Aspergillosis in humans is caused primarily by Aspergillus
fumigatus and A. niger. The spore is found in rotting vegetation. The transmission of fungal spores to the human
being is by inhalation.
It primarily affects the lungs. Aspergillosis has a tendency for a hematogeneous invasion causing thrombosis
and infarction of perivascular tissues.

Involvement of the maxillary sinus is rarely seen in


aspergillosis. An extension of the infection from the
sinus can result in involvement of the adjacent soft tissue and palate producing blackish or yellowish necrotic
ulcerations.

Histoplasmosis is caused by Histoplasma capsulatum. Following inhalation of this dimorphic fungus it can cause an
acute pulmonary histoplasmosis or can assume a disseminated form in immunocompromised individuals.
The typical oral lesion, though very rare appears as an
erosion or ulcer commonly involving the tongue, palate
and buccal mucosa.

Cryptococcosis
Cryptococcosis is an opportunistic fungal infection caused
by Cryptococcus neoformans. It is usually present in bird
droppings, rotting wood and soil.
C. neoformans preferentially affects the meninges, basal
ganglia and cortical gray matter. Oral mucosal lesions appear
as supercial ulcers or as deep ulcers with indurated borders and rolled out edges.

North American Blastomycosis or


Gilchrists Disease
Gilchrists disease is caused by Blastomyces dermatidis. It
is caused by inhalation of the spore which is predominantly
found in the soil. Like most of the deep fungal infections,
207

Section III Mucocutaneous Disorders

blastomycosis has a localized form that affects the respiratory system and a disseminated form. However, unlike other
fungal infections immunosuppression does not increase the
risk of disseminated disease.
Blastomycosis is endemic to the Mississippi and Ohio
River basins in the United States and certain areas in Africa
and India.
Disseminated form of blastomycosis commonly involves
the skin, CNS and the genitourinary tract. Papulopustular
or verrucous, grayish lesions are seen on the skin surface.
Oral mucosa may exhibit ulcerations.

Paracoccidiodomycosis or South American


Blastomycosis
Paracoccidiodomycosis is caused by Paracoccidioides brasiliensis. This disease is commonly seen in Latin American and
South American regions (Brazil, Colombia, Argentina and
Venezuela).
Clinical features
It usually affects men older than 30 years of age. Farmers
are at a greater risk of acquiring this disease. After inhalation, the fungus usually remains dormant and the individual is asymptomatic. In an immunocompromised host,
the fungus exhibits the clinically active state.
Lung is the rst site of involvement. It leads to productive cough, chest pain and shortness of breath. Other symptoms include joint pains and body aches. Cervical and
axillary lymphadenopathy is seen.
Painful ulcers involve the mucosa of the oral cavity;
gastrointestinal (GI) tract and upper respiratory tract are
common. Oral ulcers are typically seen on the lips, gingiva, and tongue.

Paracoccidioidomycosis
The paracoccidioidomycosis is one of the most prevalent
deep systemic mycoses. It is more frequently observed
in patients from South America or Central America and
is an important expression of the spectrum of pathology in Latin America. Brazil accounts for approximately 70% of the cases reported in the literature.
Immigrants from these regions may carry it elsewhere
or people visiting these endemic areas may acquire the
infection.
Knowing paracoccidioidomycosis is important to
the dentist, since the oral mucosa provides an important substrate to the saprophytic life of the fungus, and
the disease has frequent oral and dermatological manifestations, usually the first to be detected. In spite of
that, few cases have been reported in the English language literature. Although a primarily lung infection,

208

paracoccidioidomycosis is frequently diagnosed because


of mouth lesions. In this sense, the dentist plays a fundamental role in the diagnosis of this pathology.
Oral lesions are usually extensive, can be found on
up to 78.9% of the cases investigated, and frequently
affect more than one area of the oral mucosa. The
mucous and mucocutaneous lesions of paracoccidioidomycosis have a signicant clinical diagnostic value,
since they provide direct observation of the lesion and
easy access to the anatomopathological and mycological examination, in addition to their high prevalence.
The main clinical feature in the oral lesions is a granulomatous mulberry-like surface and ulceration.
Because of the chronic character and progressive
extension of the ulcerated oral lesions, they may resemble other infections and neoplastic diseases. In the clinical routine, the patients are mistakenly diagnosed as
having mainly squamous cell carcinoma, tuberculosis,
sarcoidosis, leishmaniasis, Wegeners granulomatosis,
histoplasmosis, actinomycosis, lupus erythematosus,
lymphoma, or syphilis.
The predilection for male patients, in what seems to
be a result of a protective effect of female hormones such
as -estradiol, which inhibits transformation of the
hyphal form of the organism to the pathogenic yeast
form as well as is a consequence of the professional
outdoor activities of males. It is postulated that after
menopause, women are more susceptible to the disease.
However, possible genetic factors associated to the HLA
antigen may facilitate the appearance of mycosis.
The fungus Paracoccidioides brasiliensis is easily
recognized under hematoxylin and eosin (H&E) staining, inside or outside of giant cells, as birefringent,
double-contoured cyst-like structures with a diameter
ranging from 1 to 30 m. Typically, H&E stained slides
reveal epithelial pseudoepitheliomatous hyperplasia,
granulomatous response and microabscesses. The underlying connective tissue displays a chronic granulomatous reaction, with epithelioid cells and giant cells. The
number and organization of granulomas are variable.
Disorganized granulomas tend to predominate in the
oral lesions. The periodic acid-Schiff (PAS) and GrocottGomori methenamine silver are particularly useful to
highlight the yeast-like structures with multiple budding that resemble a pilots wheel or Mickey Mouse ear.
Eosinophilic inammatory inltrate is a common nding, however it is not directly related to the amount of
fungus or granulomas. Immunocytochemical techniques
may provide new information on the microscopic aspects
of this disease and should be encouraged.
The treatment scheme will depend on the severity
of the disease, and long-term follow-up is mandatory.
Even with supposedly adequate treatment, death is not
uncommon in both acute and chronic cases.

Chapter 8 Oral Ulcerative Diseases

DRUG-INDUCED ORAL ULCERS


The oral mucosa is susceptible to insult from both systemically administered drugs and locally applied drugs in
the oral cavity.
The term stomatitis medicamentosa is reserved for the
effects of systemically administered drugs and stomatitis
venenata is the term used for the effects induced by topical
application of drugs or due to contact (contact stomatitis).
Pathogenic basis of drug-induced stomatitis/
oral ulceration
Drug-induced stomatitis or ulcerations are said to be caused
either by immune mediated or non-immune mediated
pathways. These changes in the oral cavity depend on the
potential toxicity of the drug, frequency of intake, route
of drug administration and the inherent immunity of the
individual receiving the medication.
Immune-mediated pathway The medicament or one of
its components is thought to trigger an immune response.
This immune response is targeted at the surface epithelium,
thereby forming ulcers.
Non-immune mediated pathway In this form of reaction there is no evidence of an immune response and it is
not dependent on antibodies. The medication administered
will directly stimulate mast cells and lymphocytes to release
cytotoxic chemical mediators that cause stomatitis and oral
ulcerations.

Stomatitis Medicamentosa
Adverse effects of drugs are generally manifested over the
skin surface. However, literature review reveals that the
oral cavity can sometimes be the only site of involvement.
It is a known fact that no medication is safe and that every
drug has the potential to cause damage to the body including the oral cavity. These drug reactions affecting the oral
mucosa can be in the form of stomatitis, lichenoid reactions, erosions and ulcers.

ulcers are resistant to all treatment modalities and persist


for months.
Management
The suspected medication should be replaced by an alternative drug wherever possible. Patients can be advised to
apply topical anesthetic agents over the ulcer. Tetracycline
mouthwashes and topical steroids are effective in managing drug-induced oral ulcers.

Stomatitis Venenata (Contact Stomatitis)


Contact stomatitis is relatively rare when compared to
contact dermatitis. The inherent qualities of the oral
mucosa and the oral environment make it more resistant
to potentially allergic agents than the keratinized skin.
Saliva dilutes and digests or washes away allergic agents.
It also contains a high concentration of epidermal growth
factor which aids in healing of mucosal injuries if any. The
oral epithelium, which is non-keratinized in nature, has
fewer proteins; as a result there are fewer targets for the
allergens. Allergens in contact with the oral mucosa are
removed very rapidly because of the higher epithelial turnover rates of the oral epithelium.
However, in spite of the inherent protective mechanism
of the oral mucosa, topical application of medicaments can
elicit a localized mucosal reaction in some individuals.
Types of contact stomatitis
Allergic contact stomatitis and irritant contact stomatitis
are subtypes of contact stomatitis (Table 3).
The agents causing stomatitis are usually dentifrices,
mouthwashes, dental materials, cosmetic agents, food coloring and avoring agents and preservative agents. The
agents causing contact stomatitis are summarized in the
Box 1.
Management
The first step in managing contact stomatitis is by avoiding
contact with the identified or suspected irritant or allergen.

Medications causing oral ulcers


Non-steroidal anti-inflammatory drugs (indomethacin,
piroxicam and ibuprofen), anti-depressant (sertraline), COX-2
inhibitors (celecoxib, rofecoxib), anticancer chemotherapeutic agents such (cyclosporine, methotrexate, doxorubicin), anti-hypertensives (calcium channel blockers) and
miscellaneous agents like gold salts can cause stomatitis
and/or oral ulcerations. Antidepressants cause xerostomia,
which in turn results in stomatitis or ulceration.
Drug-induced oral ulcers are generally solitary and typically seen over the lateral margins of the tongue. These
ulcers are often surrounded by a white halo. Most of the

Table 3

Contact stomatitis: types

Irritant contact stomatitis

Allergic contact stomatitis

No previous history regarding


exposure to suspected irritant

Previous history regarding exposure


to allergen is required

Clinical signs are seen within


minutes to hours of exposure
to irritant

Clinical manifestations usually seen


after 48 hours of subsequent exposure
(a type IV hypersensitivity reaction)

Activation of immunologic
Activation of memory T-cells
mediators without involvement
of memory T-cell function

209

Section III Mucocutaneous Disorders

Box 1

Common agents causing contact stomatitis

Oral cleansing aids


Dentifrices (contain peppermint, cinnamon)
Mouthrinses (chlorhexidine)
Dental floss (contains colophony or rosin)
Dental materials
Free monomer (in acrylic appliances)
Nickel (content of orthodontic wires)
Mercury (dental amalgam fillings)
Gold (constituent of crowns, fillings)
Denture adhesives (contains rosin which is resin obtained from
conifers)
Eugenol (in periodontal packs, cements)
Phenol
Cosmetics (contain rosin derivatives, propolis and ricinoleic acid)
Lipsticks
Lip balms
Sunscreens
Latex

Table 4

Blood disorders causing oral ulcers

RBC disorders

WBC disorders

Anemia

Quantitative
disorders

Qualitative
disorders

Lazy leukocyte
syndrome

Iron deficiency
Pernicious
Sickle cell anemia
Thalassemia

Leukemia
Agranulocytosis
Cyclic neutropenia
Multiple myeloma

WBC Disorders
WBC disorders can cause oral ulcerations and necrotizing
lesions which are commonly seen on the gingiva, floor of
the mouth, buccal mucosa and pharynx. These ulcers are
characterized by the lack of the inflammatory halo and
generally associated with necrosis and foul smell. Cyclic
neutropenia is associated with recurring oral ulcers. The
treatment is directed at the cause of the ulceration.

Food substances (containing preservatives, coloring and flavoring


agents, sea food, fruits such as apples, pears, etc.)

IMMUNOLOGIC DISORDERS
Patients are instructed to avoid smoking. Toothpaste and
mouthwashes with strong flavoring agents are best avoided
(baking soda can be an effective alternative to tooth pastes).
Topical triamcinolone acetonide or flucinonide 0.05% gel
can be used.

ERYTHEMA MULTIFORME
Described in Chapter 7 on Vesiculobullous Disorders.

BLOOD DISORDERS CAUSING ORAL ULCERS


Blood disorders are associated with increased risk of oral
ulcers. Necrosis is generally a prominent feature of these
ulcers. Other clinical signs and symptoms and a hemogram will help the diagnosis.
The red blood cell (RBC) and white blood cell (WBC)
disorders that cause oral ulcers are summarized in Table 4.

RBC Disorders
Iron deficiency anemia is characterized by the presence
of glossitis and glossodynia, angular cheilitis and atrophic
areas on the tongue due to papillary atrophy. Patients with
pernicious anemia exhibit glossitis, burning tongue, angular cheilitis, papillary atrophy, and recurrent oral ulcerations. Sickle cell anemia and thalassemia exhibit oral
ulcerations. These patients are relatively more likely to
develop osteomyelitis.
210

Aphthous Ulcers (Recurrent Aphthous Stomatitis,


Aphthae, Canker Sores)
Recurrent aphthous stomatitis (RAS) is a common condition characterized by recurring ulcers confined to oral
mucosa in patients with no other signs of disease. Patient
presents with multiple round or ovoid ulcers generally
with well-defined borders and erythematous halo surrounding the periphery of the ulcer. Literature review reveals
that approximately 25% of the population is affected with
this condition.
Etiopathogenesis
Although many theories were proposed to explain the etiology of RAS, there appears to be no single causative factor.
Various etiological factors have been proposed, such as
hereditary, trauma, deficiency states, psychological factors,
endocrine disorders, allergic conditions, infections, blood
dyscrasias, drugs, GI diseases, urological disorders, dermatological disorders and immunologic origin, etc.
Lehner (1964) and Dolly (1969) were of the opinion that
RAS belonged to the group of autoimmune diseases. Lehner
in 1969, found elevated levels of IgG and IgA in the sera
of patients with RAS. A uorescent antibody technique
showed both IgG and IgM were binding by epithelial cells
of the spinous layer of oral mucosa in RAS patients.
Greenspan et al (1981) implicated antibody dependent
cellular cytotoxicity as a pathogenic mechanism in RAS.
Thomas and coworkers (1990) showed that T lymphocytes
from RAS patients had increased cytotoxicity to oral epithelial cells.

Chapter 8 Oral Ulcerative Diseases

Clinical features

Individuals may experience burning sensation which


may appear 248 hours before the ulcer appears.
During the initial periods, a localized area of erythema
develops within hours, a small white papule forms,
ulcerates and gradually enlarges over the next
4872 hours.
The ulcers are usually regular and well defined. They
are rimmed by an erythematous halo (Figure 11) and
the ulcer is covered with a yellowish-gray fibrinous
pseudomembrane.
The number and size of the ulcers vary based on the
type of RAS.

Figure 11

Ulcers are usually seen on the non-keratinized oral


mucosa (commonly on the buccal and labial mucosa).
Ulcers are rarely seen in the heavily keratinized palate
or gingiva.

Types of recurrent aphthous stomatitis


Three forms of RAS are clinically recognized, namely,
minor, major, and herpetiform.
Minor aphthous ulcers (Mikulicz ulcer) The minor RAS are
tiny round to ovoid ulcers that mainly involve the nonkeratinized oral mucosa (such as the buccal mucosa, labial
mucosa, floor of mouth, ventral surface of the tongue). In
most individuals one to six ulcers measuring about 24 mm
in diameter are present at any given point of time. The ulcers
are surrounded by an erythematous halo (Figure 12A, B).
These ulcers heal in about a weeks time without scarring.
Major aphthous ulcers (Suttons ulcers; periadenitis
mucosa necrotica recurrents) Like the name suggests
these ulcers are larger in size (almost up to 1 cm in size)
when compared to minor RAS. Major RAS involve even
the keratinized areas of the oral mucosa (such as the palate
and dorsum of tongue). These ulcers usually occur in very
few numbers ranging from one to six at a time. They persist for a longer duration and heal in about 26 weeks
with scarring.

Aphthous ulcer on the upper labial mucosa. The ulcer is


surrounded by an erythematous halo. Courtesy: Department
of Oral Medicine and Radiology, MCODS, Mangalore

Herpetiform ulcers These are present as crops of tiny


pin head sized ulcers which coalesce together. These may
be present both on the keratinized as well as the nonkeratinized mucosa. These ulcers typically begin as tiny
vesicles that subsequently ulcerate. These are extremely
painful and tend to heal in about 10 days and almost
immediately recur.

Figure 12
A

(A) A minor aphthous ulcer on the lower labial mucosa. (B) A minor aphthous ulcer on the lateral margin of the tongue.
The ulcer is surrounded by the characteristic erythematous halo. Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

211

Section III Mucocutaneous Disorders

Table 5

Comparison of recurrent aphthous ulcer and recurrent intraoral herpes

Recurrent aphthous stomatitis


(RAS)

Recurrent intraoral herpes


(RIHS)

Non-specific etiology

Viral etiology

Wide range of age group

Middle age

Freely movable mucosa involved

Attached mucosa

Single or 23 ulcers at a time


except in herpetiform where crops
of pinpoint ulcers occur

Multiple pinpoint ulcers

Non-specific findings on H/P

Tzanck cells on smear

No antibody titers

Convalescent sera show viral


antibodies

Corticosteroids used

Corticosteroids contraindicated

Table 5 compares clinical features of recurrent aphthous stomatitis and recurrent intraoral herpes.
Diagnosis
The diagnosis of RAS is done by exclusion. Hematological
examination can be performed to rule out blood dyscrasias. Ocular, genital, skin, or rectal lesions should not be
present to make a diagnosis of aphthous stomatitis.
Management
The primary goals of therapy for RAS are relief of pain,
reduction of ulcer duration, and restoration of normal oral
function. Secondary goals include reduction in the frequency
and severity of recurrences and maintenance of remission.
Topical medications, such as antimicrobial mouthwashes
and topical corticosteroids, can achieve the primary goals
but have not been shown to alter recurrence or remission
rates. Systemic medications can be tried if topical therapy
is ineffective.
Levamisole has shown variable efcacy in reducing
ulcer frequency and duration in patients with minor recurrent aphthous ulcer (RAU). Dose: 150 mg per day for 3 consecutive days followed by a gap of 2 weeks. Then repeat
for 3 days. This is to be done 6 times (total therapy time is
3 months and total number of tablets is 18). Thalidomide
is effective but, because of its toxicity and cost, should be
used only as an alternative to oral corticosteroids.

DERMATOLOGICAL DISORDERS
Pemphigus
Pemphigus is a chronic, autoimmune skin disorder which is
considered to be the most dreaded, dramatic and devastating
of all dermatologic disorders. Pemphigus vulgaris, vegetans,
212

foliaceous and erythematoses are the four histopathological


variants of the disease. Pemphigus vulgaris is the most
severe form.
Clinical features
It is commonly seen in Jews and predominantly affects
adults with no sex predilection. Bullae of varying sizes are
seen on skin and mucosal surfaces. The bullae on the skin
are tense; however in the oral cavity they rupture almost
immediately to form ulcers or erosions (Figure 13A, B). These
ulcers typically have peripheral tissue tags. Nikolskys sign
(lateral pressure applied over apparently normal skin or
mucosa causes sliding of the skin) is positive. Ashboe
Hansen sign, also known as bulla spreading sign (pressure
applied over a bulla makes it spread) is positive. Desquamative gingivitis is commonly seen in pemphigus vulgaris
(Figure 14).
Diagnosis
The diagnosis of pemphigus vulgaris is made based on the
typical clinical signs. Histopathologically, the presence of
intraepithelial bulla is characteristic of pemphigus vulgaris.
Immunofluorescent studies exhibit a positive fluorescence
under the fluorescent microscope with the antibody binding
to the immunoglobulin deposits in the intercellular substance. Other non-specific findings associated with pemphigus vulgaris are a raised ESR and hypoalbuminemia.
Management
The mortality associated with untreated pemphigus vulgaris
is about 10%. Systemic corticosteroids are effective in managing the condition. Prednisolone 0.51 mg/kg/day or about
4080 mg/day is administered. Cyclophosphamide is given
at an initial dose of 50 mg/day and the dose escalated to
100 mg/day. Mouthwashes like benzydamine hydrochloride
0.15% will help in managing pain. Antiseptic oral rinses
such as chlorhexidine gluconate 0.2% can be used.

PEMPHIGOID
Bullous pemphigoid and benign mucous membrane pemphigoid cicatricial pemphigoid are the two variants of
pemphigoid.

Bullous Pemphigoid
Bullous pemphigoid is commonly seen in women in the 6th
and 7th decades of life. It is characterized by the appearance of bullae over the skin, which rupture to give rise to
erosive areas, which heal spontaneously.
Not all cases of bullous pemphigoid involve the oral
cavity. Intraorally small bullae are seen especially on the

Chapter 8 Oral Ulcerative Diseases

Figure 13
A

(A) Ulcers in the vestibular region in pemphigus vulgaris. (B) Erosions on the hard palate in pemphigus vulgaris.
Courtesy: Dr Sumanth

Figure 14

Ultrastructural studies reveal the loss of attachment of


the epithelium and basement membrane to the underlying
connective tissue or lamina propria.

GASTROINTESTINAL DISORDERS
ASSOCIATED WITH ORAL ULCERS

Desquamative gingivitis in pemphigus vulgaris.


Courtesy: Dr Francisco Snchez, Morelia City, Mexico

gingiva and buccal mucosa. Patients may complain of


mild pain. These bullae rupture over a period of time to
form erosions or ulcers. Histopathologically subepidermal
bullae formation is seen.
Bullous pemphigoid is treated with systemic steroids.
Azathioprine and cyclophosphamide have also been used
successfully.

Cicatricial Pemphigoid
Cicatricial pemphigoid is a chronic subepidermal blistering
autoimmune disease. It is characterized by the presence
of vesicles involving the oral, genital, and conjunctival
mucosa. The oral lesions are generally erosions or shallow
ulcers on the facial gingiva, buccal mucosa, palate, tongue,
and lower lip. The ulcers exhibit a distinct outline and heal
with scarring in about one month.

Gastrointestinal diseases that may be associated with oral


ulcers include gastroesophageal reflux disease (GERD),
inflammatory bowel diseases (Crohns disease, ulcerative
colitis) and celiac disease. These patients have symptoms
of gastrointestinal discomfort along with oral ulcers. Generally barium meal and gastroscopic examination will confirm involvement of the GI tract.

Gastroesophageal Reflux Disease


Gastroesophageal reflux disease arises out of the passage
of gastric contents into the esophagus. GERD is considered the most common upper GI tract disorder with the
prevalence ranging from 6 to 10% of the population.
However, heartburn which is the most common symptom
of GERD is reported by 59% of the population. Gastroparesis, increased abdominal distention, hiatal hernia, and
myopathy causing defective GI motility are the common
causes for GERD.
Clinical features

Patients complain of pain burning sensation extending from epigastrium to the neck (heart burn) which is
commonly felt after a meal.
Chest pain that mimics anginal pain.
213

Section III Mucocutaneous Disorders

Esophagitis, esophageal ulceration and stricture.


Patients may complain of chronic coughing episodes.

Clinical features

Oral manifestations

Erosion of palatal surfaces of teeth leading to dentinal


hypersensitivity and occasional pulpal involvement.
Mucosal atrophy, erythema and ulceration.
Dysgeusia.

Crohns Disease
Crohns disease is a chronic inflammatory bowel disease
that can affect any part of the GI tract. It causes fissures,
transmural inflammation, and non-caseating granulomas of
the GI tract.
It generally affects males and females equally, however
it affects white males more frequently.
Clinical features

It has a bimodal peak of incidence. Crohns disease


affects individuals in the 2nd and 3rd decades of life
and in the 6th and 7th decades of life.
Individuals may complain of diarrhea or constipation,
abdominal pain, and intermittent fever.
Some patients may present with extra intestinal manifestations characterized by arthritis and erythema
nodosum.

Oral findings
Oral mucosal involvement is characterized by the presence
of ulcers, angular stomatitis and superficial hemorrhagic
ulcers. It is estimated that approximately 510% of the
patients with ulcerative colitis exhibit oral manifestations.

Celiac Disease
Celiac disease is an autoimmune gluten-dependent enteropathy characterized by intestinal malabsorption and subtotal or total atrophy of intestinal villi which improves
after gluten-free diet.

Oral findings

Clinical features

Many patients present with oral manifestations before any


systemic manifestations are evident. Halme in 1993 reported
that the severity of oral lesions may be used as a marker
to judge the severity of the intestinal impairment. On an
average approximately 89% of the patients may exhibit
oral manifestations prior to intestinal involvement.
Patients may present with:

1.

Diffuse painful swelling of the lips, gingiva and other


areas of the oral mucosa.
Oral ulcers and angular cheilitis.
The characteristic feature of Crohns disease is the
cobblestone appearance of the buccal mucosa.
Histopathological finding of non-caseating granulomas is typical of Crohns disease.
Difficulty in eating and swallowing due to the presence
of ulcers and fissures.

Ulcerative Colitis
Ulcerative colitis is a chronic inflammatory bowel disorder
sharing the similar clinical features of Crohns disease
except that the involvement is restricted to the mucosa
and submucosa of the colon.
214

Ulcerative colitis may occur at any age. However, it


most commonly affects individuals between the 2nd
and 4th decades of life.
Males and females are equally affected.
Patients may complain of abdominal pain and diarrhea associated with blood and mucus.
Loss of appetite, dehydration, fatigue and loss of
weight.
Some patients may complain of severe abdominal
cramps and the constant desire to empty bowels.
Handlers in 1999 reported extra intestinal manifestations such as ulcerations on the buttocks, abdomen,
thighs and face.

2.

3.
4.
5.

Infants present with growth retardation, diarrhea,


vomiting and abdominal distention.
Patients who are not treated in time may present with
short stature, pubertal delay, iron and folate deficiency with anemia, and rickets.
Young children may be depressed and irritable.
Adults may report of episodic or nocturnal diarrhea
and weight loss.
Other extra intestinal manifestations reported in
literature include infertility, peripheral neuropathy,
convulsions, psychiatric disturbances and increased
incidence of bone fractures.

Oral findings
Patients may present with oral ulceration that may mimic
ulceration of recurrent aphthous stomatitis.

NEOPLASTIC ULCERS
Neoplastic lesions that exhibit oral ulcerations are squamous cell carcinoma, adenocarcinoma, mucoepidermoid
carcinoma and metastatic carcinoma.

Chapter 8 Oral Ulcerative Diseases

Clinically, these ulcers exist for long periods of time, and


induration is a prominent feature. However, biopsy will
help in diagnosing the nature of the ulcers. The treatment
for most of these ulcers is surgery/radiation or combination
of both. The prognosis depends upon the stage of diagnosis.

ULCERS OF UNKNOWN ETIOLOGY


Necrotizing Sialometaplasia
Necrotizing sialometaplasia is a non-neoplastic, self-limiting, inflammatory condition of the salivary glands. Abrams
et al in 1973 described this condition for the first time. The
clinical and histopathological picture of necrotizing sialometaplasia resembles those of a malignancy, which often
leads to its misdiagnosis. It is proposed that necrotizing
metaplasia occurs due to vascular ischemia.

PFAPA Syndrome (Marshalls Syndrome)


In 1987, Marshall et al reported a condition with periodic
fever. This was termed Marshalls syndrome. However, this
condition was later referred to as PFAPA which included
periodic fever, aphthous stomatitis, pharyngitis and cervical
adenitis.
Diagnostic criteria for PFAPA syndrome
(proposed by Thomas et al)
1.

Clinical features

Literature review reveals that it affects individuals


from an early age of 8 months to 70 years. However, it
is commonly seen to affect individuals in the 4th and
5th decades of life.
The minor salivary glands of the palate (75% involvement) are very frequently involved followed by other
minor salivary glands in the retromolar pad area, buccal mucosa, tongue, incisive canal, and labial mucosa.
Involvement of the parotid and submandibular salivary glands are also reported.
Lesions of necrotizing sialometaplasia can present as
ulcers or well-defined submucosal swellings.
The typical ulcer has a crater like form, usually measuring 13 cm in diameter.
Erosion of the palatal bone may be appreciated in
some cases.

Diagnosis
Based on clinical appearance alone necrotizing sialometaplasia cannot be diagnosed. Generally, a histopathological
evaluation of the lesion is necessary to establish the correct diagnosis. Malignant ulcers, Wegeners granulomatosis, and extranodal lymphoma can be considered in the
differential diagnosis.

MAGIC syndrome (mouth aphthae, genital lesions and


interstitial chondritis)
Behets syndrome
Reiters syndrome
StevensJohnson syndrome
Ramsay Hunt syndrome

2.

3.
4.
5.

Regularly recurring fevers with an early age of onset


( 5 years of age)
Symptoms in the absence of upper respiratory tract
infection with at least one of the following clinical
signs:
a. aphthous stomatitis
b. cervical lymphadenitis
c. pharyngitis
Exclusion of cyclic neutropenia
Completely asymptomatic interval between episodes
Normal growth and development.

MAGIC Syndrome
Literature review reveals that the symptom complex of
mouth and genital ulcerations associated with inflamed
cartilage (polychondritis) was first described in 1995. Apart
from the typical ulcers involving the oral cavity and the
genital regions, polychondritis is present. It involves the
auricles, lungs, heart, and the vascular system. Patients may
also complain of associated symptoms such as fatigue, malaise, and fever. Use of immunosuppressive agents such as
azathioprine, methotrexate, or cyclophosphamide is the
modality of choice to manage symptoms and signs associated with MAGIC syndrome.

Reiters Syndrome

SYNDROMES ASSOCIATED WITH ORAL


ULCERS
The syndromes that are associated with ulcerative lesions
affecting the oral cavity are:

PFAPA syndrome (periodic fever, aphthae, pharyngitis,


adenopathy)

Reiters syndrome is named after Hans Reiter who described


a classical triad of arthritis, non-gonococcal urethritis, and
conjunctivitis, in 1916. However, in the recent years the
term Reiters syndrome is used to refer to peripheral arthritis lasting longer than one month, associated with urethritis, cervicitis, or diarrhea. It is usually seen following a
gastrointestinal or genitourinary infection. Reiters syndrome secondary to gastrointestinal infection is seen in
215

Section III Mucocutaneous Disorders

children whereas Reiters syndrome secondary to genitourinary infection is seen in adults.


It is generally seen in individuals in the second and
third decades. Peripheral arthritis is the most characteristic
feature. It usually affects the lower limbs. Mucocutaneous
lesions of Reiters syndrome are seen in adults. Balanitis
and vulvitis are typical of Reiters syndrome. Oral ulcers
and erosions are seen in some patients. Histopathologically it is difcult to distinguish these lesions from
psoriasis.

Behets Syndrome
Behets syndrome is named after Hulusi Behet, a Turkish
dermatologist who described a triad of RAUs, genital ulcerations, and uveitis leading to blindness, in 1937.
There are two widely used diagnostic criteria for
Behets disease, namely, the International Study Group
Criteria for diagnosis of Behets syndrome and ODuffy
criteria.
International Study Group Criteria for
diagnosis of Behets syndrome
Oral ulcers (major/minor/herpetiform RAUs) occurring at
least thrice in a year and the presence of at least two of the
following:

Recurrent genital ulcerations


Recurrent eye lesions (uveitis, retinal vasculitis and
cells in the vitreous)
Skin lesions (erythema nodosum/papulopustular lesions/
acneiform nodules)
Positive pathergy test.
ODuffy criteria
The ODuffy criteria require the presence of oral ulcers
(recurrent aphthous ulcerations) and the presence of any
two of following:

Genital ulcers
Uveitis
Cutaneous pustular vasculitis
Synovitis
Meningoencephalitis.

The diagnosis requires the exclusion of inflammatory bowel


disease, systemic lupus erythematosus (SLE), Reiters syndrome, and herpetic infections.
Oral ulcers
Oral ulcers are characteristic of this disease. Usually, oral
ulcerations are the first clinical finding. For diagnostic

216

purposes the presence of at least three episodes of ulcers in


a year is required. Painful crops of ulcers are seen which
typically heal without scarring.
Genital ulcers
Vulva and vagina in females and scrotum and penis in males
are the common sites for ulcers. These ulcers are painful
and usually heal with scar formation.
Ocular involvement
Patients complain of increased lacrimation, conjunctival
erythema, blurring of vision, eye pain and photophobia.
Other clinical findings
Patients can present with non-specific pustular skin rashes,
erythema nodosum and folliculitis. Arthralgias and arthritis can be seen. Patients may frequently complain of
abdominal pain, diarrhea, and melena. Involvement of the
central nervous system is the most dreaded manifestation
of Behets disease. Patients are also susceptible to deep
vein thrombosis and arterial disease as a result of vessel
involvement.

StevensJohnson Syndrome
StevensJohnson syndrome is characterized by the presence of minute blisters on the skin. Detachment of the
skin is limited to about 10% of the body surface area. Skin
detachment involving 30% or more of the body surface
area associated with epidermal necrosis is referred to as
toxic epidermal necrolysis. Clinically another variant is
considered which is characterized by skin detachment
between 10 and 29% of the body surface area and is termed
StevensJohnson syndrometoxic epidermal necrolysis
overlap.
Clinical findings
Patients complain of fever and myalgia. The initial presentation of the condition is an erythematous rash on the face
and trunk that rapidly spreads to involve other parts of the
body. Occasionally blisters are seen within the rash.
StevensJohnson syndrome and toxic epidermal necrolysis usually begin with fever, headache, cough, and body
aches, which may last from 1 to 14 days. This is followed
by the appearance of a at red rash on the face and trunk,
that often spreading later to the rest of the body in an
irregular pattern. The areas of rash enlarge and spread,
often forming painful blisters in the center. The skin over
the blisters can be easily slided off.
Blisters are seen on oral, ocular and genital mucosa that
subsequently ruptures to form ulcers. Patients will complain

Chapter 8 Oral Ulcerative Diseases

Table 6 Diagnostic protocols


Acute

Chronic

Single

Multiple

Single

Multiple

Recurrent

Traumatic ulcer
Aphthous ulcer

Herpetic gingivostomatitis
Recurrent intraoral herpes
Herpangina
Hand, foot and mouth disease
Chicken pox
Herpes zoster
Infectious mononucleosis
HIV infection
ANUG
Stomatitis medicamentosa
Stomatitis venenata
Herpetiform aphthous ulcers
Minor aphthous ulcers
Leukemia
Cyclic neutropenia

Infected traumatic ulcer


Major aphthous ulcer
Necrotizing sialometaplasia
Tuberculous ulcer
Syphilitic ulcer
Cancrum oris
Fungal ulcer
Malignant ulcer

Multiple major aphthous ulcers


Behets syndrome
Reiters syndrome
Pemphigus vulgaris
Benign mucous membrane
Pemphigoid
Erosive lichen planus
Lichenoid reactions

Aphthous ulcers
Cyclic neutropenia
Behets syndrome
Reiters syndrome
Lichen planus
Pemphigus
Pemphigoid

Table 7 Diagnostic protocols: investigations


Acute

Chronic

Single

Multiple

Single

Multiple

Recurrent

Generally no need
of investigations
Routine hemogram
may be performed

Hemogram to rule out


hematological malignancies
Tzanck smear
Antibody titers in recurrent
viral infection
Paul Bunnell test for infectious
mononucleosis
Bone marrow study for
leukemia

Biopsy
In case of TB, Mantoux
test, ESR, lymphocyte
count, chest X-ray, PCR
In case of syphilis, VDRL
test, FTA-ABS test or TPI
assay
Special stains in case of
suspected fungal infections

Biopsy for histopathologic


examination and DIF
Indirect IF
Routine hemogram with
ESR
Serum protein level
Patch test in case of
suspected lichenoid
reactions

For cyclic
neutropenia, TC
and DC thrice in a
week for 68 weeks
Hemogram
Pathergy test in
Behets syndrome

difculty in eating and swallowing. Increased salivation


may be an associated complaint.

Step 3: Correlate the history and clinical findings and


draw a differential diagnosis
Step 4: Investigations to establish the diagnosis (Table 7).

DIAGNOSTIC PROTOCOL
Step 1: Determine whether ulcers are acute or chronic,
single or multiple or recurrent (by history) (Table 6).
Step 2: Note the features of the ulcer(s) and associated
symptoms:
1. Size, shape, location, surrounding area, tissue tags at
periphery, tenderness, foul smell, bleeding, induration
of base, edges, margins, floor
2. Presence of skin lesions (e.g. lichen planus, pemphigus,
pemphigoid, erythema multiforme, StevensJohnson
syndrome, etc.)
3. Systemic symptoms (fever, malaise, etc.) seen in viral
infections, ANUG, TB, erythema multiforme, etc.

Step 5: General guidelines for managing oral ulcers:


1. Patient is advised to discontinue oral habits such as
smoking/pan chewing/alcohol.
2. In viral ulcers, rest is important and adequate hydration
to be ensured.
3. The treatment should be directed at the cause.
4. Symptomatic relief with topical anesthetic/analgesic
preparations.
5. Antiseptic ointments/gels to prevent secondary infection.
6. Topical steroids in ulcers taking longer time to heal
(triamcinolone acetonide in Orabase).
7. Systemic steroids in case of erythema multiforme,
pemphigus, pemphigoid, erosive or vesiculobullous
lichen planus and allergic stomatitis.

217

CHAPTER

Dermatological Diseases
K Srinivas, Sarita Dimri, Ravikiran Ongole

Lichen Planus

HaileyHailey Disease (Familial Benign


Chronic Pemphigus)

Psoriasis

Dariers Disease (Keratosis Follicularis)

Ectodermal Dysplasia

Reiters Syndrome

EhlersDanlos Syndrome

Pachyonychia Congenita

Incontinentia Pigmenti (BlochSulzberger


Syndrome)

Dyskeratosis Congenita

Pityriasis Rosea

Kawasaki Disease (Mucocutaneous Lymph


Node Syndrome)

Xeroderma Pigmentosum

Acanthosis Nigricans

Tuberous Sclerosis Complex (Epiloia,


Bournevilles Disease)

GoltzGorlin Syndrome

Graft-versus-host disease

Acrodermatitis Enteropathica

Diagnostic Signs in Dermatology

Epidermolysis Bullosa

LICHEN PLANUS
Lichen planus (LP) has also been known as lichen ruber
planus. It is one of the most common dermatologic, immunopathological diseases to affect the oral mucous membrane. The management of oral lichen planus continues to
challenge even the most experienced oral physician.
The term lichen planus is derived from a Greek word
lichen which means tree moss and a Latin word planus
which means at. The strange name of the condition was
provided by the British physician Erasmus Wilson, who
rst described the lesion in 1869. Thibierge rst described
the oral lesions systematically in 1885.
Fitzpatrick et al (1993) described LP as a unique cutaneous entity consisting of an eruption of papules distinct in
color and conguration, in patterns and location of appearance and in microscopic as well as gross structure.
Andreasen categorized oral LP into six types, namely,
reticular, papular, plaque-like, atrophic, erosive, and bullous.
Lichen planus has been associated with various diseases
such as hepatitis C, oral cancer, and diabetes mellitus.
218

Etiopathogenesis
An interplay of host, lifestyle, and environmental factors
has been implicated in the etiopathogenesis of LP. It is
believed that LP is caused due to cell-mediated immunity
initiated by endogenous or exogenous factors.
Clinical features
The onset of LP occurs most commonly during the 5th or
6th decade. No sexual predilection is evident. The typical
cutaneous lesions of LP present as flat topped, purple, polygonal, pruritic papules and plaques most commonly occurring
on the flexor surfaces of the arms, wrists, ankles, and legs.
Oral lesions may be observed in up to 75% of patients
with cutaneous LP and in approximately 25% of cases it
can be the only manifestation of the disease. Conversely,
only 1020% of patients whose initial presentation is oral
LP will develop cutaneous LP. The oral lesions have been
observed in up to 14% of the population.
Oral LP almost invariably occurs as a bilateral disease
and it involves the posterior buccal mucosa followed less
commonly by the tongue, gingiva, hard palate, and the

Chapter 9 Dermatological Diseases

Unknown antigenic change in oral mucous membrane

Figure 1

Focal accumulation of Langerhans cells within


the epithelium

Activated helper/inducer T lymphocyte in


the lamina propria

Expression of ICAM and HLA-DR on the


surface of keratinocytes

Influx of cytotoxic/suppressor T-cells within


the epithelium

Keratinocyte damage

Basal cell degeneration

Pyknotic and shrunken basal cells (Civatte bodies)

Apoptosis of keratinocytes

Linear lesions of LP occurring as a result of scratching


characteristic of Koebners phenomenon. Courtesy:
Department of Oral Medicine and Radiology,
MCODS, Mangalore

Atrophic and erosive lesions involving the gingiva results


in desquamative gingivitis which is characterized by bright
red areas involving the full width of attached gingiva.

Failure of phagocytosis of apoptotic cells

Investigations
Colloid bodies (underlying dermis)

labial mucosa. Although any site can be involved, palatal


and sublingual lesions are very uncommon.
Clinically oral LP appears as radiating white or gray
velvety thread like lesion, which consists of papules in linear, annular or retiform arrangement. A tiny white elevated dot is present at the intersection of the white lines
known as Wickhams striae or Honiton lace.
An isomorphic response (Koebners phenomenon) is common occurrence in LP, and develops in areas previously
subjected to some type of trauma (Figure 1). Reticular is
the most common type, consisting of slightly raised ne
whitish lines in an interlocking lace like keratotic pattern.
Papular lesions are small (0.51.0 mm) white raised papules. Plaque type closely resembles leukoplakia with a
reticular surrounding. Atrophic type appears as inamed
areas of mucosa covered by thin red appearing epithelium.
Erosive type presents with atrophic mucosa with ulcers.
Bullous form is very rare and is characterized by formation of large thin walled bullae.
Papular, plaque like, atrophic and erosive lesions are
very frequently accompanied by reticular lesions. All
forms of oral LP are generally asymptomatic, but atrophic,
erosive and bullous forms are associated with pain and
burning sensation.

Biopsy of the lesion should be done to confirm the diagnosis. In situations where histopathology does not confirm
the diagnosis then immunofluorescence studies of biopsy
specimens should be done. Direct immunofluorescence
demonstrates a shaggy band of fibrinogen in the basement
membrane zone in 90100% of cases. Specimens for immunofluorescence should be stored in Michels/Bouins solution or normal saline and then sent to histopathology.
Differential diagnosis
Reticular form
Plaque form

Lichenoid reactions
Leukoplakia, hyperplastic candidiasis, traumatic keratosis
Atrophic form
Speckled leukoplakia, anemic
stomatitis, systematic lupus
erythematosus and discord
lupus erythematosus
Erosive and bullous form Vesiculobullous lesions
Annular form
Erythema circinata migrans.
Management
The lesions of oral LP appear, regress and reappear in some
what unpredictable fashion. Asymptomatic LP need not be
treated. The treatment of symptomatic LP is necessary.
The role of Candida in the causation of oral LP has been
debated, therefore a smear for candida needs to be made and
219

Section III Mucocutaneous Disorders

if positive, a topical antifungalclotrimazole (available as


Candid gum paint in India) should be given for 14 days.
Steroid-resistant cases can be treated using topical
tacrolimus 0.1% (available as Tacroz and Tacrovate), cyclosporine rinse and systemic hydroxychloroquine sulfate
200 mg o.d. for 36 months (available as tablet HCQS).
Other modes of treating oral LP are topical and systemic
retinoids, psoralen ultraviolet A (PUVA) therapy, dapsone,
mesalazine and levamisole.
Erosive LP is a premalignant condition with a malignant
transformation rate of 0.10.3%. It has to be supplemented
with systemic vitamin A preparations for chemoprevention.
However most lesions of erosive LP do not respond to
conventional steroid therapy unless supplemented by intralesional steroids and especially so if ulcerations are present.
Treatment of oral lichen planus is given in Flowchart 2
on page no 153.

EPIDERMOLYSIS BULLOSA
Epidermolysis bullosa (EB) is a diverse group of disorders
that have as a common feature blister formation with tissue
separation occurring at variable depths in the skin and/or
mucosa depending on the specific EB type. There may be
marked oral involvement, potentially creating devastating
alterations in the soft and hard tissues. Oral tissue fragility
and blistering is common to all EB types.
Classification

Epidermolysis bullosa simplex


Epidermolysis bullosa simplex with muscular dystrophy
Epidermolysis bullosa atrophicans genaralisata graves
Epidermolysis bullosa dominant dystrophic/hypertrophic
form
Scarring epidermolysis bullosa with dermolytic vesicles.
The current classication proposed for epidermolysis
bullosa is mentioned in Chapter 7 on Vesiculobullous
Disorders.
Etiopathogenesis
Pertaining to hereditary forms pathogenesis appears to be
related to genetic defects in basal cells, hemidesmosomes
or anchoring connective tissue filaments depending on the
disease subtype. The acquired non-hereditary type is often
precipitated by exposure to specific drugs, and type VII
collagen antibodies located below the lamina densa are
found.
Clinical features
Epidermolysis bullosa simplex Epidermolysis simplex is
seen in neonates and infants. Nails, feet, hand and neck
220

develop vesicles and bulla in response to friction. Oral


vesicles are mild and small and heal without scarring.
Epidermolysis bullosa simplex with muscular dystrophy
An autosomal recessive disorder that appears at birth.
Multiple bullae are seen frequently involving the oral mucosa.
Extremities develop more bullae which result in scarring that
eventually leads to muscular dystrophy and deformity.
Epidermolysis bullosa atrophicans generalisata graves
An autosomal recessive disorder that develops in neonates
within hours after birth. Nail beds are usually the first area
of involvement with shedding of nails, remaining skin
surface progressively develops bullae. Many infants die
within a few months and survivors have nail distortion,
growth retardation, anemia, scarring and skin lesions.
Large fragile vesicles and bullae are frequently seen in the
oral cavity, especially in the posterior hard palate and soft
palate. Enamel hypoplasia and enamel pits leading to
dental caries are usually seen. Another routinely encountered feature is perioral crusting.
Epidermolysis bullosa dominant dystrophic/hypertrophic
form An autosomal dominant form, which is very mild;
20% of patients develop lesions before 1 year of age.
Vesicles and bullae begin to develop and gradually lessen
with age. Dystrophic nails and scarring is prominent. White
mucosal epithelial inclusion cysts may be seen on the
tongue, buccal mucosa and palatal mucosa.
Scarring epidermolysis bullosa with dermolytic vesicles
An autosomal recessive disorder that appears shortly after
birth. Bullae are seen on the feet, fingers, buttocks, back
and the occiput. Oral vesicles prone to scar formation are
seen. Hypoplastic enamel and enamel pits are commonly
found.
Differential diagnosis
Lesions of pemphigus vulgaris, erythema multiforme and
dermatitis herpetiformis mimic epidermolysis bullosa. Histopathological and immunofluorescent studies will help in
differentiating these conditions.
Management
Treatment is often frustrating because conventional therapy
with corticosteroids and immunosuppressive agents frequently does not result in significant clinical improvement.
Various therapeutic modalities have recently been used
which include cyclosporine, colchicine, plasmapheresis,
extracorporeal photochemotherapy and intravenous gamma
globulins.
Although the data are preliminary, they suggest that
intravenous immunoglobulins may be a promising treatment modality for resistant, non-responsive or refractory
EB acquisita.

Chapter 9 Dermatological Diseases

Dental management

Etiopathogenesis

The majority of individuals with mild EB subtypes may


receive dental treatment with only minor modifications in
approach.
Individuals with EB can retain their dentition using
conventional restorative techniques. With aggressive
preventive interventions and management of developing
malocclusions using serial extraction, it is also possible
to reduce the likelihood of rampant caries, achieve an
acceptable occlusion without the need for active tooth
movement or appliance therapy, and allow these individuals to benet from maintaining a natural healthy
dentition.

Although the cause of psoriasis is unknown, it is now widely


accepted that psoriasis involves an increase in the rate of
epithelial cell proliferation. It is proposed that the increased
epithelial turnover rate of psoriasis is associated with cell
damage.
There also appears to be a strong genetic component to
the pathogenesis of psoriasis. Thirty-ve percent of patients
with psoriasis have a positive family history. Studies on
the major histocompatibility complex (MHC) have shown
a strong association between B13, Bwl7, Bw37, and Cw6
antigens and development of psoriasis.
Clinical features

PSORIASIS
Psoriasis is a non-contagious skin disorder that most commonly appears as inflamed, edematous skin lesions covered
with a silvery white scale.
Types

Guttate psoriasis
Pustular psoriasis
Inverse psoriasis
Erythrodermic psoriasis.

Psoriasis is more common in whites and in women. Approximately 1015% of new cases begin in children younger than
10 years. The median age at onset is 28 years. Typical skin
lesions of psoriasis appear as well-circumscribed erythematous patches with overlying thick silvery scales (Figure
2A, B). Lesions may occur in any location, but most commonly involve the scalp and the anterior hairline, torso,
bony prominences of the extremities, nails, perianal and
perineal areas. The course of the disease is unpredictable
and characterized by spontaneous episodes and relapses.
If the deep scales are removed, one or more tiny bleeding points are disclosed, which is popularly referred to as
Auspitzs sign.

Figure 2
A

Erythematous patches on the forearms along with silvery scales in psoriasis. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

221

Section III Mucocutaneous Disorders

The oral counterpart of psoriasis is rare. The rst descriptions of oral lesions of psoriasis have been attributed to
Oppenheim and Thimm (1903).
Van der Waal and Pindborg described four types of oral
psoriatic lesions.

Well-defined, gray to yellowish white, tiny, round to


oval lesions.
Lacy, circinate, white elevated lesions on the oral mucosa
and the tongue paralleling skin lesions.
Fiery red erythema of the oral mucosa including the
tongue seen primarily in the acute form of psoriasis.
A geographic tongue that occurs more frequently among
patients with psoriasis than without.

Clinical features
The condition is characterized by hypodontia, hypotrichosis, and hypohidrosis. Neonates exhibit excessive scaling
of the skin and unexplained pyrexia. Patients present with
sparse hair and eyebrows (Figure 3A, B).
As the age progresses frontal bossing, saddle nose, sunken
cheeks, thick/everted lips wrinkled and hyperpigmented

Figure 3
A

Histopathology
Histopathologically, intraepithelial microabscesses (Munros
abscesses) are common. However, these are not specific for
the disease.
Management
Oral lesions should be treated with topical corticosteroids.
The topical steroids that are available in India are triamcinolone acetonide0.1% with orabase (Kenacort oral paste,
TESS cream), clobetasol propionate0.05% (Clobetamil
cream, Tenovate skin cream).
Psoriatic arthritis
Psoriatic arthritis is a systemic disorder and inflammatory
condition and this disease may be the major contributing
factor to temporomandibular dysfunction (TMD) symptoms
and signs. TMD signs and symptoms are found more frequent and more severe in the patients with psoriatic arthritis
of other joints than in the patients with psoriasis without
arthritis. TMD signs and symptoms in psoriasis are mainly
caused by the related joint involvement that directly affects
the masticatory system.

ECTODERMAL DYSPLASIA
The ectodermal dysplasias comprise a large and heterogeneous group of disorders (about 170) characterized by a
variety of congenital defects in structures of ectodermal
origin including skin, hair, teeth, nails, and sweat glands.
Out of these the most common and best studied disease is
anhidrotic or hypohidrotic ectodermal dysplasia (Christ
SiemensTouraine syndrome).
Etiopathogenesis
It is an inherited X-linked recessive trait associated with
the repressed expression of a gene on the X-chromosome
in the positions from q13 to q21.
222

(A) A boy with sparse scalp hair in ectodermal dysplasia.


Courtesy: Dr Sumanth KN. (B) Photograph showing
hair loss of the eyebrows and scalp hair. Courtesy:
Department of Oral Medicine and Radiology,
MCODS, Mangalore

Chapter 9 Dermatological Diseases

Figure 4

Hypoplastic and conical primary maxillary central incisors in


ectodermal dysplasia. Courtesy: Dr Sumanth KN

Figure 5

Figure 6

Hypoplastic and malformed maxillary second primary molars


as well as underdeveloped alveolar ridges in ectodermal
dysplasia. Courtesy: Dr Sumanth KN

malformed (Figure 6). Orthopantomograph will help to


conrm the absence of teeth (Figure 7).
Differential diagnosis
Distinct condition if all the three components are present.
However, for single component of disease the differential
diagnosis is isolated oligodontia, Witkop tooth nail syndrome and trichodental syndrome.
Management
There is no treatment available and the treatment is symptom related. For xerostomia, pilocarpine 5 mg one tab is
given three times a day. Salivary substitutes can be used.
Crowns for malformed teeth and dental implants for edentulous areas can be recommended.

Hypoplastic and malformed mandibular second primary


molars as well as underdeveloped alveolar ridges in
ectodermal dysplasia. Courtesy: Dr Sumanth KN

skin around the eyes are seen. Patients may present with
fever of unknown origin because of the inability to sweat.
Oral manifestations
Anodontia/oligodontia is often seen. The remaining teeth are
usually malformed. Both deciduous and permanent teeth are
affected. Most common missing teeth are molars. Malformed teeth have truncated and conical crowns and shortened roots (Figures 4 and 5).
Dry mouth, high palatal arch and cleft palate may be
seen in some individuals. The alveolar ridges are usually

EHLERSDANLOS SYNDROME
The term EhlersDanlos syndrome (EDS) was coined after
the names of a Danish dermatologist, Edvard Ehlers (1901)
and a French dermatologist, Henri Alexandre Danlos
(1908) who reported patients exhibiting thin, hyperplastic
skin, loose jointedness, and hemorrhagic tendencies.
It is a group of inherited disorders characterized by
excessive looseness (laxity) of the joints, hyperelastic skin
that is fragile and bruises easily, and/or easily damaged
blood vessels. The diagnosis of EDS encompasses any of
six types of connective tissue disorders that are hereditary
in nature and exhibit a characteristic defect in collagen
metabolism.
There are six major types of EDS that are characterized
by distinctive features.
223

Section III Mucocutaneous Disorders

Figure 7

Orthopantomograph showing multiple missing teeth in ectodermal dysplasia. Courtesy: Dr Sumanth KN

EDS was initially subdivided into seven types following


a meeting of various authors in Berlin, Germany. However
owing to its complex nature, another widely accepted classication consisting of six types of EDS was proposed in
Villefranche, France in 1997.
Villefranche classification of EDS

Classical EDS (similar to Berlin Type I [gravis] and


Berlin Type II [mitis])Type V collagen defects.
Hypermobility EDS (similar to Berlin Type III [hypermobile])unknown collagen defects.
Vascular EDS (similar to Berlin Type IV [arterialecchymotic])Type III collagen defects.
Kyphoscoliosis EDS (similar to Berlin Type VI [ocularscoliotic])defect in lysyl hydroxylase.
Arthrochalasia EDS (similar to Berlin Type VIIa and
VIIb [arthrochalasis multiplex congenita])defect in
Type I collagen.
Dermatosparaxis EDS (similar to Berlin Type VIIc
[human dermatosparaxis])defect in procollagen
N-peptidase.

Etiopathogenesis
Different forms of EDS have different modes of inheritance.
Family history is a risk factor in some cases. Various subtypes are inherited as autosomal dominant/recessive and
X-linked traits. A variety of genetic mutations cause abnormality in collagen that will result in the disease.
Clinical features
Symptoms
Joint dislocation/subluxation/joint pain, increased
joint mobility, joints popping, early arthritis, doublejointedness and flat feet
Easily damaged, bruised, and stretchy skin which is
very soft and velvety

224

Easy scarring and poor wound healing


Premature rupture of membranes at birth
Visual difficulties.

Signs
Excessive joint laxity and hypermobility
Soft, thin, or hyperextensible skin
Mitral valve prolapse
Signs of platelet aggregation failure
Rupture of intestines, uterus, or eyeball (seen only in
vascular EDS, which is rare)
Deformed cornea.
Oral manifestations
Scarring on the chin and forehead, a history of repeated
luxations of the TMJ, epicanthus, hypertelorism, a narrow
curved nose, sparse hair and hyperelasticity of the skin.
Fragile mucosa and gingivaearly-onset generalized
periodontitis leading to premature loss of deciduous and
permanent teeth. Tooth mobility is often encountered.
Hypoplasia of the enamel is commonly seen. Premolar
and molar teeth can present with deep ssures and long
cusps. Microdontia is sometimes present. Irregularities in
the dentin structure and dentinal tubules may also be seen.
Radiographic examination often reveals pulp stones
and roots that are short and deformed.
The tongue is very supple. Approximately, 50% of those
with the syndrome can touch the end of their nose with their
tongue (Gorlins sign), compared to 810% of the normal
population and the palate is commonly vaulted.
Investigations

Collagen typing performed on a skin biopsy sample


Collagen gene mutation testing
Lysyl hydroxylase or oxidase activity
Echocardiograph (heart ultrasound).

Chapter 9 Dermatological Diseases

Differential diagnosis
Marfans syndrome, generalized familial joint hypermobility syndrome, cutis laxa, pseudoxanthoma elasticum and
Larsens syndrome.
Management
There is no specific cure for EDS, so individual problems
and symptoms must be evaluated and cared for appropriately. Genetic counseling is recommended for prospective
parents with a family history of EDS.
Dental considerations

Mitral valve prolapse indicates prophylactic antibiotics


are for relevant procedures.
Inferior alveolar nerve blocks should be given with
great care to avoid causing hematoma.
Forces used in orthodontic treatment should be
lighter than usual, given the fragility of the periodontal
ligament and relapses are common dictating a longer
period of retention.
Ideally, oral surgery should be avoided. It is imperative
to test blood coagulation values before proceeding
with surgery. Since sutures do not hold well wounds
should be covered with acrylic dressings.

PACHYONYCHIA CONGENITA
Pachyonychia congenita (PC) is a rare autosomal dominant keratin disorder that typically affects the nails and
palmoplantar skin, and often the oral mucosa, tongue,
larynx, teeth, and hair.
Mller made the rst documented observation in 1904.
Jadassohn and Lewandowsky published the next reports
in 1906. In the dermatologic literature, PC is better known
as JadassohnLewandowsky syndrome. PC is also known
as Touraines polykeratosis congenita, palmoplantar keratoderma.
Etiopathogenesis
The disease results from mutations in the genes encoding
epidermal keratinocyte keratins. The mutation is likely to
have a deleterious effect on protein structure as it interferes with the assembly of polypeptides forming the keratin
skeleton of epidermal cells (Bowden, 1995).
Clinical features
Onychodystrophy, palmoplantar keratoderma and follicular keratosis in areas of friction are characteristic features. Epidermal inclusion cysts and pilosebaceous cysts
are often seen in PC. Thickened or coarse curly hair is
usually seen. Laryngeal involvement is usually present

as hoarseness and occasionally as a life-threatening


respiratory stridor.
Oral manifestations
Oral findings present soon after the birth and may be the
earliest sign of the disease. Focal or generalized white
opaque thickening of oral mucosa (oral leukokeratosis) is
commonly seen on the buccal mucosa, tongue and lips.
Intermittent angular cheilitis is also seen in some cases.
Patients sometimes present with natal and prenatal teeth.
Investigations
Molecular DNA analysis will help in identifying the condition.
Biopsy may be performed to differentiate oral leukokeratosis from leukoplakia.
Though no specic treatment exists for the condition, it
is believed that the clinical manifestations of the condition
become less severe with advancing age.

DYSKERATOSIS CONGENITA
Dyskeratosis congenita, also known as ZinsserEngman
Cole syndrome and HoyeraalHreidarsson syndrome, is a
rare, progressive bone marrow failure syndrome characterized by the triad of reticulated skin hyperpigmentation,
nail dystrophy, and oral leukoplakia.
It is a pre-malignant condition. It is genetically heterogeneous, with X-linked recessive, autosomal dominant
and autosomal recessive subtypes. It is related to telomerase dysfunction. Telomeres are repeat structures found at
the ends of chromosomes that function to stabilize chromosomes. With each round of cell division, the length of
telomeres is shortened and the enzyme telomerase compensates by maintaining telomere length in germline and
stem cells. Because telomeres function to maintain chromosomal stability, telomerase has a critical role in preventing cellular senescence and cancer progression.
Rapidly proliferating tissues with the greatest need for
telomere maintenance (e.g. bone marrow) are at greatest
risk for failure.
Clinical features
Mucocutaneous features The mucocutaneous features are
the most consistent features of the disease. Reticulated skin
hyperpigmentation affecting the neck, face, chest, and
arms is the most common finding occurring in approximately 90% of patients. Telangiectasia, atrophy (pokilodermia) dystrophic nails and palmoplantar keratoderma,
hyperhidrosis, blepharitis, conjunctivitis, epiphora include
other signs which are less frequently seen.
Leukoplakia, which is the third feature of the classic
clinical triad, has been reported in 80% of the affected
225

Section III Mucocutaneous Disorders

patients. This can occur on any mucosal surface, but has


been most frequently reported affecting the oral mucosa.
The specic intraoral sites affected include lingual mucosa,
buccal, mucosa and the palate, with the tongue being the
most frequently affected. The other sites reported include
the urethra, glans penis, vagina and anorectal region.
Patients have a recognized increased risk of malignancy
from pre-existing mucosal leukoplakia, reaching an incidence of approximately 35% with a peak in the third
decade of life.
Non-mucocutaneous features The non-mucocutaneous
features include bone marrow failure, pulmonary disease,
ophthalmic, skeletal, dental, genitourinary, gastrointestinal and neurological abnormalities. One of the most common features of this disease is bone marrow failure
resulting in peripheral cytopenias.
Bone marrow failure is reported as the principal cause
of death in 70% of patients as a consequence of bleeding
or opportunistic infections.
Oral manifestations
Manifestations in the oral cavity other than leukoplakia
include hyperpigmentation of the buccal mucosa, severe
periodontal disease, hypocalcified teeth and taurodontism.
Crops of vesicles with patches of white necrotic mucosa
infected with Candida are another commonly encountered
feature.
The oral lesions can be histopathologically evaluated
for assessing the degree of dysplasia.
Management
Pancytopenia responds to androgen therapy in about 50%
of patients. Supportive care is important. Bone marrow
transplant has cured about 25% of a small number of patients.
Oral leukoplakia should be treated conventionally.
Dental considerations
It is imperative to test blood coagulation values before
proceeding with surgery in patients with aplastic anemia
and pancytopenia.

PITYRIASIS ROSEA
Pityriasis rosea (PR) is an acute self-limiting disease, probably infective in origin, affecting mainly children and
young adults, and characterized by a distinctive skin eruption and minimal constitutional symptoms.
Etiology
The cause of PR is uncertain, but many epidemiological and
clinical features suggest that an infective agent may be
226

implicated. Recently herpes like particles have been found


in 71% of PR lesions. Involvement of two herpes viruses,
HHV-6 and HHV-7 has been suggested as a cause of eruption. There are various reports associating PR like eruptions with drugs like metronidazole, barbiturates, captopril,
clonidine, gold and ketotifen. However, reported epidemiological evidence for infectivity includes occasional family
history or household outbreaks, seasonal and year to year
to fluctuations.
Clinical features
The first manifestation of the disease is usually the
appearance of the herald patch which is sharply defined,
bright red, round or oval plaque of 25 cm covered with
fine scales usually seen on the thigh or upper arm, trunk
or the neck in 5090% of cases. After an interval of
515 days, the general eruptions begin to appear in crops
at 23 days interval as dull pink colored oval small plaques
covered by fine, dry, silvery scales in Christmas tree pattern (long axis of the lesion characteristically follow the
lines of cleavage parallel to the ribs) on the upper chest
and back.
Involvement of oral mucous membrane is unusual but
ill-dened red patches with some desquamation or with
punctuate hemorrhages, or bullae may be observed.
The lesion of PR can be large (PR gigantea), urticarial
(PR urticata), vesicular, pustular, purpuric and erythema
multiforme like.
Differential diagnosis

Seborrheic dermatitis
Guttate psoriasis
Secondary syphilis
Pityriasis lichenoides.

Treatment and prognosis


Since the disease is asymptomatic and self-limiting, no
treatment is required. Oral erythromycin in a dose of 200 mg
four times a day has been shown in a study by Sharma
et al to hasten the clearance of the lesions. If the itch is
troublesome or the appearance is distressing, a topical steroid or UVB irradiation can be helpful.
The skin lesion commonly fades after 36 weeks and
may leave temporary hypo- or hyperpigmentation. Second
attack of PR occurs in about 2% of cases after an interval
of few months or many years.

XERODERMA PIGMENTOSUM
Xeroderma pigmentosum (XP) is a rare autosomal recessive disease characterized by photosensitivity, pigmentary
changes, premature skin aging, neoplasia and abnormal

Chapter 9 Dermatological Diseases

DNA repair. Some patients with XP also have neurological


complaints.
Etiology
Hebra and Kaposi first reported this disorder in 1874 and
the term xeroderma pigmentosum meaning pigmented
dry skin was introduced in 1882.
Inheritance is autosomal recessive and there are at least
eight different subtypes that are recognized, designated
complementation groups AG and XP variant.
Cleaver rst reported in 1968 that broblast from most
patients with typical XP lack the normal capacity to repair
UV radiation damage to DNA. Epstein et al in 1970 showed
that DNA repair was defective in vivo. Approximately,
80% of patients with XP show a defect in the initiation of
DNA excision repair of UV photoproducts in all cell types:
epidermal cells, dermal broblasts, lymphocytes, conjunctival cells, corneal cells and amniotic uid cells.
Clinical features
Skin is normal at birth and first symptoms are noted
between the 6th month and the 3rd year in 75% of cases
as freckling and increasing dryness on light exposed surfaces followed by acute sunburn or more persistent erythema telangiectasia and angiomas on unexposed skin
and on the lingual and buccal mucosa. Superficial ulcers,
healing with difficulty leave disfiguring scars and contractures may produce ectropion. Keratoacanthomas,
actinic keratoses, small round white atrophic spots and
crusted vesiculobullous lesions are also seen.
Malignant tumors like basal cell carcinoma, squamous
cell carcinoma may develop as early as the 3rd or 4th year.
The disease is often fatal before the age of 10 years and
worldwide two-thirds die before 20 years of age.
Ocular symptoms
The eyes are affected in 80% of cases and presents as photophobia and conjunctivitis as early symptoms and ectropion,
symblepharon, ulceration, vascular pterygium, corneal opacities and epitheliomas of lid conjunctiva and cornea may
develop later.
Neurological symptoms
Neurological symptoms occur in 20% of XP patients
with one or more of the following: mental retardation,
areflexia or hyporeflexia, spasticity, ataxia, sensorineural
deafness, dysphasia and abnormal electroencephalographic
findings.
Oral manifestations
Oral manifestations which often occur before 20 years of
age, include development of squamous cell carcinoma of
the lower lip and tip of the tongue.

Diagnosis
The unscheduled DNA synthesis assay (following UV irradiation of the cells in culture) is the standard laboratory
method for diagnosis of XP. Prenatal diagnosis by amniocentesis and molecular genetic techniques allow for earlier
and more reliable results.
Treatment
Patients must be protected from sunlight by every possible
meansby using sunblock creams, sunglasses with side
shields, two layers of clothing and broad brimmed hat.
Early and adequate excision of all tumors is essential.
Topical 5-uorouracil may be useful for early or premalignant lesions. A recent clinical trial by Yarosh et al
used the microbial enzyme T4 endonuclease V applied
regularly as a topical liposome lotion for over a period of
1 year, signicantly reduced the onset of both new basal
cell carcinoma and actinic keratoses.
The prognosis is poor. Most patients die 30 years earlier
than the normal population, either directly from cutaneous malignancy or from complications associated with the
treatment of the cancer.

ACANTHOSIS NIGRICANS
Acanthosis nigricans (AN) is an acquired dermatologic
condition characterized by the development of a velvety,
brownish alteration of the skin. The cutaneous lesions itself
is benign, yet it is significant because it represents a cutaneous marker for internal malignancy.
Etiology
Acanthosis nigricans has a variety of known causes
whose common mechanism is likely to be stimulation of
tyrosine kinase growth factor receptor signaling pathway
in epidermis.
In insulin resistance syndrome, high levels of circulating insulin directly or indirectly activate the insulin-like
growth factor 1 receptor (IGF1R), which is a transmembrane protein related to the insulin receptor.
Tumor-derived growth factors are preserved to be involved
in malignant AN.
Clinical features
Earliest changes are pigmentation, dryness and roughness
of the skin which in the affected areas is grayish brown or
black, palpably thickened and covered by small papillomatous elevations, which give it a velvety texture. As the
thickening increases, the skin lines are further accentuated
and the surface becomes mammillated or rugose and larger
warty excrescences develop. Most common sites are axillae,
227

Section III Mucocutaneous Disorders

the back and sides of neck, anogenital region and the


groin and flexures.
Oral lesions of AN have also been reported and may
occur in 2550% of affected patients, especially those with
malignant forms. The lesions appear as diffuse, nely papillary areas of mucosal alteration that most often involve
the tongue or lips, and rarely buccal mucosa.
Types of AN
1.
2.
3.
4.
5.
6.
7.
8.

Inherited forms of acanthosis nigricans


Benign acquired acanthosis nigricans
HAIR-AN syndromehyperandrogenism, insulin resistance and acanthosis nigricans
Autoimmune acanthosis nigricans
Drug-induced acanthosis nigricans
Malignancy-associated acanthosis nigricans
Tripe palms
Nevoid acanthosis nigricans.

Management
Treatment is of the underlying cause or is otherwise symptomatic and of little help. Removal of the tumor in the
malignant form may allow some improvement. A case of
hereditary benign AN improved dramatically with etretinate.
Although AN itself is a harmless process, the patients should
be evaluated to ascertain which form of disease is present.

GOLTZGORLIN SYNDROME
GoltzGorlin syndrome is also referred to as focal dermal
hypoplasia syndrome or Goltz syndrome. We should be
aware that this syndrome is not the same as Gorlin syndrome or GorlinGoltz syndrome, which is basal cell nevus
syndrome.
This uncommon genetic condition is transmitted as an
autosomal dominant trait. It is characterized by typical
skin defects and widespread involvement of various organ
systems. It affects the eyes, skeletal system, urinary system, cardiovascular and central nervous system and the
gastrointestinal system.
Clinical features
Almost 90% of the individuals who present with this syndrome are females. When it occurs in males the condition
is lethal. The clinical features are usually evident at birth
and the signs and symptoms progress with advancing age.
Patients are usually short statured with sparse hair over
the scalp, pubic region, eyebrows and eyelashes. Patients
may complain of hypohidrosis. Other features include nail
dystrophy and syndactyly, polydactyly and lobster-claw
deformity of the hands. Diffuse cortical cerebellar atrophy
and recurrent respiratory infections may be seen.
228

Skin manifestations
As the name suggests there is a focal loss of the dermis
characterized by the outpouching or herniation of the subcutaneous fat. Based on the degree of melanin pigmentation, the lesion has varied appearances. Erythematous
macules are evident in fair skinned individuals whereas
areas of hypo- or hyperpigmentation are seen in darker
individuals. The lesions are typically confined to the lines
of Blaschko. The common sites that are affected are the
forearms, thighs and cheeks.
Some authors describe the presence of raspberry like
papillomas. Papillomas are usually present at the skin and
mucosal junction such as the perioral, periocular, perianal
and perivulvar regions.
Facial features
Patients may have an asymmetrical face with a pointed chin.
The eyes are usually sunken and ears may appear to be
protruded and asymmetric. Colobomas of the iris, choroid,
retina, or optic disk are seen in almost 35% of the patients.
Occasionally, hypertelorism and blue sclera may be seen.
Oral features
Occasionally, cleft lip and palate associated with this syndrome have been reported. Both the deciduous and permanent
dentition may be affected. Teeth are usually hypoplastic
and microdontic. Oral papillomas may be seen in any part
of the oral mucosa. However, the lips, gingiva, tongue and
buccal mucosa are the common sites.
Other relatively rare ndings include split/double lingual
frenum, high palatal vault and cleft lip/palate.
Radiographic findings
The characteristic finding is the presence of osteopathia striata (longitudinal striations) in the metaphysis of the long
bones and the sacral bone. Orthopantomograph may reveal
the presence of multiple taurodonts.
Treatment and prognosis
No definitive treatment is possible for the condition. The
prognosis and severity of the condition depends on the
organ system that is involved.

ACRODERMATITIS ENTEROPATHICA
Acrodermatitis enteropathica (AE) is a rare disease transmitted as an autosomal recessive trait. It was first recognized in 1936 by Thore Brandt and further investigated by
Danboly and Closs. Although deficiency dermatitis caused
by low dietary zinc has the exact clinical and histological
features but the term should be reserved only for genetic
causes of zinc deficiency.

Chapter 9 Dermatological Diseases

Etiology

Clinical features

The gene defect appears to involve SLC 39 A4 on


8q24 which encodes a ZIP protein responsible for the zinc
transport in enterocytes. Zinc absorption in patients of
AE is low about 23% compared with 2767% in normal
adults.

The condition usually presents in the third or fourth decade


as flaccid vesicopustules, crusted erosions or expanding
circinate plaques appearing in areas exposed to friction.
Flexural disease may be hypertrophic and malodorous with
soft, flat, moist vegetations and fissures. Asymptomatic
longitudinal white bands are present in the nails of some
patients and fine palmar pits have been documented.
Herpes simplex virus and contact dermatitis, both irritant and allergic, may exacerbate HaileyHailey disease.

Clinical features
The disease typically starts after weaning or earlier if the
infant is not given breast milk. The child turns peevish,
withdrawn and photophobic and develops a vesicobullous
dermatitis on the hands, feet and periorificial areas. The
scalp hair is lost. Diarrhea is often present. Growth is stunted
and there is a decreased resistance to infection. Wound
healing is poor and skin lesions do not heal.
Differential diagnosis

Atopic dermatitis
Cutaneous candidiasis
Epidermolysis bullosa
Seborrheic dermatitis.

Diagnosis
Low serum of zinc and alkaline phosphatase (a zinc
dependent enzyme) may aid in the diagnosis of zinc
deficiency.
Treatment and prognosis
Zinc sulfate for AE was introduced between 1973 and
1974. Oral zinc in a dose of about 2 mg/kg per day was
found to clear all clinical manifestations. Prolonged therapy up to adult age is necessary.

HAILEYHAILEY DISEASE
(Familial Benign Chronic Pemphigus)
HaileyHailey disease is a rare autosomal dominant
intraepidermal blistering disease which is characterized by
recurrent vesicles and erosions usually affecting the neck,
axilla and groin. The condition was described by Hailey
brothers in 1939.

Differential diagnosis

Pemphigus vegetans
Dariers disease
Impetiginized eczema
Candidal intertrigo.

Treatment and prognosis


Loose, cool clothing will reduce friction and sweating.
Topical steroids with antibacterial agents may be effective.
Rarely systemic corticosteroids may be required for widespread disease. Oral treatment of herpes simplex should be
considered in patients with unresponsive painful disease.
Long remissions are common and many patients may
improve in old age.

DARIERS DISEASE
(Keratosis Follicularis)
Dariers disease, described independently by White and
Darier in 1889, is an autosomal dominant condition characterized by a persistent eruption of hyperkeratotic papules,
histological examination with a distinctive overlying dyskeratosis.
Etiology
It is caused by mutations in ATP2A2 gene at chromosome
12q24.1, which encodes the sarco and endoplasmic reticulum calcium ATPase type 2 (SERCA2) which is a member of
a family of ion pumps that maintain high calcium concentration in endoplasmic reticulum.
Clinical features

Etiology
HaileyHailey disease is caused by mutations in ATP2C1,
a gene on chromosome 3q21 that encodes a P-type calcium
transport adenosine triphosphate (ATPase). The cellular
process that may be affected by mutation includes gene
transcription, post-translational modifications and trafficking of adhesion proteins and the assembly of adhesion
junctions.

Characteristic lesion of Dariers disease is a firm rough papule, which is skin colored, yellow brown or brown seen on
seborrheic areas which exacerbate on sun exposure,
coalescent papules form irregular warty fissured plaques
or papillomatous plaque masses which, in the flexures,
become vegetating and malodorous. On the scalp, heavy
crusting has a characteristic spiny feel on palpation
with loss of hair. The external auditory meatus may be
229

Section III Mucocutaneous Disorders

blocked by keratotic debris. Palms and soles show


minute pits or, in older subjects, punctuate or filliform
keratosis.
Frequency of oral lesions ranges from 15 to 50% but is
usually asymptomatic and is discovered on routine examination. They consist of multiple, normal to white colored
at topped papules that if numerous enough to be conuent, result in cobblestone mucosal appearance. The lesion
primarily affects the hard palate and alveolar mucosa.
If palate lesions are prominent, the condition may
resemble inammatory papillary hyperplasia or nicotine
stomatitis.
Nail changes include red or white longitudinal bands of
varying width, often ending in a pathognomonic notch at
the free margin of the nail. The nails are brittle.
Treatment
Many patients with mild disease require no treatment other
than emollients, simple hygiene and advice to avoid excessive sun exposure. In severe disease oral and topical retinoids are usually effective.

REITERS SYNDROME
Reiters syndrome is characterized by the presence of
a non-suppurative polyarthritis exceeding a duration of
1 month associated or preceded closely by a lower urogenital or enteric infection in young men who carry the
HLA-27 antigen. It was named after Professor Hans Reiter,
who in 1916 reported a German officer who developed
urethritis conjunctivitis and arthritis following an episode
of bloody diarrhea.
Inammatory eye involvement and mucocutaneous
manifestations are common. The classical triad of arthritis,
conjunctivitis, and urethritis is observed only in 33% of the
cases. The less stringent criteria of American College of
Rheumatology, comprising of peripheral arthritis of more
than 1 month duration, occurring in association with urethritis or cervicitis exhibit a sensitivity of 84.3% and specicity of 98.2% when compared with other arthropathies.
Etiology
The etiopathogenesis of Reiters disease centers on the
determination of the role of probable infective triggering
agents and the proneness of certain individuals to develop
the condition due to genetic susceptibility (Table 1).
Clinical features
The earliest features of Reiters disease usually presents
within 14 weeks of exposure. Fever, constitutional complaints and features of urethritis or enteritis usually precede arthritis.
230

Table 1

Infectious organisms associated with the onset of


Reiters disease

Urogenital pathogens

Enteric pathogens

Chlamydia trachomatis
C. psittaci
C. pneumoniae
Ureaplasma urealyticum
Neisseria gonorrhoeae

Shigella flexneri, serotype 2a, 1b


Salmonella typhimurium
S. enteritidis
S. paratyphi
Yersinia enterocolitica
Campylobacter jejuni

Genitourinary tract involvement Urethritis is the most


common presentation and manifests as dysuria with
mucoid or mucopurulent discharge. Acute abacterial cystitis with increased micturitional frequency and chronic
prostatitis may occur. In females, persistent urogenital
involvement may manifest as cervicitis, urethritis and
vaginitis.
Arthritis The arthropathy is typically an acute asymmetric additive and ascending inflammatory oligoarthritis of
weight bearing joints. Symptoms may range from slight
arthralgia with no visible signs to marked erythema,
edema, tenderness and exquisite joint pains with complete
immobility. Characteristic features of the arthropathy of
reactive arthritis and Reiters syndrome are oligoarticular,
predominantly lower limbs, asymmetrical dactylitis,
enthesitis and lower back/buttock pain.
Cutaneous lesions The classic skin lesions of keratoderma blenorrhagica manifests as thickened, heaped up,
crusted and yellowish scaly lesions on an erythematous
base affecting the acral lesion. Circinate balanitis affects
about 2040% and occurs in up to 85% of men with
sexually acquired Reiters disease has been shown in a
study by Martin et al. In uncircumcised males, it appears
as painless, serpiginous, erosive, geographic lesions on the
glans penis and in circumcised males as hyperkeratotic
papules.
Nail involvement is seen in 15% of cases as yellowish
discoloration, subungual hyperkeratosis and onycholysis.
Ocular involvement Conjunctivitis is the only presentation and is mild, transient and recurrent. Keratitis and uveitis can occur.
Musculoskeletal features Plantar fasciitis, the classical
lovers heel occurs in 25% of patients. It is often associated with calcaneal spur; both are highly suggestive of
Reiters disease.
Oral manifestations
The oral lesions which occur in slightly less than 20% of
the patients are described in various ways. Some reports

Chapter 9 Dermatological Diseases

mention painless erythematous papules distributed on the


buccal mucosa and palate while other reports describe
shallow, painless ulcers that affect the tongue, buccal
mucosa, palate and gingiva. Some authors have even
described that geographic tongue may be a component of
Reiters syndrome, probably because geographic tongue
bears a superficial resemblance to the lesion of circinate
balanitis.
Treatment and prognosis
Therapeutic intervention in Reiters disease should aim
at suppression of inflammation, optimum joint protection,
relief of pain, patient education, and when appropriate,
eradication of infection; NSAIDs is the mainstay of
treatment. Indomethacin (75150 mg/day), phenylbutazone (200600 mg/day), naproxen (375750 mg/day) and
diclofenac sodium (100200 mg/day) can be used. Systemic
corticosteroids (4060 mg) prednisolone are indicated for
the patients with florid disease, severe pain, wasting, fever,
high ESR, posterior uveitis, pericarditis and in those who
have failed to respond to NSAIDs.
Conjunctivitis is self-limiting and requires no treatment.
One percent atropine and steroid drops for iritis and systemic steroids for posterior uveitis can be given.
Keratoderma blenorrhagica and circinate balanitis require
hygiene and topical steroids. Methotrexate and azathioprine
should be considered as second line of therapy.
The prognosis and course of individual patient is varied
and unpredictable. Severe disability occurs in less than
15% of cases and is usually secondary to debilitating
lower extremity disease, aggressive axial involvement or
blindness. Death is rare and is usually attributable to cardiac complications.

Teeth and jaw changes are seen in 6595% of cases


and are of considerable diagnostic importance because,
in contrast to many dermatologic features, they persist
through life. The changes are delayed eruption, changes in
dental contour, hypodontia/microdontia, micrognathia/
prognathia.
Hair are sparse and thin and partial baldness is seen in
3570%.
Central nervous system changes are seen in 1040% of
cases as microcephaly, mental retardation, spastic paralysis,
convulsions and epilepsy.
Structural anomalies are most frequently related to
neurological system and is seen in 14% of the cases as body
asymmetry, scoliosis, spina bida, syndactylia, ear anomalies, additional ribs and skull malformations.
Breast anomalies are seen in 1% of the cases as hypoplasia or additional nipples.
Dental defects are frequentdelayed dentition, partial
anodontia, and cone-or peg-shaped teeth are the most
usual.
Diagnostic criteria
No evidence of IP in a first degree female relative.
Major criteria
Typical neonatal rash
Erythema
Vesicles
Eosinophilia
Typical hyperpigmentation
Mainly trunk
Blaschkos line
Fading in adolescence
Linear atrophic hairless lesions

INCONTINENTIA PIGMENTI
(BlochSulzberger Syndrome)
Incontinentia pigmenti (IP) is a rare X-linked dominant
disease that affect skin, eyes, hair, teeth and central nervous
system and manifest itself during early neonatal period.
The disease was first described by Garrod in 1903, its pathogenesis in 1926 by Sulzberger and localization of rash in
1985 by Happel.
Clinical features
Four stages are differentiated according to the changes in
the skin are shown in (Table 2).
Nail dysplasia is found in 4060% of cases. Eye
changes are seen in one-third of the cases as speckled diffuse hypopigmentation in the retina (a pathognomonic feature), microphthalmia, lenticular hemorrhage, retrolental
broplasia, cataract and atrophy of the optic nerve.

Minor criteria (supportive evidence)


Dental involvement
Alopecia
Woolly hair/abnormal nails
Retinal disease.
At least one major criterion is necessary to make a firm
diagnosis of sporadic IP. The minor criteria, if present, will
support the diagnosis.
Evidence of IP in a first degree female relative
The evidence of IP is likely in a primary female relative
of an affected female if any of the following features are
demonstrable, alone or in combination.

Suggestive history or evidence of typical rash


Skin manifestation of IP
Hyperpigmentation
Scarring
231

Section III Mucocutaneous Disorders

Table 2

Four stages are differentiated according to the changes in the skin

Stages

Clinical features

Stage 1 vesicular

Linear vesicles, pustules, or blisters with erythema along Blaschkos line

During infancy, possible in childhood

Stage 2 verruciform

Keratotic papules and plaques

At the age of 28 weeks

Stage 3 pigmented

Hyperpigmented macules along the Blaschkos line in the mastoid,


axillary, and inguinal sites; the localization of secondary rash may not
coincide with that of the primary rash

At the age of 1240 weeks

Stage 4 depigmented

Brownish macules begin to disappear; hyperpigmentation becomes more


apparent during examination under Woods lamp; in the site of lower
limbs there remains linear hypopigmentation and skin atrophy

Continues from infancy to childhood

Hairless streaks
Alopecia at vertex
Anomalous dentition
Woolly hair
Retinal disease
Multiple male miscarriages.
Differential diagnosis
In acute stage of disease, herpes simplex infection, impetigo, candidosis, epidermolysis bullosa congenita. In later
stage, differentiated from post-inflammatory pigmentation
and hypomelanosis of Ito.
Treatment and prognosis
The vesicles should not be touched and the skin must be kept
clean to avoid infection. Local anti-inflammatory treatment with steroids may be applied.
Timely diagnosis of IP prior to pregnancy and early
genetic consultation of pregnant women with IP to evaluate
the risk of damage for the children of such women are
essential.

KAWASAKI DISEASE
(Mucocutaneous Lymph Node Syndrome)
This condition is usually seen in children, often affecting
those below 2 years of age, characterized by fever and generalized exanthem with lymphadenitis. The disease was
first described in 1967 by Kawasaki from Japan.

Time of manifestation

Clinical features
The onset is acute, with a high fever, which lasts for at least
57 days. The mucosa and conjunctiva are injected. In the
mouth, the lips are dry and fissured, the tongue appears red
with prominent papillae (strawberry tongue) and the throat
is injected. After 34 days there is generalized exanthema.
The area affected on the limbs becomes edematous followed
by scaling. There is accompanying cervical lymphadenitis,
although not always present and may only involve one
node. Fever resolves in 12 weeks.
Complications
In about one-fourth of cases there is accompanying
myocarditis which may be followed by symptomatic coronary artery disease and in 12% by myocardial infarction.
Other complications include arthralgia, arthritis, severe erythema multiforme, iritis, proteinuria, hepatitis and aseptic
meningitis.
Diagnosis
Abnormalities on investigation includes leukocytosis and
thrombocytosis with a raise ESR. The raised platelet count
is most often seen in the post-acute phase.
Treatment
Intravenous gammaglobulin in high doses (2 g/kg in a single effusion over 10 hours) is very helpful in reducing the
overall mortality and complication of the disease. Shortterm use of aspirin is also helpful in reducing the risk of
platelet aggregation.

Etiology
Various hypotheses have been advanced to account for its
symptoms. These include rickettsial illness, exposure to
house-dust mite. It has been suggested that bacterial
superantigens cause disease through wide scale activation of immune mechanism with cytokine release bringing
other cell types, including vascular endothelium, into an
uncontrolled immunological reaction.
232

TUBEROUS SCLEROSIS COMPLEX


(Epiloia, Bournevilles Disease)
Tuberous sclerosis (TSC) is a genetic disorder of hamartoma formation in many organs, particularly the skin,
brain, eye, kidney and heart. The characteristic skin lesions
are angiofibroma, shagreen patch, periungual fibroma and

Chapter 9 Dermatological Diseases

ash leaf white macules classically, although not invariably


seen in combination with epilepsy and mental retardation.
Sherlock coined the term epiloia indicating the diagnostic clinical triad of epilepsy, low intelligence and adenoma
sebaceum.
Etiopathogenesis
The inheritance of tuberous sclerosis is determined by single autosomal dominant gene, with variable expression.
It is recognized that about half the TSC families are linked
to 9q34 (TSC1) and other half to 16p13 (TSC2). TSC1 gene
has not yet been coded but TSC2 gene encodes a protein
named tuberin which shows homology to the catalytic
domain of the GTPase activating protein Rap1 which is
involved in the regulation of cell proliferation and differentiation.
Approximately, 6070% of TSC cases are thought to
be the result of new mutations, but before genetic counseling of the normal parent of an affected child, both parents
should be fully investigated. A study by Flinter et al
showed that about 30% of normal parents had TSC.
Clinical features
Onset before the age of 5 years with cutaneous changes or
with epilepsy is usual, although the disease may remain
latent until adolescence. Diagnostic criteria determined
by a committee of the US National Tuberous Sclerosis
Association have been modified. A definitive diagnosis of
TSC requires two major features.
Major features
Facial angiofibroma or forehead plaque
Non-traumatic ungular or periungual fibroma
Shagreen patch (connective tissue nevus)
Multiple retinal nodular hamartoma
Cortical tuber
Subependymal nodule
Subependymal giant cell astrocytoma
Cardiac rhabdomyoma, single or multiple
Lymphangioleiomyomatosis and/or renal angiomyolipoma
Hypomelanotic macules (3)

Suggestive features requiring further investigation


Multiple randomly distributed pits in dental enamel
Hamartomatous rectal polyps
Bone cyst
Cerebral white matter radial migration lines
Gingival fibromas
Non-renal hamartomas
Retinal achromic patch
Confetti skin lesions
Multiple renal cysts
Skin tags
Positive family history in first degree relatives.

Skin lesions
Skin lesions are found in 6070% cases. Lesions of four
types are pathognomonic:

Angiofibromas usually appear between the ages of


310 years and often become more extensive at
puberty and then remain unchanged. Firm, discrete,
red brown, telangiectatic papules 110 mm in diameter,
extend from the nasolabial furrows to the cheeks and
chin.
Periungual fibromas (Koenens tumors) appear at or
after puberty as smooth, firm 510 mm in length, flesh
colored excrescences emerging from nail fold.
Shagreen patch is an irregularly thickened, slightly
elevated, soft skin colored plaque, usually in the lumbosacral region.
Ash leaf macules are present at birth or in infancy and
are 3 cm in length, most easily detectable by examination under Woods light, are frequently present on the
trunk or limbs.

Mental deficiency
Mental deficiency is present in 6070% of cases and may
be progressive, but if mental development has been normal throughout the childhood subsequent deterioration is
uncommon.
Epilepsy is seen in almost all mentally retarded patients
and in some 70% of those with average intelligence. It
usually begins in infancy or early childhood, thus often
preceding the skin lesions by many years.
Ocular signs
Ocular signs occur in 50% of the cases but are hard to
detect. Retinal phacomas, pigmentary and other retinal
abnormalities and hypopigmented spots on iris can occur.
Cardiac and renal tumors, pulmonary changes, gastrointestinal tumors and endocrine and other metabolic disturbances can occur.
Oral manifestations
Oral manifestations of tuberous sclerosis include developmental enamel pitting on the facial aspect of the anterior
permanent dentition in 50100% of patients. These pits
are readily appreciated after applying a dental plaquedisclosing solution to the teeth.
Multiple brous papules affect 1156% of patients seen
predominately on the anterior gingival mucosa. Diffuse
gingival enlargement and radiolucencies of the jaws that
represents dense brous tissue proliferation is also seen.
Treatment and prognosis
The cosmetic appearance may be improved by removing
angiofibromas with pulsed dye vascular laser (585 nm).
233

Section III Mucocutaneous Disorders

Neurosurgery should be considered when epilepsy is controlled by drugs and there is fixed, circumscribed, electroencephalographic focus. The treatment of lesions in other
organs is unsatisfactory and surgical procedure may be
required for relief of symptoms.
Patients affected by this condition have a slightly reduce
life span compared with the general population, with deaths
usually related to CNS or kidney disease.

GRAFT-VERSUS-HOST DISEASE
Graft-versus-host disease (GVHD) occurs when immunocompetent cells from a donor recognize and react against
foreign tissue antigen in an immunocompromised host.
Moderate to severe acute GVHD affects 935% of patients
undergoing standard allogenic bone marrow transplantation, despite using HLA matched sibling donors and
immunosuppression after grafting.

followed by a faint red maculopapular rash leading to desquamation or even toxic epidermal necrolysis.
Chronic GVHD occurs 314 months after the transplant. When the condition is localized it occurs as hypopigmented nodular areas which eventually soften and atrophy.
Generalized GVHD starts as erythematous rash and
becomes lichenoid. With advancing time scleroderma like
changes appear.
The oral mucosal manifestations of GVHD depend on
the duration and severity of the attack and the target
oral tissue. Sometimes the oral lesions of GVHD are the
only signs of disorder. It is estimated that 3375% of
patients suffering from acute GVHD and about 80% of
patients suffering from chronic GVHD will have oral
involvement. Patients will present with ne reticular network of white striae that resembles oral lichen planus
involving tongue, labial mucosa and the buccal mucosa.
Atrophy, ulceration and xerostomia of the oral mucosa
can be present.
Treatment and prognosis

Etiology
Billingham described the original criteria for development
of a GVHD in 1966:

Genetically determined histocompatibility difference


between donor and recipient.
Immunocompetent cells in the grafted tissue able to
recognize foreign histocompatibility antigens in the
host and to react against them.
Inability of the host to recognize and react against the
grafted tissue.
Clinical features
Acute GVHD occurs within 60 days of bone marrow transplantation and most often after 710 days. Mild fever is

Diagnostic Signs in Dermatology


Antenna sign: This sign is seen in keratosis pilaris. Individual
follicles show a long strand of keratin glinting when examined
in side light resembles like antenna is known as antenna sign.
Asbo-Hansens phenomenon (bulla spread phenomenon):
Refers to the ability to induce peripheral extension of a blister
as a consequence of applying lateral pressure to the border of
intact blister. This is seen in pemphigus.
Auspitzs sign: This sign is seen in plaque type of psoriasis.
When the surface of the typical plaque is lifted from the base,
punctuate bleeding points occur at the sites of scale removal.
Caf-aulait spots: These are light to dark brown wellcircumscribed round to oval cutaneous macules, which vary in
size from 1 to 20 cm. These are usually present at birth or
appear during infancy. Isolated lesions are found in 1033% of
234

Prophylactic use of cyclosporine, methotrexate, prednisolone combination therapy has reduced incidence of acute
GVHD. T-cell depletion by using anti-T cell receptor antibodies is successful.
Granulocyte colony stimulating factor, used to enhance
engraftment may reduce the incidence of GVHD. Once the
disease is established, treatment with high dose steroids or
cyclosporine is of value symptomatically and antilymphocyte globulin may be of additional benet.
The prognosis depends on the extent to which the disease progresses and whether it can be controlled. Mortality
is caused by the disease itself and severe superinfection
due to immunosuppressive therapy. It is believed that about
55% of the patients with mild GVHD survive compared to
the 15% survival rate in severe GVHD.

normal population. Multiple caf-au-lait spots especially


more than six in number and exceeding 1.5 cm in diameter are
seen then underlying systemic disease is suspected. It is seen in
neurofibromatosis (outline is like the coast of California),
Albrights syndrome (outline is like coast of Maine), Fanconis
anemia, Blooms syndrome and Cowdens syndrome.
Carpet tacks sign: Usually seen in discoid lupus erythematosus. Removal of the scale shows its undersurface to be covered
with the horny plugs which filled the follicles, resembling
carpet tacks.
Cerebriform tongue sign: The sign is originally described by
Premalatha and coworkers (1981). Oral lesions in pemphigus
vegetans are hyperplastic masses which on the tongue can give
rise to cerebriform appearance.
Crowes sign: The sign is seen in neurofibromatosis. Axillary
freckling seen in neurofibromatosis is known as Crowes sign.

Chapter 9 Dermatological Diseases

Dariers sign: This sign is observed in mastocytosis. Gentle


rubbing of the urticaria pigmentosa skin lesion causes local
itching, redness and whealing and is known as Dariers sign.
This sign is due to the local histamine release in the lesional
skin.

Id reaction: It is an allergic manifestation of candidiasis, the


dermatophytoses, and other mycoses characterized by itching
and vesicular lesions that appear in response to circulating
antigens at sites that are often far distant from the primary
fungal lesion itself.

Deck-chair sign: This sign is noted in papuloerythroderma of


Ofuji. Papuloerythroderma of Ofuji is a rare, intensely pruritic
eruption of unknown etiology, consisting of wide spread
coalescing sheets of uniform erythematous papules. The lesion
characteristically spares the compressed abdominal body folds,
and this is known as deck-chair sign.

Koebners phenomenon: Linear lesions occurring as a result of


external trauma such as scratching is called Koebners phenomenon. This phenomenon can be seen in psoriasis and lichen
planus.

Dimple sign: This sign is usually seen in dermatofibroma. If


the overlying epidermis is squeezed the dimple will be seen,
indicating the tethering of the overlying epidermis to the
underlying lesion.
Dubois sign: Usually seen in congenital syphilis. Very short
little finger seen occasionally as late stigmata in congenital
syphilis is known as Dubois sign.
Flag sign: Commonly seen in kwashiorkor and rarely in severe
ulcerative colitis and after extensive bowel resection. Alternating
white and dark bands occur along individual hair is known as
flag sign. Intermittent protein malnutrition leads to this sign.
Forschheimers sign: Originally described by Forschheimer, is
observed in rubella. An enanthema is present in up to 20% of
patients during the prodromal period or on the first day of the
rash, and are confined to the soft palate. This presence of enanthema is known as Forschheimers sign.
Gorlins sign: Ability to touch the tip of the nose with the
tongue in patients with EhlersDanlos syndrome.
Groove sign: Originally described by Greenblatt in lymphogranuloma venereum (LGV). Enlargement of lymph nodes above
and below the inguinal ligament may give to bubo a grooved
appearance known as groove sign.
Headlight sign: Vascular stigmata associated with atopic dermatitis. Perinasal and periorbital pallor is termed as headlight
sign.
Hertoghes sign: Cutaneous stigmata associated with atopic
dermatitis. Thinning of the lateral eyebrows is known as
Hertoghes sign.
Higoumenakis sign: This sign is commonly seen in congenital
syphilis. Irregular thickening and enlargement of the sternoclavicular portion of the clavicle is known as Higoumenakis
sign. It is the result of periostitis and usually is unilateral than
bilateral.
Hutchinsons sign: This sign is observed in subungual malignant melanoma as well as herpes zoster ophthalmicus. A longitudinal melanotic streak accompanied by periungual
pigmentation in subungual malignant melanoma is known as
Hutchinsons sign. In ophthalmic nerve zoster, appearance of
vesicles on the side of the nose indicates the involvement of the
nasociliary nerve, and this is known as Hutchinsons sign.

Koebner effect: In patients with psoriatic arthritis of TMJ,


who have disabling movements of the mandible, surgery is
indicated and surgery may be complicated by psoriasis
forming on the surgical scar, which is referred to as Koebner
effect.
LeserTrlat sign: This sign often occurs as a manifestation of
visceral malignancy. Internal malignancy associated with sudden development of numerous seborrheic keratoses, in an eruptive fashion with or without pruritus, is generally accepted as
the sign of LeserTrelat.
Nikolskys sign: It was named after Pytor Vasilyenich Nikolsky
who was the first to describe this finding. On applying gentle
mechanical pressure (e.g. blowing air or applying pressure with
a mirror handle) on affected tissue will result in the formation
of a lesion. Nikolskys sign is seen both in the skin and oral
mucosa. It is seen in pemphigus, paraneoplastic pemphigus,
mucous membrane pemphigoid, epidermolysis bullosa, linear
IgA bullous disease, lupus erythematosus, graft-versus-host
disease and toxic epidermal necrolysis.
Nose sign: This sign is evident in exfoliative dermatitis. Nose
and perinasal area is characteristically spared in exfoliative
dermatitis involving the other parts of the face and body is
known as nose sign.
Oil drop sign: This sign is usually seen in psoriasis. Circular
areas of discoloration of the nail bed and hyponychium may
resemble oil drop below the nail. Histologically there are areas
of psoriatic change below the nail bed and hyponychium.
Ollendorfs sign: This sign is observed in secondary syphilis.
In secondary syphilis, the papule is exquisitely tender to the
touch of a blunt probe, which is termed positive Ollendorfs
sign.
Oslers sign: This sign is seen in alkaptonuria. By the third
decade of life, the deposition of pigment in alkaptonuria
becomes apparent. In the early stages, the sclera is pigmented
which is termed Oslers sign.
Psoriasiform lesions: Lesions that have histopathological
similarities to psoriasis are termed as psoriasiform lesions.
Examples of such lesions are Reiters syndrome, geographic
tongue and erythema circinata migrans (ectopic geographic
tongue).
Romanas sign: This sign is observed in American trypanosomiasis also known as Chagas disease. Unilateral edema of the
eyelids, inflammation of the lacrimal gland associated with the

235

Section III Mucocutaneous Disorders

preauricular lymphadenopathy is known as Romanas sign. This


sign is due to portal of Trypanosoma cruzi in the conjunctiva.
Sailors skin: Skin damage (dry, wrinkled skin) due to prolonged exposure to the sun and wind. Some authors use the
term farmers skin. Actinic elastosis or solar elastosis is one
such dermal condition where sailors skin can be appreciated.

236

(18861954). It is basically a type of exfoliative cytology. In


pemphigus, acantholytic cells are seen and in herpes multinucleated giant cells with Lipschutz bodies are seen.

Thumb sign: This sign is positive in Marfans syndrome.


Completely opposed thumb in the clenched hand projects
beyond the ulnar border, known as thumb sign. It is simple
screening test for Marfans syndrome.

Wickhams striae: It is seen in lichen planus. On skin, there


are flat-topped papules with violaceous hue and the surface of
these papules is covered by characteristic very fine grayish
white lines called Wickhams striae. In the oral cavity the disease appears as radiating white lines. At the intersection of
these white lines a tiny white elevated dot is present known as
striae of Wickham or Honiton lace.

Tzancks test: The examination of fluid from a bulla (a blister)


in search of Tzanck cells characteristic of varicella (chicken
pox), herpes zoster, herpes simplex, and pemphigus vulgaris.
It was named after a Russian dermatologist Arnault Tzanck

Wimbergers sign: This sign is observed in early congenital


syphilis. Radiological examination shows loss of density on
the medial side of the upper end of the tibia is known as
Wimbergers sign.

SECTION

IV

Diseases of
Specific Structures

10 Temporomandibular Disorders
11 Diseases of Salivary Glands

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CHAPTER

Temporomandibular
Disorders

10

Shibu Thomas, Joanna Baptist,


Ravikiran Ongole, Thomas Zachariah

Components of Temporomandibular Joint

Clinical Evaluation of Temporomandibular


Joint

Clinical Evaluation of Muscles of Mastication


and Accessory/Cervical Muscles

Disorders Associated with Deviation/


Alteration in the Form of Articular Surfaces

Articular Disk Defects


Disk Thinning and Perforation
Adherence and Adhesions
Disk Displacement
Disk Displacement with Reduction
Disk Displacement without Reduction
Displacement of DiskCondyle Complex
(Hypermobility and Dislocation)

Osteoarthrosis
Osteoarthritis
Juvenile Idiopathic Arthritis
Polyarthritides
Traumatic Arthritis
Infectious Arthritis/Septic Arthritis
Rheumatoid Arthritis
Psoriatic Arthritis
Hyperuricemia

TMJ Ankylosis

Masticatory Muscle Disorders


Acute Disorders
Chronic Conditions

Congenital, Developmental and Acquired


Disorders of the TMJ

Neoplasms Affecting the TMJ

Condylar Fractures

Inflammatory Joint Disorders


Synovitis or Capsulitis
Retrodiscitis

The temporomandibular joints (TMJs) are two joints


between the mobile mandible and the fixed temporal bone.
Each joint contains two joint spaces which are separated
by a fibrocartilaginous articular disk.
The TMJ is a compound joint. It can also be considered as
ginglymodiarthroidal joint (capability of both hinge type and
sliding/gliding movement). The use of the term compound
joint is justied based on the fact that the TMJ is composed
of three bones, namely, the mandibular condyle, squamous portion of temporal bone and the non-ossied articular
disk. The TMJ is the articulation between the condyle of the
mandible and the squamous portion of the temporal bone.

COMPONENTS OF TEMPOROMANDIBULAR
JOINT
Glenoid Fossa and Articular Eminence/
Protuberance
The glenoid fossa or mandibular fossa is a well-defined hollow area on the inferior portion of the squamous temporal

Degenerative Joint Diseases

bone. The convex articular eminence forms the anterior


limit of the joint. The glenoid fossa is covered by a thin
layer of fibrocartilage.

Mandibular Condyle
The condyle is elliptically shaped with its long axis oriented
mediolaterally. The dimension of the condyle is roughly
20 mm in the mediolateral direction and approximately
810 mm in the anteroposterior direction. The articulating
surface of the condylar head is covered by fibrocartilage
(Figure 1).

Articular Capsule and Articular Disk


The articular capsule is a fibrous membrane that surrounds
the joint and incorporates into the articular eminence. It
attaches to the articular eminence, the articular disk and
the neck of the mandibular condyle. Superiorly, it is attached
to the temporal bone and inferiorly to the neck of the condyle. The anatomical and functional boundaries of the
239

Section IV Diseases of Specific Structures

Figure 1

Figure 2

The biconcave articular disk.


Courtesy: Dr Arturo Mann
Skeletal components of TMJ (condylar head and
the glenoid fossa). Courtesy: Dr Arturo Mann

TMJ are defined by the articular capsule. The inner surface


of the capsule is covered by the synovial membrane that
aids in the secretion of the synovial fluid. The articular
capsule confines the synovial fluid to the articulating surfaces. Temporomandibular ligaments provide additional
reinforcement to the capsule on its lateral wall.
Articular disk is a biconcave oval structure with a thin
intermediate zone and a thick posterior and anterior border.
These thick posterior and anterior bands act as wedges,
giving the disk a self-seating capacity with the condyle
functioning against the intermediate zone. The importance
of this feature cannot be overemphasized; the contour of
the disk with the thick bands helps prevent the displacement of the disk from the condyle during translation. An
absence of blood vessels and nerves in the intermediate
zone of the disk enables this part of the disk to act as a
pressure-bearing area (Figure 2).
The disk is a brous, saddle-shaped structure that separates the condyle and the temporal bone. The meniscus
varies in thicknessthe thinner, central intermediate zone
separates thicker portions called the anterior band and the
posterior band. Posteriorly, the meniscus is contiguous with
the posterior attachment tissues called the bilaminar zone.
The bilaminar zone is a vascular, innervated tissue that plays
an important role in allowing the condyle to move forward.
The meniscus and its attachments divide the joint into
superior and inferior spaces. The superior joint space is
bounded above by the articular fossa and the articular
eminence. The inferior joint space is bounded below by the

240

condyle. Both joint spaces have small capacities (passive


volume of the upper joint space is 1.2 ml and the passive
volume of the lower joint space is 0.9 ml).
The condyle articulates with the inferior surface of the
disk to form the lower joint, the diskcondyle complex, where
only hinge or rotatory movement occurs. Translation or
sliding movements occur in the upper joint, composed of
the diskcondyle complex articulating with the mandibular
fossa of the temporal bone.
During functional movements of the mandible, stability
within the TMJ is achieved by maintaining the thin intermediate zone of the disk between the condyle and the
eminence.
The disk also serves as a shock absorber to counteract
the many forces acting on the joint during both function
and parafunctional activity.

Synovial Fluid
The main functions of the synovial fluid are to nourish the
avascular articulating cartilage and provide lubrication
between the articulating surfaces during function.
Synovial uid is a clear straw-colored thixotropic uid
which is composed of mucin with some albumin, fat, epithelium, and leukocytes. Synovial uid also contains lubricin
secreted by synovial cells. It is mainly responsible for socalled boundary layer lubrication, which reduces friction
between opposing surfaces of cartilage. Synovial uid is
made of hyaluronic acid and lubricin, proteinases and collagenases.
During movement, the synovial uid held within the
cartilage is squeezed out mechanically to maintain a layer

Chapter 10 Temporomandibular Disorders

of uid on the cartilage surface (so-called weeping lubrication). Boundary lubrication is a function of water physically bound to the cartilaginous surface by a glycoprotein.

Discal Ligaments
The medial and lateral portions of the articular disk are
attached to the corresponding poles of the condyles via nonelastic, short discal ligaments. These ligaments are vascularized and innervated.
These ligaments restrict the movement in the lower joint
to hinge or rotatory action when viewed in a sagittal plane.
Discal ligaments cause the disk to move passively with
the condyle in an anterior and posterior direction during
condylar translation. These ligaments permit very little
lateral excursion.

Posterior Attachment or Retrodiscal Tissue or


Bilaminar Zone
The retrodiscal tissue is confined to the space between the
articular disk and the posterior wall of the articular capsule.
It is richly vascularized and well innervated.
It is attached anteriorly to the posterior band of the articular disk and posteriorly to the tympanic plate and posterior aspect of the condyle. The retrodiscal tissue contains
loosely associated collagen bers and a meshwork of elastic
bers.
The upper retrodiscal lamina is elastic in nature and
exerts a posterior traction on the disk. The inferior retrodiscal lamina is non-elastic and restricts forward rotation
of the disk on the condyle.

Ligaments Associated with Temporomandibular


Joint
The ligaments associated with the TMJ have three major
functions: stabilization, guidance of movement, and movement limitation.
The ligaments that have been associated with the TMJ
include lateral ligament (temporomandibular ligament),
stylomandibular ligament, sphenomandibular ligament,
discomalleolar ligament (Pintos ligament) and Tanakas
ligament.
The lateral ligament is comprised of two parts: a deep
part (horizontally oriented) and a supercial part (vertically oriented). The horizontally oriented portion of the
lateral ligament limits retrusion and laterotrusion. In this
manner, the sensitive retrodiscal tissue is protected from
injury.
The vertically oriented portion of the ligament limits
opening of the jaw. The vertically oriented supercial part
of the temporomandibular ligament contains nerve endings

(Golgi tendon organs) which play an important role as static


mechanoreceptors for protection of these ligaments around
the TMJ.
Accessory ligaments of TMJ include the stylomandibular
and sphenomandibular ligaments.
The stylomandibular ligament runs from the styloid
process downward and forward to the medial surface and
border of the angle of the mandible. The stylomandibular
ligament functions by limiting excessive mandibular
protrusion.
The sphenomandibular ligament arises from the spine
of the sphenoid bone and extends downward and forward
to insert on the lingula of the mandible along the lower
border of the mandibular foramen. The sphenomandibular
ligament restricts protrusive, mediotrusive as well as passive
jaw opening.
Discomalleolar ligament was described by Pinto in 1962.
This ligamentous structure connects the malleus in the
tympanic cavity and the articular disk and capsule of the
TMJ. It is estimated that only 29% of the TMJs reveal
the presence of this ligament.
This anatomical relationship between the middle ear and
the TMJ is believed to be one of the explanations for the
aural symptoms associated with TMJ dysfunction.
Tanakas ligament was described in 1986. This ligament
provides a cord like reinforcement to the medial wall of
the articular capsule.

Muscles of Mastication
Various mandibular movements such as opening, closing, protrusion and retrusion occur under the coordinated movements of the muscles of mastication, namely,
the masseter, temporalis, medial pterygoid and lateral
pterygoid.
Masseter muscle
Masseter muscle arises from the lower border and inner
surface of the anterior two-thirds of the zygomatic arch,
passes inferiorly and posteriorly, and inserts on the outer
surface of the mandibular ramus (Figure 3). The deep fibers
of the masseter muscle (pars profunda) are vertically oriented
whereas the superficial fibers (pars superficialis) are more
oblique. This muscle is responsible for elevating the mandible to aid in jaw closure and for clenching and crushing
action.
Temporalis muscle
The temporalis is a broad, fan-shaped muscle that arises
from the temporal fossa (superior and inferior lines of the
temporal bone). Via a strong tendon it inserts into the
upper anterior border and the medial aspect of the coronoid

241

Section IV Diseases of Specific Structures

process, and into the anterior border and adjacent medial


surface of the mandibular ramus.
The anterior bers run obliquely downward and posteriorly (serve as elevators and also maintain the postural
(resting) position of the mandible, with the teeth slightly
apart), the middle part of the temporalis muscle helps
in closure of the jaws and the posterior bers which are
oriented in a horizontal direction help in retrusion of the
mandible and gentle ner movements to achieve a position
of intercuspation.
Medial pterygoid muscle
The medial pterygoid muscle originates from the pterygoid
fossa (medial surface of the lateral pterygoid plate). Some
of the fibers also originate from the maxillary tuberosity.

Figure 3

Temporal muscle

Masseter muscle

Schematic diagram showing the location of the temporalis


and masseter muscle

The muscle fibers extend inferiorly, posteriorly and laterally


to insert into the medial surface of the ramus, approximating
the angle of the mandible. Here it joins with the masseter
to form a muscle sling (Figure 4A, B).
The medial pterygoid primarily aids in jaw closure. It
also participates in protrusion of the mandible.
Lateral pterygoid muscle
The lateral pterygoid muscle comprises two functionally
distinct entities: (i) the smaller, superior head arises from
the infratemporal surface of the greater wing of the sphenoid and runs backward in a nearly horizontal direction;
(ii) the larger, inferior head arises from the lateral surface
of the lateral pterygoid plate and runs backward in a
somewhat oblique upward direction. Both heads merge
posteriorly into a tendon that inserts in the following way:
the upper fibers, which correspond more to the superior
head, insert into the anterior surface of the capsule and
disk; the inferior fibers, which correspond mainly to the
inferior head, attach mostly to a depression (pterygoid fovea)
on the inner side of the anterior surface of the mandible
(Figure 5). Studies on the run and the attachment of the
lateral pterygoid muscle on 41 cadavers by Abe et al (1993)
showed the presence of a third intermediate belly of the
lateral pterygoid muscle.
Both the heads of the lateral pterygoid muscle function
as independent antagonistic muscles. Contraction of
the inferior head pulls the condyle forward down the slope
of the articular eminence (opening of the mandible and
protrusion); whereas the superior head is active during
mandibular closure and contracts in conjunction with
the mandibular elevation muscles. It also exerts a holding
or bracing action on the condyle when the teeth are
held together and during power strokes. The superior head
also acts to rotate the disk anteriorly on the condyle

Figure 4
A

Lateral pterygoid muscle


(upper head)
Lateral pterygoid muscle
(lower head)
Temporal muscle
Medial pterygoid muscle

Schematic diagram showing the medial pterygoid muscle

242

Chapter 10 Temporomandibular Disorders

Figure 5

Schematic diagram showing the lateral pterygoid muscle

when the diskcondyle complex is moving upward and


backward against the eminence. By keeping the disk
between the condyle and eminence, the superior head
of the lateral pterygoid muscle aids in maintaining joint
stability.
Suprahyoid muscles
The digastric, mylohyoid, geniohyoid, stylohyoid muscles
are grouped under suprahyoid musculature owing to their
anatomic location. These muscles are considered accessory
muscles of mastication and help in jaw opening along with
the lateral pterygoid muscle.
Mandibular movements
Forward movement or protraction The articular disk
glides forward over the upper articular surface, the head of
the mandible moves along with it. The movement in the
opposite direction is referred to as retraction.
Slight mouth opening The mandible moves on the
undersurface of the disk like a hinge.
Wide mouth opening The hinge like movement is followed by gliding of the disk and the head of the mandible,
as in protraction. At the end of this movement the articular disk comes and rests against the articular eminence.
Chewing movements/lateral excursions In these movements the condylar head of one side glides forward
along the disk but the head of opposite side merely rotates
on a vertical axis. This moves the chin forward and to
one side.

Arterial Supply, Venous Drainage and


Sensory Innervation of TMJ
The TMJ and the muscles of mastication are primarily fed
by the maxillary artery and superficial temporal artery.
The blood supply to the condylar head is also derived from
the inferior alveolar artery via the bone marrow.
The venous drainage is via the supercial temporal vein,
maxillary plexus and the pterygoid plexus. The mandibular branch of the trigeminal nerve is the motor supply to the
muscles of mastication.
The TMJ is innervated predominantly by the articulotemporal nerve, masseter and the temporal nerves. Four
types of receptors aid in proprioception: Rufni mechanoreceptors (type I), pacinian corpuscles (type II), Golgi tendon organs (type III) and free nerve endings (type IV). The
joint capsule, lateral ligaments and genu vasculosum in
the bilaminar zone typically contain these receptors. Comparatively, the anteromedial portion of the capsule contains very few type IV receptors.

CLINICAL EVALUATION OF
TEMPOROMANDIBULAR JOINT
Temporomandibular joints are located about 1.5 cm anterior to the tragus of the ear. The two TMJs, considered
together, compromise only one part of the total articulation between the lower jaw and the skullfacial skeleton
complex. The other important contribution is made by the
interdigitations of the mandibular and maxillary dentition,
and function and health of the joint is directly related to
condition of the teeth.
The history of presenting illness should include the onset
and course of signs and symptoms. Past history should
include the details regarding arthritis, infections, degenerating diseases, parotitis, ear disorders, muscular disorders,
trauma, past dental treatment, diet/nutritional adequacy
and habits like clenching, gum chewing, etc. and the individual lifestyle.

Examination of Temporomandibular Joint


The TMJ is examined by a thorough inspection, palpation,
and auscultation.
The face is inspected for any obvious asymmetry, scars
(may be indicative of previous surgeries, trauma), swelling/
ulceration/sinus openings in the pre-auricular region. Observe
for deviation/deection (Figure 6) of mandible on mouth
opening.
The TMJs can be palpated by extra-auricular and intraauricular methods. Palpation can be done standing at
10 oclock or 11 oclock positions by the clinician. Intraauricular palpation can be achieved by placing the little
243

Section IV Diseases of Specific Structures

Figure 6

supra-orbital ridge to above the ear. The patient is asked to


report any discomfort or pain.
Masseter
Masseter is palpated bilaterally in the area overlying the
anterior border of the mandibular ramus. The area of palpation is directly above the attachment of the body of the
mandible.
Pterygoids
Palpation of the pterygoid muscle is difficult because of
the inaccessibility of the muscle.
Medial pterygoid

Deflection of the mandible to the left side.


Courtesy: Department of Oral Medicine and Radiology,
Manipal College of Dental Sciences, Mangalore

nger inside the external auditory meatus. During mandibular movement the posterior poles of the condylar head
can be palpated with the pulp of the little nger. Intraauricular palpation may also be used to elicit capsular
tenderness.
Extra-auricular examination of the TMJ is achieved by
placing the index ngers in the pre-auricular region about
1.5 cm medial to the tragus of the ear. The lateral pole of
the condyle is accessible during this examination.
Palpatory examination of the TMJ should include
the assessment of mouth opening, range of mandibular
movements, joint tenderness, detection of clicks and/or
crepitus.

CLINICAL EVALUATION OF MUSCLES OF


MASTICATION AND ACCESSORY/CERVICAL
MUSCLES
Tenderness of the muscles of mastication results from stress
and fatigue which are characteristics of temporomandibular dysfunction.
The muscles to be examined should include the temporalis, masseter, medial and lateral pterygoids, digastric,
cervical and sternocleidomastoid muscles.
Temporalis
Temporalis is palpated simultaneously with the fingertips aligned in a row from the hairline just above the

244

Medial pterygoid can only be palpated near its insertion


by placement of the index finger laterally and posteriorly
into the floor of the mouth toward the medial surface of
the angle of the mandible.
Lateral pterygoid
Tenderness of the lateral pterygoid can occasionally be
detected by indirect application of pressure. The index finger
or back end of the handle of an instrument is positioned
distal and posterior to the maxillary tuberosity and posterior pressure is exerted to compress tissue against the muscle
(Figure 7).
Alternatively, the medial and lateral pterygoid muscles
can be assessed by functional evaluation. These can be
achieved by asking the patient to perform simple tasks like
opening the mouth against resistance (Figure 8) and closing the mouth against resistance.
Digastric muscle
Digastric muscles are palpated with the fingertips aligned
roughly parallel to the inferior border of the mandible in
the submental and submandibular region.

Cervical Examination
Temporomandibular disorders/myofascial pain disorders
often have musculoskeletal problems in other regions that
are particularly associated with neck. Check for mobility
of the neck and examine for range and symptoms.
Patient is rst asked to look to the right and then to the
left. There should be at least 70 rotation in each direction.
Next patient is asked to look upward as far as possible
(extension) and then downward (exion). Any pain is
recorded and any limitation of the movement determines
muscular or vertebral problem. Sternocleidomastoid/trapezius/posterior cervical muscles are often part of neck
disorder and may refer pain to face and head.

Chapter 10 Temporomandibular Disorders

Figure 7

length of the muscle is palpated down to its origin near


the clavicle.
Posterior cervical muscles

Use of the back end of a mouth mirror to elicit


tenderness at the site of the attachment of the lateral
pterygoid muscle

Trapezius, longissimus (capitis and cervices) splenius


(capitis and cervices) and levator scapulae.
The posterior cervical muscles do not directly affect
mandibular movements; however, they do become symptomatic during temporomandibular disorders and therefore are routinely palpated. They originate at the posterior
occipital area and extend inferiorly along the cervicospinal region. Because they are layered over each other,
sometimes it is difcult to identify them individually.
These muscles can be examined by slipping ngers
behind the patients head. Those of the right hand palpate the right occipital area and those of the left hand
palpate the left occipital area, both at the origins of the
muscle (the patient is questioned regarding any discomfort). The ngers then move down the length of the neck
muscles through the cervical area and any patient discomfort is recorded.
Trapezius

Figure 8

Trapezius, an extremely large muscle of the back, shoulder


and neck, does not directly affect jaw function but is a
common source of headache and is easily palpated. It
commonly has trigger points (TrPs) that refer pain to the face
and hence the purpose of its palpation is to search for active
TrP. The upper part is palpated from behind sternocleidomastoid, inferolaterally to the shoulder and any TrP are
recorded.
Splenus capitis
Splenus capitis is palpated for general pain, tenderness,
and TrP. Its attachment to the skull is a small depression
just posterior to the attachment of the sternocleidomastoid.
Palpation is begun at this point and moves inferiorly as
the muscle blends into the other muscles.

Occlusal Evaluation

Functional evaluation of lateral pterygoid muscle


(opening mouth against resistance)

Sternocleidomastoid
Palpation is done bilaterally near its insertion on the outer
surface of the mastoid fossa behind the ear. The entire

Examining the dentition and occlusion is an important


part of the physical examination of a TMJ disorder or orofacial pain patient. It may provide very useful information
about the existence of bruxism or other oral habits and
their possible effects on the dentition, periodontium or
other oral structures. Such an examination can also determine whether there has been a progressive change in the
occlusal relationship (midline shift, anterior open bite,
unilateral posterior open bite, etc.) that may indicate the
presence of such conditions as unilateral condylar hyperplasia, rheumatoid arthritis, or neoplasm. Noting the number of missing teeth particularly loss of posterior occlusal

245

Section IV Diseases of Specific Structures

support is important since this situation may predispose


the TMJs to degenerative joint disease (osteoarthrosis)
especially in the presence of bruxism.

DISORDERS ASSOCIATED WITH DEVIATION/


ALTERATION IN THE FORM OF ARTICULAR
SURFACES

Imaging Protocol

Changes associated with the articular surfaces include those


of the mandibular condyle and glenoid fossa. The changes
that can be appreciated are condylar head flattening
(Figure 9), flattening of the glenoid fossa or bony irregularities over the condylar head.
Thinning of the articular disk borders and perforations
are common changes associated with change in form of
the disk.

Decision should be taken considering the following:

Clinical situation
Cost
Radiation dose.

These depict the osseous structures of the joint with varying degrees of bony detail.

Plain films, panoramic radiographs, conventional and


computed tomography

CT can be reserved for the evaluation of:

Foreign body giant cell reaction to implants


Suspected tumors
Ankylosis
Complex facial fractures
MRI is indicated for soft tissues, including disk
position and contour
MRI when contraindicated, arthrography is recommended.

Disorders of TMJ
Dimitroulis in 1998 described temporomandibular disorders as a collective term used to describe a number of
related disorders involving the TMJ, masticatory muscles
and occlusion with common symptoms such as pain,
restricted movement, muscle tenderness and intermittent
joint sounds.
The disorders of the TMJ may exhibit a wide variety
of symptoms and signs. The symptoms and signs that are
frequently associated with temporomandibular disorders
include: pain on mouth opening, limitation of mouth
opening, pain on chewing, joint noises (clicking and/or
popping, grating), pain in the region of the joint and/or
muscles, pain around the region of the ear, temporal region
and cheeks, subjective hearing loss, occlusal irregularities,
attrition of teeth, headache (frontal, temporal, suboccipital), tinnitus, muscle hypertonicity and hypertrophy of jaw
muscles, neck pain and difculty in swallowing.
TMJ disorders may arise from macro trauma such as
in road trafc accident (RTA), excessive mouth opening
(yawning, biting onto a large chunk of food) or from
repeated micro trauma such as in parafunctional habits
(bruxism), uneven occlusal loading (malocclusion, high
points in restorations, poorly contoured crowns). Other
causes include stress, underlying systemic diseases, arthritis and developmental abnormalities. See Box 1 for classication of TMJ disorders.
246

Clinical features
Patient is usually asymptomatic. Over a period of time the
patient is accustomed to a new pattern of mouth opening,
thereby avoiding pain during mandibular movements.
Occasionally, a click may be evident during the opening
and closing movements. What is interesting about the
clicks associated with condition is that the click is evident
at the same point both during opening and closing. Whereas
in click associated with disk displacement, the opening
click is usually evident after 20 mm of mouth opening and
the closing click is felt just short of occlusion of teeth.
This condition can be managed by instructing the
patient to develop a path of mandibular movement that
avoids the interference and to chew on the affected side.
This will minimize the intra-articular pressure in the ipsilateral joint.

ARTICULAR DISK DEFECTS


Disk Thinning and Perforation
It is believed that the disk wears out over a period of time.
Hence, elderly individuals may generally present with
thinning of the disk which may ultimately perforate. The
other causes include excessive occlusal loads from parafunctional habits such as bruxism, clenching and trauma.
The thinnest intermediate portion of the disk may show
a circular hole with irregular or fragmented border. A perforated disk will expose the articular surface of the joint
leading to degenerative changes.
Clinical features
On auscultation of the TMJ, crepitus or grating noises may
be heard. In the early phases of the process pain may be a
presenting complaint. Once the disk is perforated occlusion
may be altered when teeth are in maximum intercuspation.
Disk changes are readily evident on MRI and arthrography.
Degenerative changes can be appreciated on traditional
imaging modalities and CT.

Chapter 10 Temporomandibular Disorders

Box 1

Classication of temporomandibular disorders

I. Disorders of the TMJ


Deviation in form
Articular surface defects
Disk thinning and perforation
Adherence and adhesions
Disk displacement
Disk displacement with reduction
Disk displacement without reduction
Displacement of diskcondyle complex
Hypermobility
Dislocation
Inflammatory conditions
Capsulitis and synovitis
Retrodiscitis
Degenerative diseases
Osteoarthrosis
Osteoarthritis
Juvenile idiopathic arthritis
Polyarthritides
Ankylosis
II. Masticatory muscle disorders
Acute conditions
Reflex muscle splinting
Myositis
Muscle spasm
Chronic conditions
Myofascial pain
Hypertrophy
Fibromyalgia
III. Congenital, developmental and acquired disorders of
condylar process
Congenital and developmental disorders
Condylar hyperplasia
Condylar hypoplasia
Aplasia
Acquired disorders
Neoplasms
Fractures

Figure 9

Orthopantomograph (OPG) showing flattening of the


condylar head on the right side

Cholitgul et al (1990) evaluated 15 patients who


were reported to have disk perforation at arthrography.
Eleven patients reported pain. Clicking and crepitation
was common. Deviation of the mandible at maximum
mouth opening toward the affected side was seen in nine
patients. The muscles of the affected side were tender on
palpation. The disk perforation was located in the posterior attachment in most joints. An anterior disk displacement was found in almost all patients. They concluded
that most joints with disk perforations were osteoarthrotic
and the most severe clinical and radiological ndings
are associated with an anterior disk displacement without
reduction.

Adherence and Adhesions


Adherence refers to a transient phase in which the condylar head and the articular disk (inferior joint space) or the
articular disk and the glenoid fossa (superior joint space)
may adhere together. However, prolonged periods of adhesion may result in a permanent state of adhesion (true
adhesions).
The causes for adhesion are long periods of static loading
of the joint (e.g. jaw clenching during sleep) and hemarthrosis caused by macro trauma or surgery.
Normally, when the joint is loaded, weeping lubrication
is exhausted and boundary lubrication takes over to prevent
adhesions. But when the jaw is subjected to long periods
of static loading, the boundary lubrication is not sufcient
to compensate for the exhaustion of weeping lubrication,
resulting in adherence of the disk either with the upper or
lower joint compartment.
Clinical features
Patients may complain of a stiff jaw, dull aching pain and
limited mouth opening, especially if they habitually clench
their teeth. However, the limitation in mouth opening
characteristically corrects following a single click when
the patient makes attempts to open the mouth.
True adhesions may cause elongation of the collateral
discal ligaments and anterior capsular ligaments. Hence,
during translatory movements the condyle is ahead of the
articular disk thereby appearing that the disk is posteriorly
dislocated. It is thus hypothesized that posterior disk displacements may result from disk adhesions.
Clinically, restriction of the condylar movements to
rotation alone, is typical of adhesions between disk and
superior joint space (mouth opening may be restricted to
about 25 mm). However, when the adhesion occurs between
the disk and the inferior joint compartment, rotational
movement is inhibited and the translatory cycle is normal
(patient can open the mouth to a normal interincisal distance but experience a jerk or limitation when attempting
to open the mouth to its full extent).
247

Section IV Diseases of Specific Structures

Disk Displacement
Disk displacements are also termed as internal derangement. The internal derangements could include disk displacement with reduction and disk displacement without
reduction.
Anterior disk displacement is common and it usually
occurs when there is elongation of the disk attachment and
deformation or thinning of the posterior border of the disk,
which in turn permits the articular disk to get displaced in
an anterior direction on the surface of the condyle. In normal conditions, when the teeth are in occlusion, the posterior band of the disk ends at the apex of the condyle. In
anterior disk displacement, the posterior band of the articular disk terminates ahead of the condylar apex. The most
common causes for internal derangement include trauma,
clenching and biting on hard substances.

Disk Displacement with Reduction


It is characterized by an anterior or anteromedial displacement of the disk upon mouth opening. However, on closing the mouth the disk returns to a more normal position
relative to the condyle on opening (Figure 10).
Clinical features
Clicking sound may be heard during mandibular opening
and closing. The opening click may be heard during any
phase of the translatory cycle and the closing click may be
felt as the disk again becomes displaced. Mandible may be
deviated to the affected side. Muscle splinting may result
in joint tenderness and limitation of mouth opening.

Disk Displacement without Reduction


In this condition the condylar head is unable to pass under
the displaced disk. The reasons for the condyle to be trapped
include: thickening of posterior band, change in shape of
disk from biconcave to biconvex and decrease in tension
in the posterior attachment. Such a trapping of the disk in

front of the condyle, limiting the condylar translation in the


affected joint results in a closed lock (Figure 11).
Clinical features
It is generally a painful condition as the articular capsule,
discal ligaments and posterior attachment are inflamed.
Patient may present with pain and severe limitation in mouth
opening (maximum of 2530 mm). Mandible is deflected
to the ipsilateral side on mouth opening. There is limitation
in protrusive movements. Chronic cases may present with
joint crepitus. Lateral excursions are limited.

Displacement of DiskCondyle Complex


(Hypermobility and Dislocation)
Occasionally during the terminal phases of the translatory
cycle, as the condyle moves past the articular eminence
it may suddenly move forward to facilitate a wide mouth
opening referred to as subluxation (hypermobility, partial
dislocation).
Hypermobility may occur due to joint laxity seen as a
genetic predisposition (EhlersDanlos syndrome), following
dental procedures that require prolonged mouth opening
(endodontic procedures, third molar extraction), excessive
yawning and during endotracheal incubation for general
anesthesia.
Clinical features
Many patients describe the sudden forward movement as
a feeling of a thud sound. This condition is usually painless unless it becomes chronic. Patients may exhibit a tapered/
elongated face. Hypermobility may be distinguished from
anterior disk displacements in which the click is associated
only with wide opening and absence of closing click.

Dislocation (Open Lock)


Dislocation of the condyle is a common condition that
may occur in an acute or chronic form. It is characterized

Figure 10
Resting phase

Early translatory phase

Late translatory phase

Open click

Phases of anterior disk displacement with reduction

248

Chapter 10 Temporomandibular Disorders

by inability to close the mouth with or without pain.


Dislocation has to be differentiated from subluxation which
is a self-reducible condition. When the mouth is opened,
the head of the condyle should not pass beyond the apex
of articular eminence. In case of laxity of capsular structures, a wide open position allows the condyle to move pass
the articular eminence which cannot be reduced by the
patient. Dislocation can occur in any direction with anterior dislocation being the most common one. Various predisposing factors have been associated with dislocation
like muscle fatigue and spasm, the defect in the bony surface like shallow articular eminence, and laxity of the capsular ligament. People with defect in collagen synthesis like
EhlersDanlos syndrome, Marfan syndrome are said to be
genetically predisposed to this condition.
Clinical features

Lateral dislocation has been described by Allen and


Young in 1969 in two subgroups: type 1 is the lateral subluxation and type 2 is a complete dislocation where the
condyle if forced laterally and superiorly to the temporal
fossa. It is accompanied by the fracture of body of mandible
at symphysis.
Superior dislocation as described by Zecha in 1977 is
the dislocation of condyle in the middle cranial fossa and
associated with fracture of glenoid fossa. It is said to be
most probably due to the small rounded shape of the condyle which fails to impinge in the margins which is stronger
than the central area.

INFLAMMATORY JOINT DISORDERS


Synovitis or Capsulitis

The condition is characterized by inability to close the mouth


after wide opening. Bilateral dislocation is more common
than unilateral dislocation. However, when the dislocation
is unilateral, the chin is deviated to the contralateral side.
Palpation in the preauricular region reveals an empty joint
fossa and may reveal the condyle anterior to the joint. The
inability to close the mouth is due to the spasm of the
masticatory muscles. A typical facial expression (elongated
face) is due to anxiety related to the thought of not being
able to close the mouth (Figures 12A, B and 13A, B).

Synovitis and capsulitis are clinically considered as a single disorder. Synovitis refers to inflammation of the synovial tissues and inflammation of the capsular ligaments is
referred to as capsulitis. Various causes have been attributed to these inflammatory conditions such as trauma,
opening the mouth excessively, chronic condylar displacement in a posterior direction and sometimes from a direct
spread of inflammatory products from the surrounding
structures.
Clinical features

Types of dislocation
Depending upon the position the condyle occupies, Heslop
in 1956, described the anterior dislocation in which the
condyle moves anterior to the articulating eminence. It is
one of the most common type of dislocation. It represents
the pathological forward extension of normal translatory
movement of head of condyle. The anterolateral variant
was described by Morris and Hutton in 1957.
Helmy in 1957 described the posterior variant in which the
head of condyle is displaced posterior to its usual position.
It is usually associated with a fracture of base of skull or
the anterior wall of bony meatus.

Continuous pain that exacerbates during function is characteristic of this condition. Limitation in jaw movements is
another common finding. In some individuals malocclusion
in the posterior teeth is seen due to inferior displacement
of the condyle resulting from the edema.

Retrodiscitis
Inflammation of the retrodiscal tissues (retrodiscitis) results
from a traumatic injury which may indirectly cause the
condylar head to impinge on the retrodiscal tissues.

Figure 11
Resting phase

Early translatory phase

Late translatory

Phases of anterior disk displacement without reduction

249

Section IV Diseases of Specific Structures

Figure 12
A

(A) Elongated face in bilateral condylar dislocation. (B) OPG showing bilateral condylar dislocation.
Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

Figure 13
A

(A) Normal facial appearance following reduction of the dislocated condyles. (B) Normal positions of the condyle in the glenoid
fossa after reduction. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

Chronic disk displacement and dislocation may also result


in insults to the retrodiscal tissues.

However, patient should be instructed to chew on the


affected side as this will relieve occlusal load on the side
affected thereby hastening the healing process.

Clinical features
Inflammation of the retrodiscal tissues may lead to a forward and downward placement of the condyle thereby
producing a same-sided malocclusion of posterior teeth
and heavy contact in the anterior teeth of the opposite
side. Continuous pain is felt in the TMJ region, which
exacerbates on clenching.
250

DEGENERATIVE JOINT DISEASES


Osteoarthrosis
Osteoarthrosis is a non-inflammatory degenerative disorder
of a joint affecting articular tissues and subchondral bone.

Chapter 10 Temporomandibular Disorders

Figure 14

Ely cyst in the mandibular condyle. Courtesy: Department of Oral Medicine and Radiology,
Manipal College of Dental Sciences, Mangalore

It is believed that excessive load on the TMJ leads to


degeneration of the fibrous articular tissue covering the
condyle. Osteoarthrosis occurs secondary to displacement
of the disk.
Clinical and radiographic features
Patients will exhibit restricted movement of the mandible.
Mouth opening may be associated with deflection toward
the affected side. Auscultation may reveal crepitus during
opening and closing the mouth. The condition is painless.
Long-standing osteoarthrosis leads to the formation of
multiple cystic areas in the medullary region of the condyle
which in turn may collapse to form erosive areas altering
the condylar morphology. Some authors suggest that osteoarthrosis is a burned out or resolved phase of osteoarthritis.
Management
Occlusal irregularities, if any, may be corrected to prevent
TMJ overloading.

Osteoarthritis
Osteoarthritis is characterized by pain secondary to TMJ
synovial inflammation. It is usually seen in elderly and
relatively more frequently in women.
Clinical features
Almost all the patients report of a gradual onset of symptoms. The condition is self-limiting and even in the absence
of active treatment the symptoms subside over a period of
time, and the TMJ movements revert back to an acceptable
level.

In the early stages of osteoarthritis patient may complain


of pain that exacerbates after function and relieved by rest.
However, as the condition worsens pain may be present
even at rest. TMJs are usually stiff in the early morning
hours and cold climatic conditions may exacerbate the pain.
On clinical examination, the TMJ may exhibit very limited range of movement. Mouth opening will result in
deviation of the mandible to the same side. Some patients
may present with an anterior open bite. Crepitus, myositis
and masticatory muscle spasm are other characteristic features of osteoarthritis.
Radiographic features
Various radiographic findings may be seen based on the
extent and severity of the degeneration and the simultaneous remodeling. Radiographs may reveal a reduction in
the size of the joint compartments or a total lack of space,
flattened condylar head, erosion on the articulating surface, subchondral sclerosis and osteophytes.
These osteophytes may eventually break off to lie on the
joint space and may be detected on MRI and arthrography
as joint mice or loose bodies. Another characteristic nding
is the presence of subchondral bone cysts (Ely cyst). These
pseudo cysts (Figure 14) are areas of degeneration, containing brous tissue, granulation tissue and osteoid. In
severe cases, as the posterior slope of the articular eminence erodes, the glenoid fossa enlarges in size.

Juvenile Idiopathic Arthritis


The juvenile idiopathic form of arthritis is a chronic, inflammatory, systemic disease typically beginning before 16 years
of age. It may affect one or more joints of the body.
251

Section IV Diseases of Specific Structures

Clinical features

Figure 15

The condition is characterized by peripheral arthritis. An


immunoinflammatory pathogenesis is considered as the
etiology. Based on the clinical expression at the onset
and the first 6 months of the disease, three types have been
described: oligoarticular (four or fewer involved joints),
polyarticular (five or more involved joints), and systemic
(presence of arthritis and severe systemic involvement).
Patients present with chronic synovitis, arthralgia,
and impaired joint mobility. Chronic inammation in the
joint results in degenerative changes thereby causing pain,
joint sounds, and limited movement. Alterations in facial
growth, such as micrognathia, retrognathia, facial asymmetry, and anterior open bite, also occur due to condylar
involvement. Other extra-articular manifestations of disease include fever, rheumatoid rash, cardiac disease and
chronic uveitis.

Polyarthritides
Polyarthritides represent a group of disorders characterized
by inflammation of the articular surfaces of the joint. It
resembles osteoarthritis as it exhibits degenerative changes
in the articular cartilage and underlying bone along with
inflammation of the capsule and synovial tissues.
Clinically, tenderness may be elicited on TMJ palpation.
The TMJ area may exhibit swelling and erythema. The
patients may have limited function. Crepitus is a characteristic nding. Patients symptoms may aggravate with parafunctional habits. Radiographs reveal surface changes in
the glenoid fossa and attening of the articular eminence.

Traumatic Arthritis
Occasionally a major traumatic episode can result in inflammatory changes that ultimately lead to articular surface
changes. Patients may complain of restricted mouth opening and pain. On palpation a soft end feel is typically
evident.

Limitation in mouth opening and deviation of the


jaw in septic arthritis. Courtesy: Department of Oral
Medicine and Radiology, Manipal College of
Dental Sciences, Mangalore

Swelling, tenderness and rise in local temperature are characteristic of septic arthritis. Limitation in mouth opening
and deviation of the jaw to the affected side are other ndings (Figure 15). Affected side may reveal tender cervical
lymphadenopathy.
Synovial uid and blood studies will aid in the diagnosis. The commonly isolated organisms from a previously
normal TMJ are gonococcal species and from TMJ with
previous history of arthritis, Staphylococcus aureus has
been isolated. Untreated cases of septic arthritis can lead
to brain abscess, ankylosis and osteomyelitis of temporal
bone. Ankylosis and facial asymmetry may be a common
complication in children.

Rheumatoid Arthritis
Infectious Arthritis/Septic Arthritis
This form of arthritis is generally seen in patients with
previously existing joint disease or with underlying systemic illness. The highest incidence of septic arthritis is
seen in individuals on long-term immunosuppressive drugs
or corticosteroids.
Otherwise sterile articular surfaces and joint spaces
may become infected secondary to blood borne bacterial
infection or extension of infection from adjacent sites such
as the molar teeth, middle ear and parotid gland.
Clinically patient gives a history of constant pain in
the TMJ region which typically aggravates with function.
252

Rheumatoid arthritis (RA) is a chronic inflammatory, autoimmune disorder, which may involve many of the diarthrodial joints (usually in a symmetrical fashion) in the
body characterized by persistent synovitis. Women are three
to four times more affected than men. The age of onset
varies between 25 and 55 years.
Though the exact nature of RA is still unknown, it is
believed that the inammation of the synovial membranes
extends into the surrounding connective tissues and articular surfaces (this reactive macrophage laden broblastic
proliferation from the synovium that extends to the joint
surface is called pannus), which then become thickened
and tender. The cells of the synovial membrane express

Chapter 10 Temporomandibular Disorders

enzymes that cause destruction of the articular surface,


eventually leading to a brous ankylosis.

Figure 16

Clinical features
TMJ afflicted with RA may produce pain, joint stiffness,
limited mouth opening, joint sounds and open bite. The
reported prevalence of TMJ involvement by RA varies
widely from 4.7 to 88%.
The American Rheumatism Association (1987) laid down
guidelines for diagnosis of RA. According to these guidelines, the patient must present three or four of the following symptoms for more than 6 months: morning stiffness
for more than 1 hour; arthritis in three or more joints; arthritis in the hands; symmetrical arthritis; rheumatoid nodes;
presence of rheumatoid factor; radiographic alterations.
Laboratory investigations
The level of rheumatoid factor, erythrocyte sedimentation
rate, C-reactive protein, thrombocyte count and plasma
tumor necrosis factor- will aid in the diagnosis.
Radiographic features
The characteristic radiographic findings include generalized decreased density of bone, severe erosion of the condylar head (occasionally only the neck of the condyle may
be remaining), subchondral sclerosis, flattening of the condylar head, subchondral cysts and osteophyte formation.
In some individuals, the condyle may assume a sharpened
pencil shape owing to the erosion of the anterior and posterior condylar surfaces (Figure 16).
A modied grading system for the evaluation of TMJ
abnormalities based on the degree of bony destruction of
the mandibular condyle can be summarized as:

Grade 0 (normal): well-defined cortical outline of the


condyle
Grade I (mild): presence of cortical destruction and
irregular margin of the condyle
Grade II (moderate): bony destruction or erosion of
the condyle or evident flattening, with deviation from
normal joint morphology
Grade III (severe): complete or almost complete destruction of the condyle.

Psoriatic Arthritis
Psoriatic arthritis (PA) is present in about 57% of the
patients suffering from psoriasis. The diagnosis can be
made when patients present with erosive polyarthritis with
negative rheumatoid factor and psoriatic skin lesions are
seen long before TMJ is affected. The skin lesions are seen
long. This condition affects the fingers and spine along
with the TMJ. Eighty-five percent of the patients present
with pitting of the nails.

Pencil-shaped condyle on the right side and condylar head


flattening of the left side. Courtesy: Department of
Oral Medicine and Radiology, Manipal College of
Dental Sciences, Mangalore

Clinical features
Unlike rheumatoid arthritis, the TMJ symptoms associated
with PA are unilateral. Patients present with pain over the
TMJ, limited mandibular movement and deviation of the
mandible to the affected side. Radiographically, the TMJ
changes are generally similar to those that are seen in
rheumatoid arthritis, however in some patients extensive
sclerotic changes may be evident.

Hyperuricemia
Gout is considered a true crystal deposition disease. Gout
may be described as a pathological response of the periarticular tissues to the presence of monosodium urate monohydrate crystals. Though a chronic state of hyperuricemia
is required for the development of gout, it alone is not sufficient to predispose to gout. It is estimated that 95%
of hyperuricemic individuals may not develop gout. Gout
commonly affects the first metatarsophalangeal joint (50%)
and other joints such as the ankle, knee, wrist, elbow and
the TMJ.
Clinical features
Crystal deposition may be seen in tissues adjacent to the TMJ.
Occasionally, monosodium urate crystals may be evident
in the synovial fluid aspirate.

TMJ ANKYLOSIS
Ankylosis is an intra-articular condition where there is
fusion between the bony surfaces of the joint, the condyle
and the glenoid fossa. The term ankylosis is derived from
253

Section IV Diseases of Specific Structures

a Greek word which means stiffening of a joint as a result


of a disease process. Ankylosis of the mandible with immobility of the joint may be of an osseous, fibro-osseous, or
cartilaginous variety.
Ankylosis must be distinguished from its counterpart
pseudoankylosis. Hypomobility of the joint due to coronoid
hyperplasia or due to brous adhesions between the coronoid and tuberosity of the maxilla or zygoma (e.g. as in
V-shaped fracture of the zygomatic arch impinging on
coronoid leading to brous or bony union) are also examples of pseudoankylosis. Even though jaw movement is
restricted as in bony ankylosis, the pathology is extraarticular in these cases.
Etiopathology
Trauma Most cases of ankylosis result from condylar
injuries sustained before 10 years of age. A unique pattern
of condylar fractures is seen in children. Condylar cortical
bone in children is thin with a broad condylar neck and
rich subarticular interconnecting vascular plexus. An intracapsular fracture leads comminution and hemarthrosis of
the condylar head. This sort of intracapsular burst fracture
is called mushroom fracture. This results in the organization of a fibro-osseous mass in a highly osteogenic environment. Moreover, immobility leads to ossification and
consolidation of the mass, resulting in ankylosis. Ankylosis may also occur in trauma sustained during forceps
delivery.
Laskin (1978) had outlined various factors that may be
implicated in the etiology of ankylosis following trauma:

Age of patient: Younger patients have significantly


higher osteogenic potential and rapidity of repair.
Moreover, the articular capsule is not as well developed
in younger patients, thus permitting easier condylar
displacement out of the fossa and thereby damage to
the disk. Finally, there is a greater tendency for prolonged self-imposed immobilization of the mandible
post-traumatically in children.
Type of fracture: The condyle in children has a thinner
cortex along with a thick neck, which predisposes them
to a higher proportion of intracapsular comminuted
fracture. In contrast, adults have a thinner condylar
neck which usually fractures at the neck, thus sparing
the head of the condyle within the capsule.
Damage to articular disk: The direct contact between a
comminuted condyle and the glenoid fossa either from
a displaced or torn meniscus is the key factor in the
development of ankylosis.
Period of immobilization: Prolonged mechanical immobilization or muscle splinting can promote osteogenesis and consolidation to set in an injured condyle.
Total immobility between articular surfaces after condylar injury leads to a bony type of fusion, whereas
some movement leads to a fibrous type of union.
254

Local infections Otitis media, mastoiditis, osteomyelitis


of temporal bone, parotid abscess, infratemporal or submasseteric space or parapharyngeal infections, furuncle,
actinomycosis (the source of infection is contiguous, from
adjacent structures).
Systemic conditions Tuberculosis, meningitis, pharyngitis, tonsillitis, rubella, varicella, scarlet fever, gonococcal
arthritis, ankylosing spondylitis (the route of spread is
hematogeneous).
The local and systemic infections may pass along as
septic arthritis which may not always cause ankylosis.
Staphylococcus species, Streptococcus species, Hemophilus
inuenzae, Neisseria gonorrhoeae are the most likely
causes of septic arthritis. The infection may take either the
hematogeneous, contiguous, or by direct inoculation. The
synovium with its high vascularity and lack of a limiting
basement membrane is vulnerable to infection.
Arthritis/inflammatory conditions About 50% cases in
juvenile RA (Stills disease) also have TMJ involvement
along with polyarthritis. Osteoarthritis may also lead to
ankylosis.
Neoplasms Sarcoma, osteoma and condroma may also
result in ankylosed joint. The pathogenesis of ankylosis is
generally the same in all the non-traumatic conditions
degenerative, destructive, and inflammatory changes in
disk followed by repair leading to ankylosis. Destruction
of the disk leads to bony contact between the condyle and
glenoid fossa.
Classification of ankylosis according to tissues
involved and extent

True ankylosis or pseudoankylosis


Extra-articular or intra-articular
Fibrous, bony, or fibro-osseous
Unilateral or bilateral
Partial or complete.

Classification of ankylosis by Topazian (1966)

Type I: Fibrous adhesions in or around the jointrestricted condylar gliding.


Type II: Formation of a bony bridge between the
condyle and glenoid fossa.
Type III: Condylar neck is ankylosed to the fossa
completely.
Grading of TMJ ankylosis
Sawhney (1986) graded TMJ ankylosis into four types:

Type I: Flattening or deformity of condyle with little


joint space on radiograph. There is minimal bony
fusion, but extensive fibrous adhesions around joint.
Some movement is possible.

Chapter 10 Temporomandibular Disorders

Type II: Bony fusion on the outer edge of articular surface, but no fusion on the deeper aspect of the joint.
Type III: A bridge of bone exists between the ramus
and zygomatic arch. The upper articular surface and
the articular disk on the deeper aspect are still intact.
Medially, a displaced atrophic condyle still exists and
which is functional. Type III ankylosis results from a
fracture-displaced condyle, compared to the crushing
types of condylar injuries as in types I and II.
Type IV: Total TMJ obliteration between ramus and
skull by large bony mass. It is the most common type.

Figure 17

Clinical features
The clinical features of ankylosis depends on:

Type of ankylosis: Unilateral versus bilateral, bony


versus fibrous, extent of joint involvement.
Age of onset and duration of ankylosis: The deformity
will be severe if it occurs before the age of 5 years.
Clinical features of unilateral ankylosis
Facial features

Obvious facial asymmetry.


Chin receded with hypoplastic mandible on affected
side, resulting in deviation of chin and mandible
toward affected side.
Unilateral vertical deficiency on the affected side.
Roundness/fullness on affected side; foreshortened
mandible, flatness and elongation on normal side as it
grows toward the affected side.
Loss of the normal bilateral symmetrical divergence
from the mental region toward the angle.
The lower border of the mandible on the affected side
has a concavity that ends in a well-defined antegonial
notch.
Markedly elongated coronoid process.

Intraoral features

Occlusal cant with deviation of maxillary and mandibular midlines toward affected side.
Class II Angle malocclusion present on the affected
side with unilateral crossbite on the opposite side.
The mouth opening is restricted: amount of opening
depends upon degree of ankylosis.
Clinical features of bilateral ankylosis
Facial features

Symmetrical defect.
Retrognathic mandible with a short ramus and a small
body.
Often microgenia, small chin.
Bird-face deformity (Figure 17) or Andy Gump facies.
Convex profile.

Bird face deformity. Courtesy: Department of Oral Medicine


and Radiology, Manipal College of Dental Sciences, Mangalore

Relatively short hyomental distance with tight suprahyoid musculature.


Cervicomental angle may be reduced or completely
absent.
Obstructive sleep apnea may be present due to oropharyngeal airway narrowing in cephalocaudal,
anteroposterior, and transverse directions.

Intraoral features

Mouth opening would be less than 5 mm (Figure 18) or


may be nil at times.
Generally a class II malocclusion, although class I
occlusion may also be seen.
Incompetent lips and proclined lower anteriors.
Open bite with protrusion of both upper and lower
anteriors resulting from the protrusive action of
tongue because of decreased tongue space.
Severe crowding, multiple impacted teeth with oral
health maintenance problems, leading to caries and
periodontal problems.

The key clinical difference between intra-articular and


extra-articular ankylosis is the ability or limited ability to
translate the mandible. If the ankylosis has an extraarticular origin, translation and anteroposterior movement
may not be as limited as rotational movement.
Radiographic features
In fibrous ankylosis, joint may appear normal or the
articulating surfaces may be irregular. The joint space is
255

Section IV Diseases of Specific Structures

Figure 18

Management
The goals of management should include restoration of
mouth opening and joint function, facilitation of condylar
growth, correction of facial profile and to relieve upper
airway obstruction.
Surgical correction of ankylosis is best achieved by
condylectomy, gap arthroplasty, coronoidectomy, interpositional arthroplasty (with autogenous or alloplastic grafts)
and secondary procedures such as orthognathic surgery
and distraction osteogenesis. Surgical correction should be
followed by active physiotherapy.
When ankylosis is left untreated it may result in abnormal facial growth and development, speech defects, nutritional impairment, respiratory distress syndrome, conditions
related to poor oral hygiene and psychological impact on
the patient.

Restricted mouth opening. Courtesy: Department of


Oral Medicine and Radiology, Manipal College of
Dental Sciences, Mangalore

MASTICATORY MUSCLE DISORDERS


Acute Disorders
Reflex Muscle Splinting

Figure 19

Muscle splinting or protective co-contraction is a CNS


response to actual tissue injury/a threat of injury. Like the
name suggests, in the event of an injury or threat of
potential injury the sequence of muscle activity is modified such that the tissue is protected from any further
insult. High points in a newly fabricated crown, biting on
hard food substance, etc. may lead to a reflex muscle
splinting.
Clinical features
Patient may report of muscle weakness following the tissue injury. Pain is experienced only during function and is
not evident at rest. Limited mouth opening which can
improve when the patient attempts to open the mouth
gently is another characteristic feature. The affected muscle may feel tight/stretched on palpation.
Management and prognosis

Orthopantomograph showing bony ankylosis in the right side


and elongated coronoid process. Courtesy: Department
of Oral Medicine and Radiology, Manipal College
of Dental Sciences, Mangalore

markedly decreased. In bony ankylosis, the joint space


may be obliterated, completely or partly by an osseous
bridge (Figure 19). Other features include deepening of the
antegonial notch and compensatory elongation of the coronoid process on the affected side.
256

Usually removal of the cause and resting the affected muscle is sufficient. Moist heat fomentation will aid in hastening the recovery process. Patient should be advised not to
overuse the affected the muscle. Muscle relaxants can be
used for a short period of time.

Myositis
Inflammation of the muscle that results from a local cause
is referred to as myositis. The causes of myositis include
traumatic injuries, muscular strain and orodental infections.

Chapter 10 Temporomandibular Disorders

However, myositis usually arises out of a long standing, severe


and neglected muscle splinting and myospasm.
Clinical features
The involved muscle is painful and usually associated with
a swelling. Like all muscular disorders, the pain exacerbates when the muscle is under function. Muscular dysfunction occurs secondary to muscle pain and inflammatory
exudate as opposed to muscle contraction. Untreated
myositis results in a myofibrotic contracture.

Muscle Spasm (Myospasm)


Myospasms of the muscles of mastication are uncommon.
It is a CNS-induced tonic muscle contraction. In this condition, all the motor units of the affected muscle contract
resulting in shortening of the muscle length resulting
in an acute spasm. Certain local muscle conditions have
known to predispose to myospasms such as muscle fatigue,
alteration in the local electrolyte balances and deep pain.
Muscles that have already been overused or those that have
been weakened because of protective splinting more likely
undergo a spasm. Certain tranquilizers may also cause masticatory muscle spasm.
Clinical features
Patient usually presents with limited mouth opening. Pain is
usually dull and continuous with occasional periods of acute
pain. The pain may be referred to the face, temple region
and the ear. Malocclusion is another characteristic feature.
Analgesics can be prescribed. Moist heat fomentation
will help in relaxing the muscle. Local anesthetic without
vasoconstrictor can be injected into the affected muscle
to relieve pain and facilitate speedy recovery. Occlusal
bite guards may be given to counteract the effects of parafunctional habits if any.

in spasm, with increased tension and decreased exibility.


It usually presents with regional muscle pain distributed in
one or two quadrants of the body. Taut bands are groups
of muscle bers that are hard and tender on palpation.
Tender spots are specic sites of localized pain.
Predisposing factors
Acute muscular injury sustained as a result of macro
trauma or sudden wide mouth opening or a sustained state
of muscular contraction such as injuries due to bad posture, muscular tension and clenching/bruxism can predispose to MFP.
Pathophysiology
Precipitating factors of MFP may cause the facilitated
release of acetylcholine at motor end plates, sustained
muscle fiber contractions and local ischemia with release
of vascular and neuroactive substances, and muscle pain.
More acetylcholine may then be released, thus perpetuating the muscle pain and spasm. Local muscle fibrosis may
occur after a prolonged period of time.
Clinical features
Laskin included the following signs and symptoms for the
diagnosis of MFP:

Unilateral, dull pain in the ear or preauricular region,


that is worse on awakening
Tenderness in muscle of mastication on palpation
(localized TrP)
Limitation/deviation of mandible on opening.
A more comprehensive description of the clinical features
are described below.
Primary finding

Chronic Conditions

Myofascial Pain

Costen (1934) first described a symptom complex, TMJ


pain dysfunction syndrome, which included facial and
head pain and TMJ dysfunction. Laskin (1969) was the
first to coin the term myofascial pain dysfunction syndrome. Myofascial pain (MFP) can arise in any skeletal
muscle such as those in the head (commonly the muscles of
mastication), neck, lower back and shoulders.
Traditionally, MFP is believed to arise from TrP (trigger
point) in a muscle. TrPs are minute sensitive areas in a
muscle that spontaneously or upon compression cause
pain to a distant region, known as the referred pain zone.
In recent times, MFP includes muscle pain from taut
bands (TB) with TrP or tender spots (TS). The muscles are

Patient complains of pain in one or more masticatory


muscle
Tenderness or pain upon manipulation/palpation of
masticatory muscle with replication of chief complaint
Tender site pain can be referred to other orofacial
areas (TrP)
Pain aggravated by mandibular function
Acute malocclusion.

Secondary findings

Restricted range of motion (ROM)


Maximum assisted opening maximum unassisted
opening pain free opening
ROM increases by use of vapocoolants
Limited function
Clinical or behavioral indications of hyperfunction/
parafunction
Acute malocclusion.
257

Section IV Diseases of Specific Structures

Possible findings

TMJ pain
Joint sounds
Inflammation
Restricted range of motion unmodified by assisted
opening/vapocoolant
Hypertrophy
Myalgia secondary to systemic disease.
Other reported symptoms include: musculoskeletal symptoms (fatigue, stiff joints and swelling), neurological symptoms (tingling, numbness, blurred vision, muscle twitching
and excessive lacrimation), and otologic symptoms (ear
pain, tinnitus, diminished hearing, dizziness and vertigo).
Other symptoms that patients report of include: dentinal
hypersensitivity and cutaneous hypersensitivity.
Referral pattern for myofascial pain
1.
2.

3.
4.

Medial pterygoid muscle: Pain referred to posterior


part of mouth and throat, TMJ and infra-auricular area.
Lateral pterygoid muscle: Inferior head refers pain to
the TMJ area and the superior head refers to the zygomatic area.
Masseter muscle: Pain is referred to the posterior mandibular and maxillary teeth, ear and TMJ.
Temporalis muscle: Pain is referred to all maxillary
teeth and upper portion of face.

Management
The management of MFP requires a multi-pronged
approach. In the short term, the aim is to abolish the TB,
TrP and TS for pain relief. In the long-term, achieving
muscle flexibility and eliminating associated precipitating
factors is the objective.
Counseling Patient should be counseled about the nature
of the condition and encouraged to discontinue parafunctional habits and consume soft diet.
Physiotherapy Physical modalities are useful supplementary treatments that help in controlling muscle pain and
spasm. Moist heat application to the affected site increases
blood flow and increases vascularity, resolution of inflammation and fibrosis. It also increases flexibility of connective tissue and decreases muscle spasm and pain. However
moist heat fomentation provides superficial heat with limited
subcutaneous penetration. Ultrasound, on the other hand,
provides deep heat with higher subcutaneous penetration.
Trigger point therapy Spray and stretch technique and
local injections are used.
Refrigerant spray such as ethyl chloride or uoromethane
can be sprayed onto the skin surface from a distance of
about 18 inches at an angle of 30. The skin surface should
be stretched manually during the spray. The spray anesthetizes the site and facilitates the patient to stretch the
258

muscle in spasm. Alternatively, 0.5% procaine without


epinephrine can be injected into the trigger point.
Medication NSAIDs and skeletal muscle relaxants (chlorzoxazone, methocarbamol) can be used. Patients who are
anxious can be prescribed 2 mg of diazepam three times
a day and 5 mg at bed time for a 2-week period. This will
help in controlling the anxiety and relaxing the muscles.
Such individuals should be counseled not to drive and to
avoid using heavy machinery.
Occlusal splint therapy The occlusal splint helps in
maintaining a harmonious relation between the TMJ and
muscles. It also aids in re-establishing a coordinated pattern of activity in the absence of tooth influence. The most
important function of the splint is that it helps in the resolution of micro trauma to muscle.
Other treatment modalities include isokinetic jaw exercises, biofeedback, acupuncture and hypnotherapy.
Transcutaneous electric nerve stimulation (TENS) The
TENS temporarily activates afferent nerves, thereby modulating pain. The electrical impulses are produced in a
handheld battery-operated device. TENS has been proven
to be useful in controlling masticatory muscle and neurogenic pains. The impulses generated have a duration of
2 millisecond with an interval of 0.51.5 second. The operating voltage is about 4 volts. TENS is believed to have
physiological (rhythmic contractions of muscles increase
blood supply), neurological (electrical stimulation inhibits
pain conduction), pharmacological (releases endorphins)
and psychological (placebo) effects.

Muscular Hypertrophy
Enlargement or hypertrophy of the masticatory muscles is
a relatively rare condition. The hypertrophy is clinically
evident as a localized firm non-tender swelling along the
body of the affected muscle.
Legg was the rst to describe bilateral enlargement of
the masseter and temporalis muscles. However, literature
review reveals the description of muscular hypertrophy of
the masseter, temporalis and the pterygoid.
Masticatory muscle enlargement can be either congenital
or acquired. Usually, the acquired form is a result of parafunctional jaw habits such as bruxism or masticatory
hyperfunction (chewing hard food, chewing gum). Some
authors believe that emotional stress may result in chronic
forceful clenching of the jaws and bruxism, resulting in
hypertrophy of the muscle (Figure 20).
Muscular hypertrophy should be differentiated from conditions such as lipomatosis, vascular tumors, liposarcoma,
rhabdomyosarcoma and inltrative leukemia and lymphoma.
MRI and ultrasound will help in revealing the homogeneous
enlargement of the muscles.

Chapter 10 Temporomandibular Disorders

Figure 20

However, one should be careful to distinguish tender


points associated with myofascial pain from those seen in
bromyalgia. Only tender points associated with myofascial
pain refer pain, produce a jump response on palpation
and cause central excitatory response.
Clinical features
Fibromyalgia is more common in women compared to men
(9:1). The peak onset of disease is between 45 and 60 years
of age. Patients have also reported of paresthesia, symptoms of irritable bowel syndrome, dysmenorrhea and
Raynauds phenomenon.
Official diagnostic criteria for fibromyalgia

Masseteric hypertrophy. Courtesy: Department of


Oral Medicine and Radiology, Manipal College of
Dental Sciences, Mangalore

Orthopantomographs may reveal enlarged ramal region


and a prominent antigonial notch in masseteric hypertrophy. Anteroposterior radiographs show bone spurs at the
mandible angle (it is estimated that 20% of normal population may also show bone spurs). Guggenheim and Cohen
reported that bone spurs are caused by periosteal irritation
and new bone deposition responding to increased forces
exerted by the muscle bundles.
Management
In normal circumstances muscular hypertrophy needs no
specific treatment. However, when cosmetic compulsions
are paramount, various non-surgical and surgical treatment modalities may be considered.
It has been suggested that cessation of the parafunctional habit such as bruxism may result in muscular atrophy.
Premature contacts, poorly contoured restorations and malocclusions should be corrected.
Minute doses of botulinum toxin type A may be injected
into the affected muscle. Surgical options include partial
or complete resection of the enlarged muscle and reduction of bone prominence from the mandibular angle.

Fibromyalgia
Fibromyalgia is a syndrome characterized by chronic widespread musculoskeletal pain, stiffness, non-restorative sleep,
and fatigue. Occasionally, many of the patients may mimic
patients of chronic fatigue syndrome. The characteristic feature of fibromyalgia (FM) is the presence of non-inflammatory muscle and connective tissue tender points that are
widespread, involving all four quadrants of the body.

The diagnostic criteria were developed by the American


College of Rheumatology in 1990.

History of widespread pain: Pain is considered


widespread when all of the following are present: pain
in the left side of the body, pain in the right side of the
body, pain above the waist, and pain below the waist.
In addition, axial skeletal pain (cervical spine or anterior chest or thoracic spine or low back) must be present. In this definition, shoulder and buttock pain is
considered as pain for each involved side. Low back
pain is considered lower segment pain.
Pain in 11 of 18 tender point sites on digital palpation:
Digital palpation should be performed with an approximate force of 4 kg/cm2. For a tender point to be considered positive, the subject must state that the palpation
was painful. Tender is not to be considered painful.
Note: For classification purposes, patients will be said to
have fibromyalgia if both criteria are satisfied. Widespread
pain must have been present for at least 3 months. The
presence of a second clinical disorder does not exclude
the diagnosis of fibromyalgia.
The 18 tender points are depicted in Figure 21:
1, 2 (Occiput): bilateral, at the suboccipital muscle insertions.
3, 4 (Low cervical): bilateral, at the anterior aspects of the
intertransverse spaces at C5C7.
5, 6 (Trapezius): bilateral, at the midpoint of the upper
border.
7, 8 (Supraspinatus): bilateral, at origins, above the scapula spine near the medial border.
9, 10 (Second rib): bilateral, at the second costochondral
junctions, just lateral to the junctions on upper surfaces.
11, 12 (Lateral epicondyle): bilateral, 2 cm distal to the
epicondyles.
13, 14 (Gluteal): bilateral, in upper outer quadrants of
buttocks in anterior fold of muscle.
15, 16 (Greater trochanter): bilateral, posterior to the trochanteric prominence.
259

Section IV Diseases of Specific Structures

Figure 21

Figure 22
Back

Front

Occiput
Trapezius

Lower cervical

Supraspinatus

2nd rib

Gluteal

Lateral
epicondyle

Greater
trochanter

Knee

Unilateral posterior open bite. Courtesy: Department


of Oral Medicine and Radiology, Manipal College
of Dental Sciences, Mangalore

Schematic diagram showing tender points in fibromyalgia

17, 18 (Knee): bilateral, at the medial fat pad proximal to


the joint line.
Management
Fibromyalgia can be treated effectively with amitriptyline
(tricyclic antidepressant). Amitriptyline improves the sleep
quality and minimizing pain. NSAIDs and muscle relaxants
have also been tried successfully.

CONGENITAL, DEVELOPMENTAL AND


ACQUIRED DISORDERS OF THE TMJ
Developmental disturbances affecting the condyle such as
aplasia, hypoplasia and hyperplasia have been described in
Chapter 2 on Developmental Disturbances.

Malignant tumors such as chondrosarcoma, synovial sarcoma, brosarcoma, osteogenic sarcoma and multiple
myeloma have been reported to affect the TMJ structures.
Distant metastasis to the TMJ have been reported to occur
from primaries in the breast, lungs, prostate, liver, uterus,
pancreas and rectum.
The clinician needs to be aware of these uncommon
neoplasms as they tend to mimic the clinical features of
other common temporomandibular disorders such as limited
jaw movements, restricted mouth opening, deviation or
deection during mouth opening and joint sounds. As the
condition advances it may result in extension of the tumor
mass into the middle cranial fossa or invade posteriorly
through the glenoid fossa and present as a lesion of the
middle ear or external auditory canal. When the tumor mass
extends laterally it can produce a preauricular swelling mimicking a parotid gland tumor. Cranial nerves may be involved
if the tumor mass extends into the infratemporal and pterygopalatine fossae.
Clinical features

NEOPLASMS AFFECTING THE TMJ


Both benign and malignant tumors can affect the TMJ
structures that include the articular disk, synovial membrane, articular capsule, glenoid fossa and most importantly the condyle. Malignant tumors are rare and reports
of metastasis to the TMJ from distant sites are very few in
number. Despite this fact, one should also look out for
locally invasive lesions originating from the middle ear
and parotid.
The common benign tumors that affect the TMJ include:
osteoma, chondroma, osteochondroma and osteoblastoma.
260

Benign tumors All the benign tumors share the similar


features of slow growth of the tumor mass, gradually
developing malocclusion (generally unilateral posterior
open bite, Figure 22), deflection of the mandible to the
unaffected side, facial asymmetry (Figure 23A, B), joint
noises and restriction in jaw movements. Benign tumors
are usually painless.
The tumors are usually seen in the 2nd and 3rd decades
of life. They may radiographically present as a welldened nodular mass extending from the condylar head,
unlike hyperplasia where there is uniform enlargement of
the condylar head (Figure 24). Another distinguishing

Chapter 10 Temporomandibular Disorders

Figure 23
A

Facial asymmetry in patient with osteochondroma of the condyle. Courtesy: Department of


Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

Figure 24

Orthopantomograph showing uniform enlargement of the


condylar head on the right side. Courtesy: Department of
Oral Medicine and Radiology, Manipal College
of Dental Sciences, Mangalore

feature between the two is that the hyperplasia occurs


usually as a reactive lesion to trauma, whereas benign
tumors arise spontaneously. The most common benign
tumor to affect the TMJ is osteoma followed by osteochondroma. Osteomas may occur as single isolated lesion
or as a part of Gardners syndrome. Benign osteoblastomas
though frequently seen in the 2nd decade of life, may occur
anywhere in the 1st to 8th decades of life. These benign
tumors often produce a tender swelling and patients usually give a history of trauma.
Malignant tumors Chondrosarcomas account for about
13% of the sarcomas affecting the facial bones and jaws.
It is usually seen in women in the 5th decade of life.
Low-grade tumors have excellent prognosis (however high

recurrence rates are common), whereas high-grade tumors


may metastasize through the lymphatics. Many of the
patients complain of a rapidly growing swelling (in the preauricular region) and pain, diminished hearing and
restricted mouth opening.
Synovial chondrosarcoma (SC) may usually originate as
a primary from the synovium or secondarily in an already
existing synovial chondromatosis. These tumors generally
occur in women in the 5th and 7th decades of life. SC presents as a soft tissue mass resulting in TMJ dysfunction and
pain. Radiographs reveal clumps of calcications occurring
in a soft tissue mass. The articulating surfaces may show
erosion. Joint space may occasionally exhibit freely lying
cartilaginous nodules.
Synovial sarcomas arise from the pluripotential mesenchyme. These tumors originate in close proximity to tendons, tendon sheaths and joint capsule. They are said to
represent about 5% of all soft tissue sarcomas. These tumors
are relatively slow growing and painless and usually present
as mass in the pre-auricular region. Synovial sarcomas are
usually present in the 2nd and 4th decades of life. Strikingly
50% of these tumors show calcications radiographically.
Recurrences are common and the lung is the most preferred
site for metastasis. Synovial sarcoma is unique in the
sense that it is one sarcoma that metastasizes (20% of the
cases) to the lymph nodes.
Osteosarcomas may be seen in any age group ranging
from the 2nd to the 6th decade of life. The clinical features
include mild pain, malocclusion and restricted mouth
opening and other mandibular movements. Radiographs
reveal extensive destruction of bone. Metastasis to the
lungs is common.
261

Section IV Diseases of Specific Structures

Multiple myeloma and occasionally a solitary plasmacytoma may affect the TMJ in males over the 6th decade of
life. Patients usually present with pain and limited mouth
opening. Large tumors may exhibit pre-auricular swelling.
Radiographs reveal well-dened punched-out radiolucent
areas without a sclerotic rim. Occasionally pathological
fractures may be seen.
Metastatic tumors Metastasis to the jaws is rare and the
condyle is almost never a location. However, isolated
reports have described TMJ dysfunction and pathologic
fracture as the presentation features. There have been various theories suggested to explain the cause for very less
chances of metastasis to the condyle. Some of these include
lack of abundant red marrow, relatively sluggish pace of
blood flow, separate vascular supply from the circular penetrating branches of the maxillary and superficial temporal
arteries and an osseous plate that cuts off the condylar marrow cavity from the spongiosa of the rest of the mandible.
Synovial chondromatosis is an idiopathic condition,
which has been one of the more commonly reported conditions associated with loose joint bodies. It is thought to
represent a cartilaginous metaplasia associated with an
abnormal synovium, rather than a true neoplasia. It presents with multiple cartilaginous nodules located within
the joint space. Symptoms include joint swelling, pain,
limited movement and joint noise.

CONDYLAR FRACTURES
Condylar fractures are the most common among fractures
involving the mandible. It is estimated that of all the mandibular fractures approximately 2552% involve the condyle (Figure 25).
Lindhal in 1977 described three major sources of condylar injuries:
1.

2.

3.

262

When kinetic injury is imparted to a static individual


(such as in interpersonal violence i.e. a blow to the
chin). Usually in such cases, fracture of the parasymphysis may be seen on the side of trauma along with
condylar neck fracture on the contralateral side.
When kinetic injury is imparted to a moving individual
against a static surface (such as in a parade ground
fracture, or injury sustained when an individual falls
on the floor like in an epileptic fit). In these instances
symphyseal fracture is usually associated with bilateral condylar neck fractures.
When a moving individual strikes against another
moving object, a summation of the kinetic energies of
the first two varieties occurs leading to a severe form
of injury (such as in road traffic accidents). Such injuries may cause bilateral parasymphyseal along with
bilateral condylar neck fractures.

Classification of Condylar Fractures


I. Lindhals classification of condylar fractures
A detailed and comprehensive classification of mandibular condylar fractures was proposed by Lindhal in 1977.
In order to categorize the condylar fractures it is mandatory that radiographs be taken in two planes at right
angles to each other.
This classication takes into consideration three parameters, namely, the level of fracture, relationship of the fractured condylar segment to the mandible and the relationship
of the condylar head to the glenoid fossa.
1. Level of fracture (Figure 26)
a. Intracapsular head or condylar head fracture: Vertical
fractures (anteroposterior sagittal split), compression
fractures (results in a mushroom-shaped expansion of
the condylar head) and comminuted fractures are the
subtypes of the fractures of the condylar head.
b. Condylar neck fractures: These fractures are seen at
the inferior attachment of the capsule.
c. Subcondylar fractures: These fractures occur inferior to
the condylar neck. The subcondylar region corresponds
to the area extending anteriorly from the inferior-most
point of the sigmoid notch to the point of maximum
curvature of the posterior border of the mandible.
2. Relationship of the fractured condylar segment to the
mandible The relationship of the fractured condylar segment with the remainder of the mandible is categorized
into: undisplaced (fissure fracture), deviated (angulated
fractured segment without overlap), displaced with medial
overlap of the fractured segment, displaced with lateral
overlap, anterior and posterior overlap and fractured fragment with no contact with the remainder of the mandible.

Figure 25

Condylar fracture marked on a dry skull specimen

Chapter 10 Temporomandibular Disorders

Figure 26

Intracapsular
fracture

Extracapsular
fracture

Subcondylar
fracture

Schematic diagrams showing various levels of condylar fractures

3. Relationship of the condylar head to the glenoid fossa


There are three subtypes under this category, namely, no
displacement (radiographically the joint space appears
normal), displacement (increased joint space but the mandibular condyle is related to the glenoid fossa and dislocation (condylar fragment is totally out of the glenoid fossa,
usually dislocated in an anteromedial direction).
II. MacLennans classification
MacLennan considered the relationship of the fractured
condylar fragment to the mandible for his classification.
Four broad categories have been described: (i) no displacement, (ii) fracture deviation (simple angulation of the
condylar fragment in relation of the remainder of the
mandible as seen in greenstick fractures), (iii) fracture displacement (overlap of the condyle and the remainder of
the mandible) and (iv) fracture dislocation (complete disruption of the condylar head from the glenoid fossa).
III. Classification of condylar neck fractures
Spiessl and Schroll classified condylar neck fractures into
six different types:
1.
2.
3.
4.
5.
6.

Type I: Condylar neck fracture without serious dislocation


Type II: Deep seated condylar neck fracture with dislocation
Type III: High condylar neck fracture with dislocation
Type IV: Synovial deep seated condylar neck fracture
with luxation
Type V: High condylar neck fracture with luxation
Type VI: Head or intracapsular fracture.

Clinical signs and symptoms of condylar


fractures
Unilateral condylar fractures may present with a distinct
swelling over the TMJ region. Occasionally, bleeding from

the ear on the side of fracture (laceration of anterior wall


of the external auditory meatus) may be evident.
Ecchymosis of the skin just below the mastoid process on
the side of fracture may be seen. This is due to the downward tracking of the hematoma around the fractured condyle to an area beneath the external auditory canal. This
clinical appearance should not be misunderstood as the
Battles sign which is a similar sign seen in the base of
skull fractures.
Traumatic injuries to the condyle (involvement of the
condylar growth center) during the period of mandibular
growth may result in stunted and inhibited growth producing a hypoplastic mandible. Occasionally, limited joint
function may be seen secondary to hemorrhage and subsequent bone formation within the joint spaces. The higher
the fracture is located and greater the degree of displacement of the fragments, the less favorable are the expected
functional results. When the fracture fragments are displaced at least by 5 mm and displaced by a minimum of
30, a severely dislocated fracture can be considered.
The condylar neck is usually very slender (about 4.9 mm)
and hence very amenable to fractures (Figure 27). The
condylar neck usually fractures secondary to a blow to the
chin or parasymphyseal region.
When the fracture line runs above the level of insertion
of the lateral pterygoid muscle within the capsule of the
joint, then very minimal bony displacement is evident.
However, when the fracture occurs below the level of muscle insertion, condylar displacement is usually seen in the
direction of the pull of the muscle (anteriorly, inferiorly
and medially directed forces) (Figure 28).
In severe cases the mandibular condyle may be impacted
through the glenoid fossa and the patient may not be able
to open the mouth.
On palpation, following trauma, the patient may
experience severe tenderness over the temporomandibular
region. Paresthesia of the lower lip may be seen when the
bleeding from the condylar region trickles down across the
base of the skull to exert pressure over the mandibular
263

Section IV Diseases of Specific Structures

Figure 27

Figure 28

Posteroanterior (PA) view showing medial displacement of


condylar neck fracture
Cropped orthopantomograph showing condylar neck fracture

division of the trigeminal nerve as it exits from the foramen ovale.


Patient may not be able to protrude the mandible and
may have a limited ability to exhibit lateral excursion of the
mandible to the opposite side. Unilateral fracture causes
shortening of the ramus and molar occlusal gagging on
the same side. Bilateral condylar fractures usually present
with all the clinical signs and symptoms of the unilateral
fractures occurring on both the sides.
Bilateral displacement of the condylar fragments may
result in an anterior open bite. Condylar fractures usually

264

occur in association with symphyseal or parasymphyseal


fractures. Long-standing condylar fractures may present
with a hollow over the condylar head region. However,
this hollowing due the medial displacement of the condylar fragment may not be appreciated due to the edema
following immediate injuries.
Routine CT studies of suspected closed head injury
encompass the calvaria to the cranial base. It is at the
cranial base that the glenoid fossa appears. An empty
glenoid fossa sign is when there is no condyle associated
within the fossa. This is suggestive of a condylar neck
fracture.

Diseases of Salivary Glands


Carol M Stewart, Indraneel Bhattacharyya,
Madhu K Nair, James C Pettigrew,
Seunghee Cha, Joseph Katz

Developmental Disturbances

Aplasia/Agenesis and Related Aberrancy of


Salivary Glands
Hyperplasia of Minor Salivary Glands

Non-inflammatory Conditions of
Salivary Glands

Salivary Gland Tumors

Benign Tumors
Pleomorphic Adenoma (Benign Mixed Tumor)
Canalicular Adenoma
Basal Cell Adenoma
Papillary Cystadenoma Lymphomatosum
(Warthins Tumor)
Oncocytoma (Oxyphilic Adenoma)

Inflammatory Conditions of Salivary Glands


Mucocele
Ranula
Sialolithiasis, Salivary Duct Stone, Salivary Calculi
Sialadenitis
Non-specific Sialadenitis
Bacterial Sialadenitis
Subacute Necrotizing Sialadenitis
Cheilitis Glandularis
Necrotizing Sialometaplasia
Chronic Sclerosing Sialadenitis (Kuttner Tumor)

11

Sialadenosis
Anorexia/Bulimia-related Sialadenosis
Sialadenosis Associated with Alcoholic Cirrhosis
Diabetes Mellitus
Medication-induced Sialadenosis
Orofacial Granulomatosis
Sarcoidosis

Saliva, Xerostomia, Hyposalivation, and


Sialorrhea
Saliva
Hypofunction and Xerostomia
Xerostomia and Salivary Gland Hypofunction
due to Medications
Xerostomia and Salivary Gland Hypofunction
due to Radiation Therapy
Sjgrens Syndrome
Benign Lymphoepithelial Lesion (Mikuliczs Disease)
Sialorrhea

CHAPTER

Malignant Tumors
Mucoepidermoid Carcinoma
Intraosseous Mucoepidermoid Carcinoma
Acinic Cell Adenocarcinoma
Malignant Mixed Tumor (Carcinoma Ex Pleomorphic
Adenoma)
Metastasizing Mixed Tumor
Adenoid Cystic Carcinoma
Polymorphous Low-Grade Adenocarcinoma

Viral-induced Salivary Gland Pathology


Mumps
Human Immunodeficiency Virus (HIV)

Salivary glands and saliva play a critical role in maintenance of oral and systemic health. Salivary glands are frequently involved in a wide array of conditions which
result in glandular dysfunction. These may be subdivided
into five categories which include:
1.
2.
3.

Developmental disturbances
Saliva and salivary flow alterations
Inflammatory conditions

4.
5.

Non-inflammatory conditions
Tumors.

Many of these conditions result in salivary gland hypofunction, enlargement, pain and facial nerve paresthesia
that will prompt the patient to seek evaluation and treatment from the dentist. This chapter will address each of
these five subgroups focusing on the etiology, clinical features, diagnosis and treatment of these conditions.
265

Section IV Diseases of Specific Structures

DEVELOPMENTAL DISTURBANCES
Aplasia/Agenesis and Related Aberrancy
of Salivary Glands
Congenital aplasia or agenesis of the major salivary glands
is an uncommon finding, characterized by partial or total
lack of development of the gland. Agenesis may involve
one gland, pairs, or multiple glands, and be unilateral or
bilateral. It may be a single independent finding or be
associated with other developmental anomalies.
Congenital agenesis of major salivary glands was rst
reported by Gruber in 1985. A recent search of the world
literature reported 30 documented cases. Three cases of
unilateral aplasia of the parotid have been reported. As it
may be asymptomatic and go unnoticed, the true incidence
is unknown. Bilateral agenesis is more common, with
10 cases reported in the English literature. Sometimes congenital absence of one parotid or submandibular gland is
associated with hypertrophy of the contralateral gland.
Aplasia may occur as a single event or with autosomal
dominant inherited developmental conditions such as rst
branchial arch anomalies, hemifacial microsomia and mandibulofacial dysostosis. Parotid gland aplasia may be associated with malformations of the lacrimal apparatus as
well. A combination of multiple developmental anomalies
is found in the lacrimo-auriculo-dento-digital (LADD)
syndrome (LevyHollister syndrome). This is an autosomaldominant multiple congenital anomaly disorder characterized by hypoplasia, aplasia or atresia of the lacrimal and
salivary systems, ear anomalies, hearing loss, digital malformations and dental alterations. As the parotid gland
develops during the 4th week of uterine life, and the submandibular and sublingual, and minor glands develop
between 6th and 12th weeks, association of salivary gland
aplasia with other congenital abnormalities is easily
understood. Bilateral aplasia of the parotid gland has also
been reported in a patient with Downs syndrome. In ectodermal dysplasia, aplasia of the submandibular glands and
alterations in salivary gland function have been reported
as well.
Clinical features and diagnosis
Salivary gland agenesis may be asymptomatic if only partial agenesis occurs or if the condition is isolated to one
gland. If more extensive involvement occurs, agenesis can
produce profound hyposalivation in children resulting in
advanced dental caries, candidiasis, ascending sialadenitis, and even laryngitis and pharyngitis. A child with subjective xerostomia and functional hyposalivation should
be carefully examined for salivary gland dysfunction to
include partial or complete salivary gland agenesis. Familial parotid gland aplasia has been reported, hence examination of the siblings of a child with agenesis, might be
266

prudent. Sometimes, congenital absence of salivary glands


is not noticed until adulthood resulting in unfortunate
sequelae. However, clinical suspicion of salivary gland
agenesis should be heightened in the setting of the nondrooling baby. Lack of complete development of the submandibular gland duct has been reported in two infants
which presented as unilateral cystic swellings in the floor
of the mouth. Both cases responded to simple incision and
decompression of the fluid-filled ducts. Early treatment is
important to avoid feeding difficulties and possible later
complications such as ranula or sialadenitis.
Diagnostic imaging
When a unilateral glandular anomaly is observed clinically, bilateral imaging should be considered to examine
for possible lesions on the contralateral side. Computed
tomography (CT) can be used to demonstrate congenital
total or partial absence of salivary glands.
Management
Salivary gland aplasia has been associated with rampant
dental decay in children. Treatment for potential hyposalivation resulting from salivary gland agenesis would
include frequent dental examinations, salivary stimulants
for glands that might remain, meticulous home care and a
customized fluoride program.

Hyperplasia of Minor Salivary Glands


Clinical features
Adenomatoid hyperplasia of the minor salivary glands is a
rare lesion characterized by localized swelling that clinically mimics a neoplasm. The lesion most often develops
on the hard or soft palate, although it has been reported in
other oral minor salivary gland sites. The most common
presentation is during the 4th to 6th decades of life. The
typical presentation is a painless, indolent palatal swelling
which may be soft or firm to palpation. The overlying
mucosa is usually normal in color, although some lesions
are red or bluish in color. The etiology is uncertain. In one
report, the occurrence of adenomatoid hyperplasia on the
palate occurred in patients who were tobacco smokers or
denture wearers or both. The authors, Barrett and Speight
suggested that chronic, local trauma could be a factor in
the development of the condition.
Histopathology
Histopathologic examination demonstrates lobular aggregates of normal appearing mucous acini that are greater in
number (hyperplasia) than normally would be found in the
area. These glands may appear to be increased in size
(hypertrophy). Chronic inflammation, if present, is usually
mild and localized. Shimoyama et al reported that Ki-67

Chapter 11 Diseases of Salivary Glands

staining for cell proliferative activity demonstrated no statistically significant differences among adenomatoid hyperplasia and a matched group of normal palatal salivary
glands. The conclusion was that adenomatoid hyperplasia
had limited growth potential.
Treatment
To determine the true nature of a clinical enlargement, a
biopsy is necessary. After the diagnosis of adenomatoid
hyperplasia has been established via histopathologic examination, no further treatment is indicated.

SALIVA, XEROSTOMIA, HYPOSALIVATION


AND SIALORRHEA
Saliva
Saliva is an essential fluid for maintaining oral and systemic health and a satisfactory quality of life. While saliva
is sometimes considered bothersome during restorative
procedures, the alteration in quality and/or quantity of
saliva has serious sequelae for the patient. Saliva is the
product of three paired major salivary glands (the parotid,
submandibular, and sublingual), and minor glands found
in the hard and soft palate, lips, tongue, and buccal mucosa
(Figure 1). Major salivary glands are composed of ductal
and acinar structures. The acinar cells are the secretory
components and ductal cells are the branching network
that transports saliva into the oral cavity. The acinar cells
of the parotid gland are purely serous elements and upon

Figure 1

stimulation, parotid secretions account for at least half of


the volume of whole saliva. Serous secretions are watery
and contain digestive enzymes, water, salts, and ions. They
aid in mastication, clearing agents from the oral cavity, and
facilitate swallowing and speech. Fluid from the parotid
gland enters the oral cavity through the main excretory
duct, Stensens duct, located in the buccal mucosa next to
the maxillary second molars. In the submandibular gland,
the acinar components are mixed mucousserous, but
predominantly serous. At rest, the submandibular gland
secretions account for approximately two-thirds of the
unstimulated saliva production. Whartons duct is the
main duct of the submandibular gland and enters the floor
of the mouth on either side of the lingual frenum. The
sublingual gland, the smallest of the three major glands, is
located above the mylohyoid muscle. Acinar elements are
mixed, but predominantly mucous. The mucin produced
facilitates lubrication and swallowing. The main excretory
duct of the sublingual gland, Bartholins duct, may join
Whartons duct resulting in a blending of secretions, or
open into the oral cavity with a separate sublingual papilla.
Numerous sublingual ducts may join the submandibular
gland duct or open separately into the floor of the mouth.
Minor salivary glands are named according to their
locationlingual (anterior and posterior), labial, buccal,
palatine and glossopalatine. Table 1 summarizes the nomenclature for the major and minor salivary glands and their
acinar components.
In health, approximately 750 ml of saliva is produced in
a day. The principal control of salivary secretion is mediated by sympathetic and parasympathetic innervation. The
adrenergic ( and ) receptors are regulated by the sympathetic nervous system and the muscarinic receptors by
the parasympathetic nervous system. At least ve muscarinic-cholinergic receptor subtypes exist and it has been
determined that the muscarinic receptor that medicates
secretion of saliva is the M3 subtype. The parasympathetic

Table 1

Parotid
gland
Sublingual
gland
Submandibular
gland

Major salivary glands. Courtesy: Roger Hoover

Major and minor salivary glands and secretion

Glands

Type of secretion

Parotid

Purely serous

Submandibular

Mixed, however
predominantly serous

Sublingual

Mixed, however
predominantly mucous

Lingual minor salivary glands


Anterior lingual (glands of Blandin and
Nuhn)
Posterior lingual (glands of von Ebner)

Primarily mucous
Purely serous

Labial and buccal minor salivary glands

Mixed

Glossopalatine and palatine minor salivary


glands (Webers glands)

Purely mucous

267

Section IV Diseases of Specific Structures

nerve stimulation leads to an increased volume of saliva,


whereas the sympathetic stimulation has an effect on protein content and salivary composition.
Saliva plays a major role in the local and systemic protection of the oral cavity, oropharyngeal region, and the
upper gastrointestinal tract. Normal quantity and protein
composition is essential for buffering the acidity of the
oral cavity, lubrication of tissues, maintaining the integrity of the oral tissues, providing antimicrobial proteins
and digestive enzymes, and remineralization of the teeth.
Lack of saliva, hyposalivation, may increase a patients susceptibility to dental decay, oral ulcers, fungal infections,
and dysphagia or difculty in swallowing.
Saliva contains many antimicrobial proteins that help
maintain a normal oral ora. The histatins provide antifungal properties, and proline-rich proteins help reduce
bacterial colonization by modifying the ability of organisms to attach to tissues. Mucins are salivary glycoproteins
that play a role in mucosal lubrication and assist in aggregation of oral microorganisms. Statherin and proline-rich
proteins have calcium-binding properties to assist remineralization. These proteins combined with the cleansing and
ushing ability of saliva constitute signicant protective
mechanisms for the oral cavity and upper gastrointestinal
system. Of special importance to the dentition is the presence
of buffers to help maintain a neutral pH and the remineralizing capacity. The pH range of saliva will vary from 6.7 to
7.4 in health. Of concern is pH below 5.5, which will promote enamel dissolution and increase caries susceptibility.

Hypofunction and Xerostomia


Altered saliva production, both qualitatively and quantitatively, creates significant oral health concerns for the
patient and challenges the dentist to provide appropriate
patient education and treatment. Patients frequently present with the complaint of a dry mouth. Xerostomia is the
subjective sensation of dry mouth and may be determined
by questioning individuals about their perceptions of oral
dryness. The need to sip water while eating dry foods, difficulty in swallowing food without liquids, and a feeling
of too little saliva in the mouth have been correlated with
salivary gland hypofunction. Hyposalivation is the production of inadequate or less than normal amount of saliva,
usually from gland hypofunction. A few simple chairside
assessments could be performed to quickly assess oral dryness. The lack of salivary pooling in the floor of the mouth
is a basic clinical indicator of hyposalivation. Another
indicator is the cracker sign. If a patient states that they
cannot eat a cracker without drinking fluids, xerostomia
and hyposalivation should be suspected. Another indicator
is the lipstick sign. Patients with hyposalivation may
have lipstick adhere to the incisal edges of the anterior
teeth because they lack saliva that would normally prevent adherence. Another clinical clue to hypofunction is
268

the mouth mirror test. The clinician places the mirrored


surface of the mouth mirror over the buccal mucosa and
attempts to move it. If the mirror glides effortlessly over
the tissue, one can deduce that salivation is adequate.
The prevalence of xerostomia in the population varies
widely due to the lack of a clear denition for xerostomia.
Some clinicians use the terms xerostomia and hyposalivation interchangeably. Hyposalivation or salivary gland
hypofunction results when the salivary gland ow rate is
lower than normal. Dening normal is problematic due
to variations in the literature on collection methods, time
of day collections were performed, and the inability to
control for medications. Unstimulated whole salivary
ow rates of less than 0.15 ml/min might provide a good
reference for hyposalivation. The determination of hyposalivation and xerostomia do not consistently correlate as
one might expect. Patients with salivary gland hypofunction are sometimes without complaints of oral dryness, or
xerostomia. Conversely, patients with complaints of dry
mouth may not have reduced salivary ow rates. Xerostomia and salivary hypofunction affect the oral health-related
quality of life. Reported reasons include the negative impact
of oral dryness on speaking, eating, and wearing dental
prostheses. Both xerostomia and salivary gland hypofunction require a careful systematic evaluation to determine
causative factors.
Dry mouth has a variety of causes as indicated in Box 1.
Common causes of salivary gland dysfunction leading to
hyposalivation include medications, irradiation to the head
and neck, and autoimmune diseases such as systemic lupus
erythematosus (SLE) and Sjgrens syndrome (SS). Other
systemic conditions affecting salivary glands include sarcoidosis, sialadenosis, and viral infections such as HIV and
hepatitis C.
Mouth-breathing, tobacco smoking, alcohol use, and consumption of beverages containing caffeine can contribute
to oral dryness as well. Age-related hyposalivation has
been reported due to structural changes in salivary glands
with increasing age. Other studies have reported no agedependent decrease in saliva ow rate in healthy elderly
populations. The incidence of xerostomia will increase and

Box 1

Possible causes of salivary gland hypofunction

Medications
Radiation to head and neck
Systemic diseases
Sjgrens syndrome
Sarcoidosis
Systemic lupus erythematosus
Primary biliary cirrhosis
Viral infections
HIV
Hepatitis C

Chapter 11 Diseases of Salivary Glands

the oral manifestations will continue to be a challenge for


the clinician.
Treatment of xerostomia is symptomatic and supportive, but should be aggressively proactive in prevention of
dental decay associated with salivary hypofunction. Patient
education and patient empowerment so they become participants in their oral healthcare are key to successful
outcomes. Hydration, dietary modications and meticulous
oral hygiene are especially helpful. Symptomatic treatment is aimed at minimizing the subjective complaints, and
includes drinking water or nely crushed ice chips and
sugar-free uids. Patients should be advised that caffeine
can contribute to the feeling of oral dryness and consequently, caffeine-free and sugar-free drinks should be
strongly encouraged. Avoiding alcohol, including alcoholbased mouthrinses, spicy foods, and strong avorings,
such as cinnamon and mint, should also minimize oral discomfort. Articial saliva is helpful for many patients due
to the coating action, but does not provide long-lasting
relief. Some patients nd relief by chewing sugar-free gum
or sucking on sugar-free candies. Lip balms and moisturizers may be helpful as well.
Because patients with hyposalivation are at increased
risk for dental decay, oral applications of topical uorides
should be initiated. The uoride is incorporated into the
enamel of the teeth to increase resistance to demineralization and decay. Fluoride products are available over-thecounter as rinses and as more highly concentrated brush-on
gels (0.4% stannous uoride gel). Prescription products
are available which provide 1.1% neutral sodium uoride
treatment in convenient brush-on gels or rinses. These
should be used after regular toothbrushing in the evening
just before retiring. Patients should be reminded to avoid
rinsing, eating or drinking for 30 minutes following the
uoride application. Stannous uoride or neutral sodium
uoride treatments can be provided using uoride carriers, or custom trays fabricated from a cast of the patients
mouth. The carriers are particularly helpful in treating
severe hyposalivation resulting from head and neck radiation therapy. Preventive uoride programs should be customized by the dentist to meet the specic needs and
conditions of the patient.

cause subjective complaints of dry mouth and many


induce hyposalivation. The drugs most frequently implicated in dry mouth include the tricyclic antidepressants,
antipsychotics, atropinics, beta blockers and antihistamines.
In another study as reported by Thomson, the unstimulated (resting) salivary flow rate was reduced among individuals who were older, female, or taking antidepressants,
and higher among smokers or people who were taking
hypolipidemic drugs. Other studies have correlated dry
mouth with the number of medications taken, rather than
specific types of medications. Field et al have demonstrated that medication is a better predictor of risk status
for dry mouth than either age or gender. Medications that
induce salivary hypofunction are a concern among the
elderly, but xerostomia can also be a concern for young
adults. Thomson et al in his study involving a large cohort
of 32-year-old subjects, reported that the prevalence of
xerostomia was found to be 10%, with no apparent gender
difference. There was a strong association between xerostomia and diminished oral health-related quality of life.
Xerostomia was significantly higher among those taking
antidepressants, iron supplements, or narcotic analgesics,
and those subjects taking antidepressants at both 26 and
32 years of age demonstrated 22 times the odds of reporting
xerostomia.
A study of medications and caries among older individuals by Thomson et al revealed that an adjusted coronal caries increment (AdjCI) was higher among males and
those taking a beta blocker or an anti-asthma drug for the
previous 5 years. Several classes of drugs have been associated with dry mouth (Box 2). The most common groups
include those with: (i) anticholinergic effects such as tricyclic antidepressants, drugs for urinary retention and overactive bladder, antipsychotics, diuretics, and antihistamines;
(ii) sympathomimetic drugs such as antihypertensives, antidepressants, decongestants, and bronchodilators; (iii) skeletal muscle relaxants; (iv) benzodiazepines; (v) proton pump
inhibitors; and (vi) anti-migraine agents. Dry mouth has

Box 2

Drugs associated with xerostomia and hyposalivation

Tricyclic antidepressants

Xerostomia and Salivary Gland Hypofunction


due to Medications
Jacobsen and Chavez in their article describe that individual above 65 years of age comprise 13% of the population, but consume approximately one-third of all drugs
prescribed. Loesche et al and Foc have reported many
studies that have demonstrated a link between dry mouth
in the elderly and polypharmacy. Shinkai et al reported
that in a group of 1,163 adults (age range 3281 years),
57% reported dry mouth to be the most frequent side
effect of their medications. Hundreds of medications can

Antipsychotic medications such as phenothiazines


Diuretics
Antihistamines
Anti-migraine agents
Proton pump inhibitors and H2 antagonists
Anti-HIV drugs such as dideoxyinosine and protease inhibitors
Opioids
Benzodiazepines
Decongestants
Selective serotonin reuptake inhibitors (SSRIs)

269

Section IV Diseases of Specific Structures

been reported to be a consequence of cytotoxic drugs such


as 5-uorouracil. Medications used for treatment of HIV
have also been associated with dry mouth. These include
didanosine and protease inhibitors.
It is important for the dentist to inquire about all medications, both prescription and over-the-counter agents,
during the health history review. Sometimes the dentist
can provide assistance by sharing concerns of medicationinduced hyposalivation with the primary care physician.
In some situations, the dentist might suggest medications
such as pilocarpine or cevimeline to promote salivation.
These medications will be discussed in the section on
Sjgrens syndrome.

Xerostomia and Salivary Gland Hypofunction


due to Radiation Therapy
The role of saliva in oral health and function relates both
to its fluid characteristics and to its specific components.
The water (fluid) phase accounts for 99% of the volume and
the remainder is salts and proteins. Essential functions of
these components include flushing, buffering the acidity,
and mucosal coating to maintain tissue integrity. Mucosal
coating and tissue lubrication are essential for speech, taste
perception, mastication, and swallowing. Cancer patients
undergoing treatment for head and neck disease often
experience severe difficulties maintaining such functions.
Salivary function can also be diminished by radioiodine
therapy for thyroid carcinoma, especially if multiple doses
are administered. Deterioration of oral health and radiationinduced oral dryness has a significant influence on patients
overall quality of life during and after treatment.
Together with surgery, radiation therapy is the main
treatment for head and neck tumors. All or part of the
major and minor salivary glands may be included within
the radiation eld due to the site and extension of the
tumor and the lymphatic spread. Exposing the glands to
radiation often results in severe salivary gland hypofunction
and changes in saliva composition. A profound decrease
in salivary ow occurs during the 1st week of radiation
therapy and continues throughout the course of therapy.
In general, fully irradiated parotid glands exposed to doses
exceeding 60 Gy sustain permanent damage resulting in
severe hypofunction, and there is no recovery of gland
function over time. Partial salivary ow recovery may
occur at lower doses.
Radiation mucositis may begin during the 2nd week of
therapy. Primary sites are intraoral mucosal surfaces within
the direct portals of radiation. A whitish discoloration will
appear from keratin accumulation, which is followed by
sloughing, revealing atrophic erythematous, and friable
mucosa. Ulceration then develops producing burning and
pain which is exacerbated by eating and oral hygiene.
Symptomatic support for radiation mucositis is important
to assist the patient in maintaining adequate nutrition.
270

The mucositis will slowly resolve 23 weeks after cessation of the treatment. A loss of taste has been reported
which generally is recovered after 6 months.
Minimizing the probability of osteoradionecrosis (ORN)
includes a dental examination at least 2 weeks prior to the
initiation of radiation therapy to address or remove teeth
that have a hopeless long-term prognosis. Daily uoride
treatments in custom carriers and close follow-up aid in
reducing the incidence of xerostomia-induced dental caries.
Due in part to more efcient radiation techniques, the incidence of ORN has been declining in radiation patients over
the last two decades. Advances in radiation techniques,
including the use of fractionated radiation doses, have
minimized the incidental damage to adjacent tissues. Furthermore, use of three-dimensional dosimetric intensitymodulated radiation therapy (IMRT) has been shown to
reduce late salivary toxicity, since the portion of tissue
exposed to low radiation doses has a potential for repair.
Based on recent publications, the prevention of ORN remains
controversial. A recent report compiled by Chang et al after
reviewing a large series of ORN studies stated that extraction of teeth with poor prognosis before radiation therapy
did not appear to reduce the risk of ORN. The investigation
of IMRT by Wu et al to achieve sparing of the parotids and
yet achieve higher tumor control appears to show promise.
Until additional evidence is available to dene guidelines,
a pre-radiation referral for a dental evaluation is necessary.
To facilitate prevention of ORN, irradiated dental patients
should maintain a high level of oral health. Pre- and posttherapy close collaboration by a multidisciplinary team
can be invaluable for patients receiving head and neck
radiation therapy.

Sjgrens Syndrome
Sjgrens syndrome (SS) is a chronic autoimmune disease
affecting the exocrine glands, primarily the salivary and
lacrimal glands. Patients most commonly complain of a
subjective persistent feeling of dry mouth (xerostomia)
and of dry eyes (keratoconjunctivitis sicca). This is due
to lymphocytic infiltrates and destruction of salivary and
lacrimal glands and systemic production of autoantibodies. In 1933, Henrik Sjgren, a Swedish ophthalmologist,
presented his doctoral thesis entitled Zur Kenntnis der
Keratoconjunctivitis Sicca, and described the clinical
and histopathological aspects of the disease.
Sjgrens syndrome occurs worldwide and while it
may occur at any age, the peak incidence is between 40
and 50 years. Sjgrens syndrome has one of the highest
female-to-male ratio (9:1) of any autoimmune rheumatic
disease. In addition to ocular and oral dryness, a wide
spectrum of extraglandular manifestations may occur as
well. The musculoskeletal, hematological, vascular, pulmonary, gastrointestinal, dermatological, renal and nervous
systems may be involved. Patients with SS have an increased

Chapter 11 Diseases of Salivary Glands

risk of developing lymphoma. Early reports estimated that


patients with SS had up to 44 times increased risk of
developing lymphoma compared with the general population. Chronic fatigue, depression, and a diminished quality
of life are also common components of SS.
Classification
Two forms of the disease are recognized. Primary SS is the
presence of sicca syndrome, xerostomia, or dry mouth,
and xerophthalmia, or dry eyes together, with no other
autoimmune disease. Secondary SS is sicca syndrome plus
another associated autoimmune disease such as rheumatoid
arthritis (RA), SLE, or scleroderma. Based upon the classification criteria applied, the prevalence of SS may range
from 0.5 to 3.0% of the population. All classification systems use a combination of both subjective and objective
findings in the diagnostic process. The most recent 2002
criteria include subjective symptoms of dry mouth and dry
eyes, and the following objective tests: ocular signs by
Schirmers test and/or Rose Bengal score; focal sialadenitis
by histopathology; salivary gland involvement by either
salivary scintigraphy, parotid sialography or unstimulated
salivary flow rate; and autoantibodies of SS-A/Ro and/or
SS-B/La specificity. Box 3 presents the 2002 AmericanEuropean Consensus Group Criteria for SS.
Etiopathogenesis
Currently, the etiology of SS is not clearly understood, but
appears to be multifactorial. It has been suggested that
environmental agents may trigger SS in genetically predisposed individuals. Experimental and clinical evidence
suggest that immune reactivity is modulated by gender.
Immune reactivity is higher in females than males, and
lymphocytes and monocytes from female subjects show
higher antigen presenting activity and mitogenic responses.
Taiym et al have found higher prolactin levels in SS
patients than controls. Estrogens might be pro- or antiinflammatory, based on dose-related metabolite conversions. The role of sex hormones in rheumatic autoimmune
diseases has yet to be clarified. Potential mechanisms
underlying SS include disturbances in apoptosis, circulating autoantibodies against the ribonucleoproteins Ro and
La or cholinergic muscarinic receptors in salivary and lacrimal glands or cytokines. These processes interfere with
normal glandular function; and as the mucosal surfaces
become sites of chronic inflammation, the disease appears
to enter a self-perpetuating inflammatory cycle.
While a genetic predisposition to SS appears to exist,
no simple Mendelian inheritance pattern has been demonstrated. Cases of two or more individuals with SS per family and SS in twins have been described. However, the level
of genetic contribution is not known. Because large twin
studies in SS are lacking, the twin concordance rate cannot
be estimated. Familial clustering of different autoimmune

Box 3

European American Consensus Group criteria for


Sjgrens syndrome

Ocular symptoms (must have 1 of 3)


1. Daily dry eyes 3 months
2. Recurrent sand or gravel sensation in the eyes
3. Use of tear substitutes more than 3 times per day
Oral symptoms (must have 1 of 3)
1. Feeling of dry mouth for more than 3 months
2. Recurrent or persistently swollen salivary glands as an adult
3. Need frequent liquids to aid in swallowing dry food
Ocular signs (1 of 2)
1. Schirmers test, performed without anesthesia ( 5 mm in
5 minutes)
2. Rose Bengal score or other ocular dye score ( 4 according to
van Blijstervelds scoring system)
Histopathology in minor salivary gland biopsy
Focal lymphocytic sialoadenitis, with focus score 1 (focus is
50 lymphocytes per 4 mm2 tissue adjacent to normal appearing
mucous acini)
Salivary gland involvement (1 of 3)
1. Unstimulated whole salivary flow ( 1.5 ml/15 minutes)
2. Parotid sialography showing the presence of diffuse sialectasis
(punctuate, cavitary of destructive pattern) without evidence of
obstruction in the major ducts
3. Salivary scintigraphy, showing delayed uptake, reduced
concentration and/or delayed excretion of tracer
Autoantibodies
Antibodies to SS-A/Ro or SS-B/La or both
For primary SS
a. Any 4 of the 6, as long as either item 4 (histopathology) or
item 6 (serology) is positive
b. Presence of any 3 of the 4 objective criteria items
(items 3, 4, 5, 6)
For secondary SS
In the presence of another connective tissue disease, the presence
of item 1 or 2 plus any 2 from 3, 4, and 5
Exclusion criteria
Past head and neck radiation
Hepatitis C infection
Acquired immunodeficiency syndrome (AIDS)
Pre-existing lymphoma
Sarcoidosis
Graft-vs-host disease
Use of anticholinergic drugs (since a time shorter than four-fold
half-life of the drug)
Source: Vitali et al. Annals of Rheumatic Diseases 2002;61:55458.

diseases and co-association of multiple autoimmune diseases has been reported by Becker et al. Reports have
also indicated that a SS proband may have relatives with
other autoimmune diseases in approximately 3035% of
the cases. Assessing human leukocyte antigen (HLA)-DR
and HLA-DQ gene segments in patients with SS reveals an
increased use of haplotypes B, Drw52 and DR3. Correlations
271

Section IV Diseases of Specific Structures

have been found between presence of HLA-DR haplotype


and the presence of Ro/LA in SS. Gene polymorphisms
have been analyzed, but no clear-cut relationship between
these and primary SS have been identied. Clustering of
non-major histocompatibility complex (MHC) susceptibility candidate loci in human autoimmune diseases supports
a hypothesis that, in some cases, clinically distinct autoimmune diseases may be controlled by a common set of
susceptibility genes.

Figure 2

Clinical features and diagnosis


Dry mouth and dry eyes are the most common complaints
of patients with SS. Patients ocular concerns may include
a history of dry eyes, a sensation of sand or gravel in the
eyes, and/or frequent ( 3 times per day) use of tear substitutes. Objective ocular tests for dry eyes include a
Schirmers test for tear production. Using sterile strips of
filter paper placed just inside the lower lid, tear production
can be assessed by measuring the length of wetness on the
filter paper. Less than 5 mm of wetness in 5 minutes, without local anesthesia is considered a positive test, meeting
the 2002 Sjgrens consensus criteria. A second ocular test
utilizes Rose Bengal staining of the cornea, and measures
areas of increased dye intensity. With the use of a slitlamp, the stain will detect devitalized tissue. The ocular
dryness is sufficient to produce disruption in the integrity
of corneal and conjunctival epithelium and dye will accumulate in these areas. The total areas identified are used to
determine the extent of ocular damage. Patients with complaints of ocular dryness, especially if combined with other
symptoms of SS, should be referred to the ophthalmologist
for evaluation. Untreated keratoconjunctivitis sicca can
progress to corneal ulcerations and even blindness.
The most frequent oral signs and symptoms a dentist
will encounter are xerostomia, a subjective sensation of
oral dryness, and hyposalivation, or a diminished salivary
ow rate. These will vary between patients, and the subjective dryness may not directly correlate with objective
measures of hyposalivation. Initial indications of a diminished salivary output would be a lack of pooling in the oor
of the mouth, thick or frothy saliva, and observing examination gloves sticking to the tongue or buccal mucosa.
Patients may complain of difculty chewing and swallowing, difculty wearing their dentures, and altered taste.
They will relate the necessity for drinking liquids to aid in
swallowing food or to enhance their ability to speak. They
may admit to keeping water by their bedside at night or
frequently waking with a dry mouth. Patients with SS frequently carry water with them and often need to sip every
1015 minutes during a consultation appointment. Upon
intraoral examination, the tongue may appear ssured,
slightly erythematous, and sometimes depapillated. If the
patient complains of a burning tongue and dysgeusia,
oral candidiasis should be suspected (Figure 2). Salivary
272

Xerostomia and fissured tongue.


Courtesy: Dr Carol Stewart

Figure 3

Oral cavity of Sjgrens syndrome patient showing dental


caries and fissured tongue. Courtesy: Dr Carol Stewart

ow rate is diminished in primary SS patients compared


with controls. In addition to quantitative changes, the protein content of the saliva is altered as well. Proteins necessary for buffering the oral acidity, countering fungal and
microbial organisms may be altered. The lack of adequate
salivary ow and qualitative changes in protein content
may predispose the patient to dental decay, particularly in
the cervical area, tooth loss, candidiasis and oral ulcerations (Figure 3). The change in saliva is linked to the
lymphocytic inltrate in the glands and subsequent damage to the functional units.
From one-fourth to two-thirds of patients with primary SS will have a diffuse enlargement of the major salivary glands during the course of their disease (Figure 4).

Chapter 11 Diseases of Salivary Glands

Figure 4

Figure 5

Sjgrens syndrome patient with enlarged parotid gland.


Courtesy: Dr Carol Stewart

This swelling may be unilateral or bilateral, intermittent or


constant in nature. If the parotid swelling initially is unilateral, it often becomes bilateral with time. It commonly
produces mild to no discomfort. However, diminished ow
will enhance a patients susceptibility to bacterial infection
in the glands and recurrent sialadenitis, which will produce
pain. Although SS is considered primarily a disease of
middle-aged females, it has also been reported in children
and adolescents. Recurrent bilateral parotitis in children
and adolescents should include the possibility of SS in the
differential diagnosis.
Conventional sialography renders useful information
about the gland architecture and changes within it. Waterbased radiopaque dye is injected into the major gland
ducts followed by conventional imaging. Peripheral ducts
within the glands are usually affected rst with the inner
ductal structure relatively well preserved. However, punctuate collections of the contrast material may be visible in
the early stages of the disease followed by globular or
larger collections as the condition progresses as shown in
Figures 57. Once extensive intraglandular destruction has
taken place and infection has become established, dilatation of central ducts is noted. Abscesses within the gland
may be noted with a uniform distribution, unlike focal
abscesses caused by other types of infections. However,
sialography is an invasive procedure and other imaging
modalities may be considered.
Imaging with CT and MRI is common. The glands
enlarge with time, assuming a denser appearance on CT.
A honeycomb appearance is not infrequent but this is also
seen with granulomatous conditions. Bilateral enlargement with cystic and solid lesions is noted (Figure 8A, B).
In the early stage, the parotids appear normal. Multiple
cysts appear during the intermediate stage. These eventually grow with time. If the mass assumes an invasive

Sialograph of Sjgrens syndrome.


Courtesy: Dr James Pettigrew

Figure 6

Sialograph of Sjgrens syndrome of the submandibular


salivary gland. Courtesy: Dr Ajit Auluck and
Dr Chandrakant Shetty

appearance, malignant transformation may be suspected.


Foci of calcication within the glands are not uncommon.
Heterogeneous enhancement may therefore be expected
(Figure 9A, B). The glands could eventually appear smaller
in size. In MRI, numerous punctuate areas appear within
the glands with low signal intensity on T1 and T2 weighted
images as the disease progresses. This is considered diagnostic of the condition. But, a lymphoma arising in a
benign lymphoepithelial lesion (BLEL) does not have characteristic features that would help differentiate it from
other tumors. However, it may be considered in patients
who present with a parotid mass. Function of the glands is
273

Section IV Diseases of Specific Structures

directly correlated with the amount of fat deposition,


thereby indicating that a monitoring of this feature may
be useful in diagnosing the condition. Another imaging
technique that is useful is magnetic resonance sialography.
It has been shown to be highly accurate with excellent
sensitivity and specicity. Globular, punctuate or a lytic
appearance is typical of the condition. If cysts develop
within BLEL, these are detected using CT or MR. The absence
Figure 7

Sialograph of Sjgrens syndrome showing atelectasia.


Courtesy: Dr James Pettigrew

of lymphadenopathy helps exclude HIV-related lymphoepithelial cyst formation.


Another test to conrm altered salivary gland function
is whole unstimulated sialometry. Sialometry is the measurement of salivary ow rate. It is instrumental in reaching a diagnosis of hyposalivation (below normal salivary
ow rate), a common nding in patients with SS. In an ideal
situation, patients should not eat, drink, smoke, or brush
their teeth for 90 minutes before the sialometric assessment. The patient is asked to expectorate into a preweighed
container, while sitting upright for 15 minutes. After reweighing the tube post-collection, dividing by 15 and applying the conversion factor (1 g 1 ml), a ow rate can be
determined. Unstimulated salivary ow 1.5 ml/15 min or
0.1 ml/min is considered consistent with Sjgrens diagnosis. After an SS diagnosis has been established, periodic
ow rates (every 36 months) may provide meaningful
information to assess disease progression. Subsequent salivary assessments should be collected at the same time
each sampling, preferably either 9:00 AMnoon or 1:00
PM3:00 PM, to avoid uctuations due to circadian rhythm
of salivary secretion and composition. Often, an SS patient
will be prescribed a sialogogue to enhance salivary ow.
Periodic ow rates are helpful to track medication efcacy
as well.
Lymphocytic inltration in the lacrimal and salivary
glands is a major feature of SS. One of the criteria for classication of SS includes the biopsy of the labial salivary
glands. A 1.5-cm incision is made on normal appearing
mucosa of the lower lip lateral to the midline (Figure 10).

Figure 8
A

Sjgrens syndrome. CT images showing diffuse sialadenitis affecting the submandibular and parotid glands bilaterally.
Courtesy: Dr Madhu Nair

274

Chapter 11 Diseases of Salivary Glands

Figure 9
A

Chronic Sjgrens syndrome. Contrast CT demonstrating a granular appearance of parotid glands that have been
reduced in size. Courtesy: Dr Madhu Nair

Figure 10

Sjgrens labial salivary gland biopsy procedure.


Courtesy: Dr Carol Stewart

Five or more accessory salivary gland lobules are examined


histopathologically for the presence of focal chronic
inammatory aggregates. A focus is 50 or more lymphocytes and some plasma cells within a 4 mm2 eld in the
salivary gland biopsy specimen. As noted in Figure 11A, B,
these aggregates are adjacent to normal-appearing acini

and are found throughout the glands. A nding of more


than one focus within a 4 mm2 area of glandular tissue is
supportive of a SS diagnosis. Manthorpe et al have reported
an interesting fact that the focus scores are lower in SS
patients who are cigarette smokers.
While the labial salivary gland biopsy is widely considered one of the best diagnostic tools for SS, it is not 100%
reliable. Personal experience has shown that minor salivary gland histopathology may not present the classic picture, yet be supportive of an SS diagnosis. Some SS patients
may show areas of classic patchy lymphocytic foci with
other areas more consistent with chronic sclerosing sialadenitis in conrmed primary SS patients. In addition, salivary gland biopsies of patients with long-standing SS
demonstrate areas of brosis more prominently than the
classic criteria allow. In more chronic cases, repeated biopsy
attempts reveal only brosis and no viable labial salivary
gland lobules. Sampling and timing of the biopsy may be
more critical than previously considered.
Laboratory diagnosis values
Patients presenting with signs and symptoms of SS should
have an appropriate laboratory assessment. Common findings include a positive rheumatoid factor (RF). RFs are
autoantibodies against antigenic determinants that are
present on the Fc portion of human IgG, and are found in
sera and saliva of 6080% of patients with primary SS.
A positive RF does not confirm that the patient has rheumatoid arthritis. Positive antinuclear antibodies (ANA) are
275

Section IV Diseases of Specific Structures

Figure 11
A

Sjgrens labial salivary gland histopathology (5 and 40). Courtesy: Dr Carol Stewart.
(A) Magnification 5; (B) magnification 40

found in most patients, particularly anti-SS-A/anti-Ro and


anti-SS-B/anti-La. Reports have demonstrated that precipitating autoantibodies to Ro and La occur in patients with
SLE, but are more prevalent in primary SS, occurring in
6080% (anti-Ro) and 4060% (anti-La) of SS patients.
Management
The patient with SS must be treated by a multi-specialty
team for an optimal outcome. The rheumatologist will
monitor the inflammatory components related to core disease and any extraglandular manifestations. The ophthalmologist will manage the ocular health of the patient on
a routine basis. A variety of treatment modalities might be
appropriate to help maintain ocular secretions, such as
lachymal duct plugs and laser occlusion. Prescription eye
drops containing 0.05% cyclosporine emulsion may help
some patients with ocular moisture. Many patients use overthe-counter artificial tears as well. As many SS patients
seem to be sensitive to agents in cosmetics and preservatives in over-the-counter products, hypoallergenic products
may be preferred.
The dental management for patients with SS is critical
to their long-term oral health. Patients demonstrating
hyposalivation may also demonstrate increased susceptibility to dental decay. Follow-up visits every 4 months
may assist in monitoring and treating active dental caries.
Patients should be educated and empowered to assist in
the management of their own oral health. Articial saliva
substitutes and oral hygiene products that contain lactoperoxidase and lysozyme (e.g. Biotene toothpaste and
mouthrinse) may be helpful. Meticulous home care with
a home uoride program customized for the patient is
essential. Nutritional counseling might be helpful, which
276

includes minimizing carbonated drinks and avoiding snacking on sticky sugary processed foods. Salivary stimulants
such as sugar-free gums and lozenges will assist in enhancing the salivary ow. If available, xylitol sweetened gums
and lozenges are benecial due to their reported anticariogenic effects. Prescription sialogogues, such as pilocarpine
and cevimeline can be very helpful as long as functional
salivary gland tissue remains. However, prescription sialogogues are not recommended for all SS patients. These
should not be used in patients with uncontrolled asthma
or narrow-angle glaucoma, and should be used with caution with certain types of cardiovascular disease, eye, lung,
and liver conditions. Consultation with the patients rheumatologist before prescribing these medications is prudent
to conrm the lack of contraindications. Not only are SS
patients more susceptible to dental decay and candida,
their periodontal status should be monitored as well. While
some reports indicate no signicant difference between
the periodontal status of SS patients and controls, others
report more severe periodontitis in SS patients. Patients
should be given all assistance possible to maintain their
dentition in the optimal condition. As many of these
patients are taking bisphosphonates for osteoporosis, the
option of implant replacements for lost teeth, or implant
supported dentures is one that should be approached with
utmost care and patients informed consent. The potential of
bisphosphonate-associated osteonecrosis should be reviewed
with the patient prior to extractions, implants, or any oral
surgical procedures.
While SS often follows an indolent course, of critical
importance is the concern for development of lymphoma.
Kassan et al reported that SS patients have 40 times higher
risk of development of lymphoma than the normal population. Lymphoma has been reported by Voulgarelis et al

Chapter 11 Diseases of Salivary Glands

Figure 12

immunosuppressives are reserved for treatment of severe


extraglandular manifestations of SS. Anti-B-cell therapy
is a new potential therapy for the glandular and extraglandular manifestations in addition to the management of
lymphoma associated with SS. Gene-transfer modalities
used in animal models continue to show future promise.
The dentist should be an integral part of the medical management team, along with the rheumatologist and ophthalmologist, for optimal patient care.

Benign Lymphoepithelial Lesion


(Mikuliczs Disease)

Palatal MALT lymphoma and carious roots in


Sjgrens syndrome patient. Courtesy: Dr Carol Stewart

in 4.3% of patients with SS. These tumors may arise in the


salivary gland or within lymph nodes. What was considered a BLEL in the past might currently be diagnosed as a
low-grade non-Hodgkins B-cell lymphoma of the mucosaassociated lymphoid tissue (MALT) lymphoma. Figure 12
demonstrates a patient with SS demonstrating a bluish
area in the hard palate, which was diagnosed as BLEL. In
addition, SS patients may develop caries that involve root
surfaces. MALT is normally found in Peyers patches in the
ileum of the lower gastrointestinal tract, where it plays a
role in normal humoral immune response. Mononuclear
cell lymphocytic inltrates in the exocrine glands can
develop into marginal zone B cell lesions or acquired
MALT. A recent enlargement or persistent parotid enlargement could be a lymphoma. MALT lymphomas have even
been discovered though SS labial salivary gland biopsies.
Patients with SS have an increased risk of developing
monoclonal B-cell MALT lymphoma due to perhaps prolonged autoimmune inammation or persistent antigenic
stimulation to virus or bacteria. Occasionally, high-grade
lymphomas develop which can demonstrate aggressive
behavior. A patient demonstrating a persistent swelling of
the major salivary glands or lymph nodes, or sudden
parotid gland enlargement or pain should be evaluated to
rule out possible lymphoma.
Currently, SS patients suffer from diminution in quality
of life resulting from the sicca complex, extraglandular
manifestations, and the depression from disease chronicity
and anxiety associated with development of lymphomas.
Educating patients and helping them to understand their
disease and empowering them with knowledge is an important management strategy. The prognosis for SS patients
may improve as greater understanding of the pathogenesis
is achieved through continued research. Currently, systemic

In the late 1800s, Johann von Mikulicz-Radecki described


a patient with an unusual bilateral painless swelling of
the lacrimal glands and all the major and minor salivary
glands. Histopathologic examination showed an intense
lymphocytic infiltrate, with features that were recognized
as the BLEL. The clinical presentation became known as
Mikuliczs disease and the term was used to describe cases
of bilateral parotid and lacrimal enlargement. With time,
the histopathological diagnosis of these cases proved to
be inconsistent with Mikuliczs disease. The clinical picture of symmetrical lacrimal and salivary gland enlargement was attributed to other diseases such as tuberculosis,
sarcoidosis and lymphoma. Consequently, these cases were
later described as Mikuliczs syndrome, restricting the
term Mikuliczs disease for use with a histopathologic
diagnosis of BLELs. Over the years, the use of these terms
became interchanged and confusing, so their use has been
discouraged.
Clinical features
Mikuliczs disease is reportedly characterized by symmetric
and persistent swelling of the lacrimal glands and either or
both of the major salivary glands (parotid and submandibular) and the exclusion of other diseases that may mimic
this presentation, such as sarcoidosis, viral infection or
lymphoproliferative disorders. Many cases of BLELs were
a component of SS. The lymphoepithelial lesion was commonly found in adults, primarily women, and usually in the
parotid gland. The affected gland was diffusely enlarged,
asymptomatic or mildly painful.
Diagnosis
Microscopic examination demonstrates a heavy lymphocytic infiltrate associated with the destruction of the salivary acini. The ductal epithelial cells and surrounding
myoepithelial cells become hyperplastic, and form groups
of cells known as epimyoepithelial islands. These islands,
once considered benign, are currently recognized to be
indicative of low-grade salivary lymphoma of the MALT.
A review of Mikuliczs initial case report concluded that
277

Section IV Diseases of Specific Structures

Mikulicz actually reported the first case of MALT lymphoma, based on the published histopathology. The authors,
Ihrler and Harrison further urged that the terms Mikuliczs
disease and Mikuliczs syndrome should no longer be used.
Conversely, a recent report by Yamamoto et al concluded
that Mikuliczs disease is a distinct entity and different
from SS both clinically and histopathologically. Additionally, the authors reported that Mikuliczs disease was an
IgG4-related systemic disease.
Treatment
The affected gland must be surgically removed. Fortunately,
most MALT lymphomas are low-grade tumors that tend to
remain localized with good survival rates. Occasionally,
tumors transform to high-grade lymphomas with aggressive
behavior.

Sialorrhea
Clinical features
Sialorrhea or ptyalism is a condition characterized by
increased salivary flow. Sialorrhea can occur with various
neurologic disorders, infections, the secretory phase of
the menstrual cycle, heavy metal poisoning, Wilson disease, paroxysmal sialorrhea, and rabies. Older aged individuals in chronic care facilities and chronically debilitated
with cerebrovascular accident may demonstrate chronic
drooling.
Parkinsons disease (PD), amyotrophic lateral sclerosis
(ALS), and cerebral palsy are neurodegenerative diseases
associated with sialorrhea. The appearance of excess saliva
in neuropathologic conditions may be due to excessive
saliva, but is usually related to impaired cerebral control
of orofacial function. Weakness of the facial and perioral
muscle tone inhibits the normal retention, movement,
and/or swallowing of saliva. Excessive salivation has been
reported in familial dysautonomia (FD) due to submandibular and sublingual salivary gland hyperactivity. These
changes may be the result of ongoing parasympathetic
denervation characteristic in FD. The consequences of
drooling are not restricted to medical issues, but can
cause major social handicaps. Severe psychosocial consequences and social stigmatization may be emotionally
devastating for patients and families. Drug-induced sialorrhea has been reported as well. Major medication groups
associated with drooling are anti-psychotics, particularly
clozapine, and direct and indirect cholinergic agonists that
are used to treat dementia of the Alzheimers type and
myasthenia gravis. Other drugs cited include risperidone,
lithium and digoxin. Heavy metal toxins, such as mercury
and thallium produce sialorrhea as does exposure to irreversible acetylcholinesterase inhibitors such as insecticides
and nerve agents.
278

Patients reporting to the dental ofce will present due


to concern about the unknown condition which carries
signicant social stigmas. The patient may bring their spit
cup with them and describe their saliva as foamy. Several
conditions should be considered.
Minor sialorrhea may be associated with minor oral
irritations and ill-tting or new dentures. Episodic sialorrhea may be a subtle manifestation of gastroesophageal
reex disease (GERD). Excessive saliva is produced as a
protective buffering mechanism in patients with GERD.
This is called water brash. A similar condition of sialorrhea with unknown etiology termed idiopathic paroxysmal sialorrhea is reported to consist of episodes of
increased salivary ow occurring 1 or 2 times per week at
25 minutes in duration. The episodes are preceded by a
prodrome consisting of nausea or epigastric pain, but
without progression to vomiting. These may be variants of
the same condition. Sialorrhea may be associated with
esophageal obstruction (foreign body, cancer, or stricture
formation), infection, and nasogastric intubation with
symptomatic sequelae of sialorrhea.
Treatment
Treatment of sialorrhea depends on its etiology. Some
causes of mild or transitory sialorrhea may need no treatment. If the salivation is believed to be due to GERD,
referral to their physician for evaluation and treatment
would be appropriate. If the condition is due to inadequate
motor control, speech therapy might improve the situation, if the patient is able to cooperate. Botulism toxin
injected into the parotid gland has been reported to have
efficacy for ALS and PD as reported by Lagalla et al and
Contarino et al. Surgical techniques might be needed to
modify the salivary glands or ductal structures. A recent
report by McAloney et al showed efficacy and safety from
bilateral submandibular duct relocation and bilateral sublingual gland excision. The prognosis of sialorrhea will
vary with the degree to which the causal factors can be
managed.

INFLAMMATORY CONDITIONS OF
SALIVARY GLANDS
Inflammatory conditions are the most common pathology affecting the salivary glands. Dentists should be familiar with their clinical manifestations and recommended
treatment.

Mucocele
The mucocele is a common lesion that results from rupture
of a salivary gland duct and spillage of mucin into the

Chapter 11 Diseases of Salivary Glands

surrounding tissues. For that reason, the term mucus extravacation phenomenon is used to describe this lesion. The
rupture of the gland or duct may be due to local trauma,
but many cases develop without a history of trauma. These
will be found most frequently in the lower lip.
Clinical features
Mucoceles typically present as fluctuant, non-ulcerated
dome-shaped mucosal swellings that range from 2 mm to
several centimeters in size. Mucoceles have been reported
in patients of all ages. The lesions typically have a bluish
translucent hue due to the spilled mucin under the tissue
surface (Figure 13). Deep mucoceles may appear normal in
color, and may feel firmer to palpation than superficial
ones. Duration may be days to years. Patients will often
report that the lesion intermittently gets larger, and then
shrinks. This history is consistent with the nature of the
lesion which will enlarge, sometimes during eating, and
then spill contents into the surrounding tissue, and eventually shrink in size. The most common location is the
lower lip, but mucoceles may also be found in the buccal
mucosa, anterior ventral tongue and floor of the mouth
(ranula).

and plasma cells. The lumen is filled with an eosinophilic


coagulum containing inflammatory cells.
Treatment
Treatment of the mucous retention phenomenon is excision. If only incised, the contents will be released, but the
lesion may recur when the area has healed.

Ranula
Clinical features
Ranula is the term used for mucoceles that occur in the
floor of the mouth in association with ducts from the submandibular or the sublingual gland. Generally these are
larger than mucoceles occurring in other locations and can
elevate the tongue. The ranula is usually located lateral
to the midline and appears as a dome-shaped fluctuant
swelling in the floor of the mouth as seen in Figure 14.
The color may be translucent blue or normal in color if
deep seated. A rare plunging type that has herniated
through the mylohyoid muscle has been described by
Davison et al.

Histopathology

Histopathology

They consist of a circumscribed cavity in the connective


tissue, producing an elevation of the mucosa with thinning
of the epithelium. The cavity wall is made up of a lining of
compressed fibrous connective tissue and fibroblasts. The
connective tissue wall may demonstrate granulation tissue
infiltrated by polymorphonuclear leukocytes, lymphocytes

The histopathology of a mucocele and ranula are similar,


however, the ranula may be a true cyst with an epithelial
lining. Spilled mucin may elicit a granulation tissue
response that contains foamy histiocytes.

Figure 13

Treatment
Treatment of a ranula includes unroofing the lesion, excision of the lesion, or removal of the sublingual gland.
Figure 14

Mucocele of the lower lip. Bluish dome-shaped lesion of


short duration on the mucosal aspect of lower lip.
Courtesy: Dr Indraneel Bhattacharyya

Ranula. Courtesy: Dr Praveen, Department of Oral Medicine,


KLE Institute of Dental Sciences, Bangalore

279

Section IV Diseases of Specific Structures

Sialolithiasis, Salivary Duct Stone,


Salivary Calculi

Figure 15

Clinical features
Sialoliths are calcified bodies that develop within the salivary gland or ductal system. These are one of the most
common salivary gland conditions. These are believed to
develop from deposition of calcium salts around a focus
of material within the duct lumen. Solitary or multiple sialoliths can form. The initiating focus may consist of desquamated epithelial cells, bacteria, foreign bodies, or mucus.
Sialoliths most commonly occur in the submandibular
gland (8090%), but may develop in the parotid and sublingual gland as well. Multiple stones are more common in
the parotid glands than other major glands. Minor gland
calculi are occasionally seen in labial glands and buccal
mucosa. These usually form in young and middle-aged
adults, but may develop at any age. The classic presentation is an intermittent postprandial salivary gland swelling that gradually subsides over the next 23 hours.
Patients report moderately severe pain, just before, during
and after meals due to stimulation of salivary flow and the
pressure produced against the occluded duct. Recurrent
and chronic obstruction causes stasis, inflammation, and
infection, which can result in persistent enlargement.
Sialoliths may be round or elongated and measure from
2 mm to 2 or more centimeters in diameter. The involved
duct may contain a single stone or multiple stones. Upon
excision and gross examination, these appear yellow in
color. The cause is uncertain, but sialolith formation can
be promoted by chronic sialadenitis and partial duct
obstruction.

Occlusal radiograph of sialolith in submandibular gland.


Courtesy: Dr Carol Stewart

Figure 16

Diagnostic procedures
Conventional radiographs can successfully image most
sialoliths as they appear as radiopaque masses. Smaller
sialoliths that are not fully calcified pose a diagnostic challenge. Underexposed radiographs can sometimes demonstrate the presence of the sialolith. Occlusal films help
identify stones in the submandibular gland as shown in
Figures 15 and 16. If a panoramic film is generated, multiple calcifications may be identified as shown in Figure 17.
It is possible for multiple calcifications to appear superimposed on the mandible and mimic a bony lesion. A sialograph of Whartons duct depicts ductal enlargement
proximal to the sialolith in Figure 18. However, Rabinov
and Weber report that up to 20% of salivary calculi are
radiolucent. If not calcified, the stones may not be evident
on these films. Non-contrast CT is often considered the
best single modality for the diagnosis of calculi. Most stones
not seen on conventional radiographs can be detected by
CT. Sialographs are useful in detecting non-calcified sialoliths, but sialography is an invasive procedure with potential to dislodge the stone deeper into the gland, as well as
280

Occlusal radiograph of sialolith in submandibular gland.


Courtesy: Dr James Pettigrew

facilitate retrograde spread of any existing bacterial infection as a result of stasis. In addition, sialography can cause
increased pain when acute sialadenitis exists. Dormant
infections can get worse after sialography; thus necessitating the use of antibiotics. Contrast CT examination, on
the other hand, can image non-calcified sialoliths if these
are larger. In Asia and Europe, ultrasound imaging is the
mainstay of imaging.

Chapter 11 Diseases of Salivary Glands

Figure 17

invasive treatment modality that does not require removal of


the gland for sialolithiasis. Commonly associated with sialolithiasis is acute or chronic sialadenitis, which is described
in the next section.

Sialadenitis

Panoramic film of multiple sialoliths in parotid gland.


Courtesy: Dr James Pettigrew

Sialadenitis or an inflammation of the salivary glands


may arise from a variety of infectious and non-infectious
conditions. Non-infectious causes of salivary gland dysfunction include disorders such as SS, sarcoidosis, radiation therapy, medications, and congenital anomalies were
discussed in the previous sections. The infectious causes,
which will be discussed in the following sections, commonly include bacterial and viral infections. Salivary
stones or sialoliths are also associated with salivary gland
dysfunction of the major and minor glands. Conditions
that predominately affect the minor salivary glands, such
as cheilitis glandularis and necrotizing sialometaplasia
will be reviewed as well.

Figure 18

Non-specific Sialadenitis

Sialograph of submandibular gland showing dilatation of


Whartons duct proximal to sialolith. Courtesy:
Dr Ajit Auluck and Dr Chandrakant Shetty

Histopathology
The histopathologic features include a calcified mass that
exhibits concentric laminations surrounding a central focus
of amorphous debris. The associated duct will demonstrate
squamous, oncocytic or mucous cell metaplasia.
Treatment
Small stones may be removed by massaging and manipulation to move the stones toward the duct orifice or peripheral/
transoral ductotomy. Large stones may require excison of
gland and/or associated duct. Lithotripsy has been tried with
limited success. Sialoendoscopy provides a new minimally

Non-specific sialadenitis may manifest as chronic parotitis, also called chronic recurrent parotitis. The cause of the
parotid gland enlargement may be multifactorial and
include decreased salivation either from decreased production or decreased secretion, stasis and an ascending
retrograde infection. Sometimes, no predisposing factor is
identified. This entity is usually unilateral, painful (mild to
severe), and characterized by intermittent exacerbations of
swelling and remission. Massaging or milking the gland
will reveal cloudy or purulent secretions. In a large series,
Bhatty et al reported that the mean age was 46 years,
with mean duration of symptoms of 4.6 years. The swelling may last for several hours or several weeks. The condition establishes a cycle of blockage and infection, which
becomes self-perpetuating. Fever and malaise may be
present. Remissions last from weeks to years. The extent of
the gland destruction may increase over time with each
episode as does the pain intensity. The disease tends to
progress and may lead to the formation of a fibrous mass
in the affected gland.
Diagnostic imaging
Sialography will demonstrate the parotid duct system. A
sausage-like pattern reflects areas of duct wall dilatations
and stricturing that result from the effects of the ascending bacterial infection. Because sialography may result in
retrograde spread of infection into the gland, other imaging modalities are preferred. CT scan may show increased
density due to the normal parotid gland fat being replaced
by inflammation and fibrosis. Contrast CT will show
enlargement of the gland and its duct in the absence of
281

Section IV Diseases of Specific Structures

a causative agent such as a sialolith. Figure 19 shows unilateral gland and duct enlargement of the right submandibular gland. Figure 20AC show non-specific sialadenitis
in the right parotid and submandibular glands.
Histopathology
The histopathology is consistent with non-specific sialadenitis with marked infiltrate of inflammatory cells. The
histology may show mild chronic sialadenitis or widespread

involvement of the gland with areas of destruction. Acinar


loss and fibrosis will be present in varying amounts.
Treatment
Treatments include antibiotic therapy during an acute
attack, sialogogues, increased fluid intake and parotid
gland massage. When surgical intervention is appropriate,
a superficial parotidectomy has a high success rate with
minimal long-term complications.

Bacterial Sialadenitis

Figure 19

Bacterial sialadenitis may arise from a bacterial infection


involving any of the salivary glands. Acute bacterial sialadenitis most commonly occurs in children younger than
2 months and in elderly persons who are debilitated by
systemic illness, or who have had surgical procedures. However, persons of all ages may be affected. The most common pathogens are Staphylococcus aureus and anaerobic
bacteria.
Clinical features

Unilateral enlargement of the right submandibular


gland and duct, consistent with low-grade sialadenitis.
Courtesy: Dr Madhu Nair

Acute sialadenitis is seen in the parotid gland and is


bilateral in 1025% of case. The affected gland is swollen
and painful, and the overlying skin may be erythematous.
The patient may present with a low-grade fever and trismus. Milking the gland may reveal a purulent discharge.
Acute suppurative sialadenitis is most frequently due to
S. aureus, but also may arise from streptococci, including
Streptococcus pneumoniae and Streptococcus pyogenes and
gram-negative aerobic bacilli including Escherichia coli.
A study of acute sialadenitis from all three major glands

Figure 20
A

Non-specific sialadenitis noted in the right parotid and submandibular glands. Courtesy: Dr Madhu Nair

282

Chapter 11 Diseases of Salivary Glands

with 47 specimens as reported by Brook revealed a broad


spectrum of microbes present in the purulent fluid. The predominant aerobes were S. aureus and Hemophilus influenzae, while anaerobes were gram-negative bacilli, including
Prevotella, Porphyromonas, Fusobacterium and Peptostreptococcus species.

necrosis. The ducts tend to be atrophic and do not show


squamous metaplasia characteristic of necrotizing sialometaplasia. Based on the clinical and histopathologic features, some prefer to consider SANS a separate non-specific
inflammatory condition of the minor salivary glands with
unknown etiology.

Histopathology

Treatment

The diagnostic features of acute sialadenitis will include


neutrophils within the ductal system and acini.

Subacute necrotizing sialadenitis is self-limiting and heals


within 23 weeks. It generally requires no treatment.

Diagnosis
A history of preceding events may aid in making the diagnosis. Predisposing factors can include dehydration, malnutrition, immunosuppression, dental infection, anticholinergic
medications, tracheotomy, sialectasis, ductal obstruction,
neurosurgical, and abdominal surgical procedures.
Treatment
Treatment for acute sialadenitis includes appropriate antibiotic therapy based on culture and sensitivity findings.
Rehydration is important to improve salivary flow. If an
abscess has formed, surgical drainage may be required. If
the condition is severe, surgical removal of the gland may
be necessary. In debilitated patients, the condition may be
fatal due to spread of infection and sepsis. Prompt recognition by the dentist with appropriate referral otorhinolaryngologist for definitive treatment is essential for a
good outcome.

Subacute Necrotizing Sialadenitis


Clinical features
Subacute necrotizing sialadenitis (SANS) is a form of salivary inflammation that occurs most commonly in young
adults and teens. The lesion involves minor salivary glands
of the hard and soft palate, and presents as a localized
palatal swelling covered by erythematous, intact mucosa.
The nodule may be accompanied by abrupt onset of pain.
An infectious or allergic origin has been suggested. Some
diagnosticians have questioned whether SANS represents
a separate entity or part of the spectrum of necrotizing
sialometaplasia. Unlike necrotizing sialometaplasia, SANS
does not ulcerate or slough necrotic tissue.
Histopathology
Subacute necrotizing sialadenitis is characterized by a
heavy mixed inflammatory infiltrate consisting of neutrophils, lymphocytes, histiocytes, and eosinophils. There is
an absence of acinar cells and those present may exhibit

Cheilitis Glandularis
The term cheilitis glandularis was first used by Volkmann
in 1870 to describe a disorder that presented with a
chronic, suppurative inflammation of the lower lip characterized by swelling of the mucous glands, dilated openings, and mucopurulent discharge. Cheilitis glandularis is
an uncommon inflammatory condition of the minor salivary glands, and most commonly affects the lower lip of
adult males. The etiology is unknown, however associated
factors have been suggested. These factors include tobacco,
poor oral hygiene, bacterial infections, possibly heredity,
and actinic damage.
Clinical features
Cheilitis glandularis most commonly affects the lower lip,
but it has been reported in the upper lip, palate, and buccal
mucosa. Affected individuals experience swelling and
eversion of the lower lip as a result of hypertrophy and
inflammation of the glands as seen in Figure 21. The openings of the minor salivary ducts are inflamed and dilated,
and pressure on the glands may produce mucopurulent
secretions emanating from the ductal openings. The condition most frequently occurs in middle-aged men, but
women and children have been reported as well.
Historically, cheilitis glandularis has been classied into
three types, based on the severity of the disease. These are
(i) simple, (ii) supercial suppurative (Baelzs disease), and
(iii) deep suppurative (cheilitis glandularis apostematosa).
The supercial suppurative type demonstrates painless
crusting, swelling, and induration of the lip with supercial and deep ulceration. This type seems to be the result of
secondary infection of the simple type. The deep suppurative type, also known as cheilitis glandularis apostematosa,
myxadenitis labialis, or cheilitis glandularis suppuritiva
profunda, is a deep-seated infection associated with abscess
formation and spontaneous expression of suppurative material from the ducts. The latter two types represent progressive stages of the diseases with bacterial involvement
and demonstrate increased inammation, suppuration, and
ulceration of the lip.

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Section IV Diseases of Specific Structures

Figure 21

Cheilitis glandularis. Courtesy: Department of Oral Medicine,


MCODS, Mangalore

Histopathology
Histopathologic features consist of non-specific chronic
inflammation, dilated secretory ducts, dilated ducts containing mucin, areas of fibrosis, and areas of chronic sclerosing sialadenitis. The ductal lining may show oncocytic
metaplasia and atrophy of the acini. Concomitant dysplastic changes may be seen in the surface epithelium.
Diagnosis
The differential diagnosis for cheilitis glandularis would
include orofacial granulomatosis and multiple mucoceles.
Orofacial granulomatosis, which will be described in the
next section, is a non-tender, persistent swelling of the lips
usually with oral ulcerations. Histologic findings would
include non-caseating giant cell granulomas. Definitive
diagnosis of cheilitis glandularis requires a biopsy along
with the clinical picture.
Treatment
The treatment for cheilitis glandularis may vary depending on the severity of the condition. It may be treated with
lip balms, sunscreens, topical steroids, intralesional steroids, systemic antihistamines, and/or antibiotics. If conservative therapy fails, surgical resection or vermillionectomy
may be indicated. A significant percentage of cases of deep
suppurative type have been associated with the development
of squamous cell carcinoma of the overlying epithelium.
Because actinic damage has been implicated in many cases of
cheilitis glandularis, malignant degeneration could be associated with susceptibility to environmental factors, especially sun damage versus considering cheilitis glandularis
284

Figure 22

Necrotizing sialometaplasia of the palate. A well-defined ulcer


that began after 1 week of seating porcelain fused to metal
(PFM) crown on tooth number 3. Patient reported mild
discomfort and that the lesion was progressively getting
larger. Courtesy: Dr Indraneel Bhattacharyya

as a true malignant condition. Radiation therapy was used


in the past, but is no longer recommended due to associated complications.

Necrotizing Sialometaplasia
Clinical features
Necrotizing sialometaplasia is an uncommon, benign, but
locally aggressive inflammatory lesion of salivary gland
tissue which both clinically and histologically may mimic
a salivary gland malignancy. In 1973, it was described by
Abrams and colleagues as a reactive necrotizing inflammatory process of the minor salivary glands of the hard
palate. While the etiology is unknown, the prevailing theory is that local ischemia of the salivary tissue leads to
local infarction. Most patients are in the 4th or 5th decade,
but the lesion has been reported in all ages, except children. In a large series as reported by Brannon et al, males
were affected more often than females, and whites were
affected more commonly than African-Americans by a
ratio of 5:1. Most lesions occur in the posterior hard palate, usually unilateral (Figure 22). Bilateral and midline
lesions may occur as well. Other intraoral sites such as the
retromolar pad, buccal mucosa, lower lip, and tongue have
been affected. Early lesions may present as a non-ulcerated
swelling in the posterior palate with or without pain.
Within 23 weeks, the necrotic tissue sloughs and leaves
a crater-like ulcer ranging from 1 cm to more than 5 cm.
Commonly, patients do not seek treatment until the ulcer
occurs. They may report a feeling of fullness in the area,
prior to the ulceration. Pain may or may not be a complaint
even though the ulcer may be quite large.

Chapter 11 Diseases of Salivary Glands

Diagnostic imaging

Diagnostic imaging

A palatal soft tissue attenuation focus with no characteristic appearance may be noted on CT and MRI. Osseous
changes are not noted. Lesions in the parotid are also sometimes seen. Ultrasonography may detect multiple foci of
hypoechoic nature within the parotids. Contrast CT demonstrates high attenuation areas within the parotids while
MRI can clearly show well-delineated masses that are hypointense on T1 and isointense on T2 weighted contrasted
images. Findings could resemble those of benign tumors
such as pleomorphic adenomas. Alternatively, a more diffuse margin on CT can be misconstrued for a malignant
tumor. The condition can also appear in other locations
within the sinonasal and upper aerodigestive tracts.

Ultrasound imaging results in the gland appearing


enlarged and lobular with a cirrhotic pattern of numerous
hypoechoic regions against a heterogeneous background.
The presence of lymph node enlargement is sometimes
noted on CT/MRI. Diffuse enlargement of the gland with
enhancement may be noted on CT.

Histopathology
Biopsy is necessary to confirm the diagnosis and rule out
malignant disease. The histopathology includes ulcerated
mucosa, pseudoepitheliomatous hyperplasia of the epithelium, acinar necrosis, and squamous metaplasia of salivary
ducts. Coagulation necrosis has been seen in early lesions.
Inflammatory cells may be found with fibrosis and granulation tissue. While mucous cells are necrotic, the lobular
architecture of involved glands is preserved. The lesion
can be misdiagnosed as squamous cell carcinoma or
mucoepidermoid carcinoma in the absence of an adequate
representative section of the lesion.

Treatment
The treatment is surgical removal.

VIRAL-INDUCED SALIVARY GLAND


PATHOLOGY
Mumps
Clinical features

Chronic Sclerosing Sialadenitis (Kuttner Tumor)

Epidemic parotitis or mumps is a moderately infectious


disease caused by a virus of the paramyxovirus group.
Generally, mumps is a disease of childhood with an incubation period of 23 weeks. The virus may be in the saliva
of affected persons and dissemination through droplets is
common. The patient will complain of fever, fatigue, and
present with a painful unilateral, or more commonly, bilateral parotid enlargement. The infection may also involve
the submandibular gland. Clinical features include a flulike illness with fever, headache, vomiting, and pain below
the ear. This is followed by firm, somewhat rubbery swelling of the salivary glands, sometimes elevating the ears.
The glands are extremely tender to palpation and milking
them may produce a thick white secretion from Stensens
ducts. The swelling may last approximately 1 week. Other
organs may be involved which include the testes, ovaries,
pancreas, and mammary glands.

Clinical features

Prognosis and treatment

The Kuttner tumor, a chronic inflammatory condition of


the salivary glands, was first described by Kuttner in 1896.
Clinically, the condition cannot be distinguished from a
true neoplasm. The submandibular gland is affected more
commonly than any other salivary gland. It is usually
localized to the superficial aspect of the submandibular
gland, but may involve the deep aspect. It manifests as a
firm, enlarged gland. Etiology may be sialolithiasis (about
one-third of all cases), autoimmune sialadenitis or idiopathic. Recent reports suggest that pathogenesis probably
has an immunologic background.

When the disease affects the adult male, orchitis, inflammation of the testicles, is a complication approximately
20% of the time. The orchitis is usually unilateral, but can
occur bilaterally. Even with involvement of both testicles,
sterility is only a rare complication of orchitis. In adults,
dyspnea secondary to severe swelling of the salivary gland
which required a tracheostomy, has been reported by
Ishida et al. The mumps vaccine has been available since
1968, which has resulted in a marked decline in the incidence of the disease.

Treatment
Once the diagnosis has been established, no specific treatment is indicated. The lesion will heal by secondary intention with no intervention within 410 weeks.

Histopathology
The histolopathologic features consist of chronic sclerosing
sialadenitis, specifically chronic inflammation and fibrosis. It may be seen with sialolithiasis.

Human Immunodeficiency Virus (HIV)


Clinical features
Benign lymphoepithelial lesions (BLEL) in AIDS or AIDSrelated parotid cysts (ARPC) are frequently reported in HIV
285

Section IV Diseases of Specific Structures

infected patients, and may develop later in the course of


the disease. The term ARPC is preferred to help differentiate between AIDS-related lesions and BLELs. HIV-positive
status alone is needed to manifest with BLEL and therefore,
the term BLEL-HIV is most appropriate. Approximately 5%
of patients with HIV-1 develop parotid enlargement. These
cysts can be single or multiple and usually involve the
superficial lobe of the parotid gland. These are usually bilateral, often cystic, and sometimes accompanied by cervical
lymphadenopathy. These may be soft or firm to palpation
and can produce significant cosmetic deformities. Symptoms of dry mouth, ocular dryness, and arthralgia can occur,
along with normal or reduced salivary flow rates. The
pathogenesis of HIV-associated salivary gland disease may
include hyperplasia of intra-parotid lymphoid tissue.

to the increased use of medications to control AIDS-related


infections. Bilateral enlargement in imaging studies is more
common even in the absence of such clinical findings.
On T1 weighted images, cysts may appear with low signal intensities. Inhomogeneity of lesions is noted sometimes, primarily with solid lesions. On T2 weighted images,
the cysts appear hyperintense and well-dened, as do reactive lymph nodes.
T1 coronal and axial fast uid-attenuated inversionrecovery (FLAIR) MRI images depict bilateral cysts within
the parotids quite well (Figure 23A, B). On ultrasonographic studies, the cystic lesions appear with some internal septations, generating little echo. On the other hand,
solid lesions appear with the same characteristics of solid
tumors.

Histopathology

Treatment

The AIDS-related swellings reflect the lymphoid hyperplasia or lymphoepithelial cyst formation. The cyst wall may
contain germinal centers and a dense infiltrate of lymphoid cells.

Sometimes, patients seek treatment only when the cosmetic


deformity from the enlarged glands becomes very prominent. Highly active antiretroviral therapy is an effective
treatment approach. Because HIV-associated salivary gland
disease can clinically resemble SS, the differential diagnosis of bilateral parotid enlargement should include HIV
infection. While the parotid manifestation is considered to
have a benign course, progression to lymphoma is possible. Consequently, periodic monitoring is indicated. Any
change in growth pattern would require biopsy. Rosso et al
suggest that annual ultrasonography evaluation should be
done to identify possible malignant transformation of
BLELs in vertically infected children.

Diagnostic imaging
Contrast enhanced CT or MRI is advised to help delineate
the internal architectural details. Cystic and solid tumors
can appear within the parotids. Bilateral enlargement is
noted on advanced imaging modalities with associated
cervical and nasopharyngeal lymphadenopathy. Adenoids
and tonsils may appear enlarged as well. However, reactive adenopathy may not be seen on these studies, owing

Figure 23
A

Axial and coronal T1 FLAIR MRI images showing cysts in the parotids bilaterally in an HIV-positive individual.
Courtesy: Dr Madhu Nair

286

Chapter 11 Diseases of Salivary Glands

NON-INFLAMMATORY CONDITIONS OF
SALIVARY GLANDS

Figure 24

Sialadenosis
Sialadenosis (sialosis) is a non-inflammatory, non-neoplastic, often recurrent condition which most commonly
manifests as a bilateral enlargement of the parotid and/or
submandibular glands. In a recent report of 65 cases of
sialadenosis as described by Satoh and Yoshirara, age
ranged from 19 to 71 years and the male:female ratio was
5:3. The salivary gland enlargements are usually slow
growing, may be unilateral or bilateral, and are sometimes
associated with pain. The condition is usually associated
with an underlying systemic disorder. These disorders
include diabetes, hypothyroidism, pregnancy, alcoholism,
malnutrition, obesity, anorexia nervosa, bulimia, and medications that affect the autonomic nervous system. Treatment depends upon identification of the underlying cause.
As patients with these conditions will commonly present
to the dental office, an understanding of the causes and
effective management strategies is essential for optimal
patient care.

Anorexia/Bulimia-related Sialadenosis
Clinical features
Eating disorders are not uncommon in young women who
seek to be thin or have a more ideal figure. These disorders
include anorexia nervosa and bulimia nervosa. Anorexia
involves deliberate lack of food intake and bulimia includes
binge eating with self-induced purging. It has been estimated that up to 19% of college-going women have bulimia.
Only 510% of people with bulimia are male. Sometimes
the frequent purging of acidic gastric fluids will produce a
characteristic enamel erosion on the lingual surfaces of
the maxillary anterior teeth (Figure 24). However, if measures are taken to neutralize the oral pH and maintain oral
hygiene, these signs may not be present.
Parotid sialadenosis has been reported to occur in
1066% of people with bulimia. Bilateral parotid gland
enlargement has been the presenting sign in some cases
and one report by Mignogna et al also included bilateral
palatal minor gland enlargements in addition to the parotid
gland involvement. Schlienger et al reported a case where
a 24-year-old female consulted physicians for 3 years for
treatment of a painless parotid swelling which was initially
confused with SS. Eventually, bulimia was conrmed.
Unilateral parotid gland and submandibular gland swelling may also occur in sialadenosis associated with bulimia, but less frequently. Bulimics may purge several times
per day. Emetics, diuretics, and laxatives frequently are
used as adjunctive agents for weight reduction, but may
not be revealed during a routine medical history review.

Perimyolysis. Characteristic pattern of dental erosion of the


lingual enamel resulting from purging and vomiting
associated with bulimia. Courtesy: Dr Carol Stewart

Pathogenesis
While the specific pathogenesis has not been determined,
it is generally accepted that multiple emetic episodes cause
an autonomic neuropathy. The enlargement is believed
to affect the autonomic innervation of the salivary acini,
causing disruption of the intracellular secretory cycle.
This may lead to excessive accumulation of secretory
granules, with marked enlargement of the acinar cells. Due
to sympathetic nerve dysfunction, zymogen (a precursor
of amylase) production and storage may increase. Individual acinar cells enlarge because of zymogen granule
engorgement.
Diagnosis
Because patients with bulimia and anorexia do not frequently disclose their condition, a broad medical evaluation will be required. The diagnostic assessment would
include tests to rule out SS (ANA, anti-SS-A/Ro, anti-SSB/La, rheumatoid factor, hepatitis C virus, complete blood
count [CBC], serum angiotensin-converting enzyme, immunoglobulin disorder [IgA, IgM, albumin, urine Bence Jones
protein], hepatic disorder [glutamic oxaloacetic transaminase and glutamic pyruvic transaminase], diabetes [fasting
blood glucose], and hypokalemia [serum electrolytes]).
Salivary secretion may be decreased or normal. Sialography may be helpful in establishing the diagnosis. Sialography may demonstrate a leaess tree pattern which is
thought to be caused by compression of the ner ducts by
the hypertrophic acinar cells. Splaying of the ducts within
the enlarged gland may be seen, with the ducts appearing
normal. In early stages of the disease however, there may
be no sialographic changes. CT scan of the parotids may
show a bilateral enlargement of the parotid glandular
parenchyma with increased glandular density, brosis
or fatty inltration that are characteristic of advanced
287

Section IV Diseases of Specific Structures

changes. CT is non-specic. The changes could be misconstrued for a lipoma; however, the absence of a brous
capsule is helpful in differentiating between these conditions; ultrasound and MRI are useful and non-invasive
approaches.
Histopathology
The histopathological report of a salivary gland biopsy
will reveal hypertrophy of the acinar cells, sometime 23
times greater than normal size. The nuclei are displaced to
the cell base, and the cytoplasm is engorged with zymogen
granules. Significant inflammation is not observed.
Treatment
Therapy will include psychological counseling with an
eventual goal of cessation of vomiting. This may result in
a gradual reduction of the salivary gland enlargement.
Pilocarpine hydrochloride drops have shown efficacy in
reducing parotid gland enlargement in bulimic patients. In
cases refractory to treatment, parotidectomy may be considered to improve unacceptable esthetics in patients with
bulimia.

Sialadenosis Associated with Alcoholic


Cirrhosis
Clinical features
Salivary gland enlargement, usually the parotid glands,
may occur in some patients who ingest large quantities of
alcohol on a long-term basis with resultant liver damage.
The enlargement results from an ethanol-produced peripheral autonomic neuropathy that causes disordered salivary metabolism and secretion. Increased intracytoplasmic
zymogen granules within the acinar cells are believed the
cause of parotid enlargement.
Diagnosis
In alcohol associated sialadenosis, 4060% of the adult
patients with hepatic damage presented with parotid
enlargement. The histopathology of parotid glands reveals
an increase in fatty infiltration, edema and fibrosis without
inflammation. Diagnosis would be assisted by the patients
history of alcohol intake. The dentist could request liver
enzymes and bilirubin tests to aid in making the diagnosis.
Elevated levels would prompt the dentist to refer the patient
to an internal medicine specialist for evaluation and a
radiologist for imaging.
Diagnostic imaging
On CT, the parotid will demonstrate increased density with
time, as the fat is replaced with increased acinar hypertrophy.

288

Treatment
Treatment should focus on the underlying liver disease as
well as the oral complications. When the liver disease is
managed, the parotid glands may reduce somewhat in
size. In addition to sialadenosis, the dentist should also be
aware of salivary changes that increase caries risk susceptibility. The parotid gland flow rate in patients with alcoholic cirrhosis has been reported to be less than flow rates
in healthy controls. Diminished buffer capacity and less
attention to oral hygiene will put the patient at increased
risk for dental decay. In addition, patients who consume
large quantities of wine will have increased risk for dental
erosion due to the erosive potential of wines due to their
acidity. The pH of wine is reported to range from 3.0 to 3.8
and the pH at which enamel dissolves is reported to be pH
of 5.0 to 5.7. Treatment will include patient education and
complete dental evaluation.

Diabetes Mellitus
Clinical features
Diabetes mellitus is a disorder of carbohydrate metabolism mediated through decreased production of insulin
or tissue insensitivity to the effects of insulin, resulting
in hyperglycemia. Two types of presentations are recognized, although overlap is seen. Type I is characterized by
a lack of insulin production and is commonly diagnosed
during childhood, and Type II may present in obese children and adults, due to decreased sensitivity to insulin.
The complications include kidney failure, blindness, neuropathies, and atherosclerosis. Oral symptoms may include
dry or burning mouth, gingival inflammation. Sialadenosis has been reported in diabetes mellitus. The sialadenosis is believed due to an autonomic neuropathy, as in
alcoholism and nutrition-induced sialosis. With autonomic disturbances in sympathetic innervation, alteration
in protein synthesis occurs. Cytoplasmic swelling develops
from engorgement by intracytoplasmic zymogen granules. As a result, the parotid acini may double in size
(hypertrophy) resulting in clinically obvious parotid gland
enlargement.
Diagnosis
Long-standing, bilateral, painless enlargement of the
parotid glands may be observed. These are soft in consistency and follow the outline of the parotid glands, without nodularity. Milking the parotid glands may reveal
fluid of normal volume and consistency. Lower resting
and stimulated saliva flow rates in diabetics versus normal
controls have been reported as well. Levels of calcium are
increased and salivary magnesium, zinc and potassium
are reduced.

Chapter 11 Diseases of Salivary Glands

Diagnostic imaging
CT scan may show enlarged parotid glands without masses,
but demonstrating decrease in density due to significant
fat infiltration of the gland.
Histopathology
The histopathology associated with parotid gland biopsies
of diabetic patients when compared with those from alcohol associated sialadenosis is characterized by an increased
number of lipid intracytoplasmic droplets in the acinar
and ductal cells, and abundant adipose infiltration in the
stroma.
Treatment
While proper glycemic control should be the treatment goal,
this does not result in a significant reduction in the parotid
enlargement. Cosmetic improvement may be obtained with
gland removal, but the riskbenefit ratio must be considered.

Medication-induced Sialadenosis
Medication-induced sialadenosis has been reported for
a number of medications that affect the autonomic nervous system. Antihypertensive agents, psychotropic drugs,
-adrenergic agents, and bronchodilators have been implicated. Mauz et al reported a case were valproic acid was
associated with bilateral parotid and submandibular gland
sialadenosis.

Orofacial Granulomatosis
Clinical features
Orofacial granulomatosis was first introduced in 1985
by Wiesenfeld and encompass a spectrum of clinical presentations that share common histopathologic findings
of non-caseating giant cell granulomas. The conditions
included in this category are MelkerssonRosenthal syndrome, cheilitis granulomatosa, Crohns disease, sarcoidosis, and tuberculosis. Clinical presentation will vary, but
the most frequent site affected is the lips. Patients present
with a non-tender, persistent enlargement of the upper or
upper and lower lips. When this presentation is combined
with fissured tongue and facial paralysis, the clinical condition is called MelkerssonRosenthal syndrome. Involvement of the lips alone is called cheilitis granulomatosa.
Signs and symptoms include edema, erosions, paresthesia
or taste alterations.
Histopathology and diagnosis
The diagnosis is confirmed upon characteristic histopathologic findings. Scattered aggregates of non-caseating

granulomatous inflammation are found, often surrounding vessels. Granulomas contain histiocytes and multinucleated giant cells. Special stains for fungal organisms and
acid-fast bacteria are negative. No foreign bodies or inclusions are identified in the tissue.
Treatment and prognosis
Upon receiving the histopathologic findings, the clinician
must determine the initiating cause. Treatments have included
intralesional corticosteroids, radiotherapy, sulfasalazine,
hydroxychloroquine sulfate, azathioprine, cyclosporine A,
methotrexate, metronidazole, and other antibiotics. Most
clinicians treat the lips with intralesional corticosteroids
with variable success. Spontaneous remissions occur as
well. The prognosis is variable as there is no clearly effective treatment to date.

Sarcoidosis
Sarcoidosis is an immune-mediated multisystem disease
of unknown origin, characterized by the presence of epithelioid non-caseating granulomas in the involved organs.
Sarcoid granulomas are commonly encountered in the
lungs, with lymph node involvement, but may be seen in
many other sites. Sarcoidosis may also affect the heart,
liver, spleen, bones, skin, eyes, lymph nodes, parotid glands
and the oral cavity and may first manifest in the oral and
maxillofacial region. The disease occurs worldwide and
may affect either gender. Geographically, there appears
to be a higher incidence among central and northern
Europeans. It usually arises in the 2nd to 4th decades of
life, with a slight female predominance. In the United States,
sarcoidosis primarily affects African Americans, who tend
to have more acute symptoms, extrapulmonary manifestations and higher mortality rate at an earlier age compared
to whites. The most prominent manifestation of the disease involves the lungs with acute dyspnea, cough, and
chest pain being common symptoms. Chest radiographs
reveal bilateral hilar lymphadenopathy, diffuse parenchymal infiltrates or both. Less commonly, sarcoidosis develops slowly over months or years, especially among whites.
In some cases, patients have no symptoms, and the disease
is discovered on routine chest radiographs. Mortality rates
are similar among races. Approximately, one-fourth of
those with chronic sarcoidosis die of respiratory failure as
reported by Keller. Skin lesions occur nearly 25% of the
time. These often appear as chronic, violaceous indurated
lesions that are termed lupus pernio and frequent the nose,
ears, lips and face. Symmetric elevated indurated purplish
plaques are also commonly seen on the limbs, back and
buttocks. Scattered, non-specific, tender erythematous nodules known as erythema nodosum, frequently occur on
the lower legs.

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Section IV Diseases of Specific Structures

Enlargement of the major salivary glands may be the


rst sign of the condition. Diagnosis can be difcult and
prolonged due to the non-specic symptoms. Examination
may reveal bilateral parotid and submandibular gland
enlargement of recent onset, asymptomatic or mildly symptomatic, and rm and sometimes nodular upon palpation. Facial nerve involvement at presentation may be
mistaken for malignancy. Glandular size does not uctuate upon eating. Milking the parotid glands may demonstrate delayed ow and sialometry may be below normal.
The inltration of major salivary glands and subsequent
xerostomia predispose patients to dental decay and fungal
infections. An analysis of 45 published cases as reported
by Blinder et al revealed an age range between 5 and
69 years, with highest prevalence between 30 and 40 years.
The study reported lesions in the jaws, buccal mucosa, palate, lips, gingiva, and oor of the mouth. Sarcoid lesions
in the buccal mucosa and tongue present as submucosal
nodules and indurations or supercial ulcerations. In gingival lesions, erythematous swelling is generally seen with
some supercial ulcerations in the anterior labial gingiva.
Lesions in the oor of the mouth may present as ranulas.
In many cases, the lesions in the buccal mucosa, gingiva
and tongue were the rst clinical manifestation of the disease. Bony jaw lesions appear as diffuse, poorly dened
radiolucencies which may be associated with tooth mobility. Lesions in maxilla, mandible and condyle have also
been reported.
Histopathology and laboratory
investigations
Because the differential diagnosis of oral dryness and
bilateral parotid enlargement would include sarcoidosis,
SS, MALT lymphoma, sialadenosis, Warthins tumor, and
HIV-associated salivary gland disease, biopsy of the
enlarged glands is sometimes required. The histopathologic
findings from salivary gland biopsy usually demonstrate
non-caseating granulomas. Tightly clustered aggregates of
epithelioid histiocytes are present with a surrounding rim
of lymphocytes, mixed with Langhans giant cells. The granulomas often contain laminated basophilic calcifications
known as Schaumann bodies or stellate inclusions known
as asteroid bodies. However, neither is specific for sarcoidosis. The differential diagnosis for granulomatous diseases
would include infectious agents such as mycobacteria,
fungi, bacterial and parasitic organisms, hypersensitivity
to environmental agents, and other autoimmune disorders
such as Wegeners granulomatosis.
Referral to appropriate physicians to evaluate the
lungs, heart, central nervous system, eyes, skin and lymph
nodes would be required for a comprehensive diagnostic
evaluation and management. The serum angiotensinconverting enzyme (sACE) is considered a diagnostic tool

290

for sarcoidosis. Secretion of angiotensin-converting enzyme


by granuloma-forming epithelioid cells results in elevated
serum levels in 8090% of cases. However, this is supportive and non-diagnostic for sarcoidosis. When bone lesions
occur, hypercalcemia may be observed. Other laboratory
ndings in sarcoidosis might include anemia, leucopenia,
thrombocytopenia, and an elevated erythrocyte sedimentation rate.
Treatment
Treatment will be determined by the onset and course of
the disease. Spontaneous regression is common. In approximately 60% of patients, the symptoms resolve spontaneously within 2 years without treatment. Of those affected,
one-fifth can be treated with corticosteroids. Those with
refractory disease may be treated with methotrexate, azathioprine, and cyclophosphamide which will impact dental
care. A recent refractory case was successfully treated with
infliximab. A small percentage of patients die of pulmonary, cardiac or CNS complications. Consultation with the
physician is essential for quality dental care.

SALIVARY GLAND TUMORS


Salivary gland tumors represent 23% of all head and
neck neoplasms. Salivary gland neoplasms may be either
benign or malignant. Almost 80% of salivary gland neoplasms occur in parotid glands; and two-thirds to fourfifths of the parotid tumors are benign. Nearly half of the
submandibular gland tumors are malignant and up to 80%
of tumors of the minor salivary glands are malignant.
In general, the smaller the salivary gland, the greater is
the probability of malignancy. Tumors of the sublingual
gland are rare and comprise approximately 1% of all salivary gland neoplasms; however, the majority of sublingual gland tumors, 7090%, are malignant. Minor glands
are a common site for salivary tumors, and may involve
the palate, buccal mucosa, and labial mucosal glands.
These tumors comprise approximately 1020% of salivary
gland tumors, with nearly half being malignant. Clinical
presentation and behavior will vary with each specific type
of tumor. Diagnosis will depend on clinical presentation,
imaging, and the distinctive histopathology. Fine-needle
aspiration (FNA) technique has been used to identify salivary gland neoplasms, but with mixed performance. A
retrospective analysis as reported by Hughes et al found
false-positive rates with benign lesions and malignant
cases with false-negative rates. These were most commonly associated with lymphoma, actinic cell carcinoma,
low-grade mucoepidermoid carcinoma, and adenoid cystic
carcinoma.

Chapter 11 Diseases of Salivary Glands

BENIGN TUMORS

Figure 25

Pleomorphic Adenoma (Benign Mixed Tumor)


Clinical features
The pleomorphic adenoma or benign mixed tumor is the
most common salivary neoplasm and accounts for over
half of the tumors in the parotid and submandibular glands.
The name mixed tumor comes from the morphologic
complexity and differentiation of tumor cells which vary
between tumors and within the same tumor. While high in
variability of cell type, the cells are rarely pleomorphic.
While most common in the parotid gland, pleomorphic
adenomas may occur in any major gland or in the minor
salivary glands. Figure 25 shows a pleomorphic adenoma
of the parotid gland with elevation of the ear lobe. Onset is
commonly between the 4th and 6th decades, but they may
occur in young adults and children. There is a slight female
predilection. Facial nerve involvement demonstrated by
facial nerve paralysis is rare. The tumor presents as a
slow-growing, painless, rm and non-tender mass that is
mobile in early stages. The tumor may have intermittent
growth periods. As size increases, the tumor becomes more
irregular and nodular upon palpation. The overlying skin
seldom ulcerates. Local discomfort is noted with an
increase in size. The intraoral site of preference is the hard
palate (Figure 26) and sometimes the lip.

Pleomorphic adenoma of the parotid gland showing elevation


of the ear lobe. Courtesy: Dr Ajit Auluck

Figure 26

Diagnostic imaging
Sialography demonstrates displacement of the ducts around
the benign tumor which itself is well delineated with
definitive margins (ball-in-hand appearance). CT shows a
similar picture, with a higher degree of attenuation within
the tumor mass that demonstrates homogeneous density.
A lobulated appearance is also not unusual. The margins
may appear vague if there is associated inflammation
or hemorrhage. Differentiation from a malignant lesion
becomes difficult. Occasionally, the mass appears with lower
attenuation similar to a cyst. A mixed appearance is also
noted if cystic change or necrosis exists. Bleeding within
the tumor mass can result in the presence of increased
attenuation foci within the gland. Dystrophic calcifications are not uncommon. Figure 27A, B demonstrates the
radiographic features of a persistent pleomorphic adenoma
on contrast CT. Figure 28 demonstrates an axial plain CT
scan of a pleomorphic adenoma of the parotid gland.
Figure 29 shows a parotid gland pleomorphic adenoma via
an axial CT scan heterogeneously enhancing post contrast.
MRI, on the other hand, can clearly demonstrate the benign
nature of the lesion with distinct margins. Most often, the
apparent lobulation noted in CT is not noted, with the
mass appearing solitary. The mass presents with a low T1
weighted and high T2 weighted intensity consistent with

Pleomorphic adenoma. Large dome-shaped firm sessile


swelling of the hard palate. The lesion had eroded palatal
shelf bone and was fairly destructive. The patient reports
that the lesion had been present more than 2 years.
Courtesy: Dr Indraneel Bhattacharyya

the nature of its contents and constitution. Bleeding foci


appear with higher signal intensity on both types of images.
Necrosis, on the other hand, appears with low T1 signal
intensity and high T2 intensity. Larger lesions can be inhomogeneous. A low intensity capsule can be seen on T2
weighted studies and on fat-suppressed, contrast enhanced
T1 weighted images. This feature may not be seen with
recurrences as the capsule may have been penetrated at the
time of previous surgical intervention. Presence of calcific
foci is difficult to appreciate. The tumor exhibits moderate

291

Section IV Diseases of Specific Structures

Figure 27
A

Persistent but stable, known pleomorphic adenoma in the left prestyloid parapharyngeal space. Courtesy: Dr Madhu Nair

Figure 28

Axial plain CT scan of pleomorphic adenoma of


parotid gland. Courtesy: Dr Ajit Auluck and
Dr Chandrakant Shetty

solid contrast enhancement. Recurrent pleomorphic adenomas may be multifocal, along with malignant tumors
such as the acinic cell carcinoma and oncocytoma.
Referral to a radiologist plays an essential role in diagnosis and localization of salivary gland tumors in the major
glands. Ultrasonography results in generation of hypoechoic
areas within a well-dened homogeneous mass. Detection
of deep lobe tumors is difcult using ultrasonography.
292

Figure 29

Axial CT scan showing heterogeneously enhancing


post-contrast pleomorphic adenoma of parotid gland.
Courtesy: Dr Ajit Auluck and Dr Chandrakant Shetty

Histopathologic features
The pleomorphic adenoma is usually a well-circumscribed,
encapsulated tumor, composed of a mix of glandular epithelium and myoepithelial cells within a hyalinized, eosinophilic, mesenchymal stroma. The epithelium may form
ducts, cystic structures, and islands or sheets of cells. Myoepithelial cells often comprise a large percentage of the

Chapter 11 Diseases of Salivary Glands

Figure 30

carcinoma ex pleomorphic adenoma. Malignancy will be


further discussed in the section on malignant salivary
gland tumors.
Monomorphic adenoma

Pleomorphic adenoma, histopathologic microscopic image


of pleomorphic adenoma stained with hematoxylin and
eosin (magnification 20). Proliferation of islands, strands
and duct-like formations of myoepithelial cells in a
cartilaginous and fibrous connective tissue stroma.
Courtesy: Dr Indraneel Bhattacharyya

tumor cells with variable morphology. Some demonstrate


eccentric nuclei and eosinophilic hyalinized cytoplasm
resembling plasma cells, called plasmacytoid myoepithelial cells. Areas may include chondroid material and even
osteoid adjacent to ductal epithelium and myoepithelial
cells (Figure 30). Tumor cells may be found in the connective tissue capsule from incomplete capsule development,
capsular penetration, pseudopodia, and satellite nodules.
Treatment and prognosis
The accepted treatment for pleomorphic adenomas is surgical excision. For tumors occurring in the superficial lobe
of the parotid gland, excision of the tumor and superficial
parotidectomy with conservation of the facial nerve is recommended. For deep lesions, parotidectomy is usually
necessary. Submandibular gland tumors are treated by total
removal of the gland with the tumor. Tumors of the hard
palate are generally excised, with incision down to the
periosteum. The tumor and overlying mucosa are removed
and submitted for histopathological examination. In very
rare situations, the pleomorphic adenoma can be intraosseous, arising from ectopic salivary tissue. Clinically and
radiographically, these may resemble lesions of odontogenic
origin, such as a lateral periodontal cyst. With complete
removal of the tumor, prognosis is excellent. Recurrence is
generally associated with incomplete removal and seeding
of the primary tumor. Benign pleomorphic adenomas may
become malignant. This transformation may take place in
long-standing untreated tumors or in recurrent ones. In
addition, the malignant component may be present at the
initial excision. These rare malignant lesions are termed

The term monomorphic adenoma was originally used to


distinguish the pleomorphic adenoma from a group of
benign salivary gland tumors composed of more uniform
cells or a single cell type. Currently, the term is used in
more than one classification scheme with differing interpretations and significance. Basal cell adenomas and canalicular cell adenomas have been termed monomorphic
adenomas due to their uniform histopathology. Due to confusion in nomenclature, the term monomorphic adenoma
should be replaced with the specific name of the adenoma
being discussed. The following sections will describe these
specific types.

Canalicular Adenoma
Clinical features
The canalicular adenoma is an uncommon tumor that
occurs almost exclusively in the minor salivary glands and
has a marked predilection for the upper lip. The buccal
mucosa is the second most common location. The tumor
appears in older adults and demonstrates a female predilection. The clinical presentation is a slowly growing painless mass that ranges from several millimeters to 2 cm.
It may be firm or fluctuant to palpation. The overlying
mucosa may be bluish or normal in color. It may be multifocal and have multiple nodules in the upper lip or
buccal mucosa.
Histopathology
The tumor is named so for its histologic pattern which consists of uniform columnar or cuboidal cells forming canallike ductal structures. The cells may appear in a double row
and enclose cystic spaces of varying size. The spaces are
filled with an eosinophilic coagulum, and the supporting
stroma is loose and fibrillar with fine vascularity. Large
cystic spaces may be created and the epithelium may demonstrate papillary projections into the lumina.
Treatment and prognosis
Treatment consists of surgical excision and the outcome is
very good. Recurrence is rare.

Basal Cell Adenoma


Clinical features
The basal cell adenoma was first reported as a distinct
lesion by Kleinsasser and Klein in 1967. The basal cell
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Section IV Diseases of Specific Structures

adenoma is an uncommon, benign salivary tumor which


primarily occurs in the parotid gland. The glands of upper
lip and buccal mucosa are the second most common site.
It usually appears as a firm and mobile slow-growing
mass. The tumor may present at any age, but is most common in older adult females. It presents as a slowly growing
freely movable mass, with a clinical appearance similar
to a pleomorphic adenoma and other parotid neoplasms.
A special subtype, the membranous basal cell adenoma
often appears with coexisting dermal cylindromas of the
scalp, often occurring in combination with skin appendage tumors. Multiple bilateral tumors may develop within
the parotids.
Diagnostic imaging
Basal cell adenomas of the parotid gland often present as
small well-marginated tumors and appear as masses with
central large cysts or solid masses with microcytes on CT
and MRI scans. On 2-phase helical CT scans, the enhancement patterns and imaging architecture of basal cell adenomas are related to the histologic subtype of the tumor.
On the 2-phase CT scan, the histologically solid-looking
tumors show marked contrast enhancement on the early
phase and subsequent decrease in attenuation on the
delayed phase. Lee et al described that tumors with large
cystic areas showed gradual and additional enhancement
on the delayed phase and were classified as tubular or
trabecular subtype on histopathologic evaluation.
Histopathology
The tumor is encapsulated, and it is named so because of
basaloid appearance of the tumor cells. The basaloid
hyperchromatic peripheral cells show a palisaded arrangement, similar microscopically to a basal cell carcinoma.
The central cells have paler staining nuclei. Cells may also
be in ribbons or cords. The trabecular subtype demonstrates narrow cord-like epithelial strands, and the tubular
subtype is characterized by the formation of small round,
duct-like structures. The membranous basal cell adenoma
is characterized by palisading of peripheral cells and an
excessive hyaline basal membrane. Multiple large lobular
islands of tumor give the appearance of a jigsaw puzzle.
The islands are surrounded by a thick layer of hyaline
material, similar to the microscopic appearance of the
dermal cylindroma.
Treatment and prognosis
Treatment consists of surgical removal and recurrence is
rare, with one exception. Likely owing to its multifocal
nature, the membranous subtype has a higher recurrence
rate than other subtypes. Malignant basal cell adenomas
(basal cell adenocarcinoma) may arise de novo or from
malignant change of pre-existing basal cell adenomas.
These have a good prognosis.
294

Papillary Cystadenoma Lymphomatosum


(Warthins Tumor)
Clinical features
Warthins tumor is a benign neoplasm that occurs
almost exclusively in the parotid gland. It represents the
second most common benign parotid tumor. The pathogenesis is unclear. The traditional theory suggests that
they arise from heterotopic salivary gland tissue in parotid
lymph node. Aguirre et al suggested that they develop
from a proliferation of salivary gland ductal epithelium
that is associated with secondary formation of lymphoid
tissue. The lesion is a slow-growing, painless nodular
mass of the parotid and may be firm or doughy upon palpation. While uncommon, they have been reported in the
submandibular and minor salivary glands by Fantasia
and Miller. The onset is generally in the 6th to 7th decade
of life, with males being slightly more commonly affected
than females. Kotwall reported that smokers have eight
times higher risk of developing a Warthins tumor than
non-smokers. Klussmann and workers, in a large series
of 185 patients with Warthins tumor reported that 89%
of the subjects were smokers and 66% were heavy smokers. Bilateral Warthins tumor was seen in 17% of these
patients.
Diagnostic imaging
CT will reveal a well-delineated, homogeneous, noncalcifying mass with a well-defined wall. Cystic appearance is quite common as are multiple lesions. Figure 31A, B
demonstrates the cystic appearance of the lesion on contrast CT. The intrinsic mass demonstrates no evidence of
perineural spread.
MRI demonstrates a homogeneous or inhomogeneous
appearance depending on the size of the tumor and presence of cystic changes. If solid, the lesions appear with
low intensity on T1 weighted images and high intensity
on T2 weighted images. Radionuclide imaging studies
using technetium pertechnetate studies show accumulation of the tracer within the tumor, and is considered diagnostic. Positron emission tomography (PET) also indicates
increased uptake of tracer. The differential diagnosis of
Warthins tumor on MRI includes other benign cystic
lesions. However, Warthins tumor exhibits nodularity of
the cyst wall, whereas other benign cystic lesions tend to
have smooth walls. Conversely, cystic and necrotic malignant tumors tend to be ill-dened. Warthins tumors fail to
enhance, whereas pleomorphic adenomas undergo solid
contrast enhancement.
Histopathology
Histologically, the papillary cystadenoma lymphomatosum is composed of a mixture of ductal epithelium and a
lymphoid stroma. The epithelium is usually a double row
of oncocytes with surrounding cystic spaces. The lining

Chapter 11 Diseases of Salivary Glands

Figure 31
A

Warthins tumor as noted on a contrast CT study reveals a multiseptated predominantly cystic mass within the tail of the
parotid gland on the right side. It is intrinsic to the gland and well below the main trunk of the facial nerve and its
major branches. Courtesy: Dr Madhu Nair

forms papillary projections into cystic spaces. The epithelium is supported by a lymphoid stroma which may demonstrate germinal centers.
Treatment and prognosis
The preferred treatment for Warthins tumor is surgical
removal. Malignant Warthins tumors, carcinoma ex papillary cystadenoma lymphomatosum, have been reported, but
are extremely rare.

Oncocytoma (Oxyphilic Adenoma)


Clinical features
The oncocytoma is a rare salivary gland tumor which usually occurs in the parotid gland (84%), but has been reported
in the submandibular gland and minor salivary glands.
Clinically, it cannot be distinguished from other benign
salivary gland tumors. The name oncocytoma is from the
resemblance of the tumor cells to normal oncocytes, which
are found in salivary glands, respiratory tract, breast, thyroid, pancreas, parathyroid, pituitary, liver and stomach.
The oncocytoma occurs in elderly persons and is somewhat more common in women than in men. The tumor usually measures from 3 to 5 cm in diameter and appears as a
discrete encapsulated mass. It is usually asymptomatic.
Histopathology
Histologically, the oncocytoma is a tumor of ductal cells
that are enriched with mitochondria, giving the cell a
swollen eosinophilic appearance.

Treatment and prognosis


The treatment of choice is surgical excision. It does not
have a high recurrence rate. Malignant transformation is
uncommon.

MALIGNANT TUMORS
Adenocarcinomas of salivary gland origin are quite varied
in their histologic features and clinical behavior. These are
diagnosed based on their microscopic features. The parotid
is the most common site, followed by minor salivary glands.
In the parotid, the lesions are usually firm to palpation
and may produce damage to the facial nerve. The presence
of enlarged lymph nodes raises the suspicion of malignancy, but also occurs in inflammatory conditions. The
presence of nodal metastasis is a poor prognostic indicator. Intraorally, minor salivary glands of the hard palate
are the most common location for adenocarcinomas followed by buccal mucosa, lips and base of tongue.

Mucoepidermoid Carcinoma
Clinical features
Mucoepidermoid carcinoma is one of the most common
malignant salivary gland tumors. It was first described by
in 1945 by Stewart, Foote and Becker. It occurs in individuals from the second to the seventh decade. While it is
rarely seen in the first decade of life, it is the most common malignant salivary gland tumor in children. Some
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Section IV Diseases of Specific Structures

tumors have been associated with a previous history of


radiation therapy to the head and neck region. There are
three grades: low, medium and high. Low-grade tumors
have a limited potential to metastasize to regional lymph
nodes. High-grade tumors tend to be solid rather than
cystic and behave aggressively like a squamous cell carcinoma. Mucoepidermoid carcinoma most commonly presents in the parotid gland where it may initially appear as
a painless swelling. Intraorally, tumors are found in the
palate (Figure 32), buccal mucosa, retromolar area, and
base of tongue. These may present as slowly enlarging,
painless masses. The low-grade lesions contain cysts which
may be filled with mucoid material. These intraoral lesions
may resemble a mucocele, especially when located in the
retromolar area. More high-grade tumors grow rapidly and
produce pain early in the process. Facial nerve paralysis is
a common feature in high-grade tumors. As these tumors
tend to infiltrate surrounding tissue, they may metastasize
to regional lymph nodes.

Figure 32

Mucoepidermoid carcinoma in the hard palate. Well


circumscribed raised lesion of 4 months duration on the hard
palate with large central umbilicated ulceration with rolled
borders. Courtesy: Dr Indraneel Bhattacharyya

Histopathology
Mucoepidermoid carcinoma is composed of cells from stratified squamous lines, mucous cell lines, and a third celltype, the intermediate cell. The mucous cells have abundant
foamy cytoplasm that stains positively with mucicarmine
stain. The epidermoid cells frequently demonstrate features
of squamous epithelium, intercellular bridges, but rarely
show keratinization. The intermediate cell is basaloid in
appearance and may be the origin of the other mucous and
epidermoid cells. A lymphocytic infiltrate is commonly seen.
Low-grade tumors show all cell types. Prominent cyst formation, a high proportion of mucous cells, and minimal
atypia are characteristic features. High-grade tumors consist of solid islands of squamous and intermediate cells,
which can show pleomorphism and mitotic activity. Few
mucus producing cells are present, which allow the
lesion to be confused with a squamous cell carcinoma. The
intermediate-grade tumor shows features that rank in
between the low- and high-grade tumors (Figure 33).
Treatment
Treatment may vary according to the tumor location, grade,
and staging. Surgical removal of the lobe or gland may be
adequate. High-grade or large tumors merit wider resection,
similar to that employed for squamous cell carcinoma. For
patients with evidence of metastatic disease or large highgrade tumors, radical neck dissection may be indicated.
Postoperative radiation therapy may be employed as well.
Prognosis
Patients with low-grade tumors and complete excision
have a good prognosis. Patients with high-grade tumors
have a poorer prognosis. In a large series reported by
Goode et al, most patients (75%) were tumor free after the
296

initial treatment. Twenty-one patients (9%) had local


recurrence only, 12 (5%) demonstrated metastasis and survived, and (11%) died of their disease. Clinical features
associated with metastasis or deaths were more advanced
age, tumor size, and preoperative symptoms. In a recent
series of mucoepidermoid carcinomas of the minor salivary
glands as reported by Triantafillidou et al, immunohistochemical assay of Ki-67 antigen expression correlated with
tumor grade. Prognosis in this series of 15 tumors was a
function of the histological grade, adequacy of excision
and clinical staging.

Intraosseous Mucoepidermoid Carcinoma


Clinical features
Intraosseous mucoepidermoid carcinoma most frequently
appears in the posterior jaws, mandible more frequently
than the maxilla. It has been reported in all ages, from
1 to 85 years. Most cases occur in the 4th and 5th decades.
Diagnosis
The radiographic picture of central mucoepidermoid carcinoma may resemble an ameloblastoma or odontogenic
cyst. Based on radiographic imaging, Inagaki classified
these lesions into three categories: cystic, rarefying, and
infiltrative. He reported that those with the infiltrative
type were histologically poorly differentiated tumors, and
these patients died of their tumors. Radiographic findings
correlated with histologic findings and prognosis in this
limited series. Other salivary lesions that have appeared
centrally in the jaws include pleomorphic adenoma, adenoid cystic carcinoma and malignant mixed tumor.

Chapter 11 Diseases of Salivary Glands

Figure 33

Acinic Cell Adenocarcinoma


Clinical features
Acinic cell adenocarcinoma is a malignant salivary gland
tumor characterized by histologic appearance showing serous
acinar differentiation. The majority of acinic cell carcinomas are found in the parotid gland, and only rarely in the
intraoral minor glands. The age range is broad with a peak
incidence in the third decade of life. Similar to many salivary
gland tumors, it may be a slow-growing mass. In a large
series as reported by Ellis and Corio, tumors were usually
less than 3 cm in diameter and were slow growing. Pain
was a common symptom, but not indicative of prognosis.
Histopathology

Mucoepidermoid carcinoma, histopathology: Microscopic


image of mucoepidermoid carcinoma stained with
hematoxylin and eosin (magnification 20). Large aggregates
of intermediate cells interspersed with cells with clear
cytoplasm and mucous cells. The cellular aggregates are
arranged in clusters separated by thin fibrous connective
tissue septa. The peripheral cells appear more epidermoid
with reduced cytoplasm and hyperchromatic nuclei.
Courtesy: Dr Indraneel Bhattacharyya

Variation in presentation on CT is noted depending on


the degree of differentiation of the tumor mass. Welldifferentiated lesions have well-dened margins and may
mimic a benign tumor with or without cystic changes. More
aggressive types have ill-dened margins and show signs
of local tissue destruction. Contrast enhanced CT shows an
inhomogeneous enhancement with well-dened margins.
Poorly differentiated lesions show enhancing mass with
irregular margins and lymphadenopathy. MRI shows inhomogeneous low to intermediate signal intensities on T1
and T2 weighted images. Nuclear medicine studies do not
reveal any tracer uptake. MRI is the recommended imaging modality as perineural spread and deeper involvement
are better delineated. Perineural spread is sometimes noted
along cranial nerve VII.
Histopathology
Most centrally occurring mucoepidermoid carcinomas show
the same variability and grades as found in salivary gland
tumors. Most are low-grade lesions, although high-grade
lesions have been reported as well.
Treatment and prognosis
The treatment for intraosseous mucoepidermoid carcinoma is surgery, sometimes with adjuvant radiation therapy. Radical surgical resection provides a better long-term
prognosis than conservative measures such as curettage.
Metastasis has been reported in a small number of cases.

The acinic cell adenocarcinoma may be composed of cells


that exhibit varying degrees of differentiation, but resemble serous acinar cells. Four growth patterns have been
described: solid, papillary cystic, follicular and micro-cystic.
The micro-cystic variety was most commonly seen in a
large series as described by Ellis and Corio.
Treatment and prognosis
Treatment usually consists of parotid gland lobectomy
or parotidectomy. Submandibular tumors are treated by
removal of the gland. In a recent series as reported by
Hoffman and coworkers, worse survival was associated
with high-grade lesions, age more than or equal to 30 years
and the presence of metastatic disease. Although a better
outcome was not statistically demonstrated for combined
therapy, surgery with irradiation is the most common management in the United States for cases with regional metastases, high-grade, and microscopic positive margins.

Malignant Mixed Tumor


(Carcinoma Ex Pleomorphic Adenoma)
Description and clinical features
Malignant mixed tumors are the malignant counterpart to
the pleomorphic adenoma, or benign mixed tumor. In
many cases, there are no obvious differences in clinical
presentation of benign versus malignant pleomorphic adenomas. The carcinoma ex pleomorphic adenoma is characterized by malignant transformation of the epithelial
component of a previously existing benign pleomorphic
adenoma. Most of these are seen within the parotid gland,
followed by the submandibular gland. These also occur in
the minor salivary glands and sublingual gland. This lesion
affects an older age group than the benign counterpart,
usually occurring around 5070 years of age. The common
clinical presentation is rapid expansion of a long-standing
asymptomatic mass, new onset of pain, paresthesia, and/
or fixation to the skin. Although pain or recent rapid
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Section IV Diseases of Specific Structures

growth is common, cases may present as a painless mass,


similar to a benign lesion. The risk for malignant transformation increases with the duration of the tumor.
Histopathology
The histolopathologic features will vary widely. In some
lesions, the benign areas will be difficult to locate due to
an abundance of malignant areas. In other tumors, the
bulk is benign with small areas demonstrating the malignant features. Areas of the benign pleomorphic adenoma
may be present with areas of malignant changes to the
epithelial component. The changes include hypercellularity,
increased abnormal mitotic activity, areas of hyalinization
and necrosis. The malignant component will demonstrate
extracapsular invasion. Sites of poorly differentiated carcinoma may be found as well.
Treatment and prognosis
Carcinoma ex pleomorphic adenoma is treated by wide excision, often with local lymph node dissection, and adjuvant
radiation therapy. A recent study reported by Chen and
coworkers showed significant improvement in a 5-year
local control from 49 to 75% through the use of postoperative radiotherapy. It was also associated with improvement in survival among patients without evidence of
cervical lymph node metastasis.

Metastasizing Mixed Tumor


Clinical features
The metastasizing mixed tumor is also quite rare. Most
patients have a history of a pleomorphic adenoma which
was excised many years earlier. The majority of cases originate in the parotid gland, but the primary tumor may
occur in the submandibular gland or minor glands. Metastases are most frequently in the bones, lung or regional
lymph nodes.
Histopathology
Both lesions, the initial benign mixed tumor and the tumor
at the metastatic site show histopathologic features of the
benign mixed tumor. Microscopic malignant changes are
not observed.

neck (43%), and lung (36%). The 5-year disease-free survival was 50%. Chemotherapy and radiotherapy were of
limited value.

Adenoid Cystic Carcinoma


Clinical features
Adenoid cystic carcinoma is a common, well-defined
malignant salivary gland tumor that may occur in any
salivary gland. In one series as reported by Jones et al,
nearly half of the tumors arising in the oral cavity occurred
in the hard palate, and the remainder occurred in other
minor glands, the submandibular and parotid glands.
Adenoid cystic carcinoma occurs in the 5th, 6th and 7th
decades of life; rarely before the age of 20. Most series
show an equal gender distribution. In the major glands, it
commonly presents as a slow-growing swelling or mass.
The patient may be aware of the lesion for months or years.
Pain intensity may grow as the lesion progresses. Fixation
to deeper structures occurs in later stages. As with other
malignant salivary gland tumors, involvement of the facial
nerve is a serious finding. Adenoid cystic carcinoma of the
intraoral minor glands presents as a swelling or mass, usually in the palate. Eventually, pain and ulceration develop.
Jones et al described one study that reported a better survival rate if tumors were in the hard palate versus other
sites in the head and neck. The specific survival rate was
40% at the age of 20 years. Adenoid cystic carcinoma may
also appear in the tongue, and centrally in bone.
Histopathology
Several histologic types are recognized. The classic pattern,
the cribriform type, is recognized by the arrangement of
tumor cells in the Swiss cheese pattern. Tumor cells have
deeply basophilic nuclei with scant cytoplasm (Figure 34).
Other patterns include the tubular type and solid type. In
the tubular pattern, tumor cells form multiple small ducts
or tubules within a hyaline stroma. The solid variant is
composed of sheets of tumor cells, with cellular pleomorphism and mitotic activity, and focal necrosis. It is associated with a poorer prognosis than the cribriform type.
Perineural invasion is a highly characteristic feature of
adenoid cystic carcinoma, but perineural invasion is seen
in other salivary malignancies, particularly the polymorphous low-grade adenocarcinoma.

Treatment and prognosis


Treatment consists of surgical excision of the primary tumor
and the metastatic sites. In a recent report of a review of
44 cases as reported by Nouraei, most patients had local
recurrences before metastasis. The mean presentation-tometastasis latency was 16 years. Bone was the most common site for metastases (45%), followed by the head and

298

Diagnostic imaging
Parotid lesions appear with well-defined margins while
minor gland masses have ill-defined margins. Retrograde
spread along facial or mandibular nerve is not uncommon.
Contrast MRI is the optimal imaging modality to visualize
such extension. Varying degrees of nerve involvement

Chapter 11 Diseases of Salivary Glands

Figure 34

Polymorphous Low-Grade Adenocarcinoma


Clinical features
Polymorphous low-grade adenocarcinoma (PLGA) was first
described in 1983 and termed lobular carcinoma due to
its resemblance to lobular carcinoma of the breast. It is a
low-grade salivary gland tumor that occurs primarily in
the minor salivary glands. Common presentation is a palatal mass that may range in size from 0.4 mm to 6 cm. The
average age of occurrence in a large series as reported by
Castle et al was 58 years with a range from 23 to 94 years.
The tumors were infiltrative and characterized by a polymorphous growth pattern.
Histopathology

Adenoid cystic carcinoma, histopathology:


Microscopic image of adenoid cystic carcinoma stained
with hematoxylin and eosin (magnification 20). Invasive
islands of neoplastic epithelial cells forming duct-like
structures containing a pale mucoid material imparting
the classic Swiss cheese appearance. The tumor cells are
basaloid in appearance with hyperchromatic basophilic
nuclei and scanty eosinophilic cytoplasm.
Courtesy: Dr Indraneel Bhattacharyya

can be imaged using MRI. CT also detects some changes


related to nerve involvement. Widening of the nerve
canal and obliteration of fat at the cranial foramina is
evident on contrast CT but early subtle changes are not
discernible.
Treatment and prognosis
Surgical excision is the treatment of choice with radiotherapy as it metastasizes to the lymph nodes. Metastatic
spread most commonly involves the lungs and bones. In
addition, metastatic spread to the kidney and liver has
been reported. Regardless of the treatment modality, the
overall prognosis is poor.

The neoplastic cells are isomorphic with vesicular nuclei.


Individual tumors may demonstrate multiple patterns,
including solid, ductotubular, cribriform, trabecular, and
single file growth. The histologic features may resemble
adenoid cystic carcinoma. Neurotropism is frequently
identified. Mitotic activity is not prominent.
Treatment
Wide local excision is the treatment of choice. Local recurrences may occur despite having negative margins after
surgery. Local recurrence may appear 15 years after initial
surgery. Regional nodal metastasis and lung metastasis
have been reported by Pogodzinski et al, 20 years after the
procedure. These occurrences support the need for prolonged follow-up. Recently, PLGA was reported by RuizGodoy et al in the parotid gland in a 60-year-old male.
Treatment included a superficial parotidectomy and postoperative radiotherapy (46 Gy). Transformation from PLGA
in the palate to a high-grade carcinoma has been reported
as well.
Prognosis
Conservative, but complete surgical excision is the treatment of choice for these tumors, with a reported 97% survival rate. While these have a tendency to recur, the metastatic
potential is low.

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SECTION

Cysts and Tumors


of Orofacial
Region

12 Cysts of Orofacial Region


13 Tumors of Orofacial Region
14 Oral Cancer

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CHAPTER

Cysts of Orofacial Region


Ravikiran Ongole, Sunanda C, NVS Sekhar
Reddy, Joanna Baptist, Thomas Zachariah

Classification of Cysts of Orofacial Region

Theories of Cyst Expansion

Odontogenic Cysts
Gingival Cyst of Infants
Eruption Cyst
Dentigerous Cyst

Lateral Periodontal Cyst


Botryoid Odontogenic Cyst

Pseudocysts
Traumatic Bone Cyst
Aneurysmal Bone Cyst
Stafnes Bone Cyst

Odontogenic Keratocyst
Gingival Cysts of Adults

Inflammatory Cysts
Periapical Cyst
Residual Cyst
Paradental Cyst
Mandibular Infected Buccal Cyst

Orthokeratinized Odontogenic Cyst

12

Cysts of Soft Tissues of Mouth, Face and Neck


Anterior Median Lingual Cyst

Calcifying Epithelial Odontogenic Cyst

Glandular Odontogenic Cyst

Thyroglossal Duct Cyst

Non-odontogenic Cysts

Lymphoepithelial Cyst

Nasopalatine Duct Cyst

Cystic Hygroma

Nasolabial Cyst

Dermoid, Epidermoid and Teratoid Cysts

Mid-palatal Raphe Cyst of Infants

Parasitic Cysts

Cysts of Maxillary Antrum and Salivary


Glands

The word cyst is derived from Greek word kystitis meaning bladder. Kramer (1974) defined cyst as a pathological
cavity having fluid, semifluid or gaseous contents and
which is not created by the accumulation of pus. It is frequently, but not always, lined by the epithelium. Cysts may
arise due to trauma, inflammation and degeneration or
retention. They are called true cysts if lined by epithelium
and, pseudocysts (false) if not lined by epithelium. During
the initial stages, when the cysts are small they are usually
asymptomatic. Secondary infection may result in the
formation of abscess, cellulitis, osteomyelitis and subsequent sinus formation. As the cyst enlarges it may cause

Nasopharyngeal Cyst

Cysticercosis
Hydatid Cyst
Trichinosis

displacement of roots of teeth, resorption of roots, paresthesia, expansion of the cortical plates and eventually
result in pathologic fracture of the jaw.

CLASSIFICATION OF CYSTS OF
OROFACIAL REGION
1.
2.
3.

True cysts of the oral cavity (odontogenic and nonodontogenic)


Pseudocysts of the oral cavity
Cysts of the associated structures of the orofacial region.

303

Section V Cysts and Tumors of Orofacial Region

True Cysts of Oral Cavity (Lined by Epithelium)

Figure 1

Developmental cysts
Odontogenic cysts
Gingival cyst of infants
Eruption cyst
Dentigerous cyst
Odontogenic keratocyst*
Orthokeratinized odontogenic cyst
Gingival cyst of adults
Lateral periodontal cyst and botryoid odontogenic
cyst
Calcifying odontogenic cyst
Glandular odontogenic cyst
Non-odontogenic cysts
Nasopalatine duct cyst
Nasolabial cyst
Mid-palatal raphe cyst of infants
Inflammatory cysts
Radicular cyst
Residual cyst
Paradental cyst
Buccal bifurcation cyst

Pseudocysts of Oral Cavity (Not Lined by


Epithelium)

Aneurysmal bone cyst


Stafnes bone cyst
Traumatic bone cyst

Cysts of Associated Structures of Orofacial


Region

Cysts of the salivary glands


Cyst associated with the maxillary antrum
Anterior median lingual cyst
Nasopharyngeal cyst
Thyroglossal duct cyst
Branchial cleft cyst
Cystic hygroma
Parasitic cysts

*Odontogenic keratocyst (OKC) has been redesignated as keratocystic


odontogenic tumor by the World Health Organization (WHO). OKC should
not be included in the classification of cysts anymore.

THEORIES OF CYST EXPANSION


Malcolm Harris (1975) summarized various theories that
explain cyst expansion. Mural growth theory, hydrostatic
enlargement, and role of bone resorbing factors are the
theories that have been proposed by various authors to
explain enlargement of cysts.
304

Enlargement of the cyst at the peripheries


due to active division of the cells of the epithelium
lining the cyst

Mural Growth Theory


The mural growth theory is explained by two propositions.
1. Peripheral cell division: It is proposed that the cyst
enlarges at the peripheries because of active division of
the cells of the epithelium lining the cyst (Figure 1). It is
believed that the division of these cells is a response to
any irritating stimulus. The theory further suggests that
once the stimulus is withdrawn the cyst regresses in size.
This theory has not found many supporters as cyst regression will result in irregular inner surface of the cyst as the
bone surrounding the cyst offers resistance. One should
remember that the contents of the cyst will support the
cystic lining and it can cause rapid resorption of surrounding bone to accommodate the enlarging cyst.
2. Accumulation of cellular contents: This theory was
proposed by Kramer (1974) to explain the enlargement of
OKCs. He proposed that as mural squames are shed off the
lining epithelium they accumulate, thereby increasing the
cyst volume. The sites of expansion and growth are represented by finger-like projections which are zones of active
cell division or proliferation (Figure 2).
It is also believed that these nger-like extensions are
formed because keratocysts have very poor bone resorbing
properties. Hence, they proliferate along the cancellous
bone which is less dense than the cortical bone. This explains
the fact why keratocysts very rarely cause expansion or
resorption of the cortical plates.
Kubota et al (2000) studied the role of interleukin-1
alpha (IL-) and matrix metalloproteinase-9 (MMP-9) in
the expansion of odontogenic cysts. They found that an active
form of MMP-9 was present in OKC uids more frequently
than dentigerous cyst and radicular cyst uids. However,
proMMP-9 was present in all cyst uids.

Chapter 12 Cysts of Orofacial Region

Figure 2

enters and accumulates within the cyst thereby aiding its


enlargement.

Role of Bone Resorbing Factors


Harris et al (1973) proposed that cyst tissue (capsule) contains a combination of prostaglandins E2 and E3, which
are considered very potent bone resorbing factors. It is
believed that the leukocytic and bone resorbing factors
aid in bone resorption. It is believed that the keratocyst
secretes comparatively lesser amount of bone resorbing
factors per unit surface area compared to other cysts (periodontal cyst, radicular cyst). This explains the burrowing
nature or intramedullary growth of the keratocyst.

ODONTOGENIC CYSTS
Finger-like projections which are zones of active cell
division or proliferation

Kubota et al (2002) in their study showed that interleukin


(IL)-1 stimulates enzymatic degradation of the extracellular matrices of the bone around the cysts. This induces
expansion of OKC.
Oka et al (2005) studied the effects of positive intracystic uid pressure in OKCs. They proposed that the positive intracystic pressure may play a crucial role in OKC
growth via stimulating the expression of IL-1 in epithelial
cells.

Hydrostatic Enlargement of Cysts


It has been proposed that accumulation of fluids within
the cystic cavity will cause expansion of the cyst wall. The
fluid accumulation can occur from secretion by the goblet
cells that line the follicular cysts or by transudation or
exudation from capsular capillaries in periodontal cysts
as proposed by Main (1970) and hemorrhage in follicular
and periodontal cysts as proposed by Harris and Pannell
(1973).
James (1926) and Tratman (1939) proposed the osmotic
theory or dialysis to explain hydrostatic enlargement of cysts.
The cyst wall and the capillaries in the cystic capsule are
made up of high molecular weight proteins like brin and
2-globulins which aid in increasing the permeability of
the capsular capillaries and the cyst walls.
It was found that the mean osmolality of cystic uid is
10 milliosmoles higher than that of serum. This gradient
helps in the accumulation of all the shed degenerated cells
from the lining of the cyst. As the cyst has inadequate
lymphatic drainage, the uid from the capsular capillaries

The odontogenic cysts are derived from epithelium associated with the development of dental apparatus. It is estimated that odontogenic cysts make up approximately
90% of the jaw cysts. These cysts are generally lined by
stratified squamous epithelium. However, some developmental or fissural cysts in the maxilla will have respiratory
epithelium as the lining.

Gingival Cyst of Infants


Gingival cyst of infants or newborns is an odontogenic cyst
which is developmental in nature. Like the name suggests
these cysts are seen in infants. These cysts are seldom
seen after 3 months of age. They arise from the epithelial
remnants of dental lamina called cell rests of Serres.
Clinically, the cyst is seen on the crest of the maxillary and
mandibular dental ridges and appears creamish white.
These cysts are usually minute in size and rarely exceed
3 mm in diameter and commonly occur on the maxillary
alveolar ridge.
Histopathological evaluation reveals a keratin lled cyst
lined by parakeratinized epithelium. Gingival cysts in infants
need no treatment as they tend to undergo involution and
disappear. Most cysts tend to rupture spontaneously.

Eruption Cyst
The eruption cyst is a type of soft tissue cyst associated
with erupting teeth. It surrounds the crown of a tooth that
has already erupted through bone but impeded by the
overlying soft tissue. Kuczek et al (2003) reported a case
where a boy developed an eruption cyst who was administered cyclosporin A (potent immunomodulatory agent) subsequent to a cardiac transplantation. Cyclosporin A was replaced
with tacrolimus and there was no new cyst formation.
305

Section V Cysts and Tumors of Orofacial Region

The authors proposed that the formation of an eruption


cyst may be an adverse effect of cyclosporin A in children
with erupting teeth.

Figure 3

Clinical features
Eruption cysts are usually seen in childhood. These cysts
are commonly seen in the age groups of 5 and 9 years.
However, Woldenberg (2004) published a case report of
an eruption cyst in the maxilla of a 40-year-old female.
Studies by Anderson (1990), Woldenberg (2004) and
Aguil (1998) show that these cysts are more prevalent in
the maxillary arch. In a study of 24 cases of eruption cysts
by Bodner et al (2004), it was found that eruption cysts
were associated with natal teeth in two cases, with primary
teeth in 10 cases and with permanent teeth in 12 cases.
It was seen that males more commonly presented with
eruption cysts than females (2:1). The primary mandibular
central incisors and the permanent first molars were the
most common site involved. Though most of the eruption
cysts are reported as solitary entities, literature review
reveals report of a patient presenting with multiple eruption
cysts. Ramn Boj and Garca-Godoy (2000) described a
case of a 15-month-old child who had six eruption cysts
simultaneously.
On clinical examination, the cyst is visible as a soft
uctuant mass on the alveolar ridges and may vary in size
from about 1 to 1.5 cm in diameter. It may have the same
coloration of healthy oral mucosa or appear bluish or
bluish black. Eruption cyst histologically mimics dentigerous cyst.

Orthopantomograph (OPG) showing dentigerous cyst


(multilocular) associated with impacted right lower
third molar and a supernumerary tooth displaced
superiorly approximating the sigmoid notch.
Courtesy: Dr NVS Sekhar Reddy

Figure 4

Management
Usually the cysts open up spontaneously. In some children
the overlying soft tissue can be incised to facilitate the tooth
to erupt. Literature reveals that marsupialization is sufficient to manage eruption cysts.

Dentigerous Cyst (Follicular Cyst)


It is an odontogenic cyst formed by the accumulation of
fluid between reduced enamel epithelium and enamel surface. It surrounds the crown of an impacted tooth and is
attached to its neck. The crown of the involved tooth projects
into the cyst lumen. It is estimated that 10% of impacted
teeth are associated with dentigerous cysts. Dentigerous cysts
may also be seen associated with supernumerary teeth and
odontomas.

Orthopantomograph (OPG) showing dentigerous cyst


(unilocular) associated with the right upper third molar.
Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

relatively more predisposed. It grows aggressively and


produces facial asymmetry, bony expansion, displacement
and resorption of teeth. Entire ramus might be hollowed
if associated with mandibular third molar (Figure 6A, B).
In case of maxillary canine, anterior maxilla is expanded.
There will be no pain unless secondarily infected. On aspiration, yellow-colored fluid is obtained.

Clinical features
It occurs frequently in association with impacted mandibular (Figure 3), maxillary third molars (Figure 4), and
maxillary canines (Figure 5). Dentigerous cyst is commonly seen in the 2nd and 3rd decades of life. Males are
306

Radiographic features
Radiographically, dentigerous cysts exhibit three different
presentations, namely, the central, lateral and circumferential
types. In central variety, the cyst symmetrically envelops

Chapter 12 Cysts of Orofacial Region

Figure 5

Figure 6
A

Orthopantomograph (OPG) showing a dentigerous cyst


associated with the right upper canine.
Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

crown. The cyst occurs on lateral aspect of the crown in


lateral variety and envelops crown entirely in circumferential variety (Figure 7). Dentigerous cyst may appear as welldefined unilocular or multilocular radiolucency (Figure
8A, B). Occasionally these cysts may cause displacement
and resorption of the adjacent teeth (Figure 9). Large cysts
often cause expansion of the cortical plates.
Histologic features
It has no characteristic microscopic features. It has cyst lining and connective tissue wall. The connective tissue wall
consists of very loose fibrous connective tissue and sparse
collagenized myxomatous tissues. It has presence of odontogenic epithelium (Figure 10). The inflammation leads to
presence of Rushton bodies of hematogeneous origin in
the lining epithelium. Cholesterol clefts might be present.
Potential complications
The odontogenic cyst has following complications: the development of mural ameloblastoma (Figure 11), squamous cell
carcinoma and mucoepidermoid carcinoma.
Syndrome association
Multiple cysts can be formed in association with Gorlin
Goltz syndrome, cleidocranial dysplasia and Maroteaux
Lamy syndrome.

3D-reconstructed images showing hollowing of the mandible


on the right side associated with the dentigerous cyst.
Courtesy: Dr NVS Sekhar Reddy

ODONTOGENIC KERATOCYST
Odontogenic keratocyst (OKC) was first described by
Philipsen in 1956. WHO has recently designated OKC as
keratocystic odontogenic tumor (KCOT) and is defined as a
benign uni- or multicystic, intraosseous tumor of odontogenic origin, with a characteristic lining of parakeratinized
stratified squamous epithelium and potential for aggressive, infiltrative behavior.
Keratocystic odontogenic tumor is described in Chapter 13
on Tumors of Orofacial Region.

Management
Surgical removal of cyst and tooth is recommended
(Figure 12). Marsupialization is done in case of very large
cysts. The cyst recurs if incompletely removed.

Orthokeratinized Odontogenic Cyst


Philipsen in 1956, in his study of jaw cysts, described a
distinct form of OKC which showed an orthokeratinized
307

Section V Cysts and Tumors of Orofacial Region

pattern. Wright et al (1981) reported 60 cases of orthokeratinized odontogenic cyst (OOC) and compared with OKC and
found that the OOC appears to be a distinct clinicopathologic entity. It was suggested that this cyst be called OKC,
orthokeratinized variant. Iamaroon et al (2004) compared
the proliferation index of the epithelial cells between OKC,
OOC, dentigerous cyst and ameloblastoma. He concluded
that OKC should be considered a benign tumor rather than
simply an odontogenic cyst and OOC as a non-aggressive
cystic lesion.

Clinical features
Orthokeratinized odontogenic cyst usually presents as a solitary cyst in the posterior part of the mandible. It is usually
seen in males commonly in the 2nd to 5th decade of life.
In comparison to OKC it is less aggressive and has a very
low recurrence rate (2.2%). Literature review reveals that
almost two-thirds of the cases of OOC appear like dentigerous cyst on clinical and radiographic examination.
Histopathologic features
Orthokeratinized odontogenic cyst has a thin epithelial lining with a luminal surface of orthokeratin. The basal cell
layer contains flattened squamous or cuboidal cells and a
well-developed granular cell layer (Figure 13).

Figure 7
A

Radiographic features

Central

Lateral

Orthokeratinized odontogenic cyst presents either as a welldefined unilocular or multilocular radiolucency. Radiographically, OOC may resemble a dentigerous cyst when it
is unilocular and resembles ameloblastoma when it is multilocular. Occasionally, it may cause cortical plate expansion and thinning of the lower border of the mandible.
Roots of teeth may be displaced (Figure 14). However,
resorption of roots is seldom seen.
The cyst should be surgically excised (Figure 15).

GINGIVAL CYSTS OF ADULTS


Circumferential

Schematic diagrams showing various types of dentigerous cysts

Gingival cysts of adults are rare odontogenic cysts of


developmental origin. The epithelial lining of these cysts

Figure 8
A

CT images showing unilocular dentigerous cyst

308

Chapter 12 Cysts of Orofacial Region

Figure 9

Orthopantomograph (OPG) showing a dentigerous cyst associated with the impacted left lower third molar causing root
resorption of the adjacent second molar. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 10

Figure 11

23 layered
epithelium
Connective
tissue capsule
Cystic lumen

Photomicrograph of dentigerous cyst.


Courtesy: Department of Oral Pathology, MCODS, Mangalore

are thin non-keratinized and are thought to arise from the


rests of dental lamina. Some authors suggest that these
cysts arise from the traumatic implantation of surface
epithelium.
Schroeder (1976), in a book titled Scientic Foundations
of Dentistry suggested that the gingival cyst arises from
the junction epithelium which is a derivative of the reduced
enamel epithelium.
These occur as swellings on the facial aspect of the
attached or interdental gingiva, most commonly between
5th and 6th decade of life and usually do not exceed 1 cm
in size.
The common sites of involvement are the mandibular
canine and premolar region. Occasionally, these may be
seen in the lateral incisor, canine, premolar regions of the

Orthopantomograph (OPG) showing multilocular radiolucency


associated with the impacted mandibular third molar.
The radiograph showing displacement of the third molar and
the lesion extends to involve the entire ramus and apices
of the second molar. The lesion was histopathologically
diagnosed as mural ameloblastoma. Courtesy: Department
of Oral Medicine and Radiology, MCODS, Mangalore

maxilla. The swelling is soft and uctuant with a smooth


surface and usually have the same coloration as that of the
gingiva. Some authors have reported bluish and red color
swellings. The teeth in relation to these cysts are vital.
Radiographic findings
The cyst reveals no radiographic findings. However, in large
cysts superficial erosion of bone represented by a faint
shadow of radiolucency may be appreciated.
309

Section V Cysts and Tumors of Orofacial Region

Figure 14

Figure 12

Surgical specimen of dentigerous cyst.


Courtesy: Dr NVS Sekhar Reddy

Figure 13

Photomicrograph of orthokeratinized odontogenic cyst.


Courtesy: Department of Oral pathology, MCODS,
Mangalore

Hegde (2004) reported a rare nding (supposedly the


rst case in literature) calcications within cystic lumen
of the gingival cyst.
Histologic findings
Histologically, these cysts have a variety of presentations.
The epithelium generally has three forms of presentation:
(i) extremely thin epithelium, (ii) thicker stratified squamous epithelium and (iii) localized epithelial thickenings

310

Orthopantomograph (OPG) showing a multilocular


radiolucency in relation to the lower premolars, first and
second molars causing displacement of the second molar
in orthokeratinized odontogenic cyst. Courtesy: Department
of Oral Medicine and Radiology, MCODS, Mangalore

Figure 15

Gross specimen of orthokeratinized odontogenic cyst


showing keratin. Courtesy: Department of Oral Pathology,
MCODS, Mangalore

or plaque formation (similar to those evident in lateral


periodontal cyst).
The thinner form of epithelium mimics the reduced enamel
epithelium. It is generally composed of one to three layers
of at or cuboidal cells. The thicker variety may not show
any rete pegs. The nuclei are pyknotic and show perinuclear
cytoplasmic vacuolation. The localized thickening of epithelium or plaque may occasionally project into the cystic
cavity. The cells in the localized thickenings have a whorled
morphology. Rarely, these cells are swollen and clear and
are referred to as water-clear cells.

Chapter 12 Cysts of Orofacial Region

Management

Management

The cyst is removed surgically. Recurrences have not been


reported.

Lateral periodontal cysts can be effectively managed with


enucleation. A sound tooth can be retained. Recurrences
though uncommon, have been reported in literature.

Lateral Periodontal Cyst

Botryoid Odontogenic Cyst

Lateral periodontal cyst is a non-keratinized developmental


cyst occurring in the alveolar bone along the lateral aspect
of a vital tooth.
It is a relatively uncommon cyst that is slow growing,
non-expansile developmental odontogenic cyst derived from
one or more rests of dental lamina, containing an embryonic lining of 13 squamous/cuboidal cell thickness and
distinctive focal thickenings (plaques). These appear to
have no gender predilection. According to Altini and Shear
(1992), lateral periodontal cysts represent about 0.8% of
all central cysts (intraosseous) of maxillary bones. These cysts
are usually seen in adults between the 2nd and 8th decade
of life.
These are usually seen by chance in routine radiographs. These are intraosseous forming beside vital tooth.
These might even form near the crest of ridge. These cause
no symptoms unless they erode through the bone to extend
into the gingiva. Some patients may present with a swelling
on the buccal aspect of the gingiva. The most common site
of involvement is the mandibular premolar area followed
by the anterior part of the maxilla.
Many authors suggest the fact that the lateral periodontal cyst is more or less a histopathological diagnosis rather
than a clinico-radiographic diagnosis.

Botryoid odontogenic cyst (BOC) is considered as a variant


of the lateral periodontal cyst. Weathers and Waldron in
1973 first used this term to describe a multilocular cystic
lesion of the jaw that on gross morphology resembled a
bunch of grapes.
The exact nature of this cyst is still not understood.
Some authors consider the BOC as a multilocular variant of
lateral periodontal cyst. Others consider BOC and lateral
periodontal cyst as two distinct unrelated entities. They
consider BOC as a multicystic odontogenic lesion with the
histologic characteristics of lateral periodontal cysts.
Unlike the lateral periodontal cyst that usually has a unilocular appearance, the botryoid odontogenic cyst is typically polycystic (multilocular), but occasional unilocular
cases have been reported.
However, histopathologically the BOC resembles lateral periodontal cyst. Another striking difference between
BOC and lateral periodontal cyst is its rate of recurrence.
It is estimated that the recurrence rate of BOC is between
15 and 33%, which is much higher than lateral periodontal cyst.
High et al (1996) proposed the term polymorphic odontogenic cyst. This term included GOC, mucoepidermoid
intraosseous carcinoma and botryoid odontogenic cyst.
Greer Jr and Johnson (1998) studied the clinicopathologic
features of 10 botryoid odontogenic cysts. In their study
the radiographic size of the cysts varied between 5 and
45 mm radiographically.
It is believed that the size and multilocular pattern could
be the main factors responsible to the high recurrence rates
of botryoid odontogenic cyst. The high recurrence rates
warrant the need for a more aggressive treatment. Some
authors suggest the systematic use of Carnoy solution along
with enucleation and curettage.

Histologic features
The cyst is lined by a thin non-proliferating cuboidal to
stratified squamous non-keratinizing epithelium, ranging
from 1 to 5 cell layers, and thus resembling the reduced
enamel epithelium.
The cyst wall and the lining usually show no signs of
inammation. The lateral periodontal cyst presents two
important histologic features, namely, the presence of epithelial thickenings or plaques and the presence of glycogenrich clear cells either in plaques or in the supercial
layers of the lining epithelium.
Radiographic findings
The cyst may appear as a round, oval or teardrop-like wellcircumscribed interradicular radiolucent area, usually with
a sclerotic margin, lying usually between the apex and the
cervical margin of the teeth. Resorption of adjacent teeth
though uncommon, has been reported. Occasionally, loss
of lamina dura and widening of the periodontal ligament
space may be present.

CALCIFYING EPITHELIAL ODONTOGENIC


CYST (Gorlin Cyst)
It was thoroughly described by Gorlin and coworkers in
1962 and in 1963. Gold introduced the terms keratinizing
and calcifying odontogenic cyst. It reportedly accounts for
about 2% of all odontogenic pathologies affecting the maxilla and mandible. It may be found along with other odontogenic tumors. However, in 24% of the cases it is
associated with odontomas.

311

Section V Cysts and Tumors of Orofacial Region

The calcifying odontogenic cyst can either occur as an


intraosseous (central) or extraosseous (peripheral) lesion.
The peripheral form is very rare. The incisor and canine
regions are the most common sites of involvement. The
maxilla is more commonly affected. It can occur at any age.
However, most cases are seen in the 2nd decade of life.

Figure 16

Types
In 1981, Praetorius and coworkers attempted to classify
calcifying odontogenic cyst by categorizing it into two entities: cyst and neoplasm.
Cystic entity
It was classified as:

Type 1: A simple monocystic type of typical Gorlins


cyst, with or without dentinoid calcified tissue.
Type 2: Monocystic odontoma creative type, with all
the characteristics of the previous type, except that the
hard tissue was complex or compound odontoma, and
a presence of ameloblastic fibroma tissue in the cystic
wall extending into the surrounding tissue.
Type 3: Monocystic ameloblastomatous proliferating
type which was marked by ameloblastomatous proliferation both in the walls and in the lumen, and hard
dental tissue which consisted of dentinoid formation in
connection with islets of epithelia in the connective wall.

Intraoral photograph showing swelling in relation to


the attached gingiva of the right maxillary incisor and
canine region. Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

Figure 17

Neoplastic entity
It was described as an odontogenic tumor with ghost cells.
The epithelial elements consist of numerous ameloblastomatous proliferations of tissue in the connective tissue
of the stroma. Varying amounts of ghost cells are present
within the epithelial islets. The hard tissue is composed of
different amounts of dentinoid in direct contact with the
epithelium.
Clinical features
It produces slow growing painless non-tender swelling of
jaws (Figures 16 and 17). It occurs more in 2nd decade of
life. It is commonly seen in the anterior part of the jaws. In
the maxilla, the canine region is the most commonly affected
site. In the mandible, the cyst is rarely found posterior to the
first molar. Occasionally the cyst may be seen crossing the
midline. On aspiration, it yields viscous granular yellow
fluid. According to Wood et al, 68% of cases occur in mandibular molar area. At least 52% cases are associated with
unerupted tooth, occasionally associated with pain.
Radiographic features
The radiographic features are quite variable. The central
lesion may be radiolucent with a variable margin that is
312

Intraoral photograph showing expansion of the labial and


palatal cortical plates in the right maxillary incisorcanine
region. Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

smooth and well-defined or, irregular and poorly defined.


It might contain small foci of calcified material. It is usually present as a unilocular radiolucency. However, in
about 513% of the cases, it may present as multilocular
radiolucency. Intraosseous lesions may produce expansion
of the lingual cortical plate. Resorption of the roots of adjacent teeth is frequently seen (Figure 18).

Chapter 12 Cysts of Orofacial Region

Figure 18

Maxillary occlusal radiograph showing a well-defined


unilocular radiolucency in the incisorcanine region
containing radiopaque foci of calcification. Resorption of
the apex of the right central incisor can be appreciated.
Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

Differential diagnosis
Calcifying odontogenic tumor and ameloblastoma.
Management and prognosis
The management of calcifying odontogenic cyst is primarily by enucleation and curettage (Figure 19). Some authors
describe the possibility of malignant transformation. Only
eight cases till date have shown recurrences.

GLANDULAR ODONTOGENIC CYST


It is also called sialo-odontogenic cyst, mucoepidermoid
odontogenic cyst or polymorphous odontogenic cyst.
Padayechee and Van Wyk were the rst to describe a
unique cyst of the jaws in 1987 which did not t into the
standard classication of odontogenic cysts and tumors.
Due to its unique histopathologic features, they suggested
the term sialo-odontogenic cyst to denote a possible origin
or association with salivary gland tissue. Gardner et al (1988)
reported the rst series of these cysts and used the name
glandular odontogenic cyst (GOC), stating that the presence
of mucous cells in the cyst lining did not imply an origin from
salivary glands.
WHO recognized the name of this pathological entity
as GOC in 1992. It was classied as a developmental

Figure 19

Excised gross specimen of calcified odontogenic cyst (COC)


showing the cyst and the calcified mass. Courtesy:
Department of Oral Pathology, MCODS, Mangalore

odontogenic cyst, although controversy still exists regarding its origin and the terminology.
Current literature review reveals the mention of only
23 cases of GOC. These appear to be odontogenic in origin
and present as a well-dened radiolucent swelling of the
jaws with a tendency to recur following conservative
treatment. These occur over a wide age range with no gender, race or ethnic predilection.
The cyst is possibly derived from rests of dental lamina
and comprises both secretory elements and stratied squamous epithelium.
Clinical and radiographic features
Glandular odontogenic cyst is commonly seen in the anterior mandible. Occasionally maxillary involvement has been
reported. The usual complaints are swelling, pain or discomfort in the involved area (Figure 20). It is usually seen
as a slow-growing swelling. Pain is very unusual but has
been reported.
Reports in literature mention the occurrence of GOC in
a wide age range (1480 years), however it is relatively
common in the 4th and 6th decades of life.
Radiographically it may be a unilocular or multilocular
well-circumscribed radiolucency usually displacing the roots
of teeth (Figures 21 and 22).
Histopathologic features
The histopathologic features of this cyst have been described
as a combination of findings from a botryoid odontogenic
cyst and a mucoepidermoid carcinoma, often causing a
diagnostic dilemma for pathologists.
313

Section V Cysts and Tumors of Orofacial Region

Figure 20

Little inflammation
Occasional findings of hyperchromatic basal cells
within the cyst lining.

Management and prognosis


Glandular odontogenic cysts can be treated conservatively
by enucleation and curettage. It is believed that almost
55% of the cases show recurrence. The recurrence rate is
high because the thin cyst wall, tendency of epithelium to
separate from connective tissue or growth through cancellous spaces of bone and presence of microcysts makes
complete removal of the cyst nearly impossible. Thus,
some authors suggest a local block excision. However, it is
wise to follow up the patient for several years to assess
any form of recurrence.
Intraoral photograph showing minimal obliteration of the
labial vestibule in relation to the maxillary anterior teeth.
Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

Figure 21

NON-ODONTOGENIC CYSTS
Non-odontogenic cysts including developmental cysts
account for about 6% of cysts in the orofacial region.

Nasopalatine Duct Cyst


The nasopalatine duct cyst or incisive canal cyst was first
described by Meyer in 1914. Nasopalatine duct cyst is the
most common among the non-odontogenic cysts. It is
estimated that the cyst occurs in about 1% the population.
The etiopathogenesis of the cyst is still unclear. However,
it is thought that the cyst arises from a cystic degeneration
of the embryologic remnants of nasopalatine duct. Some
authors believe that trauma, bacterial infection of the nasopalatine duct or mucous retention possibly predisposes to
the formation of the cyst.
Clinical features

Maxillary occlusal radiograph showing well-defined


unilocular radiolucency extending from the mesial aspect of
the maxillary right side lateral incisor to the mesial aspect of
the left side lateral incisor, causing displacement of teeth.
Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

Gardner proposed the diagnostic criteria for GOC which


included the presence of:

A cystic cavity lined by epithelium of varying thickness with a flat interface between the epithelium and
underlying connective tissue
Variable numbers of mucous cells in the epithelium
Eosinophilic cuboidal cells in the superficial layer
Localized plaque-like thickening of the epithelium
314

Nasopalatine duct cyst is seen to affect individuals between


the 4th and 6th decades of life. The cyst is seen in the
midline of the anterior maxilla approximating the incisive
foramen. It is seen slightly more frequently in men than in
women (3:1). The cysts often present as asymptomatic
swelling of the palate but can present with painful swelling or discharge (mucoid or purulent in nature). The maxillary central incisors may occasionally be displaced. The
associated teeth are vital. A clear or straw-colored fluid is
obtained on aspiration.
Histologic features
The nasopalatine duct cyst may be lined by various types
of epithelium such as stratified squamous epithelium, pseudostratified columnar epithelium or cuboidal epithelium.
Abrams (1963), Gnanasekhar (1995) and Swanson (1991)

Chapter 12 Cysts of Orofacial Region

Figure 22

Orthopantomograph (OPG) showing well-defined unilocular radiolucency extending from the mesial aspect of the maxillary
right side lateral incisor to the mesial aspect of the left side lateral incisor. Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

reported that about 9.8% of the nasopalatine duct cysts


are lined by respiratory epithelium.
Radiographic features
Radiographically, nasopalatine duct cyst is apparent as a
well-defined round, oval or inverted pear-shaped radiolucency. Occasionally, the nasal spine is superimposed over
the radiolucency imparting it a heart shape.
It is located in the midline in the anterior maxilla. The
cyst is typically located in the interradicular region, apical
to the maxillary central incisor teeth. The cyst is well corticated, unless infected. Adjacent teeth are usually displaced.
However, the roots are rarely resorbed.
Large cysts can cause expansion of the palatal cortical
plate and occasionally cause destruction of the oor of
the maxillary antrum. Radiographically, when the diameter of the incisive canal exceeds 6 mm, a nasopalatine cyst
should be considered. On MRI, the cyst is identied as a
high-intensity, well-marginated lesion, indicating the presence of proteinaceous material.
Management
The cyst can be successfully managed with enucleation.
It has low recurrence rates.

NASOLABIAL CYST
Nasolabial cyst is classified as developmental, non-odontogenic soft tissue cyst. It occurs in the nasolabial region.
It is estimated that the nasolabial cyst accounts for only
0.7% of the cysts of the jaws. The nasolabial cyst is also

known by other names such as Klestadts cyst, nasoalveolar


cyst, nasal vestibule cyst, nasal wing cyst and mucoid cyst
of the nose. Though the exact etiology for the cyst formation is unknown, Bruggeman (1920) suggested that the
cyst possibly originates from the remnant of embryonic
nasolacrimal duct.
Clinical features
Nasolabial cyst is usually seen in the 4th and 5th decade
of life. It is reportedly seen 34 times more commonly in
women. Clinically patients present with a soft tissue swelling that may cause obliteration of the nasolabial fold, and
elevate the ala of the nose. Intraorally, a swelling is seen
in the labial vestibule. However, about 11% of the cases
present with bilateral involvement. A nasolabial cyst is usually not painful, unless it is secondarily infected. The cyst is
fluctuant on palpation. The cyst may rupture spontaneously
or drain orally, nasally or sometimes drains extraorally
through a fistula. Occasionally, the swelling may encroach
upon the lateral wall of the nasal vestibule causing nasal
obstruction. Large infected cysts can cause referral of pain
to the maxillary anterior teeth.
Radiographic findings
Although nasolabial is a soft tissue cyst, it can occasionally cause erosion of the underlying maxillary bone which
may be appreciated on radiographs. Intraoral periapical
radiographs and maxillary occlusal radiographs are generally sufficient to evaluate the extent of the cyst. Localization technique may help in excluding cysts of odontogenic
origin. Alternatively, the content of the cyst may be
aspirated and a radiopaque contrast agent can be injected
into the cyst followed by a posteroanterior projection or
315

Section V Cysts and Tumors of Orofacial Region

occlusal radiograph. Posteroanterior view will reveal a


spherical or kidney-shaped (bean-shaped) cyst. The cyst
may cause depression of the underlying labial surface of
the maxillary bone (secondary to pressure). The cyst may
also cause distortion of the curve of the bracket-shaped
line produced by the inferior margin of the anterior bony
aperture of the nose. Literature review reveals rare cases of
root resorption.
Histologic features
Almost all cysts are lined with pseudostratified columnar
epithelium. Sixty percent of the specimens show the presence of goblet cells.
Management
Nasolabial cysts have been managed with injection of
sclerotic substances, marsupialization and surgical removal.
However, surgical excision is the treatment of choice.
Occasionally, perforation of the nasal mucosa is seen owing
to the close relation of the cyst to the nasal floor. Large
defects have to be sutured.

MID-PALATAL RAPHE CYST OF INFANTS


It is also known as median palatine, median alveolar and
median mandibular cysts.
The terms median palatine, median alveolar and
median mandibular cysts are no more used in literature. It
is believed that the median alveolar and median palatine
cysts are the anterior and posterior extensions of the wellknown incisive canal cyst. The use of the term median
mandibular cyst is controversial as most cases in literature
that describe this cyst are associated with non-vital mandibular anterior teeth (mimicking radicular cysts) or on
histopathological examination resemble keratocysts.
Two theories have been proposed to explain the origin
of the palatal cysts of the newborn: entrapment of the
epithelium along the mid-palatine raphe during fusion of
the palatal shelves in embryonic life or from remnants of the
epithelium derived from the development of palatal minor
salivary glands.
The mid-palatal raphe cyst is a developmental cyst of
non-odontogenic origin. These cysts are usually present
along the mid-palatal raphe at the junction of the hard and
soft palate. Usually four to ve cysts are seen together.
They measure between 2 and 4 mm in diameter.
Bohns nodules and Epstein pearls are common cysts that
occur in an infants palate. Bohns nodules are smooth
surfaced cysts that are found at the junction of the hard
and soft palate, and occasionally scattered all over the
palate. These nodules are usually 13 mm in size, and lled
with keratin. Bohns nodules are named after the German
pediatrician Heinrich Bohn (18321888). These are thought
316

to be derived from palatal salivary gland structures and


generally regress within the rst 34 months of life.
Epstein pearls are cystic keratin-lled nodules found
along the mid-palatine raphe and are thought to be derived
from entrapped epithelial remnants along the line of fusion.
Epstein pearls are named after Alois Epstein (18491918),
a Czech pediatrician.
Histologic features
The cyst is lined by parakeratinized stratified squamous
epithelium. Occasionally epithelial lined clefts are seen
between the cyst and the surface epithelium of the oral
mucosa. The basal cells are flat. The cystic lumen contains
concentric layers of keratin.
Management
Mid-palatal raphe cysts disappear within the first few months
of life. Studies by Moreillon and Schroeder (1982) showed
that with time the cystic epithelium differentiated, fused
with the oral epithelium and their contents were discharged.

CYSTS OF MAXILLARY ANTRUM AND


SALIVARY GLANDS
The cysts associated with the maxillary sinus are either
extrinsic or intrinsic in origin.
These can be classied as:
1.
2.

Extrinsic cysts
Intrinsic cysts
a. Mucous retention cyst
b. Serous cysts
c. The mucocele.

Extrinsic Cysts
The extrinsic variety develops in structure adjacent to sinus
and as they expand they may encroach upon the sinus air
space. Extrinsic cyst may be odontogenic in origin or infrequently non-odontogenic.

Intrinsic Cysts
This cyst is referred to in literature by a plethora of names
like mucosal cyst, mucosal antral cyst, mucous cyst,
mucous retention cyst secreting or secretory cyst, mucocele serous cyst, non-secreting or secretory cyst, mesothelial cyst, lymphangiectatic cyst, interstitial cyst, pseudocyst
and false cyst. Concurrent concept permits the usage of term
mucosal cyst. There are three types of mucosal cysts:
a.
b.
c.

The mucous (secreting or retention cyst)


The serous (non-secreting cyst)
The mucocele.

Chapter 12 Cysts of Orofacial Region

The mucocele frequently causes the expansion of the bony


antral wall whereas mucous and serous do not. If the
ostium is not occluded by intra-antral or intra-mucosal
inflammation, polyps or bony tumors, it provides an
avenue or release for expanding cystic pressure. Release
occurs either by rupture of the cyst resulting from abrupt
pressure changes accompanying sneezing or blowing of
the nose or by the cyst herniating though the ostium into
the nasal cavity, where it is subsequently ruptured. If the
ostium is blocked, cystic pressure progressively increases
and erodes the antral wall. The cysts associated with such
pressure atrophy are referred to as mucocele, an expanding
destructive cyst.

Benign Mucosal Cysts


The intrinsic benign (non-destructive) cysts are most common in maxillary sinus and are assumed to be two pathogenically different varieties:
1.
2.

A mucous or secretory retention cysts


Serous, non-secreting cysts.

Mucous Retention Cysts


The mucous retention cysts result from the obstruction of
some ducts of the seromucinous glands in the lamina propria of the sinus lining. The obstruction is secondary to
local inflammation that may be either infectious or allergic
in origin. The occluded glands continue to secrete, causing
their dilatation and resulting in accumulation of a mucoid
material forming cyst. The cyst is lined with either normal
sinus (respiratory) epithelium or a flattened cuboidal or
squamous epithelium as a result of metaplasia induced by
intracyst pressure. The liquid that collects inside the cyst
lumen may be sampled by intranasal needling as a diagnostic aid. It is thick, tenacious, white translucent and sterile.

Serous Non-secretory Cysts


The serous cysts probably arise as a result of cystic degeneration within an inflamed, thickened sinus lining or in
large mucosal polyp. As the defect in the lamina propria of
the affected mucosa becomes distended with edema fluid,
they coalesce and form a cystic space that crowds and
packs the surrounding connective tissue fibers forming the
cyst wall. This sequence of events produces the development of a distinct epithelial lining, a fact surrounded by
histological examination of these cysts. The fluid within
the cyst is believed to be a transudate from the adjacent
osmotic pressure of the cyst fluid. It is similar in composition to plasma. The cause of cyst is uncertain. It seems that
inflammation accompanying sinusitis or reported allergy
or a tooth extraction plays a role.

Figure 23

CT axial section showing a large mucosal cyst in the


right maxillary sinus

Clinical and radiographic features


The occurrence rate of this cyst is 1.4713% of general
population. This cyst is found in all age groups; about 11%
of the cysts are diagnosed in children. Males are twice more
affected compared to females. Symptoms accompanying
this cyst are general fatigue, dizziness, pain exacerbated
by jarring, a sense of fullness or numbness in the ipsilateral cheek, toothache, frontal headache, nasal obstruction
and occasional copious post-nasal discharge (when the
cyst ruptures), optic neuritis, serous otitis media and some
arthritis, specially in the knee.
Radiographically both varieties of cyst may be recognized as a single curved, homogeneous, highly radiopaque
area (normal anatomic structures can usually be observed
through the cyst) that is spherical, ovoid or dome shaped
(Figure 23). Their outlines are usually smooth, uniform and
well-dened by radiolucent air space of the sinus. The cyst
can develop any where in the cavity. The base of the lesion
may be broad or narrow. The mucous cysts usually have a
broad base while serous cysts are more pedunculated. The
lesions are usually single but multiple cysts and bilateral
involvement of the sinuses have been reported. The size of
the mucosal cyst varies from a few millimeters to more
than 1,000 mm.
The mucous cysts are usually small in size and hidden
in intrasinus uid (pus) and not recognized until it drains.
The condition of lining of the other part of the sinus also
helps to distinguish mucous variety which is associated
with thickened mucosa in majority of the cases. The serous
cysts when involved, lining appears normal. The broad
based mucous cyst will not change in position while the
serous cyst shows slight changes in contour in a radiograph
when the position of patient is altered in second projection.
Transillumination does not usually provide diagnostically useful information when compared to a radiograph.
317

Section V Cysts and Tumors of Orofacial Region

It will help in distinguishing between the mucous and serous


cysts by demonstrating different translucency. The mucous
cyst shows decreased translucency compared to serous
because the serous cyst has a high concentration of doubly
refractory cholesterol crystals. When aspirated, serous type
will show a clear, amber uid with high concentration of
cholesterol crystals. In contrast, the mucous cysts will
show thick, whitish, opalescent mucous.
Investigations
Periodic radiographic studies show benign mucosal cysts
remain stationary in size, completely disappear, decrease
or increase in size over an interval of a month. However,
majority of cysts regress spontaneously.
Surgical exploration and direct examination of the cyst
that have herniated into the mouth through the oro-antral
stula shows a round, distended, translucent mass with a
light bluish or yellowish color. The walls are thin and rupture readily, yielding a watery uid or a thicker sticky
mucoid uid.
Microscopic studies show that the vast majority of those
are non-secretory variety and that glandular elements are
not associated with these cysts. There are false cysts whose
lumina are not lined with epithelium but with the connective tissue. The outer surface of the cysts is lined with respiratory epithelium which shows areas of metaplasia. The
lumina of these serous cysts are lled with amber uid
in which there are few inammatory cells and suspended
cholesterol crystals. This layer of submucosa is sometimes
edematous and contains varying number of round cells. Its
luminal lining is composed of columnar epithelium with
some mucous glands. As a result of pressure, the lining
epithelium may undergo metaplasia and appear as at
cuboidal epithelium.
Differential diagnosis
Benign mucosal cysts of the sinus must be differentiated
from other soft tissue lesions of the sinus such as polyps,
hyperplasia of dental infection, extrinsic cyst, sinusitis and
malignant soft tissue tumors. This presents the primary concern since the character of opacities produced by the tumor
fluid or thickened mucosa is not anyway different. A large
cyst may fill sinus causing complete opacification and
obscure cystic characteristic feature. Other lesions like intrasinus fluid, calcified entities such as condensing osteitis, root
tip and other foreign bodies, antroliths and odontomas generally have characteristic outline and much denser images
when compared to mucosal antral cyst, which presents as
a homogeneous, only slightly radiopaque appearance.
Antral polyps are much less common than benign
mucosal cyst of the antrum. Antral polyps will not occur on
the oor or inferolateral aspect of the sinus and are also
associated with thickened mucosa in contrast to normal
appearing lining mucosa. Bone displacement, destruction
318

and bony sclerosis will be associated in antral polyps


and not in antral cysts. Cysts are solitary, polyps are frequently multiple. Hyperplasia as a result of chronic dental
infection is frequently seen in a radiograph of the antral
oor, adjacent to teeth with pulpoperiapical problems or
advanced periodontal diseases. Both the lesions may show
similar convex, homogeneous, faintly opaque shadows. The
differentiating feature of hyperplasia of dental infection is
the presence of a chronically infected tooth. Usually, dental
infection is not seen in association with benign mucosal
cyst or if present, is not considered as an etiological factor.

Extrinsic Cysts
Cysts like radicular, dentigerous, primodial and other
odontogenic cysts may encroach on the sinus, but rather
easily be identified by their characteristic location in the
jaws or their relationship to a tooth. Extrinsic cysts will
retain a thin curved radiopaque rim of bone which separates the cyst from the antral shadow.
Cysts associated with the salivary glands are described
in Chapter 11 on Diseases of Salivary Glands.

INFLAMMATORY CYSTS
Periapical Cyst (Radicular Cyst, Root End Cyst,
Apical Periodontal Cyst)
Periapical cyst is the most common inflammatory odontogenic cyst. It is associated with non-vital teeth. The tooth
might be deeply carious, traumatized or improperly
restored.
Etiopathogenesis
Bacteria invade the tooth followed by the death and degradation of pulp. The first line of defense in the periapical
area to seal the apex is the proliferation of epithelial rests
of Malassez in the periodontal ligament. They proliferate to
form a granulation tissue called periapical granuloma.
This consists of highly vascular tissue with immunocompetent cells like lymphocytes, macrophages, plasma cells.
As the time elapses, the central area is deprived of nourishment. The cells undergo liquefaction necrosis surrounded by epithelium to form a cyst.
Clinical features
More often (60%) these occur in the maxillary anterior
region. These might cause painless bony expansion of either
buccal or palatal cortical plate (Figure 24).
The cortex might be intact where it is hard or uctuant.
When perforated, the bone thins out and exhibits crepitus.
However, occasionally the patient may complain of pain

Chapter 12 Cysts of Orofacial Region

Figure 24

Figure 25

Straw-colored aspirant from a periapical cyst.


Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

Figure 26

Intraoral photograph showing a discolored right


maxillary central incisor and palatal swelling suggestive
of a periapical cyst. Courtesy: Department of Oral Medicine
and Radiology, MCODS, Mangalore

when the cyst is secondarily infected. Sometimes, a


cyst may be seen at the opening of lateral accessory
root canals of a tooth, this may be referred to as lateral
radicular cyst.
In deciduous teeth Periapical cysts are rarely seen in
deciduous dentition. It is estimated that only 0.53.3% of
the radicular cysts occur in deciduous dentition. Most of
the cysts are seen in relation to the mandibular molars and
generally discovered incidentally on radiographs. It has
been seen that cysts in primary teeth are characteristically
present in the interradicular region and not near the apex
of the teeth. Many authors believe that this is due to the
short and resorbed roots as well as the presence of multiple accessory canals in primary teeth. Hence, the term
periradicular cyst is more appropriate. Expansion of the
mandibular buccal cortical plate and displacement of the
underlying permanent tooth buds are usually seen associated with periradicular cysts.
On aspiration, the contents of the cyst may vary from
brown (breakdown products of blood) to straw color (presence of cholesterol crystals) depending on the content of
the cyst (Figure 25).
Radiographic features
It appears as well-defined periapical radiolucency associated with apex of affected tooth. A diagnosis of periapical
cyst is considered when the cyst measures at least 1.5 cm
or more in diameter. The lesion is continuous with the lamina dura of the tooth. The lesion will have sclerotic border

Maxillary occlusal radiograph showing a well-defined


radiolucency extending from the periapex of the maxillary
right lateral incisor. The cyst is bound by a well-defined
sclerotic border. Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

(Figure 26). In cysts that are secondarily infected and


those rapidly expanding the sclerotic border may be indistinct. The radiolucency may sometimes appear hazy due to
pus accumulation. Few cysts might expand into the sinus
and elevate the floor. Root resorption is rarely seen.
Histopathology
Most of the radicular cysts are lined by stratified squamous
epithelium (Figure 27). In instances where the periapical
cysts are in proximity to the maxillary sinus, the cyst
may exhibit pseudostratified ciliated columnar epithelium.
Rarely the periapical cysts are lined with ortho or parakeratinized epithelium.
It is estimated that 10% of the cases reveal the presence
of Rushtons hyaline bodies. These are generally found in
epithelial linings and rarely found in the brous capsule.
These are hairpin shaped, arch shaped or linear eosinophilic structures that are amorphous and brittle. Presence
319

Section V Cysts and Tumors of Orofacial Region

Figure 27

Figure 28

Orthopantomograph (OPG) showing residual cyst in the


edentulous site. Courtesy: Department of Oral Medicine
and Radiology, MCODS, Mangalore

Photomicrograph of radicular cyst showing stratified


squamous epithelium with arcading pattern, cystic lumen and
connective tissue capsule. Courtesy: Department of Oral
Pathology, MCODS, Mangalore

of cholesterol clefts is another important feature of radicular cysts. The brous capsule of the cyst is made up of dense
bundles of collagen bers. Usually chronic inammatory
cells are seen in the connective tissue approximating the
epithelium.
Simon (1980) described the presence of an epithelium
lined cavity that may open to the root canal in small periapical lesions. Simon termed this bay cyst. Subsequently
Nair et al (1990) studied 256 periapical lesions. Their inference was that 61% of the identied cysts fullled the criteria of true periapical cysts and the rest were apical
inammatory lesions that contained a sac-like, epitheliumlined cavity, continuous with the root canal. This epithelium formed an attachment that seemed to seal off the
infected root canal and its apical pouch from the periapical
region. It was suggested to term this a periapical pocket
cyst rather than a bay cyst.

It is estimated that 10% of the cysts of odontogenic origin


are residual cysts. Residual cysts are cysts that are left behind
following partial enucleation of a radicular cyst or a
retained radicular cyst after the tooth has been extracted.
Many authors believe that a residual cyst may also develop
from partial removal of a dentigerous cyst. It may also form
from a periapical granuloma after removal or exfoliation of
tooth. Subsequent cystic degeneration may take place in
the granuloma.
Clinical features
Residual cysts are mostly detected incidentally on radiographs. The cyst is evident in edentulous site (Figures 28
and 29). The patient may give a history of extraction of
the tooth because the tooth was grossly carious or fractured
to involve the pulp.
It is almost always asymptomatic. Amber-colored aspirant
is expressed on aspirating residual cysts.
Management

Differential diagnosis

Residual cysts are surgically removed. However, large


residual cysts may be marsupialized.

The lesions that might resemble cyst radiographically are


periapical granuloma, periapical scar and surgical defect.

Paradental Cyst

Management and prognosis


Root canal treatment or extraction of tooth along with the
removal of the cyst. Depending upon the size and involvement of other tissues, marsupialization or enucleation are
done. Recurrence unlikely if removed completely.
Literature review reveals descriptions of squamous cell
carcinoma originating from the epithelial lining of radicular and residual cysts.
320

Residual Cyst

Craig is credited for describing the paradental cyst in


1976. The term paradental cyst is reserved for those cysts
that are located in relation to the distal aspects of the roots
of partially erupted third molars. Most patients have an
associated chronic pericoronitis. Craig believed that the
reduced enamel epithelium provided the cells of origin of
the paradental cyst. However, other authors also believe
that the paradental cyst may originate from the cell rests
of Malassez.

Chapter 12 Cysts of Orofacial Region

Figure 29

Clinical features
It is commonly seen in young children in the 611 year
age group. The cyst causes a buccal tilting of the crown of
the involved tooth. The associated tooth is vital. On clinical examination, deep periodontal pockets may be evident
on the buccal aspect of the tooth. Occasionally, pain or
swelling may be present.
Radiographic features
Periapical radiographs, occlusal radiograph and orthopantomograph may be required to evaluate the presence of
buccal bifurcation cyst. Radiographically, the lamina dura
and the periodontal ligament space are unaffected. The cystic
radiolucency is always located on the buccal aspect of the
molar, which can be best appreciated on occlusal radiograph.
Occasionally, subperiosteal new bone may be laid down,
which may appear laminated.

Orthopantomograph (OPG) showing residual cyst in the


edentulous site. Courtesy: Department of Oral Medicine
and Radiology, MCODS, Mangalore

Management
The cyst can be managed by curettage and extraction of the
tooth. Some authors recommend enucleation.

PSEUDOCYSTS
Clinical features
Paradental cysts are mostly seen involving the mandibular
third molars. However, maxillary third molar involvement
has also been reported in literature. Most of the cysts cover
the bifurcation of the roots and are usually attached to
the buccal root surface. Teeth are vital. Both sexes may
be affected. However, males are more commonly affected.
These cysts are commonly seen in the 2nd and 3rd decades
of life.
Radiographically, a well-dened radiolucency is seen
in relation to the distal aspect of a partially erupted third
molar. Generally the distal part of the radiolucency is separate and distinct from the distal follicular space of the
third molar. The width of the periodontal ligament space is
unaffected.
Histological features resemble that of radicular cyst.
The paradental cyst is managed effectively by surgical
enucleation. The partially erupted third molar can be
removed.

Mandibular Infected Buccal Cyst


(Mandibular Buccal Bifurcation Cyst)
The first description of the mandibular infected buccal
cyst was given by Stoneman and Worth in 1983. The buccal
bifurcation cyst is an uncommon lesion associated with the
permanent mandibular first or second molar in children.
Usually, it is identified just prior to eruption.

It is also known as traumatic bone cyst, aneurysmal bone


cyst, Stafnes bone cyst.

Traumatic Bone Cyst


The term traumatic bone cyst (TBC) was used by Lucas in
1929. Though the term is popularly and widely used, literature review reveals that other terms such as solitary
bone cyst, hemorrhagic bone cyst, simple bone cyst and
unicameral bone cyst are used.
The pathogenesis of the TBC is still not well understood.
However, trauma is the most frequently discussed etiologic
factor in the formation of a TBC. According to Pommer,
trauma leads to intraosseous hematoma formation. The
blood clot liquees, unlike the normal healing process, and
adjacent bone is destroyed by enzymatic activity. Blum
and Thoma suggested that a previous traumatic episode to
the jaws contributed to the development of TBCs. Thoma
proposed that trauma initiates a subperiosteal hematoma
which causes a compromised blood supply to the area,
thereby leading to osteoclastic bone resorption. However,
even this theory is debatable as it is estimated that almost
50% of the patients do not give history of trauma. And even
if there is a history of trauma it does not coincide with the
time of the development of the cyst. Another explanation
against trauma as the etiological agent is that, trauma usually occurs on the anterior part of the mandible, whereas
the cyst occurs more frequently in the body of the mandible.
321

Section V Cysts and Tumors of Orofacial Region

Clinical features
The cyst is usually seen in the 2nd decade of life. It is
slightly more common in males. The cyst is generally
asymptomatic and hence incidentally discovered on routine
radiographic examination. Approximately 1030% of the
patients complain of pain. Traumatic bone cysts frequently
affect the mandibular body (canine to molar region), followed by the mandibular symphysis and rarely the maxillary anterior region. The ramus and condylar regions are
hardly involved.
Other features that may be noticed are tooth sensitivity,
paresthesia and delayed eruption of permanent teeth.
Aspiration may occasionally yield a straw-colored uid or
bright blood.
Radiographic features
Most TBCs are found incidentally on routine radiographic
investigations. Radiographically, it is seen as a well-defined
radiolucent area with or without a sclerotic border. The
radiolucent area is commonly seen in the body of the mandible and the symphyseal region and the anterior region of
the maxilla. The radiolucent areas can occur unilaterally,
bilaterally or in multiple sites. The cyst may extend interdentally, between the roots of teeth giving rise to a scalloped
margin. Extensive lesions may cause expansion (usually
buccal cortical plate is expanded) and erosion of the cortical plates resulting in pathological fracture. Occasionally
the mandibular canal can be displaced.
Histopathologic features
The tissue specimen for histopathological examination can
be taken during the surgical curettage. However the amount
of tissue obtained is generally insufficient for histopathological analysis. Epithelial lining is typically absent. Other
findings include presence of fibrous connective tissue and
normal bone. The lesion may exhibit areas of vascularity,
fibrin and erythrocytes. Giant cells may be occasionally
seen adjacent to the bone surface.
Management
Literature review reveals that some cases of TBC undergo
spontaneous resolution. However, the most preferred and
widely recommended treatment modality is surgical exploration followed by meticulous curettage of the bony walls.
It is believed that curettage and surgical exploration will
induce bleeding. This induced bleeding will form a clot
which will ultimately be replaced by healthy bone. Recurrences are rare after surgical treatment.

Radiographically, it is characterized by ballooned out expansion of the periosteum which is usually outlined by a wafer
thin subperiosteum. This is, in turn, bounded by an area of
disintegrated cortex.
Clinical features
Aneurysmal bone cyst is commonly seen in the 2nd decade
of life. It is rarely seen after the 3rd decade of life. It is
believed that females are more commonly affected than
males.
Literature review reveals that the mandible is more
commonly affected than the maxilla. The molar regions of
the maxilla and mandible are the most common sites of
involvement. Extensive lesions in the mandible may involve
the angle and ascending ramus of the mandible. Rare sites
of involvement such as the coronoid process of the mandible, oor of the orbit and the zygomatic arch have been
reported in literature.
Clinically the swelling is rm on palpation. Aneurysmal
bone cysts tend to enlarge rapidly and cause thinning and
perforation of the overlying cortical plate. Some patients
complain of pain. Large lesions can cause displacement of
teeth and a progressive malocclusion. Associated teeth are
vital.
Occasionally, patients may complain of difculty in
mouth opening when the cyst involves the capsule of the
temporomandibular joint.
Differential diagnosis
Aneurysmal bone cyst may mimic other lesions such as
ameloblastoma, giant cell tumor, hyperparathyroidism,
myxoma, TBC and OKC. However, on aspiration, blood
may be expressed from a vascular lesion or aneurysmal
bone cyst. Clinically aneurysmal bone cyst may be differentiated from a vascular lesion based on the absence of bruits
or thrill and lack of pulse pressure.
Radiographic features
Radiographically, aneurysmal bone cyst resembles other
cystic lesions of the jaw. It may appear as a well-defined
unilocular radiolucent lesion or sometimes exhibit internal
septa within the radiolucent lesion giving rise to a multilocular appearance (honeycomb pattern).
Dabska and Buraczewski (1969) and Wilner (1982)
described four stages in the radiographic appearance of
aneurysmal bone cysts:
1.
2.

Aneurysmal Bone Cyst


Jaffe and Lichtenstein in 1942, discovered a distinct clinicopathological entity and termed it aneurysmal bone cyst.
322

3.

Initial lytic phase: a well-defined area of bone resorption with no distinctive features is observed
Phase of active development: there is the typical subperiosteal, blow-out expansile appearance
Stabilization phase: there is a distinct peripheral bony
shell with internal septa and trabeculations, resulting
in the so-called soap bubble appearance

Chapter 12 Cysts of Orofacial Region

4.

Healing phase: Progressive ossification of the cyst


resulting in a dense bony mass of irregular structure.

Figure 30

CT scan may reveal fluid-fluid levels within the radiolucent lesion. Fluid-fluid levels are produced due to layering
of solid blood components within the cyst.
Management
Malghem et al (1989) reported three cases of spontaneous
healing of aneurysmal bone cysts in about 79 months
duration.
Aneurysmal bone cysts can be managed by surgical
curettage or by excision. Some authors have reportedly used
calcitonin injections with unpredictable results.
Szendri et al (1992) recommended direct injection of
calcitonin into the cyst as a useful non-invasive method
for the management of hypovascular aneurysmal bone
cysts.
Adamsbaum et al (2003) studied the affect of Ethibloc
(Ethnor Laboratories) injection, which is an alcoholic solution of zein (a vegetable protein dissolved in alcohol). It is
a brogenic and thrombogenic agent, on 17 patients in
the age group of 218 years. After 5 years of follow-up,
14 out of 17 patients demonstrated complete healing
manifested by increased cortical and septal thickening.
Inammatory reaction following the injection such as
pain and fever is seen. They concluded that the percutaneous direct Ethibloc injection is a safe, efcient and noninvasive treatment for aneurysmal bone cyst.
Other modalities of treatment include introduction of
demineralized bone and autogenous bone marrow that
promotes self-healing of a primary aneurysmal bone cyst.
It is estimated that 1044% of the cases exhibit recurrence. Recurrences have been reported due to difcult
access and incomplete removal of the cyst. It is advisable
to review the patients on a regular basis to evaluate for
recurrence.

Stafnes Bone Cyst


Stafnes bone cyst is also known as static bone cyst or
defect of mandible, lingual mandibular bone cavity and
latent bone cyst.
Stafne in 1942 recognized this entity. It is the developmental inclusion of submandibular glandular tissue within
or, more commonly, adjacent to the lingual surface of the
body of the mandible or indentation on the mandible
(Figure 30). Name of the cyst is derived from its radiographic appearance. It is a congenital defect.
Radiographic appearance
It appears as an ovoid radiolucency located between the
inferior canal and the inferior border of the mandible in
the region of 2nd or 3rd molars. It is differentiated from

Photograph of the mandible showing the lingual defect


which forms the site for lodgement of the submandibular
salivary gland. Courtesy: Dr Ravikiran Ongole

TBC by location which lies superior to inferior alveolar


canal. Its anterior variant is found between incisors and
premolars. Rarely, complication in the form of development of neoplasm like mucoepidermoid carcinoma from
salivary gland has been reported rarely.

CYSTS OF SOFT TISSUES OF MOUTH,


FACE AND NECK
Anterior Median Lingual Cyst
Fink in 1963 described a patient with cystic swelling present in the anterior two-thirds of the tongue on the dorsal
surface. He termed this as a retention cyst of the tongue or
glossocele. Some authors use the term intralingual cyst
originating from the foregut synonymously with anterior
median lingual cyst. Large cysts can interfere with feeding
and swallowing. Occasionally the cysts can impede closure
of the mouth.
Histologically these cysts may be lined by parakeratinized stratied squamous epithelium. The cystic capsule
may exhibit chronic inammatory cells.
The cysts can be surgically excised. However, recurrences have been reported.

NASOPHARYNGEAL CYSTS
Nasopharyngeal cysts are rare entities which may either be
congenital or acquired in nature. Most of the cysts are
asymptomatic. However, larger cysts can cause nasal
323

Section V Cysts and Tumors of Orofacial Region

obstruction, closed posterior rhinolalia (nasal quality of


voice) and conductive hearing loss.
Piero Nicolai et al (1989) modied the classication of
nasopharyngeal cysts originally proposed by Singh and
Pahor (1977).
Classification
1.

2.

Midline cysts
a. Congenital cysts
i. Cysts of bursa pharyngea embryonalis
ii. Cysts of Rathkes pouch
b. Acquired cysts
i. Retention cysts of the median recess
ii. Retention cysts of seromucinous glands
Lateral cysts
a. Congenital cysts
i. Branchiogenic cysts
b. Acquired cysts
i. Retention cysts of seromucinous glands

Lateral Cysts
These are usually branchiogenic in origin. The base of the
cyst is located between the posterior pillar and pharyngeal
opening of the Eustachian tube.
These cysts have more uid content and lesser cellular
debris compared to the midline cysts. Unlike the midline
cysts, the germinal centers are rarely present in the lateral
cysts. The inner lining of the cyst is made up of cylindrical
and ciliated epithelium.
Clinically these soft mucosal masses can be identied
by posterior rhinoscopy or by using a nasal berscope.
Choanal polyp, sphenoid sinus mucocele and juvenile angiobroma can mimic nasopharyngeal cysts.

Clinical features

Radiographic investigations

Midline cysts are usually seen in the 4th decade of life,


whereas lateral cysts are usually seen in the 6th decade of
life. Men are more commonly affected than women (3:1).

Radiographs frequently reveal a soft tissue mass with sharply


defined margins high on the posterior pharyngeal wall.
These cysts lack bony involvement.
CT scan (axial and coronal sections) with contrast agent
helps in assessing the nature of the mass, spatial relationship with adjacent structures and bone involvement.
MRI shows a characteristic high signal intensity on
T2-weighted and intermediate to high signal intensity on
T1-weighted images. The variation in signal intensity
on T1-weighted images may be related to differences in
protein content or hemorrhage in the cyst.

Midline Cysts
In the midline cysts, the retention variety is more common
than the congenital cysts.
It is believed that the retention cysts occur due to
the fusion of the median recess of the pharyngeal tonsil.
Hemorrhagic contents along with shed epithelial debris
may be evident in the cyst. The cyst wall may show lymphoid follicles with pronounced germinal centers. The inner
epithelial lining is composed of cylindrical ciliated cells. It
is believed that the presence of inammatory stimulus may
produce squamous metaplasia.
The congenital midline cysts may originate from the pharyngeal bursa (Tornwaldts bursa) or from Rathkes pouch.
The clinical and histological features of the cysts originating from the pharyngeal bursa are similar to those
of the retention cysts. However, to differentiate these cysts
a simple thumb rule can usedcysts deep to the pharyngobasilar fascia arise from pharyngeal bursa whereas cysts
originating supercial to the pharyngobasilar fascia are
more likely to be retention cysts.
The pharyngeal bursa is a tubuliform invagination lying
at the junction of the nasopharyngeal vault with posterior
pharyngeal wall and extending between the heads of the
longissimus muscles of the head just above the uppermost
bers of the superior constrictor muscle of the pharynx. It is
estimated that the pharyngeal bursa persists in about 3%
of the normal adults.
324

These cysts rarely originate from Rathkes pouch. These


cysts exhibit a median base which is attached to the nasopharyngeal vault. Histological picture of these cysts are very classical. These cysts are lined by stratied squamous epithelium
that is related to the ectodermal origin of Rathkes pouch.

Management
Temporary relief of symptoms can be achieved by aspiration of the cystic contents or injection of sclerosing agents
into the cystic lumen such as ethanolamine oleate solution.
Surgical excision of the cyst is the treatment of choice.

THYROGLOSSAL DUCT CYSTS


The thyroglossal duct cysts are said to arise from the remnants of the thyroglossal duct that failed to regress. These
cysts can be present anywhere along the course (from the
base of the tongue to suprasternal region) of the remnant
of the thyroglossal duct.
Cysts located near the foramen caecum are lined by
stratied squamous epithelium, whereas cysts located near
the thyroid gland are lined by cells similar to thyroidal
acinar epithelium. It has been reported that almost half of
the thyroglossal duct cysts contain normal thyroid tissue
in their walls.

Chapter 12 Cysts of Orofacial Region

Clinical features
Thyroglossal cysts are usually seen in the midline. However,
it is estimated that about 38% of the cysts are seen slightly
off the midline (located adjacent to the outer surface of the
thyroid cartilage, deep to the strap muscles). Almost all
cysts are present in the vicinity of the hyoid bone.
Based on the anatomic location the thyroglossal cysts
can be categorized as suprahyoid, at the level of hyoid and
infrahyoid.
About 2025% are suprahyoid, 1550% occurring at
the level of the hyoid bone, where they may be anterior or
posterior to the hyoid bone, and 2565% occurring in the
infrahyoid part of the neck.
The differential diagnosis of thyroglossal duct cysts
includes dermoid cyst, branchial cleft cyst, lymphadenopathy, and a cystic nodule arising from the thyroid gland.
Ultrasonographic features
The cyst typically appears anechoic, well-circumscribed with
increased through-transmission. However, the cyst may also
present as homogeneous or heterogeneous complex hypoechoic lesion. Some cysts may present as truly anechoic,
some as predominantly anechoic but containing internal
debris and some have a complex heterogeneous echo pattern, and few others have a uniformly homogeneous pseudosolid appearance. The coarse echo pattern is due to the
proteinaceous content of the cyst secreted by the cyst lining.
Occasionally, such a uniform echogenic appearance may
lead to a false assumption of a solid lesion. However, when
gentle but uniform pressure is applied over the cyst with the
transducer, the contents tend to shift which is suggestive of
a cystic lesion. It is estimated that about 45% of the cysts
have thick walls due to inflammation and cellular debris.
Management
Sistrunk procedure involving resection of the cyst and
tract, and excision of the middle third of the hyoid bone is
the standard procedure employed in the management of
the thyroglossal duct cyst. However, incomplete resection
will cause recurrence.
However, when a malignancy is evident, a near total or
total thyroidectomy along with the Sistrunk procedure is
recommended. The adjoining lymph nodes need to be evaluated because of the likelihood of a intrathyroidal foci of
cancer.

LYMPHOEPITHELIAL CYSTS (Branchial


Cleft Cysts)
The word branchial is derived from the Greek word bragchia,
meaning gills. The term branchial cyst was first used by
Ascherson in 1832. He believed that these cysts arose from
impaired obliteration of branchial clefts or pouches.

Howie and Proops (1982) dened branchial cysts (or


lymphoepithelial cysts) as lesions found behind the angle
of the mandible in the anterior triangle of the neck at the
junction of the upper third and lower two-thirds of the
sternocleidomastoid muscle. The cysts have a lining of stratied squamous epithelium resting on a complete or incomplete band of lymphoid tissue with part of the cyst wall
resembling a lymph node.
Golledge and Ellis (1994) dened these cysts according
to two parameters: position and histology. With regard to
position, the lesion must lie outside the midline of the
neck or within any position in the lateral aspect of the neck.
With regard to histology, the cyst lining is squamous or
columnar and is surrounded by lymphoid tissue.
Pathophysiology
Literature review reveals many theories to explain the origin
of these cysts such as branchial remnants, cervical sinus
remnants, thymopharyngeal duct remnants and squamous
epithelium inclusions in a cervical lymph node.
However, most authors agree that these cysts are congenital branchial remnants. These branchial remnants may
clinically present as a cyst, sinus or stula. If a portion of
a cleft or pouch fails to involute completely, the entrapped
remnant will form an epithelial lined cyst called a branchial cyst.
Clinical features
It is estimated that almost 17% of the cervical masses in
pediatric population are branchial cysts. They are typically
present as a mass at the anterior border of the sternocleidomastoid muscle, at the junction of its upper and middle
third. In more general terms, the cyst can occur at any
level from the hyoid bone to suprasternal notch.
It is seen to affect males and females equally. However
some authors report that the branchial cyst is slightly
more common in males.
The branchial cleft cyst is an asymptomatic slowgrowing, uctuant mass that is usually seen in the 2nd
and 3rd decades of life. It is seen in close approximation
to the external ear, angle of the mandible and upper lateral
aspect of the neck.
These cysts generally occur unilaterally. However, in
approximately 2% of the patients the cyst may occur
bilaterally (bilateral presentation may indicate a familial
tendency). Large branchial cysts can cause difculty in
swallowing, speech and breathing. Infected cysts can turn
into abscesses and form sinuses that open into the skin or
pharynx.
Diagnosis
The diagnosis of branchial cleft cyst is made by a thorough
history, clinical signs, fine needle aspiration, ultrasonography
and CT.
325

Section V Cysts and Tumors of Orofacial Region

Straw-colored uid is aspirated from the cyst. Microscopically the aspirant may contain cholesterol crystals,
squamous cells, lymphocytes and polymorphonuclear cells.
Ultrasonographic imaging will show a circumscribed
mass of homogeneous low echogenicity. CT is a useful tool
to assess the topographical plane of the cyst and its proximity to the surrounding vital structures.
Differential diagnosis
Lipoma, cystic hygroma, thyroglossal duct cysts, lipomas,
lymphomas, and dermoid cysts should be considered in
the differential diagnosis of branchial cleft cysts.
Management
Infected cyst should be managed with appropriate antibiotics. Surgical excision of the cyst is the treatment of
choice.

CYSTIC HYGROMA
Cystic hygroma is a developmental entity characterized by
progressive dilatation of the lymphatic vessels. It was first
described by Wernher in 1843. It is estimated that 75% of
the cystic hygromas affects the head and neck region.
Cystic lymphangioma or macrocystic lymphatic malformation, rst described by Redenbacker (1828), is a term
used as a synonym for cystic hygroma.
It is believed that sequestered lymphatic rests that retain
their embryonic growth potential penetrate adjacent structures or dissect along fascial planes and eventually become
canalized. These spaces retain their secretions and develop
cystic components because of the lack of a venous outow
tract.
Clinical features
Approximately 60% of the cystic hygromas are present at
birth. By the age of 2 years 90% are apparent. The posterior triangle of the left side of the neck is most frequently
affected site. On clinical examination, these are large, soft
to doughy in consistency, painless swellings that can be
compressed. The skin overlying the swelling can occasionally show a bluish coloration. Transillumination is positive
in cystic hygromas.
Staging of cystic hygroma
de Serres et al (1995) proposed a staging system based on
the anatomical location:
1.
2.
3.

326

Stage I: Unilateral infrahyoid


Stage II: Unilateral suprahyoid
Stage III: Unilateral and both infrahyoid and
suprahyoid

4.
5.

Stage IV: Bilateral suprahyoid


Stage V: Bilateral infrahyoid and suprahyoid.

Rarely secondary infection or internal bleeding can result


in a sudden increase in the size of the lesion. Extremely
large sized cystic hygromas can impinge on the airway.
Cystic hygromas are relatively more frequently seen
in Turner syndrome, Down syndrome, Noonan syndrome
and Klinefelter syndrome.
Differential diagnosis
Branchial cleft cyst, thyroglossal duct cyst and branchial
cleft cyst can be considered in the differential diagnosis of
cystic hygroma.
Radiographic features
Ultrasonography, MRI and CT can be used to image cystic
hygroma. CT and MRI demonstrate ring-like margin
enhancement with sharp demarcation of cystic areas. The
cystic areas tend to appear circumscribed and discrete.
MRI may show hyperintense areas on T2-weighted
images and hypointense areas in T1-weighted images.
Histologic features
Most of the cystic hygromas exhibit a multicystic appearance. It is estimated that only 10% have a unilocular morphology. The lesion may vary in size from a few millimeters
to several centimeters. The lumen contains cystic fluid
which may appear clear or straw colored. The eosinophilic
cystic fluid contains high levels of protein. Cystic hygromas are made up of large irregular sinuses with a single
layer of flattened epithelial lining and fibrous adventitial
coats.
Management
Asymptomatic cases of cystic hygroma are best left
untreated with regular follow-up to evaluate for infection
or secondary pressure effects on surrounding structures.
Symptomatic cases can be managed with intralesional
injections of sclerosing agents (OK-432 [an inactive strain
of group A Streptococcus pyogenes], bleomycin, pure ethanol, and doxycycline) and surgical resection of the lesion.
It is believed that the inactive bacteria used as a sclerosing agent incites an inammatory response leading to
brosis of the cystic hygroma.
Though many authors strictly oppose aspiration of lymphatic formations as it may lead to infection and hemorrhage, Burezq et al (2006) in their article discussing their
30 years experience in managing cystic hygromas report
interesting results obtained with serial aspirations. In their
5-year follow-up of 14 patients who were subjected to
aspiration, no failures were reported. It is estimated that
15% of the cases show recurrence if incompletely surgically
excised.

Chapter 12 Cysts of Orofacial Region

DERMOID, EPIDERMOID AND TERATOID


CYSTS
Dermoid Cysts
Dermoid cysts may be located anywhere on the body surface, however these are characteristically located in the
region of fusion of embryonic processes. It is estimated
that dermoid and epidermoid cysts of the oral cavity
account for about 0.01% of all oral cysts. Literature review
reveals that these cysts account for about 1.6 to 6% of all
cysts affecting the head and neck region.
Dermoid cysts are categorized by a cystic cavity lined
by epithelium which contains all skin appendages like the
hair follicles, sebaceous glands and sweat glands.
Subtypes of dermoid cysts
Epidermoid cysts The epidermoid cyst cavity is lined by
epithelium which is devoid of any skin appendages.
Teratoid cysts These cysts are lined by an epithelium
which contains skin appendages as well as certain components of the mesoderm such as muscle and bone. These
cysts may contain respiratory, gastrointestinal, and connective tissues.
Etiology
The exact etiology of dermoid cysts is still unknown.
It is believed that when epithelial tissue is traumatically
implanted in utero or when a piece of epidermis is traumatically implanted in the lines of fusion of embryonic
elements, the epithelium undergoes sequestration.
Clinical features
Dermoid cysts can occur anywhere in the body. However,
these are commonly seen at the sites of fusion of embryonic
elements. These are commonly seen on the hands and feet.
Intraorally, midline of the oor of the mouth (sublingual dermoid cysts) is most commonly involved. However,
other rare sites of involvement are the tongue, lips, uvula
and buccal mucosa.
Ultrasonographic picture
Ultrasonography produces an echogenic picture in dermoid and epidermoid cysts due to the presence of cellular
material, cholesterol crystals, and keratin within the cyst.

basal cell carcinoma arising from the wall of an epidermoid


cyst, Ikeda et al described a case where basal cell carcinoma
originated from an epidermoid cyst and Lopez-Rios et al
reported a case of squamous cell carcinoma arising in the
wall of an epidermoid cyst.

PARASITIC CYSTS
Though parasitic cysts in the head and neck region are
rare, the common cysts that may be seen are cysticercosis,
hydatid cysts and trichinosis.

Cysticercosis
Human cysticercosis is a parasitic infection caused by Taenia
solium. Other forms of Taenia include saginata and Asian
Taenia. It is believed that the Asian Taenia is an intermediate
form between solium and saginata as it is morphologically
similar to T. saginata and uses pigs as the intermediate host
like T. solium.
Ingestion of fecally contaminated food, water, fruit or
vegetables containing the ova of T. solium causes human
cysticercosis. Human cysticercosis is endemic in various
parts of the world including Mexico, Africa, South-East
Asia, Eastern Europe, Central and South America and India.
Poorly cooked meat (pork) is ingested by humans who
are the only denitive hosts. The undercooked meat includes
eggs or proglottids of the pork tapeworm. In the stomach
the larval form (Cysticercus cellulose) is released following
digestion of the outer protective layer of the proglottids.
These cysticerci are then disseminated by the arterial blood
to various tissues, preferentially to the CNS (60%), eye
(70%) and skeletal muscle (5%).
Clinical features
Clinically the condition may range from an asymptomatic
nodule to life-threatening symptoms. Individuals may complain of nausea, vomiting and severe epigastric pain. CNS
involvement may cause irritability, convulsions and loss
of consciousness.
On clinical examination, calcied nodules may be palpated anywhere in the body. In the head and neck region
the common sites for presence of calcied cysticerci include
muscles of mastication, muscles of facial expression and
cervical muscles. Some of these calcied masses may be as
large as 10 mm.

Management
Epidermoid, dermoid and teratoid cysts are best managed
by surgical excision. There is no definitive evidence for
malignant transformation of epidermoid or dermoid cysts.
However, individual case reports of such malignant changes
have been reported in literature. Dini et al reported of

Diagnosis
The diagnosis of cysticercosis should be done following
thorough evaluation of the patients lifestyle, personal
hygiene history and nature of food consumption along
with the characteristic neurological and gastrointestinal
327

Section V Cysts and Tumors of Orofacial Region

symptoms, presence of palpable firm calcified masses in


the soft tissues and specific laboratory and radiographic
imaging modalities.
Serological tests such as enzyme-linked immunosorbent
assay (ELISA) and enzyme-linked immunoelectrotransfer
blot have the highest sensitivity and specicity in detecting isolated muscular cysticercosis.
Plain radiography, CT, MRI and ultrasonography can be
used. Radiographs show well-dened, homogeneously radiopaque elongated or ovoid mass which may mimic sialolith.
However cysticercosis presents as multiple calcications.

Diagnosis

Individuals should be educated to avoid the use of poorly


cooked pork. Fruits and vegetables (especially coriander
used for garnishing and raw leafy vegetables used in salads) should be thoroughly washed before consumption.
Hands should be thoroughly washed prior to handling
food substances.
No treatment may be required once the larvae are no
more viable and have formed calcications. Occasionally,
based on the location of these calcications some patients
may present with seizures, cerebral edema and vasculitis.
In such patients, anticonvulsants and corticosteroids
should be administered.
Viable larvae can be effectively managed with antiparasitic drugs such as praziquantel and albendazole.

Imaging modalities like ultrasonography, CT and MRI help


in diagnosing these cysts. These imaging modalities help
in assessing the dimension of the cyst and its relationship
to surrounding vital structures.
In their study of hydatid cysts, Zeyrek et al (2008) and
Kktrk et al (1999) reiterated the fact that the air bubble
sign in CT image was pathognomonic for perforated pulmonary hydatid cyst.
Apart from imaging modalities, serological tests such as
hydatid immunoelectrophoresis, ELISA, latex agglutination
and indirect hemagglutination (IHA) test can be employed.
Casoni intradermal test is also less frequently used. In
this test Casoni antigen (sterile hydatid uid) is injected
intracutaneously. The presence of immediate or delayed
wheal-and-are reaction is read as a positive result. However, as the test has low sensitivity and the potential for a
severe local allergic reaction, it is not routinely used.

Hydatid Cyst

Radiographic features

Hydatid disease is caused by tapeworm (Echinococcus)


infestation. Three species of Echinococcus are of relevance
to medicine; the most common Echinococcus granulosus
(causes cystic echinococcosis), Echinococcus multilocularis
(causes alveolar echinococcosis) and the rarest Echinococcus
vogeli (causes).
Hydatid disease is endemic to the cattle and sheep rearing regions of the world such as the Middle East, India,
Africa, South America, New Zealand, Australia, Turkey and
southern Europe. Exposure to food and water contaminated by the feces of an infected denitive host or poor
hygiene in areas of infestation can lead to echinococcosis.

Plain radiographs of the involved site may be taken.


However, the findings may not be diagnostic and occasionally no findings are seen. Radiographically, well-defined
radiolucency surrounded by a slender rim of radiopacity
(calcification) may be evident.
Ultrasound may show the presence of daughter cysts
and hydatid sand (the scoleces, daughter cysts and calcareous corpuscles of Echinococcus tapeworms in the uid
within a primary hydatid cyst). CT and MRI can assess the
extent and location of the cyst.
Saint Martin and Chiesa (1984) described the presence
of falling snowakes, an ultrasound sign, as characteristic of hydatid sand.
Khanna et al (2007) reported the presence of the water
lily sign in the contrast-enhanced computed tomography
(CECT) of the chest of a patient. They suggest that the
water lily sign (presence of a thin walled cystic cavity containing a freely oating endocyst) is pathognomonic for
Echinococcus.

Management

Clinical features
Hydatid disease primarily affects the liver (5570%) and
the lung (1835%). However, the less common sites that
are affected are the brain (common in children), heart,
kidney, ureter, spleen, uterus, pancreas, diaphragm and
muscles.
Emamy and Asadian (1976), Saxena et al (1983) and
Bickers (1970) reported cases of hydatid cyst affecting the
parotid gland.
The hydatid cyst grows slowly. It is usually diagnosed
in the 3rd and 4th decades of life. Symptoms usually
328

manifest gradually unless they cause pressure effects in the


brain and eyes. The cysts grow slowly, and a cyst is rarely
diagnosed during childhood or adolescence unless the
brain or the eyes are involved. Relatively large cysts (more
than 5 cm in diameter) tend to produce pressure effects
on the adjoining structures. Abdominal tenderness, tender
hepatomegaly, fever and chills are common symptoms seen
in hydatid disease.

Management and prognosis


Hydatid cysts are best managed surgically. However, the
use of albendazole (1 month prior to surgery) and 2 weeks
of praziquantel (2 weeks prior to surgery) will sterilize the

Chapter 12 Cysts of Orofacial Region

Figure 31

Hydatid cysts. Courtesy: Dr S Suguna Hemachander,


Mamata Medical College, Khammam, Andhra Pradesh

cyst, decrease the chance of anaphylaxis, decrease the


tension in the cyst wall (thus reducing the risk of spillage
during surgery) and decreases the rate of recurrence.
During the surgery 0.5% of silver nitrate or hypertonic
saline solution can be injected into the cystic lumen which
helps in killing the daughter cysts (Figure 31) which will
reduce the opportunity for spread following spillage of the
cystic contents.

Trichinosis
Trichinosis is caused by the ingestion of undercooked meat
containing larvae of the nematode Trichinella spiralis.
These larvae enter the lymphatics and blood circulatory
system and migrate to well-vascularized striated skeletal
muscle. The parasite has a predilection for the most metabolically active muscle groups such as the tongue, diaphragm,
masseter, intercostal and pectoral muscles. The average
incubation period is between 1 and 30 days. The larvae are
estimated to have a 510 year life span.
Clinical features
The disease generally affects adults with no sex predilection. The disease process progresses through various phases
such as intestinal phase, parenteral phase and convalescent
phase. The intestinal phase of the disease presents with
diarrhea, anorexia, weakness and abdominal cramps. Some
individuals may present with macular rashes. High degree
fever (104F) is another characteristic feature. The intestinal
phase lasts for about 1 week.
In the parenteral phase the larvae migrate from the intestine into the circulation. This process may continue for many
weeks to a few months. Patients may complain of severe
myalgia. At this stage, skeletal muscles, CNS, cardiac and
respiratory system are involved.

Generally, many months after the initial intestinal phase,


encystment and repair takes place. This phase of repair is
termed convalescent phase. Patients are usually cachexic
and extremely dehydrated in this phase.
Miloro and Kinney (1994) reported trichinosis affecting
the lateral pterygoid muscle that led to degenerative changes
in the TMJ following meniscectomies.
Lopez-Lozano et al (1988) reported bilateral facial
paralysis secondary to trichinosis. Bruce (1975) and Cheung
(1997) reported oral squamous cell carcinoma associated
with trichinosis. It is proposed that trichinosis may act as a
co-carcinogen along with other chemical carcinogens.
Diagnosis
The diagnosis of trichinosis involves blood picture, polymerase chain reaction (PCR), imaging techniques and
muscle biopsy.
Eosinophilia and leukocytosis may be seen in 60% of
the patients. The erythrocyte sedimentation rate is elevated.
ELISA is 100% sensitive on 50th day of infection. PCR can
be used for parasite isolation.
CT and MRI with contrast can be used to assess involvement of the CNS. The typical nding is 38 mm ring-like
lesions. However, muscle biopsy is still the gold standard
for diagnosing this condition. Approximately 1 g of muscle
tissue is obtained from the deltoid region for histopathological studies.
Management and prognosis
Untreated patients may die of pneumonia, encephalitis, or
cardiac failure in about 48 weeks.
Antipyretics and analgesics along with albendazole
(400 mg/kg 3 times a day for 14 days) or thiabendazole
(25 mg/kg twice a day for 57 days) will prevent systemic
dissemination.
Treatment of cysts of the jaws

The surgical treatment of cystic lesions of the jaws were


essentially established by Partsch of Germany.
The treatment of benign cysts of the jaws is surgical,
and there are two main operative procedures:
1.
2.

Marsupialization of the cyst cavity


Enucleation of the cyst, followed by:
a. Primary closure of the wound, or
b. Packing of the cystic cavity until healing by secondary intention has occurred.

Marsupialization of the cyst cavity (Partsch I procedure)


It consists of removing the overlying cyst epithelium and
bone, thus essentially deroofing the cyst thereby providing
a wide communication between the cyst cavity and the
329

Section V Cysts and Tumors of Orofacial Region

oral cavity. The result is a merging of the epithelium of the


cyst with that of the oral mucosa.
Modications of marsupialization

A modification of marsupialization is antrocystectomy,


which is undertaken for large cysts encroaching upon
the maxillary antrum. A wide opening is made between
the cyst cavity and the maxillary sinus. After healing, the
cyst epithelium merges with the antral epithelium just
as it does with the oral epithelium in marsupialization.
Waldrons technique is a two-staged technique that combines the two standard procedures of marsupialization

330

initially, followed by enucleation at a later date when


the cystic cavity has shrunk adequately.
Enucleation with primary closure (Partsch II procedure)
In 1910, Partsch advocated the enucleation of a cyst capsule followed by primary closure, and hence it is known as
the Partsch II procedure. In this method, the cyst capsule is
completely detached from the bone and shelled out. The
cyst cavity is then totally free of epithelium.
This surgical procedure leaves the opening to the cyst
covered by a mucoperiosteal ap and the space lled with
blood clot which eventually organizes to form normal bone.

CHAPTER

Tumors of Orofacial Region


Srikant N, Nandita Shenoy,
Ravikiran Ongole, Mala Kamboj

Benign Odontogenic Tumors

Traumatic Neuroma
Rhabdomyoma
Leiomyoma
Hemangiomas and Vascular Malformations
Hemangioma
Vascular Malformations
Capillary Malformations
Arteriovenous Malformations
Lymphatic Malformations
Fibroma
Giant Cell Fibroma
Fibromatoses
Myofibroblastoma

Ameloblastoma
Squamous Odontogenic Tumor
Clear-Cell Odontogenic Tumor
Calcifying Epithelial Odontogenic Tumor
Adenomatoid Odontogenic Tumor
Keratocystic Odontogenic Tumor
Odontome
Ameloblastic Fibroma, Ameloblastic Fibrodentinoma,
and Ameloblastic Fibro-odontoma
Benign Cementoblastoma
Odontogenic Myxomas
Odontogenic Fibroma
Desmoplastic Fibroma

Malignant Odontogenic Tumors

Benign Non-odontogenic Tumors

Odontogenic Carcinomas

Squamous Papilloma
Verruca Vulgaris (Oral Warts)
Verrucous Hyperplasia
Condyloma Acuminatum
Focal Epithelial Hyperplasia/Hecks Disease
Keratoacanthoma/Self-healing Carcinoma
Oral Melanoacanthoma
Acquired Melanocytic Nevus
Ossifying Fibroma
Juvenile Ossifying Fibroma
Peripheral Ossifying Fibroma
Osteoma
Chondroma
Benign Chondroblastoma (Codmans Tumor)
Benign Osteoblastoma
Giant Cell Granuloma
Peripheral Giant Cell Granuloma
Pyogenic Granuloma
Fibrous Hyperplasia: Denture-related
Congenital Epulis of Newborn
Lipoma
Neurogenic Tumors
Schwannoma (Neurilemmoma)
Neurofibroma

13

Malignant Ameloblastoma (Metastasizing)


Ameloblastic Carcinoma
Primary Intraosseous Squamous Cell
Carcinoma
Solid PIOC
Clear Cell Odontogenic Carcinoma
Malignant Epithelial Odontogenic
Ghost Cell Tumor

Odontogenic Sarcomas
Ameloblastic Fibrosarcoma
Odontogenic Carcinosarcoma

Epithelial Malignant Tumors


Epidermoid Carcinoma
Verrucous Carcinoma
Basal Cell Carcinoma
Malignant Melanoma

Connective Tissue Malignant Tumors


Fibrous Tissue Origin
Fibrosarcoma
Malignant Fibrous Histiocytoma
Synovial Sarcoma
Cartilage Tissue Origin
Chondrosarcoma

331

Section V Cysts and Tumors of Orofacial Region

Adipose Tissue Origin


Liposarcoma
Bone Tissue Origin
Osteosarcoma
Ewings Sarcoma
Vascular Origin
Kaposis Sarcoma
Angiosarcoma

ODONTOGENIC TUMORS
Odontogenic tumors are lesions of great interest and
importance to oral physicians, pathologists and maxillofacial surgeons alike, who for several decades have studied
and catalogued these lesions and developed modalities for
adequate treatment.
It is estimated that approximately 9% of tumors in the
oral cavity are odontogenic in nature, out of which 94.8%
are benign and 5.2% are malignant, 58.5% of benign
odontogenic tumors are ameloblastoma.
The age predilection for benign odontogenic tumors is
around 28 years and for the malignant odontogenic tumors
is more than 40 years. Most of the tumors have mandibular
predilection with the ratio of 3.2:1, with the maximum in
case of ameloblastoma showing a rate of 12.8:1.
There are different ways of dening the content of the
term tumor in its broadest sense and not restricted to
lesions that are denitively neoplastic. Benign tumor is
dened as a growth made up of normal cells that have no
signs of cancer.
These tumors have some characteristic properties such as
new uncoordinated growth that spreads by direct extension
unlimited growth potential, do not metastasize, are encapsulated and resemble tissue of origin histologically.

BENIGN ODONTOGENIC TUMORS


These are defined as lesions derived from epithelial or
mesenchymal elements or both that are part of tooth forming apparatus. These comprise a group of lesions which
have in common the fact that they arise from the odontogenic tissue. These develop from the epithelial part of the
tooth germ, the ectomesenchymal part, or from both. Their
behavior varies from frankly neoplastic, including metastatic potential, to non-neoplastic hamartomatous. The
pathogenesis of these tumors are not clear but can be
attributed to the following etiologies.
332

Muscle Origin
Leiomyosarcoma
Rhabdomyosarcoma
Nerve Origin
Neurofibrosarcoma

Lymphoid Origin and Hematological


Malignancies

Theories of Tumor Development


These tumors have been postulated to arise from enamel
organ, remnants, epithelium of odontogenic cysts and oral
mucosal buddings.
Etiology
Various etiological and predisposing factors have been
propounded for the development of tumors such as infection, irritation, trauma, dietary deficiency, viruses, hormonal changes and genetic factors.
Classification
With the first edition of the WHO classification on tumors,
about 30 years ago, the terminology and the diagnostic
framework became available, and this modern and logically constructed classification greatly intensified research
into the subject, and markedly stimulated the urge to publish
new findings. In 2000, the International Agency for
Research on Cancer (IARC) in Lyon, France started a new
book series, WHO Classification of Tumors. The new WHO
Blue Books encompass both histopathological and genetic
criteria for tumor classification (Table 1). Clinically it also
can be classified based on site, age and gender predilection as given in Tables 24.
The common clinical features of benign tumors include:
slow growing and well-circumscribed swelling, bony expansion, displacement and abnormal mobility of teeth and
absence of lymphadenopathy.
Diagnosis of benign tumors

Complete history: Pain, loose teeth, occlusion, swellings, dysesthesia, delayed tooth eruption
Thorough physical examination: Inspection, palpation, percussion, auscultation
Plain radiographs: Panaromic radiographs and dental
radiographs at contrasting angles
Advanced imaging: CT for larger, aggressive lesions

Chapter 13 Tumors of Orofacial Region

Table 1

Classication of odontogenic tumors

1. Tumors of odontogenic epithelium without odontogenic


ectomesenchyme
a. Ameloblastoma
b. Calcifying epithelial odontogenic tumor
c. Squamous odontogenic tumor
d. Clear cell odontogenic tumor
2. Tumors of odontogenic epithelium with odontogenic
ectomesenchyme with or without dental hard tissue formation
a. Ameloblastic fibroma
b. Ameloblastic fibro-odontoma
c. Ameloblastic fibro-dentinoma
d. Odontoameloblastoma
e. Adenomatoid odontogenic tumor
f. Complex and compound odontoma
3. Tumors of odontogenic ectomesenchyme with or without included
odontogenic epithelium
a. Odontogenic fibroma
b. Odontogenic myxoma
c. Benign cementoblastoma
4. Advanced imaging
CT for larger, aggressive lesions, ultrasonography for vascular lesions
5. Obtain tissue for histopathological evaluation
a. Fine-needle aspirationto rule out vascular lesions and
inflammatory conditions
b. Excisional biopsysmall tumors and unilocular tumors
c. Incisional biopsylarger lesions prior to definitive therapy

Obtain tissue
Fine-needle aspirationrule out vascular lesions,
inflammatory conditions
Excisional biopsysmaller cysts, unilocular tumors
Incisional biopsylarger lesions prior to definitive
therapy.

Ameloblastoma
Churchill in 1934, defined ameloblastoma as unicentric,
non-functional, intermittent growing anatomically benign
but clinically persistent. These are benign, locally aggressive polymorphic neoplasms that consist of proliferating
odontogenic epithelium.
Classification
Leon Barnes has classified ameloblastoma into four types on
the basis of behavioral pattern, anatomical location, radiographic appearances and histologic features as follows:
1.
2.
3.
4.

Unicystic
Multicystic
Desmoplastic
Peripheral.

Table 2

Tumors based on the age of predilection

025 years

More than 40 years

Adenomatoid odontogenic tumor


Ameloblastic fibroma
Ameloblastic fibro-odontoma
Odontoma
Peripheral ossifying fibroma
Benign cementoblastoma
Ameloblastic odontoma

Calcifying epithelial odontogenic


tumor
Ameloblastoma
Squamous odontogenic tumor
Odontogenic myxoma
Calcifying odontogenic fibroma

Table 3

Tumors based on the gender of predilection

Male

Female

Ameloblastoma
Ameloblastic fibroma
Ameloblastic fibro-odontoma
Ameloblastic odontoma
Calcifying epithelial odontogenic tumor
Odontoma
Benign cementoblastoma

Adenomatoid odontogenic
tumor
Squamous odontogenic
tumor
Odontogenic myxoma
Calcifying odontogenic
fibroma

Table 4

Tumors based on the site of predilection

Maxilla

Mandible

Adenomatoid odontogenic tumor


Calcifying epithelial odontogenic
tumor
Ameloblastic fibro-odontoma
Squamous odontogenic tumor

Ameloblastoma
Ameloblastic odontoma
Odontoma
Benign cementoblastoma
Odontogenic myxoma
Calcifying odontogenic fibroma

Clinical features
Ameloblastomas may be present over a wide age range but
are usually diagnosed in the 4th and 5th decades of life,
although they can occur in children or the elderly. About
80% of tumors occur in the mandible, of which some 70%
arise in the molar region and ascending ramus, 20% in the
premolar region, and 10% in the incisor region. In the maxilla, most of these also occur in the molar region but about
15% involves the antrum.
The tumor is slow growing and in the early stages may
be asymptomatic and discovered as an incidental nding.
As the tumor enlarges the patient may become aware of a
gradually increasing facial deformity and expansion of the
jaw bone (Figure 1A, B). The enlargement is usually bony
hard, non-tender, and ovoid or fusiform in outline but in
advanced cases, egg-shell crackling may be elicited due to
thinning of the overlying bone. However, perforation of
333

Section V Cysts and Tumors of Orofacial Region

bone and extension of the tumor into soft tissues are late
features. In the maxilla, even large tumors may produce
little expansion as the lesion can extend into the sinus and
beyond. Teeth in the area of the tumor may become loosened, but pain is seldom a feature.
Radiographically, the ameloblastoma appears most commonly as a multiloculated radiolucency (Figure 2A, B). Roots
of teeth involved by the tumor show varying degrees of
resorption. As the tumor enlarges it may become associated
with an unerupted tooth, particularly an impacted third
molar, and the appearances may mimic those of a dentigerous cyst. Less frequently, ameloblastomas present as a
single unilocular radiolucency indistinguishable from an
odontogenic cyst.

MRI findings
Characteristic findings are: multilocularity, mixed solid and
cystic components, irregularly thickened walls, papillary projections, and marked enhancement of the walls and septa.
Histopathology
There are six histologic subtypes: follicular, plexiform,
acanthomatous, granular cells, basal cell and desmoplastic. These can be found combined or isolated and not
related to prognosis of the tumor. The two main patterns
are anastomosing epithelial strands and fields or discrete
epithelial islands. The former pattern is called the plexiform (Figure 3) type, the others the follicular (Figure 4A).

Figure 1
A

(A) Ameloblastoma involving mandible. (B) Intraoral view of ameloblastoma involving mandible.
Courtesy: Dr Foluso Owotade

Figure 2
A

(A) Radiographic features of ameloblastoma (honeycomb appearance). (B) Ameloblastoma (soap bubble appearance).
Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

334

Chapter 13 Tumors of Orofacial Region

Both may occur within the same lesion. The follicles consist of a central mass of loosely connected, angular cells
resembling the stellate reticulum of the normal enamel
organ, surrounded by a layer of cuboidal or columnar cells
resembling ameloblasts. The nuclei of the latter are situated away from the basal ends of the cells, and this is
described as reversed polarity. The follicles are separated
by varying amounts of fibrous connective tissue stroma. A
variety of changes can occur within the stellate area of the
follicles and these include cystic breakdown, squamous
metaplasia, and granular cell change. The tumor epithelium in the plexiform type is arranged as a tangled network of anastomosing strands and irregular masses, each
of which shows the same cell layers as for the follicular
pattern. Thus, each strand or mass is bounded by columnar or cuboidal cells resembling ameloblasts, while the
Figure 3

Ameloblast-like
columnar cells
Stellate
reticulum-like
cells
Interconnecting
strands

central area is occupied by stellate reticulum-like cells.


Microcyst formation is commonly seen.
When extensive squamous metaplasia, often associated
with keratin formation, occurs in the central portion of a
follicular ameloblastoma, the term acanthomaotus ameloblastoma is used (Figure 4B).
Differential diagnosis
Differential diagnosis of ameloblastoma are given in
Box 1.
Treatment
The therapeutic approach to the ameloblastoma is still a
controversy. There are problems to determine incidence,
management or recurrence rate. Not every ameloblastoma
has the same destructive potential or recurrence tendency.
For unilocular cystic lesions in young patients, curettage
or enucleation is effective treatment. Solid lesions show
high recurrence rates (5090%) necessitating tumor excision or partial resection of the jaw bone. There seems
to be more consensus in the management of ameloblastomas in children, due to the psychological impact of an
aggressive resection, and its relationship with growth and
function.
Key points on ameloblastoma are given in Box 2.

Box 1

Differential diagnosis of ameloblastoma

Dentigerous cyst

Histopathological picture showing plexiform ameloblastoma.


Courtesy: Department of Oral Pathology and Microbiology,
MCODS, Mangalore

Keratocystic odontogenic tumor


Odontogenic myxoma
Lateral periodontal cyst

Figure 4
A

B
Ameloblastic
follicles
Cystic
degeneration
Stellate
reticulumlike cells
Ameloblastlike cells
showing
palisading

Ameloblastic
follicles
Squamous
metaplasia

Stellate
reticulumlike cells

(A) Histopathological picture showing follicular ameloblastoma. (B) Acanthomatous ameloblastoma.


Courtesy: Department of Oral Pathology and Microbiology, MCODS, Mangalore

335

Section V Cysts and Tumors of Orofacial Region

Box 2

Key points related to ameloblastoma

1. A benign but locally invasive neoplasm


2. Molar region/ascending ramus of the mandible is the most
common site
3. Typically multilocular soap bubble/honeycomb appearance on
radiograph but may be unilocular
4. Follicular and plexiform types are the two main histological patterns

Literature review
Ameloblastoma is a tumor with a complex biological character and presents a high recurrence rate even in patients
treated with radical therapy. It has been reported that the
aggressiveness of ameloblastoma may be related to the
histological subtype, in fact.
Reichart et al in a review of the literature, found recurrence rates for plexiform, follicular, acanthomatous and
unicystic ameloblastoma respectively of 16.7%, 29.5%,
4.5% and 13.7%. Proliferating cell nuclear antigen (PCNA)
is a cell cycle related antigen and has been used for the
evaluation of the proliferation ability of this tumor.
Determinants of biological behavior
Location Seventy-five percent in the mandible, but worse
prognosis in the maxilla due to spongier bone that facilitates dissemination of the tumor. There is an absence of the
contention effect that provides the mandibular cortical
bone.
Arquitectonic pattern This pattern of the lesion does have
a prognostic validity. Unicystic has a better prognosis than
multicystic or solid.

Unicystic Ameloblastoma
Unicystic ameloblastoma, a variant of ameloblastoma first
described by Robinson and Martinez in 1977, refers to
those cystic lesions that show clinical and radiologic characteristics of an odontogenic cyst but on histologic examination show a typical ameloblastomatous epithelium lining
part of the cyst cavity, with or without luminal and/or mural
tumor proliferation. This type of ameloblastoma typically
presents in a younger age group than other variants of
ameloblastoma (2nd to 3rd decade) and occurs predominantly in the mandibular third molar region.
Radiographically, it appears as a well-dened unilocular
radiolucency, usually associated with an unerupted tooth,
and is indistinguishable from a dentigerous cyst. The pathogenesis of the lesion is unknown. Although it may represent
ameloblastomatous change in a dentigerous or other type
of odontogenic cyst, the possibility that it was a grossly
cystic ameloblastoma from the outset cannot be excluded.

336

Histopathology
Based on the character and extent of tumor cell proliferation within the cyst wall, several histologic subtypes of
unicystic ameloblastoma are recognized, which include
those of simple cystic nature, intraluminal proliferative
nodules and infiltrative tumor islands in the cyst walls.
The lesion presents as a cyst lined by ameloblastomatous
epithelium comprising a basal layer of columnar cells with
polarization of their nuclei away from the basal lamina,
covered by a loose, vacuolated layer of stellate epithelial
cells. The diagnosis is made based on histopathologic
examination.
Treatment
This variant is believed to be less aggressive, tends to affect
patients at a younger age and its response to enucleation
or curettage is more favorable than the classic solid or
multicystic ameloblastomas.

Peripheral (Extraosseous) Ameloblastoma


Ameloblastomas occasionally present in the gingival or
alveolar soft tissues without involving bone. Such lesions
may arise from the basal cell layer of the oral epithelium
or from extraosseous rests of the dental lamina. These are
much less invasive than intraosseous tumors and less drastic surgery is required for their treatment. Histologically,
these may resemble intraosseous types or consist mainly
of basaloid cells.

Odontoameloblastoma (OA)
This is an extremely rare mixed odontogenic tumor
appearing within the maxillary bone, with both epithelial
and mesenchymal components. It is also known as ameloblastic odontoma, although the term odontoameloblastoma
(OA) was included in the 1971 WHO classification and
seems to be more appropriate due to the behavior of the
tumor like an ameloblastoma rather than as an odontoma.
Thoma et al described in 1944 the first case, it is an ameloblastoma in which focal differentiation into an odontoma appears to have taken place.
Histopathology
The marked histological polymorphism of odontogenic
tumors make the final diagnosis difficult and in some
cases it must be made based on clinical, radiologic and
histopathologic features. Moreover, Wachter et al could not
histologically differentiate between OA and ameloblastic
fibro-odontoma, and therefore suggest that they are the
same entity.

Chapter 13 Tumors of Orofacial Region

Treatment

Radiographic features

Commonly, its clinical presentation mimics an odontoma,


and therefore the definite diagnosis is based on the
histologic analysis following a simple extirpation and
curettage.

These tumors show an irregular radiolucent area which


may or may not be clearly demarcated from the surrounding normal bone. The radiolucency contains varying
amounts of radiopaque bodies due to calcification within the
tumor. Radiographic features which have been considered
characteristic of CEOT, coronal clustering and driven snow
patterns, are seen in only a small percentage of cases.

Squamous Odontogenic Tumor


The squamous odontogenic tumor is rare. Radiographically,
it usually presents as a well-circumscribed radiolucency
with a sclerotic border associated with the roots of teeth.
Histologically, the tumor consists of irregularly shaped
islands of well-differentiated squamous epithelium in a
stroma of mature fibrous tissue. It is thought to be derived
from the rests of Malassez.

Clear-Cell Odontogenic Tumor (Carcinoma)


This is a rare jaw tumor that some consider as a carcinoma
because of reported metastases. The histogenesis is
unknown, although it is believed to be derived from odontogenic epithelium because of its primary occurrence in
the jaws. Clear-cell odontogenic tumor (carcinoma) has
been described mostly in women above the age of 60 years.
It may cause some pain.
Radiographically, the lesion is lucent and either unilocular or multilocular. This rare lesion has an aggressive
biologic behavior. Metastases to lung and regional lymph
nodes have been reported.
Microscopically, nests and cords of clear cells are seen.
Some peripheral palisading may be present.
Differential diagnosis would include clear-cell variant
of calcifying epithelial odontogenic tumor, central mucoepidermoid carcinoma, metastatic renal cell carcinoma,
and poorly xed ameloblastoma.

Histopathology
The calcifying epithelial odontogenic tumor consists of
sheets of polygonal cells with ample eosinophilic cytoplasm,
distinct cell borders, and very conspicuous intercellular
bridges. Nuclei are pleomorphic with prominent nucleoli;
cells with giant nuclei and multiple nuclei are also present.
The epithelial tumor islands as well as the surrounding
stroma frequently contain concentrically lamellated calcifications. Stromal deposits of bone and cementum may
occur (Figure 5).
Treatment
The treatment for CEOT has ranged from simple enucleation or curettage to radical and extensive resection such
as hemimandibulectomy or hemimaxillectomy. The choice
should be individualized for each lesion because the radiological and histological features may differ from one
lesion to another.
Prognosis
The prognosis of the CEOT is good with infrequent recurrence. Malignant behavior is extremely rare. Although it has

Figure 5

Calcifying Epithelial Odontogenic Tumor


The calcifying epithelial odontogenic tumor (CEOT) is a
rare, benign epithelial neoplasm, also called Pindborg
tumor. It is an aggressive tumor of epithelial derivation
usually associated with an impacted tooth in the mandible
body/ramus.

Polyherdal
epithelial cells

Calcifications

Clinical features
It occurs over a wide age range and is about twice as common in the mandible as in the maxilla. The chief sign is
cortical expansion and pain is not normally a complaint.
Most of the tumors arise in the molar or premolar area and
about half are associated with the crown of an unerupted
tooth. Although most tumors arise within bone, extraosseous lesions have been reported.

Histopathological picture showing calcifying epithelial


odontogenic tumor. Courtesy: Department of Oral Pathology
and Microbiology, MCODS, Mangalore

337

Section V Cysts and Tumors of Orofacial Region

not been established in the literature, 5 years should be the


absolute minimum follow-up necessary to assess the healing for this type of odontogenic tumor.

Figure 6
A

Adenomatoid Odontogenic Tumor


History
Adenomatoid odontogenic tumor (AOT) is a relatively
uncommon distinct odontogenic neoplasm that was first
described by Steensland in 1905. However, a variety of
terms have been used to describe this tumor. Unal et al
produced a list containing all nomenclatures for AOT
reported in the literatures. Various names like adenoameloblastoma, ameloblastic adenomatoid tumor, adamantinoma, epithelioma adamantinum or teratomatous
odontoma have been used before to define the lesion currently called AOT.

Definition
Philipsen and Birn (1971), defined it as an odontogenic
epithelial tumor with an inductive effect on the odontogenic
mesenchyme. The nature of the lesion is uncertain and it
may be hamartomatous rather than truly neoplastic.
Classification
Based on the location it can be classified as:

Follicular
Extra follicular
Peripheral.

(A) Intraoral photograph showing obliteration of the labial


vestibule and the expansion of the labial and palatal
cortical palate on the left side of the anterior maxilla.
(B) Case of adenomatoid odontogenic tumor (AOT).
Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

Clinical features
The adenomatoid odontogenic tumor usually presents
during the 2nd and 3rd decades of life. The majority of
tumors arise in the anterior part of the maxilla (Figure 6A),
especially in the canine areas, and there are usually few
symptoms apart from a slowly enlarging swelling. Clinical
features generally focus on complaints regarding a missing
tooth. The lesion usually presents as asymptomatic swelling which is slowly growing and often associated with an
unerupted tooth. However, the rare peripheral variant occurs
primarily in the gingival tissue of tooth-bearing areas.
Unerupted permanent canines are the teeth most often
involved in AOT.

Histopathology
Lesion is well encapsulated and may be solid or partly
cystic; in some cases the tumor is almost entirely cystic. It
consists of sheets, strands, and whorled masses of epithelium which in places differentiate into columnar, ameloblast-like cells. The columnar cells form duct or tubule-like
structures (hence adenomatoid) with the central spaces
containing homogeneous eosinophilic material. These are
thought to represent abortive attempts at enamel organ
formation. There is very little supporting stroma. Small
foci of calcification are scattered throughout the tumor
and occasionally tubular dentin and enamel matrix may
be seen (Figure 7).

Radiographic features
On radiographs it usually appears as a well-defined radiolucency but in some cases calcification within the tumor
may produce faint radiopacities (Figure 6B). The lesion is
often associated with an unerupted tooth and may simulate
a dentigerous cyst (simulating a target like appearance).
338

Differential diagnosis
Radiologically, it should be differentiated from dentigerous cyst, which most frequently occurs as a pericoronal
radiolucency in the jaws. Dentigerous cyst encloses only
the coronal portion of the impacted tooth, whereas AOT

Chapter 13 Tumors of Orofacial Region

Figure 7

Figure 8

Duct-like space
Calcifications
Epithelial cells
(polyherdal to
spindle-shaped)
Dentinoid
Connective tissue

Histopathological picture of adenomatoid odontogenic tumor.


Courtesy: Department of Oral Pathology and Microbiology,
MCODS, Mangalore

shows radiolucency usually surrounding both the coronal


and radicular aspects of the involved tooth.
Common neoplastic causes, such as ameloblastoma,
CEOT, ameloblastic broma and ameloblastic bro-odontoma
are easily differentiated on histology.
Treatment
All variants of AOT are well-encapsulated and show an
identical benign behavior. Conservative surgical enucleation
or curettage is the treatment of choice with only rare
recurrence.
Literature review
The histogenesis of AOT is still uncertain, although recent
findings strongly indicate that AOT is derived from a complex system of dental laminae or its remnants. It is often
considered as a hamartomatous lesion rather than a true
neoplasm.

Calcifying Odontogenic Cyst


The calcifying odontogenic cyst (COC) was first described
as a distinct entity by Gorlin et al in 1962. This lesion is
uncommon and represents about 0.03% of the biopsy lesions
and less than 2% of all odontogenic cysts and tumors.
Clinical features
The calcifying cystic odontogenic tumor occurs over
a wide age range but is usually seen below 40 years of
age. About 75% are intraosseous and either jaw may be
involved. The majority, including those located in the gingival or alveolar soft tissues, arise anteriorly to the first

Radiograph of calcifying odontogenic cyst in the anterior


maxilla. Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

permanent molar tooth. The lesion usually presents as a


slowly enlarging but otherwise symptomless swelling. The
COC normally appears as a painless, slow-growing tumor,
affecting equally the maxilla and mandible, with predilection to the anterior segment (incisorcanine area). It generally affects young adults in the 3rd to 4th decade,
without gender predilection.
Radiographically, the lesion appears as a well-dened
unilocular or multilocular radiolucent area containing varying amounts of radiopaque, calcied material. It may be
associated with the crown of an unerupted tooth (Figure 8).
Histologically, the cyst is lined by epithelium which shows
a well-dened basal layer of columnar, ameloblast-like cells
and overlying layers of more loosely arranged cells that
may resemble stellate reticulum. A characteristic feature is
the presence within the lining of masses of swollen and
keratinized epithelial cells which are usually referred to as
ghost cells since the original cell outlines can still be discerned. The ghost epithelial cells may calcify. Breakdown
of the epithelium may release keratinous debris into the
supporting connective tissue resulting in a prominent
foreign body, giant cell reaction.

Keratocystic Odontogenic Tumor


Keratocystic odontogenic tumor is more universally known
as odontogenic keratocyst, but has been renamed as there
is sufficient evidence that this lesion actually represents
a cystic neoplasm. First described by Philipsen in 1956,
the odontogenic keratocyst (OKC) was later designated by
the WHO as a keratocystic odontogenic tumor (KCOT) and
is defined as a benign uni- or multicystic, intraosseous
339

Section V Cysts and Tumors of Orofacial Region

tumor of odontogenic origin, with a characteristic lining


of parakeratinized stratified squamous epithelium and
potential for aggressive, infiltrative behavior. WHO recommends the term keratocystic odontogenic tumor as it
better reflects its neoplastic nature.
Clinical features
KCOTs comprise approximately 11% of all cysts of the
jaws. These occur most commonly in the mandible, especially in the posterior body and ramus regions (Figure 8).
They almost always occur within bone, although a small
number of cases of peripheral KCOT have been reported.
Patients may present with swelling, pain and discharge or
may be asymptomatic. Distinctive clinical features include a
potential for local destruction and a tendency for multiplicity, especially when the lesion is associated with nevoid
basal cell carcinoma syndrome (NBCCS) or GorlinGoltz
syndrome. In the recent years, published reports have
influenced WHO to reclassify the lesion as a tumor.
Several factors form the basis of this decision.

Behavior: As described earlier, the KCOT is locally


destructive and highly recurrent.

Histopathology: Studies showed the basal layer of the


KCOT budding into connective tissue.

Histopathology
Histologically, these cysts are formed with a stratified
squamous epithelium that produces orthokeratin (10%),
parakeratin (83%), or both types of keratin (7%). The epithelial lining appears corrugated when viewed under a microscope. A well-polarized hyperchromatic basal layer is
observed, and the cells remain basaloid almost to the surface. No rete ridges are present; therefore, the epithelium
often sloughs from the connective tissue. The epithelium is
thin, and mitotic activity is frequent; therefore, OKCs grow
in a neoplastic fashion and not in response to internal pressure. The lumen frequently is filled with a foul-smelling
cheese-like material that is not pus but rather collected
degenerating keratin (Figure 9AC).
Radiographic features
Radiographically, KCOT presents predominantly as a unilocular radiolucency with well-developed sclerotic borders.
These may also present as a multilocular radiolucency or

Figure 9
A

Cystic space
Stratified
squamous
parakeratinized
epithelium
Palisaded
basal cells

Corrugated
parakeratin
layer
Connective
tissue

(A) Histopathological features of keratocystic odontogenic tumor. (B) and (C) Gross specimens of the resected tumor, showing
removal of the cystic lining and the resultant hollowing in the bone. Courtesy: Department of Oral Pathology and Microbiology,
MCODS, Mangalore. (D) Orthopantomograph showing well-defined scalloped radiolucent area extending across the midline.
Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

340

Chapter 13 Tumors of Orofacial Region

unilocular radiolucency at varying ratio. The multilocular


appearance can be more of a unilocular with scalloped
borders lacking true compartment formation. Odontogenic
keratocysts of the maxilla are smaller in size compared to
the mandible. When they are large, they tend to expand
bone. No difference in site distribution is seen between
unilocular and multilocular cysts. These lesions can also
present as a small and oval radiolucency between teeth
simulating a lateral periodontal cyst. They can also appear
as a radiolucency simulating a residual apical periodontal
cyst (Figure 9D).

On CT: Increased attenuation areas in cystic cavity.


On MRI: Heterogeneous intermediate signal on T1 and
high signal on T2 weighted images.

Treatment
A review of the literature suggests that recurrence rate is
relatively low with aggressive treatment, whereas more conservative methods tend to result in more recurrences.
Recurrence
KCOTs have a high recurrence rate, reportedly between
25% and 60% and when associated with NBCCS, the recurrence rate is about 82%.

incisors and canines, followed by the antero- and posteroinferior regions.


Complex odontomas are more often found in the area
of the second and third lower molars. An increased prevalence of these tumors is observed in children and adolescents, with few differences in relation to patient sex. These
lesions are normally diagnosed by routine radiological
studies in the 2nd and 3rd decades of life. As regards
their pathogenesis, odontomas have been associated with
antecedents of trauma during primary dentition, as well as
with inammatory and infectious processes, hereditary
anomalies (Gardners syndrome, Hermanns syndrome),
odontoblastic hyperactivity, or alterations of the genetic
components responsible for controlling dental development.
Radiographic features
Odontomas manifest as a dense radiopaque lesion surrounded by a thin radiotransparent halo. Three developmental stages can be identified, based on the radiological
features and degree of calcification of the lesion at the
time of diagnosis:
1.
2.
3.

Odontome
History
Paul Broca (1867), defined it as a tumor formed by the
overgrowth of transitory/complex dental tissues.
1946 WHO classification
1. Germinated composite odontome
2. Compound composite odontome
3. Complex composite odontome
4. Dilated odontome
5. Cystic odontome
In 1950 Gorlin eliminated the term composite odontome.
Recent WHO classification
1. Complex odontome: Malformation in which all the
dental tissues are represented, individual tissues being
mainly well formed but occurring in a more or less
disorderly pattern.
2. Compound odontome: Malformation in which all the
dental tissues are represented, in a more orderly pattern;
consists of tooth-like structures called the tooth-lets.

First stage is characterized by radiotransparency due


to the absence of dental tissue calcification.
Second or intermediate stage presents partial calcification.
Third or classically radiopaque stage exhibits predominant tissue calcification with a surrounding radiotransparent halo.

Compound odontomas show an irregular radiopaque image


with variations in contour and size, composed of multiple
radiopacities corresponding to the so-called denticles. In the
complex type of lesion radiopacity is not specific; rather, a
disorganized, irregular single or multiple mass is identified
(Figure 10).
Histology
Complex odontomas consist of a usually well-delineated
mass of dental hard tissues in a haphazard arrangement.
The bulk of the lesion consists of dentin recognizable by
the presence of tubuli. Enamel plays a minor role, usually
confined to small rims in cavities in the dentin mass. The
stroma consists of mature fibrous connective tissue. Sometimes, odontomas may contain areas identical to the calcifying odontogenic cyst, including ghost cells consisting of
tiny teeth that may vary in number from only a few to
numerous. These teeth do not resemble normal teeth, but
are usually cone shaped.

Clinical features
Odontomas are the most common maxillary tumors, and
according to different sources in the literature account
for 2267% of all odontogenic maxillary neoplasms. As to
their locations, most are found in the areas of the upper

Prognosis
Odontomas are benign tumors that sometimes produce
no symptoms and constitute casual findings of routine
radiological studies. However, they usually tend to cause
341

Section V Cysts and Tumors of Orofacial Region

Figure 10

Orthopantomograph showing odontoma. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

signs and/or symptoms such as delayed eruption. If no


signs or symptoms appear then the lesions go undetected.
A very infrequent situation in relation to odontomas can
be in the form of eruption.

Basal Cell Nevus Syndrome or GorlinGoltz


Syndrome
Basal cell nevus syndrome (BCNS) was first described by
Gorlin and Goltz in 1960, is an inherited disorder, with a
high penetration and variable phenotype expression. It
has a low incidence, around 1 in 56,000 persons. Its etiology is unknown, although the latest genetic studies relate
this syndrome to a disturbance at gene level of chromosome 9 (9q22.3q31), which is passed from one generation
to the next, although there are only sporadic cases due to
spontaneous mutation.
Clinical features
It is characterized by a series of associated manifestations,
the most common being maxillary keratocysts and cutaneous basal cell carcinomas, and other less frequent ones
which can be present, such as cardiac disturbances such as
persistent ductus arteriosus, characteristic facies in the
form of mandibular prognathia, frontal and parietal prominence, marked superciliary arches, wide bridged nose and
hypertelorism, skeletal (brachymetacarpalism of the fourth
and fifth fingers, vertebrae problems, costal synostosis or
bifid ribs), skin (dermoid cysts, lipomas), neurological
(congenital hydrocephalus, calcification of the cerebral
falx, learning difficulties), sight such as blindness, congenital cataracts, strabismus), hormonal (hypogonadism)
or associated with other malignant neoplasias. The appearance of pitted depressions, due to the lack of corneous
342

strata in the palms of the hands and soles of the feet, is the
only pathognomonic data which has been described in the
literature regarding this condition.

Ameloblastic Fibroma, Ameloblastic


Fibrodentinoma and Ameloblastic
Fibro-odontoma
The ameloblastic fibroma is a rare benign tumor in which
both the epithelial and mesenchymal elements are neoplastic. In ameloblastomas only the epithelium is neoplastic. It
is important to differentiate the lesion from ameloblastoma
since, unlike the latter, it does not exhibit a locally invasive
growth pattern.
Clinical features
The ameloblastic fibroma usually occurs in a younger
age group than ameloblastoma and is uncommon in above
21 years of age. It presents as a slowly enlarging painless
swelling and arises most frequently in the premolar or
molar region of the mandible.
Radiographic features
It is a well-circumscribed lesion and does not require the
radical excision that may be necessary to affect cure with
the ameloblastoma. Radiographically, the tumor appears
as a well-defined, usually unilocular, radiolucency. It may
be associated with an unerupted tooth and mimic a dentigerous cyst.
Histopathology
The tumor consists of proliferating strands and clumps of
odontogenic epithelium lying in highly cellular fibroblastic

Chapter 13 Tumors of Orofacial Region

Box 4

Figure 11

Differential diagnosis of ameloblastic broma

CEOT
Highly cellular
mesenchymal
stroma

Proliferating
odontogenic
epithelium

Histopathological slide of ameloblastic fibroma.


Courtesy: Department of Oral Pathology and
Microbiology, MCODS, Mangalore

Box 3

Key points on ameloblastic broma and related lesions

1. Ameloblastic fibroma and fibro-odontoma are benign neoplasms


2. Ameloblastic fibro-odontoma is probably a hamartoma
3. Well-circumscribed and occur mainly in 1st and 2nd decades
4. Comprises odontogenic epithelium and richly cellular mesenchyme
5. Fibrodentinoma contains dentin
6. Fibro-odontoma enamel and dentin

tissue resembling the dental papilla of the developing


tooth. The epithelial component shows a peripheral layer
of cuboidal or columnar cells which encloses a few stellate
reticulum-like cells (Figure 11). The appearances are similar to ameloblastoma but the stellate cells are much less
abundant and cyst formation is unusual. In some lesions
dentin may be present and such tumors may be designated
ameloblastic fibrodentinoma. The dentin is usually poorly
formed and includes entrapped cells. Tubular dentin is rare.
Literature review
Tumors previously classified as dentinomas are now thought
to be examples of the ameloblastic fibrodentinoma. The
ameloblastic fibro-odontoma is a tumor which shows further inductive changes leading to the formation of enamel.
Although the ameloblastic fibroma and fibrodentinoma
are benign neoplasms, it is probable that the ameloblastic
fibro-odontoma is a hamartoma. Histologically, it is difficult
to distinguish from a developing complex odontome, to
which it is probably closely related.
Key points on ameloblastic broma are given in Box 3.
Differential diagnosis is given in Box 4.

Odontoma
COC
AFO

Benign Cementoblastoma
Cementum is a modified form of bone and, with the exception of the cementoblastoma, disorders of the jaws containing cementum-like tissue are now classified as lesions
of bone. The cementoblastoma is still classified as an
odontogenic tumor because of its unique association with
the root of a tooth. Cementoblastoma is classified as an
odontogenic tumor because of its unique association with
the root of a tooth. This is one characteristic feature that
differentiates it from osteoblastoma of bone.
Clinical features
The cementoblastoma is a rare benign neoplasm most frequently seen in patients below 25 years of age. It usually
arises in the molar or premolar area of the mandible and
is attached to the root of a tooth. Most cases involve the
mandibular first permanent molar. It presents as a slowly
enlarging swelling which sometimes gives rise to pain, but
the involved tooth is vital. Pain is main symptom, pain is
severe and not relieved by NSAIDs.
Radiographic features
Radiographic features show a well-demarcated, mottled, or
dense radiopaque mass with a radiolucent margin attached
to the root of a tooth which usually shows resorption.
Histologic features
Tumor consists of a mass of calcified cementum-like tissue
containing scattered cells lying in lacunae. Around the
periphery and in other actively growing parts of the lesion,
extensive sheets of uncalcified matrix formed by plump,
deeply staining cementoblasts may be seen.
Prognosis
Lesions which are incompletely removed may recur.

Odontogenic Myxoma
These are uncommon, benign neoplasms arising from
mesenchymal odontogenic tissue which are locally invasive neoplasm consisting of rounded, angular cells lying
in abundant myxoid stroma.
343

Section V Cysts and Tumors of Orofacial Region

Clinical features

Desmoplastic Fibroma

Commonly seen in the 3rd decade of life with higher prevalence among women, and occurs mainly in the mandibular molar area. Presents as painless swelling or incidental
finding.

This is a rare fibrous lesion of the jaws. It is benign, but


aggressive, exhibiting a biologic behavior similar to fibromatosis of soft tissue or low-grade fibrosarcoma. It is seen
in young adults, especially in the mandible.
Radiographically, desmoplastic broma is lucent, with
margins that may be distinct or poorly dened.
Histologically, these lesions exhibit an interlacing or
fascicular growth pattern of benign broblasts and collagen. They neither contain epithelial rests nor make bone.
Multinucleated giant cells are rarely present. Desmoplastic
broma should not be confused with central low-grade
osteosarcoma which is more cellular and has cytologic
atypia.

Radiographic features
Often multilocular with internal osseous trabeculae arranged
in tennis racket pattern.
MRI: Prolongation of T1 and T2, reecting rich myxoid
stroma. Gradual contrast enhancement is typically seen on
contrast-enhanced images.
Histopathology
Odontogenic myxomas consist of rather monotonous cells
with multipolar or bipolar slender cytoplasmic extensions
that lie in a myxoid stroma. Nuclei vary from round to
fusiform in appearance. Binucleated cells and mitotic figures are present, but scarce. Occasionally, the lesion contains
odontogenic epithelial rests. The lesion spreads into the
jaw bone without any encapsulation, thereby engulfing
neighboring cancellous bone.
Treatment
Excision or partial resection of the jaw bone with high
rate of local recurrence due to infiltrative growth pattern
enhancement is typically seen on contrast-enhanced
images.

Odontogenic Fibroma
This jaw tumor is considered a neoplasm that is derived
from periodontal ligament or pulp-related fibroblasts. It is
a tumor of adults and appears as a well-defined radiolucency in either jaw. It is not, however, particularly aggressive, and it infrequently recurs after simple curettage.
Histopathology
These lesions are more collagenous than myxomas but
may range from myxofibrous to densely fibrous. Characteristically seen in odontogenic fibromas are few to many
islands and strands of bland odontogenic epithelium.
Calcific deposits may also be found. A variant (granular
cell odontogenic fibroma), in which granular cells are seen
in the connective tissue, has been described. The behavior
of this tumor does not appear to be different from odontogenic fibroma. Abundant rest proliferation in follicular sacs
can occasionally simulate the appearance of odontogenic
fibroma or ameloblastic fibroma.
Clinicopathological correlation is important for the
diagnosis of these lesions.
344

Treatment
Ennucleation/excision or partial resection of the jaw bone.

BENIGN NON-ODONTOGENIC TUMORS

Squamous Papilloma
Verruca vulgaris
Verrucous hyperplasia
Condyloma accuminata.

The primary disease processes that give rise to swellings


and tumors of the oral cavity include cysts, mucous
extravasations and retention in the minor salivary glands,
foci of granulation tissue and inflammation, abscesses and
connective-tissue proliferations that are well-defined or
encapsulated, as well as infiltrative sarcomas. Both epithelial and connective-tissue disease processes can present as
tumors. From a clinical perspective the three most important
defining characteristics of any soft tissue swelling are
location, coloration, and palpable nature.
Location Certain diseases tend to occur in specific sites
to the exclusion of others, as given in Table 5.
Coloration It is dependent upon the tissues present in
the mass and the depth of the lesion. In general, yellowappearing lesions are comprised of lymphoid tissue or adipose tissue, red swellings are vascular, blue swellings are
mucinous or venous, and brown swellings contain melanin or blood pigments. Lesions with normal mucosal pink
coloration are generally composed of fibrous tissues or
some other tissues lying deeper in the connective tissues
(Table 6).
Palpable nature Based on the consistency they can be
grouped as shown in Table 7.
Human papillomavirus (HPV) and oral lesions given in
Box 5.

Chapter 13 Tumors of Orofacial Region

Table 5 Soft tissue swellings according to site

Table 7

Site

Type of lesion

Palpation characteristic

Swelling

Lips and buccal


mucosa

Fibroma, mucocele, mesenchymal tumor, salivary


tumor

Soft, fluctuant

Gingiva

Parulis, pyogenic granuloma, peripheral fibroma,


peripheral giant cell granuloma, peripheral ossifying
fibroma, gingival cyst, peripheral odontogenic tumors

Mucocele, ranula
Developmental cysts
Sialocysts
Gingival cysts
Parulis
Abscess

Soft non-fluctuant

Lipoma
Fibroma
Organized mucocele

Firm fixed

Mesenchymal tumors
Granulomas
Salivary adenomas
Adnexal skin tumors

Firm movable

Granular cell tumor


Seborrheic keratosis
Keratoacanthoma
Fibromatosis

Palate

Abscess, torus, salivary gland tumor

Dorsum of the
tongue

Fibroma, granular cell tumor, pyogenic granuloma

Ventral aspect
of the tongue

Mucocele, ranula, lymphoid aggregates,


lymphoepithelial cyst, osteocartilaginous choristoma

Table 6

Soft tissue swellings according to their color

Soft tissue swellings according to their consistency

Color

Soft tissue mass

Blue-purple

Hemangioma, varix, hematoma, peripheral


giant cell granuloma, mucocele, Kaposi sarcoma

Red

Hemangioma, pyogenic granuloma, Kaposi sarcoma

Brown

Nevus, hematoma, seborrheic keratosis, Kaposi


sarcoma, melanoma

Box 5

Black

Melanoma

Verruca vulgaris 2, 4

Yellow-orange

Lymphoid aggregates, lymphoepithelial cyst, lipoma,


granular cell tumor

Squamous papilloma 6, 11

Human papillomavirus and oral papillary lesions

Condyloma acuminatum 6, 11
Focal epithelial hyperplasia 13, 32
Squamous cell carcinoma 16, 18, 31, 33, 35

Classication based on the tissue of origin is given in


Table 8.
Papillary lesions of oral cavity
Papillary lesions are those that are tumefactive with a cauliflower surface. Some are pedunculated, others are sessile.
Some are single, others are multiple or diffusely involve
broad areas of the oral mucosa. The vast majority of papillomas are associated with or indeed caused by members of
the HPV family, yet there are a few papillary growths that
have not been associated with HPV. One lesion in particular, molluscum contagiosum, is caused by a member of the
poxvirus group.

Squamous Papilloma
A benign epithelial proliferation induced by HPV in most
cases; several subtypes have been identified, especially
HPV-6 and 11.

Proliferative verrucous leukoplakia 6, 11, 16

In the form of white lesion, usually solitary; may be


multiple.
Squamous papilloma affects the buccal mucosa, soft
palate, uvula, tongue and gingiva.
Histopathology
Epithelial hyperplasia with fibrovascular cores may be
seen. The papillary projections may be sharp to blunt
(Figure 12). Epithelium may be dysplastic in some lesions
from HIV-positive patients.
Diagnosis
Lesions of the condyloma acuminatum, verruca vulgaris,
focal epithelial hyperplasia and verrucous carcinoma may
mimic lesions of squamous papilloma.

Clinical features
Exophytic, papillary mass, measuring less than 1 cm, usually
pedunculated and soft in texture.

Treatment
Surgical excision is the preferred modality of management.
345

Section V Cysts and Tumors of Orofacial Region

Table 8

Classication based on the tissue of origin

Epithelial

Papilloma
Keratoacanthoma
Nevus

Connective tissue

Fibroma
Giant cell fibroma
Peripheral ossifying fibroma
Lipoma

Vascular tissue

Hemangioma
AV fistula
Carotid body tumor

Lymphatic origin

Lymphangioma

Neural tissue

Neurilemmoma
Neuroma
Neurofibroma
Neurofibromatosis

Muscular origin

Leiomyoma
Rhabdomyoma

Bone origin

Osteoblastoma
Osteoid osteoma
Benign osteoblastoma
Desmoplastic fibroma of bone

Cartilaginous

Chondroblastoma

Histopathology
Histological changes can be in the form of surface hyperkeratosis, granulosis and koilocytosis.
AIDS-associated oral warts may appear dysplastic
microscopically.
Differential diagnosis

AV: Arteriovenous.

Focal epithelial hyperplasia


Keratoacanthoma
Papillary squamous carcinoma
Squamous papilloma
Condyloma acuminatum.

Treatment

Hyperplastic
epithelium

Treatment may involve surgery, laser surgery, or cryotherapy. It should be noted that HPV survives in aerosol.
Topical 5-fluorouracil treatment has been used on external
lesions, but should be avoided in fair individuals as it can
cause hyperpigmentation. It should be noted, however, that
this is a specialized treatment and should only be used by
those experienced with the use of this topical medication.
Lesions tend to recur after treatment.

Connective
tissue core

Verrucous Hyperplasia

Figure 12

Blood vessels

Histopathological slide of papilloma. Courtesy: Department of


Oral Pathology and Microbiology, MCODS, Mangalore

Verruca Vulgaris (Oral Warts)


Infection of mucosal epithelium by members of the human
papillomavirus groupusually HPV-2, 4, 6, or 11.
Clinical features
Papular to nodular and exophytic appearance. The warts
may be cauliflower-like, spiked, or raised with a flat surface,
346

perioral skin lesions may be brownish. The oral mucosal


lesions are usually white to pink. It can be pedunculated or
broad based.
Sites of predilection include the lips, palate, and attached
gingiva. The incidence of oral warts due to HPV has dramatically increased in the potent antiretroviral therapy
era. Diagnosis can be based on the clinical, microscopic
and immunohistochemical demonstration of HPV common antigen.

Lesion with an unknown etiology, even though tobacco


(smokeless) association has been reported, the role of HPV
is unclear and is even hypothesized to be a possible precursor to verrucous carcinoma.
Clinical features
Presents clinically as exophytic, papillary, keratotic fronds
of epithelium or can be a part of the proliferative verrucous leukoplakia spectrum.
Histopathology
Histologic features are in the form of papillary to verruciform surface projections in which keratin varies in thickness. They can be broad, bosselated epithelial ridges with
well-differentiated cellular features and can even mimic
an early verrucous carcinoma.

Chapter 13 Tumors of Orofacial Region

Differential diagnosis
Verrucous carcinoma, papillary squamous cell carcinoma
and proliferative verrucous leukoplakia can be considered
in the differential diagnosis.
Treatment
Excision or ablation (e.g. laser, electrocautery) has been
used successfully in the management of verrucous
hyperplasia.

Condyloma Acuminatum
Described in Chapter 22 on Sexually Transmitted Diseases
on page 630.

below the epithelium; marked pseudoepitheliomatous


hyperplasia.
Diagnosis
Clinical appearance can be confusing, the symmetrical
nature, oval or round configuration, and keratotic core are
indicative of KA.
Differential diagnosis

Squamous cell carcinoma


Molluscum contagiosum
Verruca vulgaris.

Treatment

Focal Epithelial Hyperplasia/Hecks Disease


Described in Chapter 6 on Red and White Lesions on
page 165.

Keratoacanthoma/Self-healing Carcinoma
Keratoacanthoma (KA) is usually encountered on the facial
skin and lips yet can also arise, albeit rarely, in the mouth.

Observation and careful follow-up local excision, cryotherapy and intralesional chemotherapy have also been
tried. Wong et al in their study reported oral isotretinoin
to be an effective treatment of multiple as well as solitary
keratoacanthomas. Canas et al reported that successful
treatment was achieved with administration of oral
isotretinoin. Spieth et al reported that intralesional methotrexate shows to be an effective, easy and inexpensive
alternative.

Etiology
Unknown, may be related to several factors, as follows:

Oral Melanoacanthoma (Melanoacanthosis)

Oral melanoacanthoma is a benign acquired pigmentation


of the oral mucosa characterized by dendritic melanocytes
dispersed throughout the epithelium. The lesion appears to
be a reactive process.

ViralHPV subtypes 11, 13, 24, 33, 57


Altered expression of cell cycle proteins including cyclin
E, p53, PCNA
Keratinocyte dedifferentiation reflected in deficient
desmoglein production
Immunosuppression
Sun damage
May represent a highly differentiated form of squamous
cell carcinoma.

Clinical features
Clinically these are characterized by a tumefaction with
round, mounded borders that surround a central core of hard
keratinized material that may appear pale yellow or brown.
The brown appearance is caused by extrinsic pigments that
become incorporated with the excessive keratin. Intraoral
KAs are generally non-pigmented. They can be solitary on
sun-exposed areas, including lip. They initially present as
erythematous papule with rapid growth over 48 weeks;
extremely rare intraorally.

Clinical features
Oral melanoacanthoma is seen in blacks, shows a female predilection, and occurs in the 3rd and 4th decades of life. The
buccal mucosa is the most common site of occurrence. The
lesion is smooth, flat or slightly raised, and dark-brown to
black in color.
Histopathologic features
Numerous benign dendritic melanocyte cells that are normally confined to the basal cell layer scattered throughout
the lesional epithelium. Basal layer melanocytes are also
present in increased numbers.
Treatment and prognosis

Histopathology
Histopathology shows keratin plus normal, peripheral epidermis and mature, premature keratinization; no invasion

Because of the alarming growth rate of oral melanoacanthoma, incisional biopsy is usually indicated to rule out the
possibility of melanoma.
347

Section V Cysts and Tumors of Orofacial Region

Acquired Melanocytic Nevus (Nevocellular Nevus,


Mole)
Nevus refers to congenital/developmental malformations.
Acquired melanocytic nevus represents localized proliferation of cells from the neural crest, called nevus cells. They
are called as first cousins of melanocytes and represent the
most common human tumors with white adults reported
to have an average to 40 cutaneous nevi per person but
intraoral lesions are rare.

348

Treatment
No active intervention is required, unless in case of clinical
suspicion and cosmetic concern.

Ossifying Fibroma
Described in Chapter 19 on Bone Diseases and Fibroosseous Lesions on page 571.

Clinical features

Juvenile Ossifying Fibroma

Acquired melanocytic nevi begin to develop during childhood and most cutaneous lesions present before 35 years
of age with no sex predilection even though racial differences are seen.
Head and neck region is a common site of involvement.
Junctional nevus is a sharply demarcated, brown or black
macule less than 6 mm in diameter. When nevus cells proliferate become slightly elevated soft papule it is called
as compound nevus. The degree of pigmentation becomes
less; most lesions appear brown or tan. Nevus gradually
loses its pigmentation, the surface may become somewhat
papillomatous, and hairs may be seen growing from the
center intradermal nevus remains less than 6 mm in diameter. Ulceration is not a feature unless placed at a region
of recurrent trauma. Intraoral melanocytic nevi are distinctly uncommon, they may arise on the palate or gingiva,
although any oral mucosal site may be affected. More than
one in ve intraoral nevi lack clinical pigmentation and
females are more affected; the average age at diagnosis is
35 years.

Described in Chapter 19 on Bone Diseases and Fibroosseous Lesions on page 572.

Histopathologic features

Pathogenesis

The acquired melanocytic nevus is characterized by a


benign proliferation of small, ovoid nevus cells, produce
melanin. Nevus cells typically lack the dendritic processes
like melanocytes tend to be organized into small, round
aggregates (thques). When lesional cells are found at
the junction between the epithelium and the connective
tissue, this stage is known as a junctional nevus. When
the groups of cells begin to drop off into the underlying
dermis or lamina propria. Within the underlying connective tissue, the lesion then is called a compound nevus.
When found only within the underlying connective tissue
this stage is called an intradermal nevus, the intraoral
counterpart is called an intramucosal nevus. The superficial cells typically appear larger and epithelioid, with
abundant cytoplasm and the middle portion of the lesion
have less cytoplasm, are seldom pigmented, and appear
much like lymphocytes. Deeper nevus cells appear elongated and spindle-shaped, much like Schwann cells or
fibroblasts.

Chronic irritation causes an abundance of fibrous connective tissue containing immature bone. Often patients traumatize the area again, and this promotes a cycle of more
exuberant tissue formation and varying surface ulceration.
There is a close resemblance to the pyogenic granuloma.
The lighter surface color is due to hyperkeratosis produced
through trauma.

Peripheral Ossifying Fibroma


Peripheral ossifying fibromas (POF) are reactionary lesions
thought to originate from submucosal connective tissue and
the periodontal ligament. The lesions are often confused
with either the more vascular (red to pink) pyogenic granuloma, or the fibroma that demonstrates more tissue colored lesions. Peripheral odontogenic ossifying fibromas
are classified most often in literature as reactionary lesions
rather than a benign tumor.
Etiology
It is thought that an exuberance of tissue is caused by an
initiating factor such as calculus, or a food particle that
becomes lodged in the sulcus, creating an initial irritation.

Clinical features
Peripheral odontogenic ossifying fibromas occur more
often in females and can be anywhere from 1 to 2 cm in
size. They occur most often in young adults, originate
from the periodontal ligament, and occur exclusively on
the gingiva as a sessile or pedunculated mass. The lesions
are normally found on the attached gingiva. The abundance
of tissue is usually the same color as the surrounding tissue, with a smooth surface. Sometimes the surface may be
more textured, depending upon the existing oral forces

Chapter 13 Tumors of Orofacial Region

Treatment and prognosis

Figure 13

The treatment of choice is excision of the lesion with the


periodontal ligament, and no recurrence is expected in most
instances. Complete removal is indicated since peripheral
odontogenic ossifying fibromas can reoccur when they are
not adequately removed. It is advised that the lesion be
removed down to the periosteum and that the adjacent
teeth be scaled to remove any remaining irritants. This will
assist in lowering the rate of recurrence.

Osteoma
Benign, slowly growing lesion composed of well-differentiated mature bone with a predominant lamellar structure.
It is usually an incidental finding or painless hard swelling.
Peripheral ossifying fibroma in the interdental regions of the
upper lateral and canine. Courtesy: Department of Oral
Medicine, KLE Institute of Dental Sciences, Bangalore

Etiology
Sporadic form is idiopathic or may be a component of
Gardners syndrome.
Clinical features

Figure 14
Stratified
squamous
epithelium

Sporadic form with frontal and sphenoid sites predisposed


or may be multiple. Solitary lesions are rare in jaws.
Radiographic findings
Well-circumscribed, dense, sclerotic. May be subperiosteal
or medullary (Figure 15).

Connective
tissue

Histopathology

Area of
ossification

Histology reveals dense areas of normal cortical and trabeculae (Figure 16).
Diagnosis

Histopathological slide of peripheral ossifying fibroma.


Courtesy: Department of Oral Pathology and
Microbiology, MCODS, Mangalore

Radiographic features
Microscopic features: Normal cortical and trabecular
bone.

Differential diagnosis

and location in the patients mouth. Additionally, the surface epithelium may be more of a dark color depending
upon the amount of trauma and inflammation that is produced with the lesion (Figure 13).
Histopathologic features
Microscopically, the tissue is composed primarily of cellular fibroblasts with various types of calcification including
bone, cementum and dystrophic calcification. The surface
epithelium may exhibit varying degrees of ulceration
(Figure 14).

Tori, exostoses
Ossifying fibroma
Osteoblastoma
Focal sclerosing osteitis.

Treatment
Local resection, if compromising.
Prognosis
Little recurrence potential when associated with Gardners
syndrome, malignant conversion of intestinal polyps is
assured.

349

Section V Cysts and Tumors of Orofacial Region

Clinical features

Figure 15

Chondromas may be seen at any age and has no gender


preference. It is seen as a slowly growing, non-painful
swelling. The anterior maxilla, which is the site where
vestigial cartilage rests are found, is the most commonly
affected site. The posterior regions of the mandible (usually beyond the cuspids), condyle, coronoid process and
the body of the mandible are the most commonly affected
sites.
The soft tissue chondromas are usually seen affecting
the soft palate, tongue and buccal mucosa.
Syndrome association

Lower occlusal view showing osteoma. Courtesy: Department of


Oral Medicine and Radiology, MCODS, Mangalore

Figure 16

Compact bone

Haversian system

Histopathological picture of osteoma. Courtesy: Department


of Oral Pathology and Microbiology, MCODS, Mangalore

Chondroma
Chondromas are benign tumors of mesenchymal origin
composed of multiple nodules of mature hyaline cartilage.
It is estimated that chondromas represent approximately
2.38% of osteocartilaginous tumors.
Chondromas are well-recognized tumors in the bony skeleton. However, these are relatively rare in the jaw bones.
Based on the location chondromas are classied as
enchondromas (account for 80% of these tumors, located
in the medullary cavity of the long bones, diaphysis), juxta
articular chondromas (related to extraskeletal cartilage),
extraskeletal chondroma or soft tissue chondroma (rare
cartilaginous tumor, involving hands, feet, tongue and
buccal mucosa).
350

Enchondromas are associated with Maffuccis syndrome


and Olliers disease.
Enchondromatosis or Ollier disease (WHO terminology)
is dened by the presence of multiple enchondromas and
characterized by an asymmetric distribution of cartilage
lesions that can be extremely variable (in terms of size,
number, location, evolution of enchondromas, age of onset
and of diagnosis, requirement for surgery).
The condition in which multiple enchondromatosis is
associated with soft tissue hemangiomas is known as
Maffuccis syndrome.
Maffuccis syndrome is a rare non-hereditary mesodermal dysplasia characterized by the presence of multiple
hemangiomas of the soft tissue and multiple enchondromas (usually of the phalanges and long bones). The syndrome can be associated with benign or malignant tumors
(parathyroid adenoma, pituitary adenoma, hemangioendothelioma, adrenal tumor, ovarian tumor, chondrosarcoma
and breast cancer).
Radiographic features
Radiographically, chondromas exhibit ill-defined to occasional well-defined radiolucent areas. Some lesions may
show the presence of radiopaque foci interspersed within
the radiolucent zones. Extensive lesions may cause destruction of the cortical plates. Root resorption may be seen.
Histopathologic features
Histologically chondromas are characterized by the presence of lobulated masses partially subdivided in nodules of
hyaline cartilage immersed in a fibrous stoma. Frequently
there are calcified foci and even ossification. The eosinophilic cytoplasm may exhibit vacuoles (Figure 17).
Management
Long-standing chondromas can undergo a sarcomatous
change. Surgical resection is the treatment of choice. However, recurrences have been reported.

Chapter 13 Tumors of Orofacial Region

Histopathologic features

Figure 17

Connective
tissue capsule

Chondrocytes
in lacunae
Hyaline
cartilage

Histopathological feature of chondroma. Courtesy:


Department of Oral Pathology and Microbiology,
MCODS, Mangalore

Benign Chondroblastoma (Codmans Tumor)


Ernest Amory Codman, in 1931 first described this tumor
as a variant of the giant cell tumors. However, in the
1940s Jaffe and Lichtenstein renamed the Codmans tumor
as benign chondroblastoma in accordance to its chondroblastic origin.
Chondroblastoma is a rare tumor of bones accounting
for about 1% of all bone tumors. It is rarely seen in the
maxillofacial region.
In the long bones, chondroblastoma is believed to arise
from the cartilage of the growth plates, and in the temporomandibular region, possibly from the cartilage of the
condylar process.

Polygonal chondroblasts are the main proliferating cells.


These have long or oval-shaped nuclei and a prominent
cytoplasmic membrane with cytoplasmic granules consisting of hemosiderin pigment. Occasionally, multinucleated
cells can be found. Chondroid matrix can be found outside
the cytomembrane where small calcifications may occur.
The most important feature is the linear deposition of calcication surrounding individual chondroblasts, giving rise
to a chicken-wire pattern (Figure 17).
Immunostaining occasionally can be helpful in conrming the diagnosis of chondroblastoma. S-100 protein is
strongly positive. Chondroblastomas are also positive for
vimentin. Reticulin stain reveals a honeycomb pattern.
Management and prognosis
Chondroblastoma generally exhibits local aggressive behavior with infiltration and invasion to the soft and hard tissues
around.
Surgical resection is the main treatment modality. It is
estimated that, when located in the long bones, the curettage of this tumor has a success rate of 90%. When located
in the temporomandibular region, the resection can be difcult because of the complex anatomical structure, which
results in a higher recurrence rate. It is estimated that the
recurrence rate is about 55%. Radiation should be avoided
because of the risk of developing a chondrosarcoma.

Benign Osteoblastoma
Benign osteoblastoma is an osteoid and bone forming
benign tumor of bone. It is an uncommon lesion that
accounts for 1% of all bone tumors and about 3% of all
benign bone tumors.

Clinical features
Chondroblastomas are usually seen in the 3rd decade of
life. Males are slightly more commonly affected than
females (1.86:1).
In the maxillofacial and the temporal region, mandible,
maxilla and the TMJ have been reported to be affected.
Patients may complain of a local mass, auditory dysesthesia, and limitation of mouth opening.
Radiographic features
On radiographs, chondroblastoma affecting the extremities appears as round to ovoid radiolucencies which are
well-defined, expansile in nature and usually exhibit a
sclerotic margin.
Chondroblastomas affecting the condyle have been
reported to have caused resorptive defects and occasionally enlargement of the condyle.

Clinical features
Benign osteoblastoma occurs in the 2nd and 3rd decades
of life, but the age range is 578 years. As to sex incidence,
there is male predominance 23:1. Benign osteoblastoma
can arise in any bone, but there is a predilection for the
vertebra, long bones, skull and small bones of the hand
and feet. Clinically, osteoblastoma is a well-circumscribed,
solitary lesion, which measures 2 cm or more and may be
as large as 12 cm. Usually, the lesion is not painful, or if
pain is present, it is not very responsive to salicylates.
Radiographic features
Radiographically, the picture may vary in accordance with
the size of the tumor and with the extent to which the tissue
is calcified. Osteoblastomas are well-circumscribed, expansive lesions with central radiopaque areas suggesting new
351

Section V Cysts and Tumors of Orofacial Region

bone formation, but it is less likely to provoke an outstanding bony sclerosis typical of osteoid osteoma.
Histopathologic features
Histologically, benign osteoblastoma consists of a highly
vascularized, fibrocellular stroma in which there are abundant newly formed trabeculae of immature bone and
osteoid. Proliferating osteoblasts are found lining the trabeculae of immature bone and osteoid. The major problem
for pathologists is the correct differentiation between
benign osteoblastoma and a number of lesions that may
have similar characteristics. Benign osteoblastoma and
osteoid osteoma have almost identical histologic features.
Based on this histologic similarity, Dahlin and Jonson in
1954 suggested a name giant osteoid osteoma for the
lesion that is denoted as the benign osteoblastoma in the
present.
Diagnosis
The diagnostic evaluation is based on the histologic features and the clinical behavior of the lesion.
Differential diagnosis
Osteoid osteoma, ossifying fibroma, condensing osteitis,
Pagets disease, fibrous dysplasia, chondroblastoma, cementoblasoma, aneurysmal bone cyst and giant cell granuloma.
Treatment and prognosis
Surgical excision, malignant transformation (osteosarcoma)
within a benign osteoblastoma is very rare.

Giant Cell Granuloma


The term giant cell granuloma (GCG) has also been introduced to account for the lack of pre-existing trauma or
reparative tissue in some of these lesions. Central giant cell
granuloma (CGCG) is described as a benign lesion affecting
the mandible and maxilla that consists of a massive fibrohistiocytic proliferation with numerous heavily hemosidrinladen multinucleated giant cells. In 1953, Jaffe first described
giant cell reparative granuloma (GCRG) as a benign lesion
affecting the mandible and maxilla.
Etiology
Probably reactive or responsive in nature. Speculation
suggests it may represent a developmental anomaly.

predominates 3:1 over that in maxilla and anterior to


molar teeth with tendency for bony expansion. Most cases
are non-aggressive, slow growing, and asymptomatic, with
no cortical breakthrough or root end resorption. Some cases
are recurrent and exhibit aggressive behavior with pain,
perforation, and rapid enlargement.
Radiographic findings
Usually multilocular, occasionally unilocular, radiolucency
with well-defined margins but borders may be scalloped.
It can displace teeth; less commonly it resorbs tooth roots;
they may even expand bone.
MRI: Heterogeneous intermediate signal on T1 and
T2 weighted image with contrast enhancement.
Differential diagnosis

Odontogenic lesions
Ameloblastoma
Odontogenic myxoma
Odontogenic keratocyst
Non-odontogenic lesions
Hemangioma
Aneurysmal bone cyst
Traumatic bone cyst.

Peripheral Giant Cell Granuloma


Peripheral giant cell granuloma (PGCG) is, for all practical
purposes, a site-specific variant of pyogenic granuloma
embedded with osteoclast-like multinucleated giant cells
and arising exclusively from the periodontal ligament
enclosing the root of a tooth. This unique origin, of course,
means that such a lesion can only be found within or upon
the gingiva or alveolar ridge, no other site is acceptable.
It is also called variously giant cell reparative granuloma, osteoclastoma, giant cell epulis, and myeloid epulis,
this lesion was rst reported as fungus esh in 1848.
Clinical features
The usual age for diagnosis is 4th to 6th decade, but there is
no marked age predilection. More than 60% of cases occur
in females and this predilection is more pronounced in the
older age groups. Individual lesions are nodular and pedunculated, frequently with an ulcerated surface with a red,
brown or bluish hue. Generally larger than pyogenic granuloma, the lesion may exceed 4 cm in size, but most lesions
remain less than 2 cm in diameter.

Clinical features
Most cases arise in those less than 30 years of age with
female predominance. It occurs exclusivity in mandible or
maxilla; rarely in facial bones. Occurrence in mandible
352

Radiographic features
Any alveolar region may be affected and radiographs may
show either a saucerization of underlying bone, periodontitis

Chapter 13 Tumors of Orofacial Region

Inflammatory
cells

Poncet and Dor in 1897 rst described pyogenic granuloma as granuloma pyogenicum. Over the years various
authors have suggested other names such as granuloma
gravidarum, pregnancy tumor, Crocker and Hartzells disease, vascular epulis, benign vascular tumor, hemangiomatosis granuloma, epulis telangiectaticum granulomatosa,
and lobular capillary hemangioma.

Connective
tissue stroma

Etiology

Figure 18

Epithelium

Blood vessels
Giant cells

Histopathological picture of peripheral giant cell


granuloma. Courtesy: Department of Oral Pathology and
Microbiology, MCODS, Mangalore

The etiology of the lesion is unknown, though it was originally believed to be a botryomycotic infection. It is theorized that pyogenic granuloma possibly originates as a
response of tissues to minor trauma and/or chronic irritation, thus opening a pathway for invasion of non-specific
microorganisms, although these microorganisms are seldom demonstrated within the lesion.
Clinical features

of underlying tissues, or an isthmus of soft tissue connecting to an intraosseous central giant cell granuloma.
Histopathology
The peripheral giant cell granuloma is comprised of an
unencapsulated aggregation of rather primitive but uniform mesenchymal cells with oval, pale nuclei and with a
moderate amount of eosinophilic cytoplasm. Mitotic activity is not unusual in the lesion and may even be pronounced in lesions developing in children and adolescents.
Stromal cells may be spindled with a background of collagenic fibers, or may be rounded with a less fibrotic background. A thin band of routine fibrovascular tissue
separates the lesion from the overlying epithelium, often
with dilated veins and capillaries. When surface ulceration
is present, the ulcer bed consists of routine fibrinoid
necrotic debris over granulation tissue (Figure 18).
Treatment
Peripheral giant cell granuloma is treated by conservative
surgical excision followed by curettage of any underlying
bony defect and careful scaling and root planing of associated teeth. A recurrence rate of 10% or more has been
reported, hence, re-excision may be necessary.

Pyogenic Granuloma
Pyogenic granuloma or granuloma pyogenicum is a wellknown oral lesion. It is a localized granulation tissue
overgrowth in reaction to mild irritation. The name pyogenic granuloma is a misnomer since the condition is not
associated with pus and does not represent a granuloma
histologically.

Pyogenic granuloma of the oral cavity occurs at any age


and in all populations with no racial predilection. Lawoyin
et al (1997) reviewed 38 cases from Ibadan, Nigeria and
reported an average range of 575 years with the mean
age of 33 years. Most studies demonstrate a definite female
predilection with a female to male ratio of 2:1. This is
attributed to the vascular effect of female hormones that
occur in women during puberty, pregnancy, and menopause (Figure 18). The lesions tend to occur more often
during the second and third trimester of pregnancy and
such lesions are referred to as pregnancy tumors. Daley
et al (1991) in their study indicated that the clinical diagnosis of pregnancy tumor can be given when describing
a pyogenic granuloma occurring in pregnancy, because it
describes a distinct lesion not on the basis of histologic
features but on etiology, biologic behavior, and treatment
protocol.
Marks et al reported that pyogenic granulomas may
occur anywhere in the body surface and except the oral
cavity, these are common around the ngers and toes. In
the oral cavity, pyogenic granulomas show a striking predilection for the gingiva, with interdental papillae being the
most common site in 70% of the cases. These are more
common in the maxillary anterior area than any other
area in the mouth. Gingival irritation and inammation
that result from poor oral hygiene, dental plaque, and calculus or overhanging restorations may be precipitating
factors in many cases (Figure 19).
The typical clinical presentation of pyogenic granuloma is a small, deep red to reddish-purple lesion occurring on the gingiva, which is either sessile or pedunculated.
The surface may be smooth, lobulated or occasionally
warty, which is commonly ulcerated and shows a tendency
for hemorrhage either spontaneously or upon slight
trauma.
353

Section V Cysts and Tumors of Orofacial Region

Figure 19

Figure 20
Stratified
squamous
epithelium

Vascular
spaces
Inflammatory
cells
Connective
tissue

Clinical photograph of pyogenic granuloma. Courtesy:


Department of Oral Medicine and Radiology,
MCODS, Mangalore

Histopathological picture of pyogenic granuloma.


Courtesy: Department of Oral Pathology and
Microbiology, MCODS, Mangalore

Diagnosis
Although pyogenic granuloma can be diagnosed clinically
with considerable accuracy, radiographic, and histopathological investigations aid in confirming the diagnosis and
planning the treatment. Marx et al (2003) reported that
radiographs are advised to rule out bony destruction suggestive of malignancy or to identify a foreign body or sharp
restorative margin that would need to be removed with the
lesion. Long-standing pyogenic granulomas, like other irritation hyperplasias can show dystrophic calcifications. The
radiographic appearance of such calcifications varies from
barely perceptible, fine grains of radiopacities to larger,
irregular radiopaque particles that rarely exceed 0.5 cm in
diameter.
Histopathologic features
All clinically suspected pyogenic granulomas must be biopsied to rule out more serious conditions as mentioned previously. The pathology is distinct consisting of a matrix of
edematous connective tissue in which numerous thin walled
vascular channels can be seen. These vessels sometimes
are organized in lobular aggregates, and some pathologists
require this lobular arrangement for the diagnosis (lobular
capillary hemangioma). There is also moderately dense
mixed cellular infiltrate. The overlying stratified squamous
epithelium may be atrophic or hyperplastic, and is usually
degenerated or ulcerated in large areas; and the ulcer edge
may have a primitive dysplastic appearance (Figure 20).
Treatment
Treatment of pyogenic granulomas consists of conservative
surgical excision, which is usually curative. Although these
are reactive hyperplasias, they have a relatively high rate
of recurrence after simple excision, especially in pregnant
patients. Pierson and Pierson reported a recurrence rate of
354

15% has been noted. After surgical excision of gingival


lesions, curettage of underlying tissue is recommended.

Fibrous Hyperplasia: Denture-related


(Epulis Fissurata)
It is more of a reactive lesion rather than a neoplasm.
Etiology
Trauma resulting from an ill-fitting denture. Exuberant
fibrous tissue repair secondary to repeated inflammation
and trauma.
Clinical features
It is found on vestibular mucosa, usually at facial aspect of
denture flange. Clinically appears as rounded folds of
broadly based fibrous tissue surrounding the overextended
denture flange. Ulceration often noted at depth of tissue
folds and is more common in anterior segment of the jaws.
It may occur on hard palate as a polypoid or leaf-like mass
(Figure 21).
Diagnosis
Location and presence of a chronically ill-fitting denture.
Treatment
Excision of all tissue and relining or reconstruction of new
dentures after excision.
Prognosis
No recurrence anticipated with properly fitting denture.

Chapter 13 Tumors of Orofacial Region

Figure 21

Differential diagnoses
Differential diagnoses include hemangioma, fibroma, granuloma, embryonal rhabdomyosarcoma, malignant granular
cell myoblastoma, alveolar rabdomyosarcoma, chondrogenic and osteogenic sarcoma and schwannoma.
Treatment
Surgery is the only possible treatment of these tumors.
Surgery should not be radical; it minimizes the danger of
damaging underlying alveolar bone and developing tooth
buds. Delay in operation may cause airway obstruction and
feeding difficulty. The tumor should be removed during
the immediate postnatal period.

Epulis fissurata of the lower ridge. Courtesy:


Department of Oral Medicine, Manipal College of
Dental Sciences, Mangalore

Lipoma
A lipoma is a benign neoplasm composed of fat cells, oral
and oropharyngeal lipomas are rather rare.
Etiology

Congenital Epulis of Newborn


The Greek word epulis means on the gum or gum boil
and has unfortunately been used for a variety of benign
tumors and tumor-like conditions having dissimilar structures and histogenesis. Congenital epulis is a rare benign
soft tissue tumor that was also named gingival granular
cell tumor of the newborn by Eppley. Since its first
description by Neumann in 1871, more than 170 cases
have been reported.
Clinical features
It occurs in females eight times more frequently than in
males and affects the maxilla three times more frequently
than the mandible. In 10% of cases, it may have multiple
locations. The size of this nodular or lobular tumor may
vary from a few millimeters to 90 mm of diameter. It has
a firm consistency, is covered by a smooth erythematous
mucosa and is attached by a stalk to the incisor, or sometimes, canine regions. This tumor is smooth-surfaced,
pedunculated, sometimes lobulated and arises from the
alveolar crest. Its size varies from a few millimeters to
9 cm. It is almost always located on the gingiva and is
found predominantly on the maxilla. More frequent in
females.

Its cause is unknown. Trauma and metaplasia of perivascular


connective tissue have been suggested as playing a role.
Clinical features
Asymptomatic, slow-growing; usually circumscribed, sessile, or pedunculated. Usually soft and compressive with
doughy consistency. When it is located superficially, a yellowish texture can be seen. In rare instances bilateral or
multiple occurrence has been reported (Pisanty, 1976). The
most common sites include buccal mucosa, tongue, floor
of mouth; it can be deep seated with no color alteration but
surface of larger lesions often is covered with telangiectatic vessels.
Histologic examination
Histologic examination of a lipoma shows a well-delineated
mass of lobules of fat cells with fibrous septa interspersed
between them (Figure 22). In rare instances one encounters
a benign infiltrative lipoma, which should not be confused
with a liposarcoma (Bennhoff and Wood, 1978). The distinction between a benign lipoma and a low-grade liposarcoma may indeed be difficult in some cases. When fibrous
tissue is a substantial part of a lipoma, the term fibrolipoma is applied. When vascularity is a prominent feature,
the term angiolipoma is used.

Histopathology
These tumors have large cells with an eosinophilic granular cytoplasm, but the congenital epulis is covered with a
normal gingival epithelium. The congenital epulis is more
vascularized.

Differential diagnosis

Soft tissue tumor


Minor salivary gland neoplasm
Metastatic disease.
355

Section V Cysts and Tumors of Orofacial Region

Figure 22

Figure 23

Epithelium

Antoni A tissue

Connective
tissue
capsule

Verocay bodies

Adipocytes

Histopathological picture of lipoma. Courtesy: Department of


Oral Pathology and Microbiology, MCODS, Mangalore

Treatment
Surgical removal is the treatment of choice. Recurrences
have not been reported with the exception of infiltrating
and intramuscular lesions.

Neurogenic Tumors

material between them, the so-called Verocay bodies


(Figure 23).
Treatment
Management consists of conservative surgical removal.
Recurrence is rare.

Although the distinction between a schwannoma (neurilemmoma) and a neurofibroma may be debatable, most
authors adhere to the concept that there are indeed two
separate entities.

Neurofibroma

Schwannoma (Neurilemmoma)

Clinical features

A schwannoma is a benign neurogenic neoplasm composed of Schwanns cells. In a review from the literature
152 cases of oral schwannomas were collected (Gallo et al,
1977).

A neurofibroma is asymptomatic and rarely occurs as a


single lesion. Most often neurofibromas are part of von
Recklinghausens disease. Quite often the tongue is involved;
in some cases resulting in unilateral macroglossia. Moreover,
the possibility of hereditary neuropolyendocrine syndrome
consisting of mucosal neuromas, pheochromocytoma of
the adrenal glands, and medullary thyroid carcinoma
should be taken into account. In general, the mucosal neuromas in that syndrome are already present at childhood,
being the first manifestation of the syndrome (Casino et al,
1981), Skin lesions with syndromic formscaf-au-lait
macules (characteristically six or more), uniform pigmentation with smooth contoured borders are seen.

Clinical features
The tumor may occur at all ages and does not show a preference for men or women. A schwannoma is a slowly growing, rather circumscribed, submucosally located tumor that
may be painful. No characteristic clinical features appear.
It may occur at any site in the oral cavity and rarely involves
the oropharynx.
Histopathologic features
Histologically, one sees an encapsulated tumor composed
of two cell typesthe so-called Antoni type A and Antoni
type B cells. The A cells have elongated nuclei and are
often arranged in a palisade pattern, including hyalinized
356

Histopathological picture of neurilemmoma.


Courtesy: Department of Oral Pathology and
Microbiology, MCODS, Mangalore

A neurofibroma is, like a schwannoma, derived from


sheath cells. It actually may represent in many instances a
hamartoma or a reactive process rather than a neoplasm.

Radiographic findings (when intrabony lesions are


present)
Blunderbuss expansion of the inferior alveolar foramen
with uniformly expanded alveolar canal in the body of the
mandible.

Chapter 13 Tumors of Orofacial Region

Histopathologic features

Histopathologic features

In contrast to the schwannoma, a neurofibroma is not


encapsulated. Proliferating Schwann cells are haphazardly
arranged, not showing the palisade arrangement of
schwannomas.

A rhabdomyoma is a well-circumscribed tumor. Based on


histopathologic characteristics and gross morphology, two
types are recognized: fetal and adult.
The adult type is composed of large, round or polygonal
cells with a slight granular cytoplasm. The cytoplasm may
contain lipoid material. Cross-striations may be found in
just a few cells. The fetal type almost exclusively occurs in
the rst few years of life. Histologically, this type is characterized by immature skeletal muscle in varying stages of
developmental and undifferentiated mesenchymal cells.
Differentiating a rhabdomyoma from a rhabdomyosarcoma
may be difcult.

Treatment
With a single neurofibroma, management consists of surgical removal. With multiple or massive involvement, surgical removal may be impossible to carry out and is indicated
only when malignant changes are suspected. With von
Recklinghausens disease, there is a 515% risk of malignant
degeneration. This seems especially true for deeply located
lesions (Maceri and Saxon, 1984).

Traumatic Neuroma
A traumatic neuroma is a reactive hyperplasia caused by
injury of a nerve.
Clinical features
Traumatic neuromas may occur anywhere in the oral cavity.
Occurrence in the oropharynx is exceptional. The lesion usually manifests itself as a small submucosal nodule that may
be painful at palpation. No characteristic clinical features
appear.

Treatment
Management of a rhabdomyoma consists of surgical
removal.

Leiomyoma
A leiomyoma is a benign neoplasm composed of smooth
muscle cells. The source of a smooth muscle tumor in the
oral cavity is believed to be the walls of blood vessels or
undifferentiated mesenchymal cells. Occurrence of a leiomyoma in the oral cavity is rare. In two reviews of the
literature (Natiella et al, 1982; Praal et al, 1982) approximately 80 oral leiomyomas were collected.

Histopathology
Histologically, masses of irregularly arranged nerve fibers
and Schwann cells are seen to spread diffusely throughout
the tissue, mimicking to some extent the picture of a neurofibroma.
Treatment
Management consists of conservative surgical removal, if
possible, followed by coagulation of the adherent nerve.
Recurrence is rare.

Rhabdomyoma
A rhabdomyoma is a benign neoplasm of striated muscle.
It is an exceedingly uncommon tumor.
Clinical features
The male-to-female ratio is more than 2:1. The mean age of
patients with a rhabdomyoma is about 40 years. Although
extracardiac rhabdomyomas show a preference for the
head and neck, occurrence in the oral cavity and oropharynx is rare. The floor of the mouth is the most common site.
Multifocal appearance is exceptional (Schlosnagle et al,
1983). The clinical presentation is a submucosal swelling
without any specific signs or symptoms.

Clinical features
The majority of reported leiomyomas of the oral cavity and
oropharynx were small, circumscribed, and asymptomatic
swellings, covered with an apparently intact mucosa. They
were either single or multiple.
Histopathologic features
A leiomyoma is composed of whorls of smooth muscle cells.
The diagnosis of leiomyoma can be difficult to make just
from light microscopic examination. The tumor should be
differentiated from fibromatosis and schwannoma on the
one hand and leiomyosarcoma on the other hand.
Management
Management consists of surgical removal with rare
recurrence.

Hemangiomas and Vascular Malformations


Congenital vascular anomalies have been and remain
poorly understood. Since 1982, hemangiomas and vascular
malformations have been recognized as distinct entities that
exhibit unique characteristics and demand appropriately
357

Section V Cysts and Tumors of Orofacial Region

tailored treatment plans. However, hemangioma still continues to be used as a clinical and pathological description
of different types of vascular anomalies.
History
Before the 1980s, the terminology that was used to describe
vascular anomalies was confusing and ambiguous. The
descriptive terminology used in the past (port-wine stain,
strawberry hemangioma, salmon patch) conjure up visual
approximation to the lesions but have no correlation with
the biological behavior or natural history of these lesions.
Mulliken and Glowacki introduced a simple classification
in 1982 that was based on the clinical, histochemical, and
cellular criteria to distinguish between the various vascular anomalies.

Hemangioma

Treatment
The natural history of hemangiomas should influence the
timing and type of intervention. Benign neglect is often
advocated. A useful approach to the management of hemangiomas can be based on the following:

Stage of the lesion


Type of lesion
Management of residual deformity.

In general, life-threatening and sight-threatening hemangiomas should be dealt with, regardless of the stage of the
lesion. Active intervention should be considered in all disfiguring hemangiomas, but each case should be managed
on its merits after careful discussion and counseling, to prevent potential psychosocial trauma and cosmetic deformity.
Ethunandan and Mellor stated that prednisolone is the
first-line drug of choice for the treatment of life- or sightthreatening hemangiomas.

Clinical features
This is the most common tumor in white infants, and the
head and neck region is the most commonly involved site
(60%). Most lesions are solitary (80%) and girls are more
affected than boys (3:1). Multiple cutaneous lesions (three
or more) are often associated with visceral involvement.
Facial hemangiomas have a predilection for segmental
distribution and for regions of embryological fusion
(Figure 24AC). Hemangiomas usually appear soon after
birth, typically proliferate during the 1st year of life and
then involute during the childhood years (up to 12 years).
Classification
Superficial hemangiomas originate from the papillary
dermis and present as bright red macular or papular
masses.
Deep hemangiomas originate from the reticular dermis
or subcutaneous tissues and appear as bluish or relatively
colorless masses.
Compound hemangiomas have supercial and deep components and were previously called capillary cavernous
hemangiomas. The current classication of hemangiomas
and vascular malformations is summarized in Table 9.
Histopathology
The histological features are dependent on the stage of the
lesion.
Proliferative phase: The lesion is highly cellular and contains plump proliferating endothelial cells and pericytes, with
a high mitotic activity and numerous mast cells. Vascular
channels are not prominent (Figure 24D).
Involutive phase: The endothelial cells are attened, the
cell turnover is normal and there are few mast cells.
358

Vascular Malformations
These are errors of morphogenesis that are populated by
stable mature vascular endothelium.
Clinical features
Both sexes are equally affected. Vascular malformations
are always present at birth (though some may not be
apparent until a later stage) and in contrast to hemangiomas, these never proliferate or involute. Instead, these
expand slowly and relentlessly throughout life, in pace
with the growth of the patient. Trauma, puberty, and pregnancy can cause accelerated growth. Unlike hemangiomas, vascular malformations are associated with skeletal
abnormalities in up to 35% of cases. Capillary malformations may be associated with SturgeWeber and Klippel
Trenaunay syndromes.
Classification
These lesions are subclassified according to the predominant type of vessel and characteristics of flow (Box 2).
Waner et al graded these lesions according to the degree of
ectasia of the vessels into grades IIV which correlate well
with the clinical features and outcome of treatment. The
degree of ectasia increases with age and the clinical features
depend on the depth and size of the lesion. The lesions are
usually soft, compressible, and enlarge in size when venous
pressure is increased.
Histopathology
Venous malformations are characterized by an abnormal
collection of veins, which do not have any demonstrable
mitotic activity in endothelial or pericyte cells. Capillary

Chapter 13 Tumors of Orofacial Region

Figure 24
A

Proliferating
capillaries
Epithelium
Extravasated
red blood
cells

(A, B, C) Clinical photograph of hemangioma. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore
(D) Histopathological section of hemangioma. Courtesy: Department of Oral Pathology and Microbiology, MCODS, Mangalore

malformation with cobblestone appearance in an adult lack


a uniform smooth muscle layer.

Capillary Malformations
Capillary malformations never regress spontaneously.
They often darken and thicken with age and the rate of
progression is probably related to the degree of absence of
the autonomic nerves in addition to other factors such as
hormonal influences and trauma. Troilius and Wrangsjo
in their recent study have emphasized the psychological
aspects of the birthmark and have suggested earlier
intervention to counteract the undesirable psychosocial
effects.

Arteriovenous Malformations
These lesions show slow but relentless growth which is the
norm and high-grade lesions present earlier in life and
expand more rapidly, whereas low-grade lesions present

later and are more likely to expand slowly. In general,


intervention should be planned as soon as the diagnosis is
made and timely intervention will not only prevent complications, but also allow the extent of resection to be considerably reduced. The decision to intervene should be based
on the age, location, flow characteristics, morbidity of the
treatment, and the risks of an untreated lesion.

Lymphatic Malformations
These lesions are the most difficult to eradicate. Microcystic
lesions in particular are diffuse, do not respect tissues planes,
and it is difficult to distinguish involved tissue from normal
tissue.
Macrocystic lesions, on the other hand, are more localized and respect tissue planes and are more easily excised.
Hancock advocated these options for treatment which
included laser ablation, excision, and sclerotherapy. Carbon
dioxide laser should be reserved for supercial mucosal
lesions. Because uid-lled vesicles are almost always
359

Section V Cysts and Tumors of Orofacial Region

Current classification of hemangioma and vascular


malformations
1. Hemangiomas
a. Superficial (capillary hemangioma)
b. Deep (cavernous hemangioma)
c. Compound (capillary cavernous hemangioma)
2. Vascular malformations
a. Simple lesions (low-flow lesions)
i. Capillary malformation (capillary hemangioma, port-wine
stain)
ii. Venous malformation (cavernous hemangioma)
iii. Lymphatic malformation (lymphangioma, cystic hygroma)
b. High-flow lesions
i. Arterial malformation
c. Combined lesions
i. Arteriovenous malformations
ii. Lymphovenous malformations
iii. Other combinations

connected to deeper cisterns, ablation should be continued


to a suitable depth to ensure destruction of most or all of
these cisterns. Recurrences are not uncommon and can be
treated in a similar manner.
Sclerotherapy is a promising, but as yet not fully evaluated option. It can be used either as denitive treatment or
for palliation when the morbidity of operation outweighs
the benets. Ogita and Tsuto tried OK-432 (lyophilized
Streptococcus pyogenes treated with benzyl penicillin) and
has been found to be successful in treating macrocystic
lesions, with the advantage of avoiding a scar.

Fibroma
The fibroma, also referred to as irritation fibroma, is by far
the most common of the oral fibrous tumor-like growths.
While the terminology implies a benign neoplasm, most if
not all fibromas represent reactive focal fibrous hyperplasia
due to trauma or local irritation. Although the term focal
fibrous hyperplasia more accurately describes the clinical
appearance and pathogenesis of this entity, it is not commonly used.
Clinical features
A fibroma may occur at any oral site, but it is seen most
often on the buccal mucosa along the plane of occlusion of
the maxillary and mandibular teeth. It is a round-to-ovoid,
asymptomatic, smooth-surfaced, and firm sessile or pedunculated mass (Figure 25A, B). The diameter may vary from
1 mm to 2 cm. The surface may be hyperkeratotic or ulcerated due to repeated trauma. Fibromas are most often
observed in adults, but they may occur in individuals of
any age and either sex.
360

Histopathology
Histologically, a fibroma is an unencapsulated, solid, nodular mass of dense and sometimes hyalinized fibrous connective tissue that is often arranged in haphazard fascicles.
A mild chronic inflammatory infiltrate may be present. The
surface epithelium may be hyperkeratotic, either hyperplastic or atrophic, and it may be ulcerated (Figure 25C).
Differential diagnosis
The clinical differential diagnosis of a fibroma includes giant
cell fibroma, neurofibroma, peripheral giant cell granuloma, mucocele, and benign and malignant salivary gland
tumors.
Treatment
Conservative excisional biopsy is curative, and its findings
are diagnostic. Recurrence is possible however, if the offending irritant persists.

Giant Cell Fibroma


A giant cell fibroma has a distinctive histologic appearance
that sets it apart from a conventional fibroma.
Clinical features
It appears as an asymptomatic sessile or pedunculated nodule
that is smaller than 1 cm in diameter. Often, it has a bosselated
or somewhat papillary surface. Most cases are diagnosed in
persons aged 1030 years. No sex predilection has been
reported. The most common sites are the mandibular gingiva, followed by the maxillary gingiva, the tongue, and the
palate.
Histopathology
Microscopically, a giant cell fibroma is an unencapsulated
mass of fibrous connective tissue that contains numerous
characteristic large, plump, spindle-shaped and stellate
fibroblasts, some of which are multinucleated. These cells
are easily observed in the peripheral areas of the lesion,
while the more central areas contain typical fusiform
fibroblasts. The surface epithelium is often corrugated and
atrophic.
Differential diagnosis
The clinical differential diagnosis includes squamous papilloma, irritation fibroma, pyogenic granuloma, and peripheral giant cell granuloma.
Treatment
Conservative excisional biopsy is curative, and its findings
are diagnostic. Recurrence is rare.

Chapter 13 Tumors of Orofacial Region

Figure 25
A

D
Epithelium
(stretched)

Bundles of
collagen fibers

(A, B) Irritational fibroma on the buccal mucosa. Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore. (C) Histopathological picture of fibroma. Courtesy: Department of Oral Pathology and
Microbiology, MCODS, Mangalore

Fibromatoses

Histopathology

The fibromatoses represent a group of infiltrating fibrous


proliferations with a biologic behavior and microscopic
appearance intermediate between those of benign fibrous
lesions and fibrosarcomas. In the head and neck region,
these are sometimes referred to as juvenile or aggressive
juvenile fibromatoses.

Microscopically, fibromatosis is characterized by a poorly


delineated, infiltrating cellular proliferation of mature
spindle cells arranged in streaming and interlacing fascicles. Collagen production is usually prominent. Infiltration
of the adjacent structures is common at the periphery, but
cellular atypia is not present.

Clinical features

Differential diagnosis

Patients of any age may be affected, but three-quarters of


all cases are diagnosed when the patient is younger than
10 years. No significant sex predilection is apparent. The
most frequent site of occurrence is the soft tissues adjacent
to the mandible. Intraoral presentations are rare, but they
most often involve the tongue or buccal mucosa. Lesions
appear as firm, painless, poorly demarcated masses with a
variable growth rate. They are locally aggressive and often
cause resorption of the underlying bone when present.

The differential diagnosis of a soft tissue fibromatosis is


myofibroma and rhabdomyosarcoma.
Treatment
Treatment consists of wide excision. The reported recurrence
rate of 24% for oral fibromatosis is considerably lower
than the 5070% rate reported for fibromatoses of the entire
head and neck region.
361

Section V Cysts and Tumors of Orofacial Region

Table 9

Typical radiographic features

Typical radiographic feature

Condition

Tennis racket appearance

Odontogenic myxoma

Soap bubble appearance

Ameloblastoma, aneurysmal bone


cyst, central hemangioma

Honeycomb appearance

CEOC, Od. myxoma, CGCG, central


hemangioma

Driven snow appearance

CEOC

Sunburst appearance

Osteoblastoma, osteosarcoma

Sunray appearance

Osteosarcoma, central hemangioma,


osteoblastoma

Ground glass appearance

FD, Pagets, hyperparathyroidism,


ossifying fibroma

Pepper pot appearance

Hyperparathyroidism

Eggshell appearance

Ameloblastoma

Onion peel appearance

Garres osteomyelitis

CEOC: Calcifying epithelial odontogenic cyst; CGCG: Central giant cell


granuloma; FD: Fibrous dysplasia.

Myofibroblastoma
Myofibroblasts are spindle-shaped cells with features of
both fibroblasts and smooth muscle cells. Myofibroblasts
have been identified in lesions other than myofibromas, but
when they are the predominant cell type in a tumor, the
terms myofibroma (if solitary) or myofibromatosis (if multicentric) are applied.
Clinical features
Tumors of myofibroblasts may occur in either sex and in
patients of all ages, with a mean age of 26.6 years. Solitary
myofibromas have a head and neck predilection, with the
mandible being the most common site of occurrence. The
most common oral soft tissue sites are the tongue, lips, and
buccal mucosa.
Radiographic features
Intraosseous jaw lesions most often manifest as well-defined
unilocular or multilocular radiolucencies.
Differential diagnosis
The clinical differential diagnosis for oral myofibroma
includes irritation fibroma, fibromatosis, peripheral giant
cell fibroma, neurofibroma, leiomyoma, and benign and
malignant neoplasms of the minor salivary glands.
Treatment
Treatment for oral myofibromas is conservative excision.
The recurrence rate is low, and spontaneous regression has
been reported.
362

Table 10

Malignant odontogenic tumors: WHO classication


(1992)

Odontogenic carcinomas

Odontogenic sarcomas

Malignant ameloblastoma

Ameloblastic fibrosarcoma
(ameloblastic sarcoma)

Primary intraosseous
carcinoma

Ameloblastic fibro-dentinosarcoma
Ameloblastic fibro-odontosarcoma

Malignant variants of
other odontogenic
epithelial tumors

Odontogenic carcinosarcoma

Malignant changes in
odontogenic cysts

MALIGNANT ODONTOGENIC TUMORS


Odontogenesis or tooth formation depends on the various
epithelial mesenchymal interactions. Thus, both epithelial
and mesenchymal tissues may form neoplastic lesions,
either purely epithelial or mesenchymal or showing a mixture of both. To be regarded as odontogenic, the tumor
must arise in the gingiva or jaws. With their neoplastic
potential, apart from forming benign odontogenic tumors,
they can also form malignant odontogenic tumors.
Malignant odontogenic tumors are very rare jaw entities comprising only about 4% of all odontogenic tumors.
Gradual accumulation of single cases can only provide some
information about their histomorphology, clinical appearances and behavior. If they arise from epithelium they are
odontogenic carcinomas and if from mesenchyme they are
odontogenic sarcomas or they can be of mixed type.
Classification
Till date, there is no well-accepted classification of these
tumors most of which are pathologic curiosities. Nonetheless
their importance to the unfortunate individuals so afflicted
is not to be underestimated. In the recent years several
classifications have been suggested by several authors.
The most widely used being the WHO classification of
1992 given by Pindborg (Table 10).
The classication has evolved with time as new articles
have been published over the years. The latest is the WHO
classication of 2004 given by Reichert and Philipsen
(Table 11).
Etiopathogenesis
The etiopathogenesis for odontogenic carcinomas is
unknown; studies to find out more are difficult because of
the rarity of these groups of lesions. Generally, these tumors
arise de novo within the jaw bones, from epithelium contained within cyst linings, or from malignant transformation

Chapter 13 Tumors of Orofacial Region

Table 11 Malignant odontogenic tumors: WHO classication

ODONTOGENIC CARCINOMAS

(2004)
Odontogenic carcinomas

Odontogenic sarcomas

1. Metastasizing malignant
ameloblastoma

1. Ameloblastic fibrosarcoma
(ameloblastic sarcoma)

2. Ameloblastic carcinoma
a. Primary intraosseous carcinoma
b. Secondary (dedifferentiated)
intraosseous
c. Secondary (dedifferentiated)
extraosseous

2. Ameloblastic fibrodentinosarcoma
a. Ameloblastic fibroodontosarcoma

3. Primary intraosseous squamous cell


carcinoma (PIOSCC)
a. PIOSCC solid type
b. PIOSCC derived from
odontogenic cysts
c. PIOSCC derived from keratinizing
cystic odontogenic tumors
4. Clear-cell odontogenic carcinoma
5. Ghost cell odontogenic carcinoma

of benign odontogenic tumors. Odontogenic carcinomas


arise from the epithelial components of the tooth germ. In
adults, the epithelial remnants of odontogenesis consist of
the reduced enamel epithelium that surrounds the crowns
of impacted teeth for as long as they remain trapped and
unerupted within the jaws, the rests of Malassez which are
located throughout the periodontal ligament and within
edentulous areas of the alveolar bone subsequent to tooth
loss and remnants of the dental lamina located in the gingiva. Odontogenic cysts of various types may also serve as
a tissue site for malignant transformation.
Diagnosis
Diagnosis of these lesions may be complicated for two
main reasons: first, due to their low frequency, which causes
the information about their clinical and histopathological
features be scant, and secondly due to the similar histopathological pictures with benign odontogenic tumors. The diagnosis is based upon the unique histopathological features
of odontogenic carcinomas. In general, all tumors classified
as odontogenic carcinomas exhibit typical microscopic features of malignancy with the exception of the malignant
(metastasizing) ameloblastoma and the clear cell odontogenic
carcinoma. Behaviorally, all the entities in this group have
the potential for either nodal or distant metastases.
Odontogenic sarcomas are thought to arise from the
ectomesenchymal tissue. They either arise de novo or from
pre-existing ameloblastic broma. Odontogenic carcinomas are much more frequent than odontogenic sarcomas.
A rare lesion having a mixed picture is termed as odontogenic carcinosarcoma.

Terminology used to describe diverse odontogenic carcinomas is varied and confusing. We will discuss the important
lesions.

Malignant Ameloblastoma (Metastasizing)


It is defined as an ameloblastoma that metastasizes in
spite of an innocuous histologic appearance. This implies
that the primary tumor shows no feature different from
the tumors that do not metastasize. Thus, this can only be
a retrospective diagnosis, after the occurrence of metastatic
deposits. Therefore, it is the clinical behavior and not the
histology of the lesion that justifies the diagnosis of a
malignant ameloblastoma. WHO defines this as a neoplasm
in which the pattern of an ameloblastoma is combined with
cytological features of malignancy, a definition not based
on behavior but histology.
Both the primary and metastatic foci are characterized
histologically by same benign tumor islands, which lack
any feature of malignancy. The metastatic foci show typical ameloblastic differentiation of the peripheral ameloblasts with palisading and reverse polarization of nuclei.
The outer palisaded stratum of ameloblasts surrounds a
zone of stellate reticulum which may show foci of squamous metaplasia. No pleomorphism or mitotic gures are
seen. The average time from initial treatment of the primary tumor to the appearance of metastasis is 9 years.
These metastases generally only arises after many surgical
attempts at treatment of the original lesion and are often
isolated pulmonary metastases that can sometimes be
treated surgically. Some also believe that metastases may
be caused by aspiration or implantation at the time of
surgery. Metastatic deposits of this lesion are mostly seen
in lungs, lymph nodes, brain, viscera, skin and bone.
The treatment of choice of the primary tumor and recurrences is excision. Radiotherapy too has been tried but its
value is questionable. Overall, very few cases have been
reported for a denitive treatment protocol to be evolved.
Behaviorally, malignant ameloblastoma may progress to
death.

Ameloblastic Carcinoma
It is a malignant epithelial proliferation that is associated
with an ameloblastoma (carcinoma ex ameloblastoma) or
histologically it resembles an ameloblastoma (de novo
ameloblastic carcinoma). It is an aggressive neoplasm that
is locally invasive (extending out of bone to involve the
infratemporal fossa, parapharyngeal space, the masticator
space, or cervical soft tissue) and can spread to regional
lymph nodes or distant sites, such as lungs and bones and
myocardium.
363

Section V Cysts and Tumors of Orofacial Region

The term was rst used by Shafer in 1974 to denote


ameloblastoma in which there had been histological transformation. Corio used the term for ameloblastoma that
shows cytological features of malignancy but is otherwise
recognizable as an ameloblastoma and may later metastasize. Ameloblastic carcinoma may arise de novo or from a
pre-existent benign odontogenic lesion such as an ameloblastoma or an odontogenic cyst.
Carcinoma ex ameloblastoma A carcinoma directly
contiguous with an ameloblastoma is appropriately termed
as a carcinoma arising from an ameloblastoma (carcinoma
ex ameloblastoma, carcinoma in ameloblastoma). The carcinoma arises when an ameloblastoma undergoes dedifferentiation (i.e. when a less-differentiated proliferative
clone arises from an ameloblastoma). This aggressive clone
overgrows the ameloblastoma and becomes the dominant
component.
De novo ameloblastic carcinoma If a carcinoma lacks a
component of conventional ameloblastoma, its unequivocal categorization as an ameloblastic carcinoma is considerably less secure. Its diagnosis is based on subjective
interpretation. Histologically, ameloblastic carcinoma is
characterized by epithelial nests and strands similar to the
plexiform or follicular patterns. The cells exhibit cytological atypia and mitotic activity. Furthermore, areas of squamous cell carcinoma may be seen. If the lesions are entirely
composed of this component and lack resemblance to
ameloblastoma, they should be diagnosed as primary
intraosseous squamous cell carcinoma.
Clinical features
It occurs equally in both the sexes. It causes jaw swelling,
frequently causing pain and rapid growth. Mandible is
more frequently involved. Radiographically, an ill-defined
area of radiolucency is seen; sometimes showing the
presence of focal radiopacities. Root resorption, perforated
buccal and lingual cortical plates of jaw and extension
into the soft tissues illustrate the destructive potential.
Treatment could be aggressive surgery, but this may be
followed by recurrences and extensive local spread. Radiotherapy has not shown effective results, but chemotherapy
with paclitaxel and carboplatin and oral cyclophosphamide has some effect. Death has been reported because of
extensive local recurrence involving base of the skull and
cranial cavity. Prognosis is poor if the tumor has already
metastasized.
Biomarker studies for proliferation and malignant genotype (aneuploidy) have shown that ameloblastic carcinomas have a higher proliferating cell nuclear antigen (PCNA)
index and a greater degree of aneuploidy than histologically benign ameloblastoma.
A rare variant is that which arises from gingival or alveolar mucosa epithelium termed as peripheral ameloblastic
364

carcinoma. These arise de novo or as dedifferentiated carcinomas from a pre-existing benign peripheral ameloblastoma.

Primary Intraosseous Squamous Cell Carcinoma


Primary intraosseous squamous cell carcinoma (PIOC) is a
squamous cell carcinoma that occurs within the jaw bone.
It is called primary because it is not a secondary deposit.
Metastasis from a distant primary to the jaw must be excluded.
The WHO denes primary intraosseous carcinoma as a
squamous cell carcinoma arising within the jaw, having no
initial connection with the oral mucosa, and presumably
developing from residues of the odontogenic epithelium.
These are typical invasive squamous cell carcinomas and
range from well to poorly differentiated varieties. The WHO
extends the denition of PIOC to include those lesions having
a distinctively odontogenic pattern with basal-type cells
forming alveoli or arranged in a plexiform pattern with
palisading of the peripheral cells.

Solid PIOC
These occur mainly in the posterior mandible, are more
often seen in males, may metastasize to regional lymph
nodes, and have a poor prognosis. It occurs commonly in
elderly patients (mean age 50 years). These tend to occur
in the mandibular body where they may compress the
inferior alveolar nerve causing pain and/or paresthesia.
Loosening of teeth and mandibular expansions are signs.
Radiographically, these may be well-circumscribed as well
as more diffuse with irregular moth-eaten borders. The
tumors metastasize regionally and distantly and show a
3040% 5-year survival.
Cystic PIOC (PIOC arising in an odontogenic cyst, PIOC
ex odontogenic cyst) Cystic PIOC is a squamous cell carcinoma that demonstrates a cystic component with a
lumen that contains fluid or keratin and a lining of stratified squamous epithelium that exhibits cytological atypia.
Primary intraosseous carcinomas may develop from a still
recognizable precursor lesion such as the epithelial lining
of an odontogenic cyst. The linings of residual apical periodontal cyst, OKC and dentigerous cyst have shown malignant transformation. Moreover, reduced enamel epithelium
has been documented as tissue of origin in cases in which
an impacted tooth was presented within the tumor.
Co-occurrence of squamous odontogenic tumor and ameloblastomas has been reported. Most carcinomas arising
from the cyst linings are well or moderately differentiated.
Carcinoma ex dentigerous cyst The most common
odontogenic cyst to show carcinomatous changes is the
dentigerous cyst. Few cases that lacked rigorous evidence
of dentigerous cyst formation, but showed thickening of
pericoronal soft tissue that was associated with an impacted
tooth, were reported as carcinoma ex dentigerous cyst.

Chapter 13 Tumors of Orofacial Region

Intraepithelial neoplasia that involves gingival crevicular


epithelium can mimic carcinoma ex dentigerous cyst histologically. Most carcinomas arising in dentigerous cysts
occur in the mandibular molar area; however, they
occasionally are associated with impacted canine teeth.
Usually, the carcinoma is treated by surgical resection.
Histologically, the lesion demonstrates membranous connective tissue that is lined by stratified squamous epithelium that exhibits evidence of intraepithelial neoplasia
that is associated with an invasive well-differentiated or
moderately differentiated squamous cell carcinoma.
Carcinoma ex OKC Cases have been reported to arise
from cyst lining of OKC. In most, the radiographic findings
are those of a benign OKC and the unexpected carcinoma is
recognized following incisional biopsy or enucleation.
They have been usually treated by resection and postoperative radiation therapy.
Intraosseous mucoepidermoid carcinoma (central mucoepidermoid carcinoma, PIOC with mucous cells) It
arises from odontogenic epithelium or an odontogenic
cyst. It represents a cystic primary intraosseous carcinoma
that shows squamous differentiation and mucous cells;
lesional cells focally exhibit cytoplasmic mucicarmine
positively.

Clear Cell Odontogenic Carcinoma


It is also known as clear cell ameloblastic carcinoma, clear
cell ameloblastoma, clear cell odontogenic tumor. It is a
low-grade carcinoma that is composed of cells that show
uniform nuclei and clear cytoplasm. It was initially designated as clear cell odontogenic tumor, but this lesion
behaves aggressively and metastasizes too, so it is better
termed as clear cell odontogenic carcinoma (CCOC).
The anterior mandible is the site of predilection but other
jaw areas may be involved also. About 70% of females are
affected with an age range of 1789 years. The tumor has
a varied radiographic appearance. Often, it presents as a
unilocular expansile radiolucent lesion with an indistinct
periphery; however, some cases are multiloculated and
well-circumscribed. Connement of the lesion to the jaws,
presence of columnar cells resembling ameloblasts, and
the occasional presence of dentinoid structures prove it to
be odontogenic in nature.
Three histopathologic patterns have emerged. The more
common pattern is a biphasic tumor characterized by
oval and linear nests of clear cells intermixed with smaller
islands of polygonal cells with eosinophilic cytoplasm.
Occasionally, these two cell types coexist in a tumor nest
yielding a glomeruloid appearance. The nuclei are oval
and monomorphic. If pleomorphism or hyperchromatism
occur, it is generally within the nuclei of the polygonal
cells. The stroma of CCOC is distinctive. Fibroblastic cellularity is high and the collagen is mature, wrapping tightly

around the tumor cells. Squamous differentiation has also


been reported.
Metastases are found in lymph nodes and lungs.
Metastatic disease may occur more than 5 years after initial diagnosis. Differential diagnoses include metastatic
renal cell carcinoma, ameloblastoma with clear cells, clear
cell variant of CEOT and the clear cell variant of mucoepidermoid carcinoma.

Malignant Epithelial Odontogenic Ghost Cell


Tumor
It is also called odontogenic ghost cell carcinoma (OGCC),
ghost cell odontogenic carcinoma, aggressive epithelial
odontogenic ghost cell tumor, dentinogenic ghost cell
tumor. It is an ameloblastic carcinoma that shows evidence of ghost cell keratinization. It is a tumor that combines the elements of a benign calcifying odontogenic cyst
(COC) with a malignant epithelial component. The biological behavior of the tumor is unpredictable, characterized
by indolent growth and others by local aggressive growth,
and distant metastasis. The tumor apparently arises most
often from malignant transformation of a pre-existing
benign COC. OGCC has to show both the features of a
COC-ameloblastoma-like tissue together with ghost cell
keratinization as well as solid epithelial areas showing
cytonuclear atypia. Both components may be distinct from
each other or admixed.
Three distinct origins are thought: occurring de novo
with benign COC and a malignant epithelial component histologically present in the same lesion, occurring after the
recurrence of a benign COC, or arising from odontogenic
tumor. The biologic behavior of a lesion cannot be predicted
from the presence of ghost cells. The tissue that surrounds
the ghost cells gives the prognosis. Ghost cells are immunoreactive for amelogenin, a protein that is unique to the
enamel matrix.
It is seen more in males in an age range between 13 and
72 years. About 66% of the cases occur in maxilla. It is
more in Asians. Radiographically, it presents as an expansile multiloculated to poorly delineated radiolucent lesion.
Lesional tissue subjectively reveals features that warrant
a malignant interpretation, including cytologic atypia,
increased mitotic activity, an inltrative growth pattern
(perineural or intravascular invasion) and necrosis.

ODONTOGENIC SARCOMAS
These tumors may arise de novo or from a pre-existent ameloblastic fibroma or ameloblastic fibro-odontoma. Whether
an odontogenic sarcoma displays deposition of hard dental
tissues has not shown any prognostic significance. Odontogenic sarcomas arising from pre-existing ameloblastic
365

Section V Cysts and Tumors of Orofacial Region

fibroma occurs at a higher mean age (33 years) those that


develop de novo (22.9 years). The main clinical problem of
odontogenic sarcoma is relentless local growth.

pertaining to molecular events in the carcinogenesis of


odontogenic epithelium and mesenchyme, thereby shedding
more light on the origin, pathogenesis, biologic behavior,
treatment and prognosis of malignant odontogenic tumors.

Ameloblastic Fibrosarcoma
It is also known as odontogenic sarcoma, ameloblastic sarcoma. It is a malignant proliferation of connective tissue
cells that contains benign odontogenic epithelium that is
similar to ameloblastic fibroma. Typically, it presents in the
mandible with an age range from 8 to 83 years. In the mandible, posterior region is affected more. It demonstrates an
expansile radiolucency with indistinct margins, evidence of
extraosseous soft tissue extension, and sometimes, an associated impacted molar. Other radiographic appearances
include destructive/permeative, unilocular or multilocular.
Typically, the patients do not develop metastases; they
form the group of a locally aggressive neoplasm. The sarcoma is most often treated by a wide surgical excision and
postoperative radiation therapy without elective neck dissection. Ameloblastic brosarcoma has the histologic architecture similar to an ameloblastic broma.
Slender budding and branching epithelial cords of
bland cuboidal to columnar cells with uniform nuclei or
epithelial islands that are indistinguishable from those are
seen in follicular ameloblastomas are separate widely by
hypercellular connective tissue that exhibits plump polygonal to fusiform stromal cells that show mild to moderate
cytologic atypia and numerous mitotic gures in a pale
hypocollagenous myxoid extracellular matrix.
Ameloblastic brosarcoma can show focal evidence of
dentin formation or dentin and enamel formation, resulting
in the terms ameloblastic dentinosarcoma and ameloblastic
odontosacrcoma, respectively. The histologic differential
diagnosis includes low grade spindled ameloblastic carcinoma that demonstrates plump broblastic cells that are
associated with ameloblastomatous islands and sheets. The
distinction between the two is made by cytokeratin which is
found to be reactive by broblastic cells of spindled ameloblastic carcinoma.

Odontogenic Carcinosarcoma
It is a tumor architecturally resembling an ameloblastic
fibroma in which both the epithelial and the connective
tissue components show cytologic evidence of malignancy.
For these extremely rare lesions that combine carcinomatous and sarcomatous elements and recognizable as odontogenic if the epithelial component resembles that of an
ameloblastoma, the designations malignant ameloblastoma
and fibrosarcoma or odontogenic carcinoma with sarcomatous proliferations have been used.
The increase in the number of reported malignant odontogenic tumors will help in the future to attempt studies
366

EPITHELIAL MALIGNANT TUMORS


Epidermoid Carcinoma
Epidermoid carcinoma or squamous cell carcinoma is
described in detail in Chapter 14 on Oral Cancer.

Verrucous Carcinoma
Verrucous carcinoma has also been referred to as snuff
dippers cancer and Ackermans tumor. Rock and Fisher in
1960 coined the term oral florid papillomatosis.
Lauren Ackerman in 1947 rst described this less severe
variant of squamous cell carcinoma associated with spittobacco chewing habit. He suggested that verrucous carcinoma needs to be considered as a distinct entity as it
exhibits a characteristic morphologic appearance and specic clinical behavior. He noted that even extension lesions
had excellent prognosis with proper treatment.
This lesion has a predilection for mucous membranes of
the head and neck and is most commonly found in the oral
cavity followed by the larynx. Since its earlier description,
verrucous carcinoma has been also reported to occur in the
esophagus, paranasal sinuses, nasal fossae, genital and anal
mucosa, soles of feet, breast and axilla.
Enriquez et al (1980), Pomatto et al (2001) and Nooshin
Mohtasham et al (2008) reported verrucous carcinoma arising from an odontogenic cyst.
Predisposing and etiological factors
The exact etiology is still not understood. Chewing tobacco
is the primary etiologic factor for these tumors. Most of these
tumors originate from the site of the placement of tobacco.
It has been suggested that opportunistic viruses such as
HPV-6 and 16, act in tandem with frank carcinogenesis to
promote development of verrucous carcinomas. Few other
authors suggest that the lesions develop at sites of chronic
irritation and inammation.
Clinical features
Verrucous carcinoma is usually seen between the 5th and
7th decade of life and commonly in white men. It is estimated that these tumors account for about 110% of all
oral squamous cell carcinomas.
In the initial stages, verrucous carcinoma appears as
white, translucent patches on an erythematous base. As they
mature they begin to take on a cauliower-like papillomatous growth with a supercial pebbly surface (Figure 26).

Chapter 13 Tumors of Orofacial Region

Figure 26

Figure 27

Parakeratin plug
Cleft lined by
parakeratin
Epithelium with broad
pushing borders
Subepithelial band of
chronic inflammatory
cell infiltrate

Histopathological picture of verrucous carcinoma.


Courtesy: Department of Oral Pathology and Microbiology,
MCODS, Mangalore

Clinical photograph of verrucous carcinoma. Courtesy:


Department of Oral Medicine and Radiology,
MCODS, Mangalore

The common intraoral sites that are affected are the


buccal mucosa, alveolar ridge, gingiva, oor of mouth,
tongue, tonsillar regions and the vermillion border of
the lip.
Occasionally, local invasion into underlying soft tissues
and bone may be seen. The surface of the lesion may show
ulceration.
Rarely distant metastasis is seen. However, regional
involvement of the lymph nodes may be observed. Nodes
may be enlarged and tender.
The other forms of verrucous carcinoma are the Buschke
Lowenstein tumor (anourologic type) and the epithelioma
cuniculatum (palmoplantar type).
BuschkeLowenstein tumor occurs as a large cauliowerlike tumor mass that is usually restricted to the glans
penis, vagina, cervix and the perianal region; whereas epithelioma cuniculatum is seen as ulcerated large exophytic
masses associated with sinus openings especially on the skin
overlying the rst metatarsal head.
These tumors can also occur on the toes and heel.
Occasionally, these tumors may bleed or produce foul
smelling discharge. Patients may complain of difculty in
walking.
Histologic features
Histologically, verrucous carcinoma shows hyperkeratosis,
parakeratosis and acanthosis in the superficial portions.
The surface is papillary with a thick parakeratinized covering that extends into deep cleft-like interpapillary spaces.
The rete ridges are broad and bulbous, that tend to push
into the underlying connective tissue (Figure 27).

Management and prognosis


Most of the patients suffering from verrucous carcinoma
have a good prognosis. The mainstay of treatment for verrucous carcinoma is surgical excision. However, when the
tumor is not accessible for surgery, radiotherapy may be
used. Radiation therapy is planned for a 6-week period.
About 400800 cGy is administered in fractions, 612 times.
However, some authors report anaplastic transformation
(almost 30%) following radiotherapy.

Basal Cell Carcinoma


Basal cell carcinoma is also referred to as rodent ulcer. It
is the most common cutaneous malignancy, which typically affects the sun-exposed surfaces of the skin. It is a
slow growing tumor. However, long-standing tumors can
cause local destruction of tissues and metastasis is seldom
encountered. It is estimated that less than 0.1% tumors
metastasize. The most common sites of metastasis are the
lymph nodes, bones and lungs. It arises from the basal cells
of the surface epidermis or external root sheath of the hair
follicle.
Clinical features
Basal cell carcinoma is usually seen in individuals over the
4th decade of life. Men are believed to be affected twice as
commonly as women as they are more frequently exposed
to sun. However, this may not be true all the time. It has
been noticed that fair complexioned individuals are relatively more prone to develop basal cell carcinoma compared to dark complexioned individuals.
Basal cell carcinoma can have various clinical appearances. Some of the relatively common varieties are noduloulcerative type (most common variety), supercial
spreading type, pigmented, morphea-form (sclerosing) and
the cystic type.
367

Section V Cysts and Tumors of Orofacial Region

The ulceronodular type of basal cell carcinoma, in the


initial stages, appears as a large non-tender papule which
slowly enlarges and exhibits a central depression. Over a
period of time the central depressed area reveals ulceration
associated with some bleeding and crusting. The pathognomonic feature of basal cell carcinoma is a waxy, translucent, or pearly appearing ulcer with a raised pale border.
Telangiectasias are common.
The pigmented form resembles melanomas. They appear
as bluish-black or brown colored macules. However, unlike
melanocytic nevus these lesions are not necessarily uniformly pigmented.
The cystic variety of basal cell carcinoma is rare. This
form of basal cell carcinoma appears as a bluish to gray colored, mucin-lled cyst-like lesions.
The sclerosing type of basal cell carcinoma is uncommon.
The typical lesion mimics a scar. It appears as a white or
yellow waxy sclerotic plaque. It is believed that the tumor
cells initiate the proliferation of broblasts within the dermis and an increased collagen deposition (sclerosis).
The supercial type is seen as an erythematous, wellcircumscribed patch or plaque. The lesion may be associated
with the formation of a white colored scale. These lesions
may mimic lesions of psoriasis. Neville et al described the
presence of a ne elevated thread-like border at the margins
of the lesions.
It is estimated that the risk of developing a squamous
cell carcinoma is increased slightly after a basal cell carcinoma, with a 6% risk at 3 years. Patients are at increased
risk of developing malignant melanomas.
Syndromic association
Barcelos et al (2008) described BazexDuprChristol syndrome, which is a rare genodermatosis that is characterized by follicular atrophoderma, multiple milia, congenital
hypotrichosis, hypohidrosis and basal cell malformations
that include nevoid basal cell carcinomas.
The other commonly associated syndrome is GorlinGoltz
syndrome, which is characterized by basal cell epithelioma,
jaw cyst and bid ribs.
Histopathologic features
The basaloid appearance of the epithelial islands is the most
striking histopathological features of basal cell carcinoma.
The cells exhibit increased nuclear cytoplasmic ratio. Cells
show peripheral palisading (they are arranged perpendicular to the basement membrane).
The tumor has a characteristic invasive pattern with the
formation of large islands. The cells within the core of the
epithelial islands have non-discrete cytoplasmic borders
and mimic syncytium. They do not have prominent nucleoli and lack intercellular bridges. The stroma shows varying amounts of collagen deposition with abundant mucin.

368

Management
Neville et al (2007) studied the efficacy of 5% imiquimod
(commercially available in India as Imiquad 5% cream.
Imiquimod is a keratolytic) in the treatment of nodular
basal cell carcinoma after initial treatment with curettage.
In their study, 5% imiquimod was applied locally once a
day, 5 times per week for 6 weeks, following curettage.
They concluded that imiquimod cream was an effective
treatment modality.
Gross et al (2007) studied the potential of 5%
5-uorouracil cream for the treatment of small supercial
basal cell carcinoma. They used 5% 5-uorouracil cream
twice daily for up to 12 weeks. The results showed that the
histologic cure rate was 90% and the mean time to clinical
cure was 10.5 weeks.
Healsmith et al (1991) used intralesional interferon
alpha-2b (IF-2b) for the treatment of basal cell carcinoma. The injected nine intralesional injections of IF-2b
(1.5 million units dissolved in 0.20.5 ml water), 3 times
per week for 3 weeks. At a 3-month follow-up, out of the
11 tumors they treated, six tumors had resolved both clinically and histologically, three tumors had reduced in size
and one tumor grew larger.
Surgical excision for basal cell carcinoma is still the
most popular modality of treatment. It is recommended
that an excision margin of 4 mm around the tumor be maintained. Mohs micrographic surgery offers high cure rates for
basal cell carcinoma (5-year cure rate of 99% for primary
tumors and up to 95% for recurrent basal cell carcinoma).
During this surgical technique, serial frozen sections are
examined histologically until all margins are clear.

Malignant Melanoma (Melanocarcinoma)


Malignant melanoma is a malignant neoplasm, with its
origin in the neural crest cells. It was first described by
Weber in 1859. Lucke in 1869, recognized it as a distinct
clinical entity and named it as melanotic sarcoma.
It is estimated that oral melanomas represent about
12% of all oral malignancies. It accounts for about 35%
of all malignancies affecting the skin.
Apart from the oral mucosal involvement, melanomas
can be seen affecting the nasal, vulval and anorectal mucosa.
It is believed that tobacco smoke may play a role in the
development of melanoma in the palate. Other possible risk
factors include fair complexion, light hair, excessive exposure to sunlight, exposure to formaldehyde, family history
of malignant melanoma and the history of dysplastic nevi.
Clinical features
Melanoma is usually seen in the 4th to 7th decades of life.
It is seldom seen in individuals below 20 years of age.

Chapter 13 Tumors of Orofacial Region

Figure 28

Color variation: Pigmentation is not uniform and may


display shades of tan, brown or black. White, reddish
or blue discoloration is of particular concern.
Diameter: A diameter more than 6 mm is characteristic
of melanoma, although some may have smaller diameters. Any growth in a nevus warrants an evaluation.
Evolving: Changes in the lesion over time are characteristic. This factor is critical for nodular or amelanotic
(non-pigmented) melanoma, which may not exhibit
the classic criteria listed above.
Types of melanoma
Based on the clinical and pathological features, melanomas
are broadly categorized into four types:

Clinical photograph of malignant melanoma. Courtesy:


Department of Oral Medicine and Radiology,
MCODS, Mangalore

Superficial spreading
Nodular
Lentigo maligna
Acral lentiginous.

Table 12 summarizes the important features of these types


of melanomas.
Self-assessment tool for diagnosis of melanoma

Males are usually more commonly affected than females


(approximately 3:1.8). It has also been seen that melanomas are almost 5 times more common in whites than the
negroes. Melanomas are more common among Africans,
Japanese and Hispanics.
The common primary sites of involvement are the hard
palate and maxillary gingiva. Other less commonly affected
sites are the buccal mucosa, lips, tongue, oor of the mouth
and the mandible (Figure 28).
Clinically the lesion has varied presentations, ranging
from a dark blue-black to brown and to an amelanotic
variety that may appear pink. Some authors believe that
there is a deciency of tyrosine and an enzyme required
for melanin production. Others believe that this enzyme
system is intact and can produce melanin but the quantity is insufcient to be seen with histologic methods.
The latter explanation seems convincing because electron
microscopy does reveal the presence of melanosomes in
all amelanotic melanomas reported till date. Amelanotic
variants have a worse prognosis because of delayed recognition and subsequent treatment.
Melanomas may also be seen as a nodule which may
exhibit ulceration.
The indicative clinical signs for malignant melanoma
are referred to as the ABCDE warning signs.

Many authors believe that the ugly duckling sign can be


used as an effective self-examination tool. Individuals
are asked to compare the gross appearance of moles on
their body. Usually all the moles will have similar topographical appearance except for the ugly ducking or the
malignant melanoma, which will appear different from
other moles.
Scope et al (2008) assessed the effectiveness of the ugly
duckling sign as a potential screening tool for malignant
melanoma. They found that all the melanomas were generally apparent as ugly ducklings.
Differential diagnosis of melanoma includes oral melanotic macule, smokers melanosis, amalgam tattoo, melanoplakia, Addisons disease and PeutzJeghers syndrome.

1.

Asymmetry: The shape of the lesion is not the same on


both sides.
Border irregularity: The edges are ragged, notched or
blurred.

Histologic features
Histologically a high concentration of melanocytes may be
seen in the biopsy specimen. These atypical melanocytes
are larger, exhibit nuclear pleomorphism and hyperchromatism in the epithelial and connective tissue junction
(Figure 29).
Based on the extent of penetration through the dermis
to the subcutaneous fat, Clark suggested ve levels of
microstaging:

2.

Level I: Melanoma lies in the epidermis above an


intact basal lamina.
Level II: Melanoma cells that have compromised the
basal lamina, infiltrating the papillary dermis.

369

Section V Cysts and Tumors of Orofacial Region

Table 12

Melanoma: characteristic features

Type of melanoma

Characteristic features

Superficial spreading

Most common type (comprises 70% of skin lesions)


Usually arises from a pigmented dysplastic nevus
Ulceration or varied colorations (blue, black, gray, pink) are seen
Common on the head, neck, and trunk of males and the lower extremities of females

Nodular melanomas

Represent approximately 1015% of cutaneous melanomas (almost 30% of these occur in the head and neck region)
Common on the trunk of males
Usually symmetrical and uniform
Dark brown or black in color
The radial growth phase may not be evident (due to its high risk)
Amelanotic melanomas represent approximately 5% of all nodular melanomas

Lentigo maligna
melanoma

Almost 10% of the cutaneous melanomas are lentigo maligna melanoma


It originates from a melanoma in situ called lentigo maligna or Hutchinsons freckle
The Hutchinsons freckle is generally in a radial growth phase for almost 1215 years. At this time, the lesion appears as
a relatively flat brown, black and occasionally grayish-white macule
However, over a period of time this radial phase of growth turns into a phase of vertical growth indicating an invasion
into deeper planes of tissue. During this phase the flat macule exhibits nodular changes
At this stage the lesion is termed lentigo maligna melanoma

Acral lentiginous
melanoma

It is the most commonly occurring oral melanoma


In the initial stages it may appear as a macule, which slowly shows nodular appearance
It commonly affects the oral mucous membranes, palms and soles

5.
Figure 29

Level V: Melanoma extending into the subcutaneous


fat.

Management and prognosis


Melanoma is best managed with surgical excision of the
lesion with wide margins of at least 2.5 cm. However,
widespread disseminated metastatic diseases can be managed with chemotherapy and radiotherapy. Some authors
have reported good results with interferon.
It is believed that the prognosis of oral melanomas are
poorer than skin lesions. The prognosis of the condition
depends on the extent of invasion. When the invasion
limited to the epidermis, the condition is almost 100% curable. However, when the lesions are less than 1 mm in
thickness, the 5-year survival rate is about 95%, but when
the lesions are more than 4 mm in thickness, the 5-year
survival rate falls to 45%. The 5-year survival rate for oral
melanomas is about 10%.

Histopathological picture of melanoma. Courtesy:


Department of Oral Pathology and Microbiology,
MCODS, Mangalore

CONNECTIVE TISSUE MALIGNANT TUMORS


Fibrous Tissue Origin
Fibrosarcoma

3.
4.

370

Level III: Melanoma involving the papillary dermis,


extending to the papillary-reticular dermis interface.
Level IV: Melanoma extending into the reticular
dermis.

Fibrosarcoma is a malignant neoplasm of the fibroblastic origin. Fibrosarcoma may occur anywhere in the body.
Extremities are the most commonly affected. However,
only about 10% involve the head and neck region.

Chapter 13 Tumors of Orofacial Region

They can present as a soft tissue mass or as a primary


(central and peripheral) or secondary bone tumor.
The primary brosarcoma produces variable amounts
of collagen. The secondary brosarcoma of bone arises from
a pre-existing lesion or as a complication of radiotherapy
involving bone or soft tissue. It is believed that the secondary brosarcoma is very aggressive.
Patients may complain of bone pain and swelling when
the tumor involves the bone. Larger tumors may lead to
destruction of the bone architecture and pathological
fracture. Fibrosarcomas involving the soft tissues are seldom painful. They are usually seen deep to the muscular
fascia.
They affect males and females equally and commonly
seen in the 2nd to 4th decades of life. However, reports of
brosarcoma involving the tongue, gingiva and jaw bones
have been reported in young children. The common sites
that are involved include the paranasal sinuses, lip, palate
and the periosteum of the maxilla or mandible. The mandibular premolar and molar region is the most common site.
Soft tissue involvement may produce a locally invasive
swelling that may show secondary changes such as hemorrhage and ulceration. Occasionally, patients may report
of altered sensation if the tumor involves peripheral
nerves.
Radiographic features
Fibrosarcomas are evident as a solitary radiolucency with
ragged or ill-defined borders. Peripheral lesions may show
saucerization of the surface underlying bone. In many
individuals the normal bone surrounding the tumor may
show sclerosis.
The cortices show thinning or destruction in extensive
cases.
The tumor can cause destruction of the sinus, nasal
fossa or the mandibular canal based on its location.
Displacement of teeth and alveolar bone with tooth
oating in space appearance are common. Widening of the
periodontal ligament space is seen. However, root resorption is seldom evident.
Some authors have reported the presence of sunray
appearance or Codmans triangle appearance when associated with disruption of the periosteum.

Figure 30

Long fascicle
Short fascicle

Interlacing
fascicles

Histopathological picture of fibrosarcoma. Courtesy:


Department of Oral Pathology and Microbiology,
MCODS, Mangalore

muscular immunomarkers help to differentiate brosarcoma from other tumors.


Management
Radical surgical removal of the tumor is the treatment of
choice. Inaccessible tumors can be palliated with chemotherapy and radiotherapy. It is estimated that the 5-year
survival rate is approximately 30%.

Malignant Fibrous Histiocytoma


Malignant fibrous histiocytoma (MFH) is a sarcoma with
both fibroblastic and histiocytic features. MFH typically
arises in the soft tissues of the extremities and retroperitoneum, the head and neck region is rarely involved. These
tumors account for about 1020% of all sarcomas. In the
present times, it is considered as one of the most common
soft tissue sarcomas of adult life. These tumors typically
arise in the muscles and deep fascia. However, tumors
involving bone have also been reported. They can be either
benign or malignant.

Histopathologic features

Clinical features

In low-grade malignancy, spindle cells are seen arranged


in fascicles with low to moderate cellularity in a herringbone pattern. Mild degree of nuclear pleomorphism is seen.
However, high-grade malignant lesion shows extensive
nuclear pleomorphism and increased cellularity. Atypical
mitosis is present (Figure 30).
Histologically, brosarcoma mimics malignant brous
histiocytoma, liposarcoma or synovial sarcoma. However,
positive immunostaining for vimentin and negativity for

It is commonly seen in adult males. Superficially located


tumors are generally smaller in size compared to deep
seated tumors.
The tumors can affect any part of the body. The common sites of involvement include the extremities, nose,
paranasal sinuses, orbit, larynx, meninges, lungs, vagina,
ovary and submandibular glands.
The intraoral sites commonly affected are the buccal
mucosa, vestibule, lips and tongue. The jaws bones also
371

Section V Cysts and Tumors of Orofacial Region

have reportedly been involved. The painless nodular mass


may vary in size from a few millimeters to few centimeters
in size.
Fibrosarcoma can be considered in the differential
diagnosis. Other conditions that can be included in the
differential diagnosis are leiomyosarcoma, angiosarcoma
and neurobrosarcoma.
Histopathologic features
The tumor is characterized by a heterogeneous population
of pleomorphic spindle cells arranged in a typical storiform
or starry-night pattern interspersed among zones of anaplastic giant cells.
Based on the histopathological differences, malignant
brous histiocytomas have been classied as myxoid (good
prognosis), inammatory (aggressive in nature), pleomorphic and angiomatoid (very rare) varieties. The myxoid
variety has a better prognosis whereas inammatory type
is more aggressive in its course.
Management
Surgical management is the treatment of choice. Radiation
therapy could be used as an adjunct to surgery. It is estimated
that the 5-survival rate is about 65%.

Radiographic features
In the head and neck region, CT image may reveal a multilocular tumor with smooth, well-defined margins and
heterogeneous enhancement after injection of contrast
medium. Occasionally, internal calcification may be
evident.
Histopathologic features
Histopathologically synovial sarcoma is divided into
biphasic, monophasic (fibrous and epithelial) and poorly
differentiated (round cell) subtypes. A myxoid variant has
also recently been described.
The biphasic subtype is composed of spindle and epithelial cell elements. The monophasic type is composed
primarily of spindle cells and rarely epithelial cells.
The poorly differentiated subtype shares features of
both the mono-and biphasic types along with poorly differentiated areas characterized by high cellularity, pleomorphism, numerous mitoses and round cell morphology.
In some patients, necrosis may be evident.
Immunohistochemically, the epithelial-like cells are
positive for cytokeratins and epithelial membrane antigen,
and the spindle cells are positive for vimentin and bronectin.
All the subtypes are characterized by a specic t(x;18)
(p11.2;q11.2) chromosomal translocation.

Synovial Sarcoma
Knox in 1936 proposed the term synovial sarcoma as the
earliest of the cases reported, showed some histological
resemblance to synovial tissue. However, in the present
times it is widely accepted that the tumor does not arise
from the synovium.
Synovial sarcoma arises from the pluripotent mesenchymal cells of the para-articular surfaces. It commonly
affects the extremities. It is estimated that about 10% of all
soft tissue sarcomas are synovial sarcomas and around
310% occur in the head and neck region.
Clinical features
Synovial sarcomas usually affect men in the 2nd to 4th
decade of life. The common sites of involvement in the head
and neck are the hypopharyngeal and retropharyngeal
regions. Involvements of the parotid gland, tongue, buccal
mucosa, soft palate, floor of mouth, mandible and TMJ
have also been reported.
Many of the patients may complain of a steadily growing
painful mass over a period of many months. Some individuals may complain of difculty in swallowing, dyspnea
and hoarseness of voice.
Almost 50% of the synovial sarcomas may metastasize
to the lung. Other sites for metastases include the lymph
nodes and bone marrow.
372

Management and prognosis


Radical surgical excision with negative margins is the
treatment of choice. Regional lymph nodes may have to be
removed if clinical lymphadenopathy is evident. Occasionally an adjunctive radiotherapy (65 Gy) is used. Chemotherapy has been tried to prevent distant metastasis.
Almost 6090% of the patients may exhibit recurrence.
The prognosis of the sarcoma varies on the size of the
tumor and characteristics of the tumor. It is believed that
primary tumors larger than 4 cm in diameter have a poorer
prognosis. Calcifying-type synovial sarcoma has been
reported to have a relatively better prognosis. The 5-year
survival rate ranges from 36 to 76%.

Cartilage Tissue Origin


Chondrosarcoma
Chondrosarcomas are malignant tumors of the bone with
cartilaginous differentiation. The tumor cells characteristically form cartilage. They constitute about 25% of all primary bone tumors. Phemister in 1930, reported sarcomas
of bone that contained abundant cartilage as chondrosarcomas. Lichtenstein and Jaffe defined chondrosarcomas as
arising from full-fledged cartilage and never containing
osteoid or bone stroma.

Chapter 13 Tumors of Orofacial Region

Chondrosarcomas can have varied behavioral patterns,


from slowly growing tumor to a highly aggressive and
metastazing lesion. They may either occur as central or
peripheral tumors.
Clinical features
Only 510% of chondrosarcomas occur in the head and
neck region. The larynx and the nasal cavity are the most
commonly affected. The less common sites being the maxilla (anterior maxilla) and mandible (symphyseal region).
The tumor commonly affects males in the 3rd decade of
life. The tumor presents as a painless mass or swelling
associated with loosening of the associated teeth mimicking periodontal disease.
Histopathologic features
Tumors are further categorized by grade. Grade 1 represents the least aggressive in terms of histologic features,
and grade 3 represents the most aggressive. Most chondrosarcomas are pathologically classified as conventional,
but other subgroups are clear cell, myxoid, mesenchymal,
and dedifferentiated.
Evans and coworkers proposed a histological grading
system for chondrosarcoma.

Grade I lesions: These resemble benign cartilage, having a relatively uniform, lobular histologic appearance
and no metastasis.
Grade II lesions: Higher recurrence rate than Grade I
lesions. These exhibit occasional mitotic figures. The
rate of metastasis is approximately 10%.
Grade III lesions: These are more cellular and pleomorphic in appearance, with a marked increase in the
number of mitotic figures. The rate of metastasis in
grade III lesions is more than 70%.

Adipose Tissue Origin


Liposarcoma
Liposarcoma is the malignancy arising from of the adipose
tissue. Virchow was the first to describe liposarcoma. After
malignant fibrous histiocytoma, it is the second common
soft tissue sarcoma in adults.
Clinical features
Liposarcoma is commonly seen in males in the 4th to 6th
decades of life and seldom seen in children. It usually affects
the retroperitoneum, inguinal region and lower extremities. It is very rarely seen in the head and neck region (about
59% of cases). The oral cavity, larynx, hypopharynx,
scalp, orbit and soft tissues of the neck are the common
sites that are affected in the head and neck region. The
intraoral sites include the buccal mucosa, tongue, gingiva
and floor of mouth.
In the early stages, liposarcoma presents as an asymptomatic slow-growing swelling. However, over a period of
time, as the tumor enlarges, it may become symptomatic
when it impinges on the adjacent vital structures.
Histopathologic features
Liposarcoma can easily be misdiagnosed clinically. On gross
appearance, the tumor is well-encapsulated and circumscribed. The WHO distinguishes the four variants proposed
by Enzinger and Weiss based on developmental stage of
the lipoblasts and overall degree of cellularity and pleomorphism.
These four entities are: well-differentiated (subtypes
lipoma-like, inammatory, and sclerosing types), myxoid,
round-cell and pleomorphic. The dedifferentiated type is
the newer 5th type.
Treatment and prognosis

Radiographic features
Radiographically, chondrosarcomas can present as ill-defined
radiolucencies with few radiopaque foci (calcification/
ossification of cartilaginous matrix). Occasionally, these
may present as areas of dense radiopacification with illdefined margins. Involvement of the cortices can result in a
sunburst pattern.
Symmetric widening of periodontal ligament space and
resorption of the roots of teeth may be evident.

Wide surgical excision is the treatment of choice for liposarcoma. Lymph node dissection is not indicated unless
metastasis is strongly suspected.
Some authors feel that radiation therapy along with
surgical excision may improve the condition of the patient.
The 5-year survival rate is approximately 6070%.

Bone Tissue Origin


Osteosarcoma (Osteogenic Sarcoma)

Management
The treatment of choice is radical surgical excision with
negative margins. Distant metastasis is rare. However, distant metastasis to the sternum, vertebrae and lungs has
been reported.

Osteosarcomas are primary malignant bone tumors in


which mesenchymal cells produce osteoid. Osteosarcomas
of the jaws represent less than 10% of all bone tumors
and less than 1% of all malignant tumors of the head and
neck.
373

Section V Cysts and Tumors of Orofacial Region

Figure 31

Clinical photograph of paraosteal osteosarcoma. Courtesy:


Editor, JCDA. Illustration from non-squamous cell malignant
tumors of the oral cavity: an overview. Tom Daley and
Mark Darling. J Can Dent Assoc 2003;69(9):57782

mandible are the common sites affected. In the maxilla the


alveolar ridge, antrum and the palate are frequently
affected. The infraorbital rim and the zygoma have also
been reportedly affected (Figure 31).
The main symptoms of this lesion in jaw are swelling and
pain, paresthesia/anesthesia (of the lower lip and chin following involvement of the inferior alveolar nerve), loose
teeth and trismus. When the tumor extends to involve the
nasal cavity, maxillary sinus and orbit, clinical signs and
symptoms such as epistaxis, nasal obstruction, hemorrhage,
exophthalmos and blindness may be apparent.
The average time between presenting of symptoms and
diagnosis range from 3 to 5 months.
Amaral et al (2008) suggest that the differential diagnosis
for osteosarcomas of the jaw should include chondrosarcoma, Ewings sarcoma, bone metastasis, brous dysplasia,
osteomyelitis and even lesions that do not usually affect
the jaw bones as brosarcoma, leiomyosarcoma or rhabdomyosarcoma.
Radiographic features

It occurs most often in the long bones, with predilection for the distal femoral metaphysis, proximal tibia, and
humeral metaphysis.
Most of the osteosarcomas originate intramedullary (classic or conventional osteosarcoma). However, the other
relatively rare types of osteosarcomas are the juxtacortical
(periosteal and parosteal [Figure 31]) and extraskeletal.
Many authors have described osteosarcoma of the jaws
as a specic entity, with a clinical behavior different from
osteosarcoma of other skeletal bones.
Predisposing factors
The exact pathogenesis for the tumor is still unknown.
However, various predisposing factors have been proposed
such as trauma, virus, genetic mutations, pre-existing bone
cyst, Pagets disease, osteogenesis imperfecta, osteochondroma fibrous dysplasia and previous history of radiation
(radiation-induced sarcomas).
It is suggested that the average latent period between
radiation treatment and development of sarcoma is 12.5
years, following radiation dose of 45 Gy. It is believed that
individuals who harbor the mutation in tumor suppressor
genes like p53 and retinoblastoma gene are more prone to
develop osteosarcomas.
Clinical features
Osteosarcomas affecting the jaw bones are usually seen in
the 3rd and 4th decades of life. However, children have
also been affected. Males are slightly more commonly
affected.
The mandible and maxilla are equally affected. The
symphysis, ramus and posterior parts of the body of the
374

The radiographic features of osteosarcoma of the jaws may


vary from ill-defined radiolucent areas to mixed radiopaqueradiolucent lesions and dense sclerosis/radiopacification
(Figure 32AC).
The earliest radiographic change consists of a symmetric widening of the periodontal ligament space around a
tooth or several teeth as a result of tumor inltration along
the ligament space. This radiographic feature is referred to
as Garringtons sign. Occasionally, lamina dura may be lost.
The other early radiographic feature was proposed by
Yagan et al (1985). They suggested that the irregular widening of the mandibular canal, with areas of narrowing and
loss of ne parallel cortical margins of the walls of the
canal was an early sign of osteogenic sarcoma of the mandible. In some individuals, spiking resorption of the roots
of teeth are seen.
Other radiographic ndings include ill-dened motheaten destruction of bone (extensive sarcomas may cause
pathological fracture), honeycomb-like appearance, granular appearance, sunray appearance, Codmans triangle and
onion peel appearance.
Bianchi and Boccardi (1999) described three specic CT
appearances of osteosarcomas:
1.
2.
3.

Radiolucent with absence of bone formation within


the tumor
Mottled with small areas of amorphous ossification
Lamellar ossification with bony plates radiating from
a focus-like a sunburst.

Ng et al (2001) in a pioneering study described the ultrasound features of osteosarcoma of the mandible. In the
mandible they recommend that the most accessible surface
is the buccal cortex. Features such as bone thinning,

Chapter 13 Tumors of Orofacial Region

Figure 32
A

(AC) 3D-reconstructed images showing changes seen in osteosarcoma. Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

erosion, expansion, and the sunray appearance of the buccal cortex were all detected by ultrasound imaging.

Figure 33

Histopathologic features
Histologically, osteosarcomas are categorized as osteoblastic, chondroblastic, fibroblastic and telangiectatic.
The characteristic features of osteosarcoma are the presence of atypical osteoblasts. The osteoblasts are arranged
in a disorderly fashion (Figure 33). Irregular sheets of osteoid
may be seen. The telangiectatic type exhibits extensive
blood-lled spaces. However, this type is generally seen in
young adults.
Management
The choice of treatment for osteosarcoma is radical surgery along with adjuvant chemotherapy. As most of the

Osteoid
Trabeculae of bone
Chondroid tissue
Pleomorphic,
hyperchromatic
osteoblasts

Histopathological picture of osteosarcoma. Courtesy:


Department of Oral Pathology and Microbiology,
MCODS, Mangalore

375

Section V Cysts and Tumors of Orofacial Region

osteosarcoma metastasizes by hematogeneous route, there


is a rationale for addition of adjuvant chemotherapy.
Literature reveals that the 8-year metastasis-free survival
rate is 6070%.
The factors associated with poor prognosis include neural sensory alteration as a presenting symptom, increasing
age of patients and surgical margins less than 5 mm.

Ewings Sarcoma (Round Cell Sarcoma)


Ewings sarcoma is uncommon, aggressive bone malignancy
occurring in childhood. It accounts for about 47% of all
primary bone malignancies.
James Ewing (1921) was the rst to describe Ewings
sarcoma. It is believed to originate from the immature
reticulum cells or primitive mesenchymal cells of the bone
marrow.
Although Ewings sarcoma commonly affects bone, it
may also arise from soft tissues. Ewing sarcomas arising
from soft tissues are referred to as extraskeletal Ewings
sarcoma. Tefft et al (1969) rst described this variant.
The extraskeletal variety has been reported to arise in
various locations such as small intestine, vagina, kidney,
skin, larynx, esophagus, paravertebral region, or epidural
space.
Clinical features
Ewings sarcoma is usually seen in the first 2 decades of
life and affects males twice as commonly as females.
It typically affects the pelvic girdle and the long bones of
the lower extremities. Studies have shown that whites are
predominantly affected.
Only 27% of the tumors affect the maxillofacial
region. The mandibular ramus region is relatively more
commonly affected than the maxilla. About 90% of the
mandibular lesions are primary tumors and about 10% are
metastatic.
Swelling, pain, paresthesia, and loose teeth are frequent
symptoms. Occasionally, low-grade fever may be apparent.
In the initial stages of the tumor, expansion of the cortical
plates may be appreciable. However, as the tumor enlarges
and perforates through bone, as soft, tender mass may be
evident.

Histopathologic and laboratory studies


Histopathologically, Ewings sarcoma mimics eosinophilic granuloma, malignant lymphoma and metastatic
neuroblastoma.
Microscopically, tightly packed round cells, compartmentalized by brous bands with minimal stroma are seen. Individual cells have round to oval nuclei 1015 m in diameter
with a distinct nuclear membrane. Mitotic gures are commonly seen. The cytoplasm is ill dened, scanty, and pale
staining. The cytoplasm stains characteristically with periodic acid-Schiff (PAS), indicating the presence of glycogen.
Immunostaining for CD99 (Mic-2) is highly sensitive
for Ewings sarcoma. Immunostaining also shows abundant
vimentin intermediate laments. It is related to primitive
neuroectodermal tumor sharing a common karyotypic translocation t(11;12)(11;22)(q24;q12).
Leukocytosis and elevated ESR may be evident.
Management and prognosis
Ewings sarcoma is best treated with a combination of surgery, chemotherapy and radiotherapy. Surgery and radiation is used for local management. Systemic micrometastasis
is managed with chemotherapy. It is estimated that the
5-year survival rate is about 60%.
The prognosis of Ewings sarcoma may be poor when
the tumor metastasizes to other bones, lung, lymph node
and liver.

Vascular Origin
Kaposis Sarcoma
Kaposis sarcoma is a vascular tumor that was first described
by Moritz Kaposi, a Hungarian dermatologist in 1872. He
described a distinct variety of skin tumors in five male
patients in their 6th and 7th decades of life. He termed these
tumors as idiopathic multiple pigmented sarcoma of the skin.
There is a strong evidence to show that Kaposis sarcoma is caused by human herpes virus 8 (HHV-8).
Kaposis sarcoma has four distinct variants: classic or
Mediterranean, endemic or African, epidemic or AIDS
associated, post-transplant or iatrogenic immunosuppression associated Kaposis sarcoma. The histopathological
and immunohistochemical features of all forms of Kaposis
sarcoma are similar.
Clinical features

Radiographic features
Extensive ill-defined destruction of the bone may be the
only finding in jaw lesions. A laminated periosteal reaction
(onion skin/peel appearance) or sunray appearance is usually a feature of long bones. Occasionally, widening of the
periodontal ligament space, loss of lamina dura, root resorption and/or displacement and destruction of unerupted
tooth follicles are seen.
376

Classic Kaposis sarcoma usually occurs in adult males. The


classic form commonly occurs in Jewish and Italian populations. Almost all individuals suffering from the classic
form will tend to have an associated malignant lymphoma.
Intraoral ndings are extremely rare. The palate may be
involved. Though the classic variety may affect any part
of the body, lower extremities are commonly affected than
the trunk, arms and hands. The skin of the extremities may

Chapter 13 Tumors of Orofacial Region

Figure 34

Stage IV (disseminated visceral Kaposis sarcoma) has


widespread Kaposis sarcoma, usually progressing from
Stage II or Stage III, with involvement of multiple visceral organs.

The following modifications have also been proposed:

Associated opportunistic infection(s) is evident.


Patient is HIV-I seropositive.
Cutaneous anergy or other evidence of severe immunodeficiency is present.

Management

Clinical photograph of Kaposis sarcoma in a 28-year-old


HIV-positive man who presented with multifocal flat to
nodular purple lesions of the facial skin and oral mucous
membranes. Facial (black arrow), palatal and tongue
(white arrow) lesions are illustrated. Courtesy: Editor,
JCDA. Illustration from non-squamous cell malignant
tumors of the oral cavity: an overview. Tom Daley and
Mark Darling. J Can Dent Assoc 2003;69(9):57782

reveal blue to purple macules which turn into painless


nodules over a period of time (Figure 34).
Endemic Kaposis sarcoma is also referred to as African
Kaposis sarcoma. The African variety can present as
benign nodular (similar to classic, occurs in young adults),
inltrative (locally invades adjacent soft tissues and bone),
orid (widely disseminated with visceral involvement) and
lymphadenopathic type (rapidly growing tumors of lymph
nodes, seen in young children).
This association of AIDS with Kaposis sarcoma was
rst described in the early 1980s. It is considered to be the
most common form. It is estimated to appear in up to 40%
of AIDS patients and may account for up to 90% of all
cancers found in the AIDS population.
The iatrogenically induced variety is seen a few months
and years following organ transplants in post-transplant
patients. This form of the disease results from the effects of
the immunosuppressive drugs. Cessation of the therapy can
result in regression of the tumor.
Schwartz and coworkers in 1984, proposed the following
classication system for Kaposis sarcoma:

Stage I represents localized nodular Kaposis sarcoma,


with more than 15 cutaneous lesions or involvement
restricted to one bilateral anatomic site, and few, if
any, gut nodules.
Stage II includes both exophytic destructive lesions
and locally infiltrative cutaneous lesions as locally
aggressive Kaposis sarcoma.
Stage III (generalized lymphadenopathic Kaposis sarcoma) has widespread lymph node involvement, with or
without skin lesions, but with no visceral involvement.

Individual solitary lesions are surgically excised. Electron


beam radiotherapy can be used effectively. Occasionally,
intralesional or systemic chemotherapeutic agents are
used. Vinblastine is the most commonly used antineoplastic agent.

Angiosarcoma
Angiosarcoma is an uncommon malignancy originating
from the vascular endothelium of either the blood vessels
or lymphatic channels. It generally occurs in the skin and
subcutaneous or skeletal muscle and has been reported to
occur in the spleen, bone, liver, and breast. Angiosarcomas
are usually seen in the 5th decade of life. However, individuals in the age range from 6 to 90 years have also been
affected. More than half the angiosarcomas affect the head
and neck region. The scalp and forehead are the most
commonly affected sites.
Oral and salivary gland angiosarcomas are exceedingly
rare, comprising only about 2% of all angiosarcomas.
Angiosarcomas may involve the lip, buccal mucosa, oor
of mouth, gingiva, tongue and the mandible.
The intraoral lesions may appear as simple bruise in the
early stages. As the neoplasm advances, it tends to become
nodular and ultimately ulcerate.
The differential diagnosis for angiosarcoma includes
hemangioma, pyogenic granuloma, hemangiopericytoma,
Kaposis sarcoma and hemangioendothelioma.
Histopathologically, the tumor is characterized by the
presence of proliferation of endothelium-lined vascular
channels forming a network of anastomosis with increased
mitotic activity.
Management
Angiosarcomas are best treated with surgical excision and
radiation therapy.

Muscle Origin
Leiomyosarcoma
Leiomyosarcoma is a malignant mesenchymal neoplasm
exhibiting smooth muscle differentiation. It accounts for
377

Section V Cysts and Tumors of Orofacial Region

about 67% of all soft tissue sarcomas. However, it rarely


occurs in the oral soft tissues or jaw bones.
It typically affects the adults and occurs in the retroperitoneal region, gastrointestinal tract and uterus, reecting the afnity for affecting smooth muscles. These tumors
generally affect individuals over the 4th and 5th decades
of life.

Figure 35

Clinical features
Oral leiomyosarcomas may occur at any age. About 310%
of the leiomyosarcomas. Smooth muscle tumors in the oral
cavity may originate from the arterial tunica media, the
ductus lingualis, the circumvallate papillae, and pluripotential mesenchymal cells, which are rich sources of
smooth muscle tissue.
A leiomyosarcoma in the oral cavity may be primary or
secondary (metastatic from another location). The common
sites of metastatic involvement are the mandible for bony
depositions and the gingivae and tongue for soft tissue
deposits.
It is estimated that 45% of the reported cases affecting
the oral cavity occur in the jaw bones.
Clinically they may appear as painless or occasionally
painful well-circumscribed mass, rmly adherent to the
surrounding tissues. Some of these tumors may reveal
ulcerations.
Histopathologic features
Leiomyosarcoma is characterized by sheets of sweeping,
alternating bundles and fascicles of densely packed spindle cells with abundant fibrillar eosinophilic cytoplasm
and indistinct cytoplasmic borders. The nucleus is usually
centrally located and blunt-ended, squared-off or cigarshaped. Occasional cells have perinuclear vacuoles.
Massons trichrome staining and immunohistochemical evaluation for muscle antigens are helpful in differentiating leiomyosarcoma from other sarcomas. Positive
reactions for desmin, vimentin, smooth-muscle actin and
h-caldesmon have been demonstrated in this neoplasm.
Management
Radical surgical excision is the treatment of choice along
with chemotherapy and radiotherapy. It is estimated that
the 5-year survival rate is about 30%.

Clinical photograph of rhabdomyosarcoma.


Courtesy: Dr Foluso Owotade

Types of rhabdomyosarcomas
Based on their anatomical location of occurrence, these
tumors are broadly categorized as orbital, parameningeal
and non-orbital non-parameningeal forms. Parameningeal
tumors are said to have the worst prognosis.
The International Classication of Rhabdomyosarcoma
in 1994, divides this tumor into four subgroups, namely,
botryoid and spindle cell RMS, embryonal RMS, alveolar
RMS, and undifferentiated sarcoma.
Oral features
These tumors are generally seen in the first decade of life.
These are also occasionally seen in adolescents and young
adults. Clinically a rapidly growing painless mass may be
seen. Palate, tongue and alveolar ridge have been reported
as the common sites affected (Figure 35). In the advanced
stages of the disease, pain, paresthesia, loosening of the
teeth, and trismus may be seen.
Management
The primary tumors are best managed with surgical resection, multidrug chemotherapy and radiation therapy. The
5-year survival rate is estimated to be about 60%.

Rhabdomyosarcoma
Rhabdomyosarcoma (RMS) is considered as the most common soft tissue sarcoma affecting children. It is a malignant
neoplasm of skeletal muscle origin. Weber in 1854 is credited for giving the first description of rhabdomyosarcoma.
It is estimated that about 35% of RMS arises in the head
and neck.
378

Nerve Tissue Origin


Neurofibrosarcoma (Malignant Schwannoma,
Neurogenic Sarcoma)
Neurofibrosarcomas arise from the nerve sheath cells.
These account for about 10% of soft tissue sarcomas. It is

Chapter 13 Tumors of Orofacial Region

estimated that almost 50% of these tumors originate from


neurofibromatosis type 1.
Clinical features
Neurofibrosarcomas are uncommon in the head and neck
region. These are common in 4th to 6th decades of life.
The common sites affected are the lips, palate, gingiva,
buccal mucosa and mandible. Clinically the tumors appear
as rapidly growing mass of tissue occasionally associated
with pain and paresthesia.

those of fibrosarcoma but which are usually more irregular,


with wavy or comma-shaped nuclei.
Some less cellular myxoid areas may also be seen. Positive immunostaining for S100 protein is often useful.
Management

Radiographic features

The tumor is managed with surgery and radiation therapy. The tumors have a high recurrence rate as they tend
to spread along the involved nerve. It is estimated that the
prognosis for patients with neurofibrosarcoma arising de
novo is about 50% for 5-year survival, whereas it is 15% for
neurofibrosarcoma arising in cases of neurofibromatosis.

Radiographs may exhibit an ill-defined radiolucency suggestive of destruction of the bone. Widening of the inferior alveolar canal may also be seen.

Lymphoid Origin and Hematological


Malignancies

Histopathologic features
The typical histopathological feature is the presence of fascicles of atypical spindle-shaped cells, which may resemble

Tumors of lymphoid origin, namely, Hodgkins and nonHodgkins lymphoma and hematological malignancies
including leukemia and myeloma are described in Chapter 18
on Systemic Disorders and their Clinical Implications.

379

CHAPTER

14

Oral Cancer
SV Kumaraswamy, V Jeevan Prakash,
Praveen BN, Ravikiran Ongole

Incidence of Cancer of Head and Neck

Tumor Growth and Metastasis


Molecular Abnormalities

Etiology and Risk Factors


Genetic Susceptibility
Immune Status
Environmental Factors

Clinical Signs of Cancer

Clinical Examination of a Patient with


Suspected Malignancy

Tobacco

TNM Staging

Alcohol

Nodal Metastasis

Systemic Health

Diagnosis of Oral Cancer

Ionizing Radiation
Role of Viruses
Role of Nutrition
Oral Hygiene and Dental factors

Management of Oral Cancer

Surgical Treatment
Radiation Therapy
Chemotherapy

Molecular Basis of Cancer


Cellular Kinetics

Malignant tumors are popularly referred to as cancer.


However, the term tumor is scientifically more appropriate.
Tumor is defined as an autonomous new growth of tissue
or an abnormal mass of tissue, the growth of which
exceeds and is uncoordinated with that of normal tissue
and persists in the same excessive manner even after the
cessation of stimuli which evoked the change.
Hippocrates described various types of cancers. He
referred to benign tumors as oncos (swelling in Greek) and
malignant tumors as carcinos (crab or craysh in Greek).
He compared malignant tumors to a crab since the sectional
morphology of the tumor along with its vascular supply
mimicked the body of a crab with its claws and feet
outstretched.
Aulus Cornelius Celsus, a Roman encyclopedist, translated carcinos into the Latin cancer, which also means crab.
Galen, the Roman physician used oncos to describe all
tumors, which laid the foundation for the use of the present
day term oncology.
Oral malignancies may arise from the epithelium, muscle mass, odontogenic structures, specialized structures
like the tongue and the eye, from the salivary glands both
major and minor and also from the bone. However, it is
virtually impossible to describe all the forms of cancer in
this chapter.
380

As oral carcinoma is one of the most prevalent cancers


and is one of the 10 major causes of death, this chapter will
attempt to highlight the etiology, clinical features, diagnosis,
investigations and the treatment options.

INCIDENCE OF CANCER OF HEAD


AND NECK
According to the World Health Report (2004), cancer
accounted for 7.1 million deaths in 2003 and it is estimated
that the overall number of new cases will rise by 50% in
the next 20 years. Oropharyngeal cancer is more common
in developing countries than developed countries. The
prevalence of oral cancer is particularly high among men,
the eighth most common cancer worldwide. Incidence rates
for oral cancer vary in men from 1 to 10 cases per 100,000
population in many countries. In South-Central Asia, cancer of the oral cavity ranks among the three most common
types of cancer. In India, the age standardized incidence rate
of oral cancer is 12.6 per 100,000 population. More than
90% of all oropharyngeal cancers occur in patients over the
age of 45. As with other head and neck tumors, male predominance is common, with a male to female ratio of 4:1,
because of the greater use of tobacco by men.

Chapter 14 Oral Cancer

It has been estimated that 43% of cancer deaths worldwide are due to tobacco, unhealthy diet, physical inactivity
and infections. Tobacco use and excessive alcohol consumption have been estimated to account for about 90% of cancers in the oral cavity; the oral cancer risk increases when
tobacco is used in combination with alcohol or areca nut.
About 96% of all oral cancers are carcinomas and the
remaining 4% are sarcomas. Majority of oral carcinomas
are squamous cell carcinomas. It is estimated that 9 out of
every 10 oral malignancies is squamous cell carcinoma. It
is a disease of increasing age with 95% of the patients
older than 40 years of age.
In India, it is estimated that there are 22.5 million cancer patients at any given point of time with about 0.7 million new cases diagnosed every year and nearly half of
them die every year. Two-thirds of the new cancers is
diagnosed at a very advanced and incurable stage. More
than 60% of these affected patients are in the age group of
35 and 65 years. Fifty percent of all male and 25% in
female are tobacco related cancers.

ETIOLOGY AND RISK FACTORS FOR ORAL


AND MAXILLOFACIAL CANCER
The exact etiology for oral cancer is still questionable. However, it is well known that a plethora of factors predispose
an individual to developing oral cancers. Historically, the
widely known six S has been mentioned in literature,
namely, smoking, spirit, sharp teeth, sunlight, syphilis,
spicy food and sepsis. However, over a period of time
many predisposing factors have been proposed and suggested such as genetic susceptibility, environmental factors,
systemic health of an individual and abusive habits such as
the consumption of tobacco and alcohol.

Genetic Susceptibility
Family history of oral cancer is considered a risk factor.
Head and neck cancer patients show an increased susceptibility to chromosome damage by mutagens. Some studies suggest that lip cancers have shown some amount of
genetic predisposition. Mork et al (1999) reported a significantly increased odds ratio for developing head and neck
squamous cell carcinoma in female patients, aged less than
45 years, who had first-degree relatives with cancer. It is
suggested that familial oral cancer may be attributed to both
shared environmental factors within families and a common
oral cancer susceptibility gene with low penetrance.

Immune Status
It has been noticed that immunosuppressed individuals
tend to show an increased incidence of oral malignancies.

It is also a well-known fact that the host response diminishes with advancing age. HIV-positive immunocompromised individuals, may usually exhibit Kaposis sarcoma
and non-Hodgkins lymphomas.

Environmental Factors
Exposure to actinic radiation There is enough evidence
in literature to show that skin and lip cancers are more
frequently seen in individuals whose occupation necessitates long working hours in the sun such as fishermen and
farmers.
It has been reported that fair skinned individuals, people
residing in high latitudes with clear atmosphere (UV light
can penetrate easily) such as Finland and Sweden, residents closer to the equator (long periods of sunshine) such
as Greece are more susceptible to develop lip cancers.
The wavelengths of the light thought to be responsible for
the actinic damage are in the range of 2,9003,200 A.
Sunscreen lotions are effective in protecting the lip from
the damaging effects of UV light. Melanin pigment acts as
a protective agent against actinic radiation.
Atmospheric pollution Air pollution arising from industrial wastes and automobile exhausts are particularly harmful. Other sources include gases emitted from burning
firewood/coal for domestic purposes. Sulfur dioxide, carbon
monoxide, nitrogen gases have been implicated in causing
pharyngeal, laryngeal and lower respiratory tract cancers.

TOBACCO
All the forms of tobacco (smoke and the smokeless/
chewable/inhaled) such as cigarettes, pipes, cigars, beedis,
paan and snuff have been implicated in the development
of oral cancers. It is believed that tobacco use is responsible for 90% of the oral cancers in males.

Consumption of Tobacco in India


It is estimated that 8085% of tobacco is consumed for
smoking either as beedis or cigarettes (Figure 1). Almost
13% chew tobacco in the form of paan (Figure 2, betel
leaf, areca nut, tobacco, slaked lime and flavoring agents)
or gutkha. Almost 15% are addicted to both habit of chewing and smoking. Only about 13% use tobacco in the form
of snuff.

Smokeless Form of Tobacco


People in the Indian subcontinent exhibit various forms
of tobacco chewing habits such as khaini, mishri, zarda,
gutkha (Figure 3), mawa and nass. Paan is chewed (betel
quid) and the quid is usually placed in the buccal vestibule.
381

Section V Cysts and Tumors of Orofacial Region

Figure 1

Figure 3

One of the popularly consumed packets of gutkha.


Courtesy: Department of Oral Medicine and Radiology,
Manipal College of Dental Sciences, Mangalore
A typical road-side shop selling various tobacco products
ranging from cigarettes, beedis, paan to gutkha. Ironically
displaying the fact that tobacco causes cancer. Courtesy:
Department of Oral Medicine and Radiology, Manipal College
of Dental Sciences, Mangalore

Figure 4

Figure 2

Various constituents of paan. Courtesy: Department of


Oral Medicine and Radiology, Manipal College of Dental
Sciences, Mangalore

Tobacco is also used in the form of a powder for inhalation (Figure 4, snuff). Tobacco (Figure 5) contains nicotine
(nitrosamine), nitrosodiethanolamine, nitrosoproline, polonium and polycyclic aromatic hydrocarbon (tars). Areca nut
(Figure 6 contains cholinergic muscarinic alkaloids such
as arecholine and guavacoline) chewing is also widely
practiced in India.
382

Snuff used for inhalation. One of the risk factors for


causing nasopharyngeal and maxillary sinus cancers.
Courtesy: Department of Oral Medicine and Radiology,
Manipal College of Dental Sciences, Mangalore

Smoke Form of Tobacco


In India, beedi (Figure 7), cigarette and chutta smoking is
commonly seen. However, other popular forms of smoking
include use of pipe, cigar and hookah. It is believed that
cigar and pipe smoking is more hazardous than cigarette

Chapter 14 Oral Cancer

Figure 5

Processed tobacco leaf ready for use. Courtesy:


Department of Oral Medicine and Radiology,
Manipal College of Dental Sciences, Mangalore

Figure 7

Beedis made of tobacco wrapped in a tendu


(Diospyros melanoxylon) leaf, and secured with
thread at one end. The tobacco content in beedis is
approximately 1020%. Courtesy: Department of
Oral Medicine and Radiology, Manipal College of
Dental Sciences, Mangalore

Figure 6

Figure 8

Mature areca nut and the areca nut that is obtained


after it is dehusked, processed and dried. Courtesy:
Department of Oral Medicine and Radiology,
Manipal College of Dental Sciences, Mangalore

smoking. Palatal cancers are more common in individuals


who place the lit end of the beedis and cigarettes inside the
mouth (reverse smoking). It has been proposed that smoking
causes pooling of carcinogens in saliva thereby increasing
the incidence of cancers of the floor of the mouth, ventral
and lateral surface of tongue.
It is estimated that in the combustion mainstream of one
cigarette (Figure 8), there are approximately 500 mg (92%)
of gaseous content (mainly oxygen, nitrogen and carbon
dioxide and to a little extent carbon monoxide) and 8% of
particulate matter. Aromatic hydrocarbons in the form of
tars may constitute less than 1 g to 35 mg. Nicotine content
varies from 1 to 3 mg. Other constituents of tobacco smoke
include carbon monoxide, hydrogen cyanide and thiocyanate. Benzopyrene is considered the most potent carcinogen. It preferentially binds to nucleoproteins. The enzyme

Cigarettes with filters. Courtesy: Department of


Oral Medicine and Radiology, Manipal College of
Dental Sciences, Mangalore

aryl hydrocarbon hydroxylase that is principally produced


in human leukocytes, is said to increase the carcinogenic
potential of benzopyrene.
The carcinogenic properties of marijuana smoke are
similar to those of tobacco. Marijuana may interact with
mutagen sensitivity and other risk factors to increase the
risk of head and neck cancer. Marijuana smoke has a four
times higher tar burden and 50% higher concentrations of
benzpyrene and aromatic hydrocarbons than are present
in tobacco smoke.
383

Section V Cysts and Tumors of Orofacial Region

ALCOHOL
Alcohol consumption is the most important risk factor for
development of oral cancer in non-smokers. It is also considered as the second independent major risk factor for the
development of oral cancer. It is estimated that an average
consumption of over 30 ml of alcohol per day increases the
risk of oral cancer linearly with the quantity of alcohol consumed. Though any form of alcohol when consumed in large
quantities is dangerous, it is believed that dark colored drinks
are more hazardous (as they may contain higher beverage
congeners such as nitrosamines, hydrocarbons and other
impurities which are known carcinogens). Carcinogens present in the tar are insoluble in saliva but are highly soluble
in alcohol and easily absorbed in the oropharynx.
The International Agency for Research on Cancer published a monograph in 1982, which details the various methods in which alcohol predisposes to head and neck cancers.

Ethyl alcohol increases the permeability of oral mucosa.


It also dehydrates the mucosa. It has a solvent action
on the keratinocyte membrane thereby allowing the
passage of carcinogens into proliferating cells where
they may exert a mutagenic action.
The immediate metabolite of ethanol is acetaldehyde,
which readily damages cells. It is believed that those
who are rapid acetylators are at increased risk of developing cancers.
Alcoholic liver disease is common in heavy drinkers
and this minimizes the detoxification of carcinogens.
Alcohol, owing to its high calorific value, suppresses
appetite in heavy drinkers. This predisposes to nutritional deficiency which in turn is a risk factor for cancers. Compared to non-users, alcohol users are
3.6 times more likely to have oropharyngeal cancer,
5.8 times for tobacco users, and 19 times for users of
both alcohol and tobacco.

SYSTEMIC HEALTH
Candidiasis Autoimmune polyendocrinopathy candidiasis
ectodermal dystrophy an autosomal recessive disease
associated with a limited T lymphocyte defect, presumably
supports the growth of Candida albicans and predisposes
to chronic mucositis and oral cancer.
Diabetes In diabetic patients, alterations occur in the oxidative equilibrium of free radicals. Elevated blood glucose
levels can lead to excessive formation of free radicals.
Moreover, due to protein breakdown, the activity of antioxidant scavengers and enzymes is reduced. Both the
increase in free radicals and oxidative stress promote carcinogenesis.
It has been suggested that poor diabetic control is associated with an increased cancer risk due to enhanced
384

oxidative damage to DNA. Production of reactive oxygen


species and lipid peroxidation are increased in diabetic
patients, especially in those with poor diabetic control and
hypertriglyceridemia. Increased oxidative damage can be
due to superoxide radical generation by monocytes through
nicotinamide adenine dinucleotide phosphate (NADPH)
oxidase. Superoxide can undergo either enzymatic or nonenzymatic dismutation to generate hydrogen peroxide. In
the presence of transition metals, such as Fe and Cu,
both these substances contribute to the generation of
highly reactive hydroxyl radicals causing damage to cells.
Hence, patients with poorly controlled diabetes are at
great risk of developing oral cancer.
Syphilis In the older literature, syphilis was considered
an important predisposing factor for oral leukoplakia and
oral cancer. It was suggested that syphilitic infection
caused endarteritis and subsequently atrophy of the overlying epithelium. This made the tongue more vulnerable
to the etiological factors. In modern times, tertiary syphilis
is rarely encountered in clinical practice due to effective
treatment.
Trieger et al (1958) reported a study that suggests
an increased prevalence of syphilis (approximately up to
60%) in patient groups with squamous cell carcinoma of
the tongue. It was seen that this association was stronger
in males than females.
Michalek et al (1994) reported a study of 16,420 people
with syphilis resident in the United States that showed a
signicantly raised frequency of cancer of the tongue (and
Kaposis sarcoma) in males. Dickenson et al (1995) screened
63 patients of United Kingdom suffering from squamous
cell carcinoma of the tongue. Five of these patients had
serological evidence of past syphilis when detected by
both specic and non-specic tests.

Ionizing Radiation
Exposure to large amounts of ionizing radiation such as
in a nuclear mishap is a known risk for causing cancers.
Radiation exposure, known to cause DNA damage, may
be a potential source of field cancerization of the upper
aerodigestive tract.
Hashibe et al (2005) evaluated the possible risk of
developing second primary cancers following radiotherapy
for head and neck cancers in 30,221 oral squamous cell
carcinoma patients. Patients treated with radiation only or
radiation with surgery had elevated risks of developing a
second primary tumor, whereas patients treated with surgery
only did not appear to be at increased risk. They also suggested that the expected latent period between radiation
exposure and tumor occurrence, radiation became a risk
factor after 10 years of follow-up for solid cancers of the oral
cavity, pharynx, esophagus, and lung, and after 15 years
of follow-up for second primary leukemia.

Chapter 14 Oral Cancer

Role of Viruses
The role of viruses remains unclear. Varying viral genomes
have been frequently found within cancer cells. Viruses
have been known to modify the DNA and the chromosomal structures and induce proliferative changes in the
cells they infect.
Evidence of a viral carcinogenesis is perhaps strongest
for infection with human papilloma viruses (HPV). DSouza
et al (2007) in a multicenter case-control study reported that
infection with HPV-16 increased the risk of cancer of the
oral cavity and particularly oropharynx.
The role of infection with EpsteinBarr virus (EBV) and
herpes simplex viruses (HSV) remains uncertain. The role
of HSV, HSV-1 and HSV-2, as co-factors in association
with tobacco, alcohol, or HPV-16 infection has also been
proposed in causing oral cancers.
Human immunodeciency virus (HIV), due its effect on
immunosurveillance, acts as a cofactor along with other
viruses such as EBV and cytomegalovirus in predisposing
the affected individual to oral cancer.

Role of Nutrition
Various studies have shown that a diet with low vitamin A,
vitamin C, vitamin E, iron, selenium, folate and other trace
element content is associated with an increased risk of oral,
laryngeal, lung, gastric, ovarian, breast and cervical cancers. Certain dietary deficiencies may cause epithelial atrophy which renders the epithelium vulnerable to the action
of carcinogens. The relationship between sideropenic dysphagia and oral cancer is well recognized (sideropenic
dysphagia may be associated with epithelial atrophy in the
upper alimentary tract).
Garewal (1994) summarized the ndings of 54 studies
that evaluated fruit and vegetable intake in the development of cancers in the upper aerodigestive tract; he found
that 52 of the studies demonstrated a protective effect of
the antioxidant content of fruits and vegetables.
It has been shown that patients who ingest high levels
of vitamin C and ber have half the risk of developing oral
cancer as those with minimal level of consumption. Block
(1991) and Mirvish (1986) showed that a low intake of
vitamin C is associated with an increased risk of cancers of
the stomach, esophagus, oral cavity, larynx, and cervix.
Gridley et al (1992) in a study involving 2,000 individuals proposed that the use of vitamin E supplements correlated with a diminished risk for oral and pharyngeal cancers.

Oral Hygiene and Dental Factors


Though the exact etiological role of poor oral hygiene,
faulty restorations, ill-fitting dentures, sharp teeth in causing oral cancers is not substantiated, these may be the
possible contributing factors. It is believed that chronic

trauma along with other carcinogens may aid in the


malignant transformation of epithelial cells.
Shah (2003) suggests that the microorganisms from
dental plaque, by way of chemical carcinogenesis, may produce nitrosating enzymes which are toxic. It is also believed
that individuals who do not maintain good oral hygiene
(inadequate brushing) may fail to dilute the carcinogens
present in the oral cavity, especially derived from various
tobacco-related habits.

MOLECULAR BASIS OF CANCER


Though no one truly understands how these conditions
either in their individual standing or in conjunction with
other entities leads to cancer, the greater understanding of
the importance of genetics and the role of pro-oncogenes
and tumor suppressor genes has given us a more detailed
insight into the evolution of a cancerous growth. Cellular
and molecular basis of malignancy though needs more
detailed discussion it could be best summarized under the
following sections.

Cellular Kinetics
Generation time is the time required for a quiescent cell to
enter the cell cycle and give rise to two daughter cells.
Malignant cells usually have a shorter generation time than
non-malignant cells and a smaller percentage of cells in
G0 (resting phase), so a larger proliferation fraction exists.
Initial exponential tumor growth is followed by a plateau
phase when cell death equals the rate of formation of
daughter cells. Compared to large tumors, small tumors
have a greater percentage of actively dividing cells and
thus show greater rates of proliferation.

Tumor Growth and Metastasis


As a tumor grows, nutrients are provided by direct diffusion from the circulation. Local growth is facilitated by
enzymes (e.g. collagenases) and cytokines that alter or
destroy adjacent tissues. As the ratio of surface area to volume becomes smaller with increased tumor growth, tumor
angiogenesis factors are produced, forming the independent vascular supply required for further tumor growth.
Almost from inception, a tumor may shed cells into the
circulation. From animal models, it is estimated that a
1-cm tumor sheds more than 1 million cells/24 h into the
venous circulation. Although most circulating tumor cells
die as a result of intravascular trauma, a tiny number
(much less than 1 in 1 million) adhere to the vascular endothelium and penetrate into surrounding tissues, generating
independent tumors (metastases) at distant sites. Metastatic
tumors grow in much the same manner as primary tumors
385

Section V Cysts and Tumors of Orofacial Region

and may subsequently give rise to other metastases.


Experiments suggest that metastasis is not a random event
and that the primary tumor may regulate the growth of
metastatic tumors, for example, removal of the primary
tumor sometimes results in rapid growth of the metastases.

Molecular Abnormalities
Genetic mutations are largely responsible for the generation
of malignant cells. These mutations alter the quantity or
function of protein products that regulate cell growth and
division and DNA repair. Two major categories of mutated
genes are oncogenes and tumor suppressor genes.
Oncogenes are abnormal forms of normal genes (protooncogenes) that regulate cell growth. Mutation of these
genes may result in direct and continuous stimulation of the
molecular biologic pathways (e.g. intracellular signal transduction pathways, transcription factors, secreted growth
factors) that control cellular growth and division.
There are more than 100 known oncogenes that may contribute to human neoplastic transformation, for example,
the ras gene encodes the Ras protein, which regulates cell
division. Mutations may result in the inappropriate activation of the Ras protein, leading to uncontrolled cell growth
and division. In fact, the Ras protein is abnormal in about
25% of human cancers. Other oncogenes have been implicated in specic cancers. These include various protein
kinases (bladder cancer, breast cancer), bcr-abl (chronic
myelocytic leukemia, B-cell acute lymphocytic leukemia),
C-myc (small cell lung cancer), N-myc (small cell lung
cancer, neuroblastoma), and C-erb B-2 (breast cancer).
Specic oncogenes may have important implications
for diagnosis, therapy, and prognosis (see individual discussions under the specic cancer type). Oncogenes typically result from acquired somatic cell mutations secondary
to point mutations (e.g. from chemical carcinogens), gene
amplication (e.g. an increase in the number of copies of
a normal gene), or from insertion of viral genetic elements
into host DNA. Occasionally, mutation of germ cell lines
results in vertical transmission and a higher incidence of
cancer development in an offspring.
Tumor suppressor genes are inherent genes that play a
role in cell division and DNA repair and are critical for
detecting inappropriate growth signals in cells. If these
genes, as a result of inherited or acquired mutations, become
unable to function, genetic mutations in other genes can
proceed unchecked, leading to neoplastic transformation.
As with most genes, two alleles are present that encode
for each tumor suppressor gene. A defective copy of one
gene may be inherited, leaving a person with only one
functional allele for the individual tumor suppressor gene.
If an acquired mutation occurs in the other allele, the normal protective mechanisms of the tumor suppressor gene
are lost, and dysfunction of other protein products or DNA
damage may escape unregulated, leading to cancer.
386

Another mechanism that results in defective function and


transcription of tumor suppressor genes is aberrant methylation of the promoter region of these genes, which inhibits
gene transcription. Greater degrees of aberrant methylation
and greater numbers of affected genes cause tumors to be
more malignant and are associated with shortened survival in lung, bladder, and prostate cancers. In vitro alteration of the aberrant methylation has caused reversion to a
non-malignant, non-proliferative phenotype, suggesting
a potential therapeutic target.
Another important regulatory protein, p53, prevents
replication of damaged DNA in normal cells and promotes
cell death (apoptosis) in cells with abnormal DNA. Inactive
or altered p53 allows cells with abnormal DNA to survive
and divide. Mutations are passed to daughter cells, conferring a high probability of neoplastic transformation. The
p53 gene is defective in many human cancers.
Gross chromosomal abnormalities can occur through
deletion, translocation, or duplication. If these alterations
activate or inactivate genes that result in a proliferative
advantage over normal cells, then a tumor may develop.
Chromosomal abnormalities occur in certain human cancers. In some congenital diseases (Bloom syndrome, Fanconi
syndrome, Downs syndrome), chromosomes break easily,
putting children at high risk of developing acute leukemia
and other cancers.
Most cancers are likely to involve several of the mechanisms described above that lead to neoplastic conversion.
As with oncogenes, mutation of tumor suppressor genes in
germ cell lines may result in vertical transmission and a
higher incidence of cancer in an offspring. Telomeres are
nucleoprotein complexes that cap the ends of chromosomes
and maintain their integrity. Telomere shortening (with
aging) results in replicative senescence, increased genetic
instability, and potential tumor formation. Telomerase is an
enzyme that carries out telomere synthesis and maintenance, thus telomerase may potentially allow for cellular
immortality. Telomerase activity may promote tumors
through multiple, complex mechanisms, especially by subverting the normal DNA synthetic checkpoints.

CLINICAL SIGNS OF CANCER


The hardest part of treating cancer is diagnosing it early,
but it is also the most easiest part of treating cancer
because if discovered early, the lesions are amenable to
simple excision and patients have a good chance of a
5-year disease-free survival rate. It makes it easier to
remember if the clinical signs are discussed based on the
regional anatomy.
The many signs and symptoms of oral cancer (Table 1)
are usually divided into early and late presentations. They
can be so diverse that the differential diagnosis may not
lead to oral malignancy.

Chapter 14 Oral Cancer

The clinical presentation varies in most cases and there are


no two cases that are similar in presentation and treatment.
However, there could be a few similarities that are peculiar
to the geographic area that could be grouped together and
explained as an entity, for example, carcinoma of the buccal mucosa and the gingivobuccal sulcus that are peculiar to
the Indian subcontinent and have been nicknamed as
Indian Cancers. Cancers of the oor of the mouth are more
common in the western countries because of their habits.
The following section is just a brief explanation of the
various clinical signs and symptoms based on their area of
presentation.

period of time. The tumor may appear as small nodules and


enlarges to from a wart-like growth which ultimately ulcerates or may even begin as an ulceration that does not heal.
The lesion is often not painful and is noticed by the patient
only when there is a secondary infection of the ulcer. There
is induration and infiltration into the deeper tissues.
Extension into the muscle of mastication, buccinators,
alveolar mucosa and ultimately into the bone may occur
and if left unchecked which may cause perforation of the
overlying skin (Figure 10). The induration of the skin is a
bad clinical sign and necessitates wider excision along
with the overlying skin.

Carcinoma of buccal mucosa

Figure 9

The lesions develop most frequently along or inferior to a


line opposite the plane of occlusion. It usually occurs at
the regions of the third molar area (Figure 9) as there is a
habit of keeping the quid (tobacco) in that area for a long

Table 1

Clinical signs of oral cancer

Early signs

Late signs

Persistent red and/or white patch


Non-healing ulcer
Progressive swelling or
enlargement
Unusual surface changes
Sudden tooth mobility without
apparent cause
Unusual oral bleeding or epistaxis
Prolonged hoarseness of voice

Indurated area
Paresthesia, dysesthesia of
the tongue or lips
Airway obstruction
Chronic earache (chronic
serous otitis media)/otalgia
Trismus and dysphagia
Cervical lymphadenopathy
Persistent pain or referred pain
Altered vision
Epiphora

Carcinoma of the left buccal mucosa extending into the


buccal vestibule. Courtesy: Dr Abhinandan

Figure 10
A

Carcinoma causing perforation of the cheek. Courtesy: Dr Abhinandan

387

Section V Cysts and Tumors of Orofacial Region

Some cases appear to be growing outward from the surface rather than invading the tissues is called exophytic or
verrucous growth. The most common site of metastasis is
the submandibular lymph nodes as they are the primary
echelon nodes for these regions.
Carcinoma of floor of mouth
It is seen more commonly in men; reasons being cited that
they tend to smoke and abuse tobacco a lot more than
women and the chemicals that mix with the saliva tend to
pool in the floor of the mouth for a longer time. It is seen
most frequently in the anterior portion of floor. The typical
carcinoma of the floor of mouth is an indurated ulcer of
varying size, on one side of the midline. It may take the
form of wart-like growth (Figure 11), which tend to spread
superficially rather than in depth. It may spread in four
primary directions, i.e. extend to the other side crossing
the midline, may extend upward involving the base of the
tongue or may come anteriorly invading the lingual mucosa
and ultimately invade the bone causing loosening of the
anterior teeth (Figure 12). Loosening of teeth is seen only
in advanced cases. However, patients seek an early consultation because of the restriction in the movements of the
tongue often causing peculiar thickening or slurring or the
speech. There may be excessive salivation. In some cases,
there may be referred pain in the ears.
Carcinoma of oor of mouth may invade the deeper tissues and may even extend into the submaxillary and sublingual glands. Metastasis from the oor of the mouth are
found most commonly in the submandibular group of
lymph nodes and also sometimes in the facial nodes, since
the primary lesion frequently occurs near the midline where

a lymphatic cross-drainage exists, contralateral metastasis


is often present.
Carcinoma of labial mucosa
It is frequently seen in people who habitually keep a mixture
of tobacco and lime in the labial vestibule. The lower labial
mucosa (Figure 13) is more commonly involved than the
upper though the upper lip often gets involved in such cases
due to inadvertent contact exposure to the carcinogens.
The most common initial signs and symptoms are growth

Figure 12

Orthopantomograph (OPG) showing extensive destruction of


the alveolus in the anterior portion of the mandible with
teeth floating in space appearance secondary to infiltration
of the carcinoma of floor of mouth to the alveolus.
Courtesy: Department of Oral Medicine and Radiology,
Manipal College of Dental Sciences, Mangalore

Figure 11
Figure 13

Wart-like growth in the anterior portion of the floor of


the mouth suggestive of carcinoma floor of mouth.
Courtesy: Department of Oral Medicine and Radiology,
Manipal College of Dental Sciences, Mangalore

388

Carcinoma of the lower lip showing signs of extensive


induration. Courtesy: Department of Oral Medicine and
Radiology, Manipal College of Dental Sciences, Mangalore

Chapter 14 Oral Cancer

Figure 14

Ulcero-proliferative lesion on the lower lip and


labial vestibule. Courtesy: Department of Oral Medicine and
Radiology, Manipal College of Dental Sciences, Mangalore

Figure 16

Carcinoma affecting the right lateral margin of the tongue.


Courtesy: Department of Oral Medicine and Radiology,
Manipal College of Dental Sciences, Mangalore

Figure 17
Figure 15

Extensive lesions affecting the lower lip, upper lip and


the right commissure. Courtesy: Department of Oral Medicine
and Radiology, Manipal College of Dental Sciences, Mangalore

or swelling, soreness and ulceration of the lip which does


not heal (Figure 14). Advanced lesion may be ulcerativeinfiltrative type which may restrict the movement of the
lower lip. Lymph node involvement may be unilateral or
bilateral as they drain primarily into the submandibular
nodes. Occasionally, the carcinoma may spread to the corners of the mouth and extend extraorally (Figure 15).
Carcinoma of tongue
The tongue is the most common intraoral site of cancer in
most countries. Of all potential etiologic factors, cancer of
the tongue is correlated the closest with the use of tobacco

Carcinoma affecting the ventral surface of the tongue.


Courtesy: Department of Oral Medicine and Radiology,
Manipal College of Dental Sciences, Mangalore

products. Squamous cell carcinoma is by far the most


common malignancy of the tongue, typically having three
gross morphologic growth patterns: exophytic, ulcerative,
and infiltrative. The infiltrative and ulcerative types are
observed most commonly on the tongue. Lateral margins
(Figure 16) and ventral surface (Figure 17) of the tongue
are more frequently affected. The most common finding is
an indurated, ulcerated area of the tongue. The induration
may extend deep into the tongue musculature and root of
the tongue. Malignancies of the tongue may grow to significant size before they cause symptoms. Because of the
relative laxity of the tissue planes separating the intrinsic
389

Section V Cysts and Tumors of Orofacial Region

Figure 18

Carcinoma of the palate causing perforation.


Courtesy: Dr Abhinandan

tongue musculature, the cancer may spread easily and


become symptomatic only when its size interferes with
movement. Squamous cell carcinoma of the tongue may
arise in apparently normal epithelium, in areas of leukoplakia, or in an area of chronic glossitis. These lesions
are usually larger than 2 cm at presentation, with the
lateral border being the most common subsite of origin.
At this point, the patient may develop speech and swallowing dysfunction. Pain occurs when the tumor involves
the lingual nerve, and this pain may also be referred to
the ear.
Carcinomas of the tongue base are clinically silent until
they deeply inltrate the tongue musculature. These are
usually less differentiated. Because of the difculties with
direct visualization, these may extend into the oral tongue
or have clinical lymph metastases before the diagnosis is
established.
Carcinoma of palate
It is common in areas where reverse smoking is practiced
or also among people who use pipe smoke. Palatal cancer
usually manifests as a poorly defined ulcerated painful
lesion on one side of the midline (Figure 18). Most other
lesions are exophytic and with broad base and nodular
surface. It frequently crosses the midline and may extend
laterally to include tonsillar pillars or even the uvula. The
tumor of hard palate may invade the bone or occasionally
the nasal cavity whereas infiltrating lesions of the soft
palate may extend into the nasopharynx.
Carcinoma of maxillary sinus
It is caused by sinusitis, snuff and smoke abuse, occupational hazards like in boot factories, metal workers and
390

Figure 19

Carcinoma involving the right maxillary antrum and


the alveolus. Courtesy: Dr Abhinandan

others of such type. As it is seen over periods of prolonged


exposure the mean age of occurrence is 60 years. Males
are commonly affected more than females in the ratio of
2:1. It is the most common primary tumor of paranasal
sinuses comprising 8090% of cancers in this site. There is
facial pain, swelling, nasal obstruction and lymphadenopathy. Medial wall involvement leads to nasal obstruction,
discharge, bleeding and pain. Epiphora will result if the
lacrimal sac or nasolacrimal duct is obstructed. Involvement
of the floor of the sinus leads to expansion of the alveolus,
unexplained pain, numbness of teeth, loose teeth and swelling of the palate or alveolar ridge (Figure 19) and malfitting
dentures. It may erode the floor and penetrate the oral
cavity.
Lateral wall involvement leads to facial and vestibular
swelling, pain and hyperesthesia of maxillary teeth. Roof
involvement leads to diplopia, proptosis and pain over
the cheek and upper teeth. Posterior wall involvement
leads to painful trismus as the pterygoids get involved,
obstruction of Eustachian tube causing stuffy ear, referred
pain and hyperesthesia over the distribution of second and
third divisions of trigeminal nerve. It may involve the
infraorbital nerve and produce paresthesia of the cheek or
erode blood vessels giving rise to epistaxis. Paresthesia of
mandibular nerve can also occur if the tumor invades the
cranium.
Primary intra-alveolar carcinoma
These lesions are rarely seen and surface only when they
invade the overlying mucosa either on the facial or the
lingual/palatal side as an exophytic growth. Most often
they present only as a non-healing socket or as loose teeth
which on radiographs appears as hanging teeth with no

Chapter 14 Oral Cancer

bony support. There may be evidence of paresthesia as the


nerve gets involved.

Table 2
Stage

CLINICAL EXAMINATION OF A PATIENT


WITH SUSPECTED MALIGNANCY
Since most of the lesions are innocuous, they escape early
detection and present only when it is too late. Good illumination, access and aseptic techniques go a long way in
aiding proper diagnosis.
Patients should often be examined thoroughly for any
suspicious red or white lesions that have no explainable
etiology. If any etiology is found such as sharp teeth margins or ill-tting dentures and bad restorations, they should
be removed and all habits must be stopped. The lesions
should be reviewed on 2-weekly intervals and must be
recorded by photographic evidence. Oral therapy of antioxidants may sometimes make the lesion disappear but
nevertheless the risk remains and the patient must be present for 6-month follow-up.
After a proper history taking, suspicious or sinister looking lesions must be examined for: (i) extent of the lesion/
swelling; (ii) margin characteristics of the ulcerations if
any; (iii) presence or absence of induration around or on
the lesion; (iv) involvement of the overlying skin/mucosa
(v) trismus; (vi) radiating pain to the ear; (vii) foul smell;
(viii) loss of function/mobility as in the case of tongue
with slurred speech and excessive salivation; (ix) paresthesia or anesthesia of the nerve in the vicinity of the lesion;
(x) discharge from the nose or persistent post nasal drip;
and (xi) diplopia of the eye on the affected side.

TNM STAGING
The tumor-node-metastasis (TNM) staging system was first
reported by Pierre Denoix in the 1940s. The International
Union Against Cancer (UICC) eventually adapted the system and compiled the first edition of the TNM staging system in 1968 for 23 body sites. It is important to realize that
the TNM staging system is simply an anatomic staging
system that describes the anatomic extent of the primary
tumor as well as the involvement of regional lymph nodes
and distant metastasis. Tumor size and the extent of spread
are considered to be the best indicators of the patients prognosis. Table 2 summarizes the most widely accepted staging
protocol, the TNM classification of oral cancer. This system
has three basic clinical features:
1.
2.
3.

The size (in centimeters) of the primary tumor


The presence, number, size, and spread (unilateral or
bilateral) to the local lymph nodes
The presence or absence of distant metastasis.

TNM stage grouping


T stage

N stage

M stage

Stage 0

Tis

N0

M0

Stage I

T1

N0

M0

Stage II

T2

N0

M0

Stage III

T3
T1
T3

N0
N1
N1

M0
M0
M0

Stage IV A

T4a
T4a
T1
T2
T3
T4a

N0
N1
N2
N2
N2
N2

M0
M0
M0
M0
M0
M0

Stage IV B

Any T
T4b

N3
Any N

M0
M0

Stage IV C

Any T

Any N

M1

TNM Staging System for Oral Carcinoma


Primary tumor (T)
TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
Tis: Carcinoma in situ
T1: Tumor 2 cm or less in greatest dimension
T2: Tumor more than 2 cm but not more than 4 cm in
greatest dimension
T3: Tumor more than 4 cm in greatest dimension
T4 (oral cavity): Tumor invades through cortical bone,
inferior alveolar nerve, floor of mouth, or skin of face, i.e.
chin or nose
T4a (oral cavity): Tumor invades adjacent structures
(e.g. through cortical bone, into deep [extrinsic] muscle of
tongue, maxillary sinus, skin of face)
T4b: Tumor invades masticator space, pterygoid plates, or
skull base and/or encases internal carotid artery.
Note: Superficial erosion of bone/tooth socket by gingival primary is not sufficient to classify a tumor as T4.
Regional lymph nodes (N)
NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Metastasis in a single ipsilateral lymph node, 3 cm or
less in greater dimension
N2: Metastasis in a single ipsilateral lymph node, more
than 3 cm but not more than 6 cm in greatest dimension;
in multiple ipsilateral lymph nodes, not more than 6 cm in
greatest dimension; in bilateral or contralateral lymph
nodes, not more than 6 cm in greatest dimension
391

Section V Cysts and Tumors of Orofacial Region

N2a: Metastasis in single ipsilateral lymph node more


than 3 cm but not more than 6 cm in greatest dimension
N2b: Metastasis in multiple ipsilateral lymph nodes, not
more than 6 cm in greatest dimension
N2c: Metastasis in bilateral or contralateral lymph nodes,
not more than 6 cm in greatest dimension
N3: Metastasis in a lymph node more than 6 cm in greater
dimension.
Distant metastasis (M)
MX: Presence of distant metastasis cannot be assessed
M0: No distant metastasis
M1: Distant metastasis.
The individual clinical parameters in the TNM classification
system are grouped to determine the appropriate disease
stage; stages are ranked numerically from 0 (which has the
best prognosis) to IV (the worst prognosis). In general, oral
staging classifications do not use histopathologic findings
except to determine the definitive diagnosis.

NODAL METASTASIS
Involvement of regional lymphatic by primary squamous
cell carcinomas of the upper aerodigestive tract is dependent on various factors related to the primary tumor. These
include the site, size, T-stage and location of the primary
tumor. In addition to this, histomorphologic features of the
primary tumor also influence the risk of nodal metastases.
The risk of nodal metastasis increases in relation to location
of the primary tumor, as one progresses from the anterior
to posterior aspect of the upper aerodigestive tract meaning: the risk of the lips  oral cavity  oropharynx  hypopharynx. For tumors of the larynx and pharynx, the risk
of nodal metastasis increases as it progresses from the
center to the periphery, meaning the risk of regional lymph
node metastasis from carcinoma of the true vocal cord is
exceedingly small. The risk, however, increases as one
progress for the vocal cords to the false vocal cords, aryepiglottic fold, pyriform sinus, and pharyngeal wall. Nearly
two-thirds of patients with primary carcinomas of the hypopharynx present with clinically palpable regional lymph
node metastasis.
Certain primary sites have a signicantly increased risk
of nodal metastases compared to the other sites in the
same region, for example, oor of mouth versus hard palate in the oral cavity. In general, T-stage usually reects
tumor burden or invasiveness and therefore the risk of
nodal metastases increase with increasing T-stage of the
primary tumor at any site. Similarly, tumor size (large versus small) increases the risk of dissemination to regional
lymph nodes.
Certain histomorphologic features of the primary tumor
also increase the risk of nodal metastasis. Endophytic tumors
392

in that regard are more inclined to metastasize compared


to exophytic tumors. It has been well documented that
for tongue and oor of mouth cancers, tumor thickness is
related to the risk of nodal metastases. Poorly differentiated
carcinomas have a higher risk of nodal metastases compared to well-differentiated lesions. In general, if the risk of
occult metastases exceeds 1520%, then elective treatment
of regional lymph nodes is recommended due to its signicantly adverse impact on prognosis. Risk of nodal metastases from cutaneous malignancies is highly variable. Small
size (2 cm) squamous cell carcinomas of the skin of the
face and neck have a very low risk of nodal metastases.
Similarly, small cancers of the sweat gland or adnexal origin
also have a low risk of metastases to regional lymph nodes.
Therefore, elective treatment of regional lymph nodes is
generally not recommended except for patients with massive tumors. On the other hand, cutaneous melanomas have
a predictably high risk of nodal metastases with increasing
thickness and site of the primary tumor. Therefore, one
can justify elective treatment of regional lymph nodes for
thicker primary melanomas although increasing popularity of sentinel node mapping techniques negates the consideration of elective lymph node dissections.
Metastatic spread from primary carcinomas of salivary
origin is generally low (20%). Therefore, elective dissection of cervical lymph nodes is recommended for high
stage (T3T4) and high grade (poorly differentiated)
carcinomas.

Cervical Lymph Nodes


Patients who present with tumors localized at the primary
site without dissemination to regional lymph nodes enjoy
an excellent prognosis. On the other hand, once dissemination to regional lymph nodes takes place, the probability of 5-year survival, regardless of the treatment rendered,
reduces by nearly 50% of those patients with early staged
patients. Clearly, therefore, the single most important
prognostic factor in the treatment of patients with squamous cell carcinoma of the head and neck is the status of
cervical lymph nodes. Thus, management of cervical
lymph nodes becomes a vitally important component of
the overall treatment strategy for patients with cancers of
the head and neck. The patients seeking surgical intervention for malignancies in the Indian scenario is only when
it is in a very advanced stage, and all the levels of nodes
are involved and is almost inoperable.

Anatomy of Regional Lymphatics


The lymphatic drainage from the scalp and skin of the
head and neck region, the mucosa of the upper craniofacial regions, salivary glands, and the thyroid gland occurs
to specific regional lymph node groups. Surprisingly, tumor

Chapter 14 Oral Cancer

dissemination via regional lymphatic to these lymph node


groups occurs in a predictable and sequential fashion too.
Hence, specific regional lymph node groups should be
appropriately addressed in the treatment planning for any
given primary site. The plans should encompass all the
nodes both accessible to surgical ablation and those not
accessible to surgery.
The anterior half of the scalp, the skin of the forehead
and the upper part of the face drain rst to the preauricular,
periparotid and intraparotid lymph nodes are thus the rst
echelon lymph nodes. The initial drainage of the posterior
half of the scalp and the posterior aspect of the external ear
takes place to the post-auricular and suboccipital group of
lymph nodes. Cervical lymph nodes in the lateral aspect of
the neck primarily drain the mucosa of the upper aerodigestive tract. These include the submental, prevascular facial,
and submandibular group of lymph nodes located in the
submental and submandibular triangles of the neck, deep
jugular lymph nodes include the jugulo-digastric, juguloomohyoid, and supraclavicular group of lymph nodes adjacent to the internal jugular vein. Lymph nodes in the posterior
triangle of the neck include the accessory nerve and the
transverse cervical chain of lymph nodes in the oor of the
posterior triangle of the neck. Parapharyngeal and retropharyngeal lymph nodes are at risk of metastatic dissemination from tumors of the pharynx.
The central compartment of the neck includes the delphian lymph node overlying the thyroid cartilage in the
midline draining the larynx and perithyroid lymph nodes
adjacent to the thyroid gland. Lymph nodes in the tracheoesophageal groove provide primary drainage to the thyroid
gland as well as the hypopharynx, subglottic larynx, and
cervical esophagus. Lymph nodes in the anterior superior
mediastinum provide drainage to the thyroid gland and the
cervical esophagus, and serves as a secondary lymphatic
basin for anatomic structures in the central compartment of
the neck. Each anatomic subgroup of lymph nodes described
above specically serves as primary echelon lymph nodes
draining a specic site in the head and neck region. Thus,
location of a palpable metastatic lymph node may often
indicate the potential source of a primary tumor.
The Head and Neck Service at Memorial Sloan Kettering
Cancer Center has described a leveling system dividing
the lymph nodes in the lateral aspect of the neck into ve
nodal groups of levels to establish a consistent and easily
reproducible, user-friendly method for description of
regional cervical lymph nodes which establishes a common
language between the clinician and the pathologist. The
lymph nodes in the central compartment of the neck are
assigned levels VI and VII.
Level I Submental group: The lymph nodes between the
anterior bellies of the digastric muscles and above the hyoid
bone. Submandibular group: Lymph nodes in the triangular area bounded by the anterior and posterior bellies of

the digastric muscle and the inferior border of the body of


the mandible. The lymph nodes adjacent to the submandibular salivary gland and along the facial artery (facial
nodes) are included in this group.
Level II Upper jugular group: Lymph nodes around the
upper portion of the internal jugular vein and the upper
part of the spinal accessory nerve, extending from the base
of the skull up to the bifurcation of the carotid artery or
the hyoid bone (clinical landmark). The posterior limit for
this level is the posterior border of the sternocleidomastoid
muscle and the anterior border is the lateral limit of the
sternohyoid muscle.
Level III Mid-jugular group: Lymph nodes around the
middle third of the internal jugular vein from the inferior
border of Level II up to the omohyoid muscle or the inferior border of cricoid cartilage (clinical landmark). The
anterior and posterior borders are the same as those for
Level II.
Level IV Lower jugular group: Lymph nodes around the
lower third of the internal jugular vein form the inferior
border of Level III up to the clavicle. The anterior and posterior borders are the same as those for Levels II and III.
Level V Posterior triangle group: Lymph nodes around
the lower portion of the spinal accessory nerve and along
the transverse cervical vessels. It is bounded by the triangle formed by the clavicle, posterior border of the sternocleidomastoid muscle, and the anterior border of the
trapezius muscle.
Level VI Central compartment group: Lymph nodes in
the prelaryngeal, pretracheal (Delphian), paratracheal, and
trachoesophageal groove. The boundaries are: hyoid bone
to suprasternal notch and between the medial borders of
the carotid sheaths.
Level VII Superior mediastinal group: Lymph nodes in
the anterior superior mediastinum and tracheoesophageal
grooves, extending from the suprasternal notch to the
innominate artery.
Clinical features and diagnosis
Lymph nodes in the head and neck region may be present
for many reasons although the presence of a clinically
palpable, unilateral, hard, enlarged lymph node in the
adult should be considered metastatic until proven otherwise. The location of a palpable lymph node may point to
the potential site of a primary tumor. The important features to note during examination of the neck for cervical
lymph nodes are the location, size, consistency, and number of palpable lymph nodes as well as signs of extracapsular spread such as invasion of the overlying skin,
fixation to deeper soft tissues, or paralysis of cranial
nerves. Histologic diagnosis of metastatic carcinoma is usually established by a needle aspiration biopsy and cytologic
393

Section V Cysts and Tumors of Orofacial Region

examination of the smears. An enlarged metastatic cervical lymph node may be the only physical finding present
in some patients whose primary tumors are either microscopic or occult at the time of presentation. A systematic
search for a primary tumor should be undertaken in these
patients prior to embarking upon therapy for the metastatic nodes. If a thorough head and neck examination,
including fiberoptic nasolaryngoscopy, fails to show a primary tumor, then the diagnosis of metastatic carcinoma to
a cervical lymph node from an unknown primary (occult
primary) is established.

Patterns of Neck Metastasis


Dissemination of metastatic cancer to regional lymph nodes
from primary sites in the upper aerodigestive tract occurs
in a predictable and sequential fashion. Thus, all regional
lymph node groups are usually not at risk of nodal metastases initially from any primary site, in the absence of grossly
palpable metastatic lymph nodes. On the other hand, when
clinically palpable lymph nodes are present at the time of
initial diagnosis, comprehensive clearance of all regional
lymph node groups at risk is warranted. Understanding
the sequential patterns of neck metastasis therefore greatly
facilitates surgical management of regional lymph nodes
in the clinically negative neck where the lymph nodes are
at risk of harboring micrometastasis.
For primary tumors in the oral cavity the regional lymph
nodes at highest risk for early dissemination by metastatic
cancer are limited to Levels I, II and III. This means the
regional lymph node groups are contained within the
supraomohyoid triangle of the neck. The lymph node
groups contained in the supraomohyoid triangle are: submental, submandibular, prevascular facial, jugulodigastric, upper deep jugular, superior spinal accessory chain of
lymph nodes, and mid-jugular lymph nodes. Skip metastasis to Levels I, II, or III is exceedingly rare. Therefore, if the
neck is clinically negative, Levels IV and V lymph nodes
are generally not at risk of harboring micrometastasis
from primary squamous carcinomas of the oral cavity. An
exception to this observation is primary squamous cell
carcinomas of the middle third of the lateral border of the
tongue where skip metastases to Level IV have been
reported.
Tumors on the lateral aspect of the oropharynx, hypopharynx and larynx, the rst echelon lymph nodes are the
deep jugular lymph nodes at Levels II, III and IV on the
ipsilateral side and they are at highest risk of harboring
micrometastasis in the clinically negative neck. Primary
tumors which involve both sides of the midline have a
potential of microscopic dissemination of metastatic disease
to jugular lymph nodes on both sides of the neck. Similarly,
tumors of the medial wall of the pyriform sinus are
reported to have an increased risk of contralateral neck
metastases.
394

Only 2025% of patients with carcinoma of the parotid


gland develop regional lymph node metastasis. The lymph
node groups at highest risk for early dissemination of
metastatic cancer from primary carcinoma of the parotid
gland are those in the preauricular, periparotid, and intraparotid regions as well as lymph nodes in the upper deep
jugular chain and those in the upper spinal accessory chain
in the posterior triangle of the neck. Initial dissemination
of metastatic cancer from primary malignant tumors of
the submandibular salivary gland occurs at lymph nodes
in the supraomohyoid triangle. Thus, lymph nodes in the
submandibular triangle and upper and mid-jugular chain
of lymph nodes are at the risk of micrometastasis from
malignant tumors of the submandibular salivary gland in
the clinically negative neck.
Cutaneous malignant tumors of the scalp, such as squamous carcinoma and melanoma, also spread to regional
lymph nodes in a predictable fashion. A line joining the
helix of one ear to the helix of the opposite ear in a coronal
plane separates the watershed areas of the scalp. Tumors
located anterior to this line metastasize to preauricular,
periparotid and anterior cervical lymph nodes (Levels I
IV) and seldom metastasize to the posterior triangle of the
neck. On the other hand, primary tumors of the scalp posterior to this line metastasize to the suboccipital and postauricular group of lymph nodes as well as those in the
posterior triangle of the neck and the deep jugular chain
(Levels IIV).

Sentinel Node Mapping


The procedure of sentinel node mapping employs one or all
of the following three techniques: (i) radioisotope scan imaging; (ii) injection of blue dye; and (iii) use of a handheld
isotope tracer probe for localization. It has been shown that
the combination of all three techniques increases the accuracy and the yield of sentinel lymph node identification.
A preoperative technetium scan is obtained rst. This
requires injection of radioactive technetium (99mTc) labeled
sulfur colloid. Generally, 0.05 mCi of the isotope is injected
in four quadrants around the primary lesion and a gamma
camera is used for obtaining visual images at 3 minutes,
15 minutes, and a delayed image at 1 hour. Usually, the
rst lymph node identied by the technetium scan is considered the sentinel lymph node. In some patients, more
than one sentinel lymph node is identied.
Immediately prior to the surgical procedure, isosulfan
blue dye 1% (Lymphazurin) is injected similarly in four
quadrants around the primary tumor (Figure 18). No more
than 0.5 ml of the dye is injected into the subdermal plane
around the tumor. The operative procedure then is carried
out within 30 minutes of the injection. A handheld gamma
probe is used before placing the incision to localize the
lymph node seen on the preoperative scan. The background
activity is averaged from measurements in four quadrants

Chapter 14 Oral Cancer

of the neck and any node that has an in vivo 10-second


count more than three times that of the background is considered hot. Correlation is made with the preoperative scan
and this area is marked out with a marking pen on the skin.
An incision is placed directly overlying the localized sentinel lymph node and by careful alternate blunt and sharp
dissection, the blue node is localized. The handheld probe
is again used to measure the count of highest radiotracer
activity. If the blue node corresponds to the area of highest
radiotracer activity, then the lymph node is excised and
sent for pathologic analysis. The surgical area after excision of the lymph node is tested with the handheld probe
to show that the radiotracer activity is now reduced to that
observed in the adjacent background area, conrming that
the true sentinel lymph node has been excised and sent
for pathologic analysis. If the residual radioactivity in the
basin is more than 10% of the ex vivo count of the hottest
node in the basin, further exploration to nd more sentinel nodes is warranted. The radiotracer activity is measured
with a handheld probe from the lymph node ex vivo to
demonstrate that the lymph node itself has a count at least
10 times that of an adjacent non-sentinel node. This ensures
that the excised lymph node is indeed a true sentinel lymph
node. At present, opinions regarding the value of frozen
section for a sentinel node vary. Because of the special processing required by sub-serial sectioning of the lymph node
to identify occult metastasis some investigators prefer not
to send the lymph node for frozen section and wait for rush
parafn sections within 24 hours to get a more detailed
analysis of the sentinel lymph node. Further surgical management of regional lymph nodes then depends on the
pathologic analysis of the excised sentinel lymph node.

DIAGNOSIS OF ORAL CANCER


Various diagnostic tests can be employed to detect potentially malignant and malignant lesions. In routine practice,
vital staining, brush biopsy, exfoliative cytology, tissue
biopsy and various imaging modalities (plain radiographs,
CT, MRI, ultrasonography, etc.) can be used effectively.
Newer diagnostic tools such as VELscope and ViziLite
Plus, Raman spectroscopy, high performance laser spectroscopy-laser induced uorescence (HPLC-LIF) also play a
signicant role in the early diagnosis of oral malignancies.
The VELscope is based on the direct visualization of
tissue uorescence and the changes that occur when abnormal cells are present. The VELscope handpiece emits a safe
blue light into the oral cavity, causing tissue uorescence
from the surface of the epithelium through to the basal
membranewhere pre-malignant changes typically start.
By utilizing special optical lters in the VELscope handpiece the clinician is able to immediately view the different
uorescence signatures in the oral tissue to help differentiate between normal and abnormal cellular activities.

ViziLite Plus is another popular screening tool for detection of oral cancers. As ViziLite Plus is passed over oral
tissue that has been treated with the rinse solution, normal
healthy tissue will absorb the light and appear dark,
abnormal tissues will appear white.
Venkatakrishna et al (2003) developed a HPLC-LIF
technique to detect and record simultaneously spectra and
chromatograph of physiological samples. This system
enables the detection of multiple markers in a single physiological sample in a short time. Samples of saliva and
serum from normal and oral cancer subjects have been
studied with the set-up. Their study showed that body uids
like saliva and serum of normal, premalignant and malignant subjects had substantially different protein proles.
They suggest that by simultaneous recording of the
chromatographic peaks and corresponding uorescence
spectra, it is possible to carry out unambiguous discrimination between normal, premalignant and malignant
cases even when markers are present in femto/subfemto
mole quantities, which should assist in early diagnosis of
neoplasia.

Imaging Modalities
Plain radiographic examination may include the use of
OPG, occlusal and intraoral periapical radiographs. Paranasal sinus view is useful for assessing extent of bone
involvement in the maxillary sinus region.
Plain radiographs
Intraoral periapical radiographs are useful to assess finer
details such as subtle bone invasion, bony trabecular
architecture (Figure 20) and destruction of the lamina
dura. Occlusal radiographs (Figure 21) may help in evaluating destruction of bone in the anterior portion of the
jaws which cannot be assessed adequately in an OPG. The
mandible is more commonly affected than the maxilla.
The typical radiographic features of carcinoma invading
bone include: ill-defined destruction (moth-eaten appearance) of bone with ragged borders (Figure 22), cortical
plates may be thinned out leading to a pathological fracture (Figure 23), extensive lesions may cause destruction
of floor of the nasal fossa, maxillary sinus (Figure 24), and
the cortical lining of the mandibular canal. Lamina dura
around teeth are lost. However, roots of teeth show no
signs of resorption as seen in benign tumors. This destruction of bone around teeth gives rise to floating in space
appearance (Figure 25).
CT, MRI and PET
Cross-sectional imaging modalities such as CT and MRI
help in assessing the size and extent of a tumor in three
dimensions. MRI imaging is considered more sensitive in
evaluating the possibility of intracranial invasion. On the
395

Section V Cysts and Tumors of Orofacial Region

Figure 20

Intraoral periapical radiograph showing fine details of


loss of normal trabecular architecture in carcinoma involving
bone. Courtesy: Department of Oral Medicine and Radiology,
Manipal College of Dental Sciences, Mangalore

Figure 22

Orthopantomograph showing ill-defined destruction of


bone with ragged borders in the anterior portion
of the mandible. Courtesy: Department of Oral Medicine and
Radiology, Manipal College of Dental Sciences, Mangalore

Figure 23

Figure 21

Pathological fracture. Courtesy: Department of Oral Medicine


and Radiology, Manipal College of Dental Sciences, Mangalore

Lower occlusal radiograph showing destruction of bone in the


anterior portion of the mandible. Courtesy: Department of
Oral Medicine and Radiology, Manipal College of Dental
Sciences, Mangalore

other hand, the extent of bony involvement by the tumor


mass is best assessed with CT. Extensive metastasis
(involvement of carotid artery, cranium, parapharyngeal
space, etc.) may be evaluated using a CT scan with intravenous contrast or an MRI scan with gadolinium contrast.
Lymph nodes which are not amenable for clinical examination (retropharyngeal and parapharyngeal nodes) or for
FNAC may be assessed using CT and MRI.
396

Metastatic nodes can be differentiated from normal


nodes by their size, presence of central necrosis, rim
enhancement and extranodal invasion. The size criterion
for nodes in the neck which are considered radiologically
positive for metastasis is as follows: nodes larger than
15 mm in the longitudinal diameter in the jugulodigastric
area and submandibular triangle, other nodes in the neck
are considered radiologically positive if larger than 10 mm.
However, when retropharygeal nodes are larger than 8 mm
they are considered positive. When axial diameters are
considered, 11 mm and above is regarded positive for jugulodigastric nodes and 10 mm and above for other nodes
in the neck.
The shape of the node can be denoted in terms of the
LT ratio (longitudinal and transverse diameters). An LT

Chapter 14 Oral Cancer

Figure 24

Ultrasound, specially using high resolution probes


(7.515 MHz) has always been considered a powerful tool
for assessment of cervical lymph nodes. Apart from locating lymph nodes, ultrasonography can evaluate their number, shape, dimensions, margins, and internal structure.
Vital staining

Orthopantomograph showing destruction of the alveolus


in the right molar region with involvement of the floor
of the maxillary sinus. Courtesy: Department of Oral
Medicine and Radiology, Manipal College of Dental
Sciences, Mangalore

Figure 25

Orthopantomograph showing extensive destruction of


bone in the anterior portion of the mandible extending
to the molars on either side. Blue arrow indicates
thinning of the lower cortical plate. White arrows
show teeth floating in space. Courtesy: Department
of Oral Medicine and Radiology, Manipal College of
Dental Sciences, Mangalore

ratio of two nodes suggests metastasis (a rounded node is


considered positive compared to a bean-shaped node).
A newer imaging tool that is gaining favor among radiologists is the positron emission tomography (PET). PET is
advantageous for the fact that it not only helps in localizing a lesion but even demonstrates its metabolic activity.
As malignant cells are known to divide rapidly, their
increased activity is easily picked up by the PET scan.
Distant metastasis imaging
Distant metastasis from the oropharynx can be assessed
using chest radiography (traditional/CT), abdominal ultrasonography (to evaluate liver metastasis), radionuclide
imaging and blood studies (tumor markers).

In 1964, Niebel and Chomet first reported the use of toluidine blue (tolonium chloride) as a vital tissue stain to aid
in the early detection of oral precancerous and malignant
lesions. Though it is not cancer specific, it has been
reported to stain mitochondrial DNA, altered DNA in premalignant and malignant epithelial lesions and cells with
relatively increased amounts of DNA. Warnakulasuriya
and Johnson (1996) reported that toulindine blue-positive
lesions with minimal or no identifiable dysplasia on initial
biopsy were almost four times more likely to transform to
carcinoma than lesions found to be toluidine blue-negative.
Toluidine blue is also an useful adjunct to clinical examination and biopsy. Toluidine is a basic metachromatic dye
that stains for acidic tissue components and thus binds
more readily to DNA. In addition, it can help to determine
the most appropriate biopsy sites and to surgically delineate
margins. Meta-analysis of toluidine blue staining in oral
cancer screening found that its sensitivity ranged from
93.5 to 97.8%, and specicity from 73.3 to 92.9%.
TBlue630 is a patented, pharmaceutical-grade toluidine
blue-based metachromatic dye. It provides the deep blue
staining that allows identied lesions to be seen clearly
under normal light.
Exfoliative cytology
It is a known fact that dysplastic and cancerous cells tend
to have fewer and weaker connections to each other and to
their neighboring normal cells in the surrounding tissue.
Dysplastic and cancerous cells therefore, tend to slough off
or exfoliate preferentially and can easily be collected from
the surface of the lesion. A sample of these cells applied
to a microscope slide will often contain abnormalities if
obtained from a dysplastic or cancerous lesion.
Sample can be obtained using rm strokes with a tongue
blade, cement spatula or a newer technique using a brush
(referred to as brush biopsy).
The cytology is reported as:

Class I (normal)normal cells.


Class II (atypical)indicates the presence of minor
atypia but no malignant changes.
Class III (indeterminate)the cells display wider atypia
that may be more suggestive of cancer, pre-cancer, or
carcinoma in situ. Biopsy is recommended.
Class IV (suggestive of cancer)a few cells with malignant characteristics or many cells with borderline
characteristics. Biopsy is mandatory.
397

Section V Cysts and Tumors of Orofacial Region

Brush biopsy
This technique was introduced in 1999 as a substitute to
the conventional exfoliative cytology procedure. A commercially available kit is used (oral CDX).
This biopsy method utilizes a brush to obtain a complete
transepithelial biopsy specimen with cellular representation
from each of the three layers of the lesion: the basal, intermediate, and supercial layers. Unlike previous cytologic instruments, which collect only exfoliated supercial cells,
when used properly and rubbed against an area of suspect
tissue aggressively (to the point of minor bleeding) the
biopsy brush penetrates to the basement membrane, removing tissue from all three epithelial layers of the oral
mucosa. The oral brush biopsy does not require topical or
local anesthetic and causes minimal bleeding and pain. The
brush biopsy instrument has two cutting surfaces, the at
end of the brush and the circular border of the brush. Either
surface may be used to obtain the specimen. In a recent
study, paired, same site samples of tongue tissue were
obtained from patients, rst by brush biopsy and then by
surgical punch biopsy. The study demonstrated that the
brush biopsy technique, unlike cytology, sampled the full
thickness of oral epithelium.
Results of brush cytology specimen are classied into
one of the four categories:
1.
2.
3.
4.

Inadequate: incomplete trans-epithelial specimen


Negative: no epithelial abnormality
Atypical: abnormal epithelial changes of uncertain
diagnostic significance
Positive: definitive cellular evidence of epithelial dysplasia or carcinoma.

Histopathologic features
All suspicious lesions should be subjected to an excisional
or incisional biopsy and the specimen should be subjected
to histopathological evaluation.
In general, all carcinomas exhibit the following features:
epithelial dysplasia, keratinization (varies with degree of
differentiation), local invasion by break in the basement
membrane and invasion and proliferation into the underlying connective tissue (clinically manifested as xation
and induration of the lesion), metastasis by blood or lymphatic channels histopathologically seen as invasion of
tumor cells into the capillaries and lymphatic ducts permeation and perineural invasionsome of the tumor cells
may have atypical invasion pattern along the nerve
sheath.
The histopathological features are graded into three
types depending upon the degree of differentiation of the
neoplastic proliferating cells. They are:
1.

398

Well-differentiated or highly differentiated squamous


cell carcinoma

Figure 26
Normal epithelium

Dysplastic epithelium

Islands of tumor
epithelium

Keratin pearl

Histopathological features of squamous cell carcinoma.


Courtesy: Department of Oral Pathology,
MCODS, Mangalore

2.
3.

Moderately differentiated squamous cell carcinoma


Poorly differentiated squamous cell carcinoma.

Well-differentiated squamous cell carcinoma


It consists of sheets and nest of cells with characteristic
appearance of squamous origin. These cells are generally
large and show distinct cell membrane. These resemble the
cells of squamous epithelium, both structurally and functionally. The intercellular bridges are prominent (Figure 26).
The nuclei are distinctly dark staining. Increased number of mitotic gures but relatively few when compared to
moderately differentiated carcinoma. It also shows hyperchromatism prominent and multiple nucleoli and increased
nucleocytoplasmic ratio. Most prominent features are the
presence of individual cell keratinization and formation of
numerous keratin pearls of varying size.
Each keratin pearl consists of a central area of keratin
surrounded by whorls of prickle cells. Pleomorphism of
cells, keratinization, and keratin pearls deep to epithelial
surface and loss of intercellular bridges or cohesiveness may
be seen.
Moderately differentiated/less well-differentiated
squamous cell carcinoma
The tumor cells are less differentiated and have less resemblance to squamous epithelium. The characteristic shape of
an epithelial cell may not be evident. The cell to cell contacts and relation and arrangement are altered.
The greater number of mitotic gures shows that the
growth rate is more rapid. These may be of varied size and

Chapter 14 Oral Cancer

shape. Keratin pearls may not be present. Numerous epithelial islands of prickle cells with peripheral basal cells
may be seen.
Poorly differentiated squamous cell carcinoma
This is the tumor with proliferation of anaplastic cells,
highly invasive with poor prognosis. The tumor cells bear
little resemblance to their cells of origin and often will
present diagnostic difficulties because of the primitive and
uncharacteristic histologic appearance. These cells show
lack of cohesiveness and are extremely vagarious. The
mitotic figures are extremely high.
Management
There are three recognized treatment modalities for managing head and neck cancers: surgery, radiotherapy and chemotherapy. As a thumb rule, Stage I and Stage II cancers
can be managed either by surgery or radiotherapy. However,
Stage III and Stage IV cancers are managed using a combination of radiation therapy and surgery.
Based on the nature of the tumor, the treatment modality is chosen. Factors that inuence the choice of treatment include: site and location of the primary (tongue,
oor of mouth/anteriorly or posteriorly), size of the tumor
(based on T stage), proximity to the bone, status of nodal
involvement, histological typing of the tumor (cell type
and degree of differentiation), ability to achieve adequate
surgical margins and preserve functions, physical and
mental status of patient and history of any treatment.
Surgical management Surgical treatment aims at complete removal of the primary as well as the metastatic nodes.
It is never used as a palliative mode of treatment. Criteria
for choosing surgical management are: tumors which are
non-sensitive to radiation, tumors involving bone, recurrent tumors in sites that have been previously irradiated,
to reduce bulk of tumor prior to radiation therapy (debulking), where side effects of surgery are expected to be less
significant than those associated with radiation and when
nodes are to be removed.
Surgical management aims at clearance of both the
primary lesion and the involved regional lymphatics.
The extent of resection of the primary lesion depends
upon the size and the adjacent structures that may have
been inltrated.
Neck dissection (cervical lymphadenectomy) In this procedure, all lymph nodes are removed beginning from the
lower border of the mandible superiorly to the clavicular
region inferiorly, and from the trapezius muscle posteriorly to the midline anteriorly. The sternocleidomastoid
muscle, omohyoid muscle, jugular vein and submandibular
salivary gland are resected. Based on the clinical involvement of lymph nodes, neck dissections can be categorized
as prophylactic (clinically non-palpable nodes, may or

may not be microscopically involved) and therapeutic


(clinically palpable nodes and presumed to be microscopically involved).
Commando surgery A combined resection wherein the primary tumor, affected lymphatics and involved adjacent
structures are removed is referred to as a commando surgery.
Microscopically frozensection oriented histologic surgery
(MOHS) technique In this technique, surgically resected
specimens are immediately frozen and histologically analyzed to assess for clear margins. This immediate assessment
will aid in removing all tumor cells.
Radiation therapy Radiotherapy plays an important role
in the management of head and neck cancer. The majority
of new cases of invasive head and neck cancer will need
radiotherapy as a primary treatment. This radiation, in
effect, disrupts the electron orbital structure of tissue atoms,
which subsequently damages individual cells and tissue.
Normal tissue function depends primarily on cell integrity
and viability, as well as on the ability of the cells to replace
and maintain their structure and organization. Cells are
most vulnerable to injury when they are in the process of
dividing and multiplying.
The ionizing radiation exerts its effect on cells by displacing the electrons from the molecules and atoms with
which they collide, causing ionization and inducing a cascade of events that may alter the cells transiently or permanently. The most important target of ionizing radiation
is DNA. The radiation may damage the DNA directly (Direct
Target Theory), or indirectly by inducing the formation of
free radicals, particularly those that form from the radiolysis of water (Indirect Target Theory). Other cell molecules
that may also be directly or indirectly damaged include
the lipids in cell membrane and proteins that function as
critical enzymes.
In addition to anti-tumor effects, ionizing irradiation
causes damage in normal tissues located in the eld of
radiation. This becomes particularly evident in the head
and neck region, a complex area composed of several dissimilar structures that respond differently to radiation:
mucosal linings, skin coverings, subcutaneous connective
tissue, salivary gland tissue, teeth, and bone/cartilage.
Acute changes produced by radiotherapy are observed in the
oral mucosa (erythema, pseudomembrane-covered ulceration), salivary glands (hyposalivation, changed salivary
composition), taste buds (decreased acuity), and skin (erythema, desquamation).
Radiation dose The radiation dose needed for the treatment of cancer is based on location and type of malignancy, and whether or not radiotherapy will be used solely
or in combination with other modalities. Most patients with
head and neck carcinomas, treated with a curative intent,
receive a dose between 50 and 70 Gy. This dose is usually
given over a 5- to 7-week period, once a day, 5 days a week,
399

Section V Cysts and Tumors of Orofacial Region

2 Gy per fraction. The total dose for preoperative radiotherapy or radiotherapy for malignant lymphomas is usually lower.
Fractionated radiation Fractionated radiation is used
because there is a difference in the responses of tumor tissue and normal tissue. In general, normal tissue repairs
sublethal DNA damage, especially in the low-dose range,
better than tumor tissue. The sparing effect of fractionated
radiation is the largest for late-responding tissues, whereas
early-responding tissues respond more like tumor tissue.
Next to DNA-repair advantages, fractionated irradiation
allows for the re-population of tissue between fractions
(especially during the weekend, when the tumor and normal
tissues are not radiated), thereby reducing early effects.
This, however, also applies for rapidly proliferating malignant tissue. Another advantage is that fractionated irradiation allows for re-oxygenation of radio-resistant hypoxic
tumors between fractions, leading to a higher percentage
of radiosensitive oxygenated cells.
Ideal candidates for radiotherapy Small lesions less than
3 cm and superficial without necrotic areas can be readily
managed with radiation therapy. The choice of treatment
also depends on functional and cosmetic concern. If
regional excision can be accomplished without much morbidity, surgery should be the treatment of choice. On the
contrary, if the lesion involves large areas like tongue,
floor of the mouth or buccal mucosa, and if excised it
would result in morbidity, thus local irradiation would be
the treatment of choice. But if the lesion is invasive involving the bone, radiation sterilization of the tumor is not
possible without extensive normal tissue damage, therefore surgery or a combination of irradiation and surgery
may be required. Lesions that are extremely radiosensitive
such as lymphomas, radiation therapy should be the treatment of choice. If the location and clinical behavior of a
lesion indicates significant lymphatic permeation, then
radiotherapy alone or in combination with surgery is the
treatment of choice as a wider volume.
Radiation technique Radiation therapy may be administered to a localized lesion by using brachytherapy (applicators or implants) or to a region of the head and neck by
using teletherapy (external beam radiation).
External beam radiation therapy The source of radiation
can either be low energy (orthovoltage: 50300 kVp) or
high energy (cobalt-60 or linear accelerators of 4 million
electron volts). Low energy beams are used for small sized
intraoral tumors, lip, and skin cancers. The high energy
radiation provides variable penetration due to its ability to
vary the energy of the photons. It spares bone and skin.
For teletherapy, three principal eld arrangements are
planned: wedged-pair elds, parallel-opposed elds and
three-eld technique. The wedged-pair eld allows a
therapeutic dose to unilateral disease while sparing a high
400

dose to the opposite side. When a large tumor or midline


lesion is present, a parallel-opposed eld set-up or threeeld set-up may be needed, which produces relatively uniform exposure for midline disease.
Brachytherapy Brachytherapy involves inserting radioactive wires/seeds directly into a tumor, such as in the tongue.
One of the advantages of this type of therapy is there is
less radiation exposure to other parts of the body. In interstitial implant treatment, implants deliver the radiation in
the immediate vicinity of the implanted isotope and also
deliver it a relatively low dose rate, thus sparing the normal
tissues. Interstitial sources can be placed directly or preferably, after loaded into tubes or needles. The sources most
commonly used include 192Ir,137Cs,125I, and 198Au.
Another variant of these radioactive implants are applicators which are radioactive substances that are impregnated into prosthesis which may be placed on the surface
of the cancerous tissue.
Newer modalities of radiation therapy Intensity modulated radiation therapy (IMRT) is most applicable in the
treatment of head and neck cancers (especially nasopharyngeal lesions). IMRT employs a computer directed radiation source that targets the cancer more accurately than
conventional radiation therapy. This is accomplished with
computer algorithms to design treatment plans whose goals
are to maximize dose to tumor targets while limiting dose
to normal structures. Thus, the major advantage of IMRT
over conventional head and neck radiation is the potential
to significantly limit dose deposition to normal structures,
such as the parotid glands, thereby reducing the degree
of xerostomia. A potential disadvantage of IMRT is an
increased volume of normal tissue exposure. This is because
multiple small fields of radiation, called beamlets, rotate
around the patient.
Additional ability to modify dose and elds and radiation has been introduced with image-guided radiotherapy
(IGRT) in which integrated CT, guides the changes in radiation throughout the course of treatment as treatment causes
a change in volume of tumor during treatment.
Radiation therapy combined with chemotherapy The
rationale for administering drugs prior to radiation therapy is to control already disseminated tumor cells, potentiate the killing effects of ionizing radiation, be more
effective against the remaining tumor growth fraction once
radiation has reduced tumor bulk and elimination of subclinical metastasis.
Effects of radiation therapy Following radiation therapy
various mucocutaneous changes are seen in the patient.
Some of these changes include: hyperpigmentation of the
skin surface in the field of radiation, transient loss of hair,
mucositis, loss of taste, salivary dysfunction, radiation caries, fungal infections, pain, post-radiation osteoradionecrosis, and difficulty in speech and mastication.

Chapter 14 Oral Cancer

Mucocutaneous changes In about 2 weeks following


radiation therapy the skin in the radiation field turns erythematous and may show hyperpigmentation along with
mucositis. Radiation dose of about 180220 cGy per day is
sufficient to produce mucositis. It is characterized by intense
erythema of the mucosa, pain and occasionally associated
with sloughing.
Topical anesthetics in the form of viscous xylocaine,
topical analgesics (benzydamine hydrochloride) are effective
in managing radiation mucositis.
Loss of taste sensation When the taste buds are in the
radiation field there is partial or complete loss of cells in
taste buds. Patients may report of a significant change in
the perception of all types of tastes. In most patients, the
cells of the taste buds regenerate in 4 months duration.
Patients may be advised to incorporate a change in diet
to facilitate better taste perception. Zinc sulfate capsules
(220 mg twice daily with food, elemental zinc 100 mg) are
benecial.
Salivary function Radiation induces fatty degeneration,
fibrosis, acinar atrophy and cellular necrosis within the
salivary glands. Comparatively, serous acini are more radiosensitive than mucous acini. Patients present with reduced
amount of salivation and the saliva is typically thick and
ropy. Radiation-induced xerostomia may occasionally
reverse in about 12 months. However, irreversible changes
are seen at a total dose of 6,000 cGy for 5 weeks. Patients
are advised to frequently sip water and chew on sugarless
gum to stimulate salivation. If the xerostomia is very severe,
salivary substitutes such as carboxymethylcellulose can
be prescribed. Salivary stimulants such as pilocarpine
hydrochloride (5 mg 4 times a day) and bethanechol
(25200 mg/day) have also proven to be beneficial.
Radiation caries Radiation caries occurs secondary to
the alteration in the chemical composition of saliva or
reduction in salivation following radiotherapy and not
due to the direct action of radiation on the tooth. The most
common sites of involvement are the cervical areas followed by cuspal/incisal tips of teeth. Three distinct types
are seen: dark pigmentation of crown, circumferential
caries/amputation caries (generally involves cervical third)
and widespread superficial caries especially involving the
smooth surfaces of the crown.
Patients should be encouraged to maintain good oral
hygiene. Three percent hydrogen peroxide rinses and topical uoride application will help in preventing further damage to the tooth structure.
Effects on developing teeth Tooth eruption may be
delayed. The teeth may be malformed with stunted roots.
Occasionally, the tooth may not be formed.
Candidiasis Owing to the poor oral hygiene and nutritional
status, patients may present with pseudomembranous or

erythematous candidiasis. In such patients, topical application of anticandidal agents may not be effective as the
salivation is compromised.
Osteoradionecrosis Radiation therapy causes endarteritis
obliterans, which in turn results in hypovascularity, hypocellularity and finally hypoxic tissue. Owing to its inherent poor vascularity, the mandible is more commonly
affected than the maxilla.
Trauma (external, iatrogenic), periodontal diseases, illtting dentures, peridontally weak or pulpally affected
teeth in the line of radiation are predisposing factors for
osteoradionecrosis.
Patients complain of pain, foul taste, paresthesia/
anesthesia and intraoral or extraoral discharging sinuses.
Lymphadenopathy may be seen. As the condition worsens,
pathological fracture occurs. Radiographically, it is difcult
to differentiate between the ill-dened patchy destruction
of bone that is seen in cancer of the bone, osteoradionecrosis and suppurative osteomyelitis.
As a preventive measure, if extractions are planned, it
is desirable to allow as much healing time as possible.
Seven to 14 days and up to 21 days have been suggested
as healing times prior to radiotherapy.
Patients should be instructed to avoid mucosal irritants,
discontinue the use of dental appliances if they contact the
area of the lesion, maintain nutritional status, stop smoking
and alcohol consumption.
Osteoradionecrosis is best managed with topical antibiotic
(tetracycline) or antiseptic (chlorhexidine) rinses. Hyperbaric oxygen (HBO) therapy increases the oxygenation of
tissue, increases angiogenesis, and promotes osteoblast and
broblast function.
HBO therapy (Figure 27A, B) is usually carried out for a
period of 2030 dives at 100% oxygen and 22.5 atmospheres of pressure.
Sequestrated bone may be managed with limited resection or may require mandibulectomy. If surgery is required,
postsurgical HBO therapy of 10 dives is recommended.
Chemotherapy It is provided as an induction therapy
before local therapies. It is also an adjunctive modality for
other cancers. The objective of induction chemotherapy is
to promote initial tumor reduction and to provide early
treatment of micrometastases. The goal of chemotherapy
is to eradicate the rapidly growing cells of the tumor or
modify their growth. Chemotherapeutic agents affect the
rapidly dividing cells of the target tumor and the lining
epithelium, the oral ecology and the vascular, inflammatory and healing responses of the oral cavity. These alterations may result in mucositis and ulceration of the oral
mucosa. Chemotherapeutic agents also target the hemopoietic cells of the bone marrow, resulting in anemia,
thrombocytopenia and leukopenia. Unfortunately, chemotherapy is often toxic to other cells that rapidly divide
normally. These include bone marrow, hair, and the
401

Section V Cysts and Tumors of Orofacial Region

Figure 27
A

(A) Patient being shifted into the HBO chamber.


(B) Doctor monitoring the patients condition undergoing
hyperbaric oxygen (HBO) therapy. Courtesy: Sechrist
Industries, Inc., La Palma Ave, Anaheim, CA 928

mucosa of the entire gastrointestinal tract, including the


oral cavity.
The chemotherapy cycle consists of cytotoxic drug
administration followed by a rest period for healthy tissue
recovery prior to repeated drug administration. An important clinical implication of this format is that peripheral
white blood cell counts change dramatically during the
course of this cycle. Majority of the cytotoxic drugs have
more profound effect on rapidly multiplying cells, because
the most important target of action are the nucleic acids

402

and their precursors; rapid nucleic acid synthesis occurs


during cell division.
Drugs used in oral cancer chemotherapy Various drugs are
seen in cancer chemotherapy of the head and neck such as
cetuximab (epidermal growth factor receptor inhibitor),
docetaxel, cisplatin, 5-fluorouracil, leucovorin, methotrexate, and bleomycin.
We shall describe four drugs in the following text namely:
methotrexate, bleomycin, cisplatin and 5-uorouracil.
Methotrexate Methotrexate is an antimetabolic and an
inhibitor of folic acid metabolism. The rationales for intraarterial route are that, prolonged contact of the tumor cell
population with the antimetabolite will result in sequential
death of cells as the cells enter the most fragile metabolic
phase of cellular division. It can be administered either
intra-arterially or per orally. Systemic methotrexate is
given in intermittent weekly or semiweekly IV injections
of 4060 mg/m2 of body surface area.
Methotrexate is known to cause bone marrow suppression, mucositis, anorexia, nausea, emesis, renal toxicity and
hepatic dysfunction.
Bleomycin It is part of a group of antibiotics that was
isolated in Japan from Streptomysis verticillus. Bleomycin
acts by interfering with the DNA function of the cell. The
ideal dose of belomycin is 0.250.50 unit/kg given weekly
or twice weekly. However, care should be taken not to
exceed a dose of 400 units and this dose can cause pulmonary toxicity and death. Some patients may complain of
skin rashes and erythema. The greatest advantage with
bleomycin is its lack of causing myelosuppression.
Cisplatin Cisplatin is a relatively new drug which acts by
altering DNA structure. It is given IV (80120 mg/m2, IV
for 34 weeks). Dehydrated patients may suffer from renal
impairment. Hence, it is important to maintain adequate
hydration before the drug is administered.
5-Fluorouracil This drug is usually administered along
with cisplatin. Its acts by interfering with the cellular
metabolism. The standard dosage is 1,000 mg/m2/day.
Stomatitis is a common side effect. Bone marrow suppression is seen when weekly or daily bolus injections are
administered.

SECTION

VI

Teeth and
Periodontium

15 Dental Caries, Pulp and Periapical Lesions


16 Gingival and Periodontal Diseases
17 Regressive Alterations of Teeth

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CHAPTER

Dental Caries, Pulp and


Periapical Lesions
Vivekananda Pai, Ravikiran Ongole

15

Definition and Etiology

Radiographic Evaluation of Carious Lesions

Contributory Factors in Dental Caries

Fascial Space Infection

Classification of Dental Caries

Ludwigs Angina

Microbiology of Dental Caries

Osteomyelitis

Clinical Diagnostic Methods

DEFINITION AND ETIOLOGY


Dental caries is a microbial disease of the calcified tissues
of the teeth, characterized by demineralization of the inorganic portion and destruction of the organic substance of
the tooth.
The World Health Organization (WHO) denes caries as
a localized post-eruptive, pathological process of external
origin involving softening of the hard tooth tissue and
proceeding to the formation of a cavity.
Dental caries is derived from the Latin word caries which
means decay or rotten.
Etiology
Dental caries is considered as the most prevalent disease in
humans, second only to the common cold. Dental decay is
complex and multifactorial. Various theories have been proposed to explain the etiology of dental caries.
The acidogenic theory, proteolytic theory and proteolysischelation theory have been the most discussed.

Millers Chemicoparasitic Theory/Acidogenic


Theory
Willoughby Miller in 1882 suggested that dental decay is a
chemoparasitic process. He believed that caries was caused
by a variety of microorganism and the acids in the oral
cavity were synthesized by the action of microorganisms.
He recognized four important factors in his study of the
carious process which are: role of microorganisms, role of
carbohydrate substrate over the tooth surface, role of acids
and the role of dental plaque.

According to Miller, the carious process occurs in two


distinct steps: in the initial stages there is decalcication
of enamel and destruction of dentin, and in the second
stage there is dissolution of the softened residue of the
enamel and dentin.
The acidic attack which causes destruction and dissolution of the residue is carried by the proteolytic action of the
bacteria. This two-step process is supported by the presence of carbohydrates, microorganisms and dental plaque.
Role of carbohydrates
According to Millers observations, teeth decalcify when
incubated in saliva and bread/sugar mixture and show no
change when incubated with fat. His simple experiment demonstrated the cariogenic effects of carbohydrates.
However, the cariogenic potential of dietary carbohydrates varies on their physical form, chemical composition
and frequency of intake. It is a well known fact that carbohydrates which have a slow clearance rate from the oral
cavity are more cariogenic than those which have a higher
clearance rate. The risk of caries incidence increases greatly if
the dietary sugar is sticky in nature, and when there is
increased frequency of ingestion of the sugars.
Polysaccharides are less easily fermented by plaque bacteria than monosaccharides and disaccharides. Glucose,
sucrose and fructose which are highly fermentable have a
greater role to play in the causation of dental caries. These
sugars are readily broken down by the bacteria to produce
acids that in turn cause the dissolution of the hydroxyapatite crystals of the enamel and dentin.
Sucrose is readily fermented by the cariogenic bacteria
(mainly Streptococcus mutans) to produce acids, which can
405

Section VI Teeth and Periodontium

demineralize the tooth. S. mutans use sucrose to synthesize


an extracellular insoluble polysaccharide with the help of the
enzyme dextran, which helps in adhering the plaque rmly
on to the tooth surface.
The pH of plaque falls to 4.55 in about 13 minutes of
sugar intake. It is estimated that pH returns to neutral levels
in approximately 30 minutes.
The physical nature of the diet intake also has a bearing
on the incidence of carious lesions. Coarse brous foods
aid in greater clearance rate from the oral cavity thereby
minimizing the carious incidence. However, sticky rened
food and sweetened soft drinks predispose to debris accumulation and the increased likelihood of carious lesions.
Role of microorganisms
Lactobacillus acidophilus along with a combination of other
bacteria such as S. mutans and Actinomyces species are
closely associated with the causation of dental caries. It is
believed that a few types of bacteria may be intimately
involved in the initiation of the carious process whereas some
may be involved in the progression of the carious process.
Role of acids

ProteolysisChelation Theory

Miller in his observations reported that many of the microorganisms in the oral cavity were capable of producing
acids and these acids were usually present in deeper carious
lesions. In many of the lesions studied, lactic acid was
identified in carbohydrate saliva combined mixtures. A
specific microorganism, Leptothrix buccalis, was isolated
from the dentinal tubules, suggesting that the microorganisms and the acids may have a synergistic action to dissolve the organic portion of the tooth.

Some of the minor flaws of the acidogenic and the proteolytic


theories were addressed in the proteolysischelation theory. This theory was put forward by Schatz and coworkers
in 1955.
Chelation is a process in which there is complexing of
the metal ions to form complex substance through coordinated covalent bond which results in poorly dissociated
and/or weakly ionized compound. Chelation is independent of the pH of the medium.
The proteolysischelation theory considers dental caries to be a bacterial destruction of organic components of
enamel and the breakdown products of these organic components to have chelating properties and thereby dissolve
the minerals in the enamel even at the neutral/alkaline pH.
Mucopolysaccharides, lipids and citrates may also act as
secondary chelators.
Schatz and coworkers observed that there is a simultaneous microbial degradation of organic component by
proteolysis and the dissolution of inorganic part by the
process of chelation.

Role of dental plaque


Plaque as described by GV Black is a gelatinous plaque of
the caries fungus in a thin, transparent film that usually
escapes observation, and which is revealed only by careful
search. It generally consists of salivary components such
as mucin and desquamated epithelial cells and of microorganisms. However, long-standing plaque may accumulate to a
perceptible degree in 2448 hours. It is estimated that cariogenic plaque contains 2 108 bacteria/mg weight.
The pH of plaque also varies in caries free and individuals
with high caries activity. The pH is about 7.1 in caries free
individuals and approximately 5.5 in individuals with high
caries activity.

Proteolytic Theory
The initial work on the proteolytic theory was done by
Heider and Bodecker in 1878 and Abbott in 1879. Studies
showed that the organic portion of the tooth plays an
important role in the development of dental caries.
406

It is believed that enamel lamellae and enamel rods which


are composed of organic material form the pathways for the
advancing microorganisms.
It has been established that enamel contains 0.56% of
organic matter of which 0.18% is keratin and 0.17% is a
soluble protein.
Gottlieb in 1944 suggested that the initial lesion of the
carious process is due to the proteolytic enzymes attacking
the lamellae, rod sheaths, tufts and walls of tubules.
He believed that the yellow pigmentation that is characteristic of caries was due to pigment produced by the proteolytic organisms. He also proposed that the Staphylococcus
plays a vital role in initiating proteolytic activity.
Pincus in 1949 proposed that the proteolytic breakdown of the dental cuticle is the rst step in the carious
process. He proposed that the Nasmyths membrane and
the enamel proteins are mucoproteins, which are acted
upon by the sulfatase enzyme of the bacilli yielding sulfuric
acid. The sulfuric acid thus produced combines with the
calcium of the hydroxyapatite crystal and destroys the
inorganic component of the enamel.

Sucrose Chelation Theory


This theory proposes that if there is a very high concentration of sucrose in the mouth of a caries-active individual,
there can be formation of complex substances like calcium
saccharate and calcium complexing intermediaries by the
action of phosphorelating enzymes. These complexes cause
release of the calcium and phosphorus ions from the
enamel and thereby resulting in tooth decay.

Chapter 15 Dental Caries, Pulp and Periapical Lesions

Autoimmune Theory

Figure 1

According to this theory few odontoblasts, within the pulp


of few certain teeth are damaged by the autoimmune mechanisms, leading to a compromised defense mechanism and
the loss of integrity of enamel or dentin. These targeted sites
are potential sites for the development of carious lesions.

Host factor

Enzymatic Theory
Diet

This theory is based on the fact that plaque bacteria produces


enzymes. Enzymes involved may include phosphatase (dissolves apatite), chondroitin sulfatase (dissolves dentinal chondroitin sulfate), hyaluronidase (dissolves dentinal hyaluronic
acid) and proteases (dissolve dentinal collagen). All these
enzymes are produced by plaque bacteria.

Dental
caries

Time

Microorganisms

Acidenzyme Theory
Diagram depicting the contributing factors for
dental caries

This theory is a combination of the acidogenic and the enzyme


theories. It is believed that the acids produced have a
major role in enamel dissolution and the enzymes probably play a greater role in dentinal dissolution.

Levines Ionic See-saw Theory


This theory was proposed by Levine in 1977. According
to this theory, there is a chemical relationship between
enamel plaque and the factors which determine the movement of minerals from saliva/plaque to enamel and vice
versa, which was termed as the ionic see-saw mechanism.
Levine proposed that the demineralization and remineralization of enamel is a continuous process. If in a given
interval of time, more ions leave the enamel than enter it,
then there is a net demineralization, which heralds the
beginning of the carious process. It was proved that the ions
are constantly exchanged between enamel and plaque.
This theory emphasizes the importance of pH of plaque,
calcium and phosphate ion concentration at the interphase
and uoride ion concentration.

CONTRIBUTORY FACTORS IN DENTAL


CARIES
The four factors contributing to the caries process are
(Figure 1):
1.

Host factor
a. Tooth factor
i. Morphology and position in the arch
ii. Chemical nature
b. Saliva
i. Composition, pH and antibacterial activity
ii. Quantity and viscosity of flow

2.
3.
4.

Microflora
Substrate or diet (physical nature and chemical nature)
Time.

Host Factor
Tooth Factor
Morphology and position in arch
Compared to the smooth surfaces of teeth, deep pits and
fissures are more prone to carious attack because of
food lodgment and bacterial stagnation. Owing to their,
complex occlusal morphology consisting of numerous
pits and fissures, the permanent mandibular first molars
followed by the maxillary first molars and mandibular
and maxillary second molars are more prone to carious
attack.
Apart from the morphology of the tooth, the position of
the tooth in the arch has a heavy bearing on the incidence
of carious lesions.
Irregularities in the arch form, crowding and overlapping of the teeth also favor the development of caries as these
regions provide an excellent environment for plaque accumulation.
Partially impacted third molars are more prone to caries
and so are the buccally or lingually placed teeth.
Chemical nature
The chemical components of enamel such as dicalcium phosphate dihydrate and fluorapatite make the enamel resistant
to carious attack to a certain extent.
407

Section VI Teeth and Periodontium

The presence of mineral ions such as Ca, F, Zn and Fe in


higher concentrations, decreases the enamel solubility.
Higher the solubility of the enamel surface greater is the
possibility of caries development. Hence, they can be seen
in case of enamel hypoplasia.
The mineral content of enamel tends to increase with
advancing age. Such teeth have an increased resistance to
carious attack.

Saliva
Composition
Hay et al (1982) and Lagerlof (1983) in their reports reiterated the fact that human salivary secretions are supersaturated on calcium and phosphate.
The concentrations of inorganic calcium and phosphorus show considerable variation within resting and stimulated saliva. Caries prone individuals have low calcium
and phosphorus levels. Salivary proteins such as statherin,
acidic proline-rich proteins (PRPs), cystatins, and histatins
help in the maintenance of the homeostasis of the supersaturated state of saliva. According to Hay and Moreno
(1989), statherin is present in stimulated saliva in concentrations sufcient to inhibit the precipitation of calcium
and phosphate salts. Studies by Gibbons and Hay (1988)
have shown that statherin may contribute to the early
colonization of the tooth surfaces by certain bacteria, such
as Actinomyces viscosus.
The acidic PRPs account for 2530% of all proteins in
saliva, and they have high afnity for hydroxyapatite in vitro
(Hay and Moreno, 1989). The acidic PRPs bind free calcium,
adsorb to hydroxyapatite surfaces, inhibit enamel crystal
growth, and regulate hydroxyapatite crystal structure (Hay
and Moreno, 1989).
The amount and quality of acidic PRPs and agglutinins
are found to be different in caries-free and caries-active
individuals as shown by the studies of Rosan et al (1982)
and Stenudd (1999).
The role of cystatins in the caries process is still unclear.
However, they may play a minor role in the regulation of
calcium homeostasis in saliva. Phosphorylated and nonphosphorylated cystatins bind to hydroxyapatite.
Salivary flow rate, pH and buffer capacity
Saliva has the most important function of caries prevention
by way of its flushing and neutralizing effects, commonly
referred to as salivary clearance or oral clearance capacity. As a thumb rule, the higher the flow rate, the faster the
clearance and the higher the buffer capacity. Reduced salivary flow rate and the concomitant reduction of oral
defense systems may cause severe caries and mucosal
inflammation. Though, patients with impaired saliva flow
rate often show high caries incidence (Papas et al, 1993;
408

Spak et al, 1994) or caries susceptibility, it is still a mystery as to how much saliva is adequate enough.
The pH of saliva at which it ceases to be saturated with
calcium and phosphorus is referred to as the critical pH.
Normally, the critical pH is 5.5. Below this value, the inorganic content tends to demineralize. The normal pH of
resting saliva is 67.
Buffering capacity The buffer capacity of both unstimulated and stimulated saliva involves three major buffer systems: the bicarbonate (HCO3), the phosphate, and the
protein buffer systems. These systems have different pH
ranges of maximal buffer capacity. The bicarbonate and
phosphate systems have pH values of 6.16.3 and 6.87.0,
respectively.
Since most of the salivary buffering capacity operative
during food intake and mastication is due to the bicarbonate
system, sufcient saliva ow provides the oral cavity with
the neutralizing components.
The phosphate and protein buffer systems make a minor
contribution to the total salivary buffer capacity, relative
to the bicarbonate system. The phosphate system is, in
principle, analogs to the bicarbonate system but without
the important phase-buffering capacity, and it is relatively
independent of the salivary secretion rate.
Lagerlof and Oliveby in 1994 showed that a low ow
rate combined with a low or moderate buffer effect indicated poor salivary resistance against microbial attack.
It is a well-established fact that the buffer capacity of
the saliva and the caries experience are inversely related.
The buffer effect of saliva is inuenced by the hormonal
and metabolic changes, as well as by altered general health.
It is generally accepted that the buffer effect is greater in
men than in women (Heintze et al, 1983). In women, the
buffer effect decreases gradually, independent of ow rate,
toward late pregnancy and promptly recovers after delivery. Introduction of either hormone replacement therapy
in menopausal women (Laine and Leimola-Virtanen, 1996)
or low-dose oral contraceptives (Laine et al, 1991) can
slightly increase the buffer capacity.
Carbonic anhydrases (CAs) participate in the maintenance of pH homeostasis in various tissues and biological
uids of the human body by catalyzing the reversible
hydration of carbon dioxide. Recent research suggests that
salivary CA VI plays a role in protecting the teeth from
caries (Kivela et al, 1999a, b). CA VI has been reported to
bind to the enamel pellicle and retain its enzymatic activity
on the tooth surface.
It is also believed that the urea and saline in saliva
become hydrolyzed to produce ammonia and the later can
cause rise in the salivary pH. This rise in pH can counter
the attacks on the tooth surface during the progression of
caries.
Antibacterial activity The primary oral innate defense
factors are peroxidase systems, lysozyme, lactoferrin, and

Chapter 15 Dental Caries, Pulp and Periapical Lesions

histatins. In vitro studies have shown that these proteins


are known to limit bacterial or fungal growth, interfere
with bacterial glucose uptake or glucose metabolism and
promote aggregation and, thus eliminate bacteria.
Hanstrom et al (1983) and Tenovuo and Larjava (1984)
reported that the salivary peroxidase and myeloperoxidase
systems eliminate H2O2, which is highly toxic for mammalian cells.
The immunoglobulins, IgG, IgM, IgA, and secretory
IgA (sIgA), form the basis of the specic salivary defense
against oral microbial ora, including Streptococcus
mutans. The most abundantly available immunoglobulin in
saliva is dimeric slgA, which is produced by plasma cells
located in the salivary glands. Two IgA subclasses are
present in saliva; IgAl forms the major component of
immunoglobulins, although the relative amount of IgA2 is
higher in saliva than in other secretions (Tappuni and
Challacombe, 1994).
In human beings, IgG, mainly of maternal origin, is the
only detectable immunoglobulin in the saliva of neonates.
Salivary IgA is absent at birth but is generally detectable
by the age of 1 week.
The IgG concentration decreases to non-detectable levels after some months but appears again after tooth eruption (Brandtzaeg, 1989). Low concentrations of IgG can be
detected in stimulated parotid saliva (Brandtzaeg, 1989),
but most of the IgG detected in whole saliva enters the
mouth from the gingival crevicular uid, thus originating
from sera.
In most children above 3 years of age, salivary IgAs
against S. mutans can be detected, and their amount
increases with the length of exposure (Smith and Taubman,
1992). Salivary Igs can bind to the salivary pellicle, and
they are found also in dental plaque (Newman et al, 1979;
Fine et al, 1984). In the oral cavity, immunoglobulins
act by neutralizing various microbial virulence factors,
limiting microbial adherence, and agglutinating the bacteria, as well as by preventing the penetration of foreign
antigens into the mucosa. IgGs are also capable of opsonizing bacteria for phagocytes, which are reported to
remain active in dental plaque and saliva (Scully, 1980;
Newman, 1990).
Quantity and viscosity of flow
The consistency or viscosity of the saliva and the amount
of saliva produced has a significant influence on the incidence of dental caries.
The average person produces at least 500 ml of saliva over
a period of 24 hours. The unstimulated ow rate is 0.3 ml/
min, whereas the ow rate during sleep is 0.1 ml/min and
during eating or chewing, it increases to 4.0 to 5.0 ml/min.
Any reduction in this quantity of saliva as seen in diseases
such as Sjgrens syndrome, diabetes, etc. predisposes to
dental caries.

Increased viscosity of saliva may hinder its natural


cleansing action thereby promoting the deposition of plaque
on the tooth surface. Likewise when the salivary viscosity is
low, the amount of minerals and bicarbonates are inadequate thereby limiting its anticaries activity.

Microflora
The main etiological agent in occlusal and pit and fissure
caries is the S. mutans. Deep dentinal caries is commonly
associated with lactobacilli, certain gram-positive anaerobes and filaments such as Eubacterium and Actinomyces.
Root caries or cemental caries is predominantly associated with Actinomyces viscosus. However other species of
Actinomyces such as A. naeslundii and A. nocardia have
also been isolated.

Substrate and Dietary Factors


The role of diet in the causation of dental caries has been
extensively studied.
A variety of dietary factors have been implicated in the
causation of dental caries.
Physical nature of diet
It is believed that coarse and fibrous food helps in cleansing
the debris from the tooth surface thereby minimizing the
incidence of carious lesions. However, refined and sticky
starchy food aid in the formation of dental caries.
Chemical nature of diet
It is a well-known fact that food with high refined carbohydrate content has the greatest potential to give rise to carious
lesions.
The type of carbohydrate (monosaccharide, disaccharide
or polysaccharide), frequency of intake and the time for which
the ingested food remains stagnant in the oral cavity or on
the tooth surface determine the incidence and severity
of the carious lesions.
Animal studies have shown that sugar in the solid and
sticky form is more harmful to the tooth than the same amount
of sugar in a liquid form.
It is believed that vitamin B decient individuals have
lower incidence of dental caries. Vitamin B is essential for
the growth of oral acidogenic ora and also serves as a
component of coenzymes involved in glycolysis.
Vitamin D plays an important role in the normal development of teeth. Various studies have shown that the teeth
are hypoplastic and usually have higher incidence of dental caries in vitamin D deciency.
Teeth may be poorly calcied in individuals exposed to
low doses of calcium during intrauterine life and infancy.
409

Section VI Teeth and Periodontium

Such poorly calcied teeth may be susceptible to carious


attack. Higher levels of selenium is known to predispose to
the carious lesions affecting permanent teeth.
Fluoride content in the diet has no signicant role because
of its metabolic unavailability. Therefore, the uoride content
in cooking salt and its effect on reducing the incidence of
carious lesions is still questionable. However, uoridated
water minimizes the caries incidence.
Phosphates, molybdenum and vanadium in the diet
helps in minimizing the incidence of carious lesions.

CLASSIFICATION OF DENTAL CARIES


1.

2.

Dental caries based on location


a. Pit and fissure caries
b. Smooth surface caries
c. Root surface caries
Dental caries based on severity
a. According to morphology of teeth
b. According to severity and progress
c. According to age pattern
d. According to rapidity of progress.

Role of heredity
Literature review reveals various studies to assess
the genetic modifications in dental enamel, genetic modification of immune response, genetic regulation of
salivary function and inherited alterations in sugar metabolism.
Bachrach and Young (1927) compared the caries incidence of monozygotic twins with same-sex dizygotic (93
pairs) and different-sex dizygotic (78 pairs) twins. Their
results showed that the monozygotic twins had a more
similar caries incidence than dizygotic twins and that different-sex dizygotic twins had the greatest variance. The
authors concluded that heredity plays a subsidiary part in
the incidence of caries. It is believed that heredity affects
the dental decay only in as much as it controls the shape
of a tooth and its pits and ssures and its position in the
dental arch.
Senpuku et al (1998) and Acton et al (1999) have correlated specic HLA-DR types with binding S. mutans
antigens and S. mutans colonization.
Acton concluded that genes within MHC modulate the
level of oral cariogenic organisms.
Mariani et al (1994) in their study of celiac disease,
enamel defects and HLA typing observed that HLA-DR3
was associated with increased enamel defects and
HLA-DR5, 7 were associated with a reduced frequency of
enamel defects. Studies have shown that the genes in the
HLA complex are associated with altered enamel development and increased susceptibility to dental caries.
Role of immunity
Salivary IgA and immunoglobulins secreted in the gingival crevicular fluid such as IgG, IgM and IgA along with
neutrophil leukocytes and macrophages play an important
role in the prevention of dental caries. It is believed that
the immune response exerted by the gingival crevicular
immune system is more potent compared to the salivary
immune mechanism.
Salivary IgA prevents S. mutans from adhering to the
tooth surface. The IgG antibodies acting as opsonins, facilitate phagocytosis and the death of S. mutans by the action
of macrophages and neutrophil leukocytes.
410

According to Morphology of Teeth


i.

Pit and fissure caries (also called type-1 caries): Caries


occurring on anatomical pits and fissures of all the
teeth. The specific areas or surfaces involved include
occlusal surfaces of molars (Figure 2) and premolars,
buccal and lingual surfaces of molars (Figure 3) and
lingual surfaces of maxillary incisors.
The lesions are smaller in the beginning but become
wider as they spread toward the dentin due to orientation of enamel rods.
In these places there can be entrapment of food
leading to fermentation of carbohydrates with lack of
neutralization of acid produced by salivary buffers
which leads to destruction of enamel and dentin. The
enamel bordering the pit and fissure may appear
opaque and bluish-white as it becomes undermined.
Clinically these lesions appear brown or black,
with little softening and opaqueness of the surface.
When the lesion is examined by a fine explorer tip, a
catch point is often felt, where the explorer teeth
catches the area.
When the lesion reaches the dentinoenamel junction (DEJ), they spread laterally to cause undermining
of the enamel.
ii. Smooth surface caries (also known as type-2 caries):
These carious lesions occur on the smooth surfaces of
the teeth (e.g. proximal surfaces or gingival areas
of the buccal and lingual aspect of tooth).
Proximal caries usually begins just below the contact point, and appears in the early stage as a well
demarcated faint white opacity of the enamel without
apparent loss of continuity of enamel.
The white spot lesion becomes pigmented yellow
or brown and it often extends buccally and lingually.
The surrounding enamel becomes bluish white as
the lesion continues to progress (Figure 4). The surface of the affected enamel becomes rough and later
on, there is formation of a cavity (Figure 5).
iii. Root caries: Caries occurring at the cementoenamel
junction or cementum. This occurs predominantly in the
older age when there is gingival recession.

Chapter 15 Dental Caries, Pulp and Periapical Lesions

Figure 2

Figure 4

Pit and fissure carious lesion on the occlusal surface of


a mandibular molar. Courtesy: Department of
Oral Pathology, MCODS, Mangalore

The early stages of a proximal carious lesion.


The surface of the enamel reveals a bluish-black
hue with no discontinuity of the enamel surface.
Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

Figure 3

Figure 5

A carious lesion on the buccal surface of the mandibular


molar. Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

iv. Linear enamel caries: Caries occurring on the labial


surfaces of anterior teeth. This is also known as
odontoclasia. The caries occurs at neonatal zone
because of trauma at birth or metabolic disturbances.

Proximal surface carious lesion. Courtesy: KLE Societys


Institute of Dental Sciences, Bangalore

According to Severity and Progress


i.

Incipient caries: Initial carious lesion limited to the


teeth is called incipient caries and is characterized
by a virtually intact surface but a porous subsurface
(subsurface demineralization).

ii.

Incipient lesion can undergo remineralization


thereby reversing the process.
Rampant caries: This is an acute fulminating type of
carious process, which is characterized by simultaneous
involvement of multiple number of teeth (may be all
teeth) in multiple surfaces (Figure 6A, B).
411

Section VI Teeth and Periodontium

Figure 6
A

Extensive destruction of teeth in child suffering from rampant caries. Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

Rapid coronal destruction occurs within a short


span of time, causing early involvement of the
pulp.
The common age of occurrence is 48 years for
the deciduous teeth and 1119 years for the permanent teeth.
It can even occur in persons who maintain a good
level of oral hygiene regularly.
Moreover, this type of caries attacks those surfaces
of teeth, which are otherwise considered immune
to the disease.
iii. Arrested caries
Any carious lesion usually an incipient one may
become arrested, if there is a change in oral environment. Arrested caries, clinically appears as a
dark brown pigmentation with smooth surface,
referred to as eburnation, which is a Latin word
that means arrested caries.
It can be on occlusal as well interproximal surfaces.
It can occur in both enamel and dentin.
iv. Recurrent caries: It occurs at the interface of tooth and
restorative material because of many factors such as
defective cavity preparation, microleakage and combination of these (Figure 7).
v. Radiation caries: One of the complications of radiotherapy of oral cancer lesions is xerostomia, which
leads to an early development of widespread caries.

According to Age Pattern


Nursing bottle caries: A type of acute carious lesion, which
occurs among those children who take milk or fruit juice

412

Figure 7

Recurrent carious lesion beneath faulty restorations.


Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

by the nursing bottle, for a considerably longer duration


of time, preferably during sleep.
1.

2.

It has been variously attributed to prolonged use of


A nursing bottle containing milk or milk formula,
fruit juice or sweetened water
Breast feeding
Sugar or honey-sweetened pacifiers.
Invariably there is a prolonged habitual use of one of
the above after 1 year of age, usually as an aid for sleeping at night or naptime.

Chapter 15 Dental Caries, Pulp and Periapical Lesions

3.

4.

5.

Clinically presents as widespread destruction of deciduous teeth, most commonly the four maxillary incisors,
followed by the first molars and then the cuspids if the
habit is prolonged.
The lower teeth are not usually affected as they remain
under the cover of the tongue, so the absence of caries in
the mandibular incisors distinguishes this disease from
ordinary rampant caries.
Both the nursing bottle and rampant cause early pulp
involvement.

Figure 8

Because they spread at a very rapid pace and as a result,


the pulp hardly gets any time to protect itself by forming
secondary dentin.

According to Rapidity
i.

ii.

Acute dental caries


It is a form of caries which runs a rapid clinical
course and results in early pulp involvement by
carious process.
It occurs most frequently in children and young
adults, presumably because the dentinal tubules
are large and open and show no sclerosis.
The process is usually so rapid that there is little
time for the deposition of secondary dentin.
Chronic dental caries
Slowly progressing in nature and tends to involve
the pulp much later than the acute caries.
Most common in adults.
These caries lesions exhibit a large cavity with
brownish pigmentation (Figure 8).
Pain is not a common feature of chronic caries
because of the protection afforded by secondary
dentin.
The slow progression of the lesion allows sufficient time for both sclerosis of the dentinal tubules
and deposition of secondary dentin in response to
the adverse irritation.

MICROBIOLOGY OF DENTAL CARIES


The predominant group of microorganism is streptococci.
Among these strains S. mutans is responsible. These are
gram-positive organisms which are round or ovoid. These
may appear rod shaped, non-sporulating and non-motile.
These can be cultured on blood agar with formation of
refractory colonies measuring 0.51.5 mm at 37C. These
are pathogenic to human beings.
The three common organisms seen to be associated with
secondary caries are S. mutans, lactobacilli and Actinomyces
viscosus. Fontanna et al (1996) observed a denite relationship of S. mutans and secondary caries. S. mutans is also

Deep occlusal caries with brownish pigmentation.


Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

present in saliva and in dental plaque in individuals with


rampant caries due to xerostomia as well as in children
nourished with bottle milk. S. mutans and lactobacilli have
been found to increase in signicant numbers in the plaque
as well as dentin of teeth restored with amalgams having
marginal defects wider than 40 m.
Fitzergerald et al (1994) were of the view that in association with these three major microorganisms, others also
played a role in secondary caries. They found S. mutans,
S. sanguis and S. salivarius in 35%, 24% and 14% of
growth positive samples respectively. Other isolates like
S. gordonii, S. milleri, S. oralis and S. mitis were also recognized. Certain organisms, which occurred very frequently
were Propionibacterium, Bidobacterium, Eubacterium and
Peptococcus. Actinomyces were found in 46% of the samples. A. viscosus and A. naeslundii were most prevalent
followed by A. israelii and A. odontolyticus.
S. mutans can adhere to the tooth surface by glucan which
is produced by utilization of dietary sucrose. These organisms ferment mannitol and lactose with the production of
acid. These can take up dietary sucrose and breakdown
into glucose and fructose by means of the enzyme, invertase. Finally glucose and fructose is broken down to lactic
acid. These have the ability to store glucose and fructose
from degradation for the synthesis of acids in the absence of
dietary sucrose.
Clinical features of dental caries, pulp and periapical
lesions are given in Table 1.
Sequelae of pulpitis is depicted in Flowchart 1.

413

Section VI Teeth and Periodontium

Table 1

Clinical features of dental caries, pulp and periapical lesions

Extent of
carious lesion

Signs and
symptoms

Clinical findings

Clinical
diagnosis

Radiographic diagnosis

Final diagnosis

Caries involving
enamel

Asymptomatic
patient rarely
notices blackish
discoloration of
the tooth

Chalky white
discoloration of the tooth
or
blackish discoloration
of the tooth usually
seen in the pits and
fissures and proximal
aspects of teeth

Enamel
caries

May not be
evident on a
radiograph until
at least 40%
demineralization
occurs
Ill-defined radiolucency
involving the enamel cap

Enamel
caries

Caries involving
dentin

Sensitivity on
consuming hot,
cold or sweet food
Sensitivity subsides
on removal of
stimulus
Food lodgment
patient may notice
blackish
discoloration of
the tooth

Blackish discoloration
of the tooth
Catch experienced
on using an
explorer
Frank cavitation

Dentinal
caries
or
reversible
pulpitis

Ill-defined
radiolucency
involving the
dentin
(Figure 9)

Dentinal
caries

Caries involving
pulp

Dull aching pain,


which has
periods of
exacerbation
Food lodgment

Frank cavitation
involved tooth
non-tender on
percussion
Grossly decayed
tooth/root stump
(Figure 10)

Chronic
irreversible
pulpitis

Radiolucency
involving the pulp
No periapical
changes (Figure 11)
Widening of the
periodontal ligament
space at the periapex
(Figure 12)
Discontinuity of the lamina
d ura at the periapex or
ill-defined periapical
radiolucency (Figure 13)
Well-defined radiopacity at
the periapex (Figure 14)

Chronic
irreversible
pulpitis

Well-defined radiolucency
measuring 1.5 cm in
diameter at the periapex
of the tooth (Figure 15)
Well-defined radiolucency
measuring 1.5 cm in
diameter at the periapex
of the tooth bounded by
a sclerotic border

Chronic apical
periodontitis

Chronic periapical
abscess

Focal sclerosing
osteomyelitis
or condensing
osteitis seen
in young
individuals with
good immune
response or
when the
virulence of the
microorganisms
is low
Periapical
granuloma
(Figure 16)
Periapical cyst

(Contd.)

414

Chapter 15 Dental Caries, Pulp and Periapical Lesions

Extent of
carious lesion

Signs and
symptoms

Clinical findings

Clinical
diagnosis

Radiographic diagnosis

Final diagnosis

Caries involving
pulp

Pain
Food lodgment
Patient usually
avoids chewing
on the affected
side
Patient may
complain of
fever and
malaise

Frank cavitation
Involved tooth
tender on percussion
Calculus build up on
the occlusal surfaces
of the teeth on the
affected side is indicative
of unilateral chewing
Intraoral or extraoral
swelling tender on
palpation (Figure 17A, B)
Vestibular tenderness
and/or obliteration

Acute apical
periodontitis

Radiolucency involving pulp


No periapical changes

Acute apical
periodontitis

Radiolucency involving pulp


with widening of the
periodontal ligament space
at the periapex
Caries involving pulp
Generally no periapical
changes or may be
associated with widening
of the periodontal ligament
space at the periapex

Acute
exacerbation
of chronic
apical
periodontitis
Acute periapical
abscess

Dull aching pain


or asymptomatic
Food lodgment
Deep carious
lesion, grossly
decayed tooth,
root stump
Patient may
complain of
halitosis, bad
taste or a salty
taste (usually
indicative of pus
discharge)

Frank cavitation
Involved tooth nontender on percussion
Intraoral or extraoral
non-tender swelling
may or may not be
present (Figure 18)
Sinus opening on the
attached gingiva or
vestibule associated
with the affected tooth
(Figure 19) or in close
proximity (occasionally
sinus openings may be
seen distant from the
affected site as the sinus
tracts may follow the
path of least resistance
(through the bone)
Vestibule may be obliterated
When the involved tooth
is tender along with
the above findings

Chronic
periapical
abscess

Radiolucency involving
pulp with discontinuity of
lamina dura at the
periapex and or diffuse
radiolucency at the
periapex (Figure 20)

Chronic
periapical
abscess

Diffuse extraoral swelling,


tender, stretched
and shiny overlying
skin, local raise in
temperature (Figure 21)
Limited mouth opening
(extent and clinical
features of the fascial
spaces are described in
the section on fascial
space infections)
Involved tooth is carious
and tender on percussion
Presence of intraoral
swelling and vestibular
obliteration

Cellulitis

Caries involving
pulp

Caries with
pulpal
involvement

Pain
Diffuse extraoral swelling
(sudden onset)
Fever, malaise
Based on the fascial
space involved,
patient may
complain of
difficulty in eating,
swallowing, limited
mouth opening
and occasionally
difficulty in
breathing

Acute
periapical
abscess

Acute
exacerbation
of a chronic
periapical
abscess
(Phoenix
abscess)

Phoenix
abscess

Ill-defined radiolucency
involving pulp
Usually very minimal
periapical changes such
as widening of the
periodontal space or illdefined radiolucency at
the periapex may evident
at acute nature of the
condition is the reason
for the very minimal bone
changes

Cellulitis of the
infraorbital,
buccal,
submandibular
space, etc.

(Contd.)

415

Section VI Teeth and Periodontium

Table 1

Continued

Extent of
carious lesion

Signs and
symptoms

Clinical findings

Clinical
diagnosis

Radiographic diagnosis

Final diagnosis

Caries with
pulpal
involvement

Patient may
complain of dull
aching pain or may
be asymptomatic

Tooth involved shows a


deep carious lesion,
tender or non-tender
on percussion
Diffuse expansion of
the cortical plates. The
affected site may reveal
a well-defined bony
hard swelling (usually
mildly tender or
non-tender on
palpation) (Figure 22)
Occasionally egg shell
crackling of the
cortical plates may be
appreciated on
palpation

Periapical
cyst

Well-defined radiolucency
measuring 1.5 cm in
diameter at the periapex
of the tooth surrounded
by a sclerotic border
(Figures 23 and 24).
Absence of the sclerotic
border may be indicative
of an infected cyst
(Figure 25)

Periapical cyst

Clinical Diagnostic Methods


Diagnostic methods for caries in common use include
visual inspection, tactile examination with a probe, bitewing radiography, intraoral periapical radiographs and certain diagnostic aids such as fiberoptic transillumination,
endoscopic techniques, light scattering, laser fluorescence,
ultraviolet illumination, dye penetration, iodide penetration and electrical resistance.
Early diagnosis enables small lesions to be identied so
that remineralization of lesions by preventive measures can
be attempted.
In the clinical examination for dental caries every assessable surface of each tooth must be examined for localized
changes in color, texture, and translucency.
Dental caries is most prevalent in the faulty pits and
ssures of the occlusal surfaces, where developmental
lobes of the posterior teeth fail to coalesce, partially or
completely.

Visual, Tactile Methods of Caries Detection


Earlier sharp explorers were used to detect incipient fissure caries. However, in recent times it is strongly discouraged as it was found to fracture enamel and serve as a
source for transferring pathogenic bacteria among various
teeth. It was also noted that the use of an explorer did
not increase diagnostic validity compared to visual
examination.
Visual examination of the tooth surface should be carried
in a dry, well-illuminated eld.
Chalkiness or apparent softening or cavitation of the tooth
structure is diagnostic of the carious process. Occasionally
416

Flowchart 1
Enamel caries

Dentinal caries or reversible pulpitis

Chronic irreversible pulpitis

Acute

Apical periodontitis

Periapical abscess

Cellulitis

Infected

Acute
suppurative
osteomyelitis
Followed by
chronic phase

Ludwigs angina/fascial
space infections

Cavernous sinus thrombosis

Death

Sequelae of pulpitis

Chronic

Periapical
abscess

Dentoalveolar
abscess

Periapical
granuloma

Periapical
cyst

Chapter 15 Dental Caries, Pulp and Periapical Lesions

Figure 9

Figure 10
A

B
Radiograph showing proximal caries
involving dentin suggestive of dentinal caries.
Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

a brown-gray discoloration is seen. However, one should


be careful to distinguish between supercial staining and
a carious lesion.
Occlusal enamel can be evaluated for loss of translucency and change in color, which are characteristics of
caries.
Proximal surface caries is usually diagnosed radiographically. Clinically when the carious process has invaded the
proximal surface enamel and dentin, a white chalky appearance or a shadow under the marginal ridge may be seen. Careful probing with an explorer on the proximal surface may
detect cavitation (dened as a break in the surface contour of
enamel).
Proximal caries can also be detected by tooth separation or through transillumination. Brown spots on intact
hard proximal surface of enamel adjacent to and usually
gingival to the contact area are often seen in older patients
whose caries activity is low. Such a spot is no longer carious and, in fact, are more resistant to caries as a result of
uorhydroxyapatite formation. Transillumination is accomplished by placing the mirror or light source on the lingual
side of the anterior teeth and directing the light through
the teeth.
Use of a dental oss in the interdental regions along the
proximal surfaces of teeth may also be used to detect initial
proximal carious lesions. A frayed oss is usually diagnostic
of proximal caries.
Another form of smooth surface caries often occurs
on the facial and lingual surfaces of the teeth, particularly

Grossly decayed teeth and root stumps.


Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

in gingival areas that are less accessible for cleaning.


The earliest clinical evidence of incipient caries on these
surfaces is a white spot that is visually different from
the adjacent translucent enamel and will partially or
totally disappear on wetting. Drying again will cause it
to reappear. This disappearing and reappearing phenomenon distinguishes the smooth incipient caries form
the white spots resulting from non-hereditary enamel
hypocalcicaton.
In patients with attachment loss, care must be taken to
inspect for root surface caries. Carious lesion occurs on the
cemental surfaces of the teeth. Active root caries is detected
by the presence of softening and cavitation.
Advanced smooth surface caries will exhibit discoloration and demineralization and will feel soft to penetration
by the explorer. The discoloration may range from white to
dark brown, with rapidly progressive caries usually being
light in color. With slowly progressive caries in a patient
with low caries activity, darkening occurs over time because
of extrinsic staining and remineralization of decalcied
structure occasionally may harden the lesion. Such an
417

Section VI Teeth and Periodontium

Figure 11

Figure 13

Caries
involving
pulp

No periapical changes

Illustration showing the radiographic features


in chronic irreversible pulpitis. Coronal radiolucency
involving pulp with no periapical changes

Illustration showing loss of lamina dura at the


periapex and diffuse radiolucency at the periapex
suggestive of chronic periapical abscess

Figure 14
Figure 12

Widening of periodontal
ligament space at the periapex

Illustration showing the radiographic features of


chronic apical periodontitis. Coronal radiolucency
involving pulp with widening of the periodontal ligament
space at the periapex

arrested lesion may at times be rough, although cleanable


and a restoration is not indicated except for esthetics. The
dentin in an arrested remineralized lesion is termed eburnated or sclerotic.
Following a visual clinical examination the carious lesion
can be scored using the International Caries Detection and
Assessment System (ICDAS).
418

Radiograph depicting well-defined radiopacity at


the periapex suggestive of condensing osteitis.
Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

Scoring system for visual changes associated


with carious lesions (ICDAS)
Score 0: Sound tooth surface
Score 1: First visual change in enamel
Score 2: Distinct visual change in enamel
Score 3: Microcavitation

Chapter 15 Dental Caries, Pulp and Periapical Lesions

either with white light or with filtered fluorescence excited


by a blue curing light have shown an increased sensitivity
to detect initial occlusal lesions in comparison to clinical
visual examination.

Figure 15

Well-defined periapical
radiolucency less than 1.5 cm

Illustration showing the radiographic features of


periapical granuloma. Well-defined radiolucency
measuring less than 1.5 cm at the periapex

Figure 16

The histopathological picture of a periapical


granuloma. Courtesy: Department of Oral
Pathology, MCODS, Mangalore

Score 4: Underlying dark shadow from dentin with or


without cavitation
Score 5: Distinct cavity with visible dentin
Score 6: Extensive distinct cavity with visible dentin.
Endoscopic methods Initial studies by Longbottom and Pitts
(1992) on the potential benefits of endoscopic examination,

Fiberoptic transillumination Friedman and Marcus (1970)


described the use of fiberoptic transillumination for the
detection of approximal caries. The working principle is
that the decayed tooth material scatters light more strongly,
and thus has a lower index of light transmission than a
sound tooth structure.
Use of beroptic transillumination for the diagnosis of
occlusal dentinal decay was studied by Verdonschot et al
(1992) as part of a comparison of various systems available
for the diagnosis of the dentinal decay of occlusal surfaces
in vivo. They found a very low sensitivity (0.13) and a
high specicity (0.99).
Light-scattering In a study by Angmar-Mansson and
Ten Bosch (1987) to assess the scattering of light by carious lesions, incipient caries lesions looked whiter than the
surrounding sound enamel because of the strong scattering of light within the lesion. Presumably, this is primarily
due to the fact that the remaining small mineral particles
in the lesion are embedded in water rather than in mineral-rich sound enamel.
Ogaard and Ten Bosch (1993) were of the opinion that
this technique is useful only for caries lesions on smooth
surfaces.
Laser autofluorescence Visible light within the blue-green
region has been used as the light source for the development
of a sensitive method for the detection of smooth surface and
fissure caries at an early stage (Bjelkhagen et al, 1982).
The tooth is illuminated with a broad beam of bluegreen light of 488 nm wavelength from an argon ion laser.
The uorescence in the enamel occurring in the yellow
region (about 540 nm) is observed through a yellow highpass lter (520 nm) to exclude the tooth-scattered blue
laser light.
Demineralized areas appear dark in this situation. Natural
lesions (diameter 1 mm) with a lesion depth as small as
510 m can be detected and measured using laser autouorescence.
Ultraviolet illumination Ultraviolet (UV) light has been
used to increase the optical contrast between the carious
region and the surrounding sound tissue. The natural fluorescence of tooth enamel, as seen under UV illumination,
is decreased in areas of less mineral content, such as in caries
lesions, artificial demineralization, or developmental defects
(Alfano and Yao, 1981).
The caries lesion appears as a dark spot against a uorescent background. Alfano and Yao showed that the UV illumination method was more sensitive than simple visual/
tactile methods.
419

Section VI Teeth and Periodontium

Figure 17
A

(A) Intraoral photograph showing a well-defined swelling on the palatal surface of decayed maxillary molar suggestive of
an acute periapical abscess. (B) Tender extraoral swelling suggestive of an acute periapical abscess. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

Figure 18

Swelling associated with maxillary molar suggestive of


a periapical abscess. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

Foreman (1988) stated that, in UV light, there is generally


an inverse correlation between the intensity of uorescence
and the degree of mineralization in mineralized dental tissues,
just as there is with the laser uorescence method.
Penetration of dyes Various dyes, fluorescent or nonfluorescent, have been used for staining the porous caries
lesion to enhance the contrast between the carious region
and the surrounding sound enamel.
420

Figure 19

A sinus opening in the vestibule associated with


the discolored central incisor. Courtesy: Department of
Oral Medicine and Radiology, KLE Societys Institute of
Dental Sciences, Bangalore

Shern and coworkers (1990) compared sodium uorescein with potassium iodide to disclose the porosity of an
articial incipient lesion. The extent of porous (active)
white spot lesions was disclosed only by uorescein.
Van de Rijke et al (1991) presented an optical quantication of approximal in vitro caries using a uorescent dye,
Fluorol.

Chapter 15 Dental Caries, Pulp and Periapical Lesions

Figure 20

Radiograph reveals diffuse periapical


radiolucency associated with the mandibular
molar suggestive of a periapical abscess.
Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

Figure 22

Extraoral photograph showing an extraoral swelling over


the right side of the mandible which was bony hard on
palpation. Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

Figure 21
Figure 23

Well-defined periapical
radiolucency more than 1.5 cm
with sclerotic border

Extraoral photograph showing diffuse extraoral swelling


involving the left submandibular, buccal and infraorbital
fascial spaces. Courtesy: Dr Francisco Lopez Sanchez,
University of Michoacan, Morelia, Mexico

OBrien et al (1989) used a blue tracer dye to increase the


color contrast in the detection of approximal incipient caries lesions by beroptic transillumination. Articial incipient caries lesions were photographed by transillumination
with or without the blue dye added. The color difference

Illustration showing the well-defined periapical


radiolucency measuring more than 1.5 cm in
diameter suggestive of a periapical cyst

was registered by a reectance colorimeter, and a four


times increase between the lesion and the surrounding
sound area was shown with the dye.
Iodide penetration The iodide penetration method for
measuring enamel porosity of the incipient caries lesion on
421

Section VI Teeth and Periodontium

Figure 24

Figure 25

Maxillary occlusal radiograph showing a well-defined


periapical radioluceny associated with a fractured
maxillary central incisor suggestive of a periapical
cyst. Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

smooth surfaces was developed by Brudevold and coworkers


and was later improved by Zero et al.
Potassium iodide was applied for a specied period of time
to a well-dened area of the enamel surface, and thereafter the excess was removed. Permeability was estimated by
measurement of the quantity of iodide that could be eluted
from the test area.
Electrical resistance The electrical resistance method is
based on the assumption that electrical conductivity is a
function of porosity. Enamel demineralization results in
increased porosity, and saliva fills the pores and forms conductive pathways for electrical current.
Thus, the greater the amount of demineralization, the
higher the electrical conductivity through the affected enamel
is expected to be.
An instrument (Vanguard electronic caries detector) has
been designed to measure the electrical conductivity of
a tooth to evaluate the presence of lesions in the occlusal
surface by measuring the electrical conductivity from the
probe tip in the ssure through the dental pulp to a handheld earth. The electrical conductivity is expressed numerically on a scale from 0 to 9. In an in vitro study of
occlusal pit-and-ssure caries in molars, Flaitz et al (1986)
compared electrical conductivity data of extracted teeth
with the histologically measured lesion depth. The results
showed a linear relation between scale value and depth.
Ultrasonic imaging Ng et al (1988) introduced ultrasonic imaging for detecting early caries in smooth surfaces. They showed that artificial enamel lesions with less
than 57% of the sound enamel mineral content in the
422

Intraoral periapical radiograph showing a periapical


cyst with no definitive sclerotic border suggestive of
a secondary infection (infected periapical cyst).
Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

body of the lesion could be differentiated acoustically


from intact enamel on the basis of amplitude changes of the
enamel surface echo and the amelodentinal junction echo.
They also found that there was a correlation between the
mineral content of the body of the lesion and the relative
echo amplitude changes, which was explained by changes
in specic acoustic impedance. However, the authors concluded that the method is not sensitive enough to detect
changes of shallow caries lesions in vivo.
Vitality tests The tooth is said to be vital when it is capable of responding to stimuli.
To check the vitality there are three basic stimuli in the
form of thermal, electrical or mechanical:

Thermal heat/cold application


Electric pulp testing: Direct electric stimulation of sensory nerves in the pulp
Mechanical stimulation: Blowing air to the exposed
dentin and test cavity preparation.

Thermal Test
Cold test
Adjacent or contralateral unaffected teeth should be tested
for baseline comparisons because the duration of pain may
differ among individuals.

Chapter 15 Dental Caries, Pulp and Periapical Lesions

A cotton applicator tip sprayed with a freezing agent or


carbon dioxide snow, icesticks, and ethyl chloride spray
applied directly to the tooth. The cold stimulus is applied
immediately to the middle one-third of the facial surface of
the crown of the tooth/exposed metal surface of crowns
and kept in contact for 5 seconds or until a point the
patient begins to feel pain.

Figure 26

Heat test
The tooth in question is isolated. A 3-inch gutta percha
stick is warmed over a flame until it becomes soft and just
begins to glisten.
The heated stick is then applied to the middle one-third
of the facial surface of the crown. Normally a response is
appreciated in about 2 seconds.

Use of electric pulp tester. Courtesy: Department of


Oral Medicine and Radiology, MCODS, Mangalore

Interpretation of the results


1.

2.
3.
4.

No responsea non-vital pulp.


However, a false negative response can be encountered when the tooth exhibits excessive calcification,
immature apex, recent trauma and a premedicated
patient.
Momentary mild-to-moderate responsenormal pulp.
Exaggerate response that subsides quicklyreversible
pulpitis.
Painful response that lasts for several minutes after the
stimulus is removedirreversible pulpitis.

Electric Pulp Tester


Evaluation of responding nerve endings can be done with
an electrical pulp tester (Figure 26). A small electric current
delivered to the tooth causes a tingling sensation is suggestive of vital pulp.
The teeth to be tested must be isolated and dried with
2 2 inch gauze and the area must be kept dry with a
saliva ejector. The patient must be made aware of the procedure. The electrode should be coated with a viscous conductor. The electrode should then be applied to the dry
enamel of the tooth being tested on the middle one-third
of the facial surface of the crown.
The digital reading that indicates the current ow should
always start with zero. The current ow should be
increased slowly to allow the patient to respond for tingling
sensation. If a positive response is not obtained the electrode should be applied to several different locations on the
lingual and facial surfaces of the tooth to ensure that
the negative response is not due to the result of improper
electrode placement. Each tooth should be tested at least
two or three times and an average result should be recorded.
Enamel thickness inuences the results. Thinner enamel
in the anteriors yields faster response than thicker enamel
of the posteriors. Electrodes should not be applied on
restorations.

False positive response (when a patient reports sensation


in a tooth with a necrotic pulp) can be encountered under
the following conditions:

Patient anxiety
Saliva conducting the stimulus to the gingiva
Metallic restoration conducting the stimulus to the adjacent teeth
Liquefaction necrosis conducting the stimulus to the
attachment apparatus.

False negative response (although the pulp is vital, patient


does not indicate that any sensation is felt in the tooth) can
be encountered under the following conditions:

Premedication with drugs or alcohol


Immature teeth
Trauma
Poor contact with the tooth
Inadequate media
Partial necrosis with vital pulp remaining in the apical
portion of the tooth
Individuals with atrophied pulps or with high pain
thresholds.
Limitations
There is no reasonable assurance; however, these nerves
are located in an intact pulp. Necrotic and degenerating
pulp tissue often leaves an excellent electrolyte in the pulp
space. This electrolyte can easily conduct the electrical current to nerves further down into the pulp space, simulating normal pulp response. This is more complicated in a
multi-rooted tooth, where the status of the pulp varies in
each root.
Electrometric pulp tester should not be the primary
instrument of choice when assessing pulpal health. A positive cold test provides a more accurate response that is easier
423

Section VI Teeth and Periodontium

to interpret. However, neither of these tests ensures vitality


of the pulp if the results are positive.
The above mentioned pulp vitality assessment methods
rely on stimulation of A-delta nerve bers and give no
direct indication of blood ow within the pulp. These testing methods have the potential to produce an unpleasant
and occasionally painful sensation and inaccurate results
(false positive or negative can be obtained in many
instances). In addition, each is a subjective test that
depends on the patients perceived response to a stimulus
as well as the dentists interpretation of that response.
Many studies have shown that blood circulation and not
innervation is the most accurate determinant in assessing
pulp vitality as it provides an objective differentiation between
necrotic and vital pulp tissue.
The newer techniques that have been tried effectively to
evaluate the vitality of the pulp include pulse oximetry, dual
wavelength spectrophotometry and laser Doppler owmetry.

Pulse Oximetry
The pulse oximeter is a non-invasive oxygen saturation monitoring device widely used in medical practice for recording
blood oxygen saturation levels during the administration
of intravenous anesthesia.
The pulp oximeter is based on the modication of the
principle of Beers law, which relates the absorption of
light, by a solute to its concentration and optical properties at
a given light wavelength. It also depends on the absorbance
characteristics of hemoglobin in the red and infrared range.
In the red region, oxyhemoglobin absorbs less light than
deoxyhemoglobin and vice versa in the infrared region.
The system consists of a probe containing a diode that
emits light in two wavelengths:
1.
2.

Dual wavelength spectrophotometry (DWLS) is a method


independent of a pulsatile circulation. The presence of
arterioles rather than arteries in the pulp and its rigid
encapsulation by surrounding dentin and enamel make it
difficult to detect a pulse in the pulp space. This method
measures oxygenation changes in the capillary bed rather
than in the supply vessels and hence does not depend on
a pulsatile blood flow.
It detects the presence or absence of oxygenated
blood at 760 and 850 nm. The blood volume or concentration channel (760 850 nm) is arranged to respond linearly to the increase in light absorption. The oxygenation
channel (760 850 nm) senses the oxygenated blood
because of the greater absorption at 850 nm as compared
to 760 nm.
In vivo and in vitro studies were conducted to differentiate between pulp chambers that were empty, lled with
oxygenated blood or xed pulp tissue. DWLS was able to
differentiate with reproducible readings between a pulp
chamber of a vital and non-vital tooth in vivo.
In young children, in cases of avulsed and replanted
teeth with open apices, the blood supply is regained within
the rst 20 days after replantation but nerve supply lags
behind.
Repeated spectrophotometric readings taken at the start
of the replantation and continuing up to 40 days later
revealed an increase in blood oxygenation levels indicating a healing process and that the pulp of the avulsed
tooth was recovering. Hence, endodontic treatment need
not be undertaken.
A major advantage is that it uses visible light that is
ltered and guided to the tooth by beroptics. Thus, unlike
laser light, added eye protection is unnecessary for the
patient and the operator.

Red light of approximately 660 nm


Infra-red light of approximately 850 nm.

A silicon photo detector diode is placed on the opposing surfaces of the tooth, which is connected to a microprocessor.
The probe is placed on the labial surface of the tooth
crown and the sensor on the palatal surface. Ideal placement of the probe is in the middle third of the crown. If placed
in the gingival third, disturbances from gingival circulation
or any gingival trauma or bleeding will interfere with the
readings. Incisally, less of pulp tissue is present for adequate
detection of the pulse.
A number of clinical studies have proved that the pulse
oximetry is an effective and objective method of evaluating dental pulp vitality. Though the surrounding insulation of the enamel and dentin are hindrances to the
detection of a pulse in the pulp, it has proved to be a successful method in 70% of the clinical trials. It is also useful
in cases of impact injury where the blood supply remains
intact but the nerve supply is damaged.
424

Dual Wavelength Spectrophotometry

Laser Doppler Flowmetry


Laser Doppler flowmetry is a non-invasive, electro-optical
technique, which allows the semi-quantitative recording of
pulpal blood flow. The laser Doppler technique measures
blood flow in the very small blood vessels of the microvasculature.
This technique depends on the Doppler principle
whereby light from a laser diode incident on the tissue is
scattered by moving RBCs and as a consequence, the frequency broadened. The frequency broadened light, together
with laser light scattered from static tissue is photo detected
and the resulting photocurrent processed to provide a
blood ow measurement.
The Doppler shifted laser light, back-scattered out of
the tooth is detected by a photocell on the tooth surface.
The output is proportionate to the number and velocity
of the blood cells.

Chapter 15 Dental Caries, Pulp and Periapical Lesions

Radiographic Evaluation of Carious Lesions


It has been proved time and again over the years that more
dental caries are detected by intraoral radiographs than by
clinical examination alone. Radiographic detection of dental
caries is based on the fundamental principle that as the
caries process proceeds, the mineral content of enamel and
dentin decreases with a resultant decrease in the attenuation of the X-ray beam as it passes through the teeth. This
is recorded as a radiolucent image on the image receptor.
Detection of the carious lesion may be inuenced by a
number of factors such as the extent of demineralization
of the carious lesion (minimum of 40% demineralization
of the tooth structure is required to be evident on a radiograph), location of the carious lesion, exposure parameters, type of image receptor, image processing, display
system, viewing conditions, and ultimately, the training
and experience of the human observer.
Cervical burnout, abrasion, attrition, proximal wear and
restorative materials that appear radiolucent may mimic
dental caries.
Radiographs are taken to evaluate the extent of the carious
lesions and to assess periapical changes secondary to the caries attack. Intraoral periapical radiographs and bitewing
radiographs are widely used for assessing carious lesions.
White and McMullin (1986) concluded that both ultraspeed lm and xeroradiography (XR) were somewhat preferable to Ektaspeed lm. Wenzel et al (1991) compared
conventional lm radiographs, digitized lm radiographs,
and radiovisuography (RVG) for the detection of occlusal
caries in non-cavitated extracted teeth. Histologic sections
served as the validation criterion. The two digital methods
with contrast enhancement tended to perform better than,
although not signicantly different from, the other three
methods.
The authors concluded that radiography can much
improve diagnosis compared to clinical inspection.
They also concluded that digital techniques, no matter
which, improve the sensitivity without substantial loss of
specicity.
Occlusal caries
Incipient carious lesions occurring on the occlusal surface
of teeth usually begins in the pits and fissures. The carious
lesion starts at the side of the fissure than at the base and
it tends to penetrate perpendicular toward the DEJ.
Radiographs can help to detect occlusal lesions only
when the carious process reaches the dentin.
A moderate carious lesion will generally show denitive radiographic ndings such as a broad-based thin radiolucent zone in the dentin with little or no changes apparent
in the enamel.
As the carious process advances into a severe form, the
underlying dentin is extensively involved and hence fails
to support the overlying enamel structure resulting in the

breakdown of the occlusal surface. Radiographically, an


extensive ill-dened radiolucent area is seen.
Proximal caries
The proximal carious lesion is clinically apparent as a
chalky white discoloration. It is estimated that it takes
about 4 years for an initial proximal carious lesion to be
seen clinically. In the initial stages a discrete radiolucent
wedge-shaped defect or notch may be visible usually
confined to the enamel cap.
Moderate carious lesions usually involve more than the
outer half of the enamel to extend into the DEJ. Radiographically, proximal caries can present either as a triangle with its broad base at the surface of the tooth or a
diffuse radiolucent image or a combination of the above.
In advanced lesions the carious process involved the DEJ.
Radiographically, the entire thickness of enamel is involved.
The carious lesion may either present as a triangular process or appear ill-dened and diffuse or may appear as a combination of the above.
In a severe form of the proximal carious process, a radiolucent area involving more than half the dentin and
approaching the pulp chamber is characteristic.
Facial, buccal and lingual caries
Smooth surface carious lesions will usually begin along the
pits and fissures. Almost all carious lesions occurring on the
facial and lingual surface of teeth have a very sharply
defined outline. In the initial stages these lesions are round
and as the carious process advances they appear as large
elliptical defects.
Occasionally, these carious lesions may be difcult to
detect as they may be superimposed over the DEJ mimicking occlusal caries.
Generally, these lesions appear as well-dened circular
radiolucent areas surrounded by dense area of noncarious tooth structure.
Root caries
Root surface carious lesions are those that involve the cementum and dentin. These are typically seen in teeth which
exhibit gingival recession or interdental bone loss. Older
individuals are more likely to show the presence of root
surface carious lesions. Radiographically, a saucer like or
a notched radiolucency is seen at the cervical margin of
the tooth that usually extends apically along the root surface.
Recurrent caries
Recurrent caries or secondary caries occurs adjacent to a
restoration. It may result from poor marginal adaptation
of a restoration, which allows marginal leakage; inadequate extension of a restoration, incomplete excavation
of the primary carious lesion and fractured restoration.
425

Section VI Teeth and Periodontium

Radiographs show radiolucent areas adjacent to a restoration. Restorative materials such as composite, silicate and
acrylic can resemble recurrent caries. These radiolucent
restorative materials can be differentiated from recurrent
caries by their well-defined and smooth outlines (Figure 27).
Rampant caries
Rampant caries usually occurs in children. There will be
extensive smooth surface caries involving many teeth.
Radiation caries
Radiation caries can be considered as a type of rampant
caries seen in patients who receive radiation therapy for
head and neck tumors. It occurs secondary to xerostomia.
Caries begins at the cervical region and may aggressively
encircle the tooth causing entire crown to be lost with
only root fragments remaining in the jaws. Radiograph
shows dark radiolucent shadows appearing at the cervical
margins of teeth.

FASCIAL SPACE INFECTION


Cellulitis or fascial space infection is characterized by a
diffuse inflammation of soft tissues. Fascial space infections
in the head and neck region usually occur as an extension
of periapical, periodontal and pericoronal infections.

Concepts of Fascia and Fascial Spaces


Fasciae are extensive, broad sheets of dense connective tissue. Fasciae envelop anatomic structures such as the muscles, glands and organs and thereby separate structures that
must move over each other during movement. These fasciae also serve as pathways for the course of vascular and
neural structures.
Shapiro dened fascial spaces as potential spaces
between layers of fascia. These spaces are normally lled
with loose connective tissue and vital structures. The use
of the term space is a misnomer as tissues show no evidence of voids. The pus destroys the loose connective tissue
and separates the anatomical boundaries of the compartment
as it increases in volume, thus creating an abscess cavity
bounded by muscles, tissues and bone.
Superficial fascia
It is a layer of dense connective tissue that courses deep to
the subcutaneous tissue throughout the entire body. Below
the mouth the muscles of facial expression lie deep to the
superficial fascia, whereas in the upper face the muscles of
facial expression are positioned superficial to this layer. The
superficial cervical fascia is a sheet of fibrous connective
tissue that encircles the head and neck and is attached to
the fascia of the thorax, shoulders and axilla. It contains
the platysma muscle.
Deep fascia

Figure 27

Radiograph showing recurrent carious lesion below


the margins of the radiopaque restorative material.
Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

426

The deep cervical fascia is divided into the superficial or


investing layer, the middle or visceral layer and the deep
or prevertebral layer. The superficial layer of the deep cervical fascia completely encircles the neck with its attachments being superiorly: the external occipital protuberance,
the mastoid process and the zygoma, and anteriorly the
mandible and the hyoid bone and inferiorly the scapula,
the clavicle and the manubrium of the sternum. It envelops
the trapezius and sternocleidomastoid muscles. The middle
layer encircles the viscera of the neck including the pharynx,
esophagus, larynx, trachea and thyroid gland. It also encloses
the strap muscles anteriorly. The deep layer envelops the
paraspinous muscles and vertebral bodies. More importantly,
anterior to the vertebral bodies it divides into a prevertebral layer and a more anterior alar layer. This creates three
potential spaces, namely, the prevertebral space, the danger
space and the retropharyngeal space. The carotid sheath is
formed from contributions of all three layers of the deep cervical fascia and runs from the base of the skull to the level
of the clavicle.
The deep spaces of the neck can be divided into those
which involve the entire length of the neck (including the
retropharyngeal space, the danger space and the prevertebral space), those that are limited to above the hyoid bone
(the submaxillary, the sublingual and the parapharyngeal

Chapter 15 Dental Caries, Pulp and Periapical Lesions

spaces) and those limited to below the hyoid bone. Refer to


line diagrams (Figures 28 to 32).
The retropharyngeal space is the potential space that
exists between the posterior aspect of the visceral layer
and the alar division of the deep layer. It extends from the
base of the skull to the level of the rst or second thoracic
vertebrae. It contains two lateral chains of lymph nodes
separated by a midline raphe. The danger space lies between
the alar and prevertebral layers of the deep cervical fascia.
It extends from the base of the skull to the posterior mediastinum at the level of the diaphragm and is limited laterally by its fusion with the prevertebral layer and the
vertebral transverse process. The prevertebral space lies
between the vertebral bodies and the prevertebral layer of
the deep cervical fascia. It extends from the base of the
skull to the level of the coccyx.
Figure 28

The parapharyngeal space can be compared to an


inverted cone with its base lying superiorly at the base of
the skull and its apex inferiorly at the hyoid bone. It is
divided into a prestyloid and a poststyloid component. Its
medial and lateral borders are, respectively, the lateral pharyngeal wall and the supercial layer of the deep cervical
fascia as it overlies the mandible, the parotid gland and the
internal pterygoid.
The submandibular space is divided by the mylohyoid
muscle into the sublingual space above and the submaxillary
space below. These two spaces communicate freely around
the posterior edge of the mylohyoid muscle. The entire
space is bounded by the mandible anteriorly and laterally.
The hyoid bone limits its inferior aspect and the intrinsic
muscles of the base of tongue from its posterior border.
The sublingual space contains the sublingual gland, the

Figure 30

Buccinator
muscle

Temporalis muscle

Tongue

Superficial temporal space


Buccal space
Infratemporal space

Sublingual space

Lateral pterygoid muscle


Submandibular
space

Pterygomandibular space
Masseteric space
Medial pterygoid muscle

Illustration showing submandibular and buccal spaces


Masseter muscle

Illustration showing infratemporal and


superficial temporal spaces

Figure 29
Medial pterygoid muscle
Parotid gland

Parotid
space
Masseter
muscle
Submasseteric
space

Parapharyngeal space
Superior
constrictor
muscle

Peritonsillar
space

Figure 31
Lateral pharyngeal space
Prevertebral space
Retropharyngeal space
Superior constrictor muscle
Pterygoid muscle

Pterygomandibular
space

Mandible
Masseter muscle

Buccal space
Buccinator
muscle

Buccinator muscle
Mylohyoid muscle

Illustration showing pterygomandibular and


submasseteric spaces

Illustration showing retropharyngeal and


lateral pharyngeal spaces

427

Section VI Teeth and Periodontium

Figure 32
Buccopharyngeal
fascia
Alar fascia
Prevertebral fascia

Retropharyngeal
space

By lymphatics to the regional lymph nodes and eventually into the blood stream
By the blood stream.
General factors
Hosts resistance or immunocompetence of the host
Virulence of microorganisms.
Local factors Intact anatomical barriers:
Alveolar bone
Periosteum
Adjacent muscles and fascia.

LUDWIGS ANGINA
Prevertebral space

Prevertebral fasciae and prevertebral space

hypoglossal nerve and Whartons duct. The submandibular


space contains the submandibular gland.
The anterior visceral space lies in the anterior aspect of
the neck, is enclosed by the visceral layer and completely
surrounds the trachea, esophagus and thyroid gland. It
extends from the thyroid cartilage to the level of the fourth
thoracic vertebrae in the superior mediastinum.
Pain and swelling are commonly present and may help
identify the space involved. Dysphagia is more common
when the parapharyngeal and retropharyngeal spaces are
involved. Trismus is seen with involvement of the submaxillary space or anterior aspect of the parapharyngeal
space. Other symptoms may include respiratory distress if
the abscess partially compromises the airway or dental
complaints if this is the source of infection. Other ndings
may include oropharyngeal abnormalities such as swelling
of the lateral or posterior pharyngeal walls, in parapharyngeal or retropharyngeal abscess.
Nearly 40% of deep space infections are caused by mixed
ora. Other changes include the emergence of gram-negative
organism, primarily Klebsiella pneumoniae, as important
pathogens as well as an increase in the prevalence of anaerobic infections. Notwithstanding, streptococcal species, primarily alpha Streptococcus and Staphylococcus aureus, are
still the most commonly isolated organisms.
Spread of orofascial infection Infections in the head
and neck region usually spread by hydrostatic pressure,
along the path of least resistance.
Routes of spread and factors affecting spread of oral
infections (Table 2)
By direct continuity through tissues
428

The necrotizing fasciitis, Ludwigs angina, was first


described by German surgeon Karl Wilhelm Friedrich von
Ludwig in 1836.
It is a potentially life-threatening, rapidly expanding,
diffuse inammation of the submandibular and sublingual
spaces that occurs most often in young adults with dental
infections.
Clinical features
Ludwigs angina begins as a mild infection and can rapidly
progress to brawny bilateral induration of the upper neck.
Anxiety, cyanosis and sitting posture are late signs of impending airway obstruction, and indicate the need for an immediate artificial airway. The most serious complication of
Ludwigs angina is asphyxia caused by expanding edema of
soft tissues of the neck.
The symptoms include severe neck pain and swelling,
fever, malaise and dysphagia. Stridor suggests an impending
airway crisis. Patient may report of severe toothache, trismus
and foul breath. The mortality rate can go up to 2050%
if the infection spreads to the mediastinum, carotid sheath,
skull base and meninges.
Complications such as descending necrotizing mediastinitis usually occurs through the retropharyngeal space (71%)
and the carotid sheath (21%).
Predisposing factors
These include deep dental caries, severe periodontal infection, a compromised immune system and recent trauma.
Ludwigs angina in children can occur de novo, without any
apparent precipitating cause.
Mode of spread
Ludwigs angina is a rapidly progressive, potentially fulminant cellulitis involving the sublingual, submental and
submandibular spaces. It typically originates from an
infected or recently extracted tooth, most commonly the
lower second and third molars. The submandibular space is
involved by penetration of the thin inner cortex of the

Chapter 15 Dental Caries, Pulp and Periapical Lesions

Table 2

Head and neck fascial spaces

Space

Boundaries

Contents

Submental space

Lateral: Lower border of mandible and anterior bellies of digastric


muscles
Superior: Mylohyoid muscle
Inferior: Suprahyoid portion of the investing layer of deep cervical
fascia

Submental lymph nodes and anterior


jugular veins

Submandibular space

Anteromedially: The floor is formed by mylohyoid muscle, which


is covered by loose areolar tissue and fat
Posteromedially: The floor is formed by hypoglossus muscle
Superolaterally: Medial surface of mandible below the mylohyoid
ridge
Anterosuperiorly: Anterior belly of digastric
Posterosuperiorly: Posterior belly of digastric, stylohyoid and the
stylopharyngeus muscles
Laterally: Platysma and skin

Superficial lobe of submandibular salivary


gland and submandibular lymph nodes,
facial artery and vein

Sublingual space

Superiorly: Mucosa of floor of the mouth


Inferiorly: Mylohyoid muscle
Laterally: Medial side of the mandible, above the mylohyoid
muscles
Medially: Hyoglossus, genioglossus and geniohyoid muscles
Posteriorly: Hyoid bone laterally and inferiorly by mylohyoid
muscle and lingual side of mandible

Geniohyoid and genioglossus muscles, the


hyoglossus muscle complex
It also contains submandibular salivary
gland, sublingual salivary gland, lingual
nerve and hypoglossal nerve

Canine space

Inferiorly: Caninus muscle


Anteriorly: Orbicularis oris
Posteriorly: Buccinator muscle
Medially: Anterolateral surface of maxilla

Buccal space

Buccal space is the potential space between buccinator and


masseter muscle
Anteromedially: Buccinator muscle
Posteromedially: Masseter overlying the anterior border of ramus
of mandible
Laterally: By forward extension of deep fascia from the capsule of
parotid gland and by platysma muscle
Inferiorly: Limited by the attachment of the deep fascia to the
mandible and by depressor anguli oris
Superiorly: The zygomatic process of the maxilla and the
zygomatous major and minor muscles

Buccal pad of fat, Stensens duct, facial


artery

Infratemporal fossa space


(retrozygomatic space)

Bounded laterally, by ramus of mandible, temporalis muscle and


its tendon
Medially: Medial pterygoid plate, lateral pterygoid muscle, medial
pterygoid muscle, lower part of temporal fossa of the skull and
lateral wall of pharynx
Superiorly by infratemporal surface of greater wing of sphenoid
and by zygomatic arch
Inferiorly: Lateral pterygoid muscle, which forms the floor of the
fossa, and its lower head is said to mark the border between
pterygomandibular and infratemporal spaces
Anteriorly: Infratemporal surface of maxilla
Posteriorly: Parotid gland

Medial and lateral pterygoid muscles,


maxillary artery, mandibular nerve and
middle meningeal artery

Temporal space
(masticatory space)

Spaces in relation to temporalis muscle:


1. Superficial temporal spacelies between temporal fascia and
temporalis muscle
2. Deep temporal spacelies deep to temporalis muscle and skull
Communicates with infratemporal and pterygopalatine fossa
(Contd.)

429

Section VI Teeth and Periodontium

Table 2

Continued

Space

Boundaries

Contents

Parotid space

The space is formed by splitting of the superficial layer of deep


cervical fascia surrounding the parotid gland, and lies posterior
to the masticator space
Inferiorly: Stylomandibular ligament, which separates parotid
space from the mandibular space

Parotid gland and parotid lymph nodes,


facial nerve, retromandibular vein, and
external carotid artery

Submasseteric space
(masticatory space)

Anterior: Anterior border of masseter muscle and buccinator


Posterior: Parotid gland and posterior part of masseter
Inferior: Attachment of the masseter to the lower border of mandible
Medial: Lateral surface of the ramus of mandible
Lateral: Medial surface of the masseter muscle

Masseter, lateral and medial pterygoids,


part of mandible and branches of
mandibular division of trigeminal nerve

Pterygomandibular space

Lateral: Medial surface of ramus of mandible


Medial: Lateral surface of medial pterygoid muscle
Posterior: Parotid gland
Anterior: Pterygomandibular raphe
Superior: Lateral pterygoid muscle

Lingual nerve, mandibular nerve, inferior


alveolar nerve or mandibular artery,
mylohyoid nerve

Lateral pharyngeal space

Superiorly: Base of skull


Inferiorly: Hyoid bone (submandibular gland and posterior belly
of digastric)
Anteriorly: Bounded by pterygomandibular raphe
Laterally: Bounded by the ramus of mandible, insertion of medial
pterygoid muscle and deep lobe of parotid gland
Medially: Bounded by pharyngeal wall and pharyngeal constrictors
Posteriorly: Bounded by styloid muscle and upper part of carotid
sheath, prevertebral fascia

Anterior compartment: Lymph nodes,


ascending pharyngeal, facial artery,
loose areolar connective tissue
Posterior compartment: Carotid sheath
(internal jugular vein, internal carotid
artery and vagus nerve), glossopharyngeal
nerve, spinal accessory nerve, hypoglossal
nerve and cervical sympathetic trunk

Retropharyngeal space

Laterally: Carotid sheath


The retropharyngeal space is continuous with retroesophageal
space into the posterior mediastinum to the level of the sixth
thoracic vertebra
There are no middle attachments in the retropharyngeal space,
thereby permitting unimpeded inferior extension of
inflammatory and neoplastic processes into mediastinum
Spread of infection through the carotid sheath into the
mediastinum is referred to as spread of infection via the
Lincolns highway

Parapharyngeal space
Lateral pharyngeal and
retropharyngeal spaces
These spaces form a ring
around pharynx and
communicate with
submandibular space and
retromandibular space

mandible by periapical dental abscesses. Spread to the sublingual space is around the posterior margin of mylohyoid
muscle. It has, however, been reported as a result of mandibular fracture, submandibular sialadenitis, peritonsillar
abscess, epiglottitis and oral malignancies.
Microbiology
Causative bacteria include many gram-negative and anaerobic organisms, streptococci and staphylococci. The bacterial

430

isolates vary and are often mixed. Alpha-hemolytic streptococci, staphylococci and Bacteroides are commonly
reported. Other anaerobes such as peptostreptococci, peptococci, Fusobacterium nucleatum, Veillonella species and
spirochetes are also seen. A foul breath/odor usually indicates the presence of an anaerobe. Gram-negative organisms such as Neisseria catarrhalis, Escherichia coli,
Pseudomonas aeruginosa and Hemophilus influenzae have
also been reported.

Chapter 15 Dental Caries, Pulp and Periapical Lesions

Anatomical considerations
The submandibular space is composed of two spaces separated anteriorly by the mylohyoid muscle: the sublingual
space, which is superior, and the submaxillary space,
which is inferior. The spread of infection is halted anteriorly by the mandible and inferiorly by the mylohyoid
muscle. The infectious process expands superiorly and
posteriorly, elevating the floor of the mouth and the
tongue.
The hyoid bone limits the process inferiorly, and swelling spreads to the anterior aspect of the neck, causing
distortion and a bull neck appearance. This then evolves
to an infectious compartment syndrome of the submandibular and sublingual spaces.
Investigations
Conventional radiographs such as intraoral periapical
radiographs or orthopantomograph (OPG) may help to
identify the offending tooth. However, a contrastenhanced computed tomography (CECT) scan is helpful in
assessing the extent of spaces involved.
Treatment
The treatment plan for each patient should be individualized and based on a number of factors. The stage of the
disease and co-morbid conditions at the time of presentation and the resources available.
Treatment includes assessment and protection of the
airway, use of intravenous antibiotics, surgical evaluation
and, if necessary, operative decompression. Intravenous
dexamethasone and nebulized adrenaline have been used
to reduce upper airway edema in such cases to defer or
avoid airway instrumentation altogether. Distorted airway
anatomy, tissue immobility, and limited access to the
mouth make orotracheal intubations by direct laryngoscopy difcult. In advanced cases, induction of general
anesthesia is dangerous because this may precipitate complete airway closure and make mask ventilation and intubation impossible. Securing of the airway in the awake
state is therefore the safest option.
Blind nasal intubation is to be avoided as, besides having a high failure rate, it could cause catastrophic bleeding, laryngospasm, airway edema, rupture of pus into the
oral cavity and aspiration. Complete airway obstruction
could be precipitated, potentially necessitating an emergency cricothyrotomy. Classically, tracheostomy was considered as the standard of care for establishment of a
denitive airway.
Elective awake tracheostomy has been suggested for all
patients with deep neck infections to avoid the dangers
of emergency tracheostomy in a severely compromised
airway.

Endotracheal intubation is associated with high rate of


failure with acute deterioration in respiratory status resulting in emergency slash tracheostomy.
Although distorted anatomy, edema, and secretions may
contribute to difculty with beroptic intubation, in skilled
and experienced hands, exible beroptic nasal intubation is the preferred method of airway management and
has a high rate of success. Application of topical anesthesia
enables the patient to tolerate the procedure with greater
comfort.
When beroptic bronchoscopy is not feasible, not
available, or has failed, cricothyrotomy and tracheostomy
are the options. Tracheostomy may be difcult or impossible in advanced cases of neck infection because of the
position needed for the procedure and anatomical distortion of the anterior neck. The choice of airway maneuvers
must be individualized, depending on the judgment and
experience of the physician in charge.
Recommended initial antibiotics are high-dose penicillin G,
sometimes used in combination with an antistaphylococcal
drug or metronidazole. In penicillin-allergic patients,
clindamycin hydrochloride is a good choice.
Alternative choices include cefoxitin sodium or combination drugs such as ticarcillinclavulanate, piperacillin
tazobactam or amoxicillinclavulanate (Augmentin).
Intravenous dexamethasone sodium phosphate (Decadron), given for 48 hours, has been benecial in reducing
edema, which helps maintain airway integrity and enhances
antibiotic penetration.
Dexamethasone reduces edema and cellulitis, provides
the initial chemical decompression protecting the airway
and allows improved antibiotic penetration into the area.
Surgical drainage may be indicated if no clinical
improvement is seen within 24 hours.

OSTEOMYELITIS
By strict definition, osteomyelitis is the inflammation of
medullary portion of bone. However, clinical evidence has
shown that it is seldom limited to the endosteum and it usually affects the cortical plates and the periosteum.
Considering the extent of the bone involvement, osteomyelitis may best be described as an inammatory condition
of bone that usually begins as an infection of the medullary cavity which rapidly involves the haversian system and
quickly extends to the periosteum of the area.
Osteomyelitis can be broadly categorized as exogenous
osteomyelitis (47%), osteomyelitis secondary to vascular
insufciency (34%) and hematogeneous osteomyelitis (19%).
The implantation of pins, plates, screws, dental implant
and articial joint can also seed infection as a nidus for
pathogens, and therefore create postoperative osteomyelitis.

431

Section VI Teeth and Periodontium

Predisposing factors
Conditions affecting host resistance Systemic, metabolically compromised individuals (factors such as age of
patient, malnutrition, immunosuppression and congenital
or acquired pathophysiology disrupting microvascular perfusion of the calcified tissue structure and investing soft
tissue envelope).
Examples include diabetes, AIDS, use of steroids,
agranulocytosis, leukemia, severe anemia and cancer chemotherapy.
Conditions affecting jaw vascularity Conditions that
affect the vascularity of the jaw bones include radiation,
bone malignancy, osteoporosis, osteopetrosis, Pagets disease of bone, fibrous dysplasia and bone necrosis (mercury,
bismuth, arsenic poisoning, long-term chemotherapeutic
agents like bisphosphonates).

either of the two major events: extension of a periapical


abscess, periodontal abscess or post-traumatic/post-surgical
complication.
Naidu et al (2008) reported a case of osteomyelitis of
the mandibular symphysis caused by bite of a brown
recluse spider.
Other predisposing conditions include bony pathologies
such as Pagets disease and osteopetrosis, compound fractures, history of local irradiation, host-debilitating conditions such as diabetes mellitus and long-term systemic
steroid therapy.
The mandible is more prone osteomyelitis compared to
other craniofacial bones due to its morphological characteristics such as a relatively thin cortical plate and poor
vascular supply to its medullary portion. The regions in
the mandible that are at higher risk of perforation include
the lingual aspect of molar teeth and in the labial aspect
of anterior teeth (Thadepalli and Mandal, 1988).

Microbiology of osteomyelitis
Microorganisms specific for different age groups
(Osteomyelitis of other bones)
Newborns (younger than 4 months): S. aureus, Enterobacter
species, and group A and B Streptococcus species.
Children (aged 4 months to 4 years): S. aureus, group A
Streptococcus species, Hemophilus inuenzae, and Enterobacter species.
Children, adolescents (aged 4 years to adult): S. aureus
(80%), group A Streptococcus species, H. inuenzae, and
Enterobacter species.
Adult: S. aureus and occasionally Enterobacter or
Streptococcus species.
Osteomyelitis of jaw bones The microorganisms responsible for osteomyelitis affecting the jaw bones reflect the
polymicrobial nature of odontogenic infections in general
and agents associated with suppurative infection and periapical abscesses in specific.
Fusobacterium nucleatum, Prevotella intermedia, Peptostreptococcus, Actinomyces and Streptococcus species (alpha
hemolytic) are the predominant isolates from osteomyelitis
affecting the jaws.
Hosts who have serious underlying illnesses may exhibit
the presence of facultative gram-negative bacilli and S. aureus.
Mycobacterium tuberculosis, Treponema pallidum and
Actinomyeces spp. produce specic forms of osteomyelitis.
Tubercular osteomyelitis of the spine is referred to as
Potts disease. Burkholderia cepacia complex have been
implicated in vertebral osteomyelitis in intravenous drug
abusers. Systemic mycotic (fungal) infections may also
cause osteomyelitis. The two most common pathogens
involved in such infections are Blastomyces dermatitidis
and Coccidioides immitis.
Osteomyelitis of jaw bones Osteomyelitis of the mandible
occurs primarily from odontogenic infection caused by
432

Pathogenesis
With the initiation of the infection, the intramedullary
pressure increases substantially, compromising the vascularity, thus heralding the beginning of a stage of bony
necrosis.
The purulent material traverses networks of Haversian
and perforating canals, eventually accumulating under the
periosteum and lifting it from the bony cortex.
As the pus accumulates, periosteal perforation can
occur ultimately forming abscesses and often stulous
tracts within mucosal and cutaneous tissues. In chronic
cases granulation tissue, dead bone (sequestrum) separated
from surrounding healthy tissue, and eventually, a reactive sleeve of new periosteal tissue (involucrum) formation
may also be seen.

Classification of Osteomyelitis
Waldvogel classification system for
osteomyelitis

Hematogeneous osteomyelitis
Osteomyelitis secondary to contiguous focus of infection
No generalized vascular disease
Generalized vascular disease
Chronic osteomyelitis (necrotic bone).

CiernyMader staging system for osteomyelitis


Anatomic type
Stage 1: Medullary osteomyelitisinvolved medullar bone
without cortical involvement; usually hematogeneous
Stage 2: Superficial osteomyelitisless than 2 cm bony
defect without cancellous bone

Chapter 15 Dental Caries, Pulp and Periapical Lesions

Stage 3: Localized osteomyelitisless than 2 cm bony


defect on radiograph, defect does not appear to
involve both the cortices
Stage 4: Diffuse osteomyelitisdefect more than 2 cm,
pathologic fracture, infection, nonunion.
Physiologic class
A host: Healthy
B host
Bs: Systemic compromise
Bl: Local compromise
Bls: Local and systemic compromise
C host: Treatment worse than the disease.

Factors affecting immune surveillance, metabolism and


local vascularity are:

Systemic factors (Bs): Malnutrition, renal or hepatic failure, diabetes mellitus, chronic hypoxia, immune disease, extremes of age, immunosuppression or immune
deficiency.
Local factors (Bl): Chronic lymphedema, venous stasis,
major vessel compromise, arteritis, extensive scarring,
radiation fibrosis, small-vessel disease, neuropathy,
tobacco abuse.
Classification based on the clinical course and
radiographic features
Suppurative osteomyelitis
Acute suppurative osteomyelitis
Chronic suppurative osteomyelitis
Primary (no preceding acute phase)
Secondary (follows acute phase)
Infantile osteomyelitis.

Non-suppurative osteomyelitis
Focal sclerosing osteomyelitis (condensing osteitis)
Diffuse sclerosing osteomyelitis
Proliferative periostitis (periostitis ossificans)
Osteoradionecrosis.
Clinical features
Osteomyelitis may be acute, subacute or chronic, and
presents a different clinical course depending on its
nature.

Acute Suppurative Osteomyelitis


In maxilla, the disease usually remains fairly well localized to the area of infection. In mandible, bone involvement
tends to be more diffuse and widespread. It may occur at
any age. Infants affected are seriously ill and may not
survive.
In adults, there is severe pain and elevation of temperature with regional lymphadenopathy. The skin overlying the

affected bone is warm, erythematous and tender on palpation.


Patients complain of fever, malaise and anorexia.
Teeth in the area of involvement are loose and tender on
percussion. Pus discharge may be present around the sulcus of the tooth (Figure 33A, B). Patients may complain of
a fetid odor. Paresthesia and anesthesia of lip is seen. The
WBC count is elevated. If the acute phase is not controlled
within 1014 days after onset then subacute suppurative
osteomyelitis is established.
Radiographic features
Generally, no radiographic findings are associated with
acute osteomyelitis. A minimum of 40% demineralization
of bone is required to be evident. Radiographic evidence of
acute osteomyelitis may be detected at least 414 days
after onset of acute osteomyelitis. The full extent of bone
dissolution may be evident 3 weeks after the initial attack.
The radiographic features always lag behind the actual progress of the condition. Bony trabeculae appear indistinct and
fuzzy. The initial radiolucent areas appear as moth-eaten
regions with ill-defined margins.
Histopathologic features
Histologic sections show medullary spaces filled with inflammatory exudate, chiefly composed of neutrophils. Other
cells that are seen include lymphocytes and plasma cells.
Osteoblasts bordering the bony trabeculae are generally
destroyed, leading to loss of trabecular viability and slow
resorption of the bone.
Management
High dose intravenous antibiotic therapy, identification and
correction of host compromise factors is required. Careful
enquiry and investigation may reveal diabetes, autoimmune
disease, alcohol-starvation syndrome, intravenous drug
abuse, severe anemia, HIV, steroid, chemotherapy. Factors
that delay recovery should be identified and corrected. Initial
management is often aided by hospitalization. Once the
infection is controlled treatment is continued on an outpatient basis using home intravenous therapy with percutaneous indwelling catheter and antibiotic pumps.
Specimens should be obtained for Gram staining, aerobic
and anaerobic cultures and antibiotic sensitivity testing.
Conventional radiographs and bone scans should be
obtained to determine the extent of the disease and causative factors such as fractures and presence of sequestra.
Once the acute stage has resolved with antibiotics,
other procedures like sequestrectomy, debridement, direct
placement of antibiotics into the wound by means of
indwelling catheters or antibiotic impregnated beads,
hyperbaric oxygen therapy, decortication, resection of
infected bone and immediate or late bone graft reconstruction.
433

Section VI Teeth and Periodontium

Figure 33
A

Intraoral sinus opening and diffusely enlarged gingiva associated with acute osteomyelitis.
Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Antibiotic therapy Antibiotics of value in the treatment


of osteomyelitis are penicillins, extended spectrum penicillin, semisynthetic penicillins, clindamycin, cephalosporins
and metronidazole.
Many organisms responsible for osteomyelitis are now
penicillin resistant, including prevotella, porphyromonas
and fusobacterium. Therefore, a drug resistant to these
organisms such as metronidazole should be added to penicillin. Some of the newer antibiotics providing effective
coverage for the more refractory organisms include metronidazole, clindamycin, ticarcillin and clavulanic acid,
a variety of cephalosporins, carbapenems, vancomycin in
combination with other antibiotics and uoroquinolones
such as ciprooxacin.

Penicillin V, 2 g, in combination with metronidazole,


0.5 g q8h PO, for 24 weeks after last sequestrum removed
and patient without symptoms.
Or
Clindamycin, 600900 mg q6h IV, then clindamycin,
300400 mg q6h PO.
Or
Cefoxitin (mefoxin), 1 g q8h IV or 2 g q4h IM or IV, until
no symptoms, then switch to cephalexin, 500 mg q6h PO,
for 24 weeks for penicillin allergic patients clindamycin
(as above) cefoxitin (as above), if allergy not of anaphylactoid type.

Antibiotic regimen for osteomyelitis of jaw


Regimen 1: For hospitalized/medically compromised patient
or when intravenous therapy is indicated.
Aqueous penicillin, 2 million units IV q4h, in combination with metronidazole 500 mg q6h. When improved for
4872 hours switch to penicillin V, 500 mg per oral q4h, in
combination with metronidazole 500 mg PO q6h, for an
additional 46 weeks.
Or
Ampicilin/sulbactam, 1.53 g IV q6h when improved
for 4872 hours, switch to amoxicillin/clavulanate (augmentin), 875/125 mg per oral b.i.d., for an additional
46 weeks.
Regimen 2: For outpatient treatment.

434

Chronic Suppurative Osteomyelitis


This may develop after the acute phase of the disease has
regressed, or sometimes can occur without a preceding acute
phase.
Clinical features are similar to that of the acute type, except
that all signs and symptoms are milder. Pain is less severe.
Temperature is mildly elevated. Teeth may tend to become
loose and occasionally tender on palpation. Acute exacerbation may occur periodically.
Intraoral or extraoral draining stulas may be seen
(Figure 34). The cortical plates may be expanded and in
severe cases pathological fracture may be evident. The bone
is thickened and assumes a wooden character on palpation
(Figure 35). Leukocytosis is slightly more than the normal.

Chapter 15 Dental Caries, Pulp and Periapical Lesions

Figure 34

Figure 35

Extraoral draining sinus in chronic suppurative


osteomyelitis. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

Extraoral swelling in chronic suppurative osteomyelitis.


Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

Figure 36
A

Radiographs showing ill-defined radiolucent areas with moth-eaten appearance characteristic of chronic suppurative osteomyelitis.
Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Histologic features
The typical histological picture shows intertrabecular areas
of bone filled with chronically or subacutely inflamed
fibrous connective tissue. Presence of scattered sequestra
and pockets of abscess are common.

extending to involve the lower border of the mandible in


severe cases (Figure 36A, B). Evidence of sequestrum/
involucrum may be found. Extensive destruction of the
bone may cause pathologic fracture.
Management

Radiographic features
Radiographs will reveal a poorly defined radiolucency
(moth-eaten appearance) within the body of the mandible

After intraoral debridement, saucerization or decortication,


small pediatric nasogastric feeding tubes, French catheters,
or polyethylene irrigation tubes 34 mm in diameter and

435

Section VI Teeth and Periodontium

610 inches long are placed into the bone bed through
separate skin incisions along the lateral bony surface through
holes drilled into bone. These drains are held to the skin with
sutures or tape. Alternatively, two tubes may exit from one
stab incision or a single tube may be used for instillation and
suction.
The tubes are ushed with saline solution and the irrigation solution is introduced through one tube while the other
tube is connected to low pressure suction. Various irrigating
solutions can be used often containing antibiotics, wetting
agents and proteolytic enzymes.
Antibiotics in high concentration also may be placed in
direct contact with the bone manually or with an implantable
pump.
Tobramycin or gentamicin is contained in acrylic resin
bone cement beads. Impregnated chains of beads are useful,
especially in chronically infected bone associated with fractures and in chronic sclerosing osteomyelitis refractory to
systemic antibiotics. The beads and drain are left in place
1014 days and then removed through a small incision.
Hyperbaric oxygen (HBO) therapy has been used to promote healing in refractory chronic osteomyelitis.
In the acute stage, surgery should be limited to removal
of severely loose teeth and bone fragments and incision,
drainage of uctuant areas. Deeply located or extensive
abscesses may require treatment with the patient under
general anesthesia.
Sequestrectomy Sequestra can be cortical, cancellous or
cortical-cancellous and generally are not seen until at
least 2 weeks after the onset of infection. These can persist
for several months. In the chronic state, the involucrum or
shell of bone produced by the periosteum may be perforated by tracts (cloacae) through which the pus escapes to
epithelial surfaces. Sequestra are avascular, so are poorly
penetrated by antibiotics.
Once the sequestra are formed, they can be removed
with a minimum of surgical trauma.
Saucerization Saucerization is the unroofing of the bone
to expose the medullary cavity for thorough debridement.
Saucerization is useful in chronic osteomyelitis because it
permits removal of formed and forming sequestra. The procedure can be done after resolution of the acute phase. This
decompresses the bone to allow ready extrusion of pus, debris
and avascular fragments. The patient is more comfortable.
Decortication This refers to removal of chronically
infected cortex of bone. Once the disease is in its subacute or
chronic stage, use of decortication promotes resolution based
on the premise that the affected bone is avascular and harbors microorganisms. This can be used as initial treatment
of primary and secondary chronic osteomyelitis, or when
initial regimens have failed.
Resection and reconstruction Resection of osteomyelitic
area with immediate or delayed reconstruction may be
436

necessary to resolve low-grade persistent chronic osteomyelitis. Using an extraoral approach bone is debrided
until bleeding surfaces are encountered distally and proximally. Single or multiple blocks of autologous corticocancellous bone grafts are placed for immediate reconstruction.

Infantile Osteomyelitis
Infantile osteomyelitis usually occurs few weeks after
birth and generally involves the maxilla. This uncommon
condition involves risks with ocular, intracranial spread
and facial deformities.
It is believed to occur by hematogeneous route or from
perinatal trauma.
Generalized symptoms include fever, irritability, malaise, anorexia, dehydration and even convulsions and
vomiting.
Facial cellulitis is seen centered about the orbit associated
with inner and outer canthal swelling, palpebral edema, closure of the eye and proptosis. Purulent discharge from the
nose and the medial canthus may be evident.

Chronic Focal Sclerosing Osteomyelitis


(Condensing Osteomyelitis or Osteitis)
Condensing osteitis is a focal sclerosing form of osteomyelitis that occurs in very mild infection (microorganisms
of low virulence) or when the host immunity is at its
peak.
The bone reacts unusually to infection by laying down
bone rather than getting destructed. In individuals with
high tissue resistance, the infection acts as a stimulant
thereby resulting in proliferation of the tissue.
Clinical and radiographic features
Condensing osteitis is generally seen in young adults. The
mandibular first molars are most commonly affected. The
tooth in question presents with a deep carious lesion. Patients
may either present with mild pain or may occasionally be
asymptomatic.
Radiographic evaluation will reveal a deep carious
lesion approximating pulp with a well-dened radiopacity
at the periapex of one or more roots. The root outline is
usually sharply dened and visible. The boundaries of the
periapical radiopacity may appear well circumscribed or
occasionally blend with the surrounding bone.
Management
As condensing osteitis is an extension of pulpal infection
beyond the periapex of the tooth, endodontic treatment or
extraction is the only treatment option.
Eliasson et al (1984) studied the effectiveness of endodontic treatment for periapical condensing osteitis on

Chapter 15 Dental Caries, Pulp and Periapical Lesions

49 roots of 36 teeth. These patients were followed up by


means of radiographs and patient les after endodontic
treatment for a mean observation period of 4.3 years.
Their study showed that there was total regression of
periapical condensing osteitis on 36 of the 49 roots. No
condensing osteitis showed progress. They concluded that
there was rebuilding of bone structures to normal appearance after endodontic treatment of periapical condensing
osteitis.
Following extraction of the affected tooth the residual
dense bone may be remodeled. However, on occasions,
this residual sclerotic bone may remain unaltered for
many years and referred to as a bone scar.

Chronic Diffuse Sclerosing Osteomyelitis


The diffuse form of sclerosing osteomyelitis is also a proliferative response to a generalized form of mild infection.
However, a distinct difference between the diffuse form and
the focal form is that the former occurs due to an extension of a diffuse periodontal disease.
Clinical features
The diffuse sclerosing form may occur at any age. However,
it is usually seen in edentulous areas of the mandible in elderly
individuals. The disease progresses in an insidious manner
and seldom presents clinical signs and symptoms.
The chronic phase of the condition may exhibit periods
of acute exacerbation that manifests as vague pain, bad
taste, minimal suppuration and stulous tracts that may
open intraorally.
This may occur at any age, but is most common in older
persons, especially in edentulous areas. The disease is often
of an insidious nature so usually presents no clinical features.
In case of acute exacerbation there can be mild suppuration,
many times with stulous opening. In such cases, there can
be vague pain and bad taste in the mouth.
Montonen et al (2006) conducted an immunohistopathological study of diffuse sclerosing osteomyelitis in the
clinically acute and subacute phases and compared it with
healthy bone. They found that the receptor activator of nuclear
factor kappa B ligand (RANKL) was found in the lesions of
diffuse sclerosing osteomyelitis. They also observed that
the periods of acute exacerbations were characterized by
RANKL and induction of cathepsin K in mononuclear precursor cells, which subsequently seemed to differentiate
into osteoclasts or foreign body giant cells. The proportion
of bone to soft tissue increased with the duration of
disease. They concluded that RANKL-driven osteoclastogenesis and acidic cysteine endoproteinase cathepsin K
seemed to play important roles in diffuse sclerosing osteomyelitis as osteoclast-mediated bone resorption may represent the primary disease process later followed by new
bone formation.

Radiographic features
Radiographs reveal diffuse sclerotic patchy cotton-wool
appearance of bone. Extensive involvement of the mandible bilaterally and occasionally the maxilla and mandible may be affected. The borders of the patchy sclerosis are
diffuse and cannot be differentiated from the surrounding
normal bone (Figure 37).
Management
Owing to the extensive bone involvement surgical management is not indicated. In some patients the resolution
of the causative periodontal disease results in improvement
of this condition. However, antibiotics have been employed
to combat periods of acute exacerbations.

Periostitis Ossificans
(Chronic Osteomyelitis with Proliferative Periostitis)
Wood et al (1988) in their two part series of articles titled
Periostitis ossificans versus Garrs osteomyelitis. Part I.
What did Garr really say? and Periostitis ossificans versus Garrs osteomyelitis. Part II. Radiologic analysis of
93 cases in the jaws, described their opinions and observations on the use of the terms Garrs osteomyelitis and
periostitis ossificans.
1.

2.

3.

4.

The name Garr is correctly written as Garr and not


Garr as mentioned in many textbooks and articles in
scientific literature.
Garr did not describe the typical radiologic, histologic and bacteriologic features if acute osteomyelitis
since these investigative aids were not available to
him (X-rays were discovered by Rntgen only 2 years
after Garr published his article in 1893.
Chronic sclerosing osteomyelitis was never really outlined by Garr. He described recalcitrant osteomyelitis, which was essentially untreatable at that time.
The term Garrs osteomyelitis should not be used.

Gorman is given the credit for using the term periostitis ossificans in 1951 to describe a productive inflammatory condition of the mandibular periosteum. Lovemann (1941)
was probably the first to recognize the condition.
Tong et al (2006) reported a case of osteomyelitis with
proliferative periostitis. The authors believe that the term
chronic osteomyelitis with proliferative periostitis is the
most accurate description of periostitis ossicans.
Nortj et al (1988) conducted a radiological analysis
of 93 cases of periostitis ossicans occurring in the jaws.
In their study, the age at initial consultation ranged from
2 to 69 years with a mean of 13.3 years. Males were more
commonly affected than females (1.27:1). The causes
for periostitis ossicans were due to periapical lesions
437

Section VI Teeth and Periodontium

Figure 37

Orthopantomograph showing diffuse sclerosis of the mandible giving rise to cotton-wool appearance.
Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

secondary to dental caries, untreated fractures and primary tuberculosis of the mandible. Two patients in their
study had lateral inammatory odontogenic cysts.
The mandibular left rst molar was most commonly
involved. The other sites involved were mandibular second
molar, mandibular premolar, mandibular primary second
molar, angle of the mandible, mandibular third molar and
maxillary premolar.
The periosteal reaction was visible at the buccal, lingual
and inferior aspects of the mandibular body. The authors
also reported of periosteal reaction occurring in the maxilla and sigmoid notch. In their study, the number of the
periosteal laminations ranged from 1 to 12. The size of most
of the sequestra ranged from 1 to 2 mm. Larger sequestra
were seen in patients with infected fractures. The size of
the sequestra was age dependent with smaller sequestra
present in younger patients (Figure 38).
In about 63% of their patients, follicles of unerupted teeth
adjacent to the site of periostitis showed destruction. Other
changes that were noted included supraeruption of teeth,
bodily movement of unerupted tooth bud and widening of
the periodontal ligament space of the teeth inciting the
infection and occasionally of the adjacent vital teeth.
The periosteal reaction can either occur as long, narrow
periosteal reaction (common in adults) or fusiform, short and
wide periosteal reaction (seen in children).
When X-ray beams interact with successive layers of
periosteal new bone on the buccal cortical plate, they get
attenuated and the resultant image will show a patchy or
granular radiopacity in the body of the mandible on lateral projections (Figure 39A, B).
Periostitis occurring in the maxilla has been referred to
as halo-shadow, which results from periosteal stripping
and subsequent bone formation in the oor of the maxillary sinus related to a rst molar tooth.
438

Figure 38

Illustration showing formation of periosteal new bone

Radiographic investigations
Nortj et al (1988) recommended the use of lateral oblique
and panoramic radiographs (lateral radiographs) to demonstrate the periosteal reaction. If the periosteal reaction is not
evident on lateral radiographs, occlusal radiographs have to

Chapter 15 Dental Caries, Pulp and Periapical Lesions

Figure 39

Periosteal
new bone

X-rays

Patchy
radiopacity

Illustration showing the appearance of granular radiopacity in the body of the mandible on lateral projections

Figure 40

been noted. Although the incidence appears to be low


(0.21.5%) the occurrence of neoplastic disease considerably complicates the resolution of inflammatory process.
There can be surgically induced discontinuity defects,
necessitating jaw reconstruction.
Anachorectic pulpitis
Bacterial infection of an intact pulp is referred to as
anachorectic pulpitis. It is suggested that the bacteria in
the circulation may tend to affect inflamed pulp. The
tooth in question is not necessarily carious.
Focal reversible pulpitis or pulp hyperemia
It is a reversible, transient pulpitis caused due to irritation of the pulpal terminal of the dentinal tubules upon
application of thermal stimulus (especially cold stimulus). However, the pain subsides on removal of the
irritant.
Chronic hyperplastic pulpitis

Pulp polyp. Courtesy: Department of Oral Medicine and


Radiology. KLE Societys Institute of Dental Sciences,
Bangalore

be employed. The authors suggest that the posteroanterior


view of the mandible is occasionally the only radiograph that
will adequately show the periosteal reaction.
Complications of osteomyelitis
With chronic osteomyelitis, neoplastic conversion of
inflammatory metaplasia to squamous cell carcinoma has

It is an excessive exuberant proliferation of a longstanding inflamed dental pulp. Usually affects teeth
with large carious lesions. Commonly seen in children
and young adults and often associated with the primary or permanent first molars.
Clinically it appears as red to pink mass of tissue protruding from the pulp into the large open cavity of the
carious tooth (Figure 40).
There can be progressive, diffuse sclerosis of the medullary
and cortical portions of the maxillofacial skeleton, especially
mandible, over time.

439

CHAPTER

16

Gingival and Periodontal


Diseases
Praveen BN, Jeeth Rai, Francisco Lopez
Sanchez

Classification System in Periodontal Disease

Plaque Microbiology
Organisms in Various Periodontal Diseases

Periodontal diseases range from simple and early inflammation of marginal gingiva to advanced gingivitis and
subsequently periodontitis. A good classification system is
crucial in identifying and differentiating the various kinds
of periodontal diseases.
Periodontal disease classication is useful to help
establish diagnosis, determine prognosis and facilitate
treatment planning.
Different classication systems of periodontal diseases
have been used for years and also replaced by newer classication systems as the knowledge of understanding
microbiology, etiology, pathogenesis and host response
have improved vastly over the past few decades.
Currently, the most accepted classication is the 1999
World Workshop Classication System.

CLASSIFICATION SYSTEM IN PERIODONTAL


DISEASE
The classification is based on the 1999 International Workshop for Periodontal Disease.

Periodontal Diseases
Local Contributing Factors
Iatrogenic Factors

HostMicrobial Interaction
Defense Mechanism
Plaque-induced Gingivitis
Non-plaque-induced Gingivitis
Gingival Diseases Associated with Medications
Gingival Diseases Associated with Systemic Diseases
Gingival Diseases Associated with Malnutrition
Gingival Diseases Associated with Heredity
Gingival Diseases Associated with Ulcerative Lesions
Gingival Lesions Manifested in Childhood Diseases
Gingival Lesions Associated with Chicken Pox

440

Gingival Lesions Associated with Mononucleosis


Acute Inflammatory Gingival Enlargement
Gingival Changes Associated with Tooth Eruption

Gingival Diseases

Syndromes
Hormonal Factors

Sex Hormones

Stress and Psychosomatic Factors

Nutritional Factors
Effects of Vitamin Deficiency

Radiographic Evaluation of Periodontal


Diseases

I. Gingival diseases
A. Dental plaque-induced gingival diseases: These diseases
may occur on a periodontium with no attachment loss
or on one with attachment loss that is stable and not
progressing.
1. Gingivitis associated with dental plaque only
a. Without local contributing factors
b. With local contributing factors
2. Gingival diseases modified by systemic factors
a. Associated with endocrine system
i. Puberty-associated gingivitis
ii. Menstrual cycle-associated gingivitis
iii. Pregnancy-associated gingivitis and pyogenic
granuloma
iv. Diabetes mellitus-associated gingivitis
b. Associated with blood dyscrasias
i. Leukemia-associated gingivitis
ii. Others
3. Gingival diseases modified by medications
a. Drug-influenced gingival diseases
b. Drug-influenced enlargements
c. Drug-influenced gingivitis

Chapter 16 Gingival and Periodontal Diseases

B.

d. Oral contraceptive-associated gingivitis


e. Others
4. Gingival diseases modified by malnutrition
a. Ascorbic acid deficiency gingivitis
b. Others
Non-plaque-induced gingival lesions
1. Gingival diseases of specific bacterial origin
a. Neisseria gonorrhoeae
b. Treponema pallidum
c. Streptococcal species
d. Others
2. Gingival diseases of viral origin
a. Herpes virus infections
i. Primary herpetic gingivostomatitis
ii. Recurrent oral herpes
iii. Varicella zoster
b. Others
3. Gingival diseases of fungal origin
a. Candida species infectionsgeneralized gingival
candidiasis
b. Linear gingival erythema (LGE)
c. Histoplasmosis
d. Others
4. Gingival lesions of genetic origin
a. Hereditary gingival fibromatosis
b. Others
5. Gingival manifestations of systemic conditions
a. Mucocutaneous lesions
i. Lichen planus
Pemphigoid
Pemphigus vulgaris
Erythema multiforme
Lupus erythematosus
Drug-induced
Others
b. Allergic reactions
i. Dental restorative materials
Mercury
Nickel
Acrylic
Others
ii. Reactions attributed to
Toothpastes or dentifrices
Mouthrinses or mouthwashes
Chewing gum additives
Foods and additives
iii. Others
6. Traumatic lesions (factitious, iatrogenic or accidental)
a. Chemical injury
b. Physical injury
c. Thermal injury
7. Foreign body reactions
8. Not otherwise specified

II.

Chronic periodontitis
A. Localized (less than 30% of sites involved)
B. Generalized (more than 30% of sites involved)
C. Slight (12 mm clinical attachment loss)
D. Moderate (34 mm clinical attachment loss)
E. Severe (more than 5 mm clinical attachment loss)

III. Aggressive periodontitis


A. Localizedslight, moderate or severe
B. Generalized
IV. Periodontitis as a manifestation of systemic diseases
A. Associated with hematological disorders
1. Acquired neutropenia
2. Leukemias
3. Others
B. Associated with genetic disorders
1. Familial and cyclic neutropenia
2. Downs syndrome
3. Leukocyte adhesion deficiency syndromes
4. PapillonLefevre syndrome
5. ChediakHigashi syndrome
6. Histocytosis syndrome
7. Glycogen storage disease
8. Infantile genetic agranulocytosis
9. Cohen syndrome
10. EhlersDanlos syndrome (types IV and VIII)
11. Hypophosphatasia
12. Others
V.

Necrotizing periodontal diseases


A. Necrotizing ulcerative gingivitis (NUG)
B. Necrotizing ulcerative periodontitis (NUP)

VI. Abscess of the periodontium


A. Gingival abscess
B. Periodontal abscess
C. Pericoronal abscess
VII. Periodontitis associated with endodontic lesions
A. Combined periodonticendodontic lesions
VIII. Developmental or acquired deformities and conditions
A. Localized tooth-related factors that modify or
predispose to plaque-induced gingival diseases/
periodontitis
i. Tooth anatomic factors
ii. Dental restorations/appliances
iii. Root fractures
iv. Cervical root resorption and cemental rear
B. Mucogingival deformities and conditions around
teeth
i. Gingival/soft tissue recession, facial or lingual surfaces, interproximal (papillary)
ii. Lack of keratinized gingiva
iii. Decreased vestibular depth
iv. Aberrant frenum/muscle position

441

Section VI Teeth and Periodontium

v. Gingival excess
Pseudopocket
Inconsistent gingival display
Excessive gingival display
Gingival enlargement
vi. Abnormal color
C. Mucogingival deformities and conditions on edentulous ridges
i. Vertical and/or horizontal ridge deficiency
ii. Lack of gingival/keratinized tissue
iii. Gingival/soft tissue enlargement
iv. Aberrant frenum/muscle position
v. Decreased vestibular depth
vi. Abnormal color
D. Occlusal trauma
i. Primary occlusal trauma.
The current classification has many changes seen which is
drastically different from the previous classifications. The
most noticeable change is that periodontitis is now classified based on the rate of progression of the disease and not
on the age of onset.
Adult periodontitischronic periodontitis
The term adult periodontitis is discarded since this
form of periodontitis is seen in wide range of ages and
found both in primary and permanent dentitions. Hence,
the term chronic periodontitis was chosen because it does
not reflect the age of individual rather reflects the rate
of progression of periodontal disease, which is slow in
nature.
Early onset forms of periodontitisaggressive
periodontitis
The term early onset periodontitis has been discarded as
this form of periodontitis is seen in various ages and in
older individuals too. Thus, the term aggressive periodontitis was chosen. Progressive periodontal disease can be
either localized or generalized. The term localized aggressive periodontitis replaces localized juvenile or localized
early onset periodontitis. The term generalized aggressive
periodontitis replaces generalized juvenile or generalized
early onset periodontitis. The term pre-pubertal periodontitis has been discarded and is currently described as
localized or generalized periodontitis or periodontitis as
manifestations of systemic disease.

Necrotizing forms of periodontitis


Necrotizing ulcerative gingivitis (NUG) and NUP are now
collectively referred to as necrotizing periodontal disease.
NUG and NUP are different stages of same infection and
should not be classified as separate disease entities.

GINGIVAL DISEASES
Increasing evidence indicates that gingivitis is not a single
disease, but an assortment of diseases that are the end result
of a variety of different processes. Inflammation of gingiva by bacteria is most common, but pathological changes
in the gingiva can also result from systemic conditions
(e.g. puberty), drugs (e.g. amlodipine) and neoplasms (e.g.
leukemia). Hence, any disease that primarily affects gingival
tissues should be primarily classified as a gingival disease.
The gingival diseases associated with children, adolescents and young adults have several common characteristics.
Universal features include clinical signs of inammation,
signs and symptoms that are conned to the gingiva,
reversibility of the disease on removal of the etiology, and
the presence of microbial plaque to initiate or exacerbate
the severity of the lesion.

Plaque Microbiology
Oral cavity can be regarded as a single microbial ecosystem or macroenvironment because the colonization of oral
cavity starts at the time of birth. Within hours of birth the
sterile oral cavity gets colonized by facultative and aerobic bacteria, which will be followed by anaerobic bacteria
by 2nd day. By 2 years of age there will be around 400
different kinds of bacteria. After tooth eruption, a more
complex oral flora is established. However, all these species are seen to be living in harmony with the host. But,
however, there is an imbalance in this relationship between
the host and microorganisms, disease prevails which is
controlled by various other factors.
Oral environment is dominated with saliva, which is very
complex in composition. Although saliva is not a good
medium for supporting the growth of bacteria, it is likely that
organisms shed from intraoral reservoirs nd transient
residence in saliva. Oral cavity provides two types of surfaces
for colonizationsoft and hard tissue (teeth)main difference
being soft tissue desquamation; hence the colonies are shed
frequently whereas the hard surface provides a solid medium
for the bacteria to adhere and develop complex layers.

Systemic diseases and forms of periodontitis


The present classification system highlights the role of certain systemic conditions like smoking and diabetes that
can modify periodontitis and that certain systemic conditions that can cause destruction of periodontium such as
neutropenia and leukemias.
442

Terminology
Dental plaque: Dental plaque is clinically defined as a
structural resilient yellow-grayish substance that adheres
tenaciously to the intraoral hard surfaces, including
removable and fixed restoration.

Chapter 16 Gingival and Periodontal Diseases

Biofilm: Biofilm is the term that describes the relatively


indescribable microbial community associated with tooth
surface or any other hard non-shedding material.
Materia alba: Materia alba refers to soft accumulation of
bacteria and tissues cells that lack the organized structure
of dental plaque and is easily displaced with a water spray.

e.
f.
5.

Generalized aggressive
a. F. nucleatum
b. Lactobacillus
c. Eubacterium
d. A. naeslundii
e. A. actinomycetemcomitans
B. forsythus
P. gingivalis
Campylobacter

6.

NUG/NUP
a. P. intermedia
b. Fusobacterium
c. F. nucleatum
d. P. gingivalis

7.

Periodontal abscess
a. F. nucleatum
b. P. micros
c. P. intermedia
d. P. gingivalis
e. B. forsythus.

Formation of plaque
It is a complex procedure initially involving the formation
of pellicle (glycoprotein, phosphoproteins) around the tooth
surface. Then the early bacterial colonization takes place
with facultative aerobic gram-positive organisms. Some of
the early colonizers are Actinomyces and Streptococcus
sanguis which adhere to the pellicle through adhesins.
Later plaque maturation takes place with co-aggregation
of secondary colonizers including Fusobacterium nucleatum, Prevotella intermedia, Porphyromonas gingivalis,
Capnocytophaga, etc. Thus in maturation of plaque there
is a transition from the early aerobic gram-positive facultative species to an anaerobic gram-negative species.

Organisms in Various Periodontal Diseases


1.

Periodontal health
a. Streptococcus
b. Actinomyces
c. Veillonella
d. Fusobacterium

2.

Gingivitis
a. Streptococcus
b. Actinomyces
c. Peptostreptococcus
d. Eubacterium
e. Capnocytophaga
f. Fusobacterium
g. Veillonella

3.

Chronic periodontitis
a. Streptococcus
b. Peptostreptococcus
c. Eubacterium
d. Actinomyces
e. Lactobacillus
f. P. gingivalis
g. Campylobacter rectus
h. F. nucleatum
i. Selenomonas
j. Actinobacillus actinomycetemcomitans
k. Eikenella corrodens

4.

Localized aggressive
a. A. actinomycetemcomitans
b. Eubacterium
c. A. naeslundii
d. F. nucleatum

C. rectus
Veillonella

HOSTMICROBIAL INTERACTION
Health is not a static condition, it is a dynamic state in which
the living and functioning individuals remain in balance
with a constantly changing environment. These changes
in environment also cause changes in tissue activity so that
normal function can continue, a process known as homeostasis. If the environmental changes over-ride this homeostasis, the normal function cannot continue and this change
is termed as disease.

Defense Mechanism
These protect the body from attack from microorganisms
and can be classified as:

Non-specific mechanism
Specific mechanism.

Non-specific mechanisms

Bacterial balances
Surface integrity
Surface fluid and enzymes
Inflammatory reaction
Neutrophil and macrophage activity.

Specific mechanisms

T-cell response (cell-mediated immune system)


B-cell response (antibody-mediated immune system).
443

Section VI Teeth and Periodontium

Plaque bacteria produce a number of factors (virulence factor), which causes disease directly, or individually by stimulating the immune and inflammatory system. It is now
known that individuals prone to periodontal disease have
an aberrant immune inflammatory response to plaque which
is genetically determined.

Direct effects of bacteria


A. Evasion of host defense
i. Direct damage to polymorphonuclear leukocytes (PMNs) and macrophages
ii. Reduced PMN chemotaxis
iii. Degradation of immunoglobulins
iii. Modulation of cytokine function
iv. Degradation of fibrin
v. Altered lymphocyte function
B. Damage to crevicular epithelium
i. Production of volatile sulfur compounds
C. Degradation of periodontal tissues by bacterial
enzymes
i. Proteolytic enzymes
ii. Hydrolytic enzymes
Indirect effects of bacteria
i. Inflammation
ii. Production of reactive oxygen species
iii. Immunity
iv. Production of cytokines and prostaglandins
v. Production of matrix metalloproteinases (MMPs).
Host modulation: Periodontal disease is multifactorial in
nature as a result of interaction between plaque microorganism and host responses. Host modulation refers to the
alteration/modification of host response to the microbial
stimulus by the use of number of medications. The two
major categories are NSAIDs and inhibition of MMPs.

Plaque-induced Gingivitis
It is the inflammation of gingiva which results from the bacteria located at the gingival margin. The association of plaque
with gingival inflammation made it a frequently postulated
cause of gingivitis. The initial histologic changes from health
to plaque-induced gingivitis may not be evident clinically
(Page and Shroeder, 1976; Bimstein et al, 1985) but as
gingivitis progresses, clinical signs becomes more obvious.
Plaque-induced gingivitis begins at the gingival margin
and can spread into the deeper gingival component.
Clinical signs of gingival inammation involve the change
in color, contour, size, shape, consistency and surface texture are associated with a stable periodontium which exhibits no loss of periodontal attachment or alveolar bone. The
classic clinical indicators of signs of inammation are bleeding on probing and color change from pink/coral pink to
reddish pink or erythematous gingiva. In children, gingivitis is not intense as that found in young adults with similar
quantity of accumulation of dental plaque (Mattson and
Goldberg, 1985).
In the initial and established stages of gingivitis, dental
plaque is predominantly comprised of gram-positive aerobic
microorganisms including Streptococcus mitis, S. sanguis,
Actinomyces viscosus, A. naeslundii and Eubacterium spp.
As age advances, development and severity of gingivitis is
mainly dependent on the quality of the plaque rather than
the quantity and the other contributing factors like the host
immune response, environmental, genetic and the behavioral factors. The common clinical signs and symptoms of
gingivitis include redness, edema, bleeding on probing,
tenderness and enlargement (Loe et al, 1965; Suzuki, 1988)
(Figure 1).
Radiographically no changes will be seen as the inammation is conned only to the gingival sulcus. Histologic

NSAIDs
Prostaglandin E2 (PGE2), a product of cyclooxygenase pathway has been shown to increase the amount of alveolar bone
destruction by amplifying local inflammation. NSAIDs block
COX pathway thus decreasing PGE2 synthesis. A number of
NSAIDs have been used including ibuprofen, flurbiprofen,
indomethacin, ketoprofen and naproxen.

Figure 1

Matrix metalloproteinases
Matrix metalloproteinases are a family of proteolytic
enzymes secreted by a number of cells including leukocytes, epithelial connective tissue cells whose primary function is degradation of extra-cellular matrix components.
Tetracycline and other drugs of the same group show to
inhibit the MMPs production from the host, primarily the
neutrophil MMPs. In doing so they increase host resistance
to connective tissue destruction forms of tetracycline are
submicrobial dose of tetracycline/doxycycline and chemically modified tetracycline.
444

Edematous gingival margin associated with gingivitis.


Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

Chapter 16 Gingival and Periodontal Diseases

changes include proliferation of basal junctional epithelium leading to apical and lateral cell migration, vascular
dilatation and vasculitis of blood vessels adjacent to
the junctional epithelium, progressive destruction of collagen bers, cytopathologic alteration of resident broblasts and progressive inammatory cell inltrate (Page
and Shroeder, 1976).

Non-plaque-induced Gingivitis
Gingival diseases associated with endogenous
sex steroid hormones
Since the 19th century, evidence suggests that the tissues of
the periodontium are modulated by androgens, estrogens and
progesterone. Much of this evidence has come from observing
the changes in gingival tissues during distinct endocrinologic events (puberty, menstrual cycle, pregnancy, etc.).
The principal explanation for sex steroid hormoneinduced changes in the gingiva has pointed to changes of
microbiota in dental plaque, immune function, vascular
properties and cellular function in the gingiva. Sex steroid
hormones will affect the host by inuencing cellular function (in the blood vessels, the epithelium and the connective
tissue) and immune function, and together with hormoneselected bacterial populations occupying the gingival sulcus,
induce specic observable changes in gingival tissues
(Mariotti, 1994).
Puberty-associated gingivitis
Puberty is not a single episode but a complex process of
endocrinological events that produce changes in the physical appearance and behavior of adolescents. Average age
of menarche is 1213 years. The early onset of puberty, particularly for adolescent girls, increases the time of exposure
of periodontal tissues to steroid hormones and the possibility
of gingival disease.
The incidence and severity of gingivitis in adolescents
are inuenced by a variety of factors, including plaque levels, dental caries, mouth breathing, crowding of teeth and
tooth eruption (Stamm, 1986). A number of studies have
demonstrated an increase in gingival inammation in circumpubertal individuals of both sexes without a concomitant increase in plaque levels (Sutcliffe, 1972; Hefti et al,
1981). Although puberty-associated gingivitis has many
of the clinical features of plaque-induced gingivitis, this
disease will develop frank signs of gingival inammation
in the presence of relatively small amounts of local irritants
(plaque) during the circumpubertal period.

changes in the gingiva have been observed (Muhlemann,


1948). However, the number of women who exhibit overt
gingival changes fluctuating in conjunction with the menstrual cycle is small (Marriotti, 1994). The most common
gingival changes involve minor signs of inflammation during ovulation. More specifically, gingival exudates have
been shown to increase at least 20% during ovulation in
more than three-fourths of women tested (Hugoson, 1971).
Since these changes in crevicular fluid flow are not observable unless measured electronically, most young women
with gingival inflammation-induced by menstrual cycle
will present with a very mild form of the disease.
Pregnancy-associated gingival disease
Some of the most remarkable endocrine and oral alterations
accompany pregnancy as a result of the rise in plasma
hormone levels over several months. During human gestation, pregnancy-associated gingivitis is characterized by
an increase in the prevalence and severity of gingivitis
during the second and third trimesters (Loe and Silness,
1963; Hugoson, 1971). In spite of the same plaque scores,
gingival inflammation is significantly higher during pregnancy than postpartum. In addition, gingival probing depths
are higher and bleeding on probing or toothbrushing is
increased (Miyazaki et al, 1991), and gingival crevicular
fluid flow is elevated in pregnant women.
Clinical features of pregnancy-associated gingivitis is
similar to that of plaque-induced gingivitis, except for the
propensity to develop frank signs of gingival inammation
in the presence relatively little local irritation by plaque
during pregnancy.
Pregnancy tumor
Pregnancy-associated pyogenic granuloma or pregnancy
tumor was described over a century ago (Coles, 1874). The
pregnancy-associated pyogenic granuloma is not a tumor
but an exaggerated inflammatory response during pregnancy
to an irritation resulting in a solitary polypoid capillary hemangioma which can easily bleed on mild provocation (Sillis
et al, 1996). These granulomas present clinically as a painless, protuberant, mushroom-like exophytic mass attached
by a sessile or pedunculated base arising from the gingival
margin or more commonly from an interproximal papilla.
It is more common in the maxilla and may develop as early
as first trimester ultimately regressing or completely disappearing following parturition (Ziskin and Nesse, 1946).

Gingival Diseases Associated with Medications


Menstrual cycle-associated gingivitis
Following menarche, there is a periodicity of sex steroid
hormone secretion over a 2530 days periodthe menstrual
cycleduring which clinically significant inflammatory

The use of chemical for the benefit of human beings has


led to an astonishing array of drugs for the alleviation of
human afflictions as well as the creation of new maladies
that affect the gingiva.
445

Section VI Teeth and Periodontium

Drug-induced gingival enlargement

Phenytoin

The disfiguring overgrowth of gingiva is a significant outcome principally associated with antiepileptic drugs such as
phenytoin sodium, immunosuppressors such as cyclosporine and calcium channel blockers such as nifedipine, amlodipine, verapamil, diltiazem and sodium valproate (Hassel
and Hefti, 1991; Seymour et al, 1996).
Most common clinical features seen in drug-induced
gingival enlargement are as follows:

The first reported case of phenytoin-induced gingival


enlargement was reported by Kimball (1939). Phenytoin is
indicated in treatment of epileptic seizures. Phenytoin
induces gingival enlargements in approximately 50% of
patients (Angelopoulos and Goaz, 1972) (Figure 2A, B). One
prominent theory of the etiology of phenytoin-associated
gingival enlargements suggests that the growth of genetically distinct populations of gingival fibroblasts results
in the accumulation of connective tissues because of
reduced catabolism of the collagen molecule (Hassel and
Hefti, 1991).

Individual variations in the pattern of gingival


enlargement, i.e. genetic predisposition (Hassel and
Hefti, 1991; Seymour et al, 1996).
A tendency to occur more in the anterior gingiva.
A higher prevalence rate in younger age groups.
Onset within 3 months of usage of the medication,
usually involves the interdental papilla.
Usually manifests as bead-like enlargement of the
papilla and marginal gingiva, and in severe cases
gingival enlargement covers major portion of the
teeth and thereby interfere in occlusion, which is a
rare entity.
Although the condition can be found in a periodontium with or without bone loss, there is no association
with attachment loss or tooth mortality.

Furthermore, all of these drugs produce clinical lesions


and histological characteristics that are indistinguishable
from one another (Hassel and Hefti, 1991; Seymour et al,
1996). Finally, the influence of plaque on the induction of
gingival enlargement by drugs in humans has not been
fully elucidated (Hassel and Hefti, 1991); however, it does
appear that severity of the lesion is affected by the oral
hygiene of the patient.

Calcium channel blockers (Figure 3A, B)


Calcium channel blockers are a class of drugs that exert
their effects principally at voltage-gated Ca channels
located in the plasma membrane, and are commonly prescribed as antihypertensive, antiarrhythmic and antianginal agents. In 1984, calcium channel blockers were first
linked to gingival enlargements (Ramon et al, 1984) and
the prevalence of gingival lesions associated with these
drugs has been estimated to be approximately 20%
(Barclay et al, 1992). The mechanism of gingival enlargement is still under investigation, but these drugs may
directly influence the gingival connective tissues by stimulating an increase of gingival fibroblasts as well as an
increase in the production of connective tissue matrix
(Fu et al, 1998).
Cyclosporine
Cyclosporine is a powerful immunoregulating drug used
primarily in the prevention of organ transplant rejection

Figure 2
A

Enlargement of the labial and palatal aspects of the gingiva in patients using phenytoin sodium.
Gingival enlargement leads to the formation of pseudopockets. Courtesy: Dr Francisco, Mexico

446

Chapter 16 Gingival and Periodontal Diseases

Figure 3
A

Enlargement of the labial and palatal aspects of the gingiva in a patient on nifedipine. Courtesy: Dr Francisco, Mexico

(Seymour and Jacobs, 1992). The clinical features of


cyclosporine-induced gingival enlargement were first
described in 1983 (Rateitschak-Pluss et al, 1983). The drug
appears to affect 2530% of the patients taking this medication (Hassel and Hefti, 1991; Seymour et al, 1987).
Hypotheses explaining why cyclosporine affects the gingiva are diverse; but a leading theory suggests that the
principal metabolite of cyclosporine, hydroxycyclosporine
(M-17), in conjunction with the parent compound stimulates fibroblast proliferation (Mariotti et al, 1988). The
increase in cell number coupled with a reduction in the
breakdown of gingival connective tissues (Hassel and Hefti,
1991) has been postulated to be the cause of excessive
extracellular matrix accumulation in cyclosporine-associated gingival enlargements (Figure 4A, B).
Oral contraceptive-associated gingivitis
Oral contraceptive agents are one of the most widely used
classes of drugs across the globe. The earlier onset of menarche, changing social mores and increased emphasis on
family planning has increased the use of oral contraceptives in younger age groups. Case reports have described
gingival enlargement induced by oral contraceptives in otherwise healthy women with no history of gingival overgrowth (Lynn, 1967; Kaufman, 1969; Sperber, 1969); in all
cases, the increased gingival mass was reversed when oral
contraceptive was discontinued or the dosage was reduced.
Clinical studies have demonstrated that women using hormonal contraceptive drugs have a higher incidence of gingival inflammation than women who do not use these
agents (Lindhe and Bjorn, 1967; El-Ahisry et al, 1970;
Pankhurst et al, 1981) and that long-term use of oral contraceptives may affect periodontal attachment levels (Knight
and Wade, 1974). All studies recording changes to gingival

tissues by oral contraceptives were completed when dosage


levels were much higher than today. A recent clinical study
in young women found that oral contraception had no
effect on gingival tissues (Marrioti et al, 2000). It appears
that current oral contraceptives are probably not as harmful to the periodontium as the early formulations.

Gingival Diseases Associated with Systemic


Diseases
Leukemia-associated gingivitis
Leukemia is a progressive, malignant hematological disorder characterized by an abnormal proliferation and development of leukocytes and precursors of leukocytes in the
blood and bone marrow. Leukemia is classified according
to its duration (acute or chronic) and the type of cell
involved (myeloid or lymphoid) and the number of cells in
the blood (leukemic or aleukemic). There are noticeable correlations of leukemias with age. For example, acute lymphoblastic leukemia constitutes 80% of all childhood
leukemias, whereas acute myelogenous leukemia usually
affects the adults. Oral manifestations have primarily been
described in acute leukemias; they consist of cervical adenopathy, petechiae and mucosal ulcers as well as gingival
inflammation and enlargement (Lynch and Ship, 1967).
Signs of inammation in the gingiva include swollen,
glazed and spongy tissues which are red to deep purple in
appearance (Dreizen et al, 1984). Gingival bleeding is a
common sign in patients with leukemia and is the initial
oral sign or symptom in 17.7% and 4.4% of patients with
acute and chronic leukemias (Lynch and Ship, 1967).
Gingival enlargement has also been reported initially
beginning at the interdental papilla and followed by the
marginal and attached gingiva. Although local irritants
447

Section VI Teeth and Periodontium

Figure 4
B

Cyclosporine-induced gingival enlargement. Courtesy: Dr Francisco, Mexico

can predispose to and exacerbate the gingival response in


leukemia, they are not prerequisites for lesions to form in
the oral cavity (Dreizen et al, 1984).
Linear gingival erythema (LGE)
Infection with the human immunodeficiency virus (HIV)
produces an irreversible and progressive immunosuppression that renders the person infected susceptible to a variety
of oral diseases. In humans, HIV depletes CD4 lymphocytes
(T helper cells), which leads to the development of a variety
of fungal, viral and bacterial oral infections (Connor and
Ho, 1992).
Oral manifestations of HIV infection have been used to
stage HIV disease (Justice et al, 1989; Royce et al, 1991) to
identify prophylactic treatment of other serious infections
(Force, 1993), and to indicate disease prognosis (Dodd et al,
1991; Katz et al, 1992).
In the gingiva, manifestations of HIV infection were formerly known as HIV-associated gingivitis but are now known
as LGE. This condition is distinguished by a 23 mm marginal band of intense erythema in the free gingiva (Winkler
et al, 1988), which may extend into the attached gingiva as
a focal diffuse erythema and/or extend beyond the mucogingival line into the alveolar mucosa (Winkler et al, 1988).
The characteristics of LGE may be localized to one or two
teeth but more commonly involvement of marginal gingiva
is generalized.
The etiology of this gingival lesion is not well understood;
however, research has begun to investigate the relationship of periodontal pathogens and the local host response in
regard to how HIV infection affects the gingiva. The anaerobic microora from the subgingival sites of HIV-infected
patients with gingivitis seems to be essentially the same as
in non-infected patients (Moore et al, 1993). Despite the
similarities in anaerobic microora, organisms not generally associated with gingivitis in HIV-negative patients,
such as Candida species, have been identied in LGE
448

(Lamster et al, 1998). In addition, LGE lesions have been


shown to have reduced proportions of T cells and macrophages and an increased number of immunoglobulin G
plasma cells and polymorphonuclear leukocytes (Gomez
et al, 1995). These host cell responses and unusual microbiota
may be responsible for the refractory nature of this lesion
to the conventional periodontal treatment of gingivitis.

Gingival Diseases Associated with Malnutrition


Although some nutritional deficiencies can significantly
exacerbate the response of the gingiva to plaque bacteria,
the precise role of nutrition in the initiation or progression
of periodontal diseases remains to be elucidated. Studies
of the periodontal status of individuals in developed and
developing countries have failed to show any relationship
between periodontal disease and general nutrition (Russell,
1962; Waerhaug, 1967; Wertheimer et al, 1967).
Severe vitamin C deciency or scurvy was the earliest
nutritional deciency to be examined in the oral cavity (Lind,
1953). Even though scurvy is unusual in areas with an adequate food supply, certain populations on restricted diets
(e.g. infants in families of low socioeconomic class) are at
risk of developing this condition (Oefnger, 1993). In scurvy
the gingiva is typically red, swollen, ulcerated and susceptible to hemorrhage (Van Steenberghe, 1997). Although
there is no dispute about the necessity of dietary ascorbic
acid for periodontal health, in the absence of frank scurvy,
the effect of declining ascorbic acid levels on the gingiva
can be difcult to detect clinically (Woolfe et al, 1980) and
when it is detected usually has characteristics that are
similar to plaque-induced gingivitis.

Gingival Diseases Associated with Heredity


Benign, non-inflammatory fibrotic enlargement of the maxillary and/or mandibular gingiva associated with a familial

Chapter 16 Gingival and Periodontal Diseases

aggregation has been designated by terms such as gingivostomatitis elephantiasis, familial elephantiasis, juvenile
hyaline fibromatosis, idiopathic gingival fibromatosis and
hereditary gingival fibromatosis. Although there were almost
100 published reports of hereditary-associated gingival
overgrowths in the 20th century, information about the
natural history of this rare disease is extremely limited and
its etiology is unknown.
Hereditary gingival bromatosis appears to be a slowly
progressive gingival enlargement which develops upon
eruption of the permanent dentition. However, gingival
enlargement can also occur in the primary dentition
(Emerson, 1965; Jorgenson and Cocker, 1974; Lai et al,
1995; Miyake et al, 1995). The disease can be localized or
generalized and may ultimately cover the occlusal surfaces
of teeth. The enlarged gingiva is non-hemorrhagic and
rm, but there can be an overlay of gingival inammation
which can augment the enlargement. The histologic features
of hereditary gingival bromatosis include dense brotic
connective tissue as well as epithelial hyperplasia with
elongated and increased rete pegs (Johnson et al, 1986;
Clark, 1987).
Hereditary gingival bromatosis can be inherited as a
simple mendelian trait, in some chromosomal disorders and
as a malformation syndrome (Witkop, 1971; Jones et al,
1977; Takagi et al, 1991; Goldblatt and Singer, 1992; Hallet
et al, 1995). Although the specic genes for this disease have
not been identied, genetic analysis supports the presence
of two different gene loci on chromosome 2p (Shashi et al,
1999). Research into the cellular responses of this disease
suggests an accumulation of specic populations of gingival broblasts resulting in an abnormal accumulation of
connective tissues (Huang et al, 1997; Tipton et al, 1997).

Gingival Diseases Associated with Ulcerative


Lesions
Necrotizing ulcerative gingivitis has been known for centuries by numerous names including trench mouth and
Vincents infection. Acute NUG is a term used to describe
the clinical onset of the disease and should not be used as
a diagnostic classification, since some forms of NUG may
be recurrent or possibly chronic.
Onset is usually sudden with intense gingival pain, which
prompts the patient to seek professional care. Clinical signs
include papillary necrosis, giving a punched-out appearance of the gingival papilla and gingival bleeding that
requires little or no provocation (Grupe, Johnson and
Engel, 1986). Although these symptoms and signs must be
present for a diagnosis of NUG, other features may occur
such as fever, malaise, lymphadenopathy, metallic taste
and fetor ex ore (malodor) (Schluger, 1943; Wilson, 1952;
Murayama et al, 1994). Systemic reactions of acute NUG
are usually more severe in children. Signicant destruction of the gingival connective tissue is possible with NUG

but when attachment loss occurs this condition should be


considered as an NUP.
The cause of NUG may be bacterial. The four zones of the
NUG lesion include the bacterial zone (the supercial area
consisting of various bacteria and some spirochetes); the
neutrophil rich zone (follows the bacterial zone and consists leukocytes and bacteria including spirochetes); the
necrotic zone (consisting of disintegrated cells and
connective tissue elements with many large and intermediate spirochetes); and the spirochetal inltration zone
(the deepest zone that is inltrated with no other bacteria
but with intermediate and large spirobacteria but with
intermediate and large spirochetes) (Listgarten, 1965).
The cultivable ora of NUG that predominates includes
Prevotella intermedia and Fusobacterium species, while
microscopically, Treponema and Selenomonas species are
observed (Loesche et al, 1982; Rowland et al, 1993).
Additional factors include smoking (AAP, 1996), psychological stress (Moulton et al, 1952; Cohen-Cole et al, 1983),
malnutrition (Grupe and Wilder, 1956; Goldhaber and
Giddon, 1964; Johnson and Engel, 1986) and immune
suppression (Moulton et al, 1952; Rowland et al, 1993) can
predispose and individual to NUG.
Although NUG can affect any age group, it is considered to be a disease of young adults in developed countries
(Melnick et al, 1988). In developing countries, NUG is a disease found in children from families with low socioeconomic
status (Melnick et al, 1988). The onset of NUG in children
is associated with inappropriate nutrition intake, especially
low protein consumption (Sheiham, 1966; Taiwo, 1995). In
addition, viral infections such as measles can induce NUG
in malnourished children (Enwonwu, 1972; Osuji, 1990).
Even though NUG has occurred in epidemic patterns, this
disease is not considered communicable (Rosebury, 1942).

Gingival Lesions Manifested in Childhood


Diseases
Acute herpetic gingivostomatitis
The herpes simplex virus produces some of the most common acute infections in humans. Of the two herpes simplex
virus serotypes, type 1 is responsible for most oropharyngeal infections, including acute herpetic gingivostomatitis. This disease is observed in young adolescents and
adults but has its highest incidence in infants and children
younger than 6 years of age (Scott et al, 1941). There are
no predilection for either sex with the primary infection.
Following the primary infection, the virus moves through
nerves to neuronal ganglia where it remains dormant until
reactivated by various stimuli including trauma, exposure
to sunlight or ultraviolet lamps, fever, stress, fatigue, menstruation, pregnancy, upper respiratory tract infection,
allergy or gastrointestinal disturbances (Stevens, 1975;
Shafer et al, 1974).
449

Section VI Teeth and Periodontium

Although most cases of primary herpetic infection are


symptomatic (Gibson et al, 1990; McDonald et al, 1994),
the primary infection in some cases may manifest as acute
herpetic gingivostomatitis, which is characterized by several oral and systemic manifestations. The symptomatic
infection is characterized by fever, malaise, headache, irritability, dysphagia and lymphadenopathy. In the oral cavity, lesions can affect the lips, tongue and pharynx.
Initially, gingival inammation is characterized by a diffuse, erythematous, shiny appearance precedes the appearance of vesicles (White, 1998). The vesicles vary in size and
are usually discrete, spherical sacs which rupture to form
small, ragged and painful ulcers that are covered by a gray
membrane and surrounded by an erythematous, elevated
halo (White, 1998). The ulcers persist for 710 days and heal
spontaneously, leaving no scars (White, 1998).
The diagnosis for this infection is usually determined by
the patients history and clinical signs and symptoms, and
conrmed laboratory culture of the herpes simplex virus.
Lesions of recurrent aphthous stomatitis have often been
confused with acute herpetic gingivostomatitis, but can be
distinguished clinically by the absence of diffuse erythema
of gingiva, acute toxic systemic symptoms and herpes
simplex virus culture.

may be expressed. The lesion is generally self-limiting, ultimately rupturing if permitted to progress. The gingival abscess
should not be confused with the periodontal abscess, which
affects the supporting periodontal structures.

Gingival Changes Associated with Tooth Eruption


As the crown penetrates the oral mucosa, the marginal gingiva and sulcus form. During the physiologic process of
eruption, the gingival margin becomes edematous and
erythematous. It is not uncommon for erupting primary or
permanent teeth to be associated with a form of dentigerous cyst (also called eruption cyst/eruption hematoma). The
eruption cyst usually appears as a site of translucent, fluctuant, circumscribed swelling over the erupting tooth. When
the cystic cavity contains blood, the swelling appears as a
purple or deep blue fluctuant, circumscribed swelling termed
as eruption hematoma. Primary canines and molars appear
to be more frequently involved than primary incisor teeth.

PERIODONTAL DISEASES
Local Contributing Factors

Gingival Lesions Associated with Chicken Pox


Varicella, which primarily affects individuals below the age of
15 years (Preblud, 1986), produces the skin lesions characterized by vesicles and pustules that break and crust over. In the
oral cavity, small ulcers may develop in any area of the mouth;
however, lesions are found most often on the palate, gingiva and buccal mucosa (Badger, 1980). The ulcers that appear
during the course of the skin rash are usually not painful.

It is well known that the primary cause of gingival inflammation and periodontal destruction is bacterial plaque.
These factors that tend to accelerate the disease locally, are
termed as local contributing factors in the progression of
periodontal disease.
The local factors are:

Gingival Lesions Associated with Mononucleosis


Mononucleosis is produced by the EpsteinBarr virus and
is primarily a disease of children and young adults. The clinical symptoms are most prominent in young adults, and
common signs and symptoms include fatigue, malaise,
headache, fever, sore throat, enlarged tonsils and lymphadenopathy. Alterations in the oral cavity include gingival
bleeding, petechiae of the soft palate, ulceration of the
gingiva and buccal mucosa and pericoronitis.

Acute Inflammatory Gingival Enlargement


A gingival abscess is an acute, painful, rapidly expanding
lesion localized to the gingiva. Most gingival abscesses are
detected on the marginal gingiva or the papilla. Gingival
abscesses usually arise from an insult such as trauma caused
by food which forces bacteria into the tissue. Within hours,
a bright red gingival swelling will convert to a lesion that
is pointed and fluctuant mass from which purulent exudates
450

Calculus
Iatrogenic factors
Overhanging restoration
Margins of restoration
Contours
Restorative materials
Occlusion
Restorative procedures
Pontic
Improper removable partial dentures
Malocclusion
Food impaction
Orthodontic therapy
Anatomic contributing factors
Proximal contact relationship
Cervical enamel projections and enamel pearls
Bifurcation ridges
Developmental grooves
Root anatomymorphology and length
Root fusion, cemental tears
Proximity to adjacent teeth
Endodontic lesions
Caries

Chapter 16 Gingival and Periodontal Diseases

Habits
Toothbrushing trauma
Mouth breathing, tongue thrusting and other habits
Factitial injuries
Smoking
Trauma from occlusion
Trauma
Physical
Chemical
Thermal
Radiation therapy
Mucogingival problems
Cysts and tumors.

Figure 5

Calculus
Calculus is mineralized dental plaque that forms on surface
of teeth and dental prosthesis. It is one of the most important
and commonly occurring local contributing factor as it is
invariably covered with bacterial plaque on its surface.

Thick band of subgingival calculus firmly adherent to the


cervical margin of the tooth. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

Types
Supragingival calculus It is white or whitish yellow in
color hard with clay-like consistency and is easily detached
from the tooth. It is most commonly found on lingual surface
of mandibular teeth and buccal surface of maxillary teeth.
Subgingival calculus It is located below the crest of
marginal gingiva and appears dark brown or black in
color and flint-like consistency. It is firmly attached to the
tooth (Figure 5).
Composition
Calculus consists of organic and inorganic constituents.
organic contents are mainly desquamated epithelial cells,
leukocytes and microorganisms. Inorganic constituents are
mainly calcium, calcium phosphates and calcium carbonates,
magnesium phosphates and other metals.
Significance of calculus
Calculus is a local factor in periodontal disease because it
always has a layer of plaque on its surface. Because calculus
is firmly attached to the tooth through an organic pellicle,
it resists removal through routine oral hygiene techniques.
Calculus plays an important role in the progression of
periodontal disease by keeping plaque in close contact
with the periodontal tissues in gingiva.

Iatrogenic Factors

Overhanging restorations: These contribute to periodontal disease by acting as a local plaque retentive
area causing accumulation of plaque and changing
the ecology that favors the growth of microorganisms.

Margins of restoration: A subgingival margin is associated with more plaque accumulation and more periodontal destruction than supragingival margins, margins
placed at the level of gingiva.
Contours: Overcontoured restorations tend to accumulate more plaque, and the natural self-cleansing mechanism fails.
Open contours: These are associated with increased
food impaction and papillary inflammation.
Restorative materials: Silicate cements and self-curing
acrylic resins accumulate more plaque.
Restorative procedures: Rubber dam, clamps, matrix
band wedges, gingival retraction chords are shown to
cause injury to the periodontium.
Pontics: When pontics are in contact with gingival tissue, they tend to accumulate more and oral hygiene
techniques are more difficult.
Improper removable partial denture: It causes an
increase in mobility of abutment teeth and also favors
accumulation of plaque leading to gingival inflammation and periodontal pocket.
Malocclusion: Plaque control is more difficult in individuals with malocclusion. Malocclusion is usually associated
with recession if the tooth is buccally placed and plaque
control is difficult because of lack of attached gingiva.
Food impaction: It is forceful wedging of food into the
periodontium by occlusal forces. This harbors more
microorganisms in interproximal area leading to periodontal destruction.
Orthodontic therapy: Orthodontic appliances are associated with food debris and plaque accumulation and
changing the ecosystem. These also cause increase in
forces on the periodontium.
451

Section VI Teeth and Periodontium

Carious tooth: Endodontically treated tooth and root


stumps act as plaque retentive areas leading to periodontal diseases. In some instances patients with
pulpal/periapical diseases avoid chewing food from the
affected side leading to more deposition of calculus.
Anatomic contributing factors: Proximal contact
relationshipopen proximal contact may cause food
impaction, which in turn causes periodontal disease.
Cervical enamel projection and enamel pearls: Cervical
enamel projections are narrow wedge-shaped extrusions
of enamel extending from cementoenamel junction
toward the furcation area. Enamel pearls are bead-like
projections commonly found in furcation area. The
clinical significance of cervical enamel projection and
enamel pearls is that they act as a local plaque retentive area and also periodontal attachment does not take
place in them, hence leading to periodontal diseases.
Bifurcation ridges: It is a convex excrescence of cementum that runs longitudinally between the mesial and distal roots of mandibular molars. Thus, it makes removal
of plaque and calculus more difficult.
Palatogingival groove: It is a developmental groove
that begins at the cingulum and extends apically in
the anterior teeth. Most commonly it is seen in maxillary lateral incisor. These grooves act as a plaque
retentive area.
Cemental tears: It is a piece of detached cementum with
some amount of dentin attached to the alveolar bone
through periodontal ligament. This is often induced by
some form of acute trauma leads to rapid bone destruction with vertical bone loss.
Root fusion: Progression of periodontal disease is faster
if roots are fused.
Root proximity: There is a thin interseptal bone when
the roots are in close proximity, which has an increased
rest for periodontal destruction.
Extraction of impacted third molars: This results in
periodontal problems distal to second molar with pockets of recession and bone loss.

Figure 6

Cervical abrasion and localized gingival recession.


Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

Habits

Smoking
It is one of the etiological factors in ANUG. It is classified
as an environmental factor with local and systemic effects.
The local effects are peripheral vasoconstriction and localized ischemia. The individual harbors more pathogenic and
virulent subgingival microorganisms. The systemic effects
are decreased immunity with non-specific (decreased polymorphoneutrophils, chemotaxis, phagocytosis) and specific
(decreased IgG, IgA). There is also activation of proinflammatory cytokines including IL-1. TNF- IL-6 all lead to
periodontal diseases.
Since immunity and inammation are reduced in smokers there are lesser clinical signs of gingival inammation
with increased local deposits and periodontal destruction;
it is one of the etiological factor in NUG.
452

Toothbrush trauma: This can abrade the epithelium


leading to gingival recession (Figure 6). It also causes
abrasion of the tooth surface.
Mouth breathing, tongue thrusting and other habits:
Mouth breathing causes dehydration of gingival tissue
increasing their susceptibility to inflammation. Tongue
thrusting causes anterior open bite and spacing between
the teeth causing difficulty in maintaining good oral
hygiene.
Factitial injury: It is self-inflicted injury, which include
picking of gingiva with finger nail; tooth picks, pins
and other materials. This causes a direct damage to the
periodontium.
Radiation therapy: It causes soft tissue ischemia, fibrosis and osteoradionecrosis in bone. Periodontal tissue
destruction is more in patients who underwent radiation therapy.
Mucogingival problems: Mucogingival area is defined as
a generic term used to describe the mucogingival junction and its relationship to the gingiva, alveolar mucosa,
frenum, muscle attachments, vestibular fornices and the
floor of the mouth. A mucogingival deformity may be
defined as a significant departure from the normal shape
of the gingival and alveolar mucosa.

Some of the common mucogingival problems are decrease in


the width of attached gingiva, gingival recession crossing
the mucogingival junction, high frenal attachments and shallow vestibule.
Mucogingival problems are commonly associated with
plaque accumulation, as the patient cannot perform the
routine oral hygiene techniques.

Traumatic injuries: These can be physical, chemical and


thermal in nature and can cause injury to gingival and

Chapter 16 Gingival and Periodontal Diseases

supporting periodontal tissues. These directly affect


the gingiva and make routine plaque control procedures difficult.
Cysts and tumors: Some of the cysts and tumors because
of their expansile growth cause destruction of the
periodontium.

Figure 7

Systemic factors
It is well known that bacterial plaque is a main etiological
factor responsible for gingival inflammation and periodontal destruction. The bacterial plaque causes a marked host
response that varies from one individual to other, hence susceptibility of individual to periodontitis depends on various
factors, including systemic and genetic factors.
Genetic factors
Periodontal disease is multifactorial with plaque being
major factor, but some of these factors fail to explain the
variation of disease in different individuals with same
amount of local factor. This is attributed to genetic susceptibility. Genetic pleomorphism in IL-1 has been shown to
be associated with chronic periodontitis. Studies have
shown a link between susceptibility of aggressive periodontitis and the human leukocyte antigen of chromosome 6, which is responsible for production of IgG2, which
in turn is responsible for periodontal destruction. The
genetic polymorphism in the genes for the Fc- receptor
on the phagocytic cell is identified in localized aggressive periodontitis. Polymorphism in the gene promoter
region of chromosome 6, results in increased production
of TNF-, which has been shown to be associated with
periodontitis.

Extensive destruction of supporting bone and missing teeth in


PapillonLefevre syndrome. Courtesy: Department of Oral
Medicine and Radiology, MCODS, Mangalore

ChediakHigashi syndrome
It is an autosomal recessive disease that affects the production of organelles in many cells including melanocytes,
platelets and leukocytes. Neutrophils are characterized by
abnormal giant lysosomes containing enzymes and with
impaired ability to release them.
It is associated with severe gingivitis, periodontal disease
and loss of dentition at an early age.
Lazy leukocyte syndrome
It is a rare disease characterized by defect in PMN chemotaxis and an abnormal inflammatory response.
Leukocyte adhesion deficiency (LAD)

SYNDROMES
Downs syndrome
It is a congenital disease characterized by mental deficiency, growth retardation and severe periodontal disease.
Incidence is about 1:8001,000. Both deciduous and permanent dentitions are affected. The destruction increases
with age. The rapid periodontal destruction is commonly
attributed to immunologic defects.

It is a rare inherited genetic disorder resulting from inability to produce or express CD18, an integrin useful in leukocyte adhesion.
Both primary and secondary dentitions are affected in
LAD which presents as acute inammation and rapid
destruction of bone.
EhlersDanlos syndrome
It is an inherited condition affecting connective tissue with
reduction of collagen fiber production. The oral mucosa,
gingiva and periodontium are affected.

PapillonLefevre syndrome
It is an inherited autosomal recessive disease characterized by diffuse palmoplantar hyperkeratosis, severe destruction of periodontium and calcification of dura. Incidence
is 14:10,00,000. Deciduous teeth are usually lost by
56 years and permanent teeth a few years later (Figure 7).
Defects in PMNs adherence and chemotaxis has been
reported.

Hypophosphatasia
It is an autosomal recessive condition where there is a deficiency of the enzyme alkaline phosphatase and characterized by abnormal mineralization of bone and dental tissues.
There is premature exfoliation of deciduous teeth, loss
of alveolar bone, absence of gingival inammation and
absence of cementum. The permanent teeth are not affected.
453

Section VI Teeth and Periodontium

Mucopolysaccharidoses (MPS)

Figure 8

It is a group of inherited disorders characterized by disturbances in mucopolysaccharide metabolism and their


increased storage in various tissues.
These include Hurlers syndrome (MPS I) and Hunters
syndrome (MPS II).
The teeth in both these conditions are small and widely
spaced and exhibit delayed eruption. Gingival enlargement may be commonly seen.

Hormonal Factors
Diabetes: It is a complex metabolic disorder characterized
by glucose intolerance.
It is associated with:

Microvascular diseases (retinopathy, neuropathy and


nephropathy)
Macrovascular diseases (cardiovascular, cerebrovascular)
Increased susceptibility to infections
Delayed wound healing
Periodontitis.

Extensive periodontal abscess in a diabetic patient.


Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

Figure 9

Oral effects
Patients with diabetes have diminished salivary flow,
burning mouth and candidiasis.
Diabetes also has profound effect on periodontium resulting in gingivitis, gingival enlargement, periodontal abscess
formation, periodontitis and loss of teeth (Figures 8 and 9).
Pathogenesis

Alteration of bacterial flora


Altered neutrophil function
Altered collagen metabolism.

SEX HORMONES
The female sex hormones affect periodontal tissues. Estrogen
promotes keratinization and increased mucopolysaccharide content, the gingival connective tissue. Progesterone
increases the permeability and gingival blood vessels.
Changes seen are:

Puberty: There is an increased prevalence and severity


of gingivitis.
Menstrual cycle: Gingival crevicular fluid (GCF) flow
increases at the time of ovulation.
Pregnancy: The changes in gingiva usually starts
around the 3rd month of gestation and the severity of
inflammation gradually increases during pregnancy.
Gingiva becomes bright red, swollen, sensitive and
bleeds spontaneously. There is an increase in GCF production and tooth mobility. There is an increased level
454

Extensive destruction of interdental bone and loss of teeth


in a diabetic patient. Courtesy: Department of Oral Medicine
and Radiology, MCODS, Mangalore

of Prevotella intermedia during pregnancy. In some


cases a soft, pedunculated granuloma is present in the
interdental papilla, which is a slow-growing lesion
referred to as pregnancy tumor.
Oral contraceptives: These are associated with increased
GCF flow and a greater prevalence of gingival inflammation.
Menopausal gingivostomatitis: In this the gingiva
appears dry and shiny. It varies in color from pale to
bright red and bleeds easily.

Chapter 16 Gingival and Periodontal Diseases

Hyperparathyroidism: It causes a disease known as


osteitis fibrosa cystica or von Recklinghausens bone
disease.

Oral changes include increased tooth mobility. Radiographically, it shows widening of periodontal ligament
space with absence of lamina dura, closely meshed trabaculae and cystic space known as Browns tumor.

STRESS AND PSYCHOSOMATIC FACTORS


Stress and other psychosomatic factors have direct antiinflammatory and anti-immune effects or can have behaviormediated effects on the bodys defenses. Stress is also one
of the etiological factor in acute NUG.
Stress increases cortisol hormone which suppresses
immune system by suppressing neutrophil activity and
decreasing IgG and IgA production, thus allowing the
periodontal pathogens to cause more destruction.
Psychosomatic disorders can result in periodontal tissue
destruction through development of certain habits like nail
biting, using foreign objects, self-inicted gingival injuries can be seen in patients with mental disabilities.

NUTRITIONAL FACTORS
There are no nutritional factors that causes gingivitis or
periodontitis, but they produce changes in the oral cavity
including the gingiva and alveolar bone that can accelerate the process of gingivitis and periodontitis.

Scurvy is associated with enlarged, hemorrhagic, bluish,


red gingiva. Gingivitis is not caused by vitamin C deciency
but the severity of gingivitis increases with vitamin C deciency. Gingival healing is also impaired.
Vitamin C deciency also results in osteoporosis of alveolar bone, hemorrhage in the periodontal ligament and
increased tooth mobility.
Vitamin D It is necessary for the calciumphosphorus balance. Deficiency of vitamin D causes rickets in children and
osteomalacia in adults. Vitamin D deficiency in animals
causes osteoporosis of alveolar bone, uncalcified osteoid,
reduction in width of periodontal ligament, severe osteoclastic resorption of alveolar bone.
Vitamin E There is no relationship between vitamin E
deficiency and periodontal disease in humans. In animals
vitamin E accelerates gingival wound healing.
Protein deficiency In experimental animals the oral
changes of protein deficiency include degeneration of CT
of periodontium, osteoporosis, delayed wound healing and
abnormal deposition of cementum.
Hematological disorders
Leukemia: Its characterized by diffuse replacement of bone
marrow with proliferating leukemic cells, abnormal number or form of WBCs in blood and widespread metastasis.
It can be lymphocyte or myelocytic, acute, subacute or
chronic.

Effects of Vitamin Deficiency

Oral manifestations There is a widespread infiltrate of


leukemic cells in oral cavity, particularly gingiva, which
appears bluish red with enlargement and spontaneous bleeding. Oral ulceration and infections are commonly noticed
in these patients; microscopically the gingiva exhibits a
dense infiltrate of immature leukocytes.

Vitamin A In experimental animals, vitamin A cause


hyperkeratosis and hyperplasia of gingiva with a increased
rate of pocket formation. In humans studies are inconclusive.

Leukocyte disorders These are usually associated with


severe periodontal destruction as PMNs are the first line of
defense against periodontal pathogens.

Vitamin B complex Thiamin deficiency (beriberi) causes


hypersensitivity of oral mucosa, minute vesicles and erosion of oral mucosa.
Riboavin deciency (riboavinosis) causes glossitis,
angular cheilitis and seborrheic dermatitis.
Niacin deciency (pellagra) causes glossitis, stomatitis,
black tongue and severe gingival inammation with
necrosis.
Folic acid deciency causes necrosis of gingival, periodontal ligament and alveolar bone without inammation.
Vitamin C Ascorbic acid deficiency results in scurvy,
where there is defective formation of collagen fibers and
impaired osteoblastic activity. There is also an increased
capillary permeability, susceptibility to traumatic hemorrhages, hyperreactivity of contractile elements and sluggish blood flow.

Neutropenia It is a leukocyte disorder in which there is


a low count of neutrophils in blood (1,500 cells/l).
Neutropenia can be genetic, familial, idiopathic or secondary
to some kind of infections. There are many kinds of neutropenias all of which affect the periodontal health.
Agranulocytosis It is a leukocyte disorder in which there
is a low count of circulating granulocyte in blood.
Ulcerations with the absence of inflammatory reaction of
the oral cavity is one of the characteristic sign of agranulocytosis.
Gingival hemorrhage, necrosis and fetid odor are also
present.
Cyclic neutropenia It is an inherited condition where
there is cyclic depression of neutrophils in peripheral blood
at intervals varying from 15 to 55 days and manifested
455

Section VI Teeth and Periodontium

with pyrexia, oral ulceration and skin infections. Oral features include oral ulcerations, severe gingivitis, periodontal destruction and alveolar bone loss.
Chronic benign neutropenia of childhood There is moderate neutropenia with absolute lymphocytosis and monocytosis. Oral findings include bright red hyperplastic
edematous gingiva which bleeds easily and permanent
destruction with generalized bone loss.
Familial neutropenia It is an inherited condition which
can occur in benign and severe forms. There is moderate
to severe form of neutropenia in these conditions. Oral
findings are similar to that of chronic benign neutropenia
of childhood.
Chronic idiopathic neutropenia This occurs mainly in
females with persistent neutropenia from birth. Oral findings are similar to that of chronic benign neutropenia of
childhood.

Gingivitis
Presence of local factors like calculus and/or at least one of the
following clinical features:
Erythematous gingiva
Soft and edematous gingiva
Blunting of the interdental papilla
Loss of gingival stippling
Gingiva bleeds spontaneously on palpation or probing
Periodontitis
Gingivitis plus at least one of the following clinical features:
Gingival recession
Periodontal pocket
Mobility
Pathologic migration
Pus discharge from the gingival sulcus
Furcation involvement

Lazy leukocyte syndrome There is a defect in leukocytic chemotaxis and mobility associated with severe
gingivitis.

RADIOGRAPHIC EVALUATION OF
PERIODONTAL DISEASES

Chronic granulomatous disease It is an inherited condition characterized by inability of neutrophils to generate


hydrogen peroxide due to absence of the enzyme NADPH
oxidase. Oral condition includes severe and diffuse gingivitis with ulcerations.

Thumb rules

Anemia It is defined as the reduction of concentration of


hemoglobin in blood below at normal level.
Oral ndings include recurrent aphthous ulcers with
angular cheilitis, smooth and bald tongue, gingiva becomes
pale in color.
Fanconis anemia which is an inherited form of anemia
is associated with early tooth loss.
Acatalasia It is an inherited disease with the absence of
acatase enzyme in RBCs and WBCs. Catalase is responsible
for conversion of hydrogen peroxide (H2O2) to O2 and H2O;
thus preventing oxidation of hemoglobin in RBCs.
Thrombocytopenic purpura It is characterized by low
platelet count, spontaneous bleeding into skin and mucous
membrane. Oral finding includes petechia in oral cavity.
Gingiva is inflamed, soft and friable. Spontaneous bleeding
in commonly seen.
Agammaglobulinemia It is an immune deficiency resulting from a low antibody production from B cells. It is
commonly associated with severe periodontal destruction
and tooth loss.
Multiple myeloma It is a multifactorial neoplasm of
plasma cells with infiltration into maxilla and mandible.
Oral lesions include gingival ulceration with bleeding
and alveolar bone destruction.
456

Summary of the clinical features of gingivitis and periodontitis

Radiographs will not show soft tissue changes (e.g.


destruction of the periodontal ligament and pocket
depth). However, contrasting agents such as use of periodontal probe, gutta percha points may help delineate
soft structures.
Intraoral periapical (IOPA), bitewing radiographs and
orthopantomograph (OPG) reveal only two-dimensional
images of three-dimensional structures. Hence, bone
loss in different planes may not be evident in a single
radiographic projection.
The disease process is always ahead of the radiographic
presentation. It is estimated that for radiographic visualization a minimum of 40% demineralization is required.
Intraoral periapical radiographs have the best resolution when compared to CT and OPG. Early and minimal
bone changes and bone marrow morphology are hence
best appreciated in an intraoral periapical radiograph.
Infrabony defects are impossible to be detected on intraoral radiographs as one or both cortical plates superimpose over the defect.

Need for taking radiographs

Evaluate the nature and extent of the causes for periodontal destruction (subgingival calculus, overhanging
margins of proximal restorations and poorly contoured
crowns).
Assess the width of the periodontal ligament space.
Evaluate crestal bone loss.
Assessment of the pattern and extent of alveolar bone
destruction (horizontal, angular, furcation involvement).

Chapter 16 Gingival and Periodontal Diseases

Assessment of the anatomic morphology of the roots


and the crown root length.
Assessment of the location of various anatomical
structures.
Evaluation of periapical pathologies, endo-perio lesions,
bone pathology and systemic conditions resulting in
periodontal destruction.

Interpretation of radiographs

Technique and exposure parameters

Paralleling technique to be followed wherever feasible.


Use wire grids along with the film (will help in accurate assessment of bone loss).
70 kVp, 8 mA machines are most ideal.
Low contrast with long gray-scale are most suited for
evaluation of periodontal destruction. Lighter radiographs tend to depict the cortical margins.
Choice of radiographs

Orthopantomograph can be used as a scout radiograph


to evaluate generalized destruction of periodontium. It
can also be used for assessing cortical plate width and
density for implant placement and relationship of
teeth/implant to adjacent anatomical structures.
Intraoral periapical radiographs can be used for assessing height and pattern of interdental bone, involvement of furcation area, widening of the periodontal
ligament space, root resorption, periapical lesions and
endo-perio lesions.
Bitewing radiographs can be used to assess crowns
and interdental regions of a few upper and lower teeth in
one radiograph. These radiographs are used for assessing
crestal bone loss and factors that cause periodontal
destruction such as subgingival calculus deposits, illfitting crowns and poor restorative margins.
Full mouth IOPA radiographs are excellent means to
assess the periodontal status in a patient. The full mouth
series consists of 16 IOPA radiographs (excluding four
radiographs for the third molars) and four bitewings.

Radiographs have to be always mounted and viewed


using a viewer box. Wet films should not be
interpreted.
Compare the normal anatomical findings with those
that are diseased.
Normally the crestal bone is pointed in the anterior
regions and flat topped in the posterior teeth and parallel to the line joining the cementoenamel junctions
of adjacent teeth.
The crest of the alveolar bone lies about 1.5 cm below
the cementoenamel junction.
Presence of a well-defined radiopaque cortical border in the alveolar crest is indicative of healthy periodontium.
Widening of periodontal ligament space at the cervical
portion of the tooth may indicate initial periodontitis.
In healthy periodontium, the lamina dura forms a
definitive, sharp angle with the alveolar crest.
Interproximal crater (type of angular defect) is evident
as a trough-like depression that forms in the crest of
the interdental bone.

Radiographic features of periodontitis: Early to advanced stage


Localized erosion of interdental alveolar bone crest
Blunting of the alveolar crest
Loss of the sharp angle between the lamina dura and the alveolar
crest
Loss of the cortical surface of the crest
Widening of the periodontal ligament space along the lateral margins
of the tooth
Interdental horizontal/vertical bone loss
Vertical bone loss may appear either as an interproximal crater (seen
as a trough-like depression in the interdental bone below the level of
the crestal edges) or as infrabony defect (vertical radiolucency within
bone extending apically along the root from the alveolar crest)
Bone surrounding the periodontal lesion may exhibit sclerosis owing
to the inflammation.

457

CHAPTER

17

Regressive Alterations
of Teeth
Ravikiran Ongole, Sumati Nagappa
Baddannavar, Praveen BN

Classification of Regressive Alterations

Occupations Associated with Exposure to Acidic Fumes


Abfraction

Affecting Teeth

Tooth Surface Loss

Attrition

Abrasion

Erosion (Corrosion)
Causes for Corrosion
Erosion Associated with Common Food Substances
Erosion Associated with Medications
Erosion Related to Deleterious Habits
Occupation-related Dental Erosion

Classification of Tooth Wear


Classification of Severity of Tooth Wear
Classification Based on Clinical Presentation

Resorption of Teeth
Regressive Alterations of Dentin
Regressive Alterations of Pulp
Regressive Alterations of Cementum
Hypercementosis
Cementicles

With increasing oral health awareness and the advances in


healthcare delivery system the incidence of carious lesions
and periodontal diseases have drastically reduced over the
ages. As such many individuals tend to retain healthy teeth
even in their old age. However, these teeth are subject to
functional wear and tear in addition to the natural agerelated regressive alterations affecting the tooth and its
supporting structures.
Early recognition of the signs and symptoms of these
regressive changes and understanding the basic pathophysiology behind such alterations will help the physician
plan an effective treatment plan.

Secondary to other pathology


Resorption of roots of deciduous teeth
Changes in dentin
Secondary dentin
Reparative dentin
Dead tracts
Changes in pulp
Reticular atrophy of pulp
Pulp calcifications
Changes in cementum
Cementicles
Hypercementosis.

CLASSIFICATION OF REGRESSIVE
ALTERATIONS AFFECTING TEETH

TOOTH SURFACE LOSS

Tooth wear
Attrition
Abrasion
Erosion (corrosion)
Abfraction
Resorption of teeth
Internal
Internal inflammatory
Internal replacement
External
Idiopathic
458

Eccles in 1982 described tooth surface loss or tooth wear


as pathological loss of tooth tissue by a disease process
rather than dental caries. Tooth wear was earlier referred
to as wasting diseases affecting teeth.
Mair in 1992 described the term non-carious cervical
lesions or cervical wear to refer to loss of tooth substance
at the cementoenamel junction. These non-carious cervical lesions include cervical erosion, abrasion and abfraction.
Clinical studies by Kitchin (1941) have shown that cervical
wear lesions are often situated on the vestibular surfaces
of teeth, seldom on lingual surfaces and rarely on proximal surfaces. These are also more pronounced on incisors,

Chapter 17 Regressive Alterations of Teeth

canines, and premolars and more prevalent in the maxilla


than in the mandible.
The term tooth wear or tooth surface loss will include
attrition apart from the cervical wear lesions.

ATTRITION
Pindborg defined attrition as the loss of enamel, dentin or
restoration by tooth-to-tooth contact. Tooth-to-tooth friction causes the form of wear called attrition. Two types of
attrition have been described. They are physiologic and
pathologic.
Physiologic attrition is referred to as the gradual and
regular loss of tooth structure as a result of normal mastication. However, pathologic attrition is conned to local areas
or specic groups of teeth caused by abnormal friction.
The physiologic causes for attrition include mastication
and deglutition. Pathologic causes that cause attrition are
abnormal occlusion, bruxism and habits such as tobacco
and betel chewing and defective tooth structure such as in
dentinogenesis imperfecta.
Attrition involves occlusal/proximal surfaces of teeth.
It occurs more frequently in males than in females due to
greater masticatory forces. It appears as a small polished
facet on cusp tips and causes attening of incisal edges in
case of anterior teeth (Figure 1). The wear will lead to
exposure of the dentin causing hypersensitivity. The worn
surfaces of opposing teeth occlude together very accurately.

Figure 1

Attrition of the mandibular posterior teeth in a patient with


the habit of tobacco chewing. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

Wear of the proximal surface causes decrease of arch


length. Lambrechts et al (1989) reported that the rate of
attrition is about 29 m/year for molars and 15 m/year
for premolars.
Yip et al (2004) studied the differential wear of teeth
and restorative materials. They found that the lowest wear
rates for restorations and the opposing dentition occur with
metal alloys, machined ceramics, and microlled and microne hybrid resin composites.
Radiographic findings
Radiographically the morphology of the crowns is lost and
the occlusal and incisal edges of teeth are bereft of the
radiopaque enamel cap. The curved cuspal edges are reduced
to single flat plane. The incisocervical length of the crown
is shortened. Owing to the secondary dentin formation,
the size of the pulp chambers are reduced. In severe cases,
the pulp chamber and the pulp canals may be obliterated.
Occasionally, hypercementosis may be seen associated with
attrited teeth.
Clinical significance
Attrition of teeth leads to esthetic and functional disturbances. Dentinal hypersensitivity is usually the most common complaint. Severe attrition leads to pulpal exposure
(Figure 2), non-vital teeth and periapical pathology. The
razor sharp cuspal or incisal edges of teeth may cause
traumatic ulcers.

Figure 2

Severe attrition of the mandibular incisors causing exposure


of the pulp. Photograph also showing attrition of incisal
edges of maxillary central incisors. Courtesy: Department
of Oral Medicine and Radiology, MCODS, Mangalore

459

Section VI Teeth and Periodontium

It is often believed that generalized attrition will also


result in a reduction in occlusal face height (vertical dimension of occlusion). However, it has been often noticed that
in spite of the extensive loss of tooth surface the resting
facial height appears to remain unaltered primarily because
of dentoalveolar compensation. Bruxism-associated attrition may be associated with temporomandibular dysfunction.

Figure 3

Management
Patients should be educated regarding the consequences of
attrition. Sharp edges of teeth can be smoothened. Desensitizing toothpastes will help patients presenting with dentinal hypersensitivity. A soft bite guard will help break the
habit of bruxism and prevent further loss of tooth structure.
Teeth with pulpal exposure warrant endodontic treatment.
Finally, crowns may be fabricated for restoring esthetics.

ABRASION
Pathologic wearing away of tooth substance through some
abnormal mechanical process especially in the presence of
abrasive materials is known as abrasion. It usually occurs
on exposed root surfaces of teeth. Different foreign bodies
produce different patterns of abrasion. Most common type
of abrasion is toothbrush and dentifrices (toothpaste and/or
tooth powder) abrasion. Many of the residents in the villages of the Indian subcontinent use charcoal, brick and ash
to cleanse teeth. These indigenous dentifrices abrade teeth
further.

Cervical abrasion with respect to the upper molar along


with gingival recession. Courtesy: Department of Oral
Medicine and Radiology, MCODS, Mangalore

Figure 4

Clinical features
It is seen frequently on exposed root surfaces and in cervical regions of labial and buccal surfaces due to overzealous toothbrushing in horizontal manner. Maxillary teeth
are involved more than mandibular teeth, and left side is
affected commonly in case of right-handed persons and
vice versa. It appears as a V-shaped or a wedge-shaped
ditch on the root side of the cementoenamel junction in
teeth with some gingival recession (Figure 3). The exposed
dentin appears highly polished (Figure 4). Improper use of
dental floss and tooth picks may also produce such lesions
on the exposed proximal root surfaces.
In habitual pipe smokers, notching of teeth can be seen
that conforms to the shape of the pipe stem. It can also be
seen as occupation-related oral nding in carpenters and
tailors who hold objects against the teeth during work.
Exposure of dentinal tubules and the consequent irritation
of odontoblastic processes stimulates the formation of secondary dentin.
When tooth wear is accelerated by chewing an abrasive
substance between opposing teeth, the process is termed
demastication and it exhibits the feature of both attrition
and abrasion.
460

Highly polished surface of the cervically abraded


teeth. Courtesy: Department of Oral Medicine and
Radiology, KLEDC, Bangalore

Grippo et al (2004) described a term, masticatory abrasion to refer to tooth wear on the occlusal or incisal surfaces
due to friction from the food bolus. They reported that the
masticatory abrasion can also occur on the facial and lingual
aspects of teeth as coarse food is forced against these surfaces by the tongue, lips and cheeks during mastication.
Radiographic features
Radiographically, abrasive lesions caused by toothbrush
are seen as half-moon shaped, well-defined radiolucent
areas in the cervical regions of the teeth. These defects are
usually seen involving the maxillary premolar teeth.

Chapter 17 Regressive Alterations of Teeth

However, abrasive lesions caused by dental oss are


usually slender half-moon-shaped radiolucent areas in the
proximal regions of the neck of the teeth. Owing to the
normal ossing pattern, the distal surface of teeth exhibit
relatively deeper radiolucent areas compared to the mesial
surfaces of teeth. Pulp chambers may be obliterated.
Radiographically, these radiolucent areas mimic cervical
carious lesions, root surface caries and cervical burn out.

Figure 5

Management
Patients should be educated regarding the correct brushing and flossing technique. They should be advised to
discontinue any deleterious habits associated with their
occupations. Use of abrasive dentifrices should be strongly
discouraged.
Pulpal exposure is rarely a complication of cervical abrasion as the formation of secondary dentin protects the pulp
from being involved. Dentinal hypersensitivity when present can be managed with the use of desensitizing toothpastes
and mouthrinses.

EROSION (Corrosion)
Eccles in 1982 described erosion as the loss of dental hard
tissues by chemical action not involving bacteria. In simple
terms, erosion is the chemical or electrochemical dissolution
of teeth.
Grippo et al (2004) quoting the description of erosion by
The American Society for Testing and Materials Committee
on Standards proposed that the term erosion should be
replaced by the term corrosion. The American Society for
Testing and Materials Committee on Standards denes erosion as the progressive loss of a material from a solid surface due to mechanical interaction between that surface and
a uid, a multicomponent uid, impinging solid or liquid
particles. In order to explain this in simple terms Grippo
gave an example of river water owing forcefully against
the bridge supports leading to its erosion.
It is a common fact that no such powerful gush of oral
uids exists in the oral cavity. Thus, the term erosion may
be replaced by corrosion to describe chemical dissolution
of teeth.
Clinical features
Erosive lesions are usually smooth surface lesions evident
on the buccal and labial surface of teeth. Occasionally,
proximal surfaces may be involved.
Clinically, erosions appear as wide, polished and smooth
areas on the enamel approximating the cervical margin of
the tooth (Figure 5). The erosive areas are almost always
shallow and exhibit scooped-out architecture. The common teeth to be affected by erosion are the anterior teeth.

Erosive lesions on the buccal surface of the maxillary teeth.


Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

Typically, when the occlusal surfaces of posterior teeth


with restorations are eroded, the margins of the restorations
appear higher than the level of the eroded enamel.

Causes for Corrosion (Flowchart 1)


1. Endogenous/intrinsic causes
Frequent episodes of vomiting as seen in pregnancy, acid
reflux or regurgitation, anorexia nervosa and bulimia cause
corrosion of teeth. Bodecker (1945) showed that the gingival crevicular fluid is acidic and may cause corrosion when
in contact with the cervical regions of the teeth.
Typically, the enamel is translucent and thin. The common sites for erosion are the palatal surfaces of anterior
teeth and occlusal surfaces of posterior teeth. Occasionally
other sites that may be affected include the areas of pooling
of the contents of the gastric reux.
The erosion occurs from the action of hydrochloric acid
and the proteolytic enzyme pepsin that is contained in
gastric juice.
Erosion of the lingual or palatal surface of teeth due to
regurgitation of the acidic contents of the stomach, aggravated by the circular movement of the tongue is termed
perimolysis (Figure 6).
Another term used with regards to regurgitation of the
acidic contents is stress reux syndrome. This syndrome
typically affects young working adults. The acidic reux
usually occurs during the working hours at day. The regurgitated acidic contents are held in the mouth before being
swallowed again. This syndrome produces erosion of the
buccal surfaces of mandibular posterior teeth.
461

Section VI Teeth and Periodontium

Flowchart 1
Erosion

Intrinsic causes

Frequent vomiting
Anorexia nervosa
Pregnancy
Bulimia

Reflux
Gastroesophageal
reflux disease
Stress reflux syndrome

Extrinsic causes

Carbonated drinks (pH of 23)


Citrus food
Occupational hazards (wine tasters,
workers in acidic environments)

Intrinsic and extrinsic causes for tooth erosion

Figure 6

Evans and Briggs (1994) reported a pregnant woman who


had tooth surface loss on the palatal surfaces of maxillary
incisors due to prolonged pregnancy-induced vomiting.
2. Exogenous/extrinsic causes
Acids present in the food consumed such as fruits, carbonated soft drinks, etc. cause corrosion of teeth. Other causes
for corrosion include occupations where an individual is
exposed to acidic fumes, habitual sucking of lemon, tamarind, etc. Chewable forms of certain medications such as
vitamin C tablets can aggravate the corrosion of teeth.
pH of the erosive agent though an important factor for
the erosive potential, other factors such as frequency and
method of contact of the erosive agent and the proximity
of toothbrushing after exposure to the erosive substance
have a substantial bearing on the tooth erosion.

Erosive lesions on the palatal surface of the maxillary


anterior teeth. Courtesy: Department of Oral Medicine
and Radiology, MCODS, Mangalore

Pregnancy and dental erosion Laine (2002) described


the effect of pregnancy on periodontal and dental health.
He reported that the tooth environment is significantly
altered in pregnancy. He stated that a number of salivary
cariogenic microorganisms may increase in pregnancy,
along with decrease in salivary pH and buffer effect.
These changes in salivary composition in late pregnancy and during lactation may temporarily predispose the
individual to dental caries and erosion.
Rockenbach et al (2006) studied the salivary ow rate,
pH, and concentrations of calcium, phosphate and sIgA in
Brazilian pregnant and non-pregnant women. In their study,
there was no difference in salivary ow rates and concentrations of total calcium and phosphate between pregnant
and non-pregnant women. However, pregnant women had
lower pH (6.7) than non-pregnant women (7.5).
462

Erosion Associated with Common Food


Substances
Many of the commonly used food substances have an
acidic pH. Most of these commodities have a pH less than
the critical pH of 5.5 that causes demineralization of teeth.
It is believed that brushing teeth immediately after consuming acidic food may further weaken the tooth and
make it vulnerable to erosive potential of dietary acids.
Table 1 summarizes the acidic content of some commonly consumed food substances.

Erosion Associated with Medications


Pierro et al (2005) evaluated the free sugar concentration
and pH of pediatric medicines. The median of pH values of
the syrups varied from 2.6 to 6.1. In their study, most of
the pediatric syrup medicines showed high concentration
of free sugars and pH below the critical value (5.5), which
can increase their cariogenic and erosive potentials.

Chapter 17 Regressive Alterations of Teeth

Table 1

Acidic content of common food substances

Food substance

pH

Apples

2.93.5

Grapes

2.93.4

Lime

1.82.4

Oranges

2.84.0

Pineapples

3.34.1

Strawberries

3.04.2

Coffee

2.43.3

Black tea

4.2

Wines

2.33.3

7Up

3.5

2.7

2.7

Pepsi
Coke

Vinegar

2.43.4

Ketchup

3.7

Fruit jam

3.04.0

Source: Adapted from Clark et al (1990) and Gandara et al (1999).

Hellwig and Lussi (2006) described the effects of oral


hygiene products and acidic medicines. Acidic or EDTAcontaining oral hygiene products and acidic medicines
have the potential to soften dental hard tissues. Chewable
acetyl salicylic acid tablets and chewable hydrochloric
acid tablets for treatment of stomach disorders can cause
erosion of teeth. Chewable forms of vitamin C supplements
have also been known to cause erosion.

Erosion Related to Deleterious Habits


Areca nut chewing habit
Apart from the mechanical wear of tooth surface, chewing
betel quid may have the potential to cause erosion of teeth.
It is believed that the betel quid can cause a change in salivary pH and its buffering capacity.
Rooban et al (2006) studied the effect of habitual areca
nut chewing on resting whole mouth salivary ow rate
and pH. The mean pH of saliva in non-chewers in their study
was 6.77; whereas the salivary pH was 6.27 in individuals
who chewed betel quid along with lime. It is believed that
in habitual betel quid chewers, lime probably reacts with
bicarbonate buffering system by the loss of bicarbonate,
turning saliva more acidic. Lime (calcium oxide in aqueous
formcalcium hydroxide) could cause a free radical injury
or the high alkaline content of lime may react with the
salivary buffering system and alter the pH.
However, Reddy et al (1980) observed no difference in
salivary pH between the chewers and non-chewers. These

contrasting results could be explained with the different


patterns of betel quid chewing habit and the amount of
lime and other constituents that have been used in the
betel quid.
Chronic alcoholics
Harris et al (1997) studied the effects of alcohol on oral
and dental health in 107 patients. They found a high incidence of tooth wear and trauma to the dentition.
Robb and Smith (1990) studied the prevalence of pathological tooth wear in 37 chronic alcoholics. These patients
had more tooth wear compared to age and sex matched
controls. The erosion was more commonly seen in males
and those who consumed alcohol regularly than those
who had alcohol in episodic binges. Almost 40% of the
patients exhibited erosion on the palatal surfaces of the
upper anterior teeth.
Mandel (2005) suggested that the acidity of wine can
contribute signicantly to dental erosion.

Occupation-related Dental Erosion


Wine tasters
Wines primarily contain tartaric acid and to a lesser
extent malic acid, lactic acid and citric acid. Minute
amounts of succinic acid, citramalic acid, galacturonic
acid and mucic acid may be found in some wines. Carbonic
acid is usually added in champagne to produce the sparkling. The pH of wine is approximately 3.04.0. It is a
common fact that teeth that are softened after drinking
wine are highly vulnerable to attrition or abrasion. It is
also believed that wine alters the inherent salivary protection mechanism.
In studies involving wine tasters by Ferguson et al
(1996), Chaudhry et al (1997), Gray et al (1998), the erosion
of teeth was primarily conned to the maxillary incisors.
Most of the wine tasters evaluated about 2030 wines per
day and most of these tasters had been in the profession
for about 1023 years.
Chikte et al (2005) reported that wine tasters kept the
wine to be tasted in the mouth for 1030 seconds. In their
study, wine tasters exhibited almost three times higher risk
for dental erosion compared to non-taster controls.
Mok et al (2001) in their in vitro study stated that the
erosive potential of wine increased with increasing temperature of the wine.
Various in vitro studies have shown that red wine, white
wine and champagne have the potential to cause erosion of
teeth. White wine and champagne are said to cause relatively more erosion than red wine.
Piekarz et al (2008) showed that dentin is more susceptible to wine erosion than enamel. This nding supports
the hypothesis that erosion progresses much more rapidly
once the dentin is involved.
463

Section VI Teeth and Periodontium

Professional swimmers
Centerwall et al (1986) studied the extent of enamel erosion
among professional swimmers at a gas-chlorinated swimming pool. In their study, the pool water sample had a pH
of 2.7. Although the recommended pH for swimming pools
is 7.28.0. They used the term swimmers erosion for the
acid erosion of dental enamel caused by inadequately maintained gas-chlorinated swimming pools.

Occupations Associated with Exposure


to Acidic Fumes
Workers of battery and galvanizing factories, galvanizing,
pickling, plating and chemical manufacturers are constantly
exposed to sulfuric acid and hydrochloric acid and to some
amount of phosphoric, nitric and hydrofluoric acids. Inhalation of acidic fumes leads to the erosion of the incisal and
labial surfaces of anterior teeth.
Elsbury et al (1951) reported erosion of teeth in tin factory workers who are exposed to 11 mg/m3 tartaric acid dust
for 30 hours a week.
Ten Bruggen Cate (1968) reported dental erosion in individuals involved with the preparation of sanitary cleansers.
Individual studies have also shown dental erosion in
workers of silicone producing units.
Management
Piekarz et al (2008) studied the role of Tooth Mousse (GC
Corporation) in preventing erosion of teeth in wine tasters.
Tooth Mousse contains an anticariogenic remineralizing
agent CPP-ACP (a casein phosphopeptide that stabilizes
amorphous calcium phosphate nanocomplex) and has superior remineralizing properties compared to fluoride.
Studies have shown that Tooth Mousse reduces tooth
wear from attrition in both acidic and neutral environments. It has also been shown that Tooth Mousse can minimize erosion of enamel caused by citric acid. Studies have
shown that Tooth Mousse can reduce enamel, dentin and
cemental erosion.
Dentinal hypersensitivity caused by erosion can be managed with desensitizing agents. Larger erosive lesions can
be restored.

ABFRACTION
Abfraction may be described as the microstructural loss of
tooth substance in areas of stress concentration caused by
tooth flexure. Theoretically it is believed that occlusal
forces create stresses in the cervical area of the enamel
and dentin thereby predisposing the tooth to abrasion and
erosion.

464

Parafunctional habits, malocclusion, excessive masticatory load and use of dental appliances are some known
causes for abfraction.
Abfraction commonly occurs in the cervical region of
teeth, where exure may lead to the fracture of the slender
layer of enamel rods, as well as microfracture of cementum
and dentin.
Morphologically they appear as crescent-shaped lesions
along the cervical margin of the tooth. It often affects a
single tooth with adjacent unaffected teeth. It commonly
affects the mandibular dentition because of the lingual orientation and increased susceptibility to concentration of
tensile stresses in the cervical region.

CLASSIFICATION OF TOOTH WEAR


Bell et al (2002) in their study to assess tooth wear in children with Down syndrome, classified the severity of tooth
wear as follows:

Classification of Severity of Tooth Wear

Group ANo tooth wear or mild tooth wear


Small degree of physiological wear present on 12
teeth
Tooth wear that requires no clinical intervention
Group BModerate level of tooth wear
Higher than physiological level of wear on two or
more teeth that have not affected function or esthetics
Tooth wear that requires clinical intervention
Group CModerate-severe tooth wear
Pathological wear on four or more teeth, defined as
teeth with approximately two-thirds to one-half of
the clinical crown remaining
Tooth wear that requires immediate and aggressive
clinical intervention
Group DSevere tooth wear
Pathological wear on four or more teeth, defined as
teeth with one or more of the following features:
Less than one-third of the clinical crown remaining
Wear to the gum-line
Severely scooped dentin
Tooth wear of a severity rarely seen in this age group
Tooth wear that requires immediate and aggressive
clinical intervention.

Classification Based on Clinical Presentation

Group Ano wear


Group Bwell-defined facet (indicating attrition)
Group Cill-defined facet (indicating multifactorial
etiology)

Chapter 17 Regressive Alterations of Teeth

Table 2

Tooth wear index criteria

Score

Surfaces of tooth involved

Criteria

Buccal, lingual, incisal

No loss of enamel surface characteristics

Buccal, lingual, occlusal, incisal

Loss of enamel surface characteristics

Buccal, lingual, occlusal

Loss of enamel, visible dentin for 1/3 of the surface

Buccal, lingual, occlusal


incisal

Loss of enamel, visible dentin for 1/3 of the surface


Loss of enamel just exposing dentin

Buccal, lingual, occlusal


incisal

Complete loss of enamel, or pulp exposure, or secondary dentin


Pulp exposure or exposure of secondary dentin

Buccal, lingual, occlusal, incisal

Excluded from analysis missing tooth, partially erupted, orthodontic band,


composite restoration, any crowns, tooth fracture, and fissure sealant

Source: Proposed by Smith and Knight, modified by Millward et al.

Group Dwell-defined areas of dentin or pitting of


dentin (indicating erosion).

Tooth wear index criteria are given in Table 2.


Bartlett et al (2008) proposed a new scoring system for
erosive tooth wear which can be used both for scientic
and clinical purposes. They termed this scoring system as
Basic Erosive Wear Examination (BEWE).
In this system, all teeth in every sextant are assessed
and the most severely affected tooth in every sextant is
scored and the cumulative score will guide the dental practitioner in choosing the best treatment modality.
Criteria for grading erosive wear

Score 0No erosive tooth wear


Score 1Initial loss of surface texture
Score 2Distinct defect, hard tissue loss 50% of the
surface area
Score 3Hard tissue loss 50% of the surface area.
The buccal/facial, occlusal, and lingual/palatal surfaces
are examined. Once all the sextants have been assessed,
the sum of the scores is calculated.
BEWE scores

Sextant (1714)record the highest score


Sextant (1323)record the highest score
Sextant (2427)record the highest score
Sextant (3734)record the highest score
Sextant (3343)record the highest score
Sextant (4447)record the highest score

The sum of the highest scores for each sextant is taken as


the indicator for treatment planning.

Score between 3 and 8: Oral hygiene and dietary assessment, and advice, routine maintenance and observation, Repeat at 2-year intervals.
Score between 9 and 13: Oral hygiene and dietary
assessment, and advice, identify the main etiological
factor(s) for tissue loss and develop strategies to eliminate respective impacts. Consider fluoridation measures
or other strategies to increase the resistance of tooth
surfaces. Ideally, avoid the placement of restorations
and monitor erosive wear with study casts, photographs
or silicone impressions. Repeat at 6- to 12-month
intervals.
Score 14 and over: Oral hygiene and dietary assessment,
and advice, identify the main etiological factor(s) for
tissue loss and develop strategies to eliminate respective impacts. Consider fluoridation measures or other
strategies to increase the resistance of tooth surfaces.
Ideally, avoid restorations and monitor tooth wear
with study casts, photographs or silicone impressions.
Especially in cases of severe progression consider special care that may involve restorations. Repeat at 6- to
12-month intervals.

RESORPTION OF TEETH
It is defined as a condition or pathologic process resulting
in the loss of dentin, cementum and/or bone.
Types of resorption
1.

Management strategies

Score 2: Routine maintenance and observation, repeat


at 3-year intervals.

2.

Internal resorption
a. Internal replacement
b. Internal inflammatory
i. Transient
ii. Progressive
External resorption
a. External surface resorption

465

Section VI Teeth and Periodontium

Figure 7

Intraoral periapical radiograph showing external resorption


of the root apex in a long-standing periapical abscess.
Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

3.
4.

b. External inflammatory
c. Ankylosis
d. Replacement resorption
Combined internal and external
Transient apical breakdown.

Internal resorption can occur due to various causes like


chronic pulp inflammation, trauma, pulpotomy, restorative procedures, herpes zoster, hereditary, cracked tooth
syndrome, invaginated cingulum and orthodontic tooth
movement.
External resorption can be caused due to replantation
of tooth, orthodontic forces, eruption of neighboring teeth,
root fracture, trauma, necrotic pulp, chronic periapical
inammation or infections (Figure 7), root planing, citric
acid treatment and other pathological conditions like cysts
(Figure 8), ameloblastoma (Figure 9), giant cell tumor,
brous osseous lesions, hereditary conditions, bleaching
(especially causes cervical external resorption) and orthognathic surgery.
Diagnosis is often misinterpreted. External resorption
can be described as internal or vice versa. Often the diagnosis can be simplied by a careful assessment of the history, particularly if it is trauma.
A pink appearance of the crown is indicative of a highly
vascular tissue which has removed sufcient enamel and
dentin to allow it to be visible through the overlying tooth
substance. Although earlier descriptions of a pink tooth as
being internal is incorrect as it may be either internal or
external in origin. In the absence of history of trauma, it is
more likely that the pink spot will indicate an external
origin.
466

Figure 8

External root resorption of the second molar secondary to the


dentigerous cyst associated with the impacted third molar.
Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

Figure 9

External root resorption of the mandibular first molar


secondary to ameloblastoma involving the body and
ramus of the mandible. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

Clinical assessment of the mobility may be of use in


differential diagnosis. A tooth displaying no mobility or held
in infraocclusion indicates ankylosis or replacement resorption. Percussion test will also produce a resonant sound.

Chapter 17 Regressive Alterations of Teeth

The key diagnostic tool is a good radiograph. The margins


of internal resorptive defect are smooth and well dened;
in contrast to that of external are rough and has moth-eaten
appearance. Most internal resorptive defects are symmetrical and external resorptive defects are usually asymmetrical. The anatomic conguration of the root canal is altered
and increased in size with internal resorption. In external
resorption, the canal is unaltered, and its outline can be followed through the resorptive defect. Radiographs exposed
at different horizontal beam angles can aid in distinguishing internal from external resorption. If the defect is internal, the relationship of the canal to the defect will remain
the same, regardless of the angles. If the defect is external,
the relationship of the defect to canal will shift as the
horizontal angle of the beam is altered. Key cells involved
in resorption are monocytes, macrophages, osteoclast, odontoclasts, dentinoclasts and cementoblasts.

Flowchart 2
Traumatic injury

Intrapulpal hemorrhage

Organizes to granulation tissue

Compresses the dentinal wall

Predentin formation stops and


odontoclasts differentiate

Internal resorption

Systemic regulatory factors


Parathyroid hormone increases osteoclastic activity by
activation of osteoclasts to increase the production of carbonic anhydrase and promotion of fusion of marrow cells
to produce multinucleated giant cells.
1,25-Dihydroxy vitamin D increases the activity of osteoclasts without increase in number and calcitonin inhibits
resorption by suppressing the osteoclastic cytoplasmic motility and producing cell retraction.

Events in resorption of teeth

structure has no relationship with the normal bone forms


of tooth, hence termed as metaplastic tissue. Radiographically, it appears as an enlargement of the pulp space. The
pulp space thus enlarged is less radiodense giving the
appearance of partial canal obliteration.

Neuronal regulatory factors

Events in resorption of teeth (Flowchart 2)

Neuropeptides released by the terminal nerve endings such


as substance P (SP), calcitonin gene related peptide (GRP),
neurokinin A, vasoactive intestinal polypeptide (VIP), etc.
increase vasodilatation, thus an increase in macrophages
and an increased osteoclastic activity, remove mechanism
of resorpion.

Treatment consists of pulp tissue removal and canal cleaning


and shaping, followed by scaling the canal system.

Internal resorption
It is also called chronic perforating hyperplasia of pulp,
internal granuloma, odontoclastoma and pink tooth of
Mummery. Resorption of internal type occurs from pulp
space/root canal space and is asymptomatic. It is usually
discovered during routine radiographic evaluation. A pink
colored discoloration is visible if extensive internal resorption occurs in the coronal portion of the tooth, as described
by Mummery. Most cases are found in the anterior region.
Etiological factors are mainly trauma and caries.
Internal resorption can be of two types: internal
replacement (metaplastic) and internal inammatory.
Internal replacement type occurs as a result of lowgrade irritation of the pulp such as chronic irreversible
pulpitis or pulp necrosis. This can occur because of trauma
or application of extreme heat to the tooth. There is concomitant resorption of hard tissue with frequent deposition
of hard tissue resembling bone or cementum. The resultant

External resorption
External resorption is the one which occurs primarily from
the periodontal space affecting the root surface. Four categories of external resorption have been described based
on the clinical and histological manifestations:

External surface resorption


External inflammatory resorption
Cervical
Apical
Ankylosis
External replacement resorption.
External surface resorption is a transient phenomenon in
which the tooth undergoes spontaneous destruction and
repair. It is found in all the teeth and considered to be a
normal physiologic response. It is a self-limiting process
and does not require any treatment.
External inammatory root resorption is described as a
bowl-shaped defect which penetrates the dentin. This
occurs following irritation or injury of the periodontium due
to trauma, periodontal infection or orthodontic treatment.
Based on location it can be cervical and apical. Cervical
467

Section VI Teeth and Periodontium

resorption occurs following injury to the epithelial cervical


attachment apparatus. It can occur because of physical
insult like trauma, surgical procedures, orthodontic treatment, bruxism and periodontal root planing. Chemical
injury as a result of 30% hydrogen peroxide can cause
cervical resorption.
Apical resorption occurs because of traumatic injury
(luxative and intrusive movements), periradicular periodontitis and orthodontic procedures.
Ankylosis is primarily associated with luxation injury,
especially avulsion. It is the union of tooth and bone with
no intervening connective tissue following extensive
resorption. Ankylosis can be further categorized as transient or progressive in nature.
External replacement resorption is caused due to luxative injury. This is a continuous process by which the tooth
is gradually resorbed and replaced by bone. It differs from
ankylosis in which it exhibits the presence of intervening
inamed connective tissue.

Regressive Alterations of Dentin


Secondary dentin Physiologic dentin deposition proceeds throughout life. It is a protective response and can
be differentiated from primary dentin by the sharp bending of tubules producing a line of demarcation. It has
incremental patterns of deposition. The tubular structures
are less regular than those of primary dentin. The deposition occurs in greater quantities in the floor and roof of
pulp chamber than on walls; so, there is reduction of pulp
chamber and pulp horns as the tooth ages.
Reparative dentin It is also known as irregular or tertiary
dentin. It is a protective response to noxious stimuli such
as caries operative procedures, restorative materials, abrasion, erosion or trauma. It is deposited at the rate of 1.5 m
per day, produced by replacement odontoblasts. Reparative
dentin has less tubules and less mineralized. There is a definite demarcation between secondary and reparative dentin which is called calcitraumatic line.
Dentinal sclerosis It is a regressive alteration in tooth
surface that is characterized by calcification of the dentinal tubules. It is also called transparent dentin. The causes
for dentinal sclerosis includes aging caries and tooth wear.
Exact mechanism of deposition of calcium salts is not
understood. Most likely source is dentinal fluid within the
tubules. Initially, only sporadic hydroxyapatite crystals
are deposited which gradually fill the tubules. This makes
it to appear transparent in transmitted light and dark in
reflected light. It decreases the permeability of dentin and
slows the carious process. It decreases the conductivity of
odontoclastic process.
Dead tracts When the odontoblasts disintegrate completely,
their empty tubules are filled with air, so they appear black
468

Figure 10

Dead tracts and reparative dentin. Courtesy: Department of


Oral Pathology, MCODS, Mangalore

in transmitted light and white in reflected light (Figure 10).


The causes for dead tracts include caries, attrition, abrasion
and erosion. These are seen more in narrow pulpal horn
areas, because of crowding of odontoblasts. More commonly
these are seen in older individuals.

Regressive Alterations of Pulp


Reticular atrophy of pulp change is seen in older individuals. Clinically asymptomatic, responds normally to vitality
tests. Histopathologically, large vacuolated spaces in pulp
are seen with decreased cellular elements. Degeneration and
disappearance of odontoblast is also seen.
Pulp calcifications Pulp calcifications (pulp stones, denticles) are nodular calcified masses appearing in either or
both the coronal and radicular portion of pulp (Figure 11).
These are usually asymptomatic until they impinge on
nerves or blood vessels. Pulp stones are classified as true
denticles or false denticles according to microscopic
appearance. True denticles are rare and resemble dentin
structurally with dental tubules and odontoblastic processes and are usually seen close to the apical foramen.
False denticles do not resemble dentin. These do not exhibit
dentinal tubules but have concentric layers of calcified
tissue. Flowchart 3 describes the formation of pulp stone.
Pulp stones can be either free, attached or embedded
according to the mode of attachment. Free dentricles are
not attached to walls of pulp space; attached stones are
attached to wall of pulp cavity, and embedded dentricles
are attached and become an integral part of dentin. Various
causes of formation of pulp stones are aging, systemic
causes like cholelithiasis, cardiac, renal lithiasis, arteriosclerosis, gout, acromegaly, and diseases such as dentin dysplasia type II, pulpal dysplasia, tumoral calcinosis, calcinosis

Chapter 17 Regressive Alterations of Teeth

universalis and EhlersDanlos syndrome. It may cause


problem during endodontic therapy. Radiographically, it
appears as radiopaque masses in pulp space (Figure 12).

Regressive Alterations of Cementum


Cementum is the mineralized dental tissue that overlies the
anatomic roots of teeth. It provides the site for attachment

of the periodontal ligament fibers that anchor the tooth to


the surrounding structures. It is avascular.
The inorganic component of cementum consists of
hydroxyapatite and uoride. It is interesting to note that
the uoride content in cementum is the highest compared
to all mineralized tissues.
Cellular cementum (presence of cementocytes) is generally seen at the apical one-third of the root; whereas the
rest of the root surface is covered by acellular cementum
(lack of cementocytes).

Figure 11
Figure 12

Radiograph revealing well-defined radiopacities in the pulp


chamber of first and second molars suggestive of pulp stones.
Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

Histologic appearance of a free pulp stone. Courtesy:


Department of Oral Pathology, MCODS, Mangalore

Flowchart 3
Process of formation of pulp stone

Local metastatic dysfunction

Trauma

Hyalinization of injured wall

Vascular damage
(thrombosis)

Fibrosis
Mineralization
(nidus formation)

Grows with time

Pulp stone

Process of formation of pulp stone

469

Section VI Teeth and Periodontium

Figure 13

Bulbous roots evident in extracted teeth specimen. Courtesy:


Department of Oral Pathology, MCODS, Mangalore

The thickness of cementum overlying the root varies


based on the location. The thickness of the cementum at
the cementoenamel junction is the thinnest and it measures
2050 m at the apex. The thickness of cementum is roughly
150200 m.

Figure 14

Intraoral periapical radiograph showing thickening of the


roots. Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

Figure 15

Hypercementosis
Hypercementosis is a non-neoplastic deposition of excessive
cementum which is continuous with the normal radiographic cementum. It is asymptomatic and seen in adulthood. The incidence of hypercementosis increases with
age. It may appear in one tooth or involving multiple teeth
(Figure 13). Hypercementosis is frequently seen in relation
to the premolars.
The cause for hypercementosis can be either due to
local factors like abnormal occlusion, inammation, nonfunctional tooth, tooth repair, root fracture, and cemental
tear or systemic factors like Pagets disease, hyperpituitarism (acromegaly and gigantism), arthritis, calcinosis,
rheumatic fever, thyroid goiter, idiopathic.
Radiographically, thickening or blunting of root is seen.
Enlarged root is surrounded by the radiolucent periodontal
ligament space and intact radiopaque lamina dura (Figures 14
and 15).
Histological section reveals deposition of cellular or
secondary cementum in concentric layers over the existing
thin layer of acellular or primary cementum. This cellular
cementum has also been referred to as osteocementum
owing to its histological resemblance to bone.
Treatment is not required but it may pose problem during
extraction.
470

Radiograph revealing bulbous roots with intact lamina dura.


Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

Cementicles
Small foci of non-neoplastic calcified tissue, which lie in
periodontal ligament along the lateral and apical root
areas are called cementicles. Calcification of epithelial cell
rest of Malassez, aging and cemental tears undergoing
remodeling have all been implicated in the formation of
cementicles. These present as circular laminated structures.
When attached to root, cementum shows roughened globular
outline on the root surface.

SECTION

System Review

VII

18
19
20
21
22
23

Systemic Disorders and their Clinical Implications


Bone Diseases and Fibro-osseous Lesions
Autoimmune Disorders
Granulomatous Diseases
Sexually Transmitted Diseases
Nutritional and Metabolic Disorders

473
568
590
605
625
633

471

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Prelims-Ongole.indd ii

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Systemic Disorders and


their Clinical Implications

CHAPTER

Arshiya Ara, Ceena Denny, Gajendra


Veeraraghavan, Seema Patil, Vishwananth R,
Sarat Gummadapu, Veena KM, Ranganath
Ratehalli, Sandeep Deshpande

Cardiovascular Disorders
Symptoms Suggestive of Cardiovascular
Disease
Chest Pain
Breathlessness or Dyspnea

Common Cardiovascular Disorders and


their Dental Considerations

Cyanotic
Acyanotic

Platelet Disorders

Thrombocytopathic Disorders

Thrombocytopenic Disorders

Rheumatic Fever
Infective (Bacterial) Endocarditis
Clinical Conditions that Warrant Use of Antibiotic
Prophylaxis
Treatment Needing Antimicrobial Prophylaxis in
Patients at Risk of Infective Endocarditis

Idiopathic Thrombocytopenic Purpura


Thrombotic Thrombocytopenic Purpura

Disorders of Coagulation

Inherited Coagulation Disorders


Hemophilia A
Hemophilia B and C
Von Willebrands Disease

Heart Failure
Classifications of Heart Failure
Oral Disease Aspects

Hematological Disorders
Red Blood Cell Disorders
Polycythemia
Anemia
Iron Deficiency Anemia
PatersonKelly Syndrome (PlummerVinson Syndrome)
Anemia due to Vitamin B12 and Folic Acid Deficiency
Aplastic Anemia
Glucose-6-phosphate Dehydrogenase Deficiency
Sickle Cell Anemia

Thalassemia
White Blood Cell Disorders
Qualitative Disorders

Respiratory Disorders

Classification of Respiratory Tract Disorders

Common Symptoms of Respiratory Diseases


Cough
Sputum
Hemoptysis
Chest Pain
Breathlessness or Dyspnea
Wheezing

Non-neoplastic Disorders
Leukopenia
Reactive Leukocytosis

Upper Respiratory Tract Infections


Viral Infections
Allergic Rhinitis
Pharyngitis and Tonsillitis

ChediakHigashi Syndrome

Acquired Coagulation Disorders


Liver Disease
Vitamin K Deficiency
Disseminated Intravascular Coagulation

Vascular Disorders (Vessel Wall)


Hereditary Hemorrhagic Telangiectasia
EhlersDanlos Syndrome
Marfans Syndrome
Scurvy

Ischemic or Coronary Heart Disease


Myocardial Infarction
Congenital Heart Disease

Bleeding Disorders
Classification of Bleeding Disorders

Angina Pectoris

Neoplastic Disorders
Leukemia
Lymphomas
Multiple Myeloma

Hypertension

18

Lower Respiratory Tract Infections


Asthma

473

Section VII System Review

Chronic Obstructive Pulmonary Disease or


Chronic Obstructive Airway Disease
Cystic Fibrosis

Granulomatous Diseases

Malignant Disorders

Categories of Disturbances of Endocrine Function


Pathophysiology of HypothalamicPituitary Axis

Other Respiratory Diseases


Legionnaires Disease (Legionellosis)
Obstructive Sleep Apnea Syndrome

Renal Disorders
Renal Diseases
Chronic Renal Failure
Uremic stomatitis

Gastrointestinal Disorders
Gastroesophageal Reflux Disease

Inflammatory Bowel Disease


Ulcerative Colitis
Crohns Disease
Hiatal Hernia
Peptic Ulcer Disease
Eating Disorders
Anorexia Nervosa
Bulimia Nervosa

General Overview of Functional Mechanisms of


Endocrine System
Hormones

CARDIOVASCULAR DISORDERS
Cardiovascular disease is quite common, though more frequent and severe in later life, can also affect young individuals. It is one of the leading causes of death in the world.
A thorough knowledge of cardiovascular diseases is necessary because of its implications in dentistry and also the
initial measures taken by the dentists in case of certain
emergency conditions can be lifesaving.
474

Thyroid Gland
Pathophysiology of HypothalamicPituitaryThyroid
Axis

Disorders Associated with Thyroid Gland


Hypothyroidism
Hyperthyroidism

Parathyroid Glands
Hyperparathyroidism
Hypoparathyroidism
Tetany

HypothalamusPituitaryAdrenal Axis
Cushings Syndrome
Endocrinopathic Pigmentation
Adrenal Insufficiency
Aldosteronism
Disorders of Adrenal Medulla
Sex Hormones

Jaundice
Hepatitis

Endocrinal Disorders

Disorders of Posterior Pituitary


(Neurohypophysis)
Diabetes Insipidus

Liver Diseases

Neuromuscular Disorders
Bells Palsy
Epilepsy
Parkinsonism
Multiple Sclerosis
Muscular Dystrophy
Oromandibular Dystonia
Myasthenia Gravis

Growth Hormone
Growth Hormone Deficiency
Growth Hormone in ChildrenDwarfism
Adult GH Deficiency
Growth Hormone Excess
Gigantism
Growth Hormone Excess in Adults

Bronchogenic Carcinoma

General Overview of Disorders of Endocrine


System

Pregnancy
Multiple Endocrine Neoplasia Type III
(Multiple Mucosal Neuroma Syndrome)

Saliva and Monitoring of Hormone Levels

Mental Health and its Relevance to Dentistry

Concepts of Mental Illness and its Classification

Diagnostic Criteria and Screening Questions

Interesting Interface between Dentistry and


Psychiatry

Management of Psychiatric Disorders

Cardiovascular history taking


Clinicians must assess the status of cardiovascular system
within the context of the patients overall health. These associated conditions can heighten cardiovascular risk during
dental care. Consequently, an initial medical history should
be obtained from all patients and it must be reviewed with
the patient at each appointment to identify serious cardiac
conditions. The clinicians should also note history of cerebrovascular disease, renal dysfunction, chronic pulmonary

Chapter 18 Systemic Disorders and their Clinical Implications

disease, diabetes mellitus, anemia, dyslipidemia, peripheral vascular disease, orthostatic intolerance and anemia.
Further an accurate record of current medication taken by
the patient, use of tobacco products, alcohol and over-thecounter and recreational drugs should be documented.

The functional capacity can be expressed in terms


of metabolic equivalent (MET) values. Functional
capacity can be classified as:
1 MET or more
Do light work around the house
Walk a block on level ground at 3.24.8 km/
hour
4 METs or more
Climb a flight of stairs or walk up a hill
Walk on level ground at 6.4 km/hour
Run a short distance
Do heavy work around the houses (scrubbing
floors, lifting or moving heavy furniture)
10 MET or more
Participate in strenuous sports (swimming,
singles tennis, football, basketball or skiing)

SYMPTOMS SUGGESTIVE OF
CARDIOVASCULAR DISEASE
Chest Pain
It is the common presentation of cardiac diseases, though can
be a manifestation of disease of the lungs, musculoskeletal
system or gastrointestinal system. Pain is usually felt behind
the sternum, radiates across the chest and down the arms,
it may also radiate to the back or to the mandible.

The functional capacity can be graded as:

Breathlessness or Dyspnea
It is a major symptom of many cardiac disorders, particularly left heart failure. Dyspnea may vary in severity from
an uncomfortable awareness of breathing to a frightening
sensation of fighting for breath.
There are three forms of dyspnea:

Orthopnea: Lying flat causes a steep rise in left atrial


pressure in patients with heart failure resulting in
pulmonary congestion and severe dyspnea. A semirecumbent position helps such patients.
Paroxysmal nocturnal dyspnea: Frank pulmonary
edema on lying flat awakens the patient from sleep
with distressing dyspnea. Symptoms are corrected by
standing upright.
Exertional dyspnea: Exercise causes a sharp increase
in left atrial pressure resulting in dyspnea.
Fatigue Exertional fatigue is an important symptom of
heart failure and is more severe toward the end of the day.
Palpitation Awareness of the heartbeat is common during
exertion or heightened emotions. However, it may be indicative of an abnormal cardiac rhythm.
Dizziness and syncope Cardiovascular disorders produce dizziness and syncope by transient hypotension
resulting in abrupt cerebral hypoperfusion. Recovery is usually rapid.
Lower limb pain or discomfort A tight or cramping pain
in lower limb muscles on exercise may be present.
Edema of legs Bilateral swelling of the legs due to edema
is a common feature of chronic heart failure.
The history should also determine the patients functional
capacity.

Functional capacity
Functional capacity refers to an individuals capacity
to perform a spectrum of common daily tasks.

Excellent (if  10 MET)


Good (710 MET)
Moderate (47 MET)
Poor ( 4 MET).

Patients are at an increased cardiac risk when unable to


meet a 4 MET demand during normal daily activity.
Physical examination
The general appearance of the patient can provide valuable information related to his/her physical and emotional
state. Pallor, cyanosis, peripheral edema, dyspnea, tremors,
CheyneStokes respiration, obesity and anxiety are clues
that suggest the presence of cardiovascular disease.
Cyanosis It is defined as the blue color of the skin and
mucous membranes due to the presence of excessive amount
of deoxygenated hemoglobin in these tissues. It is seen in
heart failure, cyanotic congenital cardiac disease and chronic
cardiac disorders.
Finger clubbing It is the obliteration of the angle between
nail base and adjacent skin of the finger. Clubbing is characterized by the thickening of the nail bed secondary to
hypervascularity and opening of the anastomotic channels
in the nail bed. It is seen in congenital cardiac disease and
infective endocarditis.
Distended neck veins Systemic fluid retention and inability of heart to pump blood into the lungs may be seen as
distention of the veins in the neck.
Swelling of legs due to peripheral edema Bilateral
swelling of both the legs may be due to chronic heart failure.
Edema is detectable by fingertip pressure over the tibial bone
for about 30 seconds, a pit due to physical displacement of
excessive tissue fluid is observed.
Blood pressure Determination of the blood pressure provides a useful clue that will confirm or rule out significant
cardiovascular disease. It should be recorded on all new
475

Section VII System Review

patients at the time of initial appointment and at all subsequent appointments on all patients with a history of hypertension, cardiovascular disease, diabetes mellitus, thyroid
disorders, adrenal disease, renal dysfunction and significant
use of tobacco, alcohol or coffee. The auscultatory method
of measurement of BP is recommended. In patients older
than 50 years, elevated systolic pressure may predict the
potential for cardiovascular morbidity and mortality.
Pulse rate and rhythm The pulse pressure closely correlates with systolic pressure and is a reliable cofactor that
will provide us with information on cardiovascular disease.
Rate below 60 or above 100 in adults and if associated with
symptoms such as sweating, weakness, dyspnea and chest
pain should be considered as a risk factor in association
with non-cardiac procedures. Further abnormalities in the
normal rhythm of the pulse should provoke a search for
any underlying cardiac diseases.

COMMON CARDIOVASCULAR DISORDERS


AND THEIR DENTAL CONSIDERATIONS
Hypertension
Hypertension is a disorder characterized by an abnormal
elevation of arterial pressure, which if sustained and
untreated, is associated with a significant increase in morbidity and mortality. The systolic or diastolic pressure or
both are elevated in hypertension.
It may be asymptomatic for long periods but ultimately
leads to damage with resultant symptoms in several organs
including kidney, heart, brain and eyes.
It is generally accepted that a sustained systolic blood
pressure of 140 mmHg or more and a sustained diastolic
blood pressure of 90 mmHg or more is abnormal.
Etiology
Majority of the patients with hypertension have no cause
for their disease. These patients are diagnosed to have
primary, idiopathic or essential hypertension. Essential
hypertension is seen in elderly, obese and individuals who
are tensed and fearful. Genetic factors also play a role.
However, a few patients have underlying systemic diseases
that produce hypertension, which is known as a secondary
hypertension.
Systemic diseases causing secondary hypertension

476

Renal disease (renal parenchymal disease, renal artery


stenosis)
Adrenal abnormalities (primary aldosteronism, Cushings
syndrome, pheochromocytoma)
Coarctation of aorta
Hyperthyroidism
Pregnancy (eclampsia)

Central nervous system (CNS) disorders (head injury,


infection, hemorrhage and brain tumors)
Autonomic hyperactivity
Sleep apnea
Drug-induced (cyclo-oxygenase [COX-1 and COX-2]
inhibitors, sympathomimetics, steroid hormones, cyclosporine and tacrolimus).
Lifestyle risk factors increasing the chances of a person
becoming hypertensive are:

Obesity
High dietary salt intake
Excess alcohol
Smoking
Physical inactivity
Stress/anxiety.

Signs and symptoms


A patient with hypertension is usually asymptomatic for
quite a few years. The early symptoms include occipital
headache, vision changes, ringing ears, dizziness, weakness
and nose bleeding. Odontalgia due to hyperemia or congestion of dental pulp has also been reported.
Untreated hypertension reduces the life span by 1020
years. Even mild hypertension that has not been treated
for 710 years increases the risk of complications. Sustained hypertension results in arterial damage (atherosclerosis) and the onset of these vascular changes in the kidney,
cardiovascular system, cerebrovascular system and eyes can
cause complications such as renal failure, coronary insufciency, myocardial infarction, congestive cardiac failure,
cerebrovascular accident (stroke) and blindness in patients.
Malignant hypertension develops in 1% of hypertensives.
The chief complication is severe ischemic damage to kidney
and renal failure. In the absence of treatment, it can be
fatal within 1 year of diagnosis.
Blood pressure is measured by the use of a sphygmomanometer, an instrument that indirectly records the diastolic and systolic pressure.
Food, exercise, alcohol and smoking should be avoided
for 30 minutes before measurement of BP and also the
patient should be at rest for at least 5 minutes.
Faulty BP readings involve using improper size cuffs or
applying the cuffs too loosely or too tightly.
Classication of blood pressure
Classification

Systolic BP
(mmHg)

Diastolic BP
(mmHg)

Normal

120

80

Pre-hypertension

120139

8090

Stage 1 hypertension

140159

9099

Stage 2 hypertension

160

100

Chapter 18 Systemic Disorders and their Clinical Implications

Malignant hypertension It is a highly elevated blood


pressure associated with organ damage (eyes, brain, lungs
and kidneys are affected). The systolic and diastolic blood
pressures are usually more than 240 mmHg and 120 mmHg
respectively.
White coat hypertension It is a phenomenon in which
patients exhibit elevated blood pressure in a clinical setting
but not when recorded by themselves at home or when
ambulatory. White coat hypertension is believed to be secondary to anxiety, some individuals may experience during
their visit to a hospital.

Therapeutic goals and pharmacologic strategies for hypertension


Therapeutic goal

Pharmacologic strategies

Reduce volume overload


Block beta-1 adrenergic
receptors
Dilate blood vessels
Reduce sympathetic outflow
from the central nervous
system

Diuretics
Beta-1 adrenergic receptor antagonists
ACE inhibitors
Angiotensin II receptor antagonists
Calcium channel blocking agents
Alpha-1 adrenergic receptor antagonists
Alpha-2 adrenergic receptor antagonists

General management

Oral side effects of antihypertensive medicines

Drugs

Side effects

Diuretics

Dry mouth, lichenoid reactions

Beta blockers

Dry mouth, lichenoid reactions, taste


change

ACE inhibitors

Loss of taste, dry mouth, ulcerations,


angioedema

Calcium channel blockers

Gingival enlargement, dry mouth, altered


taste

Alpha blockers

Dry mouth

Direct-acting vasodilators

Facial flushing possible, increased risk of


gingival bleeding and infection

Central-acting agents

Dry mouth, taste changes, parotid pain

Angiotensin II antagonists

Dry mouth, angioedema, sinusitis, taste


loss

Acute emotions should be avoided.


In patients with secondary hypertension, manage the
primary cause.
Patient should practice the following for a lifetime:
Weight lossmaintaining ideal bodyweight lowers
systolic BP reading by 520 points.
Reduction in salt intake less than 2.4 g/day
Restricting alcohol and caffeine
Stop smoking
Exercise (lowers BP by 59 mmHg)
Intake of fruits, vegetables and low fat dairy
products.
Specific management
Antihypertensive therapy

Direct-acting vasodilators: Nitroglycerin and minoxidil


directly relax vascular smooth muscle. Methyldopa and
clonidine act in the CNS to decrease sympathetic nervous system output.
Angiotensin II receptor blockers: Losartan and
telmisartan prevent angiotensin II from binding on
smooth muscle sites in arteries, promoting vasodilatation.
Diuretics: Frusemide and hydrochlorothiazide reduce
blood volume and decrease vascular resistance.
Beta blockers: Propranolol and sotolol reduce heart
rate, and force of contraction. Selective beta blockers
are preferred. Non-selective beta blockers are contraindicated in patients with asthma, because their beta
agonist action is blocked.
ACE inhibitors: Captopril, ralopril retard reninangiotensin system leading to vasodialatation.
Calcium channel blockers: Amlodipine, nifedipine,
decrease the calcium influx in smooth and cardiac muscles, reduce total peripheral resistance and decrease
force of contraction.
Alpha blocking agent: Prazosin, terazosin prevent norepinephrine from binding to receptors in arterioles
leading to vasodialatation.

Dental considerations
Patients with controlled hypertension can receive dental
care in short appointments.
Anxiety and pain should be avoided since endogenous
epinephrine release in response to pain or fear may induce
dysrhythmias.
Preoperative reassurance and sedation with 10 mg
temazepam or 5 mg diazepam may be helpful.
Raising patients from supine position may cause postural
hypertension and loss of consciousness if patient is using
thiazides, calcium channel blockers.
Aspirating syringe should be used to give local anesthesia to avoid intravenous entry of epinephrine.
Epinephrine in local anesthesia is not contraindicated
unless systolic pressure is over 200 mmHg or diastolic pressure is over 115 mmHg.
Epinephrine containing local anesthesia should not be
given in large doses in patients taking non-selective beta
blockers since interaction may induce hypertension and
cardiovascular complications.
Gingival retraction cords containing epinephrine should
be avoided.
477

Section VII System Review

Administration of two to three cartridges of local anesthesia with epinephrine 1:100,000 will not cause cardiovascular changes.
Epinephrine should be used with caution in patients taking tricyclic antidepressants and diuretics since acute hypertensive changes and dysrhythmias, respectively may occur.

ISCHEMIC OR CORONARY HEART DISEASE


It is one of the most common medical problem in general
population. Coronary heart disease is an inflammatory
disease affecting the large and medium sized arteries of
heart resulting in inadequate or decreased coronary blood
flow. Atherosclerosis and hypertension are the major contributory factors.
Atherosclerosis basically refers to the formation of brofatty lesions in the walls of arteries. These may increase in
size to cause stenosis of the vessels reducing the blood ow
to the heart on exercise. This is known as angina. In the
later stages, the atherosclerotic plaque ruptures and exposes
the arterial blood to the plaque contents and stimulates
the formation of hemostatic plug. This occlusive thrombus
may cause myocardial infarction.
It is related to a variety of risk factors. Knowledge about
the risk factors will help the dentist to assess the risk of
cardiac problems in patients with no coronary problems.
Risk factors
Non-modifiable factors
1. Family history: Presence in patients parents, increases
the risk of occurrence in patients at an early age.
2. Gender: Men between 25 and 65 years of age are more
prone and women at post-menopausal age.
Modifiable factors
1. Total cholesterol of more than 240 mg/dl is associated
with ischemic heart disease.
Elevated LDL, decreased HDL, increased total to HDL
cholesterol and hypertriglyceridemia also contribute.
Statins and fibrates correct lipid abnormalities.
2. Hypertension: Systolic pressure more than 140 mmHg
or diastolic pressure more than 90 mmHg increases
the chances of ischemic heart disease.
3. Smoking: Women who smoke more than 19 cigarettes
per day are likely to have ischemic heart disease.
4. Other risk factors are diabetes mellitus, obesity, lack of
exercise, lack of fruits and vegetables in the diet, alcohol use, stress, elevated levels of C-reactive proteins.

Angina Pectoris
It is the most common clinical presentation of ischemic
heart disease and is infrequent before the age of 40 years.
478

It may be defined as a temporary inability of the coronary


arteries to supply the myocardium with the sufficient
amount of circulated blood. Atherosclerotic narrowing of
the coronary arteries is an important cause of this imbalance in oxygen supply. It is rarely caused by spasm of the
blood vessels. Initially, the atherosclerosis does not lead to
any symptoms. However, the obstruction becomes large
over a period of decades to cause pain. The pain of angina
is described as a sense of choking, tightness, heaviness, or
compression of the chest, sometimes radiating to the left
arm or jaws. The common precipitating causes include
physical exertion and emotions.
Levines sign is characteristic of ischemic chest pain.
It is seen in angina pectoris and myocardial infarction.
This sign described by Dr Sam Levine who observed many
of his patients suffering from chest pain hold their st
over the chest.
Variants of angina
Stable angina Pain only on exertion and relieved by rest
within 10 minutes. Stable angina is caused by fixed atheromatous plaque in one or more coronary arteries.
Unstable angina Angina at rest, angina appearing more
frequently, appearing at lower level of exertion, requiring
larger doses for relief or relief taking longer. It is caused
by dynamic obstruction of coronary artery due to plaque
rupture with superimposed thrombosis and spasms.
Prinzmetals angina Angina at rest and occurs commonly
at night caused by coronary artery spasm.
Management
Pain is relieved by nitroglycerin. Nitroglycerin lowers
peripheral vascular resistance and lowers oxygen demand
of the heart.
Drugs such as aspirin are used to inhibit platelet function.
Beta adrenergic blockers prevent the effects of cardiac
sympathetic stimulation and reduce myocardial oxygen
demand by decreasing the heart rate, ventricular systolic
pressure and peripheral arterial pressure.
Calcium channel blockers prevent calcium from entering
muscle cells (arterial or cardiac muscles) thus preventing
contraction leading to vasodilatation.
When angina does not respond to drugs, coronary angioplasty, percutaneous coronary arterioventral procedures or
bypass grafts are indicated.
Dental considerations
Preoperative nitroglycerin can be given prophylactically
before dental therapy.
Effective local anesthesia is a must. Long-acting local
anesthesia with bupivacaine can be used with vasoconstrictor to prolong the effect of local anesthesia. Aspirating
syringe is a must.

Chapter 18 Systemic Disorders and their Clinical Implications

Increased heart rate and blood pressure during long


appointments indicate need to conclude dental care.
If a person develops angina during dental treatment, the
procedure should be terminated and the patient should be
seated in semi-inclined position and the patient should be
given nitroglycerin 0.30.6 mg sublingually. If pain persists
even after 3 minutes, additional doses (up to 3 mg) every
5 minutes should be given and medical help should be
sought. If pain persists, 300 mg of chewable aspirin is given.
Moreover, morphine sulfate (IV) relieves pain and anxiety.
Nausea, bradycardia, hypertension indicating myocardial infarction may occur.
Tricyclic antidepressants are contraindicated. Conscious
sedation and general anesthesia should be deferred for
3 months in patients with recent onset angina or unstable
angina.

MYOCARDIAL INFARCTION
It is a severe form of coronary artery disease. An anginal
pain lasting longer than 30 minutes is considered to be a
myocardial infarction. The pain may be accompanied by
nausea and vomiting, tachycardia, grossly irregular pulse,
pallor and difficulty in breathing, sweating, and restlessness.
About 10% have painless infarctions.
Diagnosis
The diagnosis of acute myocardial infarction is based on the
presence of two of the following three criteria: (1) signs and
symptoms compatible with myocardial ischemia, (2) typical
ECG changesST segment elevation at the end of the PR
segment, (3) measurement of creatinine kinase (CK) and
myocardial-bound CK (CK-MB).
Elevations in the serum troponin T and troponin 1 levels,
which are sensitive markers for myocardial injury, have
also been used to test for acute myocardial infarction.
Therapeutic goals and pharmacologic strategies for coronary
heart disease
Therapeutic goals

Pharmacological strategies

Inhibit progression of
atherosclerosis

Lipid-lowering agents
HMG-Co-A reductase inhibitors

Improve circulation in
coronary arteries

Nitrated calcium channel blockers

Reduce workload

Beta-1 adrenergic receptor antagonists

Prevent thrombus formation

Antithrombotic agents

Prevent coagulation

Anticoagulants

2.

3.
4.
5.
6.

Patients within 6 months of an MI (recent MI) are at


the risk of further complications, hence, elective dental care should be deferred. However, the first 6 weeks
is more critical, and with the physicians consent,
simple emergency dental treatment under LA may be
done during the first 6 months.
Anxious patients may be given preoperative glyceryl
nitrate.
Effective local anesthesia is important.
Aspirating syringes must be used.
Use of epinephrine impregnated gingival retraction
cords should be avoided.

Management of myocardial infarction


Same as that of angina.
Additionally, patients are on platelet inhibitors. Care
should be taken to prevent signicant bleeding.
Local hemostasis should be promoted (procoagulant
materials such as collagen or topical thrombin should be
used). Local pressure should be applied for a longer duration. Injecting vasoconstrictor containing local anesthesia
directly into surgical site and using sutures is not required.

CONGENITAL HEART DISEASE


It is a common heart disease among children, present in
1% of live births. Congenital defects involving heart or
adjacent vessels may be associated with other congenital
anomalies. These congenital anomalies can be cyanotic or
acyanotic in nature.

Cyanotic
Transposition of great vessels, tetralogy of Fallot, Eisenmengers syndrome. Cyanotic defects are lethal.

Acyanotic
Atrial and ventricular septal defects, patent ductus arteriosus, coarctation of aorta, pulmonary stenosis, mitral valve
prolapse, aortic stenosis.
Causes

Idiopathic
Acquired (congenital rubella, maternal drug misuse).

Clinical features

Dental aspects
1.

Physicians consent is necessary before treating the


patient.

Most striking feature in some congenital heart disease


is cyanosis (more than 5 g reduced hemoglobin per
deciliter of blood)
Causes severely impaired development and often gross
clubbing of fingers and toes
479

Section VII System Review

Eventually polycythemia develops


Cyanosis due to right to left shunt leading to chronic
hypoxia
Shunt from left to right leads to pulmonary hypertension, direction changes later leading to cyanosis
Patients with congestive heart disease liable to infective endocarditis and others are pulmonary edema,
polycythemia, bleeding tendency, growth retardation,
fatigue and brain abscess.
Dental considerations

Antimicrobial prophylaxis
Bleeding tendencies due to platelet dysfunction and
excessive fibrinolytic activity
Dental bacteria may cause cerebral abscess
Aspiration during local anesthetic procedure is a must
due to epinephrine in local anesthesia
Gingival retraction cord containing epinephrine should
be avoided.
Oral manifestations associated with congenital
heart diseases

Delayed eruption of both the dentitions


Greater frequency of positional anomalies
Enamel hypoplasia
Teeth have bluish white skimmed milk appearance and
gross vasodilatation in pulp
Greater incidence of caries and periodontal activity.

RHEUMATIC FEVER
Rheumatic fever is the most common cause of cardiac
valve disorders. The mitral valve is affected more frequently. It results from an altered immunologic response to
a group A beta hemolytic streptococcal pharyngitis, leading to formation of Aschoffs nodules in the myocardium
which develops 13 weeks after the streptococcal infection.
Though, only 3% of cases of beta hemolytic pharyngitis
resulting in rheumatic disease, there is no way to forecast
which individuals will have rheumatic heart disease (RHD).
Common manifestations include new onset murmur,
carditis, polyarthritis, chorea, erythema marginatum, fever
and subcutaneous nodules (modied Jones criteria). The
beta streptococcal infection is conrmed by increased
serum antistreptolysin O (ASO) antibody titer or positive
throat culture. RHD resulting in valvular injury is conrmed by echocardiography for any patient with a history
of rheumatic fever, it is imperative to determine whether
the infection resulted in RHD.
Dental considerations

480

Consult with the physician

All rheumatic heart lesions are at the risk of infective


endocarditis and hence precautions and treatment similar to infective endocarditis should be carried out
Local anesthesia can be given
General anesthesia should be avoided.

INFECTIVE (BACTERIAL) ENDOCARDITIS


Infective endocarditis (IE) is a rare, potentially lethal infection, predominantly affecting heart valves. The endocardium
can also be affected. It results from bacteremia originating
from any site and representing almost any species. It is
caused mainly by bacteria as well as fungi.
Bacterial endocarditis can be dened as an infection that
affects the endocardium in valvular, mural and septal defects,
as well as in arteriovenous and arterioarterial shortcircuits.
It usually occurs in older individuals, peak prevalence
is 6th or 7th decade. It is less frequent in the young, except
in intravenous drug users. It occurs predominantly in males.
Most patients have pre-existing cardiac disease. The mitral
valve is more frequently affected followed by aortic valve
and tricuspid valve. Sterile vegetations, i.e. comprising of
platelets and brins accumulate over the damaged valves
and these get readily infected during bacteremias resulting
in infective endocarditis.
Main groups affected by
infective endocarditis

Approximate percentage of all


cases of infective endocarditis

No obvious cardiac valve disease

40%

Chronic rheumatic heart disease

30%

Congenital heart disease

10%

Prosthetic cardiac valves

10%

Intravenous drug abuse

10%

Oral microorganisms could play an important role in the


pathogenesis of infective endocarditis. Some oral microorganisms pass into the blood stream and colonize areas of
valvular endothelium on a previous sterile incipient vegetation. Staphylococcus aureus usually produces an acute
infection, whereas Streptococcus viridans, enterococci, certain gram-positive and gram-negative bacteria and fungi
may produce subacute infection. Dental treatment precedes
infective endocarditis only in 510% of cases though a
number of oral manipulations can cause bacteremia.
It is estimated that the prevalence of bacteremia following scaling and root planing is about (025%), with single
tooth extraction (2550%) and almost 5080% with multiple extractions.
The prevalence of bacteremia is about 2550% with
periodontal surgery.
It has been reported that some cases of infective endocarditis have been associated with oral infections in the
absence of dental manipulations and hence a synergistic

Chapter 18 Systemic Disorders and their Clinical Implications

effect between the presence of periodontal or periapical


infections and dental manipulations could favor the development of infective endocarditis.
Moreover, a number of studies have reported that
brushing teeth, chewing gum or eating may provoke bacteremia and that the prevalence of IE increases when these
acts are performed by patients with intraoral infections.
Because of the high morbidity and mortality associated
with IE, antibiotic prophylaxis has been advised. Though,
antibiotic therapy has not proven to prevent endocarditis
and it also carries with a risk of adverse reactions (anaphylaxis), it is still advised prophylactically for certain
treatment procedures.

Clinical Conditions that Warrant Use of


Antibiotic Prophylaxis
Cardiac conditions

Previous history of bacterial endocarditis


Prosthetic cardiac valves
Complex cyanotic congenital heart diseases
Acquired valvular dysfunction
Surgically constructed systemic pulmonary shunts
Hypertrophic cardiomyopathy
Mitral valve prolapse with regurgitation.

Neurosurgical shunts
Shunts are placed in patients with hydrocephaly to help
in the drainage of cerebrospinal fluid. The ventriculoatrial
shunt allows drainage of the CSF from the lateral ventricles
to the venous circulation. The ventriculo-peritoneal shunt
helps drain the CSF into the abdominal cavity.
Indwelling catheters and stents
Antibiotic prophylaxis is indicated only in instances where
the catheters are on the right side of the heart. Only the first
2 weeks are critical and indicated for antibiotic prophylaxis
when stents are placed in cardiac patients. The risks of developing a superinfection are very minimal after the first few
weeks as an epithelial layer develops over these stents.
Patients with renal diseases undergoing
hemodialysis
Patients receiving peritoneal dialysis do not require antibiotic prophylaxis. However, patients who have an arteriovenous shunt (made up of autogenous tissue or a silastic tube)
implanted for dialysis require antibiotic coverage during
dental procedures, as these shunts are vulnerable to infection.

Patients undergoing chemotherapy are prone to develop


infections as the chemotherapeutic agents suppress the
inherent immune system. Invasive dental procedures such
as extraction of teeth, subgingival scaling and periodontal
surgeries that might cause signicant bleeding warrant
antibiotic prophylaxis in these patients.
Patients inicted with HIV/AIDS generally do not
require antibiotic cover; nevertheless it is always wise
to perform dental procedures such as extraction of teeth
and periodontal surgeries under antibiotic cover as it
might minimize the risk of the patient acquiring a superinfection.
Patients with uncontrolled insulin-dependent diabetes
mellitus (IDDM) are vulnerable to infections. Invasive dental procedures that involve signicant amount of bleeding
may require antibiotic cover.

Treatment Needing Antimicrobial Prophylaxis in


Patients at Risk of Infective Endocarditis

Extractions
Subgingival procedures (probing, cord placement or
scaling)
Oral/periodontal/implant surgery or raising mucogingival flaps
Endodontics beyond root apex
Sialography
Intra-ligamental local anesthesia
Rubber dam, matrix or wedge placement.

Procedures for which antimicrobial prophylaxis is


not required

Dental radiography
Endodontics not beyond apex
Exfoliation of primary teeth
Impression taking
Non-surgical procedures that do not induce bleeding
Abscess incision and drainage
Suture removal
Orthodontic band removal.

Prophylactic antibiotic regimen


Patient category

Oral medications

Adults, not allergic to penicillin

2.0 g amoxicillin 1 hour before


procedure

Adults, penicillin allergic

600 mg clindamycin 1 hour before


procedure or 2.0 g cephalexin
1 hour before procedure or 500 mg
azithromycin or clarithromycin 1 hour
before procedure

Children, not allergic to


penicillin

50 mg/kg amoxicillin 1 hour before


procedure

Patients with compromised immune status


These patients are more prone to develop an overwhelming septicemia from a relatively harmless transient bacteremia because of their compromised immune status.

481

Section VII System Review

Patient category

Non-oral medications

Adults, not allergic to


penicillin

2.0 g ampicillin IM or IV within 30 minutes


before procedure

Adults, penicillin allergic

600 mg clindamycin IV within 30 minutes


before procedure or 1.0 g cefazolin IM or
IV within 30 minutes before procedure

Children, not allergic to


penicillin

50 mg/kg ampicillin IM or IV within


30 minutes before procedure

Chlorhexidine hydrochloride and povidoneiodine mouthrinses may reduce the incidence and magnitude of bacteremia before dental treatment.
Moreover, patients should be encouraged to maintain
meticulous oral hygiene.
It has been suggested by some authors that in patients
with poor oral health, antibiotic coverage should be given
for all dental procedures.

Stage D: Patients with end stage disease requiring specialized treatment such as mechanical circulatory support, continuous ionotropic infusion or cardiac
transplantation.
2. The New York Heart Association
Class one: Asymptomatic patients
Class two: Patient symptomatic with moderate exertion
Class three: Patient symptomatic with mild exertion
Class four: Patient symptomatic at rest.
Clinical manifestations
Left heart failure manifests as tachycardia, fatigue on
exertion, dyspnea on mild exercise, intolerance to cold,
paroxysmal nocturnal dyspnea and nocturnal cough.
Right heart failure is characterized by fatigue, jugular
venous distention, fullness in the abdomen, with an enlarged
liver and tenderness in the upper right quadrant. In advance
cases ascites and pitting edema of lower extremities is seen.
Management

HEART FAILURE
Heart failure is a clinical syndrome defined as chronic
inadequate contraction of the heart muscle, resulting in
insufficient cardiac output. It is basically an inability of the
heart to pump blood at a rate required by the body tissues.
It occurs frequently in the elderly population. It is a manifestation of one or more underlying conditions including:

Systemic or pulmonary hypertension


Myocardial infarction
Cardiomyopathy
Congenital heart disease
Rheumatic fever
Cardiac dysrhythmias
Pericardial disease and other infections.

Heart failure reflects impairment of either the left or right


ventricle. Left ventricular failure commonly develops in
patients with coronary artery disease, hypertension and
congenital heart disease. Right ventricular failure is mostly
caused by left ventricular failure which increases pulmonary venous pressure and leads to pulmonary arterial
hypertension. Heart failure leads to hypoperfused tissues
and congested organs.

Classifications of Heart Failure


1. American Heart Association
Stage A: Patients at risk of failure without any structural
disorder
Stage B: Patients with a structural disorder of heart, without symptoms of heart failure
Stage C: Patients with present or past symptoms of heart
failure and structural disorder
482

Reduction in physical activities, stress reduction, fluid restriction, dietary sodium restriction, weight loss, subcutaneous
heparin administration, supplemental portal oxygen, medications prescribed include diuretics, cardiac glycosides,
vasodilators, ACE inhibitors and sympathomimetic drugs.
Dental considerations

Physicians consent is a must.


Patient should avoid heavy meals just before their dental appointment since digitalis may cause nausea and
vomiting if the doses are high.
The dentist should avoid stimulating gag reflex. Rubber
dam should be used cautiously.
Patient should not be in supine position because dyspnea is worsened.
Dental treatment may precipitate dysrhythmias and
angina in uncontrolled patients.
Anxiety must be minimized and patients pain control
should be effective.
Patients should be treated in late morning, because
endogenous epinephrine peaks during early morning
and cardiac complications may arise.
Aspirating syringe should be used since epinephrine
can theoretically increase hypertension.
Bupivacaine is cardiotoxic.
Epinephrine in local anesthesia should be avoided in
patients taking beta blockers, since hypertension may
be induced.
For patients in whom significant bleeding is expected,
monitor protrombin time.
During the course of treatment, vital signs should be
monitored.
Medications such as diuretics may cause orthostatic
hypotension.

Chapter 18 Systemic Disorders and their Clinical Implications

NSAIDs other than aspirin should be avoided in patients


taking ACE inhibitors, since there is a risk of renal damage.

Special considerations
Appointment timing Most sudden cardiac arrests may
come during peak endogenous epinephrine levels (08:00
11:00 hours) and so appointments are best for late morning
or early afternoon.
Preventive strategies Dental management plans for
patients with cardiovascular diseases should include appropriate preventive strategies.
Toothbrush The use of electromechanical brushes have
been shown to be more effective than conventional brushes
in reducing plaque and gingivitis and hence should be recommended in all patients with cardiovascular disease.
Topical rinses and fluorides The use of topical agents,
such as chlorhexidine gluconate is useful to combat gingivitis and other periodontal pathosis that result from plaque
accumulation. For patients with xerostomia and a high
incidence of dental caries, preventive modalities such as
dietary analysis and counseling, and prophylaxis combined
with home fluoride use should be implemented. A topical
fluoride, 1.1% sodium fluoride in the form of a brush-on
gel, may be preferred to a topical solution.
Sialagogues Xerostomic patients, in whom the salivary
glands respond to stimulation benefit from dietary measures
such as carrots, celery, or from chewing xylitol containing
gums. Drugs such as pilocarpine hydrochloride 2.55 mg in
26 increments per day and cevimeline hydrochloride can be
used to treat drug-induced xerostomia. However, in patients
with no residual salivary gland function, salivary substitutes,
oral moisturizer, and artificial saliva provide some relief.
Local hemostatic agents They are used for surface dressing for wounds and over extraction sockets. They arrest
bleeding by creating a mechanical matrix which facilitates
blood clotting when the absorbable hemostatic agent is
applied directly to the hemorrhagic site. Examples include
absorbable gelatin sponge, microfibrillar collagen hemostat and oxidized regenerated cellulose.
Adverse drug events Dentists must have an awareness
of the potential for adverse drug events since patients with
cardiovascular diseases are frequently treated with multiple drugs. Hence, a rational approach should be developed
toward the use of pharmacotherapeutic agents in the management of odontogenic problems.

Oral Disease Aspects


Periodontal disease
Demmer and Desvarieux (2006) in their article titled
Periodontal Infections and Cardiovascular Disease: The
Heart of the Matter suggest that there is still some evidence

that supports the association between periodontal infections, atherosclerosis and vascular disease. They further
recommend that irrespective of whether there is an association between periodontal diseases and cardiovascular
lesions or not, periodontal treatment must be recommended
on the basis of the value of its benefits for the oral health of
patients, recognizing that patients are not healthy without
good oral health.
Lichenoid stomatitis Cardiovascular drugs such as diuretics, beta-1 blockers, ACE inhibitors may cause development
of lichenoid lesions. Lichenoid lesions are indistinguishable
from oral lichen planus. The diagnosis is confirmed when
condition resolves after the offending drug is discontinued.
Xerostomia Cardiovascular drugs with xerostomic side
effects include diuretics, beta-1 blockers and centrally acting sympathetic agonists. Xerostomia is usually caused due
to the drugs parasympatholytic or antimuscarinic effects.
Xerostomia can lead to complications such as high incidence in dental caries. Moreover, it can contribute to difficulties in mastication, swallowing, speech. The dryness
of the oral mucosa if persistent can lead to atrophy and
susceptibility to candidiasis and other superinfections.
Gingival hyperplasia Calcium channel blockers such as
nifedipine can cause gingival enlargement primarily affecting the labial or facial interdental papilla and it is firm and
painless. However, it is usually associated with erythema
and edema resulting in pain, bleeding, and difficulty in
mastication.
Patients on antithrombotic agents
An increasing number of cardiovascular patients are prescribed antithrombotic, anticoagulant, and thrombolytic
agents and hence special precautions need to be taken in
such patients.
Aspirin is one of the commonly prescribed antithrombotic
agents. It irreversibly acetylates cyclo-oxygenase resulting
in inhibition of thromboxane A2 mediated platelet aggregation. However, it is relatively a weak antithrombotic agent,
since the action of other mediators of platelet aggregation
are not inhibited, hence the effect of aspirin therapy on
intra- and post-operative surgical and periodontal procedures are minimal.
If the patient is also taking oral anticoagulant, signicant synergism may mandate modications of drug regimen. Measurement of patients bleeding time can be helpful
to determine the degree of antithrombotic effect and its
impact on invasive dental procedures.
Considerations for patients on anticoagulant agents
For any patient taking anticoagulant the dentist and physician must assess the risk for altered bleeding after an invasive dental procedure. Assessment includes magnitude of
invasive procedure, patients bleeding history, patients
483

Section VII System Review

bleeding prole which includes prothrombin time (PT), partial thromboplastin time (PTT), and international normalized ratio (INR).
Oral anticoagulants are commonly prescribed for arterial or venous thromboembolism. This therapy is usually
monitored by prothrombin time which is converted to INR.
For most clinical indications, a moderateintensity anticoagulant effect with a target INR of 2.03.0 and PT of 1.5
2.5 is appropriate.
Warfarin is the commonly prescribed oral anticoagulant.
Most patients can undergo minor oral surgical procedures
such as extraction and alveolectomies without alteration of
their warfarin regimen. However, to prevent serious bleeding
the preoperative assessment of the patients level of anticoagulation is necessary. Warfarin has plasma half-life of
3642 hours, hence any change in dosage requires at least
2 days to be reected in INR value. Once an acceptable range
is achieved local anesthesia (LA) can be administered with
caution to minimize hematoma formation and using meticulous local measures such as minimal trauma, application
of gelfoam and placement of sutures to ensure hemostasis.
Heparin therapy
For a patient on heparin therapy requiring an oral surgical
procedure, the drug should be discontinued approximately
4 hours before the procedure. Surgery is performed using
local anesthesia, atraumatic surgical technique, application
of local hemostatic agents and careful suturing. Postoperatively heparin therapy may be re-instituted the same
day if there is no active bleeding.
Local anesthesia
The use of local anesthetic agents with vasoconstrictors in
patients with cardiovascular disease is controversial. The two
most commonly used vasoconstrictors are epinephrine and
levonordefrin. Patients receiving LA without vasoconstrictor
have impaired pain control compared to those receiving LA
with epinephrine. Hence, patients with cardiovascular disease may be at greater risk of experiencing massive endogenous epinephrine release secondary to poor LA than they
are from the small amount of vasoconstrictor used in LA.
Some studies have found that inltration anesthesia
containing 3.6 ml of lignocaine with 180,000 epinephrine
can be given safely in CVS patients who have an exercise
capacity of more than 4 MET. Most studies have shown no
signicant changes in BP or heart rate in patients with mild
to moderate cardiovascular system (CVS) disease after dental injection of 1.85.4 ml of 2% of lignocaine with 1100,000
epinephrine. Hence, it is recommended that patients with
mild to moderate CVS disease receive the smallest amount
of LA needed to provide anesthesia with an aspirating
syringe. Moreover, use of conscious sedation to decrease
stress to minimize endogenous release of epinephrine may
help in ensuring hemodynamic stability than avoiding small
484

amount of epinephrine in LA. However, vasoconstrictors


in LA may be contraindicated in patients with severe CVS
disorders such as unstable angina, recent MI or bypass
surgeries, uncontrolled dysrhythmias, severe hypertension
and severe congestive heart failure.
Intraligamentary injection of LA with vasoconstrictor
is generally contraindicated in patients with signicant
CVS disease.
Pacemakers
It is a small implanted electronic device that stimulates the
heart to beat and pace the heart rate when it is too slow
(bradycardia). Pacemakers have pulse generators and electrode leads and these are powered by lithium batteries.
Modern pacemakers are bipolar, implanted transvenously
in the subclavian or cephalic vein and typically located in
right ventricle or on the chest wall, either with the pectoral
muscle or underneath the skin or in abdominal wall.
Dental apparatus/instruments with no known
effect on cardiac pacemakers

Electric toothbrushes
Electronic apex locators
Piezoelectric ultrasonic scalers.

Dental apparatus/instruments with likely


effects on cardiac pacemakers

Diathermy units
Electronic dental analgesia units
Electrosurgical units
Ferromagnetic seaters
Lithotripsy units
MRI (magnetic resonance imaging) units
TENS (transcutaneous electric nerve stimulation) units
Ultrasonic instrument baths.

Interference with pacemakers/defibrillators


High frequency external electromagnetic radiation can
interfere with pacemaker sensing function.
Pacemakers can be disrupted by ionizing radiation,
ultrasonic and electromagnetic interference from a wide
range of sources.
Digital phones, TV transmitters may pose interference,
but the risk is small and only used in close proximity to
the pacemaker.
Electrical appliances like remote controls, electric blankets, heating pads, shavers, sewing machines and microwave
ovens are safe.

HEMATOLOGICAL DISORDERS
Hematological diseases include abnormalities involving
RBCs, WBCs and platelets. As platelet abnormalities lead

Chapter 18 Systemic Disorders and their Clinical Implications

to defective coagulation mechanism. They will be discussed


in the section pertaining to bleeding and clotting disorders.
RBCs and WBCs perform many of the vital functions of
the body. Their qualitative or quantitative defects can lead
to derailment of internal homeostasis. The oral cavity is
equally affected and demonstrates a plethora of manifestations. These are sometimes specic for a particular disease
and many of the times, non-specic. The oral manifestations of the hematological diseases have to be identied,
underlying systemic cause treated and consideration should
be given for a patient, while undertaking a particular dental
procedure.
Hematological diseases can be broadly classied as
qualitative and quantitative defects.
Qualitative disorders
Cells affected

Disorder

WBCs

ChediakHigashi syndrome
Enzyme deficiencies
e.g. G-6-P dehydrogenase deficiency, pyruvate
kinase deficiency

RBCs

Hemoglobinopathies
e.g. Sickle cell anemia, thalassemia
Abnormal shape
e.g. Hereditary spherocytosis, hereditary
elliptocytosis

Quantitative defects
Cells affected

Disorder
Increase in number
e.g. Leukocytosis, leukemia, lymphoma

WBCs

RBCs

Decrease in number
e.g. Granulocytopenia, agranulocytosis,
cyclic neutropenia

POLYCYTHEMIA
Polycythemia is an abnormal increase in the erythrocyte
count. Polycythemia is of three types: (1) primary proliferative polycythemia (polycythemia rubra vera), (2) secondary polycythemia, and (3) apparent polycythemia.
Polycythemia rubra vera (PRV) is an idiopathic myeloproliferative disorder seen after 5th decade of life. PRV is
not only characterized by proliferation of erythrocytes, but
also granulocytes and platelets. While secondary polycythemia results from increased erythropoietin concentration,
apparent polycythemia results from decrease in plasma
uids rather than any increase in RBC concentration. RBC
levels may reach up to 612 million cells/mm3 leading to
increased blood viscosity and thrombosis. Cyanosis of the
face and extremities (due to deoxygenated blood), and
hemorrhagic tendency may be seen in the later stages of
the disease.
Oral manifestations
Polycythemia rubra vera will exhibit oral manifestations
such as petechiae, purpura, spontaneous bleeding of the
gingiva owing to hemorrhagic tendency and purple red discoloration on tongue, mucosa owing to cyanosis. Leukemic
manifestations may also be seen if PRV progresses to acute
myeloid leukemia, due to the proliferation of leukocytes.
Secondary polycythemia also exhibits petechiae, ecchymosis and purple red discoloration of tongue and mucosa.
Apparent polycythemia, which does not affect the quantity
of RBC, does not exhibit any appreciable oral changes.
Dental considerations
Bleeding tendency during dental treatment procedures warrants adequate hemostasis measures. Cytotoxic chemotherapy
should be administered prior to dental treatment procedures
if hemoglobin levels are not controlled.

Increase in number
e.g. Polycythemia

Treatment

Decrease in number
e.g. Anemia (sickle cell anemia, thalassemia and
anemia due to deficiency of vitamin B12, folic acid
and iron)

The type of polycythemia should be diagnosed first and


treated accordingly. Phlebotomy and chemotherapeutic
agents like busulfan and chlorambucil are the common
treatment options.

RED BLOOD CELL DISORDERS


Red blood cell precursors, the pluripotential stem cells,
give rise to erythroid progenitor cells on stimulation by
various growth factors. These progenitor cells are further
stimulated by erythropoietin, a hormone produced by kidney, leading to their differentiation and maturation into
erythrocytes.

ANEMIA
Anemia is defined as a reduction in the oxygen carrying
capacity of the blood. It is not a disease but rather a symptom complex due to either reduction in number of circulating RBCs or due to an abnormality in the hemoglobin
contained within RBCs. RBCs with a normal range of
56 million cells/mm3 may dwindle due to loss of blood or
due to decreased production or increased destruction.
485

Section VII System Review

Anemias can be classied in many ways. They can be


classied based on their etiology or size of the RBC with
hemoglobin concentration in two.
Classification based on etiology

Blood loss anemia: Iron deficiency anemia


Anemia due to decreased production: Aplastic anemia,
anemia due to folic acid and vitamin B12 deficiency
Anemia due to increased destruction (hemolytic anemia):
Thalassemia, sickle cell anemia, glucose-6-phosphate
dehydrogenase (G6PD) deficiency.
Classification based on size and hemoglobin
concentration

Microcytic hypochromic anemia: Iron deficiency anemia,


thalassemia.
Macrocytic normochromic anemia: Anemia due to folic
acid and vitamin B12 deficiency.
Normocytic normochromic anemia: Sickle cell anemia.
Patients suffering with any type of anemia will have
depleted oxygen carrying capacity manifesting as pallor,
weakness and difficulty in breathing (dyspnea). Hemoglobin levels below 13.5 g/dl in adult males and less than
11.5 g/dl in adult females is considered anemic. Anemias
due to increased destruction (hemolytic anemia) are further
classified based on the etiology as following:

Extracorpuscular factors causing hemolysis, e.g. autoimmunity, infections, liver disease and Rh factor
incompatibility.
Intracorpuscular factors causing hemolysis, e.g. hereditary spherocytosis, G6PD deficiency, sickle cell anemia,
thalassemia and paroxysmal nocturnal hemoglobinuria.

Genitourinary causes like menstruation, malignancies,


etc.
Trauma/surgery.
Blood loss from various sources is the most common cause
of iron deficiency. Menstruation is the most likely cause in
women between the age of 15 and 45 years. In adult and
postmenopausal women, chronic GI tract losses should be
the first consideration. In addition to clinical manifestations
common to all anemias such as fatiguability, pallor and dyspnea, iron deficiency anemia patients exhibit spoon-shaped,
cracked and split nails (koilonychia).
Oral manifestations
Iron deficiency can contribute to impaired cellular immunity, deficient bactericidal activity of polymorphonuclear
leukocytes, inadequate antibody response, and epithelial
abnormality that may cause high prevalence of oral candidiasis, angular cheilitis, and atrophic glossitis in patients.
Characteristic oral manifestations of tissue iron depletion
are glossitis and glossodynia, angular cheilitis, papillary
atrophy of tongue (Figure 1), paresthesia, pallor and dysphagia due to esophageal strictures.
Dental considerations
Increased bleeding tendency might be a problem while
treating anemic patients with hemoglobin levels less than
10 g/dl. This tendency is exhibited due to altered rheologic
interactions between cells when hemoglobin level falls
below a critical level. General anesthesia is also contraindicated in severe anemia, as oxygen carrying capacity is
severely impaired. Therfore, patients presenting with typical features of anemia should be thoroughly investigated
and referred to a physician for further investigations and
treatment.

Iron Deficiency Anemia

Diagnosis

Iron is an essential element in which it participates in


hemoglobin synthesis, electron transport for cellular respiration, DNA synthesis and other vital enzymatic reactions.
Iron deficiency anemia is one of the most common diagnoses in the world, affecting both pediatric and adult population with a variety of etiologies.

Following are the list of investigations for iron deficiency


anemia:

Causes
Inadequate ingestion/increased requirements Infants,
children and in pregnancy.
Decreased absorption or utilization
malabsorption syndrome.

Partial gastrectomy,

Blood loss

486

Gastrointestinal (GI) tract causes like peptic ulcer


Respiratory causes like infections, malignancies, etc.

Blood count: Decreased RBC and hemoglobin


Peripheral smear: Microcytic hypochromic anemia
Serum iron: Decreased
Serum iron binding capacity: Increased
Mean corpuscular volume: Decreased.

Hypochromic microcytic anemia alone is also seen in


other conditions like thalassemia and sideroblastic anemia.
Other mentioned investigations should be done to effectively rule out these latter two conditions.
Treatment
Once the diagnosis of iron deficiency has been made, the
cause of iron deficiency should be sought and treated. The
best treatment of iron deficiency is an iron salt by mouth

Chapter 18 Systemic Disorders and their Clinical Implications

Figure 1

Bald tongue and angular cheilitis in a patient with iron


deficiency anemia. Courtesy: Dr Sarat Gummadapu

(ferrous sulfate 200 mg twice daily). Oral iron may need


to be given for 3 months or more to replenish marrow
iron stores.

PatersonKelly Syndrome (PlummerVinson


Syndrome)
PatersonKelly syndrome presents as a classic triad of
dysphagia, iron deficiency anemia and esophageal webs.
Dysphagia is due to muscular degeneration in the esophagus
leading to esophageal strictures or webs. The patients are
commonly females in the age range of 4th to 7th decade
and complain of spasm in the throat or food sticking in
the throat.
Symptoms resulting from anemia (weakness, pallor,
fatigue, tachycardia) may dominate the clinical picture.
Additional features are glossitis, angular cheilitis and koilonychia. The most important etiologic factor is iron deciency. PatersonKelly syndrome can be treated effectively
with iron supplementation. Since this syndrome is associated with an increased risk of squamous cell carcinoma of
the pharynx and esophagus, patients should be monitored
closely.

Anemia due to Vitamin B12 and Folic Acid


Deficiency
Vitamin B12 (cyanocobalamin) and folic acid are needed
for the maturation of RBCs in bone marrow. A deficiency
in the daily intake or absorption of these can result in anemia. Vitamin B12 deficiency can occur due to pernicious
anemia, gastrectomy, tropical sprue, alcoholism, scleroderma and drugs such as colchicine. The most common of

all these is the pernicious anemia, which is due to atrophy


of gastric mucosa resulting in a lack of intrinsic factor
secretion. The intrinsic factor binds to vitamin B12 and is
necessary for its absorption. Autoimmunity was considered as an etiological factor for destruction of gastric parietal cells or the intrinsic factor. Pernicious anemia is
commonly seen in adult life with patients being susceptible to gastric carcinoma, rheumatoid arthritis and neuromuscular abnormalities.
Folic acid deciency causes severe anemia but does not
cause neurological abnormalities seen in pernicious anemia. It is prevalent in alcoholics, drug users and in patients
whose diet is devoid of leafy vegetables. Anticancer drugs
such as methotrexate are known to cause folate deciency
by interfering with DNA synthesis. Anemia due to deciency of vitamin B12 and folic acid is also called megaloblastic anemia because of the presence of large RBCs with
small immature nuclei.
Oral manifestations
Patients with pernicious anemia exhibit glossitis, sore or
burning tongue, angular cheilitis, papillary atrophy, recurrent oral ulcerations and taste abnormalities. The glossitis
can either be atrophic or Moellers, where a pattern of red
lines may be seen without depapillation. Atrophic tongue
occurs not only in anemias such as vitamin B12 deficiency,
folic acid and iron deficiency, but also due to diabetes,
xerostomia and candidiasis. Several hypotheses regarding
the pathogenic role of nutrient deficiencies in atrophic
glossitis have been proposed. Because cells of the tongue
papilla have a high rate of turnover, deficiencies in micronutrients needed for cell proliferation or cell membrane
stability may lead to depapillation. Nutrient deficiencies
may also contribute to oral pathology by altering the pattern of microbial flora. Burning mouth sensation can be also
encountered due to neuropathy or candidosis, which may
be precipitated by anemia. Neuropathy can be explained by
the fact that defective myelin synthesis is seen in patients
with vitamin B12 deficiency.
Oral manifestations of folic acid deciency include
angular cheilitis, aphthous stomatitis and pharyngitis.
Diagnosis
Diagnosis of pernicious anemia requires the demonstration
that megaloblastic hemopoiesis is present, vitamin B12 deficiency is present and intrinsic factor is missing. Diagnostic
tests performed and would be indicative of either vitamin
B12 deficiency or folic acid deficiency are:

Blood count: Decreased RBCs and hemoglobin


Peripheral smear: Macrocytic normochromic anemia
Mean corpuscular volume: Increased
Serum B12 assay: Decreased (in vitamin B12 deficiency)
Serum folic acid assay: Decreased (in folic acid
deficiency)
487

Section VII System Review

Schillings test: Positive (in vitamin B12 deficiency).


Antibodies to parietal cells or intrinsic factor: Present
(in pernicious anemia).

Treatment
Since oral changes would appear to precede many of the
systemic indicators of vitamin B12 deficiency, it is hoped
that the recognition of these will lead to early diagnosis
and institution of therapy. Regardless of the etiology of
vitamin B12 deficiency, high dose oral supplementation
(1,0002,000 mcg daily for 2 weeks), followed by 1,000 mcg
daily for maintenance is currently recommended. Historically pernicious anemia was treated with intramuscular
vitamin B12 supplementation. However, several studies have
demonstrated that high doses of oral vitamin B12 are just
as effective as, and are better tolerated than intramuscular
cyanocobalamin in patients with vitamin B12 malabsorption.
Management for folic acid deficiency consists of administration of oral folic acid (5 mg/day), which is given for
a period of 4 months. The differentiation of vitamin B12
deficiency and folic acid deficiency is crucial as folic acid
supplements may correct the anemia but will not stop the
neurological manifestations.

Aplastic Anemia
Aplastic anemia is a rare, potentially life-threatening failure of hemopoiesis characterized by pancytopenia and bone
marrow aplasia. Although most cases are acquired (drugs,
viruses, chemicals, toxins and radiation), some are inherited. The pathophysiology of acquired aplastic anemia is
immune mediated in most cases; autoreactive lymphocytes mediate the destruction of hemopoietic stem cells.
Fanconis anemia is an inherited aplastic anemia that
manifests in early childhood. The term anemia in aplastic
anemia is a misnomer, since all the three cellular elements
of the bone marrow are often involved (pancytopenia), i.e.
granulocytes, erythrocytes and platelets. Clinical manifestations are proportional to the peripheral blood cytopenias
and include dyspnea, fatigue and pallor (effects of anemia),
petechiae and easy bruising (effects of thrombocytopenia)
and susceptibility to infections (effects of neutropenia).

Oral manifestations
Oral manifestations like gingival bleeding, pallor, petechiae, ecchymosis; neutropenic ulcers and delayed healing
are observed in patients with aplastic anemia (effects of anemia, thrombocytopenia and neutropenia). Petechial hemorrhages were the most common intraoral finding in
patients with aplastic anemia. These petechiae might be due
to minor trauma from normal deglutition and mastication
rather than due to thrombocytopenia. Rapidly progressing
severe periodontitis, which is a feature of several quantitative and qualitative neutrophil defects like cyclic neutropenia, agranulocytosis and leukocyte adhesion deficiency
(LAD), is also evident in aplastic anemia. Bacterial sepsis
and fungal infections represent the most frequent cause of
death in this condition.
Dental considerations
Thorough oral examination should be carried out in a
patient with aplastic anemia as bleeding tendency and infections pose a serious problem. Local hemostatic measures
such as pressure pack application and systemic antifibrinolytic agents such as aminocaproic acid and tranexamic
acid should be considered. Tranexamic acid is given in
a dosage of 20 mg/kg body weight 4 times a day starting
24 hours before oral procedures and continuing for 34 days
afterwards. Chlorhexidine mouthrinses will reduce the microbial load in the oral cavity. Antibiotic prophylaxis, typically
with amoxicillin or clindamycin, and platelet transfusion
of thrombocytopenic patients, when necessary, should be
adequate to prevent serious sequelae for all dental procedures. However, intramuscular injections and nerve block
anesthesias are to be avoided because of risk of thrombocytopenia and bleeding tendency.
Management
Cause should be identified and removed. Patients with
asymptomatic cytopenias probably need no treatment.
Treatment for patients with severe cytopenias includes bone
marrow transplantation, immunosuppressive therapy and
high dose cyclophosphamide without transplantation of
bone marrow.

Diagnosis
A complete blood count, leukocyte differential, reticulocyte count, and a bone marrow aspirate and biopsy can
establish the diagnosis. Peripheral blood flow cytometry can
be done to rule out paroxysmal nocturnal hemoglobinuria.
Patients younger than 40 years should be screened for
Fanconis anemia by the use of clastogenic agents, diepoxybutane or mitomycin, which test for increased chromosomal breakage seen with this disorder. A family history of
cytopenias should raise suspicion of an inherited disorder
even when no physical abnormalities are present.
488

Glucose-6-phosphate Dehydrogenase Deficiency


Glucose-6-phosphate dehydrogenase is an enzyme in the
RBC needed for the glucose metabolism. Deficiency of this
enzyme leads to accumulation of oxidants in the RBCs.
These substances, which produce methemoglobin and denatured hemoglobin, precipitate to form Heinz bodies. The
Heinz bodies cause alteration of cell membrane by attachment, thus leading to hemolysis of cell. Beans, drugs and
infection commonly trigger the hemolysis and lead to acute
intravascular hemolysis. Clinical features such as dyspnea,

Chapter 18 Systemic Disorders and their Clinical Implications

palpitations, weakness and jaundice may be seen. Oral manifestations common to other anemias may be encountered.
Dental considerations

which is possibly stimulated by parvovirus, leading to


rapid onset of anemia. Stroke, which is the most dreaded
complication of sickle cell disease, is also a result of
vasoocclusive event in the brain.
Hemolysis in patients with sickle cell anemia leading
to jaundice.

Avoidance of triggering drugs such as dapsone and sulfasalazine. Blood transfusion can be considered prior to
dental treatment if anemia is very severe.

3.

Treatment

Manifestations of oral cavity reflect the systemic features:

Hemolytic episodes are self-limited many of the times and


most patients with drug- or infection-induced hemolysis
recover fully following treatment. Oxidant drugs should
be avoided.

Oral manifestations

Sickle Cell Anemia


Sickle cell anemia and thalassemia are described as hemoglobinopathies due to the defective globin portion of the
hemoglobin molecule. While sickle cell anemia is due to a
qualitative defect in the globin chains (valine replaces glutamic acid), thalassemia is due to a quantitative defect. The
minor alteration in the globin chain renders the hemoglobin susceptible to low oxygen tension, low temperature or
decreased pH. In the presence of latter factors, hemoglobin
forms a sickle-shaped crystal within the erythrocyte and
leads to stasis, vascular occlusion and ultimately hemolysis
of the red cells in end-capillary circulation. Sickle cell disorders, which are inherited as autosomal recessive, are of
two types: sickle cell trait and sickle cell anemia. While in
sickle cell trait (heterozygous), only one of the beta chains
is abnormal, both the beta chains are abnormal in sickle
cell anemia (homozygous). These patients with sickle cell
trait are relatively asymptomatic unless they are subjected
to extremely low oxygen tension (15 mmHg), such as in
an unpressurized aircraft.

Delayed eruption secondary to their general underdevelopment.


Pallor.
Susceptibility to osteomyelitis due to compromised
blood supply: This is a result of intravascular sickling
leading to ischemic infarction and necrosis of bone that
creates a favorable environment for bacterial growth.
Uncommon manifestations include anesthesia of mandibular nerve and asymptomatic pulpal necrosis.
Anesthesia and pulpal necrosis are caused by restriction of the microvascular blood supply.
Dental radiographs demonstrate step ladder trabecular
pattern due to hyperplasia and widening of marrow
spaces (as body tries to compensate for anemia).
Lateral skull radiographs demonstrate thickening of
diploe with hair-on-end appearance due to perpendicular arrangement of trabeculae (Figure 2).
Areas of radiopacity demonstrated on the radiograph
are suggestive of previous infarction and calcification.

Diagnosis

Peripheral smear: Normocytic normochromic cells


Complete blood count: Decreased hemoglobin
Hemoglobin electrophoresis: Demonstrates abnormal
hemoglobin.

Treatment
Clinical manifestations
Manifestations of sickle cell anemia are divided into three
categories.
1.

2.

Systemic manifestations including impaired growth and


development and increased susceptibility to infections:
Significant delay in sexual maturity, weight and height
achievement is observed. Increased susceptibility to
infection might be due to impaired splenic function or
because, macrophages are involved in phagocytosis of
the defective RBCs and may not be available for killing bacteria.
Vaso-occlusive events and organ damage: The stasis of
sickled red cells lead to vascular occlusion and infarction of the end organ. This vaso-occlusive phenomenon
leads to multiple crises. These crises are painful crises
in chest and abdomen, splenic sequestration crises due
to infarction and fibrosis of spleen, and aplastic crisis,

Patients with sickle cell anemia need regular monitoring


of their hematological state. Sickle cell anemia can only be
symptomatically treated, as there is no cure. Prompt and adequate relief of pain is of prime importance. Vigorous hydration, analgesics and appropriate antibiotics best achieve
management of the painful vaso-occlusive crisis, if there is
any evidence of infection. Dehydration is common due to the
patients inability to produce concentrated urine. Blood transfusion is advised in case of severe anemia and bone marrow transplantation was found to be successful in a patient
with homozygous sickle cell disease. Folic acid supplements
were also found to be beneficial as patients exhibit folic
acid deficiency due to the rapidly proliferating bone marrow.
Dental considerations
The main principles are to prevent trauma, infection,
hypoxia, acidosis or dehydration as these can precipitate
489

Section VII System Review

Figure 2

Oral manifestations

Lateral skull radiograph reveals hair-on-end appearance in


sickle cell anemia. Courtesy: Dr Sarat Gummadapu

sickle cell crises. Hemoglobin concentration of at least 7 g/dl


must be ensured for adequate oxygen delivery during general anesthesia for dental and other surgeries.

Developmental and growth abnormalities leading to


malocclusion, spacing and occlusal abnormalities
Pain and swelling of parotid glands due to deposition
of iron
Deciduous and permanent teeth may be discolored due
to the deposition of iron
Some cases might also show teeth with short roots,
thin lamina dura and prominent premaxilla (Chipmunk facies)
Radiographic changes include generalized rarefaction
of alveolar bone, chicken-wire appearance of enlarged
marrow spaces and coarse trabeculation. In the skull,
proliferation of marrow may completely erode the cortex, leaving only periosteum, and produce a hair-onend radiographic appearance.

Diagnosis

Peripheral smear: Normocytic normochromic cells


Complete blood count: Decreased hemoglobin and
decreased RBC
Hemoglobin electrophoreses: Demonstrates abnormal
hemoglobin.
Treatment

THALASSEMIA
Thalassemias are a group of congenital hemoglobinopathies characterized by a reduced rate of production of one
or more of globin chains (alpha or beta) in the hemoglobin
molecule. Alpha chain is reduced or deficient in alpha
thalassemia and beta chain is reduced or deficient in beta
thalassemia. Beta chains are commonly involved, when
compared to alpha chains. If affected individuals are
heterozygous for beta chains, it is called as beta thalassemia trait or beta thalassemia minor. If affected individuals
are homozygous for beta chains, then it is called as beta
thalassemia major or Cooleys anemia. In thalassemia,
imbalance in globin chain production leads to hemolysis
thus resulting in microcytic, hypochromic type of anemia.
The hemoglobin levels can even reach up to 23 g/dl.
While, beta thalassemias are most frequently found in
Mediterranean and black populations, alpha thalassemias
are found more frequently in South East Asia, Middle East
and Mediterranean populations.
Clinical manifestations
Systemic manifestations are mildly similar to sickle cell
anemia, which are indicative of severe anemia. Growth and
development of the child is retarded with ashen gray skin
color due to pallor and jaundice. Patients may also present
with cardiomegaly, splenomegaly and hepatomegaly.
490

Treatment of thalassemia major includes multiple blood


transfusions and the primary complication of the treatment
is iron overloading leading to deposition in liver, spleen,
pancreas and thyroid. Another complication is chronic active
hepatitis due to viral infection. Folic acid is also advised to
offset the increased demand associated with chronic hyperactivity of the bone marrow. Splenectomy was indicated
previously, to decrease the sequestration of RBC.
Dental considerations
A patient who has had a splenectomy is at risk of massive
infection following bacteremia. It has been suggested that
these patients receive prophylactic antibiotics like oral
penicillin or erythromycin prior to dental treatment. Hepatitis risk to the patients due to transfusion should also be
considered and universal precautions taken. Poor healing
is also a complication of the dental treatment. Surgery for
facial deformities has been used successfully.

WHITE BLOOD CELL DISORDERS


White blood cells (WBCs) or leukocytes originate from
pluripotent hematopoietic stem cells in either bone marrow or lymphoid tissue. These cells are responsible for the
protection of the body against foreign invaders such as
fungi, bacteria, viruses and parasites. Leukocytes are of
three types: granulocytes, monocytes and lymphocytes.

Chapter 18 Systemic Disorders and their Clinical Implications

While, the granulocytes and the monocytes protect the


body against invading organisms by phagocytosis, the
lymphocytes function by boosting the immunity.
White blood cell disorders can also be classied as
follows:

Oral manifestations

Gingival and periodontal disease


Increased caries incidence
Oral ulcerations
Early loss of teeth.

Classification
Qualitative disorders
ChediakHigashi syndrome

NON-NEOPLASTIC DISORDERS

Non-neoplastic disorders
Leukocytosis
Leukopenia

The number of circulating WBCs is expressed as the number


of cells found in a cubic millimeter of blood, which normally ranges from 4,500 to 11,000/mm3 in adults. The differential WBC count is an estimation of the percentage of
each cell type per cubic millimeter of blood. A normal differential count is as follows: neutrophils, 5060%; eosinophils, 3%; basophils, less than 1%; lymphocytes, 2030%;
and monocytes, 37%. The term leukocytosis is defined as
an increase in the number of circulating WBCs to more than
11,000 cells/mm3, and leukopenia as a reduction in the
number of circulating WBCs (usually to 4,500 cells/mm3).

Neoplastic disorders
Leukemia
Lymphoma
Multiple myeloma.

WBCs released by the bone marrow, circulate in peripheral


blood forming two pools of cells, a marginal one and a
circulating one. Cells in the marginal pool adhere to vessel
walls and are readily available. When infection threatens
the body, the storage and marginal pools can be called on
to help fight the invading organisms. Growth promoting
substances called colony-stimulating factors (CSFs) are
responsible for the growth of committed granulocytemonocyte stem cells. In response to infection, there will be
local release of CSFs leading to increased production of
granulocytes and monocytes in the bone marrow.

QUALITATIVE DISORDERS
Since leukocytes play a central role in host defense, it is
not surprising that defects in leukocyte function, both
genetic and acquired, lead to increased vulnerability to
infections. These qualitative defects can be:

Defects in adhesion: Leukocyte adhesion deficiency


(LAD type I)
Defects in microbicidal activity: Chronic granulomatous disease
Defects in phagolysosome function: ChediakHigashi
syndrome.

Leukopenia
A decrease in the peripheral WBC count may occur because
of decreased numbers of any of the specific types of leukocytes, but most often it involves the neutrophils (neutropenia). A reduction in the number of granulocytes in
blood is known as neutropenia or sometimes, when severe
as agranulocytosis. Affected persons are extremely susceptible to infections, which may be severe enough to
cause death. Patients may also exhibit fever, weakness and
marked fatigability.
Causes for neutropenia
Inadequate or ineffective granulopoiesis

Aplastic anemia
Leukemia
Due to cancer chemotherapeutic agents.

Accelerated removal or destruction

Idiopathic
Drugs such as aminopyrine
Splenomegaly
Overwhelming bacterial or fungal infections.

ChediakHigashi Syndrome
It is a rare autosomal recessive disorder characterized by
abnormal granules in the granulocytes. This abnormality
results in neutrophils with decreased chemotactic and bactericidal ability. Patients develop severe neutropenia as a
result of ineffective granulopoiesis and most die in childhood from infections or advanced lymphoproliferative
syndrome. Patients exhibit neuropathy, hypopigmentation,
recurrent bacterial infections and hepatosplenomegaly.

Oral manifestations
Ulcerations and necrotizing lesions may be seen on the
gingiva, floor of the mouth, buccal mucosa, pharynx or
other sites within the oral cavity (agranulocytic angina).
Ulcers lack the surrounding inflammation and are characterized by necrosis and foul smell. All of these lesions often
show massive growth of microorganisms, with a relatively
poor leukocyte response (minimal swelling and pus).
491

Section VII System Review

Treatment
Cause must be identified and all drugs should be discontinued. Infections must be prevented or treated, if present.
Current treatment efforts also include administration of
recombinant hematopoietic growth factors, such as granulocyte CSF, which stimulate neutrophil production by the
bone marrow.
Dental considerations
Oral infections in patients with severe neutropenia should
be considered potentially life-threatening because they can
lead to bacteremia and septicemia. Ulcers can be treated with
topical anesthetics and antiseptic mouthrinses. In severe
pulpal and periodontal infections, broad-spectrum antibiotics can be advised until culture reports are available.
Cyclic neutropenia
It is a rare disorder that occurs secondary to a periodic
failure of the stem cells in the bone marrow. It is characterized by transient severe neutropenia that occurs approximately every 21 days. Neutrophil count is at its bare
minimum for a period of 37 days during which the clinical
manifestations pertaining to neutropenia are observed.
The most common signs are fever, stomatitis, pharyngitis and skin abscesses. Severity of infection is directly proportional to the severity of neutropenia. Treatment and
dental considerations are similar to that of neutropenia.

Reactive Leukocytosis
An increase in the number of WBCs is a common reaction
in the variety of inflammatory states caused by microbial
and non-microbial stimuli. Leukocytosis is relatively nonspecific and can be classified on the basis of particular
white cell series affected. In response to increased demand,
increased number of immature neutrophils called bands
enters the circulation, a process called a left shift. This is
called as leukemoid reaction, which is often secondary to
viral infections. This reaction can be distinguished from
acute leukemia, as there is an orderly maturation and
proliferation of all normal myeloid elements in the bone
marrow.
Causes of leukocytosis
Physiologic

Exercise
Pregnancy
Stress

Pathologic

492

Neutrophilic leukocytosis
Acute bacterial infections
Burns

Eosinophilic leukocytosis
Allergic diseases
Parasitic infestations
Drug reactions
Certain malignancies
Basophilic leukocytosis
Malignancies
Monocytosis
Chronic bacterial infections such as tuberculosis,
systemic lupus erythematosus, etc.
Lymphocytosis
Infections due to hepatitis A, cytomegalovirus and
EpsteinBarr virus.
Oral manifestations are seen as a consequence of underlying disease process rather than the elevated leukocyte levels.
For example, in infectious mononucleosis, there is lymphocytosis and patients complain of sore throat, petechiae
and fever. Patients exhibiting these clinical signs must be
evaluated and investigated as these clinical findings can
be confused with leukemia.

NEOPLASTIC DISORDERS
Leukemia
Leukemia is a heterogeneous group of hematological disorders that arise from a hematopoietic stem cell characterized by a disordered differentiation and proliferation of
neoplastic cells. This neoplastic proliferation in marrow
results in diminished production of normal erythrocytes,
granulocytes and platelets in leukemia. These neoplastic
cells ultimately infiltrate various organs like spleen, CNS,
lymph nodes, skin and gingiva. Leukemia is categorized
according to its clinical behavior: acute or chronic; and
histogenic origin: lymphocytic or myelocytic. The classification is called as FAB (French, American, and British) and
is widely accepted. The etiology is unknown but genetic
factors, irradiation, viruses, chemicals such as benzene and
some drugs have been implicated. All types of leukemia
are more common in males compared to females.

Acute Leukemia
About 50% of all leukemias are in the acute form. Acute
leukemias are divided into two major groups: acute lymphocytic leukemia (ALL) and acute monocytic leukemia
(AML). While, ALL is more commonly seen in children,
AML is frequently seen in the adults. ALL is frequently
derived from B-lymphocytes or their precursors. The acute
leukemias have increased number of immature cells called
blasts in the peripheral circulation. As blasts accumulate
in the marrow, they suppress normal hematopoietic stem
cells.

Chapter 18 Systemic Disorders and their Clinical Implications

Clinical features
The major manifestations of acute leukemia result from
the paucity of normal RBCs, WBCs and platelets. They
have the following characteristics:

Abrupt stormy onset.


Symptoms related to depression of normal marrow
function: Fatigue, owing mainly to anemia, fever, reflecting infections due to granulocytopenia and bleeding,
secondary to thrombocytopenia.
Generalized lymphadenopathy, splenomegaly and
hepatomegaly due to dissemination of leukemic cells.
CNS manifestations such as palsies, vomiting and
headache due to meningeal spread. These features are
more common in children and in ALL.
Localized tumors or chloromas, which turn green on
exposure to sunlight, due to local infiltration of leukemic cells.
Laboratory diagnosis
Laboratory findings show WBC count sharply elevated,
sometimes reaching 100,000 cells/mm3. Platelet count is
usually depressed below 100,000 cells/mm3 and numerous
blast cells can be identified. Bone marrow aspirate reflects
the peripheral circulatory changes.
Treatment
Therapeutically, the aim is to reduce the population of leukemic clone enough to allow reconstitution with the progeny of remaining normal stem cells. Chemotherapy satisfies
the above requirement and is conveniently divided into
three phases. The purpose of the first phase (induction) is
to hit hard and induce a state of remission by killing tumor
cells with cytotoxic agents. The purpose of the second phase
(consolidation) is to consolidate the killing of remaining
leukemic cells. The purpose of the third phase (remission)
is to provide maintenance treatment to prevent any remaining leukemic cell mass from expanding. Patients are cured
when no leukemic cells remain. Chemotherapeutic agents
commonly used are vincristine, cytarabine, daunorubicin
and methotrexate.
Long-term survival occurs when the leukemic cell mass
is greatly reduced and kept from increasing over a long
period. If a patient relapses, remission again is difcult to
induce and bone marrow transplantation is then advised.
There are some regions in the body where the leukemic
cells migrate and are not acted upon by the chemotherapeutic agents. These regions are called sanctuaries (CNS in
ALL). In these patients, radiation along with intrathecal
methotrexate can be tried.

Chronic Leukemia
Onset of chronic leukemia is insidious with the course
(untreated) of the disease running up to 26 years. So

in effect, the chronic leukemias have a slower onset of


symptoms, a better prognosis, and more mature WBCs
than do acute leukemias. The two major types of chronic
leukemia are chronic granulocytic or myelocytic leukemia
(CML) and chronic lymphocytic leukemia (CLL).

Chronic Myelocytic Leukemia


Chronic myelocytic leukemia accounts for about 14% of
all leukemias, is almost exclusively a disease of adults
with the peak of presentation being at 4060 years and is
characterized by the presence of Philadelphia chromosome,
an acquired genetic defect resulting from translocation of
genetic material from chromosome 22 to chromosome 9.
CML has two phases: chronic and blastic. While malignant
cells with normal function are present in chronic phase,
cells with further malignant transformation are found in
blastic phase. Patient often survives for years before the
disease enters blast phase.
Clinical features
Some of the patients are asymptomatic and some exhibit
the following:

Shortness of breath due to anemia


Abdominal discomfort due to splenomegaly
Weight loss and fever
Bleeding tendency in the later stages.

Laboratory diagnosis

Complete blood count: Increased WBC count.


Bone marrow aspirate: Demonstrates increased cellularity and Philadelphia chromosome.

Treatment
Control of chronic phase is often successful when compared to blastic phase. Imatinib, a tyrosine kinase inhibitor
is the first line of treatment in the chronic phase. As the
disease enters blastic phase, other treatment options have
to be explored.
Allogenic hemopoietic stem cell transplantation can cure
approximately 70% of chronic phase CML patients but with
risk of complications and death due to graft-versus-host
disease (GVHD) and opportunistic infections.

Chronic Lymphoid Leukemia


Chronic lymphoid leukemia is one of the most common
leukemia, occurring predominantly in later life and increasing in frequency with advancing years. It is almost invariably B-lymphocytic in origin. In many patients it is a chance
finding with no symptoms, while others present with features of bone marrow failure or immunosuppression.
493

Section VII System Review

Clinical features

Figure 3

Recurrent infection because of (functional) leukopenia


and immune failure (reduced immunoglobulins)
Anemia due to hemolysis or marrow infiltration
Painless lymphadenopathy
Splenic discomfort.
Laboratory diagnosis

Complete blood count: Increased WBC count, platelets


and normal or reduced RBC
Blood film: Lymphocytes increased
Bone marrow aspirate: Reflects peripheral blood, infiltrated with lymphocytes.
Treatment
Supportive treatment involves treatment of hemolytic anemia with steroids, infection with antibiotics and infiltrations
with chemotherapy. Specific treatment involves administration of chlorambucil to reduce blood count and to decrease
lymphadenopathy and splenomegaly and thus successfully
palliating the disease. Fludarabine alone or in combination
with cyclophosphamide had a much greater impact on the
bone marrow and can induce complete remission.
Oral manifestations of leukemia
Leukemic patients are prone to the development of variety
of oral conditions associated with the malignancy and treatment. The oral manifestations of acute leukemias reflect
the systemic complications. The manifestations are:
Signs and symptoms related to depression of marrow
function Pallor, owing to anemia; petechiae, ecchymosis
and gingival bleeding owing to thrombocytopenia (spontaneous if platelet level falls below 20,000 cells/mm3); and
infections, owing to neutropenia. The latter can manifest
as ulcerations and can be bacterial, viral or fungal.
Neutrophils are known to play a crucial role in protective
host response to colonization. In patients with leukemia,
neutropenia is compounded by the chemotherapy thus
increasing the risk of different opportunistic fungal infections. Among the opportunistic infections present in the
oral cavity, the most frequent is candidiasis. Mucormycosis
also occurs commonly in pulmonary and rhinocerebral
sites and can become widely disseminated to other organ
systems. Viral infections are also common in leukemia,
with herpes simplex being the most common.
Signs and symptoms related to infiltration of leukemic
cells Gingival and salivary gland enlargement (Figure 3),
neural and developing tooth crypt involvement, and painless cervical lymphadenopathy.
Signs and symptoms related to treatment of leukemia
Oral ulcerations and mucositis due to chemotherapy and/or
radiation, craniofacial and dental anomalies in children
494

Gingival enlargement and bleeding in patient


suffering from acute myeloid leukemia.
Courtesy: Dr Sarat Gummadapu

(result of radiotherapy for cranial involvement), and lichenoid lesions, desquamative gingivitis due to graft-versus-host
reaction. The oral mucosal cells due to their high mitotic
index are frequently compromised, due to their susceptibility to chemotherapeutic agents, predisposing the patients to
mucositis and xerostomia. The dental anomalies encountered are microdontia, dental agenesis and arrested root
development.
Radiographic findings Most children with leukemia had
detectable radiographic changes of the jaws. These changes
include loss of lamina dura, displacement of teeth, loss of
the crypt outline around unerupted teeth, widened periodontal ligament and loss of cancellous bone trabeculation. The latter leads to an appearance of generalized
rarefaction. There are other reports that mention generalized bone loss, increased mobility and protrusion of teeth in
leukemic patients. Periodontal destruction, which is severe,
may have been due to infiltration of leukemic cells into alveolar bone.
The patients of chronic leukemia also exhibit oral hemorrhage, petechiae, ulcerations and gingival swellings.
Dental considerations
Dental treatment should only be carried out after consultation with the physician, as various aspects of management
and the probable life expectation may affect it. Preoperative
precautions should include screening for hepatitis B and
HIV. Preventive oral healthcare is essential and where
indicated, conservative dental treatment may be possible.
Management of chronic dental infections in patients with
hematologic malignancies ideally should be based on data
that correlates examination findings with outcomes of
treatment. One result of compromised hematologic status

Chapter 18 Systemic Disorders and their Clinical Implications

among dental patients with hematologic malignancy, idiopathic or drug-induced blood dyscrasias and sickle cell
anemia is that certain clinically relevant laboratory values
have been proposed as important in management protocols.
When oral surgical procedures are anticipated, a platelet
count of at least 50  109/l and absolute neutrophil count of
at least 0.5  109/l are sought by the provider to comfortably
assure effective hemostasis and reduce the risk of postoperative bacterial infection. But, in smokers, dental extractions should not be used as a means of controlling chronic
asymptomatic periodontal and pulpal diseases, as these
patients are prone to fungal infections. Oral ulcerations in
leukemic patients should be managed by topical antibacterials along with analgesic and anesthetic rinses. Removing
irritants, applying local pressure and hemostatic agents
such as absorbable gelatin or collagen sponges should be
used to manage bleeding tendency. If the patient does not
respond, then platelet transfusions might be warranted.

features of HD include Pel-Ebstein fever, a cyclic spiking


of high fever, and generalized severe pruritis. Pruritis is a
well-known cutaneous, paraneoplastic manifestation of HD.
As the disease progresses, signs and symptoms arise from
pressure and obstruction caused by enlarging nodes. Diagnosis is made from nodal biopsy or bone marrow aspirate.

Lymphomas

Non-Hodgkins Lymphoma

The lymphomas represent seventh most common malignancy


worldwide. These encompass a group of entities that vary
widely in terms of their clinical presentation and behavior.
These originate in lymph nodes or in extranodal tissue in any
part of the body, and from any type of lymphocyte. Three
types of lymphomas can be considered: Hodgkins, nonHodgkins and Burkitts. Multiple myeloma also needs a
special mention, though it is not a lymphoma, as it is a
malignancy of plasma cells, which arise from B-lymphocytes.

Non-Hodgkins lymphoma (NHL) is a lymphoproliferative


disorder of unknown cause that can occur in all races and
age groups. Unlike HD, which often begins with a single
focus of tumor, NHL is usually multifocal when first detected.
Ninety percent are of B-cell derivation. NHL has been
reported in association with AIDS and is classified based
on patterns of distribution (diffuse or nodular), cell type
(lymphocytic, histiocytic and mixed) and degree of differentiation of cells (well, moderate and poor).

Hodgkins Disease
Hodgkins disease (HD) is a disorder of unknown etiology
involving primarily the lymphoid tissue. It arises almost in
a single node or chain of nodes and spreads characteristically to the anatomically contiguous nodes. There are two
peaks of incidence, one in early adulthood and one around
fifth decade of life, and males have increased incidence when
compared to females. Four subtypes are recognized based
on histologic features (Rye system): lymphocyte predominance, nodular sclerosis, mixed cellularity and lymphocyte depletion. The lymphocyte predominance has the best
prognosis and lymphocyte depletion, the worst. HD is also
staged into four stages based on the clinical features (Ann
Arbor classification). Prognosis becomes worse as the stage
increases. Histologically, HD shows multinucleated Reed
Sternberg cells.

Treatment
The outlook after aggressive radiotherapy and chemotherapy for patients with this disease, including those with
disseminated disease, is generally very good. With current
modalities of therapy, the histologic picture has very little
impact on the prognosis; instead clinical stage appears to
be an important prognostic indication. However, long-term
survivors of combined chemotherapyradiotherapy protocols are at much higher risk of developing acute leukemia.
Currently, combination chemotherapy of doxorubicin, bleomycin, vincristine and dacarbazine is used for most patients.

Clinical manifestations
The most common presentation of NHL is a painless persistent enlargement of lymph nodes (Figure 4). Unlike HD,
extranodal lesions can occur in GI tract, Waldeyers ring,
spleen, skin and bone marrow. Signs and symptoms include
fever of unknown cause, weight loss, malaise, sweating, and
abdominal or chest pain. The clinical differences between
HD and NHL are outlined below.
Clinical differences between HD and NHL
HD

NHL

Extranodal involvement uncommon

Extranodal involvement seen

More often localized to a single axial


group of nodes

More frequent involvement of


multiple peripheral nodes

Orderly spread by contiguity

Non-contiguous spread

PelEbstein fever

Non-specific fever

Clinical manifestations
Hodgkins disease usually presents as a painless enlargement of the lymph nodes (rubbery). Extranodal involvement is rare. The signs and symptoms include fever, weight
loss, sweating, pruritis and fatigue. Characteristic clinical

Treatment
Non-Hodgkins lymphoma is radiosensitive and the treatment may include a combination of radiotherapy and chemotherapy. High dose chemotherapy with autologous stem
495

Section VII System Review

Figure 4

Enlargement of the accessory group of lymph nodes on


the right side of the face in a patient suffering from
non-Hodgkins lymphoma. Courtesy: Dr Sarat Gummadapu

cell transplantation is the treatment of choice for relapsed


disease. Commonly used drug protocols include cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP
and CVP).

Burkitts Lymphoma
Burkitts lymphoma (BL) is a B-cell neoplasm endemic in
some parts of Africa and sporadic in other areas, including
the United States. The tumor is the human cancer most
closely linked with a virus (EpsteinBarr virus). The tumor
is considered as the fastest growing human tumor as it
doubles in 13 days.
Clinical features
Both the endemic and non-African cases mainly affect
children or young adults. In both the forms, the disease
rarely arises in lymph nodes. In African patients, involvement of maxilla or mandible is the common mode of presentation, whereas abdominal tumors are more common
in North America.
Treatment
Majority of patients can be cured with aggressive chemotherapy. BL was found to be responsive to cyclophosphamide, methotrexate, vincristine and cytarabine.
Oral manifestations and dental considerations
Painlessly enlarged cervical lymph nodes are the initial
complaint in many of the cases. Suspicion of lymphoma
496

should arise if lymphadenopathy appears without signs of


infection or more than one lymph node chain is involved,
or a lymph node of 1 cm or more in diameter persists for
more than 1 month. A lymphoma may form in the oral
cavity or oropharynx but this is rare except in NHL. HD may
exhibit inflammatory gingival overgrowth, root resorption
and bone loss, which are thought to be paraneoplastic. The
most common site for non-Hodgkins extranodal lymphomas is the GI tract. In the head and neck region it occurs
within soft tissues or bone; the salivary gland, cheek,
paranasal sinuses and gingiva are the most common sites.
Maxilla is more commonly involved when compared with
the mandible. The radiographic methods used for diagnosis of malignant lymphoma include MRI, CT scanning and
ultrasound. Ceysens et al noted that the CT appearance of
extranodal NHL might often mimic other malignant and
inflammatory lesions. Further, 67Ga scintigraphy and bone
scintigraphy may also be useful for evaluating malignant
lymphoma. NHL is more commonly seen in HIV patients
presenting as a slow-growing, painless, bluish, soft masses
on the palate. Numb chin syndrome, which is the mental
neuropathy and facial and oral numbness restricted to the
distribution of the mental nerve, is also found to be frequently associated with malignant lymphoma. This might
be either due to direct invasion of tumor cells into the
nerve or the compression of the nerve by metastatic mandibular tumors, or the involvement of the trigeminal nerve
root by metastatic meningeal tumors.
More commonly, dental complications result from radiotherapy or chemotherapy administered in children with HD
during tooth development. These include agenesis, hypoplasia and blunted or thin roots. Patients with lymphoma
sometimes complain of burning mouth symptoms that may
be related to drug toxicity, xerostomia, candidiasis or anemia. Patients who have received more than 3,000 rad (cGy)
are susceptible to xerostomia and would benet from salivary substitutes or pilocarpine. Radiation also can damage
taste buds, cause trismus of masticatory muscles, and stunt
craniomandibular growth and development.

Multiple Myeloma
Multiple myeloma (MM) is a relatively uncommon malignant neoplasm of the plasma cells (which arise from the
B-lymphocytes) that often appears to have a multicentric
origin within bones. The cause of the condition is unknown,
although sometimes a plasmacytoma may evolve into
multiple myeloma. This disease makes up about 1% of all
malignancies and 1015% of hematologic malignancies.
The abnormal plasma cells in the bone marrow proliferate
from a single malignant precursor (monoclonal) and produce immunoglobulins that are not normal or functional.
This monoclonal nature of plasma cells can be differentiated from polyclonal nature of plasma cells seen in chronic
inflammation.

Chapter 18 Systemic Disorders and their Clinical Implications

Clinical and radiographic features


Multiple myeloma is typically a disease of older adults
(4th to 5th decade), with men being affected slightly more
often than women. The manifestations commonly seen are
anemia, thrombocytopenia and leukopenia due to suppression of other cells originating in the bone marrow. This may
lead to pallor, fatigue, infections and bleeding tendency. Bone
pain, due to motion or pressure against bony tumor masses
and pathological fractures. Renal failure and amyloidosis
due to deposition of abnormal proteins in kidney and various parts of the body. Bence Jones proteins, which are the
light chains of immunoglobulins, are excreted in the urine.
Hypercalcemia, due to destruction of bone: Radiographically, multiple well-defined punched-out radiolucencies
or ragged radiolucent lesions may be seen.
Oral manifestations
Macroglossia, gingival and soft tissue enlargement due to
deposition of amyloid.
Pallor, petechiae, ecchymosis and increased bleeding
tendency. The elevated serum monoclonal antibody can act
directly as a thrombin inhibitor or inhibit the interaction
of von Willebrand factor (vWF) with platelets or interfere
with brin polymerization and lead to excessive bleeding
tendency.
Jaw swelling, jaw pain, tooth mobility and paresthesia due
to tumor growth: Multiple myeloma can have three different radiographic manifestations in the jaw bone: (i) normal findings, when there is non-detectable or mild bone
resorption, (ii) multiple punched-out radiolucencies from
the focal proliferation of plasma cells inside the bone marrow and (iii) generalized bone rarefaction and osteoporotic
changes resulting from diffuse or total replacement of the
bone marrow by malignant cells.
Treatment
Chemotherapy constitutes the main modality with radiation
therapy as palliative modality of treatment for painful bone
lesions. Alkylating agent, such as melphalan or cyclophosphamide, is often used in conjunction with prednisolone,
and approximately 60% of patients respond initially to
this regimen. Complete remission is never attained and all
patients will relapse without further treatment. The prognosis is variable, but the survival of treated patients averages 3 years.
Dental considerations
Dental treatment can be complicated by anemia, infections,
hemorrhagic tendency, renal failure and corticosteroid
therapy. Bleeding may result from several causes, including
thrombocytopenia, abnormal platelet function, abnormal
coagulation or hyperviscosity.

BLEEDING DISORDERS
The integrity of circulation is maintained by blood flowing
through intact vessels lined by endothelial cells. Efficient
mechanisms have evolved to maintain the circulation as
a transport system, which both prevent blood loss from
a damaged vessel by securing hemostasis, and also prevent the cessation of flow due to thrombosis. Hemostasis
depends upon interactions between vessel wall, platelets
and clotting factors. There are two phases of hemostasis:
primary and secondary. In the initial primary phase, the
damaged vessel constricts and platelets aggregate at the
site of damage to form a plug to arrest hemorrhage within
a few minutes. This is followed by activation of the coagulation system with secondary deposition of a fibrin mesh to
secure the platelet plug. These two phases are interlinked;
damaged endothelium and the subendothelial matrix activates platelets, which then provide the optimal surface for
the binding of the clotting factors and generation of insoluble fibrin. Fibrinolysis is the major means of disposing of
fibrin after its hemostatic function has been fulfilled, and
it can be considered the rate limiting step in clotting. The
protagonists of the hemostasis are as follows:
Vessel wall
After tissue injury, serotonin and other vasoactive substances are released, which mediate the immediate reflex
vasoconstriction. This alone might be sufficient to arrest
bleeding from small vessels.
Platelets
If the defect in the blood vessel is very smalland many
small holes develop in the vasculature each dayit is often
sealed by a platelet plug rather than by a blood clot.
Platelets are minute round or oval disks, which circulate in
the blood. When these circulating platelets are exposed to
damaged vascular surfaces (in the presence of normal
vWF and endothelial cells), they are activated to produce
physical and chemical changes. These changes produce an
environment that causes the platelet to aggregate and
release ADP and platelet factors, which cause further platelet
aggregation and promotes clotting mechanism.
Clotting mechanism
Coagulation involves a series of enzymatic reactions leading to conversion of soluble plasma fibrinogen to fibrin clot.
This process involves multiple proteins, many of which are
synthesized by liver (fibrinogen, prothrombin, factors V,
VII, IX, X, XI and XII) and many are vitamin K dependent
(factors II, VII, IX and X). The scheme of reaction is a bioamplification in which, the precursor is altered to an active
form, which, in turn, activates the next precursor in the
sequence. Beginning with an undetectable biochemical
497

Section VII System Review

reaction, the coagulation mechanism results in the formation of insoluble fibrin. The clotting of blood also requires
calcium and phospholipids.
The mechanism initially proceeds by two separate pathways (intrinsic and extrinsic) that converge by activating
a third (common) pathway. The extrinsic pathway is initiated by release of tissue thromboplastin and does not
require contact activation. Tissue thromboplastin binds to
factor VII in the presence of calcium, and this complex is
capable of activating factor X to Xa. The intrinsic pathway
is initiated when factor XII is activated by surface contact
(e.g. with collagen or subendothelium), and it involves the
interaction of factors XII and XI. The activated factor XI
with the help of divalent cation (calcium) and phospholipids
converts factor X to Xa. The factor Xa heralds the initiation of common pathway. Factor Xa converts prothrombin
to thrombin, which further converts brinogen, a soluble
plasma protein, to insoluble brin. Finally, brin polymerizes to form a gel, stabilizing the platelet plug. The clot thus
formed has to be broken down after or else it may lead to
thrombosis. This critical function is carried out by TPA
(tissue plasminogen activator), which converts plasminogen to plasmin. The plasmin thus formed degrades brinogen and brin into brin degradation products (FDPs).
This phase is the brinolytic phase, which forms the rate
limiting step of hemostasis.
Laboratory investigations
A number of procedures that are performed in dentistry
may cause bleeding. Under normal circumstances, these
procedures can be performed with little risk to the patient;
however, the patient whose ability to control bleeding has
been altered by drugs or disease may be in grave danger
unless the problem is identified before undertaking any
dental procedure. An alert clinician will get suspicion
based on the history offered by the patient, which underscores the importance of meticulous history taking. The
most commonly used laboratory screening tests for bleeding disorders are bleeding time, platelet count, prothrombin
time and activated partial thromboplastin time. In addition
to this, capillary fragility test can also be conducted.
Platelet count This is usually obtained as a part of complete blood count. Normal platelet count is 150,000
450,000 cells/mm3. Decrease in the number of platelets is
called as thrombocytopenia. If the platelet count falls
below 50,000 cells/mm3, then hemorrhage may result due
to trauma or minor surgery. Spontaneous clinical hemorrhage is usually not observed with platelet counts above
10,00020,000.
Bleeding time (BT) This is a functional test of primary
hemostasis. The ivy template method is performed using
a special device that produces two small wounds keeping
the cuff of a sphygmomanometer constantly inflated at
498

40 mmHg. A piece of filter paper is used to dry the borders


of the tiny cuts every 30 seconds until no more oozing is
present. Normal ivy bleeding time is between 1 and 6 minutes and is prolonged if it is more than 15 minutes. Increase
in bleeding time could be caused by platelet defects
quantitative or qualitativeor by blood vessel defects. But
its use as a predictive screening test for oral surgical procedures has been discouraged as it is a poor indicator of
clinically significant bleeding at sites other than skin.
Prothrombin time (PT) The normal range of PT is 1113
seconds. The screening test examines the efficiency of
extrinsic and common coagulation pathways. Increase in
PT can be due to vitamin K deficiency, fat malabsorbtion,
coumarin therapy, liver disease or disseminated intravascular coagulation (DIC). Because different laboratories use
different types of reactives derived from different tissues
(lung and brain) and different species (rabbit, bovine and
human), it is necessary to standardize the PT. This has been
done using the international normalized ratio (INR). The
normal coagulation profile is reported as an INR of 1.0.
Activated partial thromboplastin time (aPTT) The normal range is 2236 seconds. The aPTT tests the coagulation factors involved in the intrinsic coagulation pathway
(factors VIII, IX, XI and XII). It is therefore elevated in conditions like hemophilia and von Willebrands disease, which
are a result of deficiency of one of these factors. It is also
elevated in heparin anticoagulant therapy.
Tourniquet test The tourniquet test for capillary fragility,
which assesses the RumpelLeede phenomenon, is useful
in identifying disorders of vessel wall integrity or platelet
disorders. After inducing stasis by inflating the sphygmomanometer cuff around the arm for 5 minutes, petechial
hemorrhages are visible on the volar aspect of the arm.

Classification of Bleeding Disorders


Bleeding disorders can be broadly classified as:
1.
2.
3.

Vascular disorders (vessel wall)


Platelet disorders
Disorders of coagulation.

VASCULAR DISORDERS (Vessel Wall)


Infections, chemicals, collagen disorders or certain types
of allergy can alter the structure and function of the vascular wall to the point at which the patient may have a
clinical bleeding problem. The vascular phase in the hemostasis begins immediately following injury and involves
vasoconstriction of arteries and veins in the area of injury.
Retraction of arteries that have been cut, and build up of
extravascular pressure by blood loss from cut vessels aids

Chapter 18 Systemic Disorders and their Clinical Implications

in collapsing adjacent capillaries and veins leading to cessation of bleeding. The various vascular disorders that may
lead to excessive bleeding tendency are:
Vessel wall disorders
1. Congenital
a. Hereditary hemorrhagic telangiectasia
b. Connective tissue disorders
EhlersDanlos syndrome
Osteogenesis imperfecta
Marfans syndrome
Cushings syndrome
2. Acquired disorders
a. Severe infections
b. Allergic manifestations
c. Drugs
Steroids
d. Others
Scurvy
Senile purpura

Hereditary Hemorrhagic Telangiectasia


It is a rare disorder with autosomal dominant inheritance.
Dilatation of capillaries and small arterioles produce characteristic small red spots that blanch on pressure in the
skin and mucous membranes, particularly the nose and
GI tract. Recurrent epistaxis and chronic GI tract bleeding
are the major problems and may cause chronic deficiency
anemia.
Perioral and intraoral angiomatous nodules or telangiectasia are common with progressive disease, involving
areas of the lips, tongue and palate that may bleed with
manipulation during dental procedures. Diascopy test is
positive unlike petechiae or ecchymoses. Mucocutaneous
lesions may bleed profusely with minor trauma or occasionally spontaneously. Iron deciency anemia has to be
treated with iron supplements, and persistently bleeding
lesions may be treated with cryotherapy, laser ablation,
electrocoagulation or resection.

EhlersDanlos Syndrome
EhlersDanlos disease is a congenital disorder of collagen
synthesis in which there is joint hyperextensibility, skin
extensibility and tissue fragility such that capillaries are
poorly supported by subcutaneous collagen leading to ecchymosis. Oral findings include bleeding after toothbrushing,
hypermobility of TMJ, fragility of oral mucosa and gingiva,
stunted teeth and pulp stones on dental radiograph.

Marfans Syndrome
The connective tissue disorder is inherited as an autosomal
dominant trait and is caused by mutations in the fibrillin

gene on chromosome 15. It is characterized by skeletal


disproportion (arm span more than height), arachnodactyly (long, thin spider-like fingers), generalized hypermobility of joints and CVS anomalies like mitral valve
prolapse, aortic incompetence, etc. The oral manifestations
are: high arched palate, bifid uvula, malocclusion and
multiple odontogenic cysts of the maxilla and mandible.
TMJ dysarthrosis is also reported.

Scurvy
Ascorbic acid (vitamin C) is the most active reducing
agent in the aqueous phase of living tissues and is involved
in the hydroxylation of proline in protocollagen to
hydroxylproline in mature collagen. It has been suggested
that high dose of vitamin C improves immune function
(including resistance to common cold) and cholesterol
turnover, but such effects remain unproven in controlled
trials. The scurvy, i.e. deficiency of vitamin C, leads to
defective formation of collagen. This impairs healing of
wounds, and causes capillary hemorrhage and reduced
platelet adhesiveness (normal platelets are rich in ascorbic
acid). Hemorrhage can occur in the muscles, joints, nail
beds and gingival tissues. Gingival involvement may
include swelling, bleeding, secondary infection and loosening of teeth. For treatment, a dose of 250 mg vitamin C,
8-hourly by mouth should saturate the tissues quickly. The
general deficiencies of the patients former diet also need
to be corrected and other vitamin supplements given if
necessary.
Investigations for vascular disorders

Bleeding time: Elevated.


Tourniquet test: Positive.

PLATELET DISORDERS
Platelet numbers or function may be impaired by many
diseases or drugs. Decrease in the number of platelets is
called as thrombocytopenia, which can occur either due to
impaired production or excessive destruction. Defect in the
function of platelets is called as thrombocytopathy, which
can occur due to drugs, liver disease or can be inherited. For
convenience, thrombocytopenic disorders and thrombocytopathic disorders are again divided into congenital and
acquired.

THROMBOCYTOPATHIC DISORDERS
Disorders of the platelet function are usually associated
with excessive bruising and gingival bleeding and, in
499

Section VII System Review

some of the acquired forms, with thrombosis. The platelet


count is normal or increases and the bleeding time is prolonged. Platelet function is abnormal due to a defect either
in the adhesion, aggregation or release of active substances. Inherited platelet disorders like Glanzmanns
thrombasthenia and Bernard-Soulier syndrome are deficient in platelet membrane glycoprotein resulting in failure of platelet aggregation. Bernard-Soulier syndrome is
also characterized by large platelets resulting in epistaxis,
menorrhagia and prolonged bleeding from tooth extractions. Storage pool disease is also an inherited thrombocytopathic disorder, which shows lack of storage pool of
platelet dense bodies, causing poor platelet function.
Medications can also reduce absolute number of platelets
or interfere with their function, resulting in post surgical
hemorrhage. Drug related platelet disorders are reversible
within 710 days of discontinuation of drug. Aspirin activates an enzyme called prostaglandin synthetase, resulting
in inactivation of cyclo-oxygenase and decreasing biosynthesis of prostaglandin and thromboxane that are needed
to regulate interactions between platelets and endothelium. A single 100 mg dose of aspirin provides rapid complete inhibition of platelet cyclo-oxygenase activity and
thromboxane production. Most NSAIDs have similar but
less signicant antiplatelet effects compared with aspirin.
Congenital

Acquired

Storage pool disease

Drug-induced (e.g. Aspirin)

BernardSoulier syndrome

Renal and liver disease

Glanzmanns thrombasthenia

Myeloproliferative disorder

THROMBOCYTOPENIC DISORDERS
These are caused by reduced platelet production in the
bone marrow or excessive peripheral destruction of platelets. The underlying cause may be revealed by history and
examination but a bone marrow examination will show
whether the platelets are reduced, normal or increased and
will provide essential information on morphology as well.
In patients with thrombocytopenia due to failure of production, no specific treatment may be necessary but the
underlying condition should be treated if possible. If the
platelet count is very low or the risk of bleeding is very
high, then platelet concentrate administration is indicated.
Idiopathic thrombocytopenic purpura (ITP), which is due
to increased destruction of platelets and thrombotic thrombocytopenic purpura are the commonly acquired thrombocytopenic disorders. MayHegglin anomaly is a rare
hereditary condition characterized by the triad of thrombocytopenia, giant platelets and inclusion bodies in leukocytes. Clinical features and the pathogenesis of bleeding of
these are poorly defined.
500

Congenital

Acquired

MayHegglin anomaly

Impaired production
Bone marrow failure
Leukemia
Aplastic anemia (drugs, chemicals)
Excessive destruction
Immune
Idiopathic thrombocytopenic purpura
Dilutional
Massive transfusion
Others
DIC
Thrombotic thrombocytopenic purpura

Idiopathic Thrombocytopenic Purpura


Idiopathic thrombocytopenic purpura (ITP) is due to
immune destruction of platelets. The antibody-coated
platelets are removed following binding to receptors on
macrophages. The condition is seen in both children and
adults. In children, it is usually acute but self-limiting and
may follow a viral infection or immunization. In adults, it
is usually less acute than in children. It is characteristically
seen in women and may be associated with other autoimmune disorders such as SLE, thyroid disease and autoimmune hemolytic anemia and also after infections with
viruses such as HIV. Platelet autoantibodies are detected in
about 6070% of the patients, and are presumed to be
present, although not detectable, in the remaining patients.
Easy bruising, purpura, epistaxis and menorrhagia are
common. In severe ITP, oral hematomas and hemorrhagic
bullae may be present.
Children do not usually require treatment. If treatment
is necessary on clinical grounds, high-dose prednisolone is
effective, given for a very short course. Intravenous immunoglobulin (IV IgG) should be reserved for very serious
bleeding or for urgent surgery. Adults with ITP having
platelet counts more than 30,000 cells/mm3 require no
treatment unless a surgical procedure is being carried out.
Otherwise, rst-line therapy consists of oral corticosteroids,
1 mg/kg body weight but IV IgG is useful where a rapid
rise in platelet count is desired, especially before surgery.
Second-line therapy involves splenectomy, to which the
majority of patients respond.

Thrombotic Thrombocytopenic Purpura


Thrombotic thrombocytopenic purpura (TTP) is a rare, but
very serious condition, in which platelet destruction leads
to profound thrombocytopenia. It is a characteristic symptom complex of fever, florid purpura, fluctuating cerebral
dysfunction and hemolytic anemia often accompanied by
renal failure. The underlying cause is not fully understood
but TTP seems to be due to endothelial damage associated

Chapter 18 Systemic Disorders and their Clinical Implications

with the presence in the circulation of very high molecular


weight multimers of vWF. TTP is associated with pregnancy,
metastatic malignancy, drugs such as mitomycin C and
infections. Microvascular infarcts occur in gingival and
other mucosal tissues in about 60% of the cases. Treatment
includes plasma exchange, using cryoprecipitate depleted
FFP (cryo-poor supernatant). Most patients are also treated
with prednisone, 1 mg/kg daily.
Oral manifestations and dental considerations
Oral manifestations Oral manifestations of vessel wall
disorders and platelet disorders are similar in which they
exhibit small pinpoint hemorrhages, called petechiae and
larger patches called ecchymosis. Platelet disorders with
severely altered hemostasis can lead to spontaneous gingival bleeding. Continuous oral bleeding over long periods
of time fosters deposits of hemosiderin and other blood
degradation products on the tooth surfaces, turning them
brown. Patients with disorders of coagulation mechanism
will exhibit bleeding due to trivial injuries, severe hemophiliacs experience bleeding into the joints (hemarthrosis)
and soft tissue hematomas. Oral bleeding occurs from sites
that are susceptible to trauma like labial frenum, tongue
and buccal mucosa. Though hemarthrosis is a common complication in hemophiliacs weight-bearing joints, it rarely
occurs in the TMJ.
Dental considerations
Basic management principles for patients with severe
defects: When severe bleeding is expected to result from
dental treatment, the goal of management is to restore the
hemostatic system preoperatively to within the requisite
parameters and to support coagulation with adjunctive medications or local measures. For reversible coagulopathies,
removal of the causative agent or treatment of the primary
illness or defect may allow the patient to return to normal
for the dental treatment period. For irreversible coagulopathies, however the missing or defective element may need
to be replaced from an exogenous source. Because of the
risks and expense of blood products, dental treatment
plans should be arranged to maximize the benet from the
transfusion by completing all procedures likely to induce
bleeding at one treatment visit, when possible.
Preventive and periodontal therapy Preventive dental
care and the maintenance of a healthy periodontium are
especially important for the patient with severe bleeding
disorder. Gingivitis can predispose the patient to spontaneous gingival bleeding. Instructions in thorough brushing
and flossing, diet and nutrition, fluoride use, and semiannual examination with gentle probing and prophylaxis
are emphasized as with normal patients. Calculus can be
removed atraumatically in stages with an ultrasonic scaler
or hand instruments to reduce hyperemia. The periodontal

patient requiring deep subgingival scaling and root planing


in areas of inflammation may require medical management
before a comprehensive initial therapy appointment.
Restorative and prosthodontic therapy Restoring carious teeth and preparing and cementing fixed prosthesis
usually produce minimal bleeding. The risk of gingival
bleeding can be reduced by the use of a thin rubber dam
and selection of an atraumatic, stable clamp or hemostatic
gingival retraction cord. Wedges and matrices can be used
with gentle handling. Removable appliances can be constructed conventionally. Attention should be paid to removal
of rough areas in trays and final prostheses that might
produce traumatic ulceration and bleeding.
Endodontic therapy Endodontic treatment of infected
teeth is especially important in the coagulopathy patient
because it may avert the need for extraction. Generally,
there are no contraindications to root canal therapy, provided the instrumentation does not extend beyond the apex.
Pulpotomies, pulpectomies and root canal therapies can be
generally performed without bleeding complications. The
minimal bleeding during pulp extirpation can be controlled intrapulpally with epinephrine or formocresol.
Orthodontic therapy There is no contraindication to
orthodontic treatment. Properly managed fixed appliances
are preferred over removable and functional ones that
reposition the mandible because they are less likely to provoke bleeding both intraorally from tissue irritation and
within the TMJ. Archwires should be secured with elastic
bands rather than free wires with sharp edges that cut the
mucosa. Careful adaptation and cementation of bands and
placement and removal of archwires are encouraged.
Pediatric dental therapy Pediatric dental patient occasionally presents with prolonged oozing from exfoliating
primary teeth. Administration of factor concentrates and
extraction of the deciduous tooth with curettage may be
necessary for the patients comfort and hemorrhage control. Pulpotomies can be performed without excessive
pulpal bleeding. Stainless steel crowns should be prepared
to allow minimal removal of enamel at gingival areas.
Pain control/local anesthesia The administration of local
anesthetics in bleeding disorder patients requires certain
precautions to prevent hematoma formation. Although
patients with mild-to-moderate disease are at low risk, those
with severe disease, especially severe hemophilia A, have
been shown to have 11% rate of hematoma formation following inferior alveolar nerve blocks. Hematoma spread to
the lateral pharyngeal, retropharyngeal and submandibular/
sublingual spaces may cause respiratory obstruction and
death. Hence, block anesthesia and some infiltration anesthesia in the patient with a severe coagulopathy (including
many mild-to-moderate hemophiliacs with factor levels
below 20%) should be avoided until the hemostatic defect is
501

Section VII System Review

corrected. For acute treatment of a forming hematoma,


application of pressure and ice are useful adjuncts to systemic correction of the hemostatic defect. Use of periodontal
ligament injections in mild-to-moderate hemophiliacs may
be effective for restorative procedures. Intrapulpal anesthesia is safe and effective following access for pulp extirpation.
An alternative to local anesthesia is nitrous oxide/oxygen
sedation which raises pain threshold and reduces anxiety.
Intramuscular injections should be avoided unless the coagulation defect has been corrected. Postoperative pain is
controlled with acetaminophen and narcotics. Aspirin and
other NSAIDs are contraindicated. When general anesthesia
is considered, oral intubation is preferred over nasal intubation, which may induce a difficult-to-control nasal bleeding.

INHERITED COAGULATION DISORDERS

Oral surgery Surgical procedures impose the highest risk


of bleeding in the coagulopathy patient. Though primary
importance is placed on systemic preoperative management such as plasma product infusion, local measures are
also extremely important in assisting clot formation and
maintenance. Surgical technique should be atraumatic,
with care taken to remove osseous fragments and granulation tissue, reappose buccal and lingual plates, and smooth
bony margins. Although having no direct effect on hemostasis, primary closure protects the blood clot, makes the
postoperative period more comfortable, and decreases the
risk of postoperative bleeding. Placement of absorbable
hemostatic agents such as bovine collagen in the apical
third of extraction sites promotes stable clots. Topical
buffered thrombin solution also has potent hemostatic
properties. It directly converts fibrinogen to fibrin and can
be applied to the bleeding site on an oxidized cellulose
product, such as oxycel or surgical. Antibiotics should be
considered when absorbable hemostatic agents are used or
signs of active infection exist because postoperative infection can lead to resumed bleeding.
The antibrinolytic epsilon-aminocaproic acid (EACA) is
an extremely useful adjunct to prevent postsurgical bleeding without the need for subsequent transfusions and to
treat gingival oozing following deep scaling and root planing. EACA prevents premature destruction of the brin clot
by virtue of its ability to inhibit plasminogen activation. The
usual adult dosage is 50 mg/kg body weight every 6 hours for
710 days. A 25% oral solution used topically and systemically is preferred over the tablet form or intravenous route.

Hemophilia A

DISORDERS OF COAGULATION
Coagulation disorders may be inherited or acquired. The
inherited disorders are uncommon and usually involve
deficiency of one factor only. The acquired disorders occur
more frequently and almost always involve several coagulation factors. The coagulation disorders can be classified
as follows.
502

The inherited disorders can result from deficiency of factors essential in the clotting cascade or deficiency of vWF.
Of the inherited coagulopathies, von Willebrands disease
is the most common. It results from the deficiency of von
Willebrands factor (vWF). Hemophilia A, caused by coagulation factor VIII deficiency, is the next most common
coagulation disorder, followed by hemophilia B, a factor IX
deficiency. Clinical bleeding can vary from mild to severe,
depending on the specific clotting factor affected and the
level of factor deficiency.

Hemophilia A is due to defective factor VIII (antihemophilic


factor, AHF). This is a glycoprotein of several components,
including factor VIII C (procoagulant that participates in
clotting cascade), VIII K:Ag (vWF, which binds to platelets
and is the carrier for factor VIII C) and VIII R:Rco (Ristocetin
cofactor, which supports platelet aggregation). In hemophilia A only factor VIII C is reduced.
Inherited as an X-linked recessive trait, hemophilia
affects males. Females are carriers as the normal X chromosome suppresses the effect of abnormal X (females have
XX chromosomal disposition). Hemophilia is denoted as
severe if factor VIII is less than 1%, moderate if factor VIII
is 15% and mild if factor VIII level ranges between 5%
and 25%. Hemophilia typically becomes apparent in childhood when bleeding into muscles or joints (hemarthroses)
follows injuries. Hemarthroses can cause joint damage and
cripple the patient, but bleeding after dental extractions is
sometimes the rst or only sign of mild disease. Bleeding
into the cranium, bladder and other sites can cause severe or
fatal complications. Hemorrhage in hemophiliacs is dangerous either because of loss of blood, or because there may
be damage to joints, muscles and nerves or pressure on
vital organs if hemorrhage is internal. This compression of
the pharynx and larynx following hematoma formation in
the neck can be fatal.
Investigations

Bleeding time: Normal


Prothrombin time: Normal
Platelet count: Normal
Activated partial thromboplastin time: Elevated
Factor VIII C: Deficient
Factor VIII R: AgNormal
Factor VIII R: RcoNormal.

Management
Bleeding is treated by administration of factor VIII concentrate by IV infusion. Factor VIII concentrate is freeze-dried

Chapter 18 Systemic Disorders and their Clinical Implications

and may be stored in domestic refrigerators at 40C. This


allows it to be administered by the patient immediately
after bleeding has started, reducing the likelihood of chronic
damage to joints and the need for in-patient care. The
majority of severely affected patients are given prophylaxis 3 times per week from early childhood in an attempt
to prevent permanent joint damage. Synthetic vasopressin
(desmopressin)IV or SC or intranasalproduces a rise in
factor VIII C proportional to the initial level of factor VIII.
It avoids the complications associated with blood products
and is useful for treating bleeding episodes in mild hemophilia and as prophylaxis before minor surgery. It is ineffective in severe hemophilia.

Hemophilia B and C
Christmas disease (factor IX deficiency) is clinically identical
to hemophilia A and inherited in the same way, but it is about
one-tenth as common as hemophilia A. Factor IX replacement
is needed before surgery and desmopressin is not used.
Concentrates used to treat factors VIII and IX deficiencies
are specific for each state, and therefore a correct diagnosis
must be made to ensure effective replacement therapy.
Factor XI deciency (PTA deciency) is one of the more
common among other congenital coagulation defects and
is sometimes known as hemophilia C. It is transmitted as
an autosomal dominant trait. Bleeding symptoms do occur
but are usually mild. In the event of major surgery or
trauma, hemorrhage can be controlled with infusions of
fresh frozen plasma.

Von Willebrands Disease


Von Willebrands disease is due to the inherited deficiency
in vWF, which is a component of factor VIII. It affects females
as well as males and is usually inherited as an autosomal
dominant condition, but a severe form of the disease may
be inherited as a sex-linked recessive trait like the hemophilia. vWF is responsible for platelet adhesion to damaged endothelium and also acts as a carrier for factor VIII,
protecting it from proteolytic degradation. Thus both bleeding time and activated partial thromboplastin time are
elevated in von Willebrands disease.
Clinical features
Von Willebrands disease causes bleeding that has features
similar to that caused by platelet dysfunction. But if severe,
it can resemble hemophilia. Three types of von Willebrands
disease have been identified. Type I and type II patients
usually have mild clinical features. Bleeding follows minor
trauma or surgery, and epistaxis and menorrhagia often
occur. Hemarthroses are rare. Type III patients have more
severe bleeding but rarely experience the joint and muscle
bleeds seen in hemophilia A.

Investigations

Bleeding time: Elevated


Platelet count: Normal
Activated partial thromboplastin time: Elevated
Factor VIII C: Decreased
vWF: Decreased.

Management
Treatment depends on the severity of the condition and may
be similar to that of mild hemophilia, including the use of
desmopressin where possible. Intermediate purity factor VIII
or vWF concentrates should be used to treat bleeding or to
cover surgery in patients who require replacement therapy.
Cryoprecipitate should be avoided because of greater risk
of transfusion transmitted infections. Aspirin and other
NSAIDs should also be avoided.

ACQUIRED COAGULATION DISORDERS


Liver Disease
Liver disease may result in a number of defects in hemostasis. The defects are:

Vitamin K deficiency: Occurs due to intrahepatic or


extrahepatic cholestasis
Reduced synthesis: Reduced synthesis of coagulation
factors may be due to severe hepatocellular damage
Thrombocytopenia: Results from hypersplenism due
to splenomegaly
Functional abnormalities: Functional abnormalities of
platelets and fibrinogen are found in many patients
with liver failure
Disseminated intravascular coagulation (DIC): May occur
in acute liver failure.

Vitamin K Deficiency
Vitamin K is necessary for carboxylation of coagulation factors II, VII, IX, X, without which these factors cannot bind
calcium. Deficiency of vitamin K may be due to inadequate stores, malabsorption and oral anticoagulants (vitamin K antagonists). PT and aPTT are prolonged and there
may be bruising, hematuria and gastrointestinal or cerebral
bleeding. Deficiency may be treated by phytomenadione
(vitamin K) 10 mg IV. Newborn babies have low levels of
vitamin K, and this may cause minor bleeding in the first
week of life (classic hemorrhagic disease of the newborn).

Disseminated Intravascular Coagulation


There is a widespread generation of fibrin within blood
vessels, owing to activation of coagulation by release of
503

Section VII System Review

procoagulant material, and by diffuse endothelial damage


or generalized platelet aggregation. There is a consumption
of platelets and coagulation factors and secondary activation of fibrinolysis leading to production of fibrin degradation products (FDPs), which may contribute to coagulation
defect by inhibiting fibrin polymerization. The consequences
of these changes are a mixture of initial thrombosis followed by a bleeding tendency due to consumption of coagulation factors and fibrinolytic activation. DIC may be
caused by malignant disease, septicemia, hemolytic transfusion reactions, trauma, burns, surgery and liver disease.
The clinical presentation of DIC varies from no bleeding at
all to profound hemostatic failure with widespread hemorrhage. Bleeding may occur from oral cavity, nose and
venepuncture sites. The underlying condition is treated
and this may be all that is necessary in patients who are
not bleeding. Transfusion of platelet concentrates, cryoprecipitate and red cell concentrates is indicated in patients
who are bleeding.
Anticoagulant therapy
Anticoagulation with warfarin is frequently used as a preventive measure for embolic phenomenon related to several conditions. Some of the most common ones are atrial
fibrillation, dilated cardiomyopathy, systolic congestive heart
failure, valvular heart disease and deep vein thrombosis.
Warfarin inhibits production of vitamin K-dependent factors II, VII, IX and X. The injudicious use of coumadin on
occasion can lead to spontaneous bleeding that can be
severe or even fatal.

RESPIRATORY DISORDERS
The lungs, with their combined surface area of more than
500 m2, are directly open to the external environment.
Thus, structural functional, or microbiological changes
within the lungs can be closely related to epidemiological,
environmental, occupational, personal, and social factors.
Primary respiratory diseases are responsible for a major
burden of morbidity and ultimately deaths and lungs are
often affected in mouth system diseases.
Respiratory infections are commonly encountered among
dental patients. The anatomic proximity of respiratory
tract with the oral cavity lead to much interplay between
oral and respiratory infections and there is a growing body
of literature pointing to a direct association between oral
pathogens and respiratory diseases. Recent studies have
reported an oral bacteria as a causative pathogen in respiratory diseases and conditions associated with signicant
morbidity and mortality and furthermore some respiratory
illnesses may have an effect on orofacial morphology and
even on dentition.

504

This section provides an overview of the more common


respiratory disorders and explores the relationship between
these conditions and oral health. A dentist with adequate
knowledge and skills to collect information pertaining to
those conditions which are likely to place these patients at
a higher risk of developing complications by receiving invasive dental treatment, can suitable modify dental treatment
to meet the needs of these patients.

Classification of Respiratory Tract Disorders


Respiratory tract disorders can be grouped as:
I.

Upper respiratory tract infections


1. Viral respiratory infections
2. Allergic rhinitis
3. Pharyngitis and tonsillitis
4. Sinusitis
II. Lower respiratory tract infections
1. Pneumonia
2. Asthma
3. Chronic obstructive pulmonary disease (COPD) or
chronic obstructive airway disease (COAD)
4. Cystic fibrosis
5. Pulmonary embolism
III. Granulomatous disorders
1. Tuberculosis
2. Sarcoidosis
IV. Malignant disorders
1. Bronchogenic carcinoma (lung cancer)
2. Nasopharyngeal T and NK cell lymphomas
V. Other respiratory disorders
1. Legionnaires disease (legionellosis)
2. Lung abscess
3. Bronchiectasis
4. Obstructive sleep apnea syndrome (OSAS)
5. Occupational lung disease.

Common Symptoms of Respiratory Diseases


Cough, production of sputum, hemoptysis, chest pain,
breathlessness and wheeze are common symptoms associated with respiratory diseases.
Cough
Cough is defined as an explosive expiration that provides
normal protective mechanism for clearing of tracheobronchial tree of secretions and foreign materials.
Origin of the cough

Common causes

Nature/characteristics

Pharynx

Post-nasal drip

Usually persistent

Larynx

Laryngitis, tumor

Harsh, barking

Chapter 18 Systemic Disorders and their Clinical Implications

Trachea

Tracheitis

Painful

Bronchi

Bronchitis

Dry or productive

Asthma

Dry or productive, worse


at night

Bronchiectasis

Productive. Changes in
posture induce sputum
production

Sputum
Sputum is matter (mucus, phlegm) that is expectorated
from the respiratory tract (usually lower respiratory tract),
that is mixed with saliva, which can then be spat from the
mouth. It is usually associated with diseases of the lower
respiratory tract.

mediastinal tumors), and pain associated with the chest


wall (rib fractures, direct invasion of chest by tumor, spinal
nerve root involvement).
Breathlessness or dyspnea
It is the unpleasant subjective awareness of the sensation
of breathing. The common respiratory causes for breathlessness include: acute severe asthma, chronic asthma,
chronic obstructive pulmonary disease, pneumonia, and
pneumothorax. Occasionally other respiratory conditions
may also predispose to dyspnea such as laryngeal edema,
inhalation of foreign object, extreme cases of pleural effusion, bronchial carcinoma and acute respiratory distress
syndrome.
Wheezing

Type

Appearance

Cause

Serous

Clear, watery, may be


frothy and pink

Acute pulmonary edema

Mucoid

Clear, gray, white and


occasionally black

Chronic bronchitis, asthma, chronic


obstructive pulmonary disease

Purulent

Yellow, green, brown

All types of bacterial infection

Rusty

Rust colored sputum


or golden yellow

Pneumococcal pneumonia

Hemoptysis
Hemoptysis is the expectoration of blood or of bloodstained sputum from the bronchi, larynx, trachea, or
lungs.
Causes for hemoptysis
Common causes

Uncommon causes

Others causes

Pulmonary infarction

Mitral stenosis

Foreign body inhalation

Bronchial carcinoma

Aspergilloma

Chest trauma

Tuberculosis

Bronchial adenoma

Iatrogenic

Lung abscess

Metastatic
pulmonary

Bronchoscopy
Transbronchial biopsy

Acute bronchitis

Malignant disease

Chronic bronchitis

Laryngeal tumors

Chronic obstructive
pulmonary disease

Chest pain
Chest pain is commonly associated with anxiety, cardiac
diseases, respiratory diseases, and disorders of the musculoskeletal and gastrointestinal system.
Chest pain associated with the respiratory system can
manifest as pleural pain (pneumonia, pulmonary infarction,
tuberculosis, malignant disease), retrosternal pain (tracheitis,

It is a continuous, coarse, whistling sound produced in the


respiratory passages during breathing. The primary causes
for wheezes to occur are either narrowed or obstructed respiratory passages or increased velocity of airflow within the
respiratory passages.
Wheezes may occur at various stages in the inspiratory and expiratory respiratory cycle. Diseases involving the brochioles may exhibit a wheeze that occurs in
the expiratory phase of respiration. Tumors, hypersensitivity pneumonitis and foreign body obstructions may
produce a monotonal wheeze throughout the inspiratory
phase.
Partial collapse of the lungs may lead to production of
wheeze that occurs at the termination of both the expiratory
and inspiratory phases. Such a wheeze usually signies the
periodic opening of deated alveoli.
Stridor is a term used for a harsh, high-pitched, vibrating sound that is heard in respiratory tract obstruction.
Obstructions in the upper airway passages (trachea, larynx, epiglottis) may produce stridor that occurs in the
inspiratory phase, whereas lower airway obstructions will
produce a stridor in the expiratory phase of respiration.
Clinical causes for wheeze

Infections (croup [laryngotracheobronchitis], whooping cough, laryngitis)


Laryngo-, tracheo- or bronchomalacia
Laryngeal or tracheal tumors, mediastinal masses
Tracheal stenosis
Emotional laryngeal stenosis
Foreign body aspiration
Asthma

Chronic obstructive pulmonary disease

Bronchorrheal states (chronic bronchitis, cystic fibrosis)


Bronchiectasis

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Section VII System Review

Interstitial fibrosis, hypersensitivity pneumonitis


Pulmonary edema
Forced expiration in normal subjects
Medications (many asthmatics wheeze following intake
of aspirin).

Oral manifestations and dental considerations

Respiratory diseases and their dental significance are listed


below.

The soft palate may reveal the presence of well-defined


minute erythematous macular lesions. Use of antihistamines for the management of upper respiratory tract infections may result in xerostomia.

UPPER RESPIRATORY TRACT INFECTIONS

Diagnosis

Viral Infections
Main causes for upper respiratory tract infections (RTI)

}}

Rhinoviruses
Respiratory syncytial viruses
Parainfluenza virus
Coxsackie viruses
Echoviruses
Adenoviruses
Influenza viruses
EpsteinBarr viruses
Beta-hemolytic streptococci

Common cold

Tonsillitis and pharyngitis

Majority of the upper respiratory tract infections are


caused by Rhinoviruses (Picornaviridae family). Other
viruses that are commonly implicated include the respiratory syncytial viruses (Paramyxoviridae family), influenza
viruses (Orthomyxoviridae family) and coxsackie viruses
(Picornaviridae family).
As rhinoviruses are the major causative factors for upper
respiratory tract infection, only they will be discussed.
Rhinoviruses spread via aerosols of respiratory droplets
and contaminated surfaces and direct person to person
contact. Once the virus enters the upper respiratory tract it
binds to intercellular adhesion molecule-1 (ICAM-1) receptors on the respiratory epithelial cells and begins to replicate
within 15 minutes of entering the hosts respiratory tract.
The infected cells release chemokines and cytokines. These
substances activate the inammatory mediators of the
host. Following an incubation period of about 10 hours the
rst symptoms begin to appear.
Rhinoviruses rarely cause lower respiratory tract disease
probably because they grow poorly at 37C.
Clinical features
The common clinical features seen in rhinovirus infections
include non-specific signs and symptoms such as fever,
sneezing, malaise, myalgia, headache, cough, rhinorrhea
with discharge (serous or purulent), nasal congestion and
oro-nasal-pharyngeal irritation.
As a consequence sinusitis and earache (obstruction
of the pharyngotympanic tube by edema or by bacterial
506

infection of middle ear) may be present. Maxillary sinusitis


may result in facial pain.

Laboratory tests are not really necessary for the diagnosis


of upper respiratory tract infections. However, the virus
may be isolated by culture or rapid diagnostic assay. A
complete hemogram may reveal increased numbers of
mononuclear cells, lymphocytes, and monocytes.
Management
Most of the infections are self-limited. The treatment is
aimed at managing symptoms. Patient should be adequately
hydrated. Antihistaminics are used to manage the rhinorrhea. Analgesics and antipyretics are used to treat fever and
myalgias.

Allergic Rhinitis
Rhinitis is the recurrent inflammation of the nasal membranes and is characterized by a symptom complex that
consists of a combination of any of the following: sneezing,
nasal congestion, nasal itching, and rhinorrhea. The eyes,
ears, sinuses, and throat may also be affected. When the
conjunctiva is also affected the term allergic rhinoconjunctivitis is used. It is estimated that almost 20% of the population suffer from allergic rhinitis. Seasonal, perennial,
sporadic/vasomotor and occupational allergic rhinitis are
some of the types of allergic rhinitis.
Environmental triggers such as pollen, dust mites, animal dander may incite a type I allergic hypersensitivity
reaction.
In susceptible individuals, exposure to certain foreign
proteins leads to allergic sensitization, which is characterized by the production of specic IgE directed against
these proteins. This specic IgE coats the surface of mast
cells, which are present in the nasal mucosa. When the
specic protein (pollen/dust mite, spore) is inhaled, it can
bind to the IgE on the mast cells, leading to immediate and
delayed release of a number of mediators such as histamine, chymase, kinins and heparin, which in turn produce
the symptoms of rhinorrhea.
Rhinits is present in two phases: the early or immediate
phase and the late phase. The early phase is seen within a
few minutes of exposure to the allergen and characterized
by nasal congestion, sneezing, itching, redness, tearing, and

Chapter 18 Systemic Disorders and their Clinical Implications

post nasal drip. The late phase usually occurs about 6 hours
after the early phase and patients present with reduction
in the frequency of sneezing and itching. However, congestion and increased mucus production is more common. This
phase may last for a few days.
Fatigue, malaise, drowsiness or sleepiness are common systemic effects of rhinitis. It is believed that allergic
rhinitis may often occur along with asthma or atopic
dermatitis.
Orofacial features and dental considerations
The readily visible facial features in allergic rhinitis are
allergic shiners, transverse nasal crease and DennieMorgan
lines. Allergic shiners is the term used to describe the
dark circles around the eyes due to vasodilation or nasal
congestion.
Rhinorrhea prompts individuals to frequently rub the
nose in an upward direction with the palm. This is classically referred to as allergic salute. Repeated rubbing of
the nose causes the formation of a transverse crease at the
tip of the nose. DennieMorgan lines are prominent infraorbital creases. These are also seen in atopic dermatitis.
The typical intraoral ndings include tonsillar hypertrophy and streaks of lymphoid tissue on the posterior part of
the oropharynx which gives rise to a cobble-stone appearance. Other symptoms include itching sensation in the palate and tongue protrusion. A study by Elad et al (2006)
showed the patients with allergic rhinitis had lower salivary ow rates compared to healthy individuals.
Gingival inflammation
Matsson and Mller (1990) studied the degree of gingival
inflammation in children with rhinoconjunctivitis due to
birch pollinosis. Their study showed that during the pollen
season, children with allergic rhinoconjunctivitis exhibit
an enhanced degree of gingival inflammatory reaction.
Dental and skeletal abnormalities
Trask et al (1987) analyzed the effects of perennial allergic
rhinitis on dental and skeletal development. The allergic
subjects were characterized by deeper palatal vault height,
retroclined mandibular incisors, increased total anterior
facial height and lower facial height, a larger gonial angle,
and greater SN, palatal, and occlusal planes to mandibular
plane angles. Also, the allergic subjects had smaller SNB
and SN-pogonion angles and an increased overjet compared to normal controls.
Martnez Esteinou and Omaa Vidal (1988) showed that
the patients with history of allergic rhinitis and nasopharyngeal obstruction (may result in mouth breathing) of
allergic origin exhibited a high palatal vault, retroinclinable maxillary incisors and increased total anterior facial
height.

Posture and allergic rhinitis


Hasegawa (1994) studied the effects of supine and lateral
recumbent positions in patients with allergic rhinitis. Their
investigations showed that posture induces complete nasal
obstruction in the supine or lateral recumbent positions in
some patients with allergic rhinitis.
Diagnostic tests
Blood tests will reveal an elevated serum IgE and eosinophil
count. Radioallergosorbent test (RAST) may be employed
to test sensitivity to specific allergens. Alternatively a skin
prick test is performed. A drop of a known allergen extract
is placed on the forearm and a lancet is used to make a
small prick on the skin through the drop. If the patient is
allergic to the test substance a small lump is seen in 1520
minutes time.
Dental considerations
Use of first generation antihistamines may result in dry
mouth. Long-term use of steroid based inhalers may cause
oral candidiasis.

Pharyngitis and Tonsillitis


Inflammation of the pharynx is referred to as pharyngitis.
It is usually caused by the direct infection of the pharynx,
primarily by viruses or bacteria. Group A beta-hemolytic
Streptococcus (GABHS) pharyngitis accounts for 1530% of
cases in children and 515% of cases in adults.
Pharyngitis may also be caused due to post nasal drip
secondary to rhinitis, gastroesophageal reux, thyroiditis,
allergies, a foreign body, chronic mouth breathing and
smoking. It is estimated that approximately 1.1% of the
visits to the primary care center are for acute pharyngitis.
It usually occurs in late winter and early spring. Transmission of typical viral and GABHS pharyngitis occurs
mostly by hand contact with nasal discharge, rather than
by oral contact. The rst symptoms are seen after an incubation period of 2472 hours.
Viral pharyngitis
The viral form of pharyngitis is characterized by the presence of rhinorrhea, cough, conjunctivitis, coryza, malaise or
fatigue, hoarseness, and low-grade fever.
The common viral causes for pharyngitis include
EbsteinBarr infection (infectious mononucleosis), coxsackie
virus infection (herpangina). Patients present with fever,
malaise and fatigue, exudative tonsillopharyngitis, generalized lymphadenopathy and hepatosplenomegaly. Almost
90% of the patients present with a classic maculopapular rash.
Coxsackie virus infection is characterized by the presence
of tonsillopharyngitis and discrete minute ulcers (23 mm)
on the anterior tonsillar pillars, uvula and soft palate.
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Section VII System Review

Bacterial pharyngitis
Patients with bacterial pharyngitis generally do not have
rhinorrhea, cough, or conjunctivitis. GABHS (mainly Streptococcus pyogenes) is the most common bacterial cause of
pharyngitis. Other less common bacterial causes include
Corynbacterium diphtheriae, Neisseria gonorrheae, Chlamydia
and Mycoplasma pneumoniae.
Pharyngotonsillitis caused by GABHS is characterized
by pharyngeal erythema and swelling, tonsillar exudate,
edematous uvula, palatine petechiae, and anterior cervical
lymphadenopathy. The infections last for about one week
when left untreated.
Scarlet fever is associated with GABHS pharyngitis and
usually presents as a punctate, erythematous, blanchable,
sandpaper-like exanthem. The rash is found in the neck,
groin, and axillae, and is accentuated in body folds and
creases (Pastias lines). The pharynx and tonsils are erythematous and covered with exudates. The tongue may be
bright red with a white coating (strawberry tongue).
The complications of GABHS infection are rheumatic
fever, peritonsillar abscess and poststreptococcal glomerulonephritis. Peritonsillar abscess occurs in fewer than 1%
of patients treated with antibiotics. Patients with peritonsillar abscess typically have a toxic appearance and may
present with a hot potato voice, uctuant peritonsillar
mass, and asymmetric deviation of the uvula.
Clinical scoring system for validation of
Streptococcal infection
Symptoms and points

Fever (subjective or measured in office): 1 point


Absence of cough: 1 point
Tender anterior cervical adenopathy: 1 point
Tonsillar swelling or exudates: 1 point.

streptococcal infections especially in the course of acute


rheumatic fever.
Management
Viral pharyngitis runs a short course and usually treated
symptomatically. Patients may be advised to use antiseptic
and analgesic mouthrinses. Acute streptococcal pharyngitis
is treated with oral penicillin V or erythromycin or IM injections of benzathine penicillin G or oral cephalosporins.
Dental considerations
GABHS may be persistent on toothbrushes and removable
orthodontic appliances, thus patients with GABHS infections should be instructed to thoroughly clean their toothbrushes and removable orthodontic and acrylic appliances
daily and also to change to a new toothbrush after the acute
stage of any oropharyngeal infection.
Amoxicillin and ampicillin should be avoided in treatment of GABHS as they tend to cause rashes, especially if
the sore throat in glandular fever is misdiagnosed as a
streptococcal sore throat.

LOWER RESPIRATORY TRACT INFECTIONS


Of the various lower respiratory tract infections, some of
those which have significant dental considerations will be
discussed below.

Asthma
Asthma is a dynamic condition characterized by chronic
airway inflammation and bronchial hyperactivity resulting
in symptoms of paroxysmal wheeze, cough, chest tightness
and dyspnea.

Age

Younger than 15 years: 1


1545 years: 0
Older than 45 years: 1.

Scoring

0 or 1 points: streptococcal infection ruled out (2%)


1 to 3 points: order rapid test and treat accordingly
4 to 5 points: probable streptococcal infection (52%),
consider empiric antibiotics.

Diagnosis
Along with the clinical findings, blood smear examination,
estimation of liver enzymes, culture for group A Streptococcus and detection of antigen will aid in the diagnosis.
Antistreptolysin O titers raise about 150 U within 2 weeks
of acute infection. They are useful for documenting recent
508

Predisposing/risk factors
Asthma originates from the interaction of multiple genetic
and environmental factors. Asthma is known to run in
families. Childhood asthma usually occurs in atopic individuals who express elaborate amounts of IgE when exposed
to common allergens/antigens.
Environmental factors are: house dust mites, automobile
exhausts, industrial gaseous wastes, climatic changes,
tobacco smoke, airborne irritants (including acrylic and
aerosolized dental materials) and pollen. Other factors that
predispose to asthma are infections (viral and bacterial
infections), drugs (-blockers, salicylates/NSAIDs cause
bronchoconstriction) and anxiety.
Extrinsic asthma is precipitated by allergens in house
dust, feathers, animal fur, molds, milk, eggs, sh, fruits,
nuts and NSAIDs; whereas intrinsic is related to mast cell
instability and hyperresponsive airways.

Chapter 18 Systemic Disorders and their Clinical Implications

Pathophysiology
It generally is believed that both genetic and environmental
factors, as well as allergens, are important in the initiation
and continuation of the airway inflammation.
Airway inammation in asthma has been characterized
as acute, subacute or chronic. The acute state of inammation is caused by the release of chemical mediators from
activated resident cells, such as local airway mast cells
undergoing histamine degranulation.
Subacute inammation is marked by early cellular inltrates, especially eosinophils that release mediators with
direct toxic effects on the respiratory epithelium.
The airway inammation is described as chronic when
lymphocytes and eosinophils mediate a persistent, ongoing inammation, thus resulting in a continuous cycle of
damage and repair. Long-standing chronic inammation
can lead to irreversible airway obstruction in some patients.
Bronchial smooth muscle contraction contributes markedly to the airway obstruction seen in asthma, while vasodilation, diapedesis and vascular permeability account for
the edematous changes. These changes are attributed to cellderived mediators. Mucus hypersecretion is also observed
and can result in the development of mucus plugs and
associated dyspnea.
Clinical symptoms and signs
Cough, shortness of breath, chest tightness, wheezing,
tachypnea and tachycardia, are usually noticed. Typically
these symptoms show ready reversal when bronchodilators
are used. In acute asthmatic attacks patients are extremely
distressed, flaring of the nares, sweating, central cyanosis,
use of accessory respiratory muscle, pulsus paradoxus and
silent chest may be seen.
Orofacial features
Asthmatic patients are known to have an increased incidence of carious lesions, reduced salivary flow, an increased
prevalence of oral mucosal changes, increased levels of
gingivitis and related orofacial abnormalities.
It is believed that the prolonged use of 2-agonists,
which is associated with diminished salivary production
and secretion results in increased caries development. This
reduction in salivary ow (26% drop in whole saliva) is
accompanied by concomitant increase in lactobacilli and
Streptococcus mutans in the oral cavity. Anti-asthmatic
medications containing fermentable carbohydrate and
sugar may also add to the bacterial build-up.
The use of corticosteroids via nebulizers leads to dysphonia, dryness of mouth and oropharyngeal candidiasis.
Linder et al (1995) reported tongue hypertrophy associated
with inhaled corticosteroid therapy in premature infants.
Since most of the asthmatics are habitual mouth breathers, gingival enlargement is routinely encountered. Use of

inhaled steroids has also been linked to increased levels of


gingivitis.
Mandel et al (1969) and Wotman et al (1973) have
shown that asthmatic children exhibit more calculus than
do healthy children. It was found that the children suffering
from asthma have increased levels of calcium and phosphorus in submaxillary and parotid saliva.
For many years the association between asthma and
dentofacial morphology has been evaluated and discussed.
It is suggested that the reason for the abnormalities is due
to the impaired nasorespiratory function. Various dentofacial abnormalities seen in asthmatics are increased upper
anterior and total anterior facial height, higher palatal vaults,
greater overjets, higher prevalence of posterior crossbites,
long and tapered facial form, increased lower facial height
and narrow maxillary arch.
Management
Patients should be educated to avoid all known allergens.
For patients with mild, intermittent asthma, the occasional
use of an inhaled short-acting 2-agonist (albuterol, terbutalin) is indicated. Bronchospasm can be managed with
aerosolized bronchodilator containing methylxanthines
such as theophylline and oxtriphylline. Steroids such as
betamethasone and triamcinolone and mast cell inhibitors
(cromolyn sodium) are also used effectively.
Dental considerations
For dental considerations see Table 1.

Chronic Obstructive Pulmonary Disease or


Chronic Obstructive Airway Disease
Chronic obstructive pulmonary disease (COPD) is caused
by chronic bronchitis and emphysema. Chronic bronchitis
is defined as the excessive production of mucus and persistent cough with sputum production for more than 3 months
in a year over 23 consecutive years.
Emphysema is dilatation of air spaces distal to the terminal bronchitis with destruction of alveoli and reduction
in the alveolar surface area available for respiratory
exchange.
Etiopathogenesis
The main etiological agent is tobacco smoke. Other etiological agents include industrial dust, automobile exhaust,
smoke emitted from traditional cooking using firewood.
The contents of smoke produce a severe inammatory
response. The respiratory epithelium is damaged and the
enzymes necessary for respiratory metabolism are impaired.
The oxygen carrying capacity of RBCs is diminished.
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Section VII System Review

Table 1

Dental considerations for asthma

Dos

Donts

Fluoride supplements for those taking 2-agonist

Barbiturates and narcotics should be avoided because they can cause


bronchospasm and reduce respiratory functions

Instruct patient to rinse mouth with water after using inhalers. Oral
hygiene measures to reduce gingivitis and periodontitis

Avoid antihistamines (promethazine, diphenhydramine) as they can


cause a drying effect and increase risk of forming tenacious mucus in
acute attack

Schedule patients appointments for late morning or later in the day, to


minimize the risk of an asthmatic attack

Dental materials such as methyl methacrylate that precipitate attack are


best avoided. Ensure that acrylic appliances are cured prior to insertion

Antifungal medications should be prescribed in patients on inhalational


corticosteroids

Drug interactions with theophylline are common (macrolide antibiotics


increase the level of theophylline, phenobarbitals may reduce the level,
tetracycline have been associated with more accentuated side effects
when given together with theophylline)

Steroid prophylaxis should be advised in patients who are on long-term


systemic corticosteroids

Avoid aspirin and other non-steroidal anti-inflammatory agents as they


might cause allergic reactions

Use stress-reducing techniques, Conscious sedation should be


performed without bronchoconstrictions (hydroxyzine)

Oxygen and bronchodilators should be available in case of an


exacerbation of asthma

Nitrous oxide can be used in mild cases

In severe asthmatics, nitrous oxide may irritate the airways

Local anesthetics containing epinephrine may be used. However,


preservatives such as sodium metabisulfite should be avoided as they
may exacerbate an asthmatic attack

In some asthmatic patients there may be an interactions between


epinephrine and 2-agonists that may producing increased blood
pressure and arrhythmias

Judicious use of rubber dams prevents reduced breathing capability


Care should be taken in the positioning of suction tips as they may elicit
a cough reflex
During an acute asthmatic attack, discontinue the dental procedure,
remove all intraoral devices, place the patient in a comfortable position,
make sure the airway is opened, and administer a 2-agonist and oxygen
and if there is no improvement, administer epinephrine subcutaneously
(1:1,000 concentration, 0.01 mg/kg of body weight, up to a maximum
of 0.3 mg) and avail medical assistance

Clinical features
Early morning productive cough, dyspnea and orthopnea
are common clinical features. Dyspnea leads to reduced
oxygen saturation, carbon dioxide build-up and respiratory failure or cor pulmonale (right sided heart failure).
Some patients with emphysema try their best to maintain normal levels of blood gases by hyperventilating. These
patients are referred to as pink panters or pink puffers.
However, patients suffering from chronic bronchitis cannot
hyperventilate and become hypoxic and hypercapneic (high
levels of carbon dioxide in blood). Such a state of hypoxemia results in central cyanosis in association with elevated
jugular venous pressure giving rise to a blue bloated appearance. These patients are referred to as blue bloaters.
Dental considerations
Patients suffering from emphysema may present with xerostomia. Occasionally, tobacco related mucosal lesions may
be seen.

510

Patients should ideally be seated upright for the treatment. Rubber dam should be avoided as it can further
compromise breathing. Drugs to be avoided include IV barbiturates, diazepam and midazolam as they cause respiratory
depression.
General anesthesia is best avoided. Wherever possible
all treatment should be performed under local anesthesia
without epinephrine. Bilateral mandibular nerve blocks
should be avoided.
Management
Patients should be advised to abstain from exposure to
smoke. Expectorants and humid environment will hasten
the recovery process. Bronchodilators (methylxanthines
theophylline, aminophyline), sympathomimetic agents
(isoproterenol, ephedrine, salbutamol) and corticosteroids
are effectively used. Acute infective phases can be managed
with antibiotics. Digitalis and diuretics are used for cor
pulmonale.

Chapter 18 Systemic Disorders and their Clinical Implications

Cystic Fibrosis
Cystic fibrosis (CF) is an autosomal recessive genetic disorder that affects the functioning of nearly all of the
bodys exocrine glands. The pulmonary manifestations are
characterized by repeated endobronchial infections, an
exaggerated inflammatory response, airways obstruction,
and bronchiectasis. It is estimated that the incidence of CF
is approximately 1 in 3,500 live births.
Pathogenesis of cystic fibrosis
Felix (2009) describes the current concept in the evolution
of cystic fibrosis. The CF gene defect leads to an absent
or malfunctioning cystic fibrosis transmembrane conductance regulator (CFTR) protein, which results in abnormal
chloride conductance on the apical membrane of the epithelial cell. In the lung, this results in airway surface liquid
depletion and, since airway surface liquid is essential to
support ciliary stability and functioning, ciliary collapse
and decreased mucociliary transport. The consequence of
this is a vicious circle of phlegm retention, infection, and
inflammation.
Clinical features specific to respiratory system
Patients present with a chronic or recurrent cough, which
can be dry at the beginning and can produce mucoid (early)
and purulent (later) sputum. Prolonged symptoms of bronchiolitis occur in infants. Paroxysmal cough followed by
vomiting may occur. Recurrent wheezing, recurrent pneumonia, atypical asthma, pneumothorax, hemoptysis, and
digital clubbing are all complications and may be the initial
manifestation. Dyspnea on exertion, history of chest pain,
recurrent sinusitis, nasal polyps, and hemoptysis may occur.
These patients may have a sweat sodium concentration
in excess of 70 mmol/l. Spirometry can be used to assess
the lung function.
Dental considerations
Swelling of submandibular gland or parotid gland may be
seen. Tooth eruption may be delayed. Enamel hypoplasia is
a common feature. Pancreatin, which is used in the treatment
of CF can cause oral ulcerations. Extensive use of antibiotics and steroids can predispose to oral candidiasis. The low
fat, high carbohydrate diet will lead to carious teeth.

GRANULOMATOUS DISEASES
Clinical features and oral manifestations of tuberculosis
and sarcoidosis have been described in Chapter 21 on
Granulomatous Diseases.

MALIGNANT DISORDERS
Bronchogenic Carcinoma
It is estimated that almost 95% of all primary lung tumors
are bronchogenic carcinomas. These carcinomas may arise
from the bronchial epithelium or the mucous glands.
Cigarette smoking is considered as the single most important etiological factor in the production of lung cancer.
Other predisposing factors include: occupation related exposure to asbestos, chromium and cadmium, and exposure to
radiation.
Clinical features
The earliest clinical signs and symptoms include: cough,
breathlessness, pleural pain and hemoptysis. Local infiltration of the tumor leads to pleural effusion, brachial neuritis and recurrent laryngeal nerve palsy (produces bovine
cough). When the superior vena cava is obstructed facial
cyanosis and edema is seen. Esophageal obstruction may
cause dysphagia.
Distant metastasis is characterized by symptoms of lassitude, anorexia and weight loss.
A wide spectrum of clinical features is appreciated based
on the site of metastasis. Common metastatic sites include
bones, liver, adrenal glands, lymph nodes, brain and spinal
cord. Palpable lymphadenopathy, particularly in the supraclavicular fossa, suggests metastasis.
Hepatomegaly is seen when there is hepatic metastasis;
cerebral metastasis leads to epilepsy, hemiplegia and disturbed vision. Bone metastasis results in pain, swelling and
in severe cases pathological fracture of the bone affected.
Dental considerations
Metastasis to the jaw bones is relatively rare. On rare occasions, the metastatic lesion may appear as a soft tissue swelling or pigmented lesion of the oral mucosa. Abraham et al
(2003) described facial pain as the presenting symptom of
lung carcinoma. They reported 31 cases with a symptom of
unilateral facial pain, although there was no metastatic
lesion in the mandible. The most frequent locations of pain
were the ear, the jaw and the temporal region, 61% occurring
on the right and 39% on the left side. The pain resolved or
partially remitted in most patients following treatment of
the carcinoma. They suggested that this pattern of referred
pain from the chest to the face presumably involves either
direct tumor invasion or compression of the vagus nerve by
malignant lymph nodes. The vagus nerve, which contains
motor, visceral and somatic afferent and parasympathetic
fibers, innervates both thoracic and cranial structures.
General anesthesia is best avoided as the respiratory
function is compromised.

511

Section VII System Review

OTHER RESPIRATORY DISEASES


Legionnaires Disease (Legionellosis)
Bacteria of the Legionella species are small gram-negative
rods that belong to family Legionellaceae. These intracellular pathogens develop in the alveolar macrophages, and less
frequently in other macrophages, monocytes and leukocytes.
Legionella commonly occurs in natural and articial
water reservoirs, less often in soil and organic matter.
Its proliferation is favored by the water temperature of
2542C, the presence of algae or protozoa, and calcium
or magnesium salt-containing sediments.
The source of infection may be air-conditioning systems, showers, fountains, dental unit waterlines and other
sources producing water mist.
Infection occurs by the inhalation of bacteria-laden
water droplet aerosol or dust. Incubation time is 210 days.
The Legionellaceae comprises more than 45 species but
Legionella pneumophila is isolated from 90% of culture
proven clinical cases of Legionnaires disease.
Infection with the Legionella rod causes legionellosis.
Three clinical types of legionellosis can be distinguished:
1.
2.
3.

Sporadic or epidemic infection in the form of legionellosis pneumonia, described as Legionnaires disease
Pontiac fevera flu-like form having a mild course
An extra-lung form in immunosuppressed patients,
often taking a severe clinical course, with the septic
syndrome, coagulation disorders, acute cardiovascular
deficiency and nephritis.

Diagnosis
Legionellosis diagnostics is based on serological studies of
the blood serum to indicate the level of antibodies, on the
patients urinalysis to determine the presence of a specific
antigen with the immunoenzymatic ELISA and radioimmunological (RIA) tests and on the bacteriological examination of the bronchial tree secretion, bronchoalveolar
washings, lung biopsy material and sputum.
Dental considerations
High- and low-speed handpieces, ultrasonic instruments and
airwater syringes produce air-water aerosols, which may
be source of infection. Both the dental team and the patient
are exposed to the infected aerosols via inhalation. By inhaling them and choking, the airwater aerosol with the droplets of 0.25.0 m in diameter, can contain Legionella.

Obstructive Sleep Apnea Syndrome


Obstructive sleep apnea syndrome (OSAS) is a disorder that
derives from the intermittent and repetitive occlusion of
the upper airway during sleep. This occlusion is due to the
512

inspiratory collapse of the walls of the pharynx, which


determines the complete closure (apnea) or partial closure
(hypopnea) of the airway. Apneas or hypoapneas are of
varying duration and have distinctive effects on cardiorespiratory homeostasis. Its repetition during sleep, sometimes several hundred times in one night, and day after
day for years, ends up producing significant alterations in
the central nervous system, in myocardial and cerebral circulation and in pulmonary and systemic circulation.
Clinical manifestations
Snoring is the most common symptom. It occurs due to the
narrowing of the pharynx and vibration of the soft parts
of the upper airway (the pharyngeal walls, the veil of the
palate and the uvula).
The main daytime manifestations are xerostomia, gastroesophageal reux, impotence, irritability, depression,
decreased libido, non-restorative sleep, concentration difculties and headaches. While nocturnal manifestations
include diaphoresis, xerostomia, salivation, altered sleeppatterns, awareness of apnea and sensation of suffocation
or panting.
These patients are usually associated with neuropsychiatric and cardiorespiratory disorders (arterial hypertension,
cardiac insufciency, bradycardia and nocturnal arrhythmias, dilated myocardiopathy, pulmonary hypertension and
ischemia).
Orofacial features and management
The most common mouth and facial characteristics found
include retrognathic jaw, a narrow palate, a wide neck,
a deviated nasal septum and relative macroglossia.
Orthognathic surgery and uvuloplastopharyngoplasty
may be useful. The treatment of choice for OSAS is with
continuous positive upper airway pressure (CPAP). This can
be achieved using a nasal mask at night. A specic level of
pressure is applied in the upper airway, preventing its collapse providing a mechanical widening of the upper airway.
Medroxyprogesterone acetate, almitrine, protriptyline
and theophylline are some of the pharmaceuticals tested so
far. However, these are not very effective. Intraoral appliance
was rst used in the 1980s. The mandibular advancement
devices (MAD) in their two versions (xed advancement
and adjustable advancement) are really efcient for managing obstructive problems of the upper airway. The MADs
carry out an anterior and inferior movement of the jaw
generating anatomical variations in the upper airway facilitating an increase in the pharyngeal area.

RENAL DISORDERS
Homeostasis, a term introduced by WE Cannon, which
means the maintenance of constant internal environment.

Chapter 18 Systemic Disorders and their Clinical Implications

The internal environment in the body is the extracellular


fluid in which the cells live. This fluid is present outside the
cell and it constantly moves throughout the body. It includes
the blood which circulates in the vascular system and fluid
present in between the cells which is called interstitial
fluid. This fluid should be maintained relatively constant
in composition for the normal functioning of the cells, since
changes in the extracellular fluid are reflected in changes
in fluid within the cells and in the cell function.
Homeostasis is essential to maintain the normal physiological activities in the body. So, whenever there is threat
to alter the physiologic activities, various systems of the
body try to regulate and adjust the functions in such a way
that the condition is brought back to normal.
The human kidney which is an important excretory organ,
situated on the posterior wall of the abdomen, one on each side
of the vertebral column, plays a signicant role in the maintenance of body homeostasis through its various functions.

Functions of Kidney
1.
2.
3.
4.

5.
6.

It excretes waste products, especially the nitrogenous and


sulfur containing end products of protein metabolism.
It helps to maintain the normal hydrogen ion concentration of body fluids and electrolytes.
It eliminates drugs and various toxic substances from
the body.
Regulations of arterial pressure by reninangiotensin
system, renin secreted by juxta glomerular apparatus
converts angiotensin I to angiotensin II which brings
about elevation of blood pressure by vasoconstriction.
It helps in the regulation of erythropoiesis through the
formation of erythropoietin secreted by glomerular cells.
It plays an important role in vitamin D metabolism,
as it brings about hydroxylation of inactive form of
vitamin D and converts to active metabolite which
helps in calcium absorption by intestine.

Nephrons that are about 1 million per kidney are the functional unit of the kidney that helps to filter wastes from
blood, modulate excretion of salts and water from the body
and allow the kidney to perform its excretory, metabolic
and endocrine functions. Since, the nephrons are incapable
of regeneration, renal function is maintained until approximately half of the nephrons are destroyed. When the kidneys compensatory mechanisms are overwhelmed, signs
and symptoms of renal failure begins to manifest.

RENAL DISEASES
1.
2.
3.
4.
5.

Acute renal failure


Chronic renal failure
Hypertensive kidney disease
Nephrotic syndrome
Specific tubular abnormalities.

Renal failure is defined as the stage of renal function in


which the kidney is no longer able to maintain the integrity
of the internal environment of the organism. Chugh (1999)
defined renal failure as the deterioration of renal function
resulting in decline in glomerular filtration rate and rise in
urea and non-nitrogenous substances in the blood.

Acute Renal Failure


Any condition that interferes with kidney function can cause
acute renal failure. In this condition, the kidney stops working entirely or almost entirely. In chronic renal failure large
numbers of nephrons are destroyed progressively until the
kidney simply cannot perform normal function.
Vascular or glomerular lesion cause hypertension but not
renal failure is referred to a hypertensive kidney disease.
In nephrotic syndrome, glomeruli have become more
permeable than normal so that large amounts of protein
are lost into the urine. Specic tubular abnormalities are
characterized by abnormal reabsorption or lack of reabsorption of certain substances by the tubules.
Many diseases which affect the kidney are associated
with alterations in the mouth or inuence the course of
the common dental disease or affect the mode of treatment
or can cause complications. Severe renal disease especially
chronic renal failure can play havoc with the skeletal
structure including the maxilla and mandible.

Chronic Renal Failure


Physicians earlier used to use the diagnostic term chronic
Brights disease for common end point of diffuse, severe
renal parenchymal disease. However, now the term chronic
renal failure or end-stage renal disease (ESRD) is preferred.
Davidson (1994) stated that chronic renal failure is irreversible deterioration in renal function. Scott (1996) dened
ESRD as a chronic, progressive disease that is characterized
by the destruction of nephrons, the kidneys functional unit.
Chugh (1999) dened chronic renal failure as slow insidious irreversible deterioration of renal functions resulting
in the development of clinical syndrome of uremia manifested by excretory, metabolic, neurological, hematological
and endocrinal abnormalities.
Etiology
Chronic renal failure may be caused by any condition which
destroys the normal structure and function of the kidney.
Harrison (1983) stated that glomerulonephritis, tubulointerstitial disease, diabetic nephropathy and nephro-sclerosis
are among the most common cause of chronic renal failure.
Guyton (1991) has given the causes for chronic renal
failure as:

Chronic glomerulonephritis
Traumatic loss of kidney tissue
513

Section VII System Review

Congenital absence of kidney tissue


Congenital polycystic disease (in which large cysts
develop in the kidney and destroy surrounding nephrons by compressions)
Urinary tract obstruction resulting from renal stones
Pyelonephritis and disease of the renal vasculature.

2.

Pathogenesis
The various by-products of protein and amino acid metabolism in a patient with uremia exert toxic effect on every
organ systems in the body. As the kidney fails, the nephron population falls. If this progresses the glomerular filtration rate falls, and the blood urea nitrogen (BUN) rises,
which results in mild azotemia (abnormal retention of nitrogen products in blood), impaired ability to concentrate urine,
nocturia and mild anemia. If this continues, frank renal
disease follows with its associated polyuria. The anemia may
become severe and hypocalcemia, hyperphosphatemia and
metabolic acidosis may occur. When azotemia is associated with adverse clinical signs and symptoms, it is called
uremia. Advanced uremia is associated with derangement
of function in many major organ systems.
Mirahamadi et al stated that the prolongation of life in
patients with end-stage uremia by the use of maintenance
hemodialysis has resulted in the occurrence of a number
of clinical syndromes that may be related to the persistence of certain biochemical abnormalities associated with
impaired renal function.
According to Harrison, urea represents some 80% or more
of the total nitrogen excreted into urine in patients with
chronic renal failure maintained on diets containing 40 g
or more of protein per day. Creatinine may cause adverse
effects in uremic subjects following conversion to more
toxic metabolites such as sarcosine and methyl guanidine.
Davidson has said that disturbances in water, electrolyte
and acidbase balance undoubtedly contribute to the clinical picture in patients with chronic renal failure, but the
exact pathogenesis of the clinical syndrome of uremia is
unknown. Almost any substance present in abnormal concentration in the plasma has been suspected of being a
uremic toxin. It is most likely that the syndrome is caused
by accumulation in body uids of a number of substances,
among which phosphate, parathyroid hormone, urea creatinine, guanidine, phenols and indoles must be included.
Scott stated that uremic syndrome primarily results from
the retention and accumulation of excretory products and
the diminished endocrine and metabolic functions of the
kidney. He has given the following laboratory ndings in
progressive renal disease.
Systemic manifestations of renal failure
Systemic manifestations:
1.

514

Gastrointestinal
a. Anorexia

3.

4.
5.

6.

b. Hiccups
c. Nausea
d. Vomiting
e. Uremic gastroenteritis
Neuromuscular
a. Drowsiness
b. Lack of concentration
c. Insomnia
d. Loss of memory
e. Mild behavioral changes
f. Errors in judgment
g. Neuromuscular irritability
h. Seizures and coma
i. Peripheral neuropathy
Hematologic
a. Normochromicnormocytic anemia
b. Bleeding
Immunologic
a. Infection
Endocrinemetabolic
a. Loss of libido
b. Decreased thyroid function
c. Amenorrhea
Cardiovascular
a. Hypertension.

Gastrointestinal The GI tract is extensively affected by


chronic renal failure. Anorexia, hiccups, nausea and vomiting are common and early manifestations of uremia.
Uremic fetor, a uriniferous odor to the breath, derives
from the breakdown of urea in saliva to ammonia and was
associated with unpleasant taste sensation. Mucosal ulcerations leading to blood loss can occur at any level of GI
tract in very late stage of chronic renal failureso-called
uremic gastroenteritis.
Neuromuscular Subtle disturbances of CNS function
including inability to concentrate, drowsiness and insomnia
are among the earliest symptoms of uremia. Mild behavioral changes, loss of memory and errors in judgment soon
follows and are associated with signs of neuromuscular
irritability, including hiccups, cramps and fasciculation
and twitching of large muscle groups. Asterixis, myoclonus and chorea are common in terminal uremia, as are
stupor, seizures and coma. Peripheral neuropathy may also
be a common complication of advanced chronic renal
failure.
Cohen stated that neuromuscular signs and symptoms
were secondary to hypertensive encephalopathy, electrolyte
disturbances and hypocalcemia. He observed that along with
neurological hyperirritability, peripheral neuropathy can
occur as a result of disturbance of the conduction mechanism rather than a loss of nerve ber. He noticed that the
predominant patient complaint was burning feet or paresthesia that may progress to muscle weakness, atrophy
and nally paralysis.

Chapter 18 Systemic Disorders and their Clinical Implications

Hematologic Patients with chronic renal dysfunction will


often have hematologic problems, most commonly anemia
and bleeding.
Normochromicnormocytic anemia occurs regularly in
chronic renal failure and contributes to fatigability and listlessness in these patients. Erythropoiesis may be depressed
due to the effects of retained toxins on bone marrow and
diminished biosynthesis of erythropoietin by the diseased
kidney. Hemolysis occurs because of hypertension, retention of waste products, altered body uid pH and electrolytes composition which create an unsuitable environment
for erythrocytes. Abnormal hemostasis, i.e. bleeding into
GI tract, pericardial sac and intracranial vault, in the form
of subdural hematoma or intracerebral hemorrhage, has
been attributed to intrinsic coagulation defect, a deciency
of platelet factor III or the anticoagulants used in conjunction with dialysis.

up to 90% of renal patients will show oral symptoms. With


renal insufficiency and uremia, patients may complain of
a bad odor and metallic taste in the mouth. This is due to
high urea content in saliva and its subsequent breakdown
to ammonia. Patients also complain of dry mouth and often
are prone to retrograde parotitis. These complications are
believed to result from a combination of direct gland
involvement, chemical inflammation, dehydration and
mouth breathing.
Frerichs (1851) was the rst to describe the oral manifestation of uremia. He stated that the condition was not
found in acute renal failure but developed slowly when
chronic uremia has been present for months or years.
Lancereaux (1887) was the rst to mention that uremic
stomatitis was a complication of uremia.
Jones and Mason (1990) mentioned the oral lesions
which can occur in renal failure as follows:

Immunologic Enhanced susceptibility to infection occurs


in chronic renal failure due to defect in leukocyte formation
and function. Mucosal barrier to infection may be defective. Anti-inflammatory steroids and immunosuppressive
drugs add further risk of infection.
Cohen has quoted reduced immune capacity in uremic
patients due to uremic intoxication and protein caloric malnutrition. He stated that uremic plasma suppresses lymphocyte responses such as granulocyte dysfunction and
suppressed cell-mediated immunity. He suggested, together
these impairments place uremic patient at a high risk of
infection.

1.
2.
3.
4
5.
6.
7.

Endocrine-metabolic Number of hormonal abnormalities including loss of libido in both the sexes, are due to
the associated hyperprolactinemia. Thyroid function was
diminished. Amenorrhea was common in female.
Cardiovascular Hypertension develops in 8090% of
patients during the course of chronic renal failure. The hypertension contributes to the development of cardiomyopthy,
atherosclerosis and progression of the renal failure itself.
Pericarditis was very common in untreated end stage renal
failure. Vascular calcification may develop and be sufficiently severe to cause inadequate perfusion of the limbs.
Dermatologic Severe pruritus was one of the important
manifestations of the clinical syndrome of hyperparathyroidism in patients with advanced uremia. The skin of the uremic
patients may be dry and there may be ecchymosis resulting
from bleeding tendencies. Pruritus has been attributed to calcium and phosphate deposition in the skin and high circulating PTH levels. In advanced uremia a white, uremic frost
may evaporate on the skin surface with a fishy scale odor.
The patient frequently complains of brittle nails.
Oral manifestations
Several changes occur in the oral cavity that is associated
with chronic renal failure and uremia. It was estimated that

Erythematopultaceous stomatitis
Ulcerative stomatitis
Hemorrhage
Hyperkeratosis and generalized pallor
Poor taste perception
Infection
Peripheral giant cell lesion.

Several mechanisms have been postulated for the pathogenesis of each form of uremic stomatitis. The oral lesion
may be a reaction to toxins in the tissues or to the action
of ammonia or to irritating ammonium compounds formed
by the action of bacteria on urea. The manifestation of
uremia in the mouth and GI tract may also be caused by
the hemorrhagic diathesis common in uremia. Local hemorrhage may cause a decrease in vitality and viability of
the affected tissues allowing bacterial infection. These
infections result in ulceration and psuedomembranous
formation.
Wysocki et al presented a case of primary hyperoxaluria
with oxalosis (accumulation of related deposits in various
extra-renal sites) involving oral tissues, including bone,
gingiva, dental pulp, periodontal ligament and dentin in a
27-year-old male patient.
Goldstein (1990) quoted Baries classication of uremic
stomatitis as follows:
Type I Erythematopultaceous, initially manifests as a red
thickening of the buccal mucosa, which later includes a
gray, thick, pasty, gluey exudate and pseudomembrane
which covers the gingiva, fauces and the oral mucosa. When
the psuedomembrane is removed with tongue blade, a
swollen, dry, red but not ulcerated mucosa is found. Associated manifestations include fetor oris, dry burning sensation, excessive saliva and perversion of taste.
Type II Ulcerative form which is similar to type I but
includes loss of integrity of the mucosa with frank ulceration. The ulcers can be superficial or deep and frequently
515

Section VII System Review

involve the gingiva. Purpura and anemia may be seen on


the mucosa. Excessive salivation is again noted.
Parotid and submandibular gland swelling may be seen
in patients with chronic renal failure without accompanying uremic stomatitis.
Ziccardi stated that restricted uid intake results in
xerostomia, the most common oral manifestation in CRF
(circulating recombinant form) patients.
McCreary et al reported lesion mimicking oral hairy
leukoplakia in a case of uremic stomatitis in a 48-year-old
male with an extensive white lesion involving dorsal, lateral and ventral surfaces of the tongue and buccal, labial
and retromolar mucous membrane and suggested that oral
manifestation of uremia should be considered in the differential diagnosis of oral hairy leukoplakia.
Wysocki et al reported a case of 31-year-old male suffering from chronic renal failure with oxalosis in which
they found tooth resorption, mobility, dental pain and
eventual tooth loss as signicant clinical problems.
Sowell stated that uremia present during development of
the dentition results in teeth with enamel hypoplasia and
brownish discoloration. Altered maxillary and mandibular
growth and resulting malocclusion may occur because of
impaired skeletal growth.
Woodhead et al (1982) in a review article of Clark
(1987) found that enamel hypoplasia was the most common nding in chronic renal failure. They observed the
anatomical location of enamel hypoplasia on the teeth
correlated well with the age of onset of advanced renal
failure. Other less frequently observed changes included
discoloration and hypocalcication of the enamel.
Scott stated that some patient may have severe erosion
of the dentition due to frequent regurgitation, resulting from
the nausea associated with hemodialysis treatments. Other
dental ndings include tooth mobility and drifting without
appreciable pathological periodontal defects and abnormal
bone healing following dental extraction.

to balance the systems, thus creating the skeletal lesions.


This increase in parathyroid activity is secondary to altered
serum calcium and phosphate levels and is therefore known
as secondary hyperparathyroidism.
The skeletal changes occurring secondary to chronic
renal failure consist of bone remodeling, osteomalacia,
ostitis brosa cystica and osteosclerosis.
Kelly (1980) quoted Lucas (1883) who stated that abnormalities of the skeletal system can occur in children with
renal disease and he used the term renal rickets to describe
the condition.
Parsons (1927) described rst radiographic interpretation of secondary hyperparathyroidism. He noted osteoporosis, bending and fracture of long bones, cortical thinning
and subperiosteal resorption.
The skeletal changes of primary and secondary forms of
hyperparathyroidism are indistinguishable from each other.
But brown tumors which appear as well-circumscribed unilocular or multilocular radiolucencies are rare in secondary
hyperparathyroidism.
Kelly et al (1980) reported that decreased density of bone,
thinning and absence of cortices and fractures and deformities of the weight bearing skeleton, periarticular, soft
tissue and vascular calcication are common in secondary
hyperparathyroidism. They suggested that alterations of
the trabecular pattern (Figure 5) have led to qualitative
terms such as chalky, ground glass, granular and salt
and pepper to describe the appearance of the bone.
Dental manifestations
Radiographic alterations of the jaw bones in chronic renal
disease are not uncommon and often represent one of the

Figure 5

Radiographic manifestations
Liu and Chu (1943) coined the term renal osteodystrophy,
which denotes osseous changes that occur in patients with
ESRD.
Skeletal changes are caused by the disorders in calcium
and phosphorus metabolism, abnormal vitamin D metabolism, and increased parathyroid activity. In chronic renal
failure, intestinal absorption of calcium is reduced because
the kidneys are unable to convert vitamin D into its active
form 1,25-dihydroxycholecalciferol which is required for
absorption of calcium from the digestive tract. Impaired
absorption of calcium because of defective kidney function and corresponding retention of phosphate causes a
decrease in the serum calcium level. This is associated with
a compensatory hyperactivity of the parathyroid glands.
The parathyroid hormone then extracts calcium from bone
516

Intraoral periapical radiograph showing altered


trabecular pattern. Courtesy: Dr Veena Hegde

Chapter 18 Systemic Disorders and their Clinical Implications

earliest detectable signs. Subperiosteal bone resorption may


be seen as a partial or complete loss of the lamina dura,
thinning of the mental foramen, inferior alveolar canal
resorption and destruction of condylar process of the mandible and maxillary sinus floor. In addition, the trabecular
pattern of the affected bone assumes a ground glass or salt
and pepper appearance. Infrequently, radiolucent brown
tumors may be seen.
Fordham and Franklin (1963) reported the rst case
associated with ESRD in a 2-year-old boy with a brown
tumor of maxilla which is clinically, chemically, radiologically and according to parathyroid ndings consistent
with secondary parathyroid hyperplasia. They observed
these changes mostly in the lower molar area superior to
the mandibular canal.
Spolnik et al found 73% of their dialysis patients dental
radiographs were abnormal. He found altered bone density
as the most common abnormality and suggested its diagnostic value in the evaluation of bone disease.
Maxwell et al examined 30 male chronic hemodialysis
patients using panoramic and periapical radiographs and
found 22 patients with abnormal jaw radiographs. They
reported pulpal narrowing and calcication in half of dialysis patients. They concluded that dental radiography was
as good a screening technique for evaluating renal osteodystrophy as hand radiography and in many cases, was
superior to axial skeleton radiography.
Scott et al stated that the manifestations of metabolic
renal osteodystrophy and compensatory hyperparathyroidism of the mandible and maxilla include bone demineralization, decreased trabeculation, ground glass appearance,
loss of lamina dura, radiolucent giant cell lesions and metastatic soft tissue calcications. He further suggested that
with such bone loss, it was not uncommon for patients to
have spontaneous fractures of the jaws from trauma as
well as to be at risk of fracture during oral and periodontal
surgical procedure.
Dental considerations
Dental treatment for patients with chronic renal disease
and transplants is recognized as an essential health service.
Dental management is complicated because of the oral disease and the medical problems seen in this population. These
patients survive under narrowly controlled conditions of
intake and activity as well as under great physiologic and
psychologic stress with medications, diet, invasive treatments, limited lifestyle and dependency on others. Dental
treatment, even minor dental procedures can present major
problems and should be considered particularly stressful
when superimposed on such situation.
Hemodialysis (Figure 6) is the most prevalent therapy
for chronic renal disease. Hemodialysis refers to the removal
of nitrogenous and toxic products of metabolism from the
blood by means of a dialysis system. Exchanges occur

Figure 6

Photograph showing a patient undergoing


hemodialysis. Courtesy: Dr Veena Hegde

between the patients plasma and dialysate (the electrolyte


composition of which mimics that of extracellular uid)
across a semi-permeable membrane that allows uremic toxins to diffuse out of the plasma while retaining the formed
elements and protein composition of blood. The usual dialysis system consists of a dialyzer, dialysate production unit,
roller blood pump, heparin rate, and pressure of dialysate
and to detect blood leaks and arterial and venous pressures.
The typical patient undergoes hemodialysis 3 times per
week, with each treatment lasting approximately 4 hours.
During treatment anticoagulants are administered.
It was estimated that 60% of hemodialysis patients
need dental treatment to prevent the complications caused
by infection or dietary difculties. Comprehensive oral
evaluation and dental treatment are part of the basic
healthcare of the chronic renal failure patients. As the
technology and medicine advance, the number of patients
with chronic renal disease who require dental care is also
increasing.
The following considerations are important when evaluating and treating the dental patient with renal disease:
1. Timing Disagreement exists over the ideal time for
dental treatment of hemodialysis patients. Carl and Wood
indicated that the dental treatment should be performed
first before hemodialysis, when the patient is free of anticoagulant. Any problems arising from medications given
by the dentists will be removed later by dialysis.
Sowell, Manton, Ziccardi, and Scott all recommend that
dental treatment should be timed so that the effects of
dialysis are present, but the effects of heparin have worn
off. This enables clotting to be well established before the
next dialysis session, when heparin will again be administered. They suggested treatment midway between dialysis
517

Section VII System Review

sessions ideally about 12 hours post dialysis is the ideal


time. Because at this time, the toxins are low in the blood,
the effect of the heparin is minimal, and the patient is best
able to respond to the stress of treatment.
2. Asepsis Scott stated that because patients undergoing
dialysis are exposed to a large number of transfusions and
blood exchanges, as well as renal failure related immunosuppression, they are at greater risk of infections such as
hepatitis B and C and HIV infection. He suggested that
these patients should be encouraged to undergo periodic
testing for hepatitis infectivity and HIV antibody.
The presence of these infections do not contraindicate
dental treatment, but rather indicate the need for special
care and meticulous techniques.
3. Hematologic and physiologic status Clinical and laboratory evaluation for anemia, bleeding disorders and leukocyte disorder may be indicated, depending on the status
of renal disease or therapeutic modality and the type of
dental treatment advised. Evaluation and stabilization of
fluid and electrolyte balance should be accomplished before
dental treatment.
The arteriovenous site should never be jeopardized.
That arm should never be used for injection of medication,
either intramuscularly or intravenously, nor should the
access site be used as an injection site. It is also essential
to avoid any factor that may occlude the arteriovenous
shunt such as a blood pressure cuff, constricting clothing
or cramped arm position. If the device is in the leg, the
patient should be allowed to stand or walk occasionally
during long procedure.
Dental procedures should be delayed for at least 2 weeks
after placement or revision of a vascular access and should
be avoided during periods of infection or thrombosis of
the access.
4. Immunosuppression and corticosteroid medication
Many renal transplant patients are on a regimen of antiinflammatory and immunosuppressive medications. Because
infections are the major cause of morbidity and death in
the renal transplant patient and a majority of septicemic
infection have been attributed to oral diseases such as periodontitis, pulpal infection and oral ulceration along with
dental treatment which provide a convenient portal of
entry for microorganism into the circulatory system.
Scott stated that the patients with chronic renal failure
who receive hemodialysis have an increased susceptibility
to the development of infective endocarditis. They suggested
antibiotic prophylaxis should be given prior to dental care
to prevent infective endocarditis, vascular access infection
and bacteremia in both renal transplant and patient undergoing hemodialysis.
Topical antifungal agents are recommended for control
of localized oral infections.
Long-term systemic steroid administration suppresses
the patients ability to respond to stress by causing adrenal
518

atrophy. Supplemental steroids should be considered before


stressed dental procedures.
5. Medications and drug therapy for dental purposes
The practitioner prescribing or administering medications
to patients with compromised renal function must be familiar with the metabolism and excretion of each of the
agents involved and the functional status of the individual
patients kidneys. To provide safe yet effective drug therapy,
modification of the usual dosage regimen may be necessary.
For drug administration for dental purposes, two dosage
categories are sufficient: (i) patients with mild to moderate
renal failure or renal insufficiency and (ii) patients with
severe renal failure or who are functionally anephric. One
of the commonly used drug in dentistry is penicillin, which
exists as either a sodium or potassium salt. Potassium salts
should be avoided due to the potential of hyperkalemia.
Other alternative drugs such as clindamycin or erythromycin, which are metabolized by the liver, can be considered.
NSAIDs should be avoided because of their nephrotoxic
effect. However, NSAIDs can be used once these patients
progress to ESRD and no longer have any residual renal
function.
6. Local anesthesia The kidney is the main excretory
organ for all the local anesthetics commonly used in dentistry and their metabolites. The use of cocaine is contraindicated since it is excreted entirely unchanged in the urine.
Goldstein recommended that slow administration of LA
not more than 25% of the maximum total recommended
dosage for the normal patient, is a practical and safe guideline for local anesthetic injections for dental purposes in
the medically controlled patient with absent renal function.

Uremic Stomatitis
Uremic stomatitis has become relatively rare, seen mostly
in cases of undiagnosed and untreated chronic renal failure.
Painful plaques and crusts are distributed predominantly
on the buccal mucosa, the oor or dorsum of the tongue,
and the oor of the mouth. The incidence has decreased
because of readily available dialysis centers throughout the
country. The most commonly accepted mechanism behind
the development of uremic stomatitis is irritation and chemical injury of mucosa by ammonia or ammonium compounds formed by the hydrolysis of urea in saliva by urease.
This occurs when the intraoral concentration of urea exceeds
30 mmol/l. Hemorrhagic diathesis from inhibited platelet
aggregation may also play a role due to local hemorrhage,
resulting in decreased vitality and viability of the affected
tissues, thus allowing bacterial infection.
There are two predominant types of uremic stomatitis.
In Type I, there is a generalized or localized erythema of
the oral mucosa and a thick gray pseudomembranous exudate which does not leave a bleeding or ulcerated base
when removed. Additional ndings may include pain, burning, xerostomia, halitosis, gingival bleeding, dysgeusia, or

Chapter 18 Systemic Disorders and their Clinical Implications

candidal infection. Type II leaves ulceration if the pseudomembranous lm is removed. This type may indicate a
more severe form of stomatitis, secondary infection, anemia or underlying systemic hematologic disturbances caused
by renal failure.
Histologically, both types of uremic stomatitis show
evidence of an intense inammatory process with heavy
polymorphonuclear leukocytic inltration and necrosis of
the oral mucosa. Bacterial colonization is most commonly
associated with Fusobacterium, Spirochaeta or Candida.

GASTROINTESTINAL DISORDERS
GASTROESOPHAGEAL REFLUX DISEASE
Gastric esophageal reflux is defined as the passage of gastric contents into esophagus. It is believed that Helicobacter
pylori, a spiral shaped bacterium located in the mucous
layer of the stomach, may inhibit or exacerbate acid reflux.
The symptoms that develop when the esophageal mucosa is
exposed to the gastric reflux are referred to as gastroesophageal reflux disease (GERD). It is a common, chronic
gastrointestinal disorder that affects approximately 30%
of the population.
Predisposing factors and pathophysiology
Genetic factors, smoking, lower esophageal sphincter abnormalities, hiatal hernia, defective esophageal peristaltic activity (common in esophagitis) and defective gastric emptying,
increased abdominal pressure (pregnancy and obesity), and
dietary behavior (diet consisting of fat, coffee, alcohol and
chocolate relax the lower sphincter and incite symptoms).
Clinical features
Gastroesophageal reflux disease is more common in adults
in their third decade of life. The common symptoms are
heartburn (mimics anginal pain, burning sensation spreading upward from the epigastrium to the neck) and regurgitation. Water brash is also a very common complaint in
patients. It is the presence of a sudden burst of salivation
in the mouth due to reflex salivary gland stimulation in
response to presence of acid in the gullet. Other clinical
findings are chest pain, cough, laryngitis and laryngeal
polyps. In severe recurrent reflux episodes, aspiration and
pulmonary fibrosis may occur.
Oral considerations
Bargen and Austin (1937) first described the association
between GERD and erosion of teeth. In the initial stages
enamel may exhibit subtle changes. As the condition progresses, complete loss of tooth structure may be seen. The
teeth typically affected are the palatal aspect of the upper
anteriors and premolars.

Patients may complain of dentinal hypersensitivity and


foul taste (dysgeusia). In chronic cases pulpal exposure may
be seen. Exposure of the oral mucosa to the acidic reux
may result in atrophy and erythema.
Complications
It is estimated that approximately 50% of patients with
reflux develop esophagitis. Based on the severity, esophagitis is divided into four grades:
1.
2.
3.
4.

Grade Ierythema
Grade IIlinear non-confluent erosions
Grade IIIcircular confluent erosions
Grade IVBarretts esophagus.

Barretts esophagus is characterized by replacement of


normal squamous epithelium with columnar epithelium.
It has been linked to the development of adenocarcinoma
of the esophagus.
Long-standing esophagitis results in signicant amount
of blood loss and subsequently resulting in iron deciency
anemia. Herbst triad, consists of nger clubbing, hypoproteinemia and iron deciency anemia associated with gastroesophageal reux.
Investigations
Gastroesophageal reflux disease is best diagnosed based on
the symptoms of water brash, heartburn and regurgitation.
Only 30% of the patients have positive esophageal findings
on endoscopy. Barium esophagographs can be used to diagnose hiatal hernia and esophageal strictures.
Management
Patients should be encouraged to consume small frequent
meals along with antacids instead of large meals. They
should be educated not to go to bed immediately after a
heavy meal. It has been suggested that the raising of the
head of the bed by about 4 inches will minimize regurgitation of the acid contents.
H2 blockers (cimetidine 400 mg, q.i.d. for 4 weeks;
ranitidine 150 mg b.i.d. up to 8 weeks), proton pump inhibitors (omeprazole 20 mg once daily for 4 weeks; lansoprazole 30 mg once a day for 4 weeks).
To reduce dysgeusia associated with acidic reux, about
half teaspoon of baking soda (sodium bicarbonate) can be
added to 250 ml of water and this solution can be used as
mouthrinse. Fluoride application will aid in remineralization of teeth.

INFLAMMATORY BOWEL DISEASE


Inflammatory bowel disease (IBD) encompasses a group of
diseases with poorly defined etiology that affect the digestive
519

Section VII System Review

tract which includes Crohns disease (CD) and ulcerative


colitis (UC). A significant number of individuals develop
extra-intestinal manifestations (hepatic manifestations
and primary sclerosing cholangitis).
Nucleotide oligomerization domain (NOD2) and human
leukocyte antigen (HLA) genes are the most extensively
studied genetic regions (IBD1 and IBD3, respectively) in IBD.
Mutations of the NOD2 gene are associated with CD and
several HLA genes are associated with UC and CD.

ULCERATIVE COLITIS
Ulcerative colitis is an IBD affecting part or whole of the
large intestine frequently lower colon and rectum. It was
first described by a physician, Sir Samuel Wilks from
London in 1859. The precise etiology of ulcerative colitis
is not well understood. A current hypothesis suggests
that primary dysregulation of the mucosal immune system
leads to an excessive immunologic response to normal
microflora.
Clinical features
Ulcerative colitis is most common between the 2nd4th
and 5th8th decades of life. Males and females are equally
affected. The characteristic symptoms and signs include
bloody diarrhea, rectal urgency and difficulty to pass stools.
The frequency of bowel movements and the amount of
blood present reflect the activity of the disease. The diarrhea is severe, possibly five to eight bowel movements in
24 hours. Patients usually complain of pain that is in both
abdominal quadrants and that is crampy in nature and exacerbated prior to bowel movement. Along with the change
in the pattern of bowel movements, the patient may have
nocturnal diarrhea.
The extraintestinal manifestations include osteoporosis,
arthritis, primary sclerosing cholangitis, uveitis, pyoderma
gangrenosum, deep venous thrombosis, pulmonary embolism. The most serious complication of ulcerative colitis is
carcinoma of the colon.

Differential diagnosis of ulcerative colitis

520

Disease

Clinical characteristics

Crohns colitis

Perianal lesions common; bleeding less


common than in ulcerative colitis

Infectious colitis

Sudden onset; pathogens present in stool;


pain may be a predominant feature

Ischemic colitis

Affects older age groups; vascular disease


often present; sudden onset, often painful

Pseudomembranous
colitis

Recent antibiotic use; clostridium toxin


detectable in stool

Oral manifestations and dental considerations


Aphthous ulcers may result from nutritional deficiencies
of iron, folic acid and vitamin B12 due to poor absorption
in the gut and/or blood loss directly related to the ulcerative colitis. Anti-inflammatory medications such as the
5-aminosalicylates, which often represent the mainstay of
therapy for IBD patients and which are excreted in saliva,
are known to cause aphthous ulcers. Pyoderma gangrenosum may occur in the form of deep ulcers that sometimes
ulcerate through the tonsillar pillar. Pyostomatitis vegetans,
a purulent inflammation of the mouth, may also occur.
These oral lesions are characterized by deep-tissue vegetating or proliferative lesions that undergo ulceration and
then suppuration. These lesions disappear with a total colectomy. Ulcerative colitis patients also can develop hairy leukoplakia, a lesion more commonly associated with AIDS.
Drugs to be avoided include NSAIDs, antibiotics,
including amoxicillinclavulanate and clindamycin which
could aggravate diarrhea. Surgical treatment is contraindicated until the disease is under control because of the
risks associated with anemia (such as delayed healing, an
increased risk of infection, the side effects of narcotic
analgesics, and depression of respiration). Long-term use
of steroids can also result in adrenal suppression. Patients
undergoing surgery require increased doses of steroids
before and after the procedure because their own adrenal
response to stress is blunted.

CROHNS DISEASE
Crohns disease was first observed by the German surgeon
Wilhelm Fabry in 1623, and was later described by and
named after physician Dr Burril B Crohn from New York.
It is an idiopathic, relapsing chronic inflammatory disease
of the GI tract categorized as IBD and is an important cause
of morbidity in children and adolescents.
The prevailing hypothesis regarding the pathogenesis of
CD is an interaction between environmental factors and an
altered immune response in genetically predisposed children,
leading to chronic inammation of the GI tract. In CD there
is a disordered regulation of mucosal and systemic immune
response resulting in the perpetuation of the inammatory
cascade. A dysregulated Th1 response (T helper 1) seems to
be crucial in the conversion of physiologic to pathologic
inammation. The immunological prole in CD is predominantly a cell-mediated response. Active mucosal inammation of the small and large intestine results in diarrhea,
protein-losing enteropathy, bleeding, abdominal pain and
stricture formation. Proinammatory cytokines and eicosanoids increase vascular permeability and cause electrolyte
secretion, and augment smooth muscle contraction. Many
cytokines promote the recruitment and activity of collagen
forming cells leading to brous tissue proliferation and

Chapter 18 Systemic Disorders and their Clinical Implications

thereby resulting in bowel wall thickening and stricture


formation. The causal role of TNF-
in the etiopathogenesis of CD has gained importance.
Clinical presentation
It can occur in all age groups and follows the same bimodal
pattern of age distribution as IBD. Early onset IBD (EOIBD),
i.e. presentation before the age of 5 years, is a unique subgroup constituting 4% of pediatric IBD. In this subset, it is
difficult to differentiate between ulcerative colitis (UC) and
CD. In UC there seems to be a preponderance of CD in
boys, whereas in India it was more prevalent in girls. CD
depends upon the site of involvement of the GI tract. It
affects the ileocecal region, typically with ulceration, fissuring and fibrosis of the wall, but can affect any part of
the GI tract. Abdominal pain and systemic symptoms are
generally more severe in CD than in UC. A dyspeptic type
of epigastric pain is seen in children with gastroduodenal
involvement. Diarrhea occurs in two-thirds of affected
children. In children with predominantly ileal involvement, constipation may be a rare presentation. Gross blood
in the stools is unusual with isolated small bowel disease
and more common when the colon is involved. Fever
occurs in approximately 50%. Fatigue, anorexia, weight
loss and diminution in growth velocity are other presenting
symptoms in children. Perirectal involvement fistulae, fissure and skin tags are important clues to the diagnosis. CD
is subcategorized as predominantly inflammatory, fistulizing or stricturing disease based on the clinical phenotype.
Crohns disease could represent a persistent infection
with a fastidious organism or an abnormal and prolonged
response to a common pathogen. Various organisms have
been linked with CD but none of them are evident in the
etiopathogenesis. In genetically susceptible individuals the
microvascular injury caused by these infections could result
in a granulomatous vasculitis of the mesenteric vessels, leading to microvascular thrombosis, multifocal gastrointestinal infarction, and nally gross pathologic sequelae such
as ulcerations, stulas, brosis and strictures.
Complications
Hemorrhage, obstruction, perforation, abscess and fistula
formation are well known in CD. Perianal disease may
present with abscess formation, perirectal and perianal fistulization and can precede the intestinal manifestation by
years. Perforation with internal fistula is another serious
complication. Carcinoma of the colon is a long-term complication of IBD. The two well-accepted risk factors for
cancer are duration and severity of the disease.
Extraintestinal manifestations include skin manifestations like erythema nodosum and pyoderma gangrenosum. Ocular manifestations such as episcleritis and anterior
uveitis are less common. Arthritis is the most common
extraintestinal manifestation in children and may occur

years before the intestinal symptoms. Hepatobiliary complications such as chronic hepatitis, sclerosing cholangitis,
cholelithiasis and elevated aminotransferase may precede
the active disease. The renal manifestations of IBD include
nephrolithiasis, hydronephrosis and enterovesical stula.
Other extraintestinal manifestations are thromboembolic
manifestations, vasculitis, pancreatitis, interstitial pneumonitis and pericarditis, others include weight loss, growth
failure, bone disease (due to malnutrition). Delay in sexual
maturation seen in some children with CD may have a
signicant effect on self-esteem and socialization.
Oral manifestations
Aphthous ulcerations are the most common oral manifestation of CD. The oral manifestations may occur along with
intestinal disease or precede it and may be the primary
presentation. Cobble stone appearance of the oral mucosa,
oral epithelial tags and folds, gingivitis, persistent lip swelling, lichenoid mucosal reactions, granulomatous inflammation of minor salivary gland ducts, candidiasis, and
angular cheilitis. Some patients may have asymptomatic
intestinal disease. MelkerssonRosenthal syndrome (facial
swelling, facial palsy and fissured tongue) and cheilitis granulomatosa may also be incomplete manifestation of CD.
High prevalence of caries and periodontitis in CD has also
been reported.
Differentiating CD from ulcerative colitis can be challenging, particularly early in the course of the disease,
but it is an important step because appropriate treatments
and potential complications vary for these two conditions
(Table 2).
Table 2

Comparison of ulcerative colitis and Crohns disease

Feature

Ulcerative colitis

Crohns disease

Sites mainly
affected

Ileum

Colo-rectum

Abdominal pain

Variable

Common

Depth of
inflammation

Mucosal

Transmural

Distribution

Diffuse, contiguous
spread; always
involves rectum;
spares proximal
gastrointestinal tract

Segmental, non-contiguous
spread (skip lesions); less
common rectal involvement;
occurs in entire
gastrointestinal tract

Iron deficiency

Common

Common

Other
complications

Vitamin B12
deficiency

Diarrhea

Severe

Less severe

Fistula and
sinus tracts

Rare

Common

Colonic
carcinoma risk

Present

High

521

Section VII System Review

Investigations
The small bowel has been defined for many years as the
black box of the gastrointestinal system due to its inaccessibility to endoscopic exploration. The conventional
radiological methods, i.e. small bowel enteroclysis (SBE)
and small bowel follow-through (SBFT), have long been
the only imaging methods providing information on the
morphological features of the small bowel valuable in the
diagnosis and management of Crohns disease. Typical small
bowel changes which can be observed by means of these
techniques include irregular thickening and distortion of
the valvulae conniventes, loops adhesions (mass-like effect)
or separated loops because of wall thickening and mesenteric inflammatory infiltration. Transverse and longitudinal
distribution of ulcerations can separate islands of thickened
internal wall, resulting in the typical cobble stone appearance. Strictures are often separated by healthy bowel tracts
(skip lesions); impaired small bowel peristalsis is commonly
observed within rigid stenotic tracts. Extrinsic compression
may be observed, due to mesenteric lymph node enlargement. Barium meal series is useful to identify small bowel
involvement and lesions such as strictures, fistulas and
ulcerations may be identified.
Bowel ultrasonography The main ultrasonography findings in CD are represented by thickening and stiffness of
the gut wall, modifications or lack of its echo stratification, reduction of peristalsis, mesenteric fibro-fatty proliferation, lymph node enlargement; in case of complications,
narrowing of the intestinal lumen, abscesses and fistula
are usually easily detectable. The use of power Doppler
methods and of oral (polyethylene glycole, PEG) and/or
intravenous (Levovist) contrast media, have been suggested to improve the diagnostic accuracy of ultrasonography, particularly in discriminating inflammatory from
fibrotic strictures and in better defining the presence of
internal fistulas.
Computed tomography Computed tomography (CT) has
been utilized for the detection of extra-enteric complications of CD, mainly intra-abdominal abscesses, but is also
suitable in the evaluation of strictures, prestenotic dilatations and fistulas. Non-enhanced CT scan is also used in
the diagnosis of post-surgical complications (intra-peritoneal abscesses, anastomotic dehiscence, extra-abdominal
abscesses and fistulas, incisional hernias, ascites, volvolus,
bowel adhesions, etc). The main findings at CT scan observed
in CD patients, are small bowel wall stratification and/or
thickening (target or double halo appearance), with or
without contrast enhancement, edema of the mesenteric fat,
engorged ileal vasa recta (comb sign), submucosal fibrofatty infiltration and mesenteric adenopathy.
Video capsule endoscopy Video capsule endoscopy
(VCE) is a potentially safe and painless endoscopic method

522

to evaluate the entire small bowel and was found to be


superior in detecting CD lesions in patients with mild clinical suspicion and negative traditional imaging studies.
Other possible applications of VCE have been suggested
in a pediatric setting, in the evaluation of post-surgical
recurrence and in the surveillance of mucosal healing after
biologic therapy. The major limitations of the use of VCE
in CD are an incomplete evaluation of the small bowel,
occurring in 2035% of patients, and by the possibility
of capsule retention, occurring in about 7% of patients
with CD.
Double balloon endoscopy Double balloon enteroscopy
(also called push and pull enteroscopy) was described for
the first time by Yamamoto et al in 2001. The principle of
the double balloon technique allows not only a complete
endoscopic evaluation of the small bowel but also makes
it possible to take biopsies and to carry out therapeutic
interventions along the whole small bowel in patients suspected of CD and negative upper and lower endoscopy.
Management
Apart from a total proctocolectomy for UC, there is no
cure for IBD. Medications, however, aid in the induction
and maintenance of remission, and target various points
along the disordered immune pathway implicated in IBD.
Aminosalicylates remain the standard induction and maintenance therapies for UC but have a more equivocal role in
CD. Antibiotics are also commonly used in CD, especially
with colonic and perianal disease. Budesonide is effective
as a first-line agent for ileal and/or right colonic CD
although maintenance benefits remain to be proven. Conventional steroids induce remission for both CD and UC
but are reserved for patients with moderate-severe disease
or for those who have failed more first-line therapy. New
therapies include anti-TNF
antibodies; recombinant cytokines and growth factors. Immunomodulators such as 6-MP
and azathioprine, as well as methotrexate, are effective
steroid-sparing and maintenance therapies. Cyclosporine
or tacrolimus can be effective for severe or refractory UC.
Anti-TNF agents have been effective for patients with
moderate-severe UC and CD, independent of concomitant
medications.

HIATAL HERNIA
Hiatal hernia is the herniation of part of the stomach into
the thoracic cavity through the esophageal hiatus in the
diaphragm. Hiatus hernias affect anywhere from 1 to 20%
of the population. It is estimated that about 9% present
with symptoms. Hiatal hernia is usually seen in the elderly
although people of any age can be affected.

Chapter 18 Systemic Disorders and their Clinical Implications

Etiology

PEPTIC ULCER DISEASE

It is believed that insufficient dietary fiber and the use of the


unnatural sitting position for defecation (need for straining at stool) may cause increased intra-abdominal pressure thereby pushing the stomach through the esophageal
hiatus in the diaphragm. Other contributing factors causing increased pressure within the abdomen include: lifting
heavy weights or frequent bending over, frequent or hard
coughing, hard sneezing, violent vomiting and obesity
(extra weight pushes down on the abdomen increasing the
pressure). Other etiological factors are hereditary, smoking,
stress and drug abuse (cocaine).

Peptic ulcer disease of the GI tract is characterized by mucosal damage secondary to pepsin and gastric acid secretion.
It usually occurs in the stomach and proximal duodenum;
less commonly, it occurs in the lower esophagus, the distal
duodenum, or the jejunum, as in unopposed hypersecretory states such as ZollingerEllison syndrome, in hiatal
hernias (Cameron ulcers), or in ectopic gastric mucosa (e.g.
in Meckels diverticulum. It is believed to affect almost 10%
of the adults (usually between 25 and 65 years) at least
once in their lifetimes.

Clinical features
The sign and symptoms include heartburn, belching, chest
pain and nausea, which tend to become worse on leaning
forward, lifting heavy objects or lying down. In severe cases,
dysphagia and painful swallowing may occur. Infants may
regurgitate blood stained food and present with difficulty
in breathing and swallowing. Occasionally pain may radiate to the jaw and along the arm mimicking anginal pain.
Other clinical features are hiccups, dry cough and increase
in the contractile force of the heart.
There are two major types of hiatus hernia: the sliding
hiatus hernia (95%), where the gastroesophageal junction
moves above the diaphragm together with some of the
stomach. The second rare type is rolling (or paraesophageal) hiatus hernia, when a part of the stomach herniates
through the esophageal hiatus beside, and without movement of the gastroesophageal junction. Occasionally, a third
type is described, which is a combination of the rst and
second.
Investigations and management
Endoscopy is more frequently used than barium studies in
the diagnosis and assessment of hiatal hernia. Manometry
and esophageal pH testing may provide useful information.
Treatment is indicated if symptoms interfere with day to
day routine of the patient. Weight reduction, diet modification, raising the head of the bed and reduction of alcohol,
caffeine and nicotine intake are all recommended.
Routinely, antacids to H2-receptor antagonists and proton pump inhibitors are sufcient. Surgery should be considered in severe and resistant cases of hiatal hernia.
Dental considerations
Since many of the medications used for treating hiatal
hernia can cause xerostomia, cervical caries is common. If
reflux into the oral cavity is present, oral manifestations are
the same as those of GERD.
Patients can be advised to frequently sip water. Salivary
substitutes can be recommended. NSAIDs should be avoided.

Etiology
H. pylori infection and the use of non-steroidal anti-inflammatory drugs are the most common causes of peptic ulcer
disease. Other medications that have been known to cause
ulcers include steroids, bisphosphonates, potassium chloride
and chemotherapeutic agents (e.g. intravenous fluorouracil).
A variety of other infections and co-morbidities are associated with a greater risk of peptic ulcer disease (e.g. cytomegalovirus, tuberculosis, Crohns disease, hepatic cirrhosis,
chronic renal failure, sarcoidosis, myeloproliferative disorder). Critical illness, surgery or hypovolemia leading to
splanchnic hypoperfusion may result in gastroduodenal
erosions or ulcers; these may be silent or manifest with
bleeding or perforation. Smoking increases the risk of ulcer
recurrence and slows healing.
Clinical features
Typical symptoms of peptic ulcer disease include episodic
gnawing or burning epigastric pain; pain occurring 25 hours
after meals or on an empty stomach; and nocturnal pain is
relieved by food intake, antacids or antisecretory agents.
A history of episodic or epigastric pain, relief of pain after
food intake, and night time awakening because of pain with
relief following food intake are the most specific findings
for peptic ulcer.
Less common features include: indigestion, vomiting
(coffee ground vomitus), loss of appetite, intolerance of fatty
foods, heartburn and a positive family history.
The serious or alarming symptoms that necessitate further
investigations and immediate treatment include: anemia,
hematemesis, melena (black tarry stools); vomiting suggests obstruction; anorexia or weight loss suggests cancer;
persisting upper abdominal pain radiating to the back suggests penetration; and severe, spreading upper abdominal
pain suggests perforation.
Diagnosis
Patients older than 55 years and those with alarming symptoms should be referred for esophago-gastro-duodenoscopy
(EGD). It is more sensitive and specific for peptic ulcer

523

Section VII System Review

disease than upper gastrointestinal barium studies and


allows biopsy of gastric lesions.
Patients younger than 55 years with no alarm symptoms should be tested for H. pylori infection and advised
to discontinue the use of NSAIDs, smoking, alcohol and
illicit drug use. Presence of H. pylori can be conrmed with
a serum enzyme-linked immunosorbent assay (ELISA), urea
breath test, stool antigen test, or endoscopic biopsy.

Anorexia has two subtypes: restricting type and bingeeating/purging type.


Diagnostic criteria for anorexia nervosa
1.

Dental considerations
Non-steroidal anti-inflammatory drugs and steroids should
be strictly avoided. Most patients present with xerostomia
secondary to the anticholinergic drugs. Anemia related
symptoms and dental considerations have to kept in mind.

2.
3.

Management
Treatment of peptic ulcer disease should include eradication
of H. pylori in patients with this infection. The recommended duration of therapy for eradication is 1014 days.
Regimen: Omeprazole 20 mg 2 times daily or lansoprazole 30 mg 2 times daily plus amoxicillin 1 g 2 times daily
or metronidazole 500 mg 2 times daily (if allergic to penicillin) plus clarithromycin 500 mg two times daily.
Surgery is indicated in patients who are intolerant of
medications or do not comply with medication regimes, and
those at high risk of complications (e.g. transplant recipients, patients dependent on steroids or NSAIDs, those with
giant gastric or duodenal ulcer, those with ulcers that fail
to heal with adequate treatment).

EATING DISORDERS
Eating disorders are associated with various medical and
psychologic consequences, including death, osteoporosis,
growth delay and developmental delay. Anorexia nervosa
and bulimia nervosa are two of the most devastating eating disorders. Eating disorders are most commonly seen
among adolescents and young adults of developed nations.
They are many times more common in females than in
males.
These disorders are seen in individuals who participate
in activities that promote thinness, such as modeling, movies
and athletics, and certain personality traits such as low selfesteem, difculty expressing negative emotions, difculty
resolving conict, and being a perfectionist. It is also seen
that up to one-third of women with type 1 diabetes may
have eating disorders.

Anorexia Nervosa
Patients with anorexia use caloric restriction or excessive
exercise to control emotional need or pain, and they are
terrified of becoming overweight.
524

4.

Refusal to maintain body weight at or above a minimally normal weight for age and height (e.g. weight
loss leading to body weight less than 85% of that
expected; or failure to make expected weight gain
during period of growth, leading to body weight less
than 85% of that expected).
Intense fear of gaining weight or becoming overweight, even though patient is underweight.
Disturbance in the way in which ones body weight or
shape is experienced, undue influence of body weight
or shape on self-evaluation, or denial of the seriousness of the current low body weight.
Amenorrhea in postmenarchal females (i.e. the absence
of at least three consecutive menstrual cycles. A woman
is considered to have amenorrhea if her periods occur
only following hormone administration.)

Bulimia Nervosa
Bulimia also has two subtypes: purging and non-purging.
Bulimia is characterized by uncontrollable binge-eating
episodes, often followed by purging behaviors such as vomiting or the use of laxatives. Patients with binge-eating/
purging-type anorexia also might binge and purge. Patients
who have bulimia may be of normal weight, or they may be
under- or overweight, whereas patients with binge-eating/
purging-type anorexia are underweight.
Diagnostic criteria for bulimia nervosa
1.

2.

3.

4.
5.

Recurrent episodes of binge eating. An episode of binge


eating is characterized by both of the following:
a. In a discrete period of time (e.g. within any
2-hour period), eating an amount of food that is
larger than what most people would eat during a
similar period of time and under similar circumstances.
b. A sense of lack of control over eating during the
episode.
Recurrent inappropriate compensatory behavior to
prevent weight gain, such as self-induced vomiting;
misuse of laxatives, diuretics, enemas, or other medications; fasting; or exercising excessively.
The binge eating and inappropriate compensatory
behaviors both occur, on average, at least twice a
week for 3 months.
Self-evaluation is unduly influenced by body shape
and weight.
The disturbance does not occur exclusively during episodes of anorexia nervosa.

Chapter 18 Systemic Disorders and their Clinical Implications

Screening for eating disorders


Morgan et al (1999) suggested the use of the SCOFF questionnaire for assessing eating disorders.

Immunological function

Acts as a sieve for antigens

Functions of bile juice

Acts as a detergent
Emulsifies fat
Absorption of fat-soluble vitamin
Excretion of hemoglobin by-products
Neutralizes any stomach acid
Bactericidal potential

SCOFF questions

Do you make yourself Sick (induce vomiting) because


you feel uncomfortably full?
Do you worry that you have lost Control over how
much you eat?
Have you recently lost more than One stone (14 lb
[6.4 kg]) in a 3-month period?
Do you think you are too Fat, even though others say
you are too thin?
Would you say that Food dominates your life?
One point for every yes answer; a score 2 indicates
a likely case of anorexia nervosa or bulimia nervosa
(sensitivity: 100%; specificity: 87.5%).

Oral manifestations
Frequent vomiting leads to erosion of the enamel on the
lingual surfaces of the maxillary teeth. Palatal ulcerations
may be noticed. Parotid enlargement may develop as a
sequela of starvation.

LIVER DISEASES
The liver has many essential functions, and liver disease
presents a number of concerns for the delivery of medical
and dental care. A number of conditions that cause liver
dysfunction may be related to lifestyle and a variety of
diseases. This section of the chapter will deal with two
common liver conditions, namely, hepatitis and jaundice,
that have important dental implications.
Functions of liver
Functions of the liver can be categorized as follows:
Nutrient metabolism

Carbohydrate
Protein
Lipids

Protein synthesis

Albumin
Coagulation factors
Complement factors
Hepatoglobin
Ceruloplasmin

Storage

Excretion

Iron
Copper
Vitamin A
Vitamin B12
Vitamin D
Bile salts
Bilirubin
Metabolism of drugs

Clinical presentation of a patient with suspected


liver disease
As a dentist it is very important to look for certain clues in
the case history that can take us toward a diagnosis of
hepatobiliary abnormality in such patients.
Ask your patient for alcohol abuse, intravenous drug
abuse, rule out familial history of liver diseases, accidental
environmental toxin exposure. Enquire if the patient is on
any hepatotoxic medications, recent travel to another country or place and whether he/she has exaggerated reactions to
certain medications or chemicals. These clues will not only
help in diagnosing any hepatobiliary abnormality but also in
deciding an appropriate treatment plan for your patients.
The symptoms associated with liver disease include: right
hypochondrial pain, abdominal distention, ankle swelling,
hematemesis and melena. They can also have pruritus,
amenorrhea, breast swellings, confusion and drowsiness.
Some important clinical signs are nail changes in the form
of clubbing of nails, leukonychia and also smooth nails.
Dupuytrens contracture, palmar erythema and apping
tremors (asterixis), spider nevi, gynecomastia and loss of
body hair may be appreciated. Patient may present with
ascites, hepatomegaly or spleenomegaly.
Investigations

Aspartate aminotransferase (AST), alanine transaminase


(ALT), alkaline phosphatase (ALP)
Gamma-glucosyl transferase
5-Nucleotidase
Serum albumin
Serum bilirubin (direct and indirect)
Prothrombin time
Viral markers.

Imaging

Ultrasonography
CT
MRI.

Jaundice
Jaundice or icterus is a yellowish discoloration of tissue
resulting from the deposition of bilirubin. Tissue deposition
of bilirubin occurs only in the presence of serum hyperbilirubinemia and is a sign of either liver disease or less
525

Section VII System Review

often, a hemolytic disorder. The degree of serum bilirubin


elevation can be estimated by physical examination.
Slight increases in serum bilirubin are best detected by
examining the sclerae, which have a particular afnity for
bilirubin due to their high elastin content. The presence of
scleral icterus indicates a serum bilirubin of at least
51 mol/l (3.0 mg/dl). The ability to detect scleral icterus is
made more difcult if the examining room has uorescent
lighting. If the examiner suspects scleral icterus, a second
place to examine is underneath the tongue. As serum bilirubin levels rise, the skin will eventually become yellow in
light-skinned patients and even green if the process is
long-standing; the green color is produced by oxidation of
bilirubin to biliverdin.

Hepatitis
Findlay and colleagues in 1939 postulated that the etiology
of this particular disease was probably a virus carried in
the blood of some apparently by inadvertent inoculation
with vaccines contaminated with human serum containing
the infectious agent.
The term serum hepatitis rst came into use in the
early 1940s as a synonym for post-inoculation hepatitis. The
present diseases now labeled hepatitis A and hepatitis B
were rst described as a single entity, separate from other
causes of jaundice, called sporadic and epidemic catarrhal
jaundice was thought to be infectious, but unknown, causative agent (Cockayne, 1912). MacCallum in 1947 suggested
that to avoid confusion in terminology, the two postulated
viruses be termed virus A, which produces infectious hepatitis after a short incubation period and virus B, which
produces serum hepatitis after a long incubation period.
Hepatitis has a number of potential causes, both infectious and non-infectious. Alcohol, prescription medications,
and drug abuse are predominant non-infectious causes,
while viruses and bacteria are important infectious etiologic factors. Viral and drug-induced hepatitis are examples
of primary hepatitis. Secondary hepatitis may occur as a
sequela of other disease entities such as mononucleosis,
syphilis and tuberculosis.

Hepatitis A
Hepatitis A is caused by the hepatitis A virus (HAV), an
enterovirus of the Picornaviridae family. HAV is a singlestranded RNA virus surrounded by a protein capsid. Transmission is primarily by the oral-fecal route. Various methods
of spread are through contact of an infected person, traveling to an endemic region, and ingestion of contaminated
food or water. Hepatitis A is typically a self-limiting disease and usually causes mild illness characterized by sudden onset of non-specific symptoms. In children of age
6 years or younger, it is usually asymptomatic. In adults,
infection may present with symptoms such as fever, fatigue,
526

abdominal discomfort, diarrhea, nausea, and/or jaundice.


Diagnosis is made based upon signs and symptoms in combination with serologic tests for IgM anti-HAV (positive with
recent infection) and IgG anti-HAV. The risk of acquiring
HAV infection for healthcare workers is quite low. One
effective method of prevention of HAV infection is the
administration of HAV immune globulin either before the
exposure or within 2 weeks following exposure. Immune
globulin provides passive immunity toward HAV.
There are currently only two vaccines available that
provide active immunization. Those considered to be at
increased risk of HAV infection are people traveling internationally, drug users, people with chronic liver disease,
and those with occupational risks should be vaccinated.
Educating healthcare providers and the public about vaccine availability and efcacy can be effective in preventing
HAV outbreaks. Recovery from hepatitis depends on virus
replication, the host response and the appearance of antibodies. Greater morbidity and mortality is associated with
very young and older patients. Although most patients
recover from viral hepatitis, sequelae include persistent
infection (or carrier state), dual infection (HDV [a defective
virus] with HBV), chronic active hepatitis, fulminant hepatitis, cirrhosis, hepatocellular carcinoma and death. Dual
infections increase the risk for fulminant hepatitis, the
latter having a mortality rate of about 80%.

Hepatitis B
Hepatitis B virus is a 42 nm DNA virus of the Hepadnaviridae
family. The DNA genome is circular and comprised of two
strands, with one strand being partially incomplete. It is a
highly infectious virus that produces three distinct particles during replication:

The Dane particle or complete virus (HBV), composed


of an outer shell and an inner core
22 nm non-infectious spherical particles
Non-infectious filamentous units.
The outer shell of the Dane particle carries the hepatitis B
surface antigen (HBsAg), which is anchored in a lipid bilayer
derived from the host cell. Internally is the inner core that
is composed of a protein known as the hepatitis B core
antigen (HBcAg), and the hepatitis B early antigen
(HBeAg), an antigenic component derived from cleavage
of the core antigen. Hepatitis B virus infection remains a
serious healthcare problem. There are 350 million hepatitis
B virus carriers worldwide, with the highest carrier rates
(820% of population) in South-East Asia, China and subSaharan Africa. Globally, 1.25 million persons die per year
as a result of hepatitis B. In 2000, 6,646 cases of type B
hepatitis were reported to the Centers for Disease Control
and Prevention (CDC) in the United States. There are over
1.5 million carriers in the United States, and an estimated
6,000 deaths occur annually due to cirrhosis and primary

Chapter 18 Systemic Disorders and their Clinical Implications

hepatocellular carcinoma associated with HBV infection.


The main causative factor for the prevalence of HBV is its
replication pattern. The steps of HBV replication provide
therapeutic targets for antiviral therapy. Nucleoside analogs
interfere with viral DNA synthesis by blocking further
synthesis when incorporated into viral DNA and or competitively inhibiting viral polymerase.
Current protocols for treatment of HBV infection use
interferon and nucleoside analogs such as lamivudine.
Other nucleosides with activity against hepatitis B currently being used are famciclovir and adefovir.

individuals infected with HBV, which may then progress to


severe fulminant infection. Transmission of HDV can occur
via infected blood or blood products and is primarily seen
in intravenous drug users and hemophiliacs. HDV may
also be transmitted through sexual activity. Serologic testing for HDV and anti-HDV is used to detect infection.
Effective prevention of HBV will protect against HDV
infection. The screening of the blood supply for HBV has
altered the epidemiology of HDV. There is currently no
treatment for HDV infection.

Hepatitis E and G
Hepatitis C
Hepatitis C virus, previously known as one of the non-A
non-B hepatitis viruses, is a small, positive-sense, singlestranded RNA virus of the Flaviviridae family. Six major
genotypes of HCV and 40 related subtypes have been
identified. The virus has a core protein and two envelope
glycoproteins. The prevalence of HCV infection worldwide
is between 0.3% and 1.5%, with an estimated 300 million
carriers worldwide. The genetic diversity of HCV, and its
ability to mutate, allows the virus to avoid neutralization
and establish a chronic infection in about 8590% of
infected persons. Eighty-five percent of patients with HCV
will develop chronic hepatitis. Chronic HCV infection is
the major cause of cirrhosis and hepatocellular carcinoma.
Acute HCV infection usually presents with mild flu-like
symptoms, while chronic disease is variable in presentation. Patients may experience non-specific symptoms such
as fatigue, nausea, and/or abdominal pain. Majority of
HCV-infected patients develop chronic active hepatitis
that is characterized by persistent and intermittent viremia, fluctuating elevations of serum alanine aminotransferase (ALT) levels and slow but progressive liver damage.
The first decade is usually marked by inflammatory cell
infiltration of the portal tracts and focal liver cell necrosis.
Mild fibrosis ensues that is followed by more severe fibrosis, and bridging between portal tracts and hepatic veins.
By the second decade after infection, fibrosis progresses to
cirrhosis in at least 20% of patients with chronic HCV
infection. Progression is more likely if patients consume
excessive amounts of alcohol.
Future treatment of hepatitis C may include agents that
specically target the virus rather than current non-specic
forms of antiviral therapy. Research is focused on targeting the helicase and polymerase crucial to HCV replication.
Other therapeutic targets are the viral proteases and the
59 and 39 strands of HCV RNA.

Hepatitis D
Hepatitis D virus (HDV, delta agent) is a defective RNA
virus that uses the HBV surface antigen as a viral envelope. HDV can occur as a coinfection or superinfection in

Hepatitis E virus (HEV) is a non-enveloped, single stranded


RNA virus that is highly unstable due to the lack of a lipid
membrane. Transmission, similar to HAV, is by the oralfecal route. The primary method of spread is through contaminated drinking water and occurs mostly in places with
inadequate sanitary precautions. Symptoms of disease commonly include malaise, nausea, abdominal pain, and/or
fever. The infection is usually self-limiting, although there
have been cases of fulminant hepatitis and chronic disease.
In pregnant patients infected with HEV, there is a higher risk
of fulminant hepatitis. There is no HEV vaccine available,
and treatment is palliative.

Hepatitis G Virus (HGV)


Hepatitis G is caused by two isolated viruses that appear
to be almost identical. They are single-stranded, positivesense RNA viruses similar to HCV. HGV is transmitted
through blood and blood products, sexual activity and
perinatal contact. Due to similar transmission routes, HGV
may be found in association with other hepatitis viruses,
especially HCV. Individuals at risk are organ transplant
and blood transfusion recipients, IV drug users, dialysis
patients, and healthcare workers with exposure to blood
and chronic HCV patients. Diagnosis is based on detection
of HGV RNA in serum 14 weeks after infection. Serum
anti-HGV indicates past infection. Although the rate of
remission is low, little evidence exists that HGV causes
significant liver damage, even with persistent viremia.

Autoimmune Hepatitis
Autoimmune hepatitis is a chronic inflammatory disease.
Although the etiology is not clear, it is thought that environmental and viral factors may cause alterations in cellular
markers on hepatocytes leading to an autoimmune response
in genetically susceptible individuals. The etiology appears
to be related to antigen specific and generalized suppressor defects that perpetuate the autoimmune response. The
main finding in autoimmune hepatitis is IgG hypergammaglobulinemia, which may be due to chronic infections
or alteration in immune response. Autoimmune hepatitis
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Section VII System Review

may lead to liver cirrhosis. Treatment protocols for autoimmune hepatitis patients usually include steroid therapy.
If remission is not obtained by steroid therapy alone, azathioprine or its metabolite (6-mercaptopurine) may be added
to the protocol.

Fulminant Hepatitis
Fulminant hepatitis is sudden, severe liver dysfunction
which may lead to hepatocellular necrosis as well as hepatic
encephalopathy. Signs of fulminant hepatitis include jaundice, hepatomegaly and right upper quadrant tenderness
during the inflammatory stage. As necrosis occurs and
progresses, the liver becomes atrophic and less readily palpable. With the onset of severe liver failure, liver enzymes,
bilirubin, prothrombin time and partial thromboplastin time
will be elevated, while hemoglobin and hematocrit will
decrease. The prognosis for fulminant hepatitis is poor, and
the treatment of choice is liver transplantation.
Clinical course of hepatitis B and C
Hepatitis B and C virus infections can occur at any age,
but are more common after puberty. The incubation period
for HBV is 45180 days and for HCV it is 14180 days.
Hepatitis B and C viruses produce symptoms in 10% and
2530% of patients, respectively. Symptoms initially are
flu-like and include fatigue, fever, loss of appetite, diarrhea,
headache, malaise, myalgia, nausea, vomiting and weakness. During acute HBV infection, about 50% of symptomatic persons become icteric within about 10 days of the
onset of symptoms. A minority become icteric with HCV
infection. Icterus is the stage of infection in which patients
demonstrate jaundice in the skin, conjunctiva of the eye,
oral mucosa, and urine as a result of serum bilirubin levels
rising three- to four-fold above normal levels (0.21.2 mg/dl).
About 10% of patients infected with HBV also demonstrate
serum sickness-like manifestations, including angioedema,
arthralgia, and a rash. As the disease progresses, abdominal pain increases and hepatomegaly and splenomegaly
develop. Two to eight weeks are required for recovery from
symptoms, with hepatomegaly and abnormal liver function
persisting for weeks to months. The course of the disease
varies with alcohol use and the viral strain and load. The
acute infection rarely requires medical treatment other than
rest and the avoidance of hepatotoxic drugs. Patients who
fail to produce an adequate immune response can develop
fulminant hepatitis or a chronic infection.
Investigations and diagnosis
The diagnosis of acute HBV infection is made by recognition of the clinical features, specific serologic tests for viral
antigens and antibodies, and elevated liver enzymes. The
hepatitis B surface antigen (HBsAg) is the first detectable
specific marker. Hepatitis B surface antigen appears in the
528

blood usually by the 4th week of infection and is followed


within a week by the hepatitis B early antigen (HBeAg).
Two to four weeks after the appearance of surface antigen,
antibodies against the core antigen (anti-HBcAg) appear.
Subsequently, antibodies against the hepatitis B early antigen (anti-HBeAg) appear by about the 16th week, and finally
the appearance of antibodies against the surface antigen
(anti-HBsAg) appear by about 28th week. Clearance of the
virus is marked by the disappearance of HBeAg, appearance
of anti-HBeAg and the eventual disappearance of HBsAg.
Failure to produce anti-HBsAg results in a chronic carrier
state. Carriers persistently display HBsAg in their serum
for more than 6 months.
The presence of the HBeAg in a carriers serum indicates
virus replication in the liver and an infectious state. Antibody against HCV (anti-HCV) can be detected in 5070%
of patients at the onset of symptoms and in 90% within
3 months after onset of infection. Anti-HCV is commonly
detected using an enzyme immunoassay (EIA) that contains
HCV antigens from the core and non-structural genes.
A supplemental recombinant immunoblot assay (RIBA) and
the qualitative reverse transcriptase polymerase chain reaction (RT-PCR) for HCV RNA can be performed for conrmation. The RIBA is often positive after the 3rd week of
infection, whereas HCV RNA can be detected in blood as
soon as 1 week after initial exposure.
Elevation of the serum bilirubin often corresponds with
the peak of the icteric phase. During recovery, the transaminase level begins to fall, however, elevations in the
bilirubin level regress more slowly. Failure of the PT to
return to normal is a signicant prognostic sign of extensive hepatic cellular destruction, indicative of a fulminant
clinical course or a chronic rather than an acute infection.
Oral manifestations
The oral cavity may show evidence of liver dysfunction with
the presence of hemorrhagic changes, petechiae, hematoma,
jaundiced mucosal tissues, gingival bleeding, and/or icteric
mucosal changes. HCV has been linked to the onset. Sjogrens
syndrome and chronic hepatitis have been associated with
lichen planus in some studies. Glossitis may be seen with
alcoholic hepatitis, especially if combined with nutritional
deficiencies. Ecchymosis and reduced healing after surgery
may also be identified. In some cases, parotid gland enlargement is evident. These oral changes often appear in combination with general signs and symptoms of liver disease
such as fatigue, malaise, confusion, weight loss, nausea, vomiting, hepatomegaly, hemorrhagic changes, spider angiomas,
edema, ascites, dark urine, and pale/clay-colored stool.
Dental considerations
Comprehensive and current medical and dental histories
should be elicited. Consultation with and/or referral to treating physician prior to dental treatment is also recommended.

Chapter 18 Systemic Disorders and their Clinical Implications

Prior to dental treatment appropriate laboratory investigations should be carried pout. These include:

Complete blood count with differential erythrocyte


count, leukocyte count, hemoglobin, hematocrit, platelet count, bleeding time
Prothrombin time, partial thromboplastin time, international normalized ratio
Liver function tests.
Medications that are metabolized in the liver and/or impair
hemostasis should be judiciously used or avoided. Medications that have to be judiciously used include: analgesics
(acetaminophen, non-steroidal anti-inflammatory agents,
opioids); anesthetics; antibiotics (ampicillin, tetracycline),
medication with antiplatelet activity (aspirin) and sedatives
(long-acting benzodiazepines, barbiturates).
Soft tissue trauma should be as minimal as possible
during dental treatment. Universal infection control measures should be practiced such as professional immunization
against HBV, disinfection of dental units, proper handling
of instruments, sterilization of instruments, good hand
washing technique and personnel protective gear.

NEUROMUSCULAR DISORDERS
BELLS PALSY
Bells palsy is a lower motor neuron disease of the facial
nerve (cranial nerve VII) characterized by acute unilateral
peripheral facial weakness involving muscles innervated
by the facial nerve. Bilateral weakness is very rare and
occurs in less than 1% of patients.
Bells palsy is named after the 19th century Scottish
anatomist and surgeon Sir Charles Bell (17741842), who
rst described the condition along with the anatomy and
function of the facial nerve.
The annual incidence of Bells palsy is about 20 per
100,000 persons, with equal numbers of men and women
affected and the incidence increases with age. There is no
predilection for either side of the face. It occurs more commonly in patients with diabetes and in pregnant women.
Patients who have had one episode of Bells palsy have an
8% risk of recurrence. About 10% of those with Bells
palsy have a family history of the condition.
Etiopathogenesis
Etiology Common condition affecting 15-to 45-year-old
age group, both sexes. The cause is unknown, but site of
damage is probably the portion of facial nerve lying within
the facial canal (stylomastoid).
Inammation of facial nerve in the canal with demyelination and edema further hazards with blood supply.
Inammation of the nerve initially results in a reversible

neurapraxia, but ultimately Wallerian degeneration ensues.


Herpes zoster virus shows more aggressive biological behavior than herpes simplex virus type 1 because it spreads
transversely through the nerve by way of satellite cells.
It is commonly seen in pregnancy, diabetes, inuenza,
cold or any other respiratory illness. It is immunologically
mediated; probably caused by herpes virus, mainly herpes
simplex virus type 1 and herpes zoster virus.
Clinical features
Bells palsy is generally considered as a condition based
on exclusion. Patients report of no history of trauma, local
infection, tumor, or CNS disease. They present with peripheral dysfunction of the facial nerve, involving all distal
branches. The onset is usually abrupt and maximal facial
weakness is observed at 2472 hours. Generally, the unilateral facial weakness is complete. However, in about
one-third of the patients only partial weakness is noticed.
Numbness or pain around the ear on the affected side and
reduction in taste on the affected side; altered taste on the
anterior two-thirds of tongue are other important clinical
findings. Drooping of the corner of the mouth on the affected
side with drooling of saliva and loss of facial creases are
common findings. About one-third of the patients report
of hyperacusis (hypersensitivity to sounds) and inability to
close eyelid on the affected side.
Differential diagnosis
Some of the relatively common conditions that have to be
ruled out for before diagnosing Bells palsy are Ramsay Hunt
syndrome, tumors affecting facial nerve, diabetes mellitus
and sarcoidosis and Lyme neuroborreliosis.
Investigations
Electromyography can confirm the presence and severity
of nerve damage. Radiographic evaluation of the cerebellopontine angle, internal acoustic canal and mastoid region
can be undertaken to eliminate presence of tumors.
Management
Spontaneous improvement is generally seen within 6 months
in most cases. However, about 15% show incomplete recovery and exhibit residual nerve dysfunction including partial palsy and motor synkinesis (involuntary movement
accompanying a voluntary one).
It is believed that the treatment is more likely effective
before 72 hours and less effective after 7 days. Older
patients are less likely to recover completely. The combination of acyclovir 400 mg 5 times/day and prednisolone
(4060 mg daily for a week) is believed to be more effective than steroid alone.
Acyclovir (400 mg ve times per day for 10 days) helps
in limiting the damage to nerve from any associated herpetic infection.
529

Section VII System Review

Supportive measures include: protecting the cornea


with an eyepad or surgical placement of gold weights in the
upper lid. Articial tear substitutes should be used. Bells
palsy and blepharospasm can be treated with injections of
botulinum toxin.
Facial exercises can be benecial in patients with Bells
palsy. These should be performed while standing in front
of a mirror and include trying to raise the eyebrows, opening and closing the eyes, blowing, and whistling.

EPILEPSY
The word epilepsy is derived from the Greek word epilambanein meaning to take or to seize. Epilepsy can be defined
as a chronic neurological disorder characterized by frequently recurrent seizures. A seizure manifests as an episodic disturbance of movement, feeling or consciousness
caused by sudden synchronous, inappropriate and excessive
electrical discharges that interfere with the normal functioning of the brain.
Epilepsy usually affects young children (genetic predisposition to epilepsy associated with chromosome 12 anomalies) and elderly individuals who have a history of stroke,
tumors and Alzheimers disease.
Clinical types of epilepsy

Primary or idiopathic epilepsy (70%): Cause of seizures


is unknown.
Secondary or acquired epilepsy: Cause of seizure is
known such as head trauma (loss of consciousness
 30 minutes), metastatic brain tumors, stroke, infections, hypertension and diabetes as well as electrolyte
imbalances, dehydration and lack of oxygen. High doses
and withdrawal from chronic use of drugs such as
heroin, cocaine, barbiturates, amphetamines and alcohol can also lead to seizures.

Generalized seizures There are two basic forms of generalized seizures, namely, tonic-clonic (grand mal) seizures
and absence (petit mal) seizures.
Grand mal seizures are usually seen in childhood or
at teenage. These seizures begin after a brief period of aura
(warning signs like irritability, headache, nausea). The seizures begin with abrupt loss of consciousness. The tonic
phase is characterized by rigidity of the arm, leg, chest
and back muscles. The patient may fall, pupils become
dilated and the spine becomes extended (opisthotonos).
Following this phase there is a clonic phase characterized
by repetitive jerking and twitching movements of the limbs,
tongue and lips. Tongue biting, frothy salivation and
vomiting may occur. In this phase, bowel and bladder control may also be lost. The seizures usually last for about
23 minutes. Following this is the post ictal phase in
which the patient is tired and goes to sleep for as along as
12 hours.
Status epilepticus When tonic-clonic seizures last more
than 5 minutes or recur in a series of three or more seizures
without return to consciousness between attacks, a serious
neurological emergency called convulsive status epilepticus
has developed.
Absence (petit mal) seizures Absence (petit mal) seizures
are seen in childhood. These are called absence seizures as
these are not preceded by aura or warning signs. These
seizures last for about 30 seconds and may only present as
rapid eye blinking or stare, and brief loss of consciousness.
However, these recur very frequently almost up to 100 attacks
in a day.

Classification of seizures and clinical features

Diagnosis and dental considerations

Broadly, seizures can be classified as partial or generalized. A seizure is termed partial when the electrical
discharge causing it occurs in a specific area of the brain
or generalized when the discharge affects the entire brain
cortex.

Apart from a good clinical history, diagnostic tools such as


electroencephalography (EEG) and MRI help in diagnosing
the type of epilepsy. The number of decayed and missing
teeth, the degree of abrasion and periodontal indexes are
significantly higher in patients with epilepsy. Patient may
present with minor oral injuries such as tongue biting, soft
tissue lacerations and fractured teeth; but also frequently
lead to tooth injuries.
It is believed that enzyme-inducing antiepileptic drugs
such as phenytoin, phenobarbital, carbamazepine alter the
metabolism and clearance of vitamin D and have been associated with osteopenia and osteomalacia. Such patients have
an increased risk of fracture. Hence, these patients should
be supplemented with 1,000 mg of calcium and 400 IU of
vitamin D per day.

Partial seizures Partial seizures are further subdivided


into simple and complex. In simple seizures consciousness
is not impaired, whereas in complex seizures there is
impaired consciousness. There are several types of simple
partial seizures: motor seizures, sensory seizures, autonomic seizures and psychic seizures.
Motor seizures may cause patients to clench and grind
teeth and facial muscles/muscles of mastication may
become stiff. Unpleasant odors and taste disturbances may
530

be seen in sensory seizures. Partial seizures usually last


from 30 seconds to 2 minutes. In 30% of patients with
partial seizures, the partial seizure evolves into a secondary generalized seizure. In such cases, the excessive electrical activity that starts in a limited area spreads to
involve both sides of the brain.

Chapter 18 Systemic Disorders and their Clinical Implications

It is estimated that about 50% of the patients using phenytoin exhibit gingival hyperplasia within 1224 months of
initiation of treatment.
Xerostomia and stomatitis have been reported rarely as
side effects of carbamazepine. Valproic acid can cause
direct bone marrow suppression, which can impair wound
healing and increase postoperative bleeding and infections.
Decreased platelet count is the most common and best
recognized hematologic effect of valproic acid.
When restoration and replacement of teeth are considered
it is best to use a xed rather than removable prosthesis
and inclusion of additional abutments should be planned
for xed partial dentures.
Rash is a common side effect of antiepileptic drugs
(almost 57%). Although most drug-associated rash is
benign, serious rashes, including StevensJohnson syndrome and toxic epidermal necrolysis do occur.
Metronidazole, antifungal agents such as uconazole
and antibiotics such as erythromycin may interfere with
the metabolism of certain antiepileptic drugs and render
them ineffective for seizure control.

PARKINSONISM
Parkinsons disease is a serious brain disorder characterized
by degeneration of the basal ganglia. Patients present with
bradykinesia (slow movements), increased muscular tone
(rigidity), tremors and loss of postural reflexes.
Etiology
The exact etiology is still unknown. Though previously no
strong genetic basis was considered, it is now believed
that genetic factors may have a role to play. Parkinsonism
may be caused by head injuries, drug abuse (phenothiazine, valproate, prochlorperazines and methyl phenyl tetrahydropyridine). Environmental exposure to toxins such
as carbon monoxide, heavy metals and herbicides/pesticides may have a crucial role in the etiology.
This led to the suggestion that many cases of apparently
idiopathic toxins such as pesticides, herbicides, manganese, heavy metals and carbon monoxide.
Clinical features
In the initial stages of the condition patients may complain
of fatigue, aching limbs, depression and mental sluggishness. It has also been seen that these patients tend to have
a tiny handwriting (micrographia). The unique feature in
parkinsonism is a unilateral presentation of the signs/symptoms initially which turns into a bilateral involvement as
the condition worsens.
Other clinical features are tremors of the hands and feet
at rest, tongue tremors, gait becomes slower, muscular
tone and rigidity increases (log wheel rigidity) and speech

becomes unclear and softer. Face becomes expressionless


with an increased blink reex. Patients generally tend to
hypersalivate and drool.
Dental considerations
Most of the orofacial findings in parkinsonism are secondary
to the medications (levodopa, bromocriptine, catechol O
methyl transferase [COMT] inhibitors) used for treating the
condition.
Local anesthesia is best used without epinephrine.
Because the epinephrine can interact with COMT inhibitors and cause hypertension and dysrhythmias. Xerostomia
may be seen when anti-muscarinic drugs are used. Levodopa
causes taste disturbances and turns the saliva red. The other
side effects of these drugs are that they produce dyskinesia
such as lip and tongue tremors (y catchers tongue).

MULTIPLE SCLEROSIS
Multiple sclerosis (MS) is a chronic inflammatory disease of
the CNS. The etiology is still not clear. It is thought that
genetic predisposition together with immunity and environmental factors could trigger the disease.
Clinical features
Multiple sclerosis is usually seen between the 2nd and 4th
decades of life. It is slightly more common in women than
in men. MS exhibits a wide variety of symptoms as a result
of the demyelination of the CNS, and a later slow down or
blocked transmission at the level of axons. Ectopic impulses
may also appear, causing paroxysms and convulsions.
Multiple sclerosis is categorized into four subtypes:
(i) relapsingremitting (RR), (ii) progressive-relapsing (PR),
(iii) secondary-progressive (SP) and (iv) primary-progressive
(PP). Almost 85% of the patients belong to the relapsingremitting subtype.
Clinically, MS usually appears with a number of symptoms of neurological anomalies which settle in a matter of
minutes or hours, and which frequently progress in later
days. The most common features are: visual and oculomotor
anomalies, optical neuritis, anterior internuclear ophthalmic
paralysis, palsies, paresthesia, lack of motor coordination
and tonic spasms. Other less common features are genitourinary dysfunction, increased frequency and urge of urination and urinary incontinence, lack of bladder control and
episodic retention of urine. In the later stages, paroxysmal
ataxia and dysarthria or shaking of upper limbs is frequently seen which indicate brain damage.
Dental considerations
Patients may be encouraged to sit upright on the dental chair
to avoid respiratory embarrassment. Hypothetically, nitrous
531

Section VII System Review

oxide causes demyelination. Hence, it is best avoided.


Facial myokymia or facial hemispasm may be seen. Patients
report of perioral paresthesia.

MUSCULAR DYSTROPHY
Muscular dystrophy (MD) is a life-threatening recessive
neuromuscular disease affecting the short arm of the
X chromosome in the p21-2 position. Of the various forms
of MD, severe generalized familial muscular dystrophy
and mild restricted muscular dystrophy have significant
orofacial findings.
Severe generalized familial muscular dystrophy is popularly referred to as Duchenne muscular dystrophy (DMD).
It is commonly seen in young male children. In the early
stages of the disease, muscle enlargement may be seen
which becomes atrophic as the disease worsens. The early
recognizable symptom is the inability to walk and run.
Muscles associated with the lower extremities, pelvis and
shoulder girdle rapidly atrophy. Similarly, muscles of the
face, larynx and pharynx are affected.
Symons et al (2002) carried out a study to assess the
dental characteristics of patients with DMD. Their study
showed that patients with DMD had high plaque and calculus accumulation, leading to gingival inammation, due
to decreased muscle function. However, the caries experience was low. Disturbances in tooth form, number and
eruption of the second premolars were observed in 39% of
patients. Anterior and posterior open bites were common,
associated with lip incompetence, mouth breathing, macroglossia and tongue thrusting. Maxillary and mandibular
arch breadths were signicantly larger, on average, in the
DMD group than in controls. Rather than a normal parabolic arch form, the dental arches in DMD patients tended
to be hyperbolic, with the posterior teeth being displaced
buccally, consistent with an imbalance between the lingual and facial musculature.
An elevated serum creatinine phosphokinase level is
typical for this condition. The disease has no known treatment as of date and usually the affected individuals do not
live beyond the 2nd decade of life.

OROMANDIBULAR DYSTONIA
Dystonia is an involuntary, repetitive, sustained (tonic)
or spasmodic (rapid or clonic) muscle contraction. Few of
the dystonias that are of interest to a dental surgeon are
cranial-cervical dystonia (CCD) and oromandibular dystonia (OMD). Multiple etiological factors are proposed for
OMD, namely, genetic predisposition, injury to the CNS,
peripheral trauma, medications, metabolic or toxic states
and neurodegenerative disease. It usually affects individuals
532

in the 5th decade of life and women are more prone to


develop OMD.
CCD is an involuntary, sustained, contraction of the
periorbital, facial, oromandibular, pharyngeal, laryngeal
or cervical muscles. OMD involves the masticatory muscles, lower facial, and tongue muscles and may result in
trismus, bruxism, involuntary jaw opening or closure, and
involuntary tongue movement.
These involuntary movements may produce inappropriate deviation of the mandible, subluxation, intraoral soft
tissue trauma and bone resorption. Dysphagia, dysphonia
and difculty with mastication also often occur with OMD.
Brueghels syndrome is an association of OMD with blepharospasm.

MYASTHENIA GRAVIS
Myasthenia gravis is described in Chapter 20 on Autoimmune
Disorders.

ENDOCRINAL DISORDERS
The specialty of endocrinology encompasses the study of
glands and the hormones they produce. The term endocrine
was coined by Starling to denote the action of hormones
secreted internally in contrast to exocrine glands which
secrete into a lumen. The term hormone is a Greek word
meaning to set in motion describing the dynamic actions
of hormones as they elicit cellular responses and regulate
physiologic processes through feedback mechanisms.
The classic endocrine glandspituitary, thyroid, parathyroid, pancreatic islets, adrenals and gonadscommunicate
broadly with other organs through the nervous system,
hormones, cytokines and growth factors. In addition to its
synaptic functions, the brain produces a vast array of peptide hormones, spawning the discipline of neuroendocrinology. The immune and endocrine systems are also intimately
intertwined. The adrenal glucocorticoid, cortisol, is a powerful immunosuppressant. Cytokines and interleukins have
profound effects on the functions of the endocrine organs.
Common endocrine diseases, such as autoimmune thyroid
disease and type I diabetes mellitus are caused by dysregulation of immune surveillance and tolerance.
Endocrinal disease can present with either overt disease
or subtle ndings to the oral health clinician. Patients with
hormonal dysfunctions caused by endocrinal diseases may
be found to have signicant abnormalities on head and neck
examination. Large pituitary adenomas frequently present
with changes in vision and loss of visual eld integrity,
and the oral health clinician may be the rst medical professional to note these diseases. For example, in active
Graves disease (one of the conditions causing excessive

Chapter 18 Systemic Disorders and their Clinical Implications

function of the thyroid), defects in the motor function of


cranial nerves III, IV and VI may be observed. In acromegaly and in Cushings disease, pituitary adenomas secrete
active hormones, causing gradual changes in facial features and orofacial structures.
In addition to the changes an oral health clinician can
observe and document on physical examination, patients
with disease caused by endocrinal dysfunction who often
have alterations in the blood levels of several circulating
hormones. Notably, abnormal hormone levels may also be
the result of previous medical or surgical therapy for underlying disease. Normally, blood levels of hormones secreted
by the endocrinal organs are exquisitely regulated. Disruption of their function can produce life-threatening conditions, adversely affecting the safety of patients during all
but the most minor clinical interventions.
Prompt recognition of endocrinal dysfunction can prevent complications of dental treatment and can provide a
safe setting for clinical and therapeutic interventions in
these patients. Even after denitive medical or surgical treatment of endocrinal diseases, patients may require lifelong
replacement of several hormones. Replacement therapy
may be indicated after partial resection or partial destruction of endocrinal tissue. As a result of the destruction of
specialized cells, the endocrinal organs may no longer be
capable of secreting selected hormones. Replacement hormone therapy may interfere with standard preoperative
instructions before dental surgery or treatment and may
require the oral healthcare clinician, in consultation with
the patients physician, to alter the medical regimen or the
preoperative instructions to ensure a safe outcome.
A general understanding of the pathophysiology, relationship and the regulation of endocrine function will
help the clinician recognize new presentations of endocrine disease. Understanding endocrine function and the
regulatory role will allow the clinician to avoid complications during the treatment of these patients with complex
disease.

General Overview of Functional Mechanisms of


Endocrine System
The hypothalamicpituitaryendocrine axes control the
major endocrine glands. Peptidergic neurons in the hypothalamus release small peptides into the anterior pituitary.
Specialized pituitary secretory cells (Table 3) respond to the
small peptides and release larger peptides into the systemic
circulation. The specific endocrine glands are the target
of specific specialized pituitary peptides. A negative feedback by the hormone product of the target organ has been
demonstrated upon the secretory pituitary cell and upon
hypothalamic neuronal secretions.
The basic functions of the endocrine system include
growth and development, sex differentiation, metabolism
and adaptation to an ever-changing environment such as

Table 3

Hormones released by the anterior pituitary gland

Cell types of the anterior


pituitary gland

Hormones released

Thyrotrophs

Thyroid stimulating hormone (TSH)

Corticotrophs

Adrenocorticotropic hormone (ACTH)

Gonadotrophs

Gonadotropins, luteinizing hormone (LH)


and follicle-stimulating hormone (FSH)

Somatotrophs

Growth hormone (GH)

Lactotrophs

Prolactin

regulation of digestion, use and storage of nutrients, electrolyte and water metabolism and reproductive functions.

Hormones
Hormones function as chemical messengers moving through
the blood to distant target sites of action (pituitary hormones like growth hormone, thyroid stimulating hormone
[TSH] and adrenocorticotropic hormone [ACTH]); act more
locally as paracrine or autocrine messengers that incite more
local effects (like histamine, bradykinin and eicosanoids).
Most are present in body fluids at all times in greater or
lesser amounts as needed.
Categories of hormones according to structure

Amines and amino acid derivativesDopamine, catecholamines and thyroid hormone


Peptides, polypeptidesGonadotropin releasing hormone (GnRH), thyrotropin-releasing hormone (TRH)
somatostatin and vasopressin
Proteins and glycoproteinsTSH, luteinizing hormone
(LH), follicle stimulating hormone (FSH)
SteroidsCortisol and estrogen
Vitamin derivativesRetinoids and vitamin D.

Mechanisms of action of hormones


Hormones interact with high-affinity receptors which are
linked to one or more effector system in the cell. Some receptors are located on the cell membrane called membrane
receptors which bind with proteins and catecholamines.
These act through second messenger mechanisms (Table 4).
Others are located in the nucleus called nuclear receptors
which bind to hormones that can diffuse into the cell like
steroids, thyroxine and vitamin D (Table 5). They modulate
the synthesis of enzymes, transport proteins or structural
proteins.
Feedback regulatory system
Positive feedbackestrogen mediated stimulation of the
midcycle LH surge. Though chronic low levels of estrogen
533

Section VII System Review

Table 4

Glucagon
Insulin
Epinephrine
Parathyroid hormone
Thyroid-stimulating hormone (TSH)
Adrenocorticotropic hormone (ACTH)
Follicle-stimulating hormone (FSH)
Luteinizing hormone (LH)
Antidiuretic hormone (ADH)
Secretin

Table 5

Hormone receptor interactionssecond messengers


like cyclic AMP

Hormone receptor interactionsintracellular interactions

Estrogens
Testosterone
Progesterone
Adrenal cortical hormones
Thyroid hormones

are inhibitory, gradually rising estrogen levels stimulate


LH secretion.
Negative feedbackeach of the hypothalamic-pituitary hormone axes is governed by negative feedback maintaining
hormonal levels in a narrow range like thyroid hormone
on TRHTSH axis.
Types of hormone actions
Action at a distant site Released into the bloodstream, the
hormones circulate as free, unbound moleculespeptide
and protein hormones like TRH and LH usually circulate
unbound in the blood or circulate as hormones attached to
transport carriers.
Steroid hormones and thyroid hormone are carried by
specic carrier proteins synthesized in the liver.
Paracrine actions Hormones acting locally on cells other
than those that produced the hormone, e.g. the action of sex
steroids on the ovary; somatostatin secreted from -cells
inhibit insulin secretion from -cells of the pancreatic islets.
Autocrine actions Hormones exerting action on the cells
from which they were produced, e.g. the release of insulin
from pancreatic -cells can inhibit its release from the same
cells, IGF-I (insulin-like growth factor I) acts on many cells
that produce it like chondrocytes, breast epithelium and
gonadal cells.
Control of hormone levels

534

Affected by diurnal fluctuations that vary with the


sleepwake cycle
GH and ACTH

Secreted in a complicated cyclic manner


Female sex hormones
Regulated by feedback mechanisms that monitor substances such as glucose (insulin) and water (ADH) in
the body.

General Overview of Disorders of


Endocrine System
Endocrinology interfaces with numerous physiologic systems and hence has no standard endocrine history and
examination is complete more so as most of the glands are
inaccessible. The examination mostly focuses on hormonal excess or deficiency as well as direct examination of
palpable glands like thyroid and gonads. It is important to
evaluate patients in the context of their presenting symptoms, review of symptoms, family and social history and
detecting subtle symptoms and signs suggestive of underlying endocrine disease. Clinical judgment based on
knowledge of disease prevalence and pathophysiology is
required to decide when to embark on investigative evaluation of these disorders. A biochemical testing for hormonal abnormality with quantitative assessment of their
levels and dynamics, imaging tests like CT, MRI, thyroid
scan and ultrasonography are used for diagnosis of endocrine disorders.

Categories of Disturbances of Endocrine


Function
Endocrine diseases can be divided into three major types
of conditions: hypofunction, hyperfunction and hormone
resistance.
Hypofunction
An organ is in the state of hypofunction if there is underproduction of hormone.
Causes

Congenital defects
Glandular destruction due to infarction, hemorrhage,
infection, inflammation, autoimmune responses, neoplastic growth or surgeries
Decline in function with aging
Atrophy as result of drug therapy or unknown reasons
Mutations in a number of hormones, hormone receptors, transcription factors, enzymes and channels can
also lead to hormone deficiencies.
Autoimmune damage to the thyroid gland (Hashimotos
thyroiditis) and pancreatic islet -cells (type 1 diabetes
mellitus) are prevalent causes of endocrine disease.

Chapter 18 Systemic Disorders and their Clinical Implications

Hyperfunction
An organ is in the state of hyperfunction if there is excessive hormone production.
Causes

Autoimmune disorders
Hormone-producing tumor of the gland
Excess hormone administration.

Hormone resistance
Hormone resistance is a state when the production of hormone is optimal but the end organs are resistant to
hormonal effects.
Causes

Inherited defects in membrane receptors, nuclear receptors, or in the pathways that transduce receptor signals.

These disorders are characterized by defective hormone


action, despite the presence of increased hormone levels.
Common acquired forms of functional hormone resistance
include insulin resistance in type 2 diabetes mellitus. The
pathogenesis of functional resistance involves receptor
downregulation and post-receptor desensitization of signaling pathways; functional forms of resistance are generally reversible.
Endocrine disorders also can be categorized as

Primary disordersthose that originate in the target


gland responsible for producing the hormone
Secondary disorderswhere the target gland is essentially normal, but its function is altered by defective
levels of stimulating hormones or releasing factors
from the pituitary system
Tertiary disorderswhich result from hypothalamic
dysfunction where both the pituitary and target organ
are understimulated.

Pathophysiology of HypothalamicPituitary
Axis (HPA)
The HPA axis can be considered the master of ceremony in
regulating the endocrine functions. The secretions of the
hypothalamus act on the pituitary which further releases
hormones to act on the end organs.
Hypothalamic hormones regulating the secretion
of anterior pituitary hormones

GH-releasing hormone (GHRH)


Somatostatin
Dopamine
Thyrotropin-releasing hormone (TRH)

Corticotropin-releasing hormone (CRH)


Gonadotropin-releasing hormone (GnRH).

Function of hormones produced by the anterior


pituitary

Body growth and metabolism (GH)


Function of the thyroid gland (TSH)
Glucocorticoid hormone levels (ACTH)
Function of the gonads (FSH and LH)
Breast growth and milk production (prolactin).

Disorders associated with hypothalamic and


anterior pituitary insufficiency
Hypopituitarism is a result of impaired production of one or
more anterior trophic hormones or impaired synthesis and
secretion of hypothalamic hormone. More often than not the
etiology is acquired disease like tumors, inflammation or
vascular changes rather than inherited disorders. The clinical manifestations depend on which hormone is deficient.

GROWTH HORMONE
The growth hormone (GH), produced by somatotropes in
the anterior pituitary is necessary for linear bone growth
in children. It stimulates cells to increase in size and divide
more rapidly by enhancing amino acid transport across cell
membranes; increases the rate at which cells use fatty acids
and decreases the rate at which cells use carbohydrates.

Growth Hormone Deficiency


Growth Hormone in ChildrenDwarfism
In children GH deficiency, GHRH receptor mutations, GH
insensitivity or nutritional deficiency which interferes with
linear bone growth result in Dwarfism. A familial mode of
inheritanceautosomal dominant or recessive or X-linked
is seen. Isolated GH deficiency is characterized by short
stature, micro penis, increased fat, high pitched voice, propensity to hypoglycemia.
Etiology of hypopituitarism

Developmental/structuralpituitary dysplasia, congenital hypothalamic defects like Kallmann syndrome


Traumaticradiation, head injury, surgery
Neoplasticpituitary adenoma, leukemia, pituitary
metastasis
Infiltrative/inflammatoryhemochromatosis, sarcoidosis, Langerhans cell disease
Vascularpituitary apoplexy, sickle cell disease
Infectionshistoplasmosis, toxoplasmosis, Pneumocystis
carinii, tuberculosis.

535

Section VII System Review

Causes of short stature

Investigations

Imaging may reveal reduced bone mineral density, structural


damage of the pituitary and abdominal scan may show
excessive omental adiposity.

Variants of normal
Low birth weight
Chronic illness and malnutrition
Functional endocrine disorders
Chromosomal disorders
Skeletal abnormalities
Unusual syndromes.

Orodental manifestations
In pituitary dwarfs eruption rate and shedding of teeth is
delayed for 13 years for teeth that normally erupt during
1st decade of life and for 310 years for teeth erupting
in the 2nd decade. Lack of third molar development is a
common finding. Clinical crowns are smaller because of
incomplete eruption of teeth. The dental arches are smaller
resulting in malocclusion. The anatomical crowns are normal in size. The roots of teeth are shorter and supporting
structures are retarded in growth. Mandibular growth is
more retarded than maxilla.

Evoked GH is less than 3 ng/ml, IGF-I level is low or normal, Concomitant gonadotropin, TSH, ACTH reserves may
be deficient, LDLcholesterol is increased.
Managment
Replacement therapy with GH at 0.150.3 mg/day, maximum 1.25 mg/day to maintain IGF-I levels in the midnormal range for age and gender matched controls. It is
contraindicated in the presence of an active neoplasm,
intracranial hypertension, uncontrolled diabetes and retinopathy. Replacement with adrenocortical and thyroid
hormones in panhypopituitarism may be necessary.

Diagnosis and investigations

Growth Hormone Excess

Assessment of height if short stature, i.e. if a patients


height is more than 3 SD below mean for age or decelerated growth, final height can be predicted using standard
scales (BayleyPinneau or TannerWhithouse).
Radiographic assessment of bone age and skeletal
maturation, i.e. degree of growth plate fusion. GH release
is pulsatile and is best measured in response to provocative stimuli like exercise, insulin-induced hypoglycemia
which normally increases GH to more than 7 g/l in children. Pituitary imaging with MRI may reveal a mass or
structural defect.

Gigantism

Management
Replacement therapy with recombitant GH (0.020.05 mg/
kg per day SC) GH insensitivity and in mutations of GH
receptor IGF-I is given which bypasses the dysfunctional
GH receptor.

Adult GH Deficiency
Growth hormone deficiency in adults is caused by hypothalamic or pituitary somatotrope damage. Infarction of
the pituitary leading to hypopituitarism in adults is called
Simmonds disease. Panhypopituitarism, loss of weight,
diminished sexual function, reduced basal metabolic rate,
atrophic skin, thin eyebrows, loss of eyelash, sharp features;
thin lips with immobile expressions are the features. Other
clinical features include impaired quality of life, increased
body fat mass, central fat deposition, reduced exercise
capacity, CVS risk factors with impaired cardiac structure
and function, abnormal lipid profile and atherosclerosis.
536

Laboratory findings

Gigantism results if GH excess occurs in children or before


the growth plates of bone fuse. This results in increased
linear bone growth. McCuneAlbrights syndrome may
account for as many as 20% of cases of gigantism.
Orodental manifestations
The teeth size is proportional to the size of the jaws and
the body. Roots may be larger than normal.

Growth Hormone Excess in Adults


Acromegaly
Growth hormone hypersecretion after the closure of
epiphyses characterized by disordered somatic growth and
proportion.
Excess GH secretion may be a result of pituitary adenomas
like GH cell carcinoma, multiple endocrine neoplasia 1,
or McCuneAlbright syndrome; or due to extra pituitary
tumor like pancreatic islet cell tumor.
Causes of acromegaly
Most common cause (95%) is a somatotrope adenoma.
Other causes ( 5%) include excess secretion of GHRH by
hypothalamic tumors, ectopic GHRH secretion by nonendocrine tumors such as carcinoid tumors or small cell
lung cancers; ectopic secretion of GH by non-endocrine
tumors.

Chapter 18 Systemic Disorders and their Clinical Implications

Excess GHRH secretion

There central and peripheral causes for excess GHRH


secretion
Centralhypothalamic hamartoma, choristoma, ganglioneuroma
Peripheralbronchial carcinoid, pancreatic islet cell
tumor, small cell carcinoma, medullary thyroid carcinoma, pheochromocytoma.
Clinical features
The condition is insidious in onset and usually occurs
between 6.6 and 10.2 years of life. Voice deepening, structural changes like facial and skeletal disfigurement, frontal
bossing and cranial ridges, enlarged hand and feet; arthropathy with joint swelling, hypermobility and cartilaginous
thickening; periarticular fibrous thickening with joint stiffening or deformities; nerve entrapment; generalized visceromegaly including the tongue, lips, nose, bones, salivary
glands, thyroid, heart, liver, spleen; abnormalities of the
spinal column like osteophytosis, disk space widening and
dorsal kyphosis, carpal tunnel syndrome, hyperhidrosis and
oily skin, facial wrinkles, nasolabial pads and heel pads
thicken. Skin tags are the markers for adenomatous colonic
polyps.
The patient is medically compromised due to symptomatic cardiac disease, hypertension and left ventricular
hypertrophy. There is an excessive deposition of mucopolysaccharides around heart muscle bers. Increased GH
and decreased glucose tolerance leads to mild-to-moderate
diabetes mellitus. Increased blood glucose levels with
increased HBA1c (used to assess the efcacy of interventional therapy in DM), accelerated aging of arteries lead to
atherosclerosis.
Other endocrine complications include:

Increased serum prolactin level with/without galactorrhea


Hypopituitarism with amenorrhea/impotence, secondary adrenal and thyroid failure
Glucose intolerance with diabetes mellitus
Hypertriglyceridemia, hypercalciuria.
The oral manifestations include mandibular overgrowth
with prognathism in adults, maxillary widening and teeth
separation, jaw malocclusion and overbite; enlarged lips,
tongue with teeth indentations on the lateral border are
common features. Soft palate hyperplasia causes sleep
apnea and airway obstruction. Patients usually present for
flaring of teeth and orthodontic treatment.

Enlargement of paranasal sinus especially the frontal


sinus.
Thickening of the outer table of the skull vault leading
to enlargement and deformity.
Radiographic features of the jaws

Enlargement of the mandible, excess condylar growth


and height of the ascending ramus
Increased angle between ramus and body of mandible
with the loss of antegonial notch
Spacing and flaring of anterior teeth with anterior
open bite
Class III skeletal relationship
Increase in thickness and height of alveolar process
Radiographic features of the teeth include hypercementosis and supraeruption of posterior teeth to compensate for the growth of mandible.

Investigations
Age and gender matched serum IGF levels is increased.
Single GH level estimation is not useful. Confirmation is
by the failure of GH suppression to less than 1 g/l within
12 hour of an oral glucose load. Prolactin levels are
increased.
CT and MRI play a pivotal role in the evaluation of these
patients. MRI is now the investigation of choice in diagnosis
of pituitary adenomas. About 8085% of micro-adenomas
are visible on unenhanced T1 weighted MRI and 3350%
are seen as areas of hyperintensity on T2 weighted MRI.
MRI is better than CT in assessment of sella in the presence
of bony skull base thickening due to brous dysplasia as
in cases of McCuneAlbrights syndrome. The distinction
between pituitary gland and abnormal brous bone tissue
at skull base is better made on MRI. The combination of
pre- and post-contrast images is useful in this regard.
However, CT of skull base plays a useful role in some cases
for detailing neural foraminal compression, especially if
surgery is being contemplated.
In one study (Akira Hagiwara et al) on T2-weighted MRI,
hypointensity was seen more commonly in adenomas that
produced GH than in those which did not; hypointensity
was nearly exclusive to densely granulated GH-producing
adenomas.
Octreotide scintigraphy, in combination with other imaging modalities, is useful in the diagnosis and follow-up of
pituitary tumors. It allows scar tissue to be differentiated
from tumor recurrence after surgical treatment and ensures
better selection of patients who will benet from medical
treatment with somatostatin analogs.

Radiographic features
General radiographic features

Management of acromegaly

Synthetic somatostatin analogoctreotide acetate suppress


integrated GH levels to  5 g/l in 70% of patients and

Enlargement or ballooning of sella turcica if an


enlarged pituitary adenoma is present.

537

Section VII System Review

 2 g/l in 60%. It normalizes IGF-I in 75% of patients.


It is given at a dose of 50 g/day 3 times a day up to
1,500 g/day.
Lanreotide, a slow-releasing preparation suppresses GH
for 1014 days after 30 mg IM.
GH antagonistspegvisomant at 10 mg/day for 2 weeks
reduces IGF-I levels.
Dopamine agonists like bromocriptine, cabergoline,
high energy stereotactic radiation therapy for tumor mass
reduction and trans-sphenoidal surgery are the modalities
of treatment.

Primary polydipsiaSecondary deficiency of ADH due


to inhibition of secretion by excessive intake of fluids.

Clinical features

Polyuria and polydipsia


Urinary output: 520 l/day
Low specific gravity: 1.010
Low osmolality:  300 mmol/kg.

Investigations

Oral health considerations


Patients may seek orthodontic treatment for malocclusion.
Bilateral growth of mandible and new onset of diabetes
mellitus is suggestive of acromegaly.

Disorders of Posterior Pituitary


(Neurohypophysis)
The neurohypophysis secretes oxytocin and vasopressin
(antidiuretic hormone). Oxytocin is released rendering
uterine contraction during child birth and release of milk
during breast feeding. The antidiuretic hormone aids in
conservation of body water. It acts on permeability of collecting ducts and tubules reabsorbing water. It also causes
arteriolar smooth muscle contraction, vasoconstriction
and increases arteriolar blood pressure.

Diabetes Insipidus
Diabetes insipidus (DI) is caused due to the decreased
secretion or action of ADH. It is characterized by production of abnormally large volumes of dilute urine.
Etiology
Cranial DIdeficient production of ADH. It is caused by
genetic defect, such as dominant, recessive DIDMOAD syndrome (DI, diabetes mellitus, optic atrophy, deafness).
Hypothalamic or high stalk lesionhistiocytosis X, sarcoidosis, craniopharyngioma, suprasellar pituitary adenoma,
basal meningitis, head injury, surgery, encephalitis.

Fluid deprivation testto distinguish between cranial


DI and psychogenic DI
Response to ADHto distinguish between cranial and
nephrogenic DI
Plasma electrolytes, calcium
Investigation of renal tract and suprasellar anatomy.
Management

Desmopressin 12 mg q day by injection or 1020 mg


b.i.d. intranasally or 100400 mg b.i.d. orally
Chlorpropamide 125250 mg/day enhances the renal
responsiveness to vasopressin
Thiazide diuretisonly drug therapy for nephrogenic DI.

THYROID GLAND
The thyroid produces two hormones, thyroxin (T4) and triiodothyronine (T3). Acting through nuclear receptors,
these hormones play a critical role in maintaining thymogenic and metabolic homeostasis; help in cell differentiation influencing growth and development in children and
mental development and attainment of sexual maturity.
Thyroxin stimulates eruptive movement and tooth size, but
has little effect on alveolar growth. After diabetes mellitus,
thyroid disease is the most common endocrine problem in
the general population and most commonly seen in women
with higher rate after the age of 50 years.

Pathophysiology of HypothalamicPituitary
Thyroid Axis
It is a classic example of endocrine feedback loop.

Idiopathic causes
Nephrogenic DIrenal tubules unresponsive to vasopressin.
Causes for nephorgenic DI are:

Genetic defectSex linked recessive, cystinosis


MetabolicHypokalemia, hypercalcemia
DrugLithium, demeclocyline, amphotericin B, aminoglycosides, cisplatin, rifampin, foscarnet
PoisoningHeavy metals
538

Hypothalamus

TRH +

Anterior
pituitary

TSH +

Thyroid

()
()

T4T3

Thyroid hormone and cortisol provide negative feedback


to the pituitary and hypothalamus. A small hypothalamic

Chapter 18 Systemic Disorders and their Clinical Implications

peptide most specific to thyroid function thyrotropinreleasing hormone (TRH); TSH, a larger peptide from the
pituitary, predominantly associated with thyroid function.
Together, these peptides control three major functions of
the thyroid: the production of thyroid hormone (T4), the
growth and proliferation of thyroid cells, and the production of thyroglobulin (a large protein that acts as a binding,
storage and maturation protein for T4). As a consequence
of driving thyroid hormone production with TSH, circulating systemic blood levels of T4 are elevated. The increased
blood levels of T4 result in decreased pituitary secretion of
TSH, forming a negative feedback loop. The negative feedback mechanism causes decrease in the specific releasing
and stimulating hormones of the hypothalamus and pituitary. Decreases in the pituitary production of the corresponding stimulating hormones, TSH and ACTH, result in
the downregulation of the hormone produced by the specific endocrine gland, T4.
Laboratory evaluation
Categorized as:
1.
2.

Screening of newborns for congenital hypothyroidism


Screening of adult patients seen for non-thyroid related
reasons.

Measures of T3, T4, and TSH-TSH immunoradiometric


assays followed by measurement of unbound circulating thyroid hormone.
TSH should not be used to assess thyroid function in
patients suspected or known pituitary disease because
secondary hypothalamic pituitary disease is associated
with a variable (low-high) TSH level which is inappropriate for the low T4 levels.
Radioiodine uptake and thyroid scanning: Thyroid
gland selectively transports radioisotopes of iodine
(123I, 125I, 131I) and 99mTc pertechnetate, allowing thyroid imaging and quantification of radioactive tracer
fractional uptake.
Tests to determine etiology of thyroid dysfunction
Autoimmune thyroid disease is detected by measuring
circulating antibodies against thyroid peroxidase and
thyroglobulin.
Resin uptake test.
Ultrasonographic scanning and ultrasonographyguided FNA biopsy of a thyroid nodule.
CT and MRI scans.
Serum or tissue thyroglobulin determination.

Etiology
Primary

Iodine deficiency
Autoimmune hypothyroidism: Hashimotos thyroiditis, atrophic thyroiditis
Iatrogenic: Treatment, subtotal or total thyroidectomy,
external irradiation of neck for lymphoma or cancer
Drugs: Iodine excess (including iodinecontaining
contrast media and amiodarone), lithium, antithyroid
drugs, p-aminosalicylic acid, interferon-
and other
cytokines, aminoglutethimide
Congenital hypothyroidism: Absent or ectopic thyroid
gland, dyshormonogenesis, TSH-R mutation.
Infiltrative disorders: Amyloidosis, sarcoidosis, hemochromatosis, scleroderma, cystinosis, Riedels thyroiditis
Transient hypothyroidism
Silent thyroiditis, including postpartum thyroiditis
Subacute thyroiditis.

Secondary

Hypopituitarism: Tumors, pituitary surgery or irradiation, infiltrative disorders, Sheehans syndrome, trauma,
genetic forms or combined pituitary hormone deficiencies
Isolated TSH deficiency or inactivity
Hypothalamic disease: Tumors, trauma, infiltrative
disorders, idiopathic.
Hypothyroidism in children is termed cretinism and that
manifesting in adults called myxedema.
Congenital hypothyroidismcretinism
Congenital hypothyroidism if undetected early results in
hypothyroidism in children termed cretinism.
Congenital hypothyroidism is due to thyroid gland dysgenesis or inborn errors of thyroid hormone synthesis,
TSHR antibody mediated.
Females have a 2:1 prediliction. The infant appears
normal at birth. The condition is diagnosed because of
prolonged jaundice, feeding problems, hypotonia, macroglossia, delayed bone maturation, umbilical hernia, sparse
and brittle hair and ngers, atrophic sweat glands. Diagnosis is established by heel prick blood estimation of T4.
If treatment is delayed permanent neurologic damage
occurs. T4 is instituted at a dose of 1015 g/kg per day
with close monitoring of TSH levels.

Disorders Associated with Thyroid Gland

Oral manifestations

Hypothyroidism

Shortened base of the skull leading to retraction of the


bridge of the nose with flaring. The face looks wider as
longitudinal growth fails. Accumulation of glycosaminoglycans leading to enlarged lips and enlarged tongue with
continuous protrusion leading to malocclusion, delayed

Primary hypothyroidism is an intrinsic disorder of the thyroid gland causing low levels of thyroid hormone with
raised TSH.

539

Section VII System Review

eruption, retained deciduous teeth but no impairment of


tooth formation.
Radiographic features

Hyperthyroidism

In children delayed closure of epiphysis and skull sutures


with the production of numerous wormian bones.
Delayed eruption, short roots and thinning of lamina
dura.
Relatively small maxilla and mandible.

Hyperthyroidism is the result of excessive thyroid function


whereas thyrotoxicosis is a state of thyroid hormone excess
the etiology of which is hyperthyroidism.

General signs and symptoms in myxedema

Primary hyperthyroidism

Patient complains of tiredness, weakness, difficulty in


concentrating and poor memory. Dryness of skin with hair
loss and intolerance to cold. Weight gain with poor appetite, constipation, menorrhagia (later oligomenorrhea or
amenorrhea), dyspnea, hoarse voice, paresthesias, impaired
hearing are the symptoms.
The signs include dry coarse skin; cool, peripheral
extremities, puffy face, hands and feet (myxedema), diffuse alopecia, bradycardia, peripheral edema, delayed tendon reex relaxation, carpal tunnel syndrome, serous
cavity effusions, decrease in renal function.

1.
2.
3.
4.
5.

Oral health considerations

Delayed eruption of permanent teeth.


Myxedemarespiratory depression, CVS depression.
Mild hypothyroidismexaggerated effects of analgesics
and sedatives in routine doses.
Increased subcutaneous mucopolysaccharidesdecrease
the ability of small vessels to constrictprolonged
bleeding.
Decreased metabolic activity in fibroblastsdelayed
wound healing.
Drug interactions with lithium, amiodarone, etc. may
induce hypothyroid stages.
Radiographic features
Radiographic features of the teeth include evidence of
periodontal disease, loss of teeth, separation of teeth and
external root resorption.
Treatment
Daily replacement dose of levothyroxin 1.6 g/kg (100
150 g).
Thyroxin sodium 1.5 mg/kg, i.e. 100150 mg/day.
Ideal dose restores TSH to normal.
Supportive therapy to correct metabolic disturbance.
External warming if temperature falls below 30C which can
result in cerebral vascular collapse. Correction of hyponatremia and hypoglycemia with hypertonic saline and IV
glucose. Hypotonic infusions should be avoided which can
lead to water retention. Parenteral hydrocortisone 50 mg

540

every 6 hourly in case of profound hypothyroidism to


counter depleted adrenal reserve.

Causes of thyrotoxicosis

6.
7.

Graves disease
Toxic multinodular goiter
Toxic adenoma
Functioning thyroid carcinoma metastases
Activating mutation of the TSH receptor (autosomal
dominant)
Struma ovarii
Drugs; iodine excess (JodBasedow phenomenon).

Thyrotoxicosis without hyperthyroidism


1.
2.
3.
4.

Subacute thyroiditis
Silent thyroiditis
Other causes of thyroid destruction; amiodarone, radiation, infarction of adenoma
Ingestion of excess thyroid hormone (thyrotoxicosis
factitia) or thyroid tissue.

Secondary hyperthyroidism
1.
2.
3.
4.

TSHsecreting pituitary adenoma


Thyroid hormone resistance syndrome; occasional
patients may have features of thyrotoxicosis
Chorionic gonadotropinsecreting tumors
Gestational thyrotoxicosis.

Clinical features
Symptoms Hyperactivity, irritability, dysphoria, heat
intolerance and sweating, palpitations, fatigue and weakness, weight loss with increased appetite, diarrhea, polyuria, oligomenorrhea, loss of libido.
Signs Tachycardia, atrial fibrillation in the elderly, tremors, goiter, warm, moist skin, muscle weakness, proximal
myopathy, lid retraction or lag and gynecomastia.
Oral manifestations
Alveolar atrophy is seen in advanced cases as a consequence of osteoporosis. Periodontitis and dental caries
appear more rapidly. The jaws and teeth development is
accelerated and earlier shedding of deciduous teeth and
accelerated eruption of permanent teeth is seen. Euthyroid
infants of hyperthyroid infants may have natal teeth. Lingual thyroid is sometimes seen. A lingual thyroid if seen

Chapter 18 Systemic Disorders and their Clinical Implications

in a euthyroid patient should not be excised unless the


presence of the thyroid gland is confirmed with radioactive
iodine scanning. Pain associated with subacute thyroiditis
radiates to the ear, jaw and occipital region. Horseness of
voice and dysphagia are other features.

Graves Disease
Hyperthyroidism with diffuse thyroid enlargement, ophthalmopathy and dermatopathy.
An autoimmune disorder characterized by abnormal
stimulation of the thyroid gland by thyroid-stimulating
antibodies (thyroid-stimulating immunoglobulins [TSI])
that act through the normal TSH receptors.
This is associated with human leukocyte antigen
(HLA)-DR3 and HLA-B8. Familial tendency is evident due
to immunologically mediated activation of broblasts in
extraocular muscles and skin with accumulation of lid lag
or retraction, proptosis, exophthlamos, diplopia, corneal
involvement, periorbital edema, chemosis, optic nerve
damage.
Dermatopathy in the form of pretibial myxedema, skin
appearance appears like orange and clubbing may be seen.
Radiographic features
In children early development and eruption of teeth with
premature loss of primary teeth is seen. In adults generalized decrease in bone density or loss of some areas of
edentulous alveolar bone is seen.
Investigations

Increased T3
Increased or upper limit normal rangeT4
Decreased TSH
Non-specific or increased serum glutamic oxaloacetic
transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase.
Routine thyroid 99mTc radionuclide imaging is helpful
in identifying patients with an unsuspected cause of
hyperthyroidism other than Graves disease.
The treatment of Graves disease is aimed at
1.

2.

Reducing thyroid hormone synthesis using antithyroid


drugs like thionamidespropyl thiouracil 100200 mg
68 hourly, carbimazole and methamizole 1020 mg
812 hourly.
Reducing the amount of thyroid tissue with 131I radioiodine or subtotal thyroidectomy.

Thyrotoxic Crisis/Thyroid Storm


Thyrotoxic crisis is a medical emergency because of exacerbation of hyperthyroidism precipitated by infection, stroke,
trauma, diabetic ketoacidosis or thyroid surgery.

Clinical features
Patients present with very high fever, extreme cardiovascular effects (tachycardia, congestive failure and angina) and
severe CNS effects (agitation, restlessness and delirium).
Management

Propylthiouracil 600 mg initially and 200300 mg/


6 hour. Propranolol to reduce tachycardia.
Glucocorticoids and antibiotics if infection present.
Orodental treatment evaluation of a patient with thyroid disorder Any patient who is asymptomatic and has
had a physical examination and normal thyroid function
test within the past 6 months is at low risk for complications during dental therapy. If otherwise the patient is
considered as at moderate risk because an asymptomatic
hypothyroid patient under thyroid replacement therapy
may become hypothyroid again because of lapses in medication or subtle metabolic shifts. Similarly, a hyperthyroid patient on propyl thiouracil or radioactive iodine
remain euthyroid only in about 30% of cases or as a complication of radioactive iodine therapy insidiously may
become hypothyroid.
A hypothyroid patient has pre-existing CNS depression
and is acutely sensitive to drugs with CNS depressing side
effects. Narcotic analgesics and sedatives can precipitate
respiratory and cardiovascular depression. Patients with
hyperthyroidism are particularly susceptible to catecholamines (epinephrine as vasoconstrictors) used in local
anesthetics and gingival retraction cords. Along with dental stress it can precipitate thyroid storm. Short of thyroid
storm it can exacerbate underlying cardiovascular pathology.
If no evaluation has been done in the past 6 months the
patients have to be referred to the physician and for laboratory evaluation especially when type V and VI procedures
are indicated.
Patients with hyperthyroidism may have elevated blood
pressure and heart rates on the basis of the effects of
thyroid hormone on sympathetic nervous system activity.
Patients with high arteriolar pressures may require increased
attention and a longer duration of local pressure to stop
bleeding. Hyperthyroidism patients who are on warfarin
(Coumarin) may have an increased metabolism of this drug,
leading to decrease in previously therapeutic coagulation
indices.
Patients with long-standing hypothyroidism may have
increased subcutaneous mucopolysaccharides due to decrease in the degradation of these substances. The presence
of excess subcutaneous mucopolysaccharides may decrease
the ability of small vessels to constrict when cut and may
result in increased bleeding from the inltrated tissues,
including mucosa and skin. Local pressure for an extended
time will probably adequately control the small-vessel
bleeding.
541

Section VII System Review

PARATHYROID GLANDS
Parathormone (PTH) is an 84 amino acid single chain peptide and is the primary regulator of extracellular calcium
concentration. It acts directly on bone inducing calcium
resorption and on the kidney where it stimulates calcium
reabsorption and synthesis of 1,25-dihydroxy vitamin D
(1,25(OH)2D) a hormone that stimulates GI calcium
reabsorption.
Continuous exposure to elevated PTH leads to increased
osteoclastic mediated bone resorption. However intermittent administration of PTH, elevating levels for 12 hour/
day leads to net stimulation of bone formation rather than
breakdown. Thus the effects of PTH are: (i) calcium removal
from bone, and (ii) bone remodeling by acting on both
osteoblasts and osteoclasts.

Hyperparathyroidism
Hyperparathyroidism (HPT) causing bone disease was first
described by von Recklinghausen in 1891 and so-called as
von Recklinghausen disease of bone. It is a generalized disorder of calcium, phosphate and bone metabolism due to
increase in PTH secretion.
Hyperparathyroidism occurs in three clinical forms:

Primary HPT is the uncontrolled production of PTH as


a result of a parathyroid adenoma (8090%) or chief
cell parathyroid hyperplasia (1015%) or a parathyroid
carcinoma (2%), (multiple endocrine neoplasia I and
MEN 2a).
Two syndromes are associated with HPT, namely,
hereditary hyperthyroid jaw tumor syndrome and
familial isolated primary hyperthyroidism with
carcinoma.
Secondary HPT is a compensatory mechanism resulting from a primary condition producing hypocalcemia
such as rickets, osteomalacia, pregnancy, chronic renal
insufficiency, calcium deprivation or maternal hypoparathyroidism.
Hypocalcemia prompts increased PTH production
with liberation of calcium from bone.
Renal osteodystrophy occurs in chronic renal
diseases.
In the kidney, the hydroxylation of 25-OH vitamin
D3 occurs which is necessary for calcium absorption
from the gut. Therefore in patient with end stage renal
disease active vitamin D is lessless calcium is
absorbed from guthypocalcemia  compensatory
PTH production.
Tertiary HPT may occur after long-standing secondary hyperparathyroidism, characterized by the development of a functional parathyroidism adenoma causing
increased production of PTH. The most common cause
is chronic renal failure.
542

Clinical features
It was described by Jackson and Frame (1972) as the tetrad
of bones, stones, abdominal groans and psychic moans
with fatigue overtones.
Mostly occur after 60 years of age and women are
affected 24 times more often than men. About 80% of
the cases are asymptomatic and the primary involvement
is in the kidneys and skeletal system. Stones refer to the
increased deposition of calcium in renal parenchyma and
a tendency to develop recurrent nephrolithiasis (renal calculi) with resulting complications like urinary tract obstruction, infection, loss of renal function and uremia. Metastatic
calcications are also seen in blood vessel walls, subcutaneous soft tissues, dura and the region around the joints. Band
keratopathy, where calcication occurs as a narrow band at
the limbic margin of the cornea of the eye is also seen.
Bones refer to the distinctive involvement of the bone.
Ostetitis brosa cystica, bone lesions which on histopathological examination show multinucleated giant osteoclasts in scalloped areas of the bone surface (Howships
lacunae) and replacement of normal cellular and marrow
elements with brous tissue.
Abdominal groans refer to subtle vague GI disturbances
such as nausea, vomiting, anorexia, pancreatitis, duodenal
and peptic ulcers.
Psychic moans may be due to CNS manifestation ranging from mild personality problems to severe psychiatric
disorders due to hypercalcemia.
Other manifestations include neuromuscular problems
with proximal muscle weakness, easy fatigability and
muscle atrophy (differentiated from other neuromuscular
disorders by regression after surgical removal of the
glands).
Orodental manifestations
One of the first signs is development of malocclusion
because of drifting of teeth. Giant cell tumors and pseudocysts of the jaws are the other possible lesions found.
Padbury et al demonstrated a signicantly greater incidence of torus/tori in the Caucasian population with the
incidence of tori nearly three times higher in HPT patients.
HPT leads to a preferential loss of cortical bone and preservation or increase in trabecular bone. It has been proposed that the presence of hypercalcemia in HPT patients is
preceded by longer periods of elevated PTH levels. It could
be that the tori represent an expansion of trabecular bone
at the expense of cortical bone in response to elevated PTH
levels with possible contribution from the mechanical
forces present in the oral cavity. Furthermore, PTH mediated
endosteal resorption has been shown to be compensated
by PTH-mediated periosteal apposition with an increase in
overall bone size.
Periodontal ligament (PDL) width in patients with a torus
was higher than those without a torus, and this intriguing

Chapter 18 Systemic Disorders and their Clinical Implications

relationship remained when issues of gender and age were


taken into account. This is consistent with the HPT patient
population having reduced radicular lamina dura density
and may reect the localized impact of PTH in the PDL
space to evoke cortical bone loss in the area adjacent to
the tooth, whereas compensatory mechanisms are taking
place for increased bone growth in the form of the tori
more laterally.
Radiographic features
The classic generalized features: Most important and reliable sign of HPT is subperiosteal erosion along the radial
margin of the middle phalanges. Initially, only the outer
surface of the cortex appears lace like but then the endosteal surface is also affected. Generalized demineralization
shows an unusual radiolucency.
Osteitis fibrosa generalisata It is also called as osteitis
fibrosa cystica as they appeared cyst-like on radiographs.
It refers to the pattern of generalized rarefaction seen in
the skeleton in approximately 13% of patients with hyperparathyroidism. It appears as radiolucent area with thin cortices and hazy indistinct trabeculae or a moth eaten image.
In regions where the trabeculae are completely missing a
cyst-like appearance is seen. Histopathologically a sparse
narrow trabeculae scattered throughout a fibrous stroma
with few osteoclasts are seen.
Brown tumors Peripheral or central tumors of bone are
seen in the late phase of the disease in 10% of the cases.
Metastatic calcication of soft tissues appearing punctuate or nodular and occur in kidneys and joints.
Radiographic features of skull Skull appears osteoporotic and this change may occur before jaw changes.
Deossification appears granular caused by loss of diploie
and thinning of cortical plates and is prominent in the
outer third of the skull termed pepper-pot skull which may
be interrupted by one or more cystic areas representing
brown tumors. Radiographically, they appear rounded with
smooth or irregular borders and with sclerotic reactive
bone margins.
Radiographic features of jaw bones Generalized demineralization characterized by lack of sharpness of trabecular pattern with a more granular appearance described as
ground glass appearance or osteoporosis fibrosa generalisata
sometimes may have a mottled or moth-eaten appearance
due to variation in density. Subperiosteal erosion at the
mandibular angle, resorption of the inferior cortex of the
mandible, lining of mandibular canal, mental foramen,
walls of antrum and nasal cavities. Resorption of the lamina dura is the first sign of deossification in the jaws. Two
relative changes are observed, namely, thickening of PDL
space and tapered appearance of roots because the lamina
dura provides a definitive edge effect accentuating the

density of the root and is rounded at apex. Some authors


feel that the loss of lamina dura occurs only in about 10%
case and is the overrated feature of HPT.
Metastatic calcication may occur in salivary gland.
Brown tumors These occur in pelvis, ribs and femurs but
most common in the jaw bones. These are either peripheral
or central, monostotic or polyostotic. These may be unilocular or multilocular without marginal scalloping. The
borders may be poorly defined and there may be a zone of
reactive bone outlining the lesion. Histologically, it is
identical to central giant cell granuloma of the jaws. If a
giant cell granuloma is found later than the second decade
the patient should be screened for serum calcium, PTH and
alkaline phosphatase.
Teeth The teeth stand out because of the osteopenic
nature of the bone. In developing or erupting tooth: (i) loss
of crypt wall, (ii) pointed and tapered roots especially at
apical third, and (iii) large pulp chambers are seen.
In erupted teeth, the pulp chambers appear large in
younger people but in adults they are narrower. Pulpal
calcications are seen in pulp chambers.
Histopathologic features
Brown tumors are characterized by a proliferation of exceedingly vascular granulation tissue with accumulation of
hemosiderin pigments giving the lesion a brown appearance. Numerous multinucleated osteoclast type giant cells
are seen and some lesions are proliferative showing parallel arrangement of spicules of woven bone set in a cellular
fibroblastic background with multinucleated giant cells
often associated with secondary HPT related to chronic
renal disease.
Investigations

Immunoassay for parathormone.


Multiple markers of bone tumors such as formation
indices (bone specific alkaline phosphatase, osteocalcin
and type I collagen peptides) and bone resorption indices (including hydroxypyridinium collagen crosslinks
and telopeptides of type I collagen).
CT and dual energy X-ray absorptiometry (DEXA) of
spine produce reproducible quantitative estimates of
bone density. Non-invasive imaging like ultrasonography, CT scanning, MRI and parathyroid (PT) scintigraphy may be used.
Management
Primary HTP: In symptomatic patients removal of hyperplastic/functional tumor is done after PTH assay.
99m
Tc-sestamibi/99mTc-pertechnetate subtraction scintigraphy (SS) as initial test for patients undergoing parathyroidectomy and helical CT anatomical detail, such as
543

Section VII System Review

the relationship with surrounding tissues and detection of


concomitant thyroid nodules, guiding the surgical exploration especially in patients with ectopic PT glands.
In asymptomatic patients who do not undergo surgery
the management is as suggested by Bilezikian et al.
Assessment

Serum calciumannually
24-Hour urinary calcium only during initial evaluation
Creatinine clearance only during initial evaluation
Serum creatinine annually
Bone densityannually
Abdominal radiographs with or without ultrasonograph at the time of initial evaluation
Secondary HTP
Restriction of dietary phosphate, administration of
bisphosphonates and vitamin D metabolite (calcitrol)
and renal transplantation.

Hypoparathyroidism
Hypoparathyroidism could be hereditary or acquired.
Decreased amount of PTH leads to hypocalcemia and
hyperphosphatemia.

Hereditary
Hypoparathyroidism associated with conditions like
DiGeorge syndromedefective development of thymus
and parathyroid glands; and polyglandular syndromes.

Acquired
Postoperative hypoparathyroidism Damage to parathyroid gland or inadvertent removal during thyroid surgery.
Infantile hypoparathyroidism Transient, associated with
maternal hyperparathyroidism or calcium deficiency.
Idiopathic hypoparathyroidism Autoimmune disease of
adrenal, thyroid or ovary in young people.

Substitution therapy1 hydroxycholecalciferol or


vitamin D 40,000120,000 g/day (13 mg daily) with
1 g elemental calcium.

Oral health considerations


It occurs during odontogenesis; pitting enamel hypoplasia
and failure of tooth eruption may occur. Presence of persistent oral candidiasis in a young patient may signal the
onset of endocrinecandidiasis syndrome.

Tetany
Tetany is defined as an increased excitability of peripheral
nerves due to hypocalcemia or alkalosis.
Causes

Hypocalcemia: Malabsorption, osteomalacia, hypoparathyroidism, acute pancreatitis.


Alkalosis: Repeated vomiting of gastric juice, excess
intake of alkalis, hyperventilation, primary hyperaldosteronism.
Clinical features
Children present with carpopedal spasm, stridor and convulsions. Main d accoucheur sign is seen (metacarpophalangeal joints flexed, interphalangeal joints of fingers and
thumb extended with opposition of the thumb). Adults present with tingling in hands, feet and around the mouth.
Latent tetany is characterized by Trousseaus sign. When
the sphygmomanometer cuff is inated on upper arm more
than systolic BP carpal spasm occurs within 3 minutes.
Chvostek sign is seen which is characterized by twitching
of upper lip when the facial nerve is tapped below the
zygomatic process.
Management
Tetany is managed with 20 ml of 10% calcium gluconate IV
or 10 ml IM. Alkalosis is treated with IV isotonic saline.

Clinical features
Calcifications of basal ganglia and extrapyramidal syndromes like choreoathetotic movement and dystonia are
more common and appear earlier. Tetany as consequence
of hypocalcemia, grand mal epilepsy, psychosis, cataracts,
papilledema, increased intracranial pressure and chronic
changes in finger nails, hair, alopecia and hypomagnesemia are seen. May be associated with autoimmune polyglandularcandidiasis syndrome.
Management

544

Usually asymptomaticno treatment.

HYPOTHALAMUSPITUITARYADRENAL
AXIS
The main function of hypothalamuspituitaryadrenal
(HPA) axis is to maintain metabolic homeostasis and to
mediate the neuroendocrine stress response. An understanding of the axis is important especially for management of
conditions which need long-term corticosteroid therapy
and management of patients on long-term corticosteroid
therapy and adrenal insufficiency.

Chapter 18 Systemic Disorders and their Clinical Implications

Hormone

Released from

Type

Actions

Corticotropin releasing hormone (CRH)

Hypothalamus

Peptide

Controls function of adrenal cortex

Adrenocorticptropic hormone (ACTH)

Anterior pituitary

Pro-opiomelanocortin (POMC)

Controls function of adrenal cortex, controls


medullary rennin and aldosterone mineralocorticoid
action in controlling blood volume and pressure

Melanocyte stimulating hormone (MSH)

Anterior pituitary

Pro-opiomelanocortin (POMC)

B-endorphins

Anterior pituitary

Pro-opiomelanocortin (POMC)

Mineralocorticoids (aldosterone)

Function in sodium, potassium and water balance

Glucocorticoids (cortisol)

Aid in regulating the metabolic functions of the


body and in controlling the inflammation.
Essential for survival in stress situations

Adrenal sex hormones (androgens)

Serve mainly as a source of androgens for women

Pathophysiology of adrenal diseases and


conditions
Acute inflammatory or septic insults activate HPA axis
through the integrated actions of proinflammatory cytokines,
bacterial toxins and neural signals resulting in cortisol elevation, restraining inflammatory response and providing
host protection. Thus, the neuroendocrine stress response
reflects the net result of highly integrated hypothalamic,
intrapituitary and peripheral hormone and cytokine signals.
Disorders affecting the adrenal glands resulting excess
or insufcient production of adrenal products. Excess production due to pathophysiologic processes as due to ACTH
secreting pituitary tumors (70% of cases) is called Cushings
disease. Iatrogenic glucocorticoids, adrenal tumors or ectopic secretion of ACTH (malignant tumor of pulmonary origin) and rarely CRH producing ectopic tumor Cushings
syndrome.
Insufcient adrenocortical function may occur primarily
due to destruction of adrenal cortex called Addisonss disease or secondarily due to hypothalamic-pituitary disease
or administration of exogenous steroids.
In clinical dentistry, cortisol deciency or excess is
overwhelmingly an iatrogenic disease, caused either by
treatment of the patient with glucocorticoidsCushings
syndrome or by patient withdrawal from previous treatmentadrenal insufciency.
Laboratory evaluation of adrenocortical function
Urine levels: A 24-hour urine free cortisol measurement is
a reliable screening test. It is higher in the day time (7 AM
7 PM) than at night (7 PM7 AM)/urinary creatinine should
also be measured to determine the accuracy and adequacy
of collection procedure.
Stimulation tests: These are useful in hormone deficiency
states. ACTH stimulation test is done to determine the functional reserve of adrenal gland for production of cortisol.

Tests for mineralocorticoid reserve and stimulation of


reninangiotensin system is by programed volume depletion such as sodium restriction, diuretic administration or
upright posture.
Suppression tests are done to document hypersecretion
of adrenal hormones by measuring the target hormone
response after standardized suppression of its tropic hormone. Examples are the pituitary-adrenal suppressibility
and an overnight dexamethasone suppression test as screening test.

Cushings Syndrome
The diagnosis of the condition presents two great challenges:
1.
2.

To distinguish between pathologic and physiologic/


other cortisol production
To determine etiology of cortisol excess.

The condition is commonly seen in the age group of 2050


years with a 5:1 female predilection. Central obesity, plethoric moon facies, cutaneous atrophy, purple striae with
easy bruising, proximal muscle wasting, osteoporosis, hypertension, diabetes mellitus, immunosuppression (including
delayed hypersensitivity reaction), psychiatric problems,
gonadal dysfunction and hypergonadism.
Characteristic central distribution of fat, thin skin with
striae and bruising and proximal muscle weakness; osteoporosis in children and young females suggest pathologic
causes rather than physiologic causes for excess cortisol
production.
Actions of cortisol

Glucose metabolism
Protein metabolism
Fat metabolism

545

Section VII System Review

Anti-inflammatory action
Psychic effect
Permissive effect.

Rapid onset with skin hyperpigmentation with severe


myopathy suggests ectopic causes of ACTH secretion. The
primary cause of death is cardiovascular disease followed
by infections and suicides.
Endocrinopathic pigmentation Bronzing of the skin and
patchy melanosis of the oral mucosa are signs of Addisons
disease and pituitary-based Cushings syndrome. The cause
of hyperpigmentation is oversecretion of ACTH, which has
melanocyte-stimulating properties. In Addisons disease,
adrenocortical insufficiency evolves as a consequence of
granulomatous infection of the cortex or autoimmune cortical destruction. As steroid hormones decrease, the feedback loop is stimulated with excess secretion of ACTH by
the neurohypophysis. With a decrease in mineralocorticoids
and glucocorticoids, the patient develops hypotension and
hypoglycemia, respectively.
In Cushings syndrome, adrenocortical hyperactivity is
observed, and if such activity is caused by a cortical secretory adenoma or cortical hyperplasia of adrenal origin,
ACTH secretion will be shut down. Alternatively, if the
hypercorticism is the consequence of a pituitary ACTHsecreting tumor that secondarily induces an adrenal hypersecretion, then melanocyte-stimulating effects may evolve.
Patients with Cushings syndrome may be hypertensive
and hyperglycemic and may show facial edema (moon
face). In both cases, the skin may appear tanned, and the
gingiva, palate, and buccal mucosa may be blotchy. These
changes in pigmentation are due to an accumulation of
melanin granules as a consequence of increased hormonedependent melanogenesis. Endocrinopathic disease should
be suspected whenever oral melanotic pigmentation is
accompanied by cutaneous bronzing. Serum steroid and
ACTH determinations aid the diagnosis, and the pigment
will disappear once appropriate therapy for the endocrine
problem is initiated.
Dental considerations
Patients who are on chronic glucocorticoid therapy have
decrease in subcutaneous collagen and the production of
other extracellular proteins by fibroblasts, which may
explain the tendency of patients with Cushings syndrome
to bleed and to bruise easily. There may also be related
defects in the walls of small blood vessels, resulting in defective constriction of these vessels during bleeding. Wound
healing is also impaired, and scar formation is less timely
and less vigorous than in a normal subject.
Patients who are on chronic glucocorticoid therapy are
considered to be immunocompromised and more than normally susceptible to infection. Antibiotic prophylaxis is
decided on the basis of the underlying disease, however,
546

and not on the basis of glucocorticoid therapy. Patients with


Cushings syndrome are also more likely to have Candida
and fungal infections, possibly due to abnormal ora on
the skin and mucosa.
Diagnosis
The diagnosis of Cushings syndrome is based on laboratory documentation of endogenous hypercortisolism.
Hematopoietic features are leukocytosis, lymphopenia and
eosinopenia.
Radiographic features
Primary radiographic feature is generalized osteoporosis
which shows a granular pattern. This demineralization
leads to pathologic fractures. The skull shows diffuse thinning with mottled appearance. The teeth may erupt prematurely and partial loss of lamina dura may be seen.

Adrenal Insufficiency
Primary Adrenal Cortical Insufficiency
(Addisons Disease)
Primary adrenal cortical insufficiency is caused by a progressive destruction of adrenal cortex. The etiology is idiopathic or may result from hemorrhage, sepsis, infectious
diseases, malignancies, adrenalectomy or drugs leading to
deficiency of the major hormones cortisol and aldosterone.
The original description of Addisons diseasegeneral languor and debility, feebleness of hearts action, irritability
of the stomach, and a peculiar change of the color of the
skin.
Another specic symptom of primary adrenocortical
insufciency is a craving for salt. Although hyponatremia
occurs in both primary and secondary adrenal insufciency, its pathophysiology in the two disorders differs. In
the primary condition, adrenocortical insufciency is
mainly due to aldosterone deciency and sodium wasting,
whereas in the secondary form, adrenal insufciency is
due to cortisol deciency, increased vasopressin secretion
and water retention.
Signs and symptoms of adrenal insufficiency

Anorexia and weight loss


Fatigue and weakness
Gastrointestinal symptoms, nausea, diarrhea
Myalgia, arthralgia, abdominal pain
Orthostatic hypotension
Hyponatremia
Hyperkalemia
Hyperpigmentation
Secondary deficiency of select hormones
Associated autoimmune conditions.

Chapter 18 Systemic Disorders and their Clinical Implications

Secondary Adrenal Cortical Insufficiency


This is a more common condition which occurs as a result
of hypothalamic/pituitary disease, surgical removal of
pituitary gland or administration of exogenous steroids.
Withdrawal of glucocorticoids after therapy increases the
release of CRH from hypothalamic peptidergic neurons.
The pituitary is stimulated to increase ACTH secretion into
the blood. After glucocorticoid therapy, however, the
adrenal glands may be atrophied and incapable of responding appropriately to increased ACTH. The inappropriate
response to the adrenal glands as a consequence of the
negative feedback mechanism and suppression of endogenous cortisol production through suppression of ACTH,
POMC and CRH resulting in adrenal insufficiency. The
production of aldosterone which is independent of ACTH
is not appreciably affected.

Acute Adrenal Insufficiency


Acute adrenal insufficiency could be a result of fulminating septicemia caused by Pseudomonas and meningococci
leading to bilateral adrenal hemorrhage in children called
WaterhouseFriderichsen syndrome. In adults, it could be
use of anticoagulants or a coagulation disorder or a chronic
insufficiency precipitating to acute stage because of stress
or profound infection.
Diagnosis of adrenal insufficiency
In patients in whom adrenal insufficiency is merely to
be ruled out, cortisol can be measured between 0800 and
0900 hours. Hormonal pattern of morning plasma cortisol
concentrations of less than 3 g/dl (83 nmol/l) are indicative of clinical adrenal insufficiency whereas concentrations of more than 19 g/dl (525 nmol/l) rule out the
disorder.
Measurement of plasma corticotropin can be used to differentiate between primary and secondary adrenal insufciency. In patients with primary adrenal insufciency,
plasma corticotropin concentrations invariably exceed
100 pg/ml (22 pmol/l), even if the plasma cortisol levels are
in the normal range. Normal plasma corticotropin values
rule out primary, but not mild secondary, adrenal insufciency. In primary adrenocortical insufciency, basal
plasma aldosterone concentrations are low or at the lower
end of normal values, whereas the PRA or concentration is
increased because of sodium wasting.
Medical management
Primary adrenal insufficiency The primary medical needs
of addisonian patient are:
1.
2.

Management of adrenal diseaseelimination of infectious disease or malignancy


Hormonal replacement therapy.

Glucocorticoid replacement equivalent to the normal


physiologic output of the adrenals, i.e. in the range of 12.5
to 50 mg. Cortisol 2530 mg or prednisone 7.5 mg per day
would be adequate. In case of emergency inject contents
of prefilled dexamethasone (4-mg) syringe should be
injected intramuscularly and physicians help sought as
quickly as possible. Mineralocorticoid replacement in the
form of 0.051 mg of fludrocortisone and adequate sodium
intake can help addisonian patients lead a normal life.
Monitoring lying and standing blood pressure and pulse,
edema, serum potassium and plasma renin activity is
essential.
Secondary adrenal insufficiency During stress in normal
individuals, plasma cortisol levels may double, suggesting
an inherent ability of the adrenal glands to increase cortisol production by 100%. In the patient with adrenal insufficiency, adrenal function is inadequate to produce adequate
cortisol in the face of stress.
Secondary adrenal insufciency due to hypothalamic/
pituitary disease may be managed as an ACTH dependent
disorder and replaced with the missing glucocorticoid.
The clinical manifestation of adrenal insufciency usually occurs when a patient on gluococorticoids is being
withdrawn from glucocorticoid therapy or when a patient
with a previous history of glucocorticoid therapy is challenged by a stressful event. Subnormal cortisol production
during acute severe illness has been termed functional or
relative adrenal insufciency.
Many patients with chronic inammatory and autoimmune diseases such as oral lichen planus, pemphigus group
of diseases, pulmonary brosis, rheumatoid arthritis and
severe asthma are on an alternate-day dosage regimen for
glucocorticoids.
Alternate-day therapy (ADT) is usually reserved for stable chronic disease and permits the reactivation of adrenal
and pituitary function on the days during which no oral
glucocorticoid is given. For patients on long-acting glucocorticoids, especially the most potent agents, no stimulation of adrenal and pituitary function may occur on the
off therapy day because of a long drug half-life. Pituitary
ACTH production takes place mainly at night. If circulating glucocorticoid levels are still elevated in the evening
hours, the ACTH produced will be insufcient to stimulate
the adrenal glands, even during off days. This is a particular problem with multiple daily dosing with glucocorticoids
such as dexamethasone, which are most potent and which
have long half-lives.
Alternate-day therapy is a strategy for limiting adrenal
insufciency and cushingoid effect. It is best managed
by using a high morning dose (78 AM) of prednisone or
another short-acting glucocorticoid. Initially, the total
dose for the 2 days should be additive; if 20 mg is given
every day, then 40 mg will be required on the on day.
Physicians usually initiate ADT by gradually increasing
547

Section VII System Review

the on day dosage while tapering the off day dosage,


thus maintaining the total dose as a constant. In patients
with recognized adrenal insufciency, alternate-day dosage can be life-threatening if signicant stress occurs on
the off day. If the patient cannot respond to stress and
does not increase the oral glucocorticoid dosage, then
severe hypotension, nausea and shock may result. The
problem of an adequate response to stress is even more
signicant in children with severe asthma; in who inhaled
glucocorticoid therapy has been shown to cause acute
adrenal insufciency.
Hence, three things have to be considered during an
ADT:
1.
2.

3.

ADT may be approached through transition schedule


that allow the patient to adjust gradually.
Supplementary non-steroid medications may be
needed on the off day to minimize symptoms of the
underlying disease.
Symptoms occurring on the off day represent relative
adrenal insufficiency rather than exacerbation of
underlying disease.

Known severe adrenal insufficiency usually requires the


premedication of the patient with 100 mg of hydrocortisone acetate intramuscularly 30 minutes before an invasive procedure. Subclinical adrenal insufficiency may be
suspected after as little as 5 days of high-dose glucocorticoid therapy ( 60 mg of prednisone).
Salem et al (1994) have recommended the following:
1.

2.

3.

548

Minor surgical stress: 25 mg of hydrocortisone equivalent (refer to Table 5) on the day of surgery. For
instance, a patient on 5 mg of prednisone every day
may be given 5 mg of prednisone or 25 mg of hydrocortisone or equivalent preoperatively.
Moderate surgical stress: 5075 mg of hydrocotisone
equivalent may have to be given for 2 days. For
instance, a patient on 10 mg of prednisone daily should
be given 10 mg of prednisone (or parenteral equivalent) preoperatively and 50 mg of intravenous hydrocortisone intraoperatively. On the first postoperative
day 20 mg intravenous hydrocortisone can be given
8 hourly (60 mg/day). On the second postoperative day,
the dosage is then tapered to the preoperative maintenance level.
Major surgical stress: 100150 mg/day of hydrocortisone equivalent may be required for 23 days. For
instance, a patient on long-term 40 mg of prednisone/
day should receive 40 mg of prednisone (or parenteral
equivalent) preoperatively and 50 mg of hydrocortisone intravenously thereafter every 8 hourly for
4872 hours.
But a patient on long-term 5 mg of prednisone/day
should receive 25 mg of prednisone (or parenteral
equivalent) preoperatively and 25 mg of hydrocortisone

intravenously thereafter every 8 hourly for 4872 hours.


The dosage is then tapered to the preoperative maintenance level.
The steroids given are within 2 hours of surgery and readiness to face any post-surgical complications exacerbating
adrenal insufficiency, liver dysfunction, sepsis and drugs
is warranted. Certain drugs like etomidate (anesthetic),
aminoglutethimide (adrenolytic), ketaconazole lower plasma
cortisol levels. Inducers of hepatic cytochrome P45 oxygenases like barbiturates, rifampicin and phenytoin accelerate
cortisol degradation. Oral anticoagulants can be potentiated by IV high doses of methylprednisolone.
Stressful conditions that can precipitate adrenal crisis

Invasive surgical procedure


The onset of infection
An exacerbation of an underlying disease
Serious life event such as the death of a family member.

Orodental treatment evaluation of patient with adrenal


dysfunction Before the dental procedure the kind and
degree of adrenal dysfunction is to be determined in consultation with the patients physician. The risk of blood
pressure variation, osteoporosis and peptic ulcers in longterm steroid users should be considered.
The BP should be taken at baseline and monitored at
every appointment. Fractures are a risk in osteoporotic
patients and periodontal bone loss is common. Excessive
neck manipulation should be avoided in such patients.
Long-term use of NSAIDs to be considered in patients on
steroids considering the risk of developing peptic ulcers.
Use of appropriate sedation techniques minimizes stress.
Antibiotic prophylaxis A short course of antibiotic therapy is useful to prevent infections and delayed wound healing due to immunosuppressive effects of steroids when
excessive manipulations of tissues are anticipated.
Patients on daily steroid therapy for non-adrenal diseases
Patients under these circumstances are usually on a maintenance dose of 560 mg of prednisone or equivalent.
Oral examination does not require additional steroid
supplements. Non-surgical Type II and some Type III and
minor surgical procedures Type IV may induce mild to
moderate stress for which doubling the maintenance dose
to a maximum of 60 mg prednisone or equivalent on the
day of procedure tapered back to maintenance dose in
2 days would be adequate.
Invasive surgeries Type V and Type VI would require
60 mg of prednisone on the day of surgery, equivalent dose
of parenteral hydrocortisone intraoperatively and 50% of
the dosage the day after, tapered to maintenance dose over
next 23 days.
Patients on alternate day steroid therapy for nonadrenal diseases Patients under these circumstances have

Chapter 18 Systemic Disorders and their Clinical Implications

Table 6

Protocol for supplementation of patients on glucocorticoid therapy who are undergoing dental care
Protocol

Dental
procedure

Previous systemic steroid use

Current systemic steroid


use

Daily alternating systemic


steroid use

Current topical steroid


use

Routine
procedures

If prior usage lasted for 2 weeks


and ceased 1430 days ago, give
previous maintenance dose

No supplementation
needed

Treat on steroid dosage day;


no further supplementation
needed

No supplementation
needed

If prior usage lasted 2 weeks and


ceased 1430 days ago, give
previous maintenance dose

Double daily dose on day


of procedure

Treat on steroid dosage day,


and give double daily dose on
day of procedure

No supplementation
needed

If prior usage ceased 1430 days


ago, no supplementation needed

Double daily dose on first


post-operative day when
pain is anticipated

Give normal daily dose on first


postoperative day when pain is
anticipated

If prior usage ceased 1430 days


ago, no supplementation needed
Extractions,
surgery, or
extensive
procedures

comparatively less adrenal suppression than on patients


on daily dosage.
Operative procedures should be scheduled on the on
day. No alterations are required for non-surgical Type II
and some Type III and minor surgical procedures Type IV.
For Type V and Type VI procedures doubling the dose to a
maximum of 60 mg prednisone and a single dose the day
after may be required followed by resumption of normal
schedule. If general anesthesia is indicated an ACTH stimulation test to determine the response of adrenals to exogenously administered steroids (Table 6).
Mineralocorticoids The main mineral corticoid is aldosterone; cortisol has primarily a glucocorticoid effect and
partially mineralocorticoid effect.
Function of aldosterone is to increase renal tubular
reabsorption of sodium and secretion of potassium thus
regulating the K concentration in ECF, reninangiotensin
system, Na concentration and ACTH.

Aldosteronism
It is the hypersecretion of the mineralocorticoid aldosterone.

Primary Aldosteronism (Conns Syndrome)


Etiology resides within the adrenal gland. It is twice common in women aged 3050 years. Clinical features include
diastolic hypertension, headaches, muscle weakness and
fatigue. Other findings include polyuria, polydipsia and
absence of edema.
Lab findings
Hypokalemia less than 2 mEq/l, hypernatremia, metabolic
alkalosis and the assessment of ratio of serum aldosterone
to plasma renin activity.

Treatment
Aldosterone antagonistsspironolactone25 to 100 mg TDS.
Secondary aldosteronism
Increased production of aldosterone in response to activation of the reninangiotensin system. It occurs in association with the accelerated phase of hypertension or on the
basis of underlying edema disorder due to overproduction
of renin.
It may present in many forms of edemacirrhosis,
nephrotic syndrome or cardiac failure and is characterized
by hypokalemic alkalosis, moderate to severe increase in
plasma renin activity and moderate to marked increase in
aldosterone.

Disorders of Adrenal Medulla


Pheochromocytoma
Tumors of chromaffin tissue that secretes catecholamines,
90% of which are derived from adrenal medulla and rest
in sympathetic ganglia.
The familial tendency is seen along with MEN type IIA
(pheochromocytoma  medullary Ca of thyroid  hyperparathyroidism) MEN type II B (multiple mucosal neuroma
syndrome, von HippelLindau syndrome and neurobromatosis I.
Clinical features
Hypertension is the most common sign and hypertensive
paroxysms or crises are alarming. It occurs in young to
mid adult life.
Pallor, palpitations, sweating, headache, anxiety, abdominal and chest pain, vomiting, constipation, weight loss,
glucose intolerance are seen.
549

Section VII System Review

Most important aspect is the precipitation of hypertensive crisis during surgery or trauma or any activity that
displaces abdominal contents. Orthostatic hypertension
and shock are expected. Any drug is not given unless a
thorough review is done.
Adverse reactions are seen with opioid, histamines,
adrenocorticotropin and glucagons that directly release
catecholamine from the tumor; drugs like tricyclic antidepressants that block neuronal uptake of catecholamines, and
indirectly acting sympathomimetic drugs like methyl dopa.

Sex Hormones
Androgens and estrogens are the essential hormones for
sexual development and fertility. The secretion of these
hormones is controlled by the HP axis, GnRH, LH and
FSH release.
The predominantly male sexual hormone, namely, the
androgens and testosterones regulate sexual differentiation, virilization and hormonal changes accompanying
puberty, development of testes, ultimately leading to spermatogenesis and puberty.
The female sex hormones, namely, the estrogen and
progesterone are essential for development of sexual characters, menstrual cycle and ovulation.

Increased metabolic breakdown of folate (a deficiency


can inhibit tissue repair).

Estrogen and progesterone

Effect ground substance of connective tissue by increasing fluidity


Concentrations increase in saliva and fluid with increased
concentrations in serum.
Oral manifestations

Pregnancy epulis
Recurrent aphthous ulcers
Herpes labialis lesions
Candida infections.

Oral changes in menopause

Thinning of the oral mucosa


Burning mouth syndrome
Gingival recession
Xerostomia
Altered taste sensation
Alveolar bone loss
Alveolar ridge resorption
Osteoporosis.

Causes of precocious sexual development

Geriatric patient and endocrine related


manifestations

Idiopathic
Gonadal disease
Adrenal disease
Hypothalamic disease
(e.g. Gonadotropin independent/dependent precocious
puberty, McCuneAlbrights syndrome).

Hypogonadism, disorders of male reproductive system and


sexual differentiation are seen in chromosomal abnormalities
like Klinefelter syndrome, Turner syndrome, cryptorchidism among a few. Klinefelter syndrome shows dental
anamolies like taurodontism.
Effects of estrogen and progesterone on oral tissues
Estrogen

Increases cellular proliferation in blood vessels (known


in the endometrium)
Decreases keratinization, while increasing epithelial
glycogen.
Progesterone

Increases vascular dilation, thus increases permeability (result in edema and accumulation of inflammatory cells)
Increases proliferation of newly formed capillaries in
gingival tissues (increased bleeding tendency)
Alters rate and pattern of collagen production.
550

Impaired glucose tolerancediabetes mellitus


Reduced thyroxin clearance and production
Increased ADH, reduced renin and aldosterone leading
to decrease in Na and increased K
Decreased testosterone leading to impotency
Decreased estrogenburning mouth syndrome and
osteoporosis
Decreased vitamin D absorption and activation leading to osteopenia and fractures.

PREGNANCY
Pregnancy is one condition where endocrine changes are
the most significant alterations due to production of
maternal and placental hormones.
Dental management guidelines during pregnancy

Developing rapport with the patient thereby reducing


anxiety since it is always a very emotional experience
for an expectant mother.
Detailed medical history and consultation with the
patients obstetrician and physician.
Monitoring vital signs and blood examination because
of development of anemia and folate deficiency during
pregnancy.

Chapter 18 Systemic Disorders and their Clinical Implications

Patient in the third trimester if positioned in a supine


position may suffer from supine hypotensive syndrome
due to compression of inferior vena cava by the uterus.
A left lateral positioning of the patient in such situation
is advisable. Always a short appointment semi-reclined
position, often changing of position is advisable.
Pregnant patients of abnormal food habits, high sugar
diet, high gag reflex and vomiting especially in the
first trimester causing high rate of caries and enamel
erosion.
Preventive program to develop healthy oral environment. Studies have shown that reducing streptococci
count in mother reduces incidence of caries in the
child.
Prenatal fluoride 2.2 mg/day in the second and third
trimesters reduces incidence of caries in the child.
Odontogenic infections, sepsis and febrility have known
to cause miscarriage.
Elimination of periodontal irritants reduces chances
of pregnancy gingivitis and pregnancy tumor. Moreover, patients with periodontal infections have higher
chances of miscarriage, preterm birth and low birth
weight.
Second trimester is the safest period for elective dental
treatment.

Prescription of drugs
It is always safe to avoid any drug during pregnancy especially during first trimester when the organs are in the formative stage. The drugs may cross the placental barrier
and may be toxic or teratogenic to the fetus since the liver
and kidneys are still immature.
In unavoidable circumstances the drugs that are
approved only may be given.
Anesthetics Local anesthetics with adrenaline are relatively safe with required amount eventhough they cross the
placental barrier. Lidocaine and prilocaine are safer than
bupivacaine, which can cause fetal bradycardia.
Analgesics The analgesic of choice is paracetamol. Ibuprofen is the next choice but is best avoided in the second
trimester. Other NSAIDs can constrict ductus arteriosus,
postpartum hemorrhage and delayed labor especially in
the third trimester. Prolonged high dose of opioids leads to
congenital abnormalities and respiratory depression.
Antibiotics Penicillins, erythromycin (except in etiolate
form) second and third generation cephalosporins, metroinidazole and clindamycin are considered safe. However,
an increased dose or more frequent administration may
be needed as the volume of distribution is increased in
pregnancy.
Tetracycline is contraindiacated as it chelates to
hydroxyapatite of developing teeth and causes enamel
hypoplasia.

Anxiolytics Benzodiazepines and barbiturates are best


avoided because of cleft palate development on prolonged
exposure or neonatal respiratory depression.
Nitous oxide is better used only in the second and third
trimesters and not more than 30 minutes with at least 50%
oxygen to prevent hypoxia.
Corticosteroids

Prednisone can be safely used.

Oral manifestations

Pregnancy gingivitis and pyogenic granuloma mostly


in the labial aspect of interdental papilla. It starts
around the 2nd month and continues until after parturition and regresses.
Dental caries and enamel erosion and halitosis.
Because of abnormal food habits and gastric regurgitation.
Chloasma gravidarum, pigmented lesion of the skin
and mucosa may have to be differentiated from other
pigmentation disorders.
Radiographs in pregnancy
Exposing the patient to X-radiation should be avoided during pregnancy because of the possible stochastic effects
(uncertain effects) especially during the first trimester because
the developing fetus is susceptible to radiation damage.
Under unavoidable circumstances exposing the patient
for dental radiographs is considered safe provided precautionary measures in minimizing radiation are established,
such as use of F-speed lms, digital sensors.
Long cone technique (200 mm FSD) ltration and rectangular collimation and use of lead aprons.
When a lead apron is used during contemporary dental
radiography the gonadal and fetal effective is less than
0.01 Sv (microsieverts). No increase in gross congenital
anamolies or intrauterine growth retardation due to exposure during pregnancy has been observed up to less than
510 cGy.
Autoimmune polyendocrinopathy-candidiasis-ectodermal
dystrophy (APECED), also called autoimmune polyendocrine syndrome (APS) type I, is a rare autosomal recessive
disease with a complex picture discovered over decades.
Chronic mucocutaneous candidiasis (MC), hypoparathyroidism (HP) and adrenocortical failure (AF) are its most
common components. To dene APS type 1, at least two of
the three major components need to be present.
1.

2.

Chronic candidiasis and T cell defect: In most cases of


APS type 1, chronic candidiasis is the first manifestation of the disease, often occurring before the age of
5 years.
Chronic hypoparathyroidism and parathyroid autoantibodies: In the course of APS type 1, candidiasis is
followed by chronic hypoparathyroidism, which usually appears before the age of 10 years and affects
551

Section VII System Review

3.

70100% of patients. When chronic hypoparathyroidism develops during the neonatal period, it is important to differentiate this from genetic diseases such
as DiGeorges syndrome (caused by a 22q11 deletion)
KenneyCaffey disease (locus mapped to chromosome
1q42q43), or the Barakat syndrome (caused by
GATA3 haploinsufficiency).
Addisons disease (AD) and adrenal cortex autoimmunity: In the course of APS type 1, AD tends to be the
third disease to appear after chronic candidiasis and/
or hypoparathyroidism, and it develops usually before
15 years of age and affects 2293% of patients. In most
cases the disease is heralded by the presence of adrenocortical autoantibodies (ACA), frequently found at the
onset of the other main clinical manifestations of this
type of APS (candidiasis and/or hypoparathyroidism).

Systemic lupus erythematosus


A hormonal component to SLE is suggested, by its high
incidence in women in their child bearing years, the many
reports of remission during pregnancy, and the finding of
increased estrogen levels in SLE patients suggest an endocrinal role.

Multiple Endocrine Neoplasia Type III


(Multiple Mucosal Neuroma Syndrome)
Multiple endocrine neoplasia types I to III (MEN I, II,
and III) is a group of familial syndromes in which neoplastic change occurs in several endocrine glands in one
individual.
MEN I involves lesions in some combination of pancreatic islets, adrenal cortex, and parathyroid and pituitary
glands; it includes ZollingerEllison (or gastrinoma) syndrome, in which multiple primary gastrin-secreting adenomas or adenocarcinomas are located in the pancreas,
duodenum, or even extra-abdominal sites such as the
parathyroid gland. Stomach ulceration and hyperplasia of
the pancreatic islets and parathyroid glands develop secondary to the excess gastrin release and account for the
characteristic presenting symptoms. Between one-quarter
and one-half of gastrinomas have other features of the
MEN I syndrome, which is not associated with any skin or
oral phakomatosis.
MEN II A which involves medullary carcinoma of the
thyroid gland, pheochromocytoma of the adrenal medulla,
and parathyroid hyperplasia or adenoma, is not associated
with any phakomatosis.
MEN II B or MEN III, a subgroup of these patients
exhibits multiple neuromas of the commissural mucosa
(which is characteristic) lips, tongue, and buccal, conjunctival, nasal, and pharyngeal mucosae, in association with
their endocrine neoplasia (this is referred to as multiple
mucosal neuroma syndrome). Since these neuromas may
552

occasionally predate any overt endocrine neoplasia, the


recognition of these oropharyngeal lesions as possible
evidence of MEN III can lead to the early and sometimes
successful treatment of the associated malignancies like
thyroid carcinoma which has a poor prognosis occurring
in 18 to 25-year-old individuals. Thickening of the lip
a characteristic bumpyor blubbery lip appearance is seen.
Marfanoid habitus, caf au lait spots, lentigines and a history of diverticulosis or lower-bowel surgery are the features.
The nding of oral mucosal neuromas in association with a
family history of carcinoma of the thyroid or pheochromocytoma clearly indicates a need to search for other evidence
of this syndrome. Endocrine abnormalities are also sometimes present in patients who have other inherited syndromes
with neoplastic associations, such as neurobromatosis 1,
McCuneAlbrights syndrome and von HippelLindau syndrome. These conditions are usually excluded from the
denition of multiple endocrine neoplasias.
Diffuse endocrine system
This group of widely scattered endocrine tissues consisting
of AUPD cells, are called so because of their properties
a high content of amines; the capacity of amine precursor
uptake; the presence of amino acid decarboxylase. The
cells of these tissue contain characteristic granules and
secrete polypeptides and amines. The origin of the tissues
is believed to be from the neural crest cells. Neuroendocrinal
tumors are rare in the oral cavity.
Merkel cell carcinoma or (MCC) or neuroendocrine carcinoma It is a rare but aggressive malignancy of the skin
with a rare intraoral occurrence. Only 14 cases of intraoral
Merkel cell carcinoma have been reported (Yoshida et al,
2001).
Factors strongly associated with the development of
MCC are:

Age more than 65 years


Sex predilectionmales
Fair skin
History of extensive sun exposure
Chronic immune suppression (e.g. kidney or heart
transplantation or HIV)
Association with other premalignant and malignant
skin lesions
Common sites in the head and neck region are the
cheeks, nose, mouth, eyelids and periocular region.
Clinical presentation
The common clinical findings include a nodule with or
without ulceration. The nodule may be usually firm and
erythematous. Pain may or may not be an associated feature. MCC very rarely occurs on mucous membranes of the
head and neck region, and it carries a particularly poor
prognosis.

Chapter 18 Systemic Disorders and their Clinical Implications

SALIVA AND MONITORING OF HORMONE


LEVELS
Saliva can be analyzed as part of the evaluation of endocrine function. The majority of hormones enter saliva by
passive diffusion across the acinar cells. Most of these hormones are lipid soluble (i.e. steroids). Small polar molecules
do not readily diffuse across cells and instead enter saliva
through the tight junctions between cells. The molecularweight cut-off for ultrafiltration is 100200. This relatively small molecular size prevents many hormones from
entering saliva from serum by means of ultrafiltration. In
addition, active transport does not appear to facilitate hormone transfer into saliva. Measurements of salivary hormone levels are of clinical importance if they accurately
reflect the serum hormone levels or if a constant correlation
exists between salivary and serum hormone levels. For
neutral steroids which diffuse readily into saliva, salivary
hormone levels represent the free serum hormone levels.
Conversely, due to their size, protein hormones do not enter
saliva through passive diffusion, but primarily through
contamination from serum as a result of outflow of gingival crevicular fluid (GCF) or from oral wounds. Furthermore,
some steroid hormones can be metabolized in the salivary
epithelial cells by intracellular enzymes during transcellular diffusion, which can affect the availability of these
hormones in saliva.
Due to their lipid solubility, steroid hormones can be
detected in saliva. Salivary cortisol levels demonstrate
excellent correlation with free serum cortisol levels. However, the actual salivary cortisol levels are lower than the
serum-free cortisol levels, possibly due to enzymatic degradation in the salivary epithelial cells during transcellular
diffusion. Salivary cortisol levels were found to be useful in
identifying patients with Cushings syndrome and Addisons
disease and also for monitoring the hormone response to
physical exercise and the effect of acceleration stress.
Contrary to cortisol, salivary cortisone, prednisone and
prednisolone levels do not accurately reect serum cortisone levels. Cortisone is a neutral steroid and therefore
readily diffuses into saliva; however, cortisol is converted
to cortisone by an enzyme present in the salivary glands
(11 -hydroxysteroid dehydrogenase). Thus, cortisone levels in saliva are higher than in serum and do not bear any
diagnostic signicance.
Salivary aldosterone levels have demonstrated a high
correlation with serum aldosterone levels with the use of a
solid-phase enzyme immunoassay. Increased aldosterone
levels were found in both the serum and saliva of patients
with primary aldosteronism (Conns syndrome).
Testosterone and dehydroepiandrosterone have also been
identied in saliva. Salivary concentrations were found
to be 1.57.5% of the serum concentrations of these hormones with direct radioimmunoassay technique. Monitoring

salivary testosterone levels may also be useful in behavioral studies of aggression, depression, abuse, violent and
antisocial behavior.
Estradiol can be detected in saliva in concentrations
that are only 12% of serum concentrations. These concentrations are similar to the serum concentrations of free
estradiol, which can diffuse into saliva. Salivary estradiol
levels followed the same trends as serum estradiol levels
during a menstrual cycle. Furthermore, salivary estriol
levels showed a very high correlation with serum levels of
free estriol in pregnant women, and salivary estriol levels
were suggested as a means for the assessment of feto-placental function.
Salivary progesterone levels showed good correlation
with serum levels during the menstrual cycle and reected
the free serum progesterone levels. Salivary progesterone
levels can be useful for the prediction of ovulation, with
serum progesterone levels, and salivary estradiol and progesterone levels can be used for the evaluation of ovarian
function. Decreased salivary estriol is suggested as a marker
of fetal growth retardation. Furthermore, an increased salivary estriol-to-progesterone ratio may be a predictor of
pre-term delivery.
In general, serum and salivary levels of protein hormones are not well correlated. These hormones are too
large to reach saliva by means of passive diffusion across
cells or by ultraltration, and the detection of these hormones in saliva is primarily due to contamination from
serum through GCF or oral wounds. Therefore, serum levels of protein hormones such as gonadotrophins, prolactin
and thyrotropin cannot be accurately monitored by means
of salivary analysis (Vining and McGinley, 1986, 1987).
Salivary monitoring of hormone levels has many advantages over the more conventional serum analysis. Hormone
evaluation often necessitates multiple sample collection in
a relatively short time interval, which makes the noninvasive collection of saliva ideal for this purpose. However,
it is important to consider the possible limitations of salivary analysis for hormone evaluation. Hormones enter
saliva by passive diffusion and ultraltration, and active
transport of hormones into saliva does not exist. Therefore,
mostly lipid-soluble and hormones with small molecular
weight can be detected in saliva. Most hormones are
protein-bound in serum, and thus salivary hormone levels
represent the free hormone levels which are available for
diffusion into saliva. This may provide more clinically useful information, since free serum hormone levels are the
biologically active fraction of hormone in serum. For accurate results, a constant and predictable correlation must
exist between salivary and serum hormone levels. However,
different hormones are bound to similar serum carrier proteins, and thus changes in levels of one hormone may
affect the free levels of others. For hormones that demonstrate a constant but low salivary-to-serum ratio, a sufciently large sample volume or a more sensitive analysis
553

Section VII System Review

method is required. In addition, many hormones exhibit


marked circadian variations. Therefore, timing of saliva
collection may affect the results. The salivary ow rate
can also affect the concentrations of certain hormones. An
increase in salivary ow rate will usually result in reduced
concentrations of molecules that reach saliva by diffusion.
However, the rate of diffusion of steroid hormones, particularly cortisol, is usually high enough to maintain a constant relationship between salivary and serum levels of the
hormone regardless of the salivary ow rate. The concentrations of hormones that reach saliva by ultraltration,
such as dehydroepiandrosterone sulfate, are more affected
by changes in salivary ow rate. Changes in salivary ow
rate may lead to changes in salivary pH. This may affect
the entry into saliva of molecules according to their pKa.
The stability of hormones in saliva is important as well for
accurate evaluation. Hormones in saliva can be degraded,
among other ways, by enzymes native to saliva, enzymes
derived from oral microorganisms, and enzymes derived
from leukocytes that enter the oral cavity from the gingival sulcus. In addition, molecules that reach saliva by passive diffusion across cells, like unconjugated steroids, may
be subjected to enzymatic degradation within the salivary
glands, prior to entering saliva. These factors have to be
considered when saliva is evaluated as an alternative for
the evaluation of serum hormone levels.

MENTAL HEALTH AND ITS RELEVANCE TO


DENTISTRY
This section aims at equipping the reader with skills to
recognize the commonly seen mental illness. In addition
to giving a broad overview of mental illness and present
day psychiatric practice we intend to focus on the interface between dentistry and psychiatry. We will also give
you a broad overview of the treatment options available
in psychiatry. In addition to making you confident in recognizing the mental illness to refer them to psychiatry,
this section will give you confidence in dealing with the
mentally ill when they develop dental problems.

History of Psychiatry
Tracing the timeline backwards, in 10,000 BC there was no
difference between medicine, magic and religion. Looking
at the history of medicine it may seem that Psychiatry as
a specialty is relatively new. However the history of Psychiatry dates back to more than 2,000 years when medicine itself had its birth as Science in ancient Greece. In
the ancient world, Psychiatric illness was believed to come
from the Gods and the curse of the devils. People have
always been fascinated and puzzled, not being able to
understand insanity. It is interesting to note the varying
554

perceptions of the public, media, arts and the society at


large toward the mad among us.
For centuries mental health problems and their treatments has been the realm of not only physicians but also
a range of other professionals including faith healers. Till
the 18th century the mentally ill were secluded in institutions and asylums. In the next stage, mid 18th century,
some physicians in England and France started recognizing themselves as having a special interest in dealing with
mental health. But still there was no treatment available
and the mentally ill were chained at large. It was Philippe
Pinel, a French physician who in 1793 started an initiative
toward the moral treatment of the mentally ill and liberated the insane from their chains.
The rst half of 20th century saw the accidental discovery of malaria being therapeutic for psychosis in tertiary
syphilis. This led to the dangerous practice of injecting
milk to induce fever. Inducing seizures by insulin coma
therapy or injecting camphor oil which was considered
a successful treatment for schizophrenia then is largely
barbaric this day in age. The biggest breakthrough for
Psychiatry came in the 1950s with the discovery of chlorpromazine and the First World Congress of Psychiatry at
Paris. Since then Psychiatry has probably seen the invention of numerous new medications, perhaps much more
than most other branch of medicine. However, present day
psychiatry has outgrown the medical model and has incorporated a bio-psycho-social model both for understanding and treating mental illness.

Concepts of Mental Illness and


its Classification
Similar to using the word illness loosely in everyday
speech, the word mental illness is used with little precision in psychiatric practice, and often synonymously with
mental disorder. In this context, mental and psychiatric
are also used interchangeably. A very diverse discussion of
the concepts of mental illness can be found in the works
of Lazare (1973), Kendell (1975), Hafner (1987) and Clare
(1997). It is probably beyond the scope of this discussion
to go into the depths of these concepts.

Definitions of Mental Illness


There have been numerous attempts to define mental illness
but none have been satisfactory and uniformly accepted.
One of the common approaches is to examine the concept
of illness as in general medicine and to identify any analogies with mental illness. In general medicine there are five
types of definitions:

Absence of health
Disease is what doctor treats
Biological disadvantage

Chapter 18 Systemic Disorders and their Clinical Implications

Pathological process
Presence of suffering.

Efforts to classify psychiatric disorders have been tried by


many over the years. Since there are no definite diagnostic
tests such as radiograph for fracture or blood test for malaria
we need different tools to provide a conceptual framework
to the psychiatric illness. Having a classificatory system
helps us to communicate with other professionals and to
decide on treatment and prognosis.

The five axes of DSM IV


Axis I

Clinical syndrome and conditions not attributable to mental


disorder that are the focus of attention and treatment

Axis II

Personality disorders

Axis III

Physical disorder and conditions

Axis IV

Severity of psychological stressors

Axis V

Highest level of adaptive functioning in the last year

Criticisms of classifications

Current Psychiatric Classifications


The two major classificatory systems in use for the psychiatric disorders are the ICD (International Classification
of Diseases)-10 and the DSM (Diagnostic and Statistical
Manual) IV and it is important to have the basic understanding of both.
International Classification of Diseases (ICD)-10,
Chapter V
The ICD is proposed by the World Health Organization
(WHO) as an aid to the collection of international statistics
about disease. The system is revised every few years and
the current edition is the tenth (ICD-10). It has 22 chapters
in it and the fifth chapter is devoted to psychiatry.
Main categories of ICD-10 Chapter V (F)
F0009

Organic including symptomatic mental disorders

F10F19

Mental and behavioral disorders due to psychoactive


substance use

F20F29

Schizophrenia, schizotypal and delusional disorders

F30F39

Mood (affective) disorders

F40F49

Neurotic, stress related and somatoform disorders

F50F59

Behavioral syndromes associated with psychological


disturbances and physical factors

F60F69

Disorders of adult personality and behavior

F70F79

Mental retardation

F80F89

Disorders of psychological development

F90F99

Behavioral and emotional disorders with onset usually


occurring in childhood or adolescence

There is no doubt that classification is needed in psychiatry and it helps the clinicians to communicate with one
another about the diagnoses given to a patient and it helps
to understand the implications of the diagnoses, in terms
of their symptoms, prognosis, treatment and sometimes
etiology. However, such classifications, on many occasions
are criticized as being inappropriate or even harmful. It can
be argued that allocating patients to a diagnostic category
distracts form the understanding of their unique personal
difficulties. It is important to combine the two because these
qualities can modify prognosis and these personal difficulties should be taken into account for a holistic treatment
of the disorder. It is also worth noting that some conditions
could be sub-threshold and resemble the disorders in the
classification but do not meet full diagnostic criteria. It is
not infrequent to see such patients presenting to a variety
of services other than psychiatry. These sub-threshold conditions are however clinically significant and it is important to recognize these conditions to reduce the psychiatry
morbidity or comorbidity.

Diagnostic Criteria and Screening Questions


We intend to introduce the readers to the common psychiatric illnesses. This section should familiarize you with the
brief epidemiological details, diagnostic criteria and screening questions to be used in everyday practice.
A functional psychiatric illness should always be diagnosed after ruling out any physical condition that can
explain the presentation. For example, a middle-aged lady
with hypothyroidism may present with depression as the
only symptom. It is important to be aware of this aspect
as any psychiatric presentation could be mimicked by an
organic condition or by alcohol/illicit drug use.

Diagnostic and Statistical Manual (DSM)


The DSM is produced by the American Psychiatric Association (APA). The first edition, DSM-I was published in 1952
as an alternative to the widely criticized ICD-6. It seems
that the DSM-I was strongly influenced by the views of
Adolf Meyer and Karl Menninger. Its simple glossary reflects
the acceptance of the then prevalent psychoanalytic ideas
in the United States. The current version is the DSM IV
and it has five axes as shown below.

Alcohol and substance use


The available epidemiological data suggests a combined
1 year prevalence rate of alcohol misuse and dependence
to be 710% (Kessler et al, 1994). An understanding of the
effects of alcohol and other substances of abuse (tobacco,
heroin, cannabis, cocaine) is important for the practice of
dentists. When such patients present with oral complications
of prolonged substance misuse, in addition to treating the
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Section VII System Review

oral condition it becomes important to liaise with the mental health services to treat the dependence. We aim to equip
you to diagnose these dependence syndromes with the diagnostic criteria which are common for all substances.
Three or more of the following to be present during the previous
year
1. Strong desire or a sense of compulsion to take the substance
(craving)
2. Difficulty in controlling substance taking behavior (loss of control)
3. Physiological withdrawal symptoms when substance use is reduced,
e.g. tremousless, anxiety and lack of sleep with alcohol withdrawal
4. Need to increase the intake over a period of time to get the same
effect (tolerance)
5. Neglect of alternative pleasures or interests (salience)
6. Continuing to use despite knowing it to be harmful
World Health Organization, 1992.

A commonly used screening tool for alcohol is CAGE which


can be administered in a minute or less is shown in the
box below.
CAGE questionnaire
1. Have you ever felt you should cut down on your drinking?
2. Have people annoyed you by criticizing your drinking?

lasts for more than 2 weeks duration. It has to be differentiated from normal sadness. Such patients have impaired
patterns of mood, thoughts and behavior which sometimes
lasts for a long period of time. It causes a lot of distress to
the person and impairs his/her quality of life. It is also
accompanied by a high rate of suicide which is at least 7%
in men and 1% in women (Blair-West et al, 1999; Weissman
et al, 1996). The 12-month prevalence of depression in the
community is between 2 and 5% and the lifetime rate lies
between 10 and 20% (Alonso et al, 2004). In 2000, the
WHO identified major depressive disorder as the fourth
ranked cause of disability and premature death in the
world (Murray and Lopez, 1997). WHO has projected that
by 2020, major depression will rise in disease burden to be
second only to ischemic heart disease. This disorder is very
common all over the world with a lifetime prevalence rate
of 17% and a recurrence rate of more than 50% (Kessler
et al, 1994; Weissman et al, 1996). People with chronic disease have a higher chance of developing depression. It is
40% for people with coronary artery disease and 25% for
patients with cancer (Musselman et al, 1998; Patten, 1999).
Neurological disorders associated with a higher frequency
of depression include multiple sclerosis, Parkinsons disease, head trauma and stroke (Patten et al, 2000; Poewe
and Luginger, 1999). Around one-third of patients with
depression develop alcohol or illicit substance misuse in
their lifetime (Baker and Dawe, 2005).

3. Have you ever felt bad or guilty about your drinking?


4. Have you ever had a drink first thing in the morning to steady your
nerves or to get rid of a hangover (eye opener)?

Most people with depression have five or six of the following:

Each Yes is scored 1 point. Score of 2 suggests significant alcohol


problems.

Feeling sad most of the time (but may feel a little better in the
evening)
Lose interest and enjoyment in life (anhedonia)
Feeling tired easily with reduced energy levels

List of commonly misused drugs

Reduced concentration in day-to-day tasks

Amphetamines

Cocaine

Find it harder to make decisions

Speedball

Heroin

Cannot cope with things that they used to

Cannabis, hashish

LSD

Feel restless and agitated

Ecstasy, ketamine

Inhalants

Lose appetite and weight

Steroids

Ether

GHB

Glue

Take 12 hours to get off to sleep, and then wake up earlier than
usual

Ritalin, diet pills, rush

THC, marijuana

Lose interest in sex

Barbiturates, Valium, Ativan

Speed

Loss of self-confidence

Opium

Crack

Feel useless, inadequate and hopeless

PCP, Angel dust

Morphine, methadone

Avoid other people

MDA, MDMA

Crystal meth

Feeling guilty about trivial issues

Grass

Freebase

Feel irritable
Feel worse at a particular time each day, usually in the morning

Depression
Depressive disorder also known as major depressive disorder or unipolar depression is a psychiatric illness which

556

Having ideas or acts of self-harm or suicide


Have a bleak and pessimistic view of the future
World Health Organization, 1992.

Chapter 18 Systemic Disorders and their Clinical Implications

Psychoses including schizophrenia and


delusional disorders
In psychotic illnesses patients suffer from strange and
unusual experiences and beliefs that are beyond our
understanding. Schizophrenia is a mental disorder that
affects around 1 in every 100 people. In one-third of the
patients it can can become severe and enduring. The most
common symptoms are hallucinations and delusions.
A hallucination is a phenomenon where people hear, see,
feel or smell something when there is nothing or nobody
to account for it. In functional psychotic illnesses the most
common is hearing voices that seem to be utterly real and
coming from the outer world although other people cannot
hear them. These voice/voices can either talk directly to
the patient or talk to each other about the patient. The
patient might report that he/she is overhearing a conversation. Though the voice can be pleasant they are more often
rude, critical and abusive, irritating and sometimes commanding. These commanding hallucinations increase the
risk of harm to self and signicant others.
Delusion is belief that the patient holds with complete
convictions although it seems to be based on a misinterpretation or misunderstanding of the situation or event. When
we ask the patient why they believe in it, their reasons do not
make sense to us or they say that they cannot explain it and
they just know it. So it is customary to dene delusion
as a false unshakable belief, which is out of keeping with the
patients social and cultural background (Hamilton, 1984).
The most common in this category are paranoid delusions
and delusions of reference or ideas of reference. The paranoid delusions or delusional ideas make the patient feel
persecuted or harassed. For example, the patient might
believe that he/she is being inuenced by the neighbours
who are using special powers or technology. Another example is where the patient starts to believe that his/her partner
is unfaithful. This belief is based on odd details that seem
to have nothing to do with sex or indelity. In such cases
other people see nothing to suggest that the belief might
be true. Ideas of reference occur when the patients start
getting a special meaning in ordinary day-to-day events
and believe that they are specially connected to them. For
example, radio or television programs are about them or
people are communicating to them in odd ways, such as
through the color of cars in the street.
People with a more severe form of psychosis suffer
from thought disorder in which their thought process is
muddled. Their ideas are disconnected in such a way that
it is hard for other people to understand. Some patients
experience as if their feelings or actions are controlled by
an external agency as if they are being controlled like a
puppet or a robot. So people experience as if their thought
process is being interfered with. It could be that their
thoughts are vanishing as though someone is taking them

out of their mind or as if the thoughts in their mind are not


their own, but someone else has put them in their mind.
While patients with schizophrenia experience any of the
above core psychotic symptoms, delusional disorders are
characterized by either a single delusion or a set of related
delusions which are usually persistent and sometimes lifelong. These delusions are clearly personal rather than being
subcultural and occur in the absence of brain disease.
Auditory hallucinations if present are only occasional
(WHO, 1992). The delusional disorders are generally more
difcult to treat. Though most of the times psychosis is
just picked up from the patients conversation, the box below
gives a list of screening questions.
These questions only form a guide to clarify when you suspect
something abnormal and only the most relevant questions should
be asked keeping in mind the educational and cultural background:
Persecution
How do you get on with others?
Do you believe that people are trying to harm you or make your life
miserable?
Is there a plot to cause harm to you?
Reference
Do people talk behind your back?
Do things seem specially arranged for you?
Do you see any reference to yourself in the TV or newspaper?
Grandiosity
How do you see yourself compared to others?
Do you have any special powers or abilities?
Are you specially chosen in any way?
Thought disorder
Are you able to think clearly?
Is there any sort of interference with your thinking process?
Do you think people around you can read your mind?
Always check for conviction, explanations and coping
How do you know this is the explanation?
Could it be your imagination or your mind playing tricks?
What do your family and friends think about this problem?
What do you intend to do about this problem?

Anxiety, stress-related and somatoform


disorders
Anxiety is a normal human feeling and we all would have
experienced it when faced with situations that we find difficult or threatening. The best example would be an examination or interview. Often people refer to it as stress
which is confusing and can mean different things. It may
refer to things that make one anxious or on the other hand
it could be a reaction to being faced with anxiety provoking situations. It is important to differentiate anxiety
from worry and fear. When anxiety is a result of a continuing problem like financial problem we call it worry.
A sudden response to an immediate threat like looking over

557

Section VII System Review

a cliff is fear. Both fear and anxiety can be helpful, helping us to avoid dangerous situations, making us alert and
motivating us to deal with problems. However, if it becomes
too strong or goes on for too long it can interfere with our
daily activities and make our lives miserable.
Anxiety causes numerous physiological (in the body)
symptoms and cognitive symptoms (in the mind) shown in
two separate boxes below.
Physiological symptoms of anxiety
Irregular hear beats (palpitations)
Sweating
Muscle tension and pain
Shakes and tremors
Butterflies in the stomach
Tightness in the chest
Breathing heavily
Dizziness
Faintness
Indigestion
Diarrhea

Cognitive symptoms of anxiety


Fear of going mad
Fear of passing out or imminent death
Fear of having a heart attack
Fear of a serious physical health problem
Feeling worried all the time
Feeling excessively tired
Unable to concentrate
Feeling irritable
Sleep problems

Phobias and social phobia


Phobia is fear of a particular situation or particular things
that are not dangerous and which most people do not
find it dangerous. We all have fears about things such as
height and spiders but, for most of us, these fears do not
interfere with the way we lead our lives. These fears are
called phobias only when they interfere with things we
would otherwise enjoy or do easily. A person with phobia
has the same intense symptoms of anxiety described above
but these arise only in the particular situations that
frighten them. At other times they do not feel anxious.
For example, a person with phobia of dogs is comfortable
when there are no dogs around. However, phobia makes
the person avoid situations in which they know they will
be anxious. This avoidance actually makes the phobia
worse as time goes on. Over time the persons life becomes
increasingly dominated by the precautions he/she needs to
558

take to avoid the fearful situation. This avoidance behavior keeps expanding to include more and more situations
and circumstances. The sufferer usually knows that there is
no actual danger, may feel silly about this fear but still is
unable to control it. Such a phobia can start after a distressing or a traumatic experience, many a times in early life.
Many of us worry before meeting new people and before
going to parties but once we are there we can cope and
enjoy the situation. Some people become very anxious about
such situations, cannot enjoy them and at worse totally
avoid such social situations. This condition is called social
phobia. Such people tend to worry about becoming the
center of attention wherever they nd themselves among
people. They worry that everybody is looking at them and
watching what they are doing. At their worst, these feelings of fear and bodily symptoms can end up in a panic
attack. A panic attack lasts for a few minutes during which
the person feels overwhelmingly anxious and is terried
of losing control, going mad or dying. These feelings reach
a peak and then pass off rapidly leaving the person feeling
weak and exhausted.
Panic disorder
Panic disorder is a type of mental illness with recurrent
and unexpected intense episodes of anxiety called as panic
attacks. A panic attack is characterized by intense apprehension and terror accompanied by physical symptoms
like palpitations, chest pain, dizziness, sweating and difficulty in breathing. These attacks have an abrupt onset
and peak in intensity within 10 minutes. These attacks are
not associated with any external event or situation and
come out of the blue. Such episodes often result in calls to
paramedics and visits Accident and Emergency Department.
Panic disorder could sometime be a lifelong illness that
remains only partially responsive to treatment. Women
appear to have more severe form of the disease than men
(Yonkers et al, 1998) and is much more commoner in women
(Barzega et al, 2001; Kessler et al, 1994).
Agoraphobia
The term agoraphobia means fear of open spaces. Such
people not only fear open spaces but also presence of a
crowd. They fear not having an immediate and easy escape
to a safe place (usually home). Such patients generally
have a fear of leaving home, fear of entering shops, crowds,
public places, or of traveling alone in trains, buses, or
planes. The severity of anxiety symptoms and the extent
of avoidance varies from patient to patient. However, for
some people it is the most incapacitating of all phobic
disorders and they become completely housebound. Some
people are terrified by the thought of collapsing and being
left helpless in the public. The lack of an immediately
available exit seems to be a key feature in these patients
with agoraphobia who tend to be women in early adult life.

Chapter 18 Systemic Disorders and their Clinical Implications

Depression and social phobia may also be present but do


not dominate the clinical picture.
People feel grief-stricken, depressed, anxious and angry
after a traumatic experience. A traumatic event is where
one is in danger; ones life is threatened or sees other people dying or being injured. The condition is called posttraumatic stress disorder (PTSD) when one starts re-living
the trauma again and again in the form of ashbacks
during the day or nightmares in sleep. In addition, they
start avoiding related situations, become emotionally
numb and hypervigilant, unable to relax. The emotional
reaction in stress is often accompanied by other symptoms
of anxiety listed in the boxes on page 558.
The questions in the box below help you to screen for
the anxiety disorders.
Panic attacks
Have you had spells or attacks when you suddenly felt anxious,
frightened, uncomfortable or uneasy, even in situations where most
people would not feel that way? Did the spells surge to a peak,
within 10 minutes of starting?
Do you feel anxious or uneasy in places or situations where you
might have a panic attack or panic-like symptoms, or where help
might not be available or escape might be difficult: like being in
a crowd, standing in a queue, when you are away from home or
alone at home, or when crossing a bridge, traveling in a bus, train
or car?
Social phobia
Have you been fearful or embarrassed of being watched, being the
focus of attention, or fearful of being humiliated? This includes things
like speaking in public, eating in public or with others, writing while
someone watches, or being in social situations.
Post-traumatic stress disorder
Have you ever experienced or witnessed or had to deal with
an extremely traumatic event that included actual or threatened
death or serious injury to you or someone else? Examples of
traumatic events include serious accidents, sexual or physical
assault, a terrorist attack, being held hostage, kidnapping, fire,
discovering a body, sudden death of someone close to you,
war, or natural disaster.
Have you had a dental appointment or a medical intervention in
the past which you found significantly traumatic? What was the
reason you found it to be traumatic? Was it because you were not
adequately prepared due to lack of information as to what was
going to happen?

Obsessive compulsive disorder


We commonly use phrases like, Hes an obsessive cricket
fan, and Shes a compulsive liar. We use these phrases
when people do things again and again, and others cannot see any reason for it. The essential features of this
disorder are recurrent obsessional thoughts and compulsive acts. Obsessions are patients own thoughts which are
repetitive and intrusive. These thoughts are almost invariably distressing to the patient, because they are violent or

obscene or simply because they are perceived to be senseless.


The person often tries to resist these thoughts but is unsuccessful. Obsessional thoughts could be in the form of ideas,
images or impulses that enters the individuals mind again
and again in a stereotyped fashion. Compulsive acts are
also known as rituals. These are stereotyped behaviors
repeated again and again. They are not inherently enjoyable and they do not result in the completion of any useful
thoughts. The individual often views the compulsions to
be reducing the anxiety caused by the obsessions. Usually
these repetitive acts are considered to be pointless and the
patient tries to resist them, only to yield to them when the
anxiety builds up. However, in very long-standing cases
the resistance may be minimal. There is often a close relationship between obsessional symptoms and depression.
The most common ritual seen is frequent hand washing as
a result of obsessive thoughts that one might be contaminated by germs, dirt or HIV. The other commonly seen
compulsion is a checking behavior.
About 1 in 50 people suffer from OCD at some point in
their lives. Men and women are equally affected. It affects
work, relationships and family life of the patient. People
with a severe OCD also cause burden on their caretakers.
Some people with mild OCD improve without any treatment. Some will slowly get worse and some get worse when
they are stressed and depressed. The mainstay of treatment
for OCD continues to be talking therapies like exposure and
response prevention and guided self-help. Antidepressant
medications can be used alone or in combination with
talking therapies for moderate to severe OCD.
Hypochondriasis
Patients with hypochondriasis are preoccupied by a fear of
having a serious disease based on the misinterpretation of
their bodily symptoms (American Psychiatric Association,
1994). This serious preoccupation persists despite negative
investigations and causes distress with impaired functioning of the patient. The central and diagnostic clinical feature is the preoccupation with the idea of having a serious
medical condition, usually one which will lead to death or
serious disability. The patient usually ruminates repeatedly
on this possibility. The minor and insignificant bodily
abnormalities, normal variants, normal functions and minor
ailments will be interpreted as signs of the serious disease.
The patient will consequently seek medical advice and
investigation but is unable to be reassured by the negative
results. Such patients may be able to accept that their worries are groundless but nonetheless are unable to stop dwelling and acting on them. Such beliefs are more often than
not over-valued ideas. However, this belief can be of a delusional intensity when the patient should be treated as for
a delusional disorder. Otherwise antidepressants, behavioral therapy and cognitive behavioral therapy (CBT) are
the mainstay of the treatment for hypochondriasis.
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Section VII System Review

Body dysmorphic disorder


Body dysmorphic disorder (BDD) is characterized by
devastating preoccupation with an imagined defect in
appearance and marked distress over the supposed deformity (American Psychiatric Association, 1994). Though
the focus of patients with BDD is by definition on physical
appearance, data exists on patients with BDD having obsessional concerns with odor (Hollander and Aronowitz, 1999).
BDD is also known as dysmorphophobia. It is an intriguing and sometimes difficult to treat condition that often
mystifies the clinicians. This disorder is characterized by
distressing and impairing preoccupation with a non-existent
or slight defect in appearance. Although BDD symptoms
may sound trivial the disorder can cause severe distress
and can lead to suicide. Individuals with BDD are preoccupied with the idea that some aspects of their appearance
is unattractive, deformed or just not right in some way.
Concerns usually focus on their face or head but can involve
any area of the body (Phillips and Diaz, 1997; Phillips et al,
1993). Concerns with bodily asymmetry, for example,
uneven buttocks are also common. BDD by proxy consists
of a preoccupation with supposed flaws in another persons
appearance, which may lead to insistence that the other
person should have surgery or dermatological treatment.
The majority of BDD patients seek often costly nonpsychiatric treatments (Phillips, 1996) and may also present
to the dental practitioners in the rst instance for surgical
treatment. However, most BDD patients appear dissatised
with such treatment and many dislike their new appearance even more (Andreasen and Bardach, 1977). Multiple
procedures may be received in search for a cosmetic solution to this psychiatric problem before it comes to a psychiatrist. Occasionally, dissatised patients sue, or even
become violent toward the physician. There are rare reports
of patients trying to perform their own surgery, as did one
man who cut his nose open and tried to replace his own
cartilage with chicken cartilage. The mainstay of evidence
based treatments for BDD includes selective serotonin
reuptake inhibitors (SSRI) and CBT.

INTERESTING INTERFACE BETWEEN


DENTISTRY AND PSYCHIATRY
Disorders on the Psychotic Spectrum
Orofacial phantom pain
Current day dentists are often faced with challenges when
patients present with orofacial pain. In the current day
competitive practice there is always an urgency to treat conditions associated with the pain. More often than not the
clinical dilemma needs to be resolved quickly and decisively.
Such situations impel the clinician to perform procedures
designed to eliminate pain such as endodontic therapy or
tooth extractions or to construct new and different dentures
560

(Marbach, 1996). Though this urgency is almost palpable,


such urgent situations create the potential for failure. It is
thus essential to be aware of the three putative neuropathologic facial pain disorders:
1.
2.
3.

Phantom tooth pain


Intraoral stump pain
Phantom bite syndrome.

1. Phantom tooth pain Reports on tooth pain of obscure


origin are relatively recent (Harris, 1974). The term phantom tooth pain was first used in 1978 (Marbach, 1978), and
since then the condition has been validated extensively as
a clinical entity (Marbach, 1993a, 1993b; Pollmann, 1984;
Rees and Harris, 1979). Phantom tooth pain is the most
common type of orofacial phantom pain reported. It usually
follows dental or surgical procedures such as pulp extirpation or tooth extraction. It is characterized by persistent
toothache with no identifiable cause. Neither repeated endodontic treatment nor tooth extraction renders the affected
area free of pain. On the contrary, procedures and other
surgical interventions such as trigeminal rhizotomy and
microvascular decompression frequently exacerbate pain
and may even enlarge its distribution. Other terms for
phantom tooth pain, such as atypical odontalgia (Brooke
and Merskey, 1994), idiopathic odontalgia and atypical
facial pain, also are in use (Bates and Stewart, 1991).
The pain is described as a constant, dull, deep ache with
occasional spontaneous sharp pains. There are no refractory
periods. Peripheral stimuli can momentarily exacerbate
the pain but have no prolonged inuence. Radiographic
and laboratory tests are negative. Sleep is undisturbed by
pain or other phantom sensations. Many patients report a
brief symptom-free period on awakening in the morning.
It resembles other phantom pain syndromes that commonly
arise following amputation and injury (Marbach, 1996).
Phantom tooth pain has only been reported in adults and
none in children (Marbach, 1996).
2. Intraoral stump pain Stump pain is a frequent squeal
of limb amputations. Davis cited this pain as a major cause
of prosthetic limb rejection among amputees (Davis, 1993).
Sherman and colleagues suggested that denture pain is the
intraoral equivalent of limb stump pain (Sherman, 1989).
Stump pain does not disappear with time or with adjustments
or replacements of the prostheses (Marbach, 1996). The
health and financial conditions of these patients improve
on treatment directed toward stump pain which is focused
away from mechanically based etiologies (Marbach, 1985).
The onset of pain is usually associated with an injury to
a peripheral nerve. Pain is often worse at the site of the
original trauma, although in chronic cases they have difficulty in localizing the pain.
3. Phantom bite syndrome Phantom bite syndrome is
often associated with an inability to adapt to changes
in dental occlusion (Marbach, 1978, 1985). Non-painful
phantom limb phenomena are common among recent

Chapter 18 Systemic Disorders and their Clinical Implications

amputees but usually fade with time (Jensen et al, 1984).


Recently orofacial phantom bite syndrome has been viewed
as a psychiatric disorder (Bonica, 1991; Jensen et al, 1984;
Marbach, 1978, 1985). This interpretation has been revised
in light of current research (Jensen et al, 1984; Melzack,
1993; Sherman, 1989). Though phantom bite syndrome
can occur at any stage of dental treatment, it is typically
associated with the construction of extensive prosthesis in
all age groups and the beginning of orthodontic treatment
in adolescents (Marbach, 1996). They usually complain of
continuous discomfort and are frequently distressed by
the lack of familiarity of their own bite (Marbach, 1996).
Seeking relief from phantom bite syndrome often becomes
an expensive and lengthy effort toward restoration of ones
original but lost bite (Marbach, 1978, 1985). Success is
rarely if ever obtained. Treatment therefore should be focused
on prevention, early detection and patient education.
Delusional bad odor
Bad breath is also known halitosis; it is a common concern
found in millions of people. There seems to be no reliable
way to assess breath odor. Some people develop faulty
perceptions about having a bad breath. Sometimes it
affects their entire life. On the other hand, some people
who have halitosis remain unaware of their condition.
Every patient has a breath odor self-image. This self-image
ranges from little or no distortion to severe psychopathology (Eli et al, 2001). Because these people go to a dentist
with a complaint of oral malodor, it becomes the responsibility of dental practitioners to identify this psychopathology. It is important for dentists to consider both
psychological and physiological factors while diagnosing
and treating such cases.
Various researchers have attempted to understand the distortions in self-perception of odors, including oral malodor,
in the context of various psychiatric disorders (Davidson
and Mukherjee, 1982; Pryse-Phillips, 1971). One relevant
example is patients who complain of various body odors
(auxiliary, fecal or genital) that appear to have no objective
basis. These patients may have somatic delusions or an
olfactory reference syndrome (ORS) (Pryse-Phillips, 1971).
Causes of delusional halitosis were presented in the literature by Davidson and Mukherjee (1982), Iwu and Akpata
(1990) and Oxtoby and Field (1994). Halitophobia also
may be considered in the context of BDD. Halitophobics
often display other psychological phenomenon, such as
compulsive toothbrushing and withdrawal from social
interactions (Rosenberg, 1996).
Olfactory reference syndrome
Patients sometimes present with persistent olfactory concerns or preoccupations with personal odor (Malasi et al,
1990; Pryse, 1971; Stein et al, 1998; Videbech, 1966). The
term olfactory reference syndrome (ORS) has been introduced to differentiate primary olfactory concerns from

those seen as a consequence of other disorders such as


schizophrenia, depression or temporal lobe epilepsy (Pryse,
1971). It is still controversial whether ORS is truly a unique
disorder or merely a part of the symptomatology of other
psychiatric conditions (Lochner and Stein, 2003). However,
it has been noted that most patients with primary ORS are
young without concurrent psychiatric disorders (Pryse,
1971). Arguably, the principal symptomatology of ORS has
sufficient overlap with anxiety and somatic disorders.
Case vignette
A 22-year-old male presented with the belief that he had malodorous
breath (halitosis) and a foul odor emanating from his armpit, feet,
and anal region. This persistent preoccupation had begun in early
adolescence, but the intensity had increased significantly over the past
7 months. Halitosis was his main concern. But collateral information
from his parents confirmed his excessive washing and frequent
change of clothes. His embarrassment about the perceived halitosis
gradually caused increasing social withdrawal and isolation and also
resulted in depressive symptoms. He remained convinced that the
halitosis had persisted, despite reassurance to the contrary by his
physician and close family members.

Schizophreniadental implications
Dentists who are familiar with the signs and symptoms of
schizophrenia are likely to feel more secure while treating
patients with schizophrenia. It makes the dentist more confident while obtaining consultative advice from the patients
psychiatrist. Dentists can provide the full range of service
to such patients and constitute to the psychotherapeutic
aspect of management. In addition to being able to communicate effectively with such patients, the dental treatment
may need to be modified because of the patients impaired
ability to think logically. It is very important for all dentists
to be aware of the local and systemic effects of psychiatric
medications and the adverse interactions between these
drugs and medications used in dentistry.
Schizophrenia can be conceptualized as a group of disorders, with variable presentations, best described in three
different dimensions: positive symptoms, disorganized symptoms and negative symptoms. The positive symptoms are
the exaggeration or distortion of normal functions, most
commonly delusions and hallucinations which are described
earlier in the chapter. Disorganized symptoms are inferred
from patients speech and are also known as thought disorder. It is manifested as rapid shifts between topics that
either have a loose logical association or are completely
unrelated. They may also exhibit inappropriate affect manifested by childish silliness and unpredictable agitation.
(Andreasen et al, 1995; Marder, 1996). They also exhibit a
range of neurocognitive impairments in the areas of memory, attention and executive functions, which in turn impairs
their vocational and social adjustment (Green, 1996).
Negative symptoms are less dramatic but equally debilitating. They include reduced emotional responsiveness (at
affect); reduced speech output and poor thought content;
561

Section VII System Review

inability to plan, initiate and persist in goal directed activities (avolition) and poor self-care in terms of washing,
bathing and cooking. They also show social withdrawal
and loss of pleasure in previously enjoyed activities (anhedonia) (Kaplan, 1994 and Sadock, 1995).
Substance abuse frequently accompanies schizophrenia. The prevalence rate of alcohol abuse in schizophrenia
is as high as 63% in some studies (Dixon, 1999). Other
commonly abused drugs are cannabis and cocaine. Some
patients seem to self-medicate their positive symptoms
with these illicit drugs which in turn makes the psychosis
worse. Abuse of these substances strongly correlates with
medical and psychosocial problems like inadequate diet,
homelessness, poor compliance with medications and
multiple episodes of the disorder (Dixon et al, 1999). More
than three-fourths of patients with schizophrenia smoke
and this is frequently associated with emphysema, lung
cancer, cardiac disease and oral cancer (McEvoy and
Brown, 1999).
Patients with schizophrenia are often having a disinterest in performing appropriate preventive oral hygiene
techniques (Friedlander and Liberman, 1991; Thomas et al,
1996). This in turn leads to the development of advanced
oral disease. This is compounded by reduced access to
care, prolonged hospitalizations, impaired nances and
paucity of clinicians who are comfortable in caring such
people. Some antipsychotics, namely, chlorpromazine and
thioridazine cause profound hyposalivation through their
anticholinergic effects (Sreebny, 1989). This is worsened
by the co-administration of antiparkinsonian agents to
counteract the extrapyramidal side effects (EPSE) of the
conventional (dopamine agonist) antipsychotics. The resultant hyposalivation causes intensication of periodontal
disease and rapid caries progression (Gupta et al, 1993).
Therefore, a lot of people with schizophrenia have a higher
requirement for periodontal treatment, dental restorations
and dental extractions (Velasco et al, 1997). The conventional antipsychotics have adverse side effects, especially
the movement disorders that mimic neurological diseases.
These movement disorders frequently have an orofacial
component and are seen to develop in a time-dependent
fashion. These movement disorders are caused by the blockade of basal ganglia dopamine D2 receptors in the extrapyramidal system (Holloman and Marder, 1997).
Effects of antipsychotic drugs on orofacial movements
Acute diagnoses which generally manifest within the first 5 days of
starting treatment:

562

Oculogyric crisis (eye turned upward)


Torticollis (head turned sideways)
Retrocollis (head turned backward)
Trismus (forced closing of the mandible)
Laryngospasm
Spasm of neck muscles
Tongue protrusion

Pseudoparkinsonian side effects generally develop in 13 months


after therapy:

Reduced eye blinking


Monotonous and soft speech
Mask-like face
Cogwheel rigidity

Tardive dyskinesia is slow to develop and is generally seen in


710 years of antipsychotic use. It is characterized by rhythmical
involuntary movements of:

Mouth (ex, puckering)


Face (ex, puffing of cheeks)
Jaw (ex, chewing movements)
Tongue (ex, protrusion)

Clozapine is another medication to be aware about. It is an


atypical antipsychotic used in patients unresponsive to other
medications (Breier, Malhotra, Su, et al, 1999). Clozapine
has a unique added advantage of reducing the cravings for
alcohol and illicit drugs (Volavka, 1999). About 0.5 to 1%
of patients on clozapine develop bone marrow suppression
causing agranulocytosis and granulopenia (Worrel, Marken,
Beckman, et al, 2000). This prevents clozapine from being
used as a first-line drug. Thus all patients on clozapine
should have periodic WBC count (Hammad, 1998). Although
clozapine is a potent anticholinergic agent, it has a unique,
unexpected side effect of sialorrhea in 85% of patients
(Clark, 1992).

Anxiety and Depressive Disorders


Depression and dental implications
A depressive disorder may be associated with extensive
dental disease (Baker and Dawe, 2005). Patients may seek
dental treatment before becoming aware of their psychiatric illness (Gatchel et al, 1996). Depression is often associated with a disinterest in performing appropriate and
timely oral hygiene techniques. It can also be associated
with a cariogenic diet, diminished salivary flow, rampant
dental caries, advances periodontal disease and oral dysesthesias (Friedlander and Mahler, 2001). Side effects of
antidepressant medications increase the incidence of dental diseases including xerostomia (Gerber and Lynd, 1998).
An appropriate dental management in such patients would
include a good dental education, the use of saliva substitutes and anti-caries agents containing fluoride. Special
precautions should be taken and every potential drug interaction should be kept in mind while prescribing analgesics
and local anesthetics (Callahan, 1996).
Depression in chronic facial pain
Depressive illness is a common and a serious disorder that
affects at least 20% of women and 10% of men during their
lifetime (Kessler et al, 1994). Approximately 15% of these

Chapter 18 Systemic Disorders and their Clinical Implications

people eventually commit suicide (Angst and Hochstrasser,


1994; Coppen, 1994). Depression has a high comorbity
with chronic facial pain, making it important for dental
practitioners to be able to identify depressive symptoms in
dental patients presenting with facial pain. The rate of
depression has been shown to be as high as 4080% in
patients with chronic facial pain (Gallagher et al, 1991;
Korszun et al, 1996). More than 40% of patients with
chronic facial pain are refractory to treatment (Friedlander
and Mahler, 2001). Thus early identification and optimal
treatment of co-morbid depressive disorder will have a significant impact on the treatment outcome for these patients.
Blumer and Heilbronn (1982) suggested that patients
with chronic pain have an underlying depression that is
masked and represented only by somatic symptoms that
are not accompanied by the usual mood symptoms, making
it more difcult for the dental practitioners to recognize
depression. On the other hand, some authors have conceptualized depression as a secondary maladaptive response
to chronic pain (Dworkin, 1991).
As a dental practitioner the most important factor is having awareness of depression as a medical disorder and having an openness to recognize the less obvious presentations
of a depressive disorder. If clinicians themselves conceptualize depression as a mental disorder or a character defect
and do not understand the neurological basis and treatability
of depressive conditions, they will not only fail to recognize
this serious condition but will also convey this prejudice
to their patients. Patients may also be resistant to even considering a diagnosis of depression particularly when they are
consulting a dentist for what they perceive to be a physical
condition such as jaw pain. Because of the time constrains
in a busy dental practice it might be worth while administering a depression rating scale such as the Beck Depression
Inventory (Beck et al, 1961) for all patients presenting with
chronic facial pain. Recognizing depressive symptoms in
patients with chronic pain is particularly challenging as
many symptoms secondary to chronic pain are also prime
symptoms of depressive illness. For example, patients with
chronic pain have a resulting poor sleep, lethargy, irritability
and weight loss due to pain while eating, which are the
core symptoms of depression. It is also important to screen
for co-morbid alcohol and substance abuse in such patients.
A broad multidisciplinary approach to the diagnosis and
treatment will improve treatment outcomes of such patients.
Antidepressant useimportance for dental practice
Many dental patients are prescribed antidepressants for
diverse therapeutic reasons such as pain control, insomnia, smoking cessation, substance abuse and eating disorders. However, antidepressants taken with other drugs may
increase the risk of complications that require special dental precautions and care. Patients receiving antidepressant
therapy commonly complain of decreased salivation and

changes in salivary viscosity (Astor et al, 1999). Xerostomia


(Peeters et al, 1998), orthostatic hypotension (Peeters et al,
1998) and cardiotoxicity (Roose et al, 1998) are significant
adverse effects of certain antidepressant medications especially when they are taken in combination with other medications (Fox, 1998). Chronic xerostomia can cause oral
mucosal changes, increased coronal and root caries susceptibility, candidiasis, partial loss of taste acuity, periodontal
disease, and difficulty in swallowing and functional prosthetic problems (Astor et al, 1999). In patients aged 60 years
or older, Thomson and colleagues (1995) reported a higher
root caries index value for those on antidepressant therapy.
Precautions related to orthostatic hypotension include
shorter dental interventions, positioning the patient up
right in the dental chair, avoiding sudden postural changes,
using caution in prescribing medications which cause
orthostatic hypotension.
The injection of local anesthetics containing vasoconstrictors often causes an increase in blood pressure. A rare
paradoxical hypertensive reaction may occur when patients
taking drugs with alpha-1 adrenergic blocking activity
(such as tricyclic antidepressant) are given with a local anesthetic containing vasoconstrictor (such as epinephrine).
This reaction occurs as epinephrine is unable to bind to
the blocked alpha-1 receptors, instead interacts with available beta-2 receptors causing vasodilatation and a resultant paradoxical hypotensive reaction (Keene et al, 2003).
Dental precautions include using a minimal quantity of local
anesthetic with sympathomimetic vasoconstrictor and taking care to prevent intravascular injections. Use of epinephrine containing homeostatic agents is contraindicated. All
these precautions are only in addition to routine monitoring of blood pressure and other vital signs (Yagiela, 1999).
Eating disordersdental implications
Dentists are likely to encounter patients who have eating
disorders and they have an important part to play in the
overall care of these patients. There are two major categories of eating disorders namely anorexia nervosa and bulimia nervosa. Anorexia occurs in upper and middle class
families while bulimia presents across all social classes
(Hugo and Lacey, 1996).
Anorexia is aversion to food, which can be conceptualized as resulting from a complex interaction between biological, individual and family factors. This aversion to food
leads to severe weight loss and its complications, both
physiological and psychological. There are two subtypes of
anorexia, restricting and binge/purge types. The difference between these two sub-categories is based on whether
the person regularly engages in binge eating or self-induced
vomiting (SIV), excessive exercise or misuse of laxatives,
diuretics or enemas. Bulimia is even more common and is
characterized by overeating followed by inappropriate compensatory behaviors with normal body weight.
563

Section VII System Review

Patients with bulimia nervosa often present with bilateral and occasional unilateral parotid gland swelling. The
incidence of parotid gland swelling is 1015% in people
with bulimia (Brady, 1985). The submandibular salivary
gland is involved infrequently. The exact pathogenesis of
these glandular enlargements has not been determined. It
is generally accepted that multiple emetic episodes cause
an autonomic neuropathy (Ascoli et al, 1993). With sympathetic nerve impairment, individual acinar cells enlarge
and lead to clinically visible gland swelling (Ascoli et al,
1993). Such an asymptomatic bilateral parotid enlargement
often presents a diagnostic dilemma to the dentists. As these
patients with bulimia nervosa and parotid gland swelling
are usually secretive about their self induced vomiting (SIV)
(purging), the diagnosis will have to be made by conducting a thorough clinical examination and serum electrolyte
study. Early recognition and prompt diagnosis when such
patients present to the dentists can avoid the later serious
medical complications. The need for these patients to seek
psychiatric care and discontinue SIV is mandatory.
Eating disorders have various orodental adverse effects.
Holst and Lange in 1939 coined the term perimylolysis to
describe the distribution of erosion on the upper palatal
surfaces secondary to vomiting, reux and regurgitation
(Holst and Lange, 1939). Several research studies till date
have shown that SIV results in increased frequency of
erosion on palatal surfaces (Hellstrom, 1977). Whether the
caries experience in eating disorder individuals is greater
than in normal population remains unclear (Hurst et al,
1977). Salivary ow increases dramatically prior to vomiting because the medullary center that controls vomiting is
connected to salivary nuclei (Edgar, 1992). With respect to
SIV, the stimulated salivary ow should therefore be altered.
Research has discovered reduced bicarbonate in bulimics
along with increased salivary viscosity (Edgar, 1992). One
study has found increased frequency of periodontal disease in patients with eating disorders (Touyz et al, 1993).
Angular cheilitis, candidosis, glossitis and oral mucosal
ulceration are possible sequelae of nutritional deciency.
There has not been any report of malignant change associated with SIV (Brady, 1980).
The dental care demanded by individuals with eating
disorders is very challenging. Although the dentist might
suspect vomiting as the cause of erosion, these patients will
not readily admit to such behavior because they can be
highly secretive and embarrassed by it. The patients motivation to reduce the frequency of SIV will increase once
the dentist is able to openly relate the progress of dental
erosion with the vomiting. Toothbrushing after vomiting
is generally regarded as inadvisable because the softened,
demineralized surface is more susceptible to toothbrush
abrasion (Milosevic et al, 1997; Robb et al, 1995).
Patients whose teeth have been damaged as a consequence of an eating disorder are most likely to present rst
to the dentists. In many cases the dentist is in a position to
564

assist in making the initial diagnosis and can inuence


progress of the medical and psychological management of
the disorder.

MANAGEMENT OF PSYCHIATRIC
DISORDERS
Broad Principles
Some patients who receive psychiatric treatment for mental health problems may be reluctant to admit it. This is
most often because of the perceived stigma associated with
mental illness. It is important and could be quite tricky for
a dentist to overcome such barriers and obtain the necessary information. It always helps to take a supportive and
non-judgmental attitude, and advise patients that such
information will be held confidential and also that it is
indispensable to provide a safe dental care.
Patients with mental health problems may be uncooperative and irritable during dental treatment. They may
appear unappreciative and may seem to have numerous
complaints that are inconsistent with the objective ndings
(Korszun and Ship, 1997). It is always benecial to liaise
with the patients psychiatrist before beginning any dental
treatment. Information requested should include at least
the latest mental state, risk assessment and the list of psychotropic medications. In addition, a history of alcohol
and illicit drug use is always useful. Such patients should
undergo a liver function test, full blood count and coagulation prole before commencing the dental treatment.

Importance of Interpersonal Communication Skills


with Special Emphasis on Dental Phobia
Communication skillswhy bother?
From personal experience of one of the authors, we state
the obvious that dentists should remember that the patient
cannot speak with a wide open dry mouth and with dental
instruments in their mouth. They should probably ask questions that generate a yes/no type of response. Moreover,
at the outset, it is useful to lay down the ground rules such
as, if in pain, raise your left hand.
Patients seeking dental treatment have apprehensions
about the nature of their problem and the procedure
involved. One of the common misconceptions that people
have is that all dental procedures are painful. Moreover,
the fear of injections and the sound and sight of drills and
other instruments keep many patients away. This may lead
to patients postponing visits to their dentists or totally avoiding it. The estimates of dental anxiety in general population
varies between 6% and 20% (Rouse and Hamilton, 1990).
Dentistpatient relationship rests a lot on the interpersonal communication. This also has a signicant impact in

Chapter 18 Systemic Disorders and their Clinical Implications

allaying dental anxiety. Corah et al (1985) have reported


that anxiety during treatment was inuenced by patients
satisfaction with the dentists technical competence, understanding and communication skills (Corah et al, 1985).
It needs to be stressed that every doctor has to approach
his/her patients with warmth and have a basic respect for
them and acknowledge the distress that the person seeking
help may be going through.
Importance of explaining the procedure to the
patients
Dentists often have to deal with anxious clients. Helping
patients overcome such anxiety can reduce the rates of
missed appointments and also better compliance on the
part of the patient during the treatment session. Various
ways of doing it can be employed such as using models,
charts or diagrams and video clippings. It is important to
check that the patient understands at every step. The very
step of explaining the procedure helps patients to be mentally prepared and allays their anxiety. It is also helpful to
obtain a verbal consent from the patient ensuring that they
are ready for the procedure.
In addition, creating a conducive environment for the
patient also helps. A survey by Bare and Dundes has
shown that a majority of anxious patients found it helpful
to have gentle music in the background, magazines and
books, adorned walls and a slightly cool temperature in the
waiting area (Bare and Dundes, 2004).
Dealing with dental anxiety/phobia
Bare and Dundes have summarized from past research the
reported causes of dental anxiety (Bare and Dundes, 2004).
Some of the common ones are:

If patients have had previous painful experiences


Belief that painful treatment is inevitable
If they feel that they lack control over the situation,
including the inability to stop a procedure they find
unpleasant
Lack of understanding of the procedure that the dentist
performs
Patients having a general fear of the unknown
Media coverage or hearing from acquaintances of
frightening tales of dentists or procedures
Experienced detached treatment by a dentist
Having fears of experiencing ridicule because of how
they react to situations arising during their visit.

It is important to provide information to the patients as


soon as possible about the nature of the problem and what
they can expect during and after the treatment. It is known
as informational control and it reduces dental anxiety
(Levitt et al, 2000).
Maggirias and Locker reported that patients who perceive that they have little control over the procedure were

more likely to report pain (Maggirias and Locker, 2002).


This again brings us to the fact that explaining the
procedure as highlighted in the previous paragraph, gives
patients a sense of control and is useful in allaying their
anxiety.
Study by Eli et al suggests that the level of patients
anxiety was affected by evaluation of the present dentist by
the patient and memories of anxiety from childhood and
also by the personality traits of the patient (Eli et al, 1997).
Some training centers have communication skills training programs for students in dentistry to teach students
micro-skills such as dealing with anxious patients. It has
been shown that communication skills training has an effect
on the knowledge and a substantial effect on the behavior
of the students (van der Molen et al, 2004).
Note:

Clear communication involves making simple and


short statements asking only one question at a time.
Active/attentive listening is a key feature of good
communication. It involves making a good eye contact and also by using non-verbal modes of communication (head nodding).
Avoid interrupting when the other person is talking.
Ask questions to clarify what the person actually
meant when unclear.
It is important to confirm that the person has understood what the doctor had to say. Have you understood/Am I clear?, Do you have any questions?
Reassure, explain that the procedure can be stopped
at any time if the patient cannot tolerate it.

Medications
Antidepressants
Antidepressants are drugs that relieve symptoms of depression. They were first developed in 1950s and have been used
regularly since then. There are almost 30 different kinds of
antidepressants which belong to the four major categories:
tricyclics, mono amine oxidase inhibitors (MAOIs), SSRIs
and serotonin noradrenaline reuptake inhibitors (SNRIs).
Antidepressants work by increasing the activity of certain
neurotransmitters mainly serotonin and noradrenaline.
Antidepressants are used to treat moderate to severe depressive illness, severe anxiety and panic attacks, OCD, chronic
pain, eating disorders and PTSD.
The tricyclic antidepressants such as imipramine, amitriptyline, nortryptiline and dosulepin cause side effects
such as dry mouth, slight tremor, tachycardia, constipation,
sleepiness and weight gain. In addition to these anticholinergic side effects, men may experience delayed ejaculation
and difculty in getting or keeping an erection. Tricyclic
antidepressants are less commonly used as they are dangerous in overdose.
565

Section VII System Review

SSRIs are the commonly used rst line treatment and


include drugs such as uoxetine, sertraline, citalopram
and paroxetine. SSRIs are generally well tolerated and less
harmful in an overdose which make them the most popular. SNRIs are very similar to SSRIs although venlafaxine
should not be used in patients with heart problem and
needs monitoring of blood pressure. MAOIs are rarely prescribed these days as they cause dangerously high blood
pressure on eating food containing tyramine known as
tyramine reaction. It is important to check for the dangerous drug interactions before prescribing if a patient is on
MAOIs. It is generally best to taper off the dose of an antidepressant as stopping it suddenly may cause withdrawal
such as stomach upset, anxiety, dizziness and u-like
symptoms. The current recommendation is that antidepressant should be continued for at least 6 months after
complete remission of symptoms. If one has suffered from
two or more episodes of depression then treatment should
be continued for at least 2 years.

antipsychotics include risperidone, olanzapine, quetiapine, amisulpiride and clozapine. Risperidone is the only
atypical antipsychotic which is available in the form of
long acting injection.
Clozapine is an atypical antipsychotic medication and
the only one that has shown to be more effective for people who do not respond to other sorts of antipsychotics.
In addition to the side effects of the atypicals mentioned
above, clozapine also produces increased salivation. The
main drawback is that it can affect the bone marrow reducing the white cell count causing agranulocytosis which
can be fatal. For this reason, patients taking clozapine need
weekly full-blood count for the rst 6 months, 2 weekly for
the next 6 months, and 4 weekly thereafter.
Most patients with schizophrenia need to take antipsychotics for a long time. On stopping the treatment, symptoms
of schizophrenia usually come back, if not immediately,
often within 6 months. It is advisable to reduce the dose of
the medication gradually, only in discussion with a psychiatrist who will monitor for early signs of relapse.

Antipsychotics
Starting from the mid 1950s several medications were
discovered that reduce the symptoms of schizophrenia
and other psychotic disorders. They came to be known as
antipsychotic medications. These older drugs are called
typical or first generation antipsychotics. They work by
reducing the action of dopamine in the brain (dopamine
antagonist). Some typical antipsychotics are chlorpromazine, haloperidol, pimozide, trifluoperazine and sulpiride.
Some of these typical antipsychotics are available in long
acting depot injection form which can be administered
once in 2 to 4 weeks for people who do not comply with
oral medications. The typical antipsychotics have more
side effects than atypicals. The side effects include stiffness and shakiness as in Parkinsons disease along with
feeling sluggish and slow in their thinking. Other side
effects include uncomfortable restlessness (akathisia) and
sexual side effects. A long-term side effect is tardive
dyskinesiapersistent movements generally of the mouth
and tongue which is difficult to treat and very disabling.
Over the last 10 years, several newer medications have
been in use. They work on a different range of chemical
messengers in the brain including the serotonin system
(serotonin dopamine antagonists). These came to be known
as atypical or second generation antipsychotics. These
atypical antipsychotics are less likely to cause parkinsonian side effects although they may cause weight gain
and problems with sexual functions. They may also help
the negative symptoms on which the older drugs have
very little effect. They also seem to have much less propensity to cause tardive dyskinesia. The common side
effects of atypicals include weight gain, sexual side effects,
glucose intolerance and increased chance of developing
Type 2 diabetes and sedation. The commonly used atypical
566

Anti-manic agents
Medications used to treat mania include mood stabilizers
such as lithium and valproate. Other medications used to
treat mania include antipsychotics and benzodiazepines.
Medications used to prevent the relapse of manic episodes
in manic depression (bipolar disorder), include drugs such
as lithium, valproate, carbamazepine and lamotrigine.
Lithium has over the last 40 years been the most commonly used drug to prevent relapse. Lithium is a safe drug
when taken at the correct dose, however it has a narrow
therapeutic window (0.6 to 0.8 mmol/l) and becomes unsafe
above this level in the blood. The common side effects
include ne tremors, metallic taste in the mouth, tiredness,
weight gain and underactive thyroid gland. Long-term treatment with lithium can cause renal impairment. It is thus
important to periodically check for serum lithium level,
thyroid functions and renal functions including creatinine
clearance. Lithium is an ion and is excreted unchanged from
the kidneys. Drugs such as diuretics and NSAIDs can dangerously increase the serum lithium levels and so it is very
important to check for drug interactions before prescribing
for a patient on lithium.
Valproate and semi-sodium valproate are becoming
widely used treatment for mania and bipolar disorder. The
common side effects of valproate include sleepiness, dizziness, increased appetite and weight gain, skin rashes and
irregular periods. Very rare side effects include pancreatitis and liver failure. It is again very important to check for
drug interactions as valproate is a hepatic enzyme inhibitor and reduces the metabolism of other medications.
Carbamazepine is usually used as a second line treatment
for bipolar disorder. Unlike valproate, carbamazepine is
a hepatic enzyme inducer and increases the metabolism

Chapter 18 Systemic Disorders and their Clinical Implications

of other medications and thus reduces their efcacy. Interestingly it reduces its own level and needs bigger doses with
longer treatment. Lamotrigine also helps to prevent mood
swings particularly of severe depressive episodes. It is however not used as a monotherapy for bipolar disorder.
Electroconvulsive therapy
Electroconvulsive therapy (ECT) is a treatment used in
psychiatry for severe mental illnesses. It was originally
developed in the 1930s and was used widely during the
1950s and 1960s for a variety of conditions. Since then its
use was declined. ECT remains a controversial treatment,
which some people have strong feelings about. There are
those who claim it can be a lifesaving procedure, while
others feel it should be banned. ECT is a way of causing
someone to have a seizure and it is this seizure that is
needed for the treatment to work. The seizure is made to
happen by passing an electric current across the persons
brain in a carefully controlled way from a specially developed ECT device. The current can be administered to the
whole brain when it is called bilateral ECT or just to the
non-dominant hemisphere called the right unilateral ECT.
The seizure itself is very similar to the seizures that occur
in people with generalized epilepsy, but it is caused on
purpose in very controlled circumstances using generalized anesthesia and muscle relaxant, just like for a surgical
operation. The aim of ECT is to cause a generalized cerebral seizure between 10 and 50 seconds long using the
right dose of electricity. The current recommendation is to
use ECT for treatment resistant severe depression, severe
mania and catatonia (NICE, 2003). ECT is used more as a
lifesaving treatment for quick resolution of very severe
symptoms and is always supplemented with a continuation of the most appropriate pharmacotherapy.
Psychological (talking therapies)
There are several types of talking treatments also known
as psychotherapy. These are different ways of helping people to overcome stress, emotional problems, relationship
problems and troublesome habits. The commonality in these
treatments is talking to another person and sometimes

doing things together. Behavioral psychotherapy tries to


change the behavioral patterns of the patients and helps
to overcome fears by spending more and more time in the
situation they fear. They are also given homework exercises
and are asked to keep a diary to practise the new skills in
between the sessions. This type of behavioral psychotherapy is effective for panic, phobias, anxiety, OCD and various kinds of social and sexual difficulties. Results are seen
quite quickly. CBT aims at changing the thinking patterns.
It emphasizes on how the thinking, behavior, emotions
and physiological symptoms are all related in a particular
instance and is influenced by the environment. It encourages a discussion on how we think and helps us to get rid
of unhelpful ways of thinking. It focuses on the present
and not on the past. CBT have achieved particular success
in the treatment of certain types of depression. Psychodynamic psychotherapy focuses on the feelings one has about
other people, family and those close to the individual. This
mode of treatment involves discussing the past experiences
and how these may have led to the present situation and
affecting the individuals life. It may involve a brief therapy
for a specific difficulty or may be long-standing with daily
sessions lasting for many years. Family therapy focuses
very clearly on the relationships, boundaries and communication styles in the family of the concerned individual.
Marital therapy is for relationship problems in a marriage,
partnership or family. In all the above forms of therapy, the
therapist may be a psychiatrist, psychologist or the mental
health professional who has had an in-depth training in
psychotherapy. These therapies are usually done under
supervision.
When to refer to a psychiatrist
As soon as you suspect a mental disorder and realize that
the patient is not seeing a psychiatrist, it is good to think
about referral. In general the earlier the mental illness is
detected the better the final outcome. Always try to reassure and encourage the patient to seek help for the mental
health problems. Be non-judgmental and explain to the
patient that treatment is available, and it is possible to
improve the quality of life with help from the mental
health services.

567

CHAPTER

19

Bone Diseases and


Fibro-osseous Lesions
Manish Juneja, Ravikiran Ongole

Fibro-Osseous Lesions

Periapical Cemento-osseous Dysplasia


Focal Cemento-osseous Dysplasia
Florid Cemento-osseous Dysplasia
Gigantiform cementoma
Ossifying Fibroma, Cementifying Fibroma and
Cemento-ossifying Fibroma
Juvenile Ossifying Fibroma (Psammomatoid and
Trabecular)
Fibrous Dysplasia

568

Bone Diseases
Osteogenesis Imperfecta
Osteopetrosis
Cherubism
Infantile Cortical Hyperostosis
Idiopathic Osteosclerosis
Gorhams Disease
Pagets Disease of Bone

FIBRO-OSSEOUS LESIONS

most bro-osseous jaw lesions can be assigned with reasonable certainty into one of the several categories:

Fibro-osseous lesions of the jaw comprise a diverse group


of conditions which are characterized by replacement of
normal bone by a tissue composed of collagen fibers and
fibroblasts that contain varying amounts of mineralized
substance which may be bone, cementum or both in
appearance. These lesions present a wide range of clinical
and radiographic patterns. The precise diagnosis of fibroosseous lesions depends on good clinical, radiological and
histological correlation.
Numerous terminologies have been used to designate
these lesions. In 1940s and early 1950s, these lesions were
commonly termed as localized osteitis brosa, osteobroma
or brous osteoma. The lesions in the skull were termed as
leontiasis ossea because of its lion-like appearance. With
advances in the understanding of these lesions a number
of classications have been proposed by many investigators.
Waldron (1985, 1993), Makek (1987), Slootweg (1996),
Fowler (2005) are a few among those who have been
accepted, although no universally approved classication
system has been presented.
The classication system that has been considered to be
most useful was given by Waldron in 1993. Waldron suggested that with adequate clinical and radiographic data,

I.
II.

Fibrous dysplasia
Reactive (dysplastic) lesions arising in the tooth-bearing
area
A. Periapical cemento-osseous dysplasia
B. Focal cemento-osseous dysplasia
C. Florid cemento-osseous dysplasia
III. Fibro-osseous neoplasms: Cementifying fibroma, ossifying fibroma or cemento-ossifying fibroma
Another classification which attracted many pathologists
was given by Fowler. He classified fibro-osseous lesions as
follows:
I.

II.

Osseous dysplasia
A. Non-hereditary
1. Periapical osseous dysplasia
2. Focal osseous dysplasia
3. Florid osseous dysplasia
B. Hereditary
1. Familial gigantiform cementoma
Fibro-osseous neoplasms
A. Conventional ossifying fibroma
B. Juvenile, active, or aggressive forms of ossifying fibroma

Chapter 19 Bone Diseases and Fibro-osseous Lesions

III. Fibrous dysplasia


A. Monostotic fibrous dysplasia
B. Polyostotic fibrous dysplasia
C. Polyostotic fibrous dysplasia with endocrinopathy
(McCuneAlbright)
D. Craniofacial fibrous dysplasia.

Periapical Cemento-osseous Dysplasia


The term periapical cemento-osseous dysplasia is used to
designate a lesion which occurs in the periapical areas and
shows cementum-like and osseous areas on histopathologic examination. The term periapical cemental dysplasia
which was used earlier to designate these lesions is somewhat incorrect as the lesion shows both cementum-like
and osseous areas. The etiology is unknown, but they appear
to originate from the periodontal ligament.
Clinical features
The periapical cemento-osseous dysplasia is a disease which
involves the periapical areas of the vital teeth in black
female patients who are older than 30 years of age. The
lesions are invariably asymptomatic and are discovered on
routine radiographic examination.
Radiographic features
The early lesions show well-defined, circumscribed radiolucent lesions involving the apices of one or several teeth.
Individual lesions are seldom more than 1.0 cm in diameter
and most are less than 0.5 cm in size. The lesions show an
increasing degree of calcification with time, which may
appear as mixed radiopaque and radiolucent lesions. The
older lesions show radiopaque masses. These lesions do
not show any bone expansion.
Histopathologic features
Not many reports appear that review the histopathologic
findings of periapical cemento-osseous dysplasia. The
lesions which are misdiagnosed as inflammatory periapical
pathologies and are subjected to histopathologic findings
have shown to be composed of cementum-like and/or
osseous trabeculae in a fibroblastic stroma. As the lesions
become older the calcified component appears to be more
prominent.
Management and prognosis
The diagnosis is done mainly on the basis of radiographic
presentation and clinical findings. Surgical intervention is
contraindicated. Early lesions showing radiolucent areas
are often misdiagnosed as periapical cysts or granulomas.
Accurate pulp testing should be done to avoid such errors.
Isolated lesions involving the apical areas of vital teeth

present greater problems in diagnosis than do multiple


lesions, particularly when the solitary lesion is in the premolar area and the patient is male or a white female.

Focal Cemento-osseous Dysplasia


The term focal cemento-osseous dysplasia was first suggested by Tomich and Summerlin in 1989. The disease is
seen in the edentulous posterior areas of females who are
in their 4th and 5th decades of life.
Clinical features
Focal cemento-osseous lesions are invariably asymptomatic
and are discovered on routine radiographic examination.
There is no swelling associated with it unless the lesions
are old and have caused bony expansion. On surgical
exploration the tissue occupying the defect is gritty, hemorrhagic and is removed by curettage in small fragments,
often with some difficulty. This helps in differentiating the
lesion from ossifying fibroma which is well circumscribed
and avascular and easy to enucleate.
Radiographic features
These are well-demarcated radiolucent or mixed radiolucent/
radiopaque area or highly sclerotic. Most lesions are less than
2 cm but larger lesions may be seen. Simple bone cysts also
may occur with focal cemento-osseous dysplasia.
Histopathologic features
Microscopically areas of cellular fibrous tissue containing
numerous small blood vessels, irregular trabeculae of
woven bone and/or cementum-like calcifications are seen.
Scattered foci of multinucleated giant cells may be seen.
Management and prognosis
The lesion shows no tendency to recur after removal.
Partial removal of the lesion is also advocated in cases
where the lesion is very large and limits the total excision.
The partial removal does not show any tendency to enlarge
or recur and the long-term prognosis seems to be excellent.

Florid Cemento-osseous Dysplasia


The term florid cemento-osseous dysplasia (FCOD) was
first suggested by Melrose et al in 1976 to describe a condition of exuberant multiquadrant masses of cementum
and/or bone in both jaws and in some cases, simple bone
cyst-like lesions in affected quadrant. Sometimes familial
tendencies have been observed. In past this condition has
been designated as sclerosing osteitis, multiple enostoses,
diffuse chronic osteomyelitis and gigantiform cementoma.
The etiology of florid cemento-osseous dysplasia is
unknown. Waldron et al have proposed that reactive or
569

Section VII System Review

dysplastic changes in the periodontal ligament might be a


cause for the disease.
Clinical features
The disease is seen exclusively in middle aged, black female
and has a striking tendency for bilateral occurrence, often
presenting symmetrically in the jaws. The disease is limited to the tooth bearing areas of the jaws. Many patients
are partially or completely edentulous when the conditions are detected. Many cases are completely asymptomatic and the disease is diagnosed during routine radiographic
examination. When the lesions are large, jaw expansion
may be noted and symptoms of dull pain or drainage are
always associated with exposure of the sclerotic calcified
mass to the oral cavity as a result of progressive alveolar
atrophy after a denture or after extraction. Laboratory
investigations show no biochemical abnormalities.
Radiographic features
Bilateral densely sclerotic lesions often symmetrically present in various areas of the jaws. These are usually mixed
with less well-defined areas of a mixed radiolucent/radiopaque pattern. Majority of the patients are edentulous at
initial presentation. If the patient is having remaining
anterior teeth, they will often show circumscribed typical
lesions of periapical cemento-osseous dysplasia. Well-defined
radiolucency representing simple bone cyst is not uncommonly seen with florid cemento-osseous dysplasia.
Histopathologic features
Microscopically florid cemento-osseous dysplasia shows
an admixture of woven bone trabeculae and droplets of
cementum-like calcifications in a fibroblastic stroma. The
cementum-like calcifications often fuse to form coalescing
masses.
Management and prognosis
The diagnosis of the disease is mainly dependent on the
radiographic and clinical presentation. However, the method
of treatment is not very satisfactory. In the asymptomatic
patient, no treatment should be considered and patient
should be kept under observations. In symptomatic patients,
where exposure of the sclerotic masses to the oral cavity is
seen, biopsy or elective extraction of teeth in the involved
area should be avoided. Antibiotic therapy should be instituted. Sequestration of cementum-like masses will occur
slowly, followed by healing. Saucerization or surgical excision of the sclerotic masses is not successful.

Gigantiform Cementoma
Gigantiform cementoma is a rare, benign fibro-cementoosseous disease of the jaws. It is characterized by formation
570

of massive sclerotic masses of disorganized mineralized


material. Both sporadic and familial occurrence has been
reported. The etiopathogenetic mechanism of gigantiform
cementoma is unknown.
The term gigantiform cementoma has been used synonymously with the terms sclerotic cemental masses, orid
osseous dysplasia, multiple enostoses and diffuse sclerosing
osteomyelitis. It was Norberg in 1930 who rst described
gigantiform cementoma. In 1971, the World Health Organization (WHO) classied gigantiform cementoma in the category of cemental lesions.
Clinical features
Gigantiform cementoma is an autosomal dominant disorder having high penetrance and variable expressivity. No
sex predilection has been observed. It typically presents
as a slow-growing, multifocal/multiquadrant and expansile lesions involving both the jaws. The lesions are usually
seen in younger age, although older patients have also
been reported. The size of the lesions seen in older patients
was comparable to those seen in younger individuals.
Thus it has been suggested that these lesions may have plateaued in their growth, probably after cessation of skeletal
growth. The characteristic clinical manifestation is of a
painless maxillary and mandibular swelling with associated facial deformity. Tooth impaction, malpositioning of
teeth and malocclusion are also seen associated with the
swelling. The enlargement of the swelling finally stops
during the 5th decade.
Radiographic features
Radiographically, gigantiform cementoma exhibits multiple
circumscribed, expansile and lobular mixed radiolucentradiopaque lesions that usually cross the midlines of the
jaws. Sometimes large masses are seen in posterior areas
of the jaws and the lesions combining in the midline. This
suggests that lesions might have started as separate posterior
masses; however, with anterior progression they became
confluent and crossed the midlines of the jaws.
Histopathologic features
Microscopically it presents a spectrum of histopathologic features, mainly characterized by variable degrees of cellularity
and variation in the amount and size of mineralized deposits.
The mineralized component is present as admixture of
small and large psammomatoid and spherical hematoxylinophilic, cementum-like calcied deposits and irregular
bony trabeculae in a broblastic proliferative background.
The brous stroma may show fascicular or storiform patterns with spindle-shaped or stellate-shaped broblasts.
The lesions are generally hypovascular, with occasionally
focally rich vascular areas exhibiting aggregates of thickwalled small blood vessels. Mitoses, hyperchromatism and
pleomorphism are not seen.

Chapter 19 Bone Diseases and Fibro-osseous Lesions

Management and prognosis


The surgical management of gigantiform cementoma is usually difficult because of the extensive involvement of the
jaws with these tumors. Surgical inaccessibility, particularly
in the posterior regions of the jaws seems to be responsible
for recurrence of the tumors. These lesions seem to have a
tendency toward recurrence when they are treated with
incomplete surgical removal. It is therefore recommended
that these lesions should be managed with conservative but
complete surgical excision whenever feasible.

Ossifying Fibroma, Cementifying Fibroma and


Cemento-ossifying Fibroma
Ossifying fibroma is the most common fibro-osseous neoplasm of the jaw. It is a bone producing, slow growing,
asymptomatic, well demarcated, benign lesion common in
maxilla and mandible. The tumor is defined as a demarcated
and occasionally capsulated lesion consisting of fibrous
tissue containing variable amounts of mineralized material
resembling bone and/or cementum or both. The term ossifying fibroma is used if the predominant component is
bone, while cementifying fibroma is defined by the presence
of cementum-like spherical calcifications. The lesions characterized by the presence of bone and cementum are referred
to as cemento-ossifying fibroma.
The 1972 WHO classication separated the cementifying
broma which was considered to represent odontogenic
tumors, from ossifying broma, which was considered to
be osseous tumors. However, it has been agreed by all that
the two represent the same pathological condition with different histological presentation. Thus, in 1992, WHO classied the lesion as cemento-ossifying broma. The origin
of the amorphous cementum-like calcications commonly
seen in these lesions is still uncertain. Many of the broosseous lesions of the skull which were excised from the
regions far away from the jaws showed cementum-like calcications which make their cemental origin very unlikely.
It is also known that bone and cementum cannot be distinguished histologically. Thus, the nomenclature represents
only a variation in the histologic presentation. The prognosis and course of the lesion remains the same.

to the tooth-bearing areas of the jaws, although posterior


mandibular lesions may extend upward into the ascending
ramus. The lesion appears as hard, localized and slow growing, painless mass that may displace adjacent structures
and cause root resorption. Exfoliation of teeth may also be
seen. Expansion is seen commonly in the inferior border
of the mandible, followed by buccal plate expansion. On
surgical exploration, the tumor is found to be relatively
hypovascular and well demarcated from the surrounding
tissue, permitting relatively easy separation from the surrounding bone. This demarcation from the surrounding
structure is not seen in fibrous dysplasia and thus can be
used to distinguish the two.
Radiographic features
The lesion appears well circumscribed in contrast to fibrous
dysplasia, the borders of which are ill-defined. Initial lesions
are radiolucent representing an osteolytic image followed by
gradual transformation into a mixed lesion and eventually
becoming radiopaque. The periodontal ligament space of
the involved teeth is clearly seen unlike fibrous dysplasia.
Eversole et al have described two basic radiological patterns: a unilocular radiolucency with or without radiopaque foci, and a multilocular radiolucency. The former
presentation is found to be more common. Expansion of
the cortical plates is a common finding. Teeth displacement
and root resorption may be seen (Figure 1).
Histopathologic features
Ossifying fibroma shows a range of histologic appearances. It shows fibrous and osseous tissues with the former
Figure 1

Etiology
Ossifying fibroma occurring in the jaw seems to arise from
the periodontal membrane, which contains pluripotential
cells capable of forming cementum, bone and fibrous tissue.
Clinical features
Ossifying fibroma shows a definite female predilection,
with the mandible (premolarmolar area) involved more
than maxilla in most of the cases. These occur mostly in
the 3rd and 4th decades of life. The lesions are restricted

Lateral cephalograph in a patient suffering from ossifying


fibroma reveals an extensive expansion of the cortical
plate in the mandible. Multilocular radiolucency is evident.
Courtesy: Department of Oral Medicine and Radiology,
MCODS, Mangalore

571

Section VII System Review

tissue predominating. The fibrous stroma is highly cellular,


with spindle-shaped fibroblastic cells arranged in whorls.
A fibrous capsule may be seen in some cases. The osseous
tissue consists of rounded or lobulated basophilic masses
(cementum-like), trabeculae of osteoid, woven or lamellar
bone, or combination of the two. Osteoblastic rimming
around the trabeculae can be seen. Focal clusters of giant
cells (osteoclasts) can be seen to be arranged haphazardly
or adjacent to the mineralized material.
The histologic differentiation of ossifying broma
from osteogenic sarcoma may occasionally cause difculty for the pathologist. Ossifying broma shows osseous
tissue which is relatively uniform and regularly arranged.
On the other hand, in osteogenic sarcoma, the bone
spicules and osteoid usually demonstrate irregularity and
haphazard arrangement along with signicant cellular
anaplasia.
Management
The ossifying fibroma can usually be excised in one piece
or removed in several large fragments. Prognosis is excellent and recurrence after removal is seldom seen. There is
no evidence of malignant transformation.

Juvenile Ossifying Fibroma


(Psammomatoid and Trabecular)
Juvenile ossifying fibroma is an uncommon lesion that
affects the jaw of children under 15 years of age. Histologically it is composed of cell-rich fibrous tissue containing bands of cellular osteoid, trabeculae of bone and
aggregates of giant cells. There are two histologic variants
of juvenile ossifying fibroma: psammomatoid and trabecular variants. The lesion is characterized by the early age
of onset, the bone pattern, the high tendency to recurrence
and the aggressive local behavior. The lesion has been
variously described as juvenile ossifying fibroma, active
juvenile ossifying fibroma, aggressive ossifying fibroma,
reticular desmo-osteoblastoma or active fibrous dysplasia.
The term juvenile (aggressive) ossifying broma was
used in the second edition of the WHO classication of
odontogenic tumors to describe a lesion affecting the jaws
of children under the age of 15 years. This term is used to
describe two distinct histopathologic variants of ossifying
broma of the craniofacial skeleton. These are referred to
here as psammomatoid juvenile ossifying broma and trabecular juvenile ossifying broma. Psammomatoid juvenile ossifying broma was rst reported by Benjamins,
in 1938, who gave it the designation osteoid broma with
atypical ossication of the frontal sinus. It was later
termed psammomatoid ossifying broma of the nose and
paranasal sinuses by Ggl, in 1949. The same lesion was
later termed juvenile active ossifying broma by Johnson
et al in 1952. Makek considered the lesion to be a variant
572

of osteoblastoma and termed it psammous desmo-osteoblastoma.


Trabecular variant of juvenile ossifying broma was
described by Reed and Hagy, in 1965. Makek described the
trabecular variant as trabecular desmo-osteoblastoma.
Etiology
Juvenile ossifying fibroma is considered to develop from
undifferentiated cells of the periodontal ligament.
Clinical features
The lesion characteristically occurs under the age of 15 years
in 79% of cases. The psammomatoid variant occurs exclusively in the extragnathic craniofacial region especially in
the orbital bones and paranasal sinuses (61.6%), and less
commonly in the jaws, maxilla (19.7%) and mandible
(7%). Few cases have been reported to occur in calvarium,
parietal, temporal and frontal bones. In mandible, the tumor
occurs more commonly in the ramus than in the body of
the mandible. There seems to be no predilection for either
sex. Patients often present with symptoms such as exophthalmus, bulbar displacement and proptosis when affecting the orbital bones and paranasal sinuses. In the jaws,
the affected region shows a painless expansive swelling of
several months. Development of aneurysmal bone cyst in
psammomatoid juvenile ossifying fibroma is commonly
reported. The cyst tends to occur more commonly in the
younger patients in the 1st and 2nd decades of life.
The trabecular variant is characterized by a progressive
and sometimes rapid aggressive growth. The tumor expands
the affected bone, leading to facial asymmetry. It occurs
more commonly in maxilla as compared to mandible. Few
cases have also been reported in sinonasal region. Slight
male predominance has been observed with an average
age range of 8.512 years. In maxilla, tumor may lead
to nasal obstruction, epistaxis and eye displacement. The
duration of the lesion is usually a few months.
Radiographic features
Radiographically, the psammomatoid variant shows welldefined expansion of the affected bone having mixed radiolucent, radiodense and ground-glass appearance. The lesion
is partially or completely surrounded with thin, corrugated
margins. Sometime multilocular appearance may be seen
representing the small cystic spaces.
The trabecular variant is expansive, well-dened and
unilocular or multilocular with cortical thinning and
perforation. The tumor mass is radiolucent with variable
calcication-induced radiopacities, occasionally demonstrating ne specks and occasionally producing a groundglass appearance. Increase in radiodensity may be observed
over time. Root resorption and displacement of involved
teeth are also observed.

Chapter 19 Bone Diseases and Fibro-osseous Lesions

Histopathogic features
Microscopic examination of psammomatoid juvenile ossifying fibroma shows well demarcated but unencapsulated
lesion composed of numerous small rounded mineralized
collagenous bodies (psammomatoid ossicles) uniformly
distributed within a cellular fibroblastic stroma. The cellularity of the fibroblastic stroma varies in different tumors
and at different sites within the same lesion. Occasional
shrunken cells, representing nuclei of osteocytes, are embedded within the ossicles, and there is usually a collagen outer
band to these mineralized bodies. Some of the ossicles
may show a basophilic center and eosinophilic fringe. In
the periphery of the lesions, some of the ossicles show a
transition into small bone trabeculae. The tumor infiltrates
and destroys the adjacent bone with focal induction of
reactive bone formation. Development of aneurysmal cyst
is followed by focal myxoid change in the stroma with hemorrhage and osteoclastic giant cells, with gradual expansion and formation of cysts with thin fibrous walls. The
differential diagnosis with other fibro-osseous lesions of
the jaw, such as cemento-ossifying fibroma, osteoid osteoma or bone dysplasia, should be made with a mandatory
pathological study, and is largely based on the nature of
the calcified products of the tumor. The mineralized tissue
of central ossifying fibroma is composed of a variable
combination of mature and immature bony trabeculae and
lobulated basophilic masses of cementum-like material.
There may be occasional concentrically laminated particles,
called cementicles, but these are not a prominent feature
of psammomatoid entity.
Microscopic features of trabecular variant of juvenile
ossifying broma shows an unencapsulated tumor mass
inltrating into the surrounding bone and reactive bone
formation at the periphery. The tumors show a characteristic loose structure with cell-rich stroma composed of
broblastic spindle cells that produce little collagen.
Anastomosing trabeculae of osteoid is seen in a pattern
that resembles paintbrush strokes. The osteoid areas
mature into woven bone trabeculae that are rimmed with
osteoblasts and show osteocytes embedded in it. Aggregates
of osteoclastic giant cells are commonly present and seen
in association with the bony trabeculae and in separate
foci in the brous stroma, usuallybut not alwaysat sites
of hemorrhage. Mitotic gures may be observed in the
stroma but are never numerous. Cystic degeneration and
aneurysmal bone cyst formation have been described in a
few cases.
Management and prognosis
Recurrence after surgical management is common and is
reported to range from 30 to 56% in psammomatoid juvenile ossifying fibroma. Recurrence may be attributed to
difficulty in proper resection caused by the location of
the lesion and the infiltrative nature of tumor borders.

Malignant change has not been reported. Fatal consequences


are extremely rare and usually caused by complications
arising from direct intracranial extension with resultant
encephalitis and meningitis.
Trabecular juvenile ossifying broma should be conservatively excised in its entirety. Recurrences are seen in
3050% of cases. More than one excision may be required
to achieve cure. No malignant transformation has been
reported.

Fibrous Dysplasia
Fibrous dysplasia of bone is an uncommon congenital skeletal disorder. It is characterized by the replacement of normal bone and marrow by fibrous tissue, within which
irregular trabeculae of woven bone are haphazardly distributed. The maturation of bone is arrested at the woven bone
stage. It may affect single (monostotic) or multiple bones
(polyostotic) and may be associated with endocrinopathies.
A paper by von Recklinghausen in 1891 was probably
the rst citation of the disease. Albright pointed out two
cases that were described by von Recklinghausen as
examples of osteitis brosa generalisata due to hyperparathyroidism were almost certainly examples of brous dysplasia. The term brous dysplasia was rst suggested by
Lichtenstein in 1938 as a designation for multiple bone
lesions that were described by Albright et al as osteitis
brosa generalisata. The lesions of brous dysplasia were
initially considered to be primarily polyostotic. Lichtenstein
and Jaffe later expanded this concept and noted that isolated (monostotic) form of disease also occurred and was
by far more common than the polyostotic. McCune and
Albright in 1936 and 1937 respectively showed an association of polyostotic brous dysplasia with abnormal skin
pigmentation, and precocious puberty because of which
this association has been termed as McCuneAlbrights
syndrome. JaffeLichtenstein described the association of
polyostotic brous dysplasia with abnormal skin pigmentation; thus it was named as JaffeLichtenstein syndrome.
Etiology
The molecular mechanism responsible for fibrous dysplasia
is a postzygotic activating mutation of the GNAS1 gene
that encodes for the Gs subunit of the heterotrimeric
G protein complex. The result is constitutive activation of
the adenylyl cyclase enzyme and overproduction of
3,5-cyclic adenosine monophosphate. The most common
GNAS1 gene mutations are a replacement of arginine by
either cysteine or histidine at codon 201 (R201C or R201H),
but other mutations have also been identified. The severity
of the disease phenotype is thought to depend on when the
mutation occurs during embryogenesis. If the mutation
occurs during the formation of the inner cell mass, all three
germ cell layers will be affected and the phenotype will be
573

Section VII System Review

McCuneAlbrights syndrome. If it occurs later in development, only one or two germ cell layers will be affected and
the phenotype is less severe. Fibrous dysplasia is considered a disease of cells of the mesenchymal stem cell/
osteoblastic lineage in which excess cyclic adenosine monophosphate impairs the ability of the stem cell to differentiate
into a mature functioning osteoblast.
Clinical features
Fibrous dysplasia is mainly diagnosed before the age of
30 years and is equally seen in both the sexes. It occurs
both in polyostotic and monostotic forms. Monostotic
form is at least six times more common than polyostotic
form.
In polyostotic form of disease two or more bones are
affected generally the long bones, ribs and skull, although
any bone may be affected. The lesions are often found
unilaterally. Painless expansion of the affected area is most
common complaint of the patient. Pathological fracture with
resultant pain and bone deformity are other symptoms.
Presence of abnormal skin pigmentation with polyostotic
brous dysplasia is termed as JaffeLichtenstein syndrome. The abnormal hyperpigmentation seen resembles
caf-au-lait spots which mean coffee with milk. The hyperpigmentation tends to be present on the same side and on
the skin overlying the lesions of brous dysplasia. The
hyperpigmented macules are well-dened and have irregular borders which sometimes distinguish them from the
lesions associated with neurobromatosis. The color can
be medium to dark brown.
Association of endocrine abnormalities with skin
hyperpigmentation and polyostotic brous dysplasia is
termed as McCuneAlbrights syndrome. A variety of
endocrine abnormalities such as accelerated skeletal growth,
acromegaly, gigantism, hyperprolactinemia, Cushings
syndrome, hyperthyroidism, hyperparathyroidism, diabetes mellitus, hypothalamic hypogonadism and hypophosphatemic rickets, gynecomastia, spermatogenesis in young
boys and sexual precocity in girls have been associated
with the disease. Sexual precocity is the most common
endocrine abnormality seen in the affected individual.
Male children exhibit enlarged genitalia and advanced
secondary sex characteristics. Female children manifest
estrogen excess.
Monostotic form of the disease is seen in 8085% of
cases. The jaws are the most common areas affected, with
the maxillary jaw being more common than the mandibular jaw. The maxillary lesions frequently involve a group
of contiguous bones separated by sutures (i.e. maxilla,
zygoma, sphenoid and occiput) and thus are not strictly
monostotic lesions. Such lesions are more appropriately
classied as craniofacial brous dysplasia. The craniofacial region is involved in up to 25% of the patients with
monostotic brous dysplasia, and in approximately 4060%
574

of those with the polyostotic brous dysplasia. Similarly,


maxillofacial brous dysplasia is the term recently described
by Mahajan et al for the lesions which are limited to the
facial bones. Painless enlargement of the affected bone is
most commonly seen. The patient usually is not able to
recall the onset of the swelling. Maxillary and mandibular
brous dysplasia is associated with signicant facial and
palatal asymmetries, heterogeneous dental anomalies (rotation, oligodontia, displacement, enamel hypoplasia and
hypomineralization, taurodontism, and others), malocclusion, and a high caries index score.
Radiographic findings
The diagnosis of fibrous dysplasia can be made by radiographs although it is not unusual for bone biopsies to be
required because of uncertainty based on radiographs alone.
The characteristics, which are somewhat variable, include
a ground-glass appearance, which occurs due to superimposition of a myriad of thin, poorly calcified trabeculae.
Ground-glass appearance can be best appreciated in a
good quality periapical or occlusal view (Figure 2). Early
lesions may be radiolucent or mottled. Mandibular lesions
sometimes may appear multilocular on the radiograph
which is an optical illusion occurring due to endosteal
cortical erosion caused by growth of the lesion contrasting
with areas of preserved normal cortex. The lesion of
fibrous dysplasia is usually ill-defined radiographically;

Figure 2

Mandibular occlusal radiograph showing expansion of the


cortical plates and ground-glass appearance in fibrous
dysplasia. Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

Chapter 19 Bone Diseases and Fibro-osseous Lesions

they tend to blend imperceptibly into the adjacent bone.


Foci of irregular or denser calcification may be seen superimposed on ground-glass appearance. Waters view of
maxillary lesions frequently shows a radiodense area that
largely obliterates the maxillary sinus and involves the
zygoma and lower rim of the orbit. Most common manifestation of fibrous dysplasia in the skull is the thickening
of the occiput and base of skull. Involved dentition shows
narrowing of the periodontal ligament space with an illdefined lamina dura that blends with the abnormal bone.
Taurodontism of the teeth may also be seen. Involvement
of the mandible results in expansion of the cortical plates
and bulging of the lower border of the mandible. When
long bones are affected in an advanced stage, there may
be a Shepherds crook deformity of the proximal femur.
Computerized tomography (CT) of brous dysplasia is
useful in demonstrating the ground-glass texture of the
lesion and is particularly helpful in dening the extent of
craniofacial disease (Figure 3).
Magnetic resonance imaging (MRI) does not provide a
characteristic appearance of brous dysplasia and therefore is a less useful imaging modality.

to be delicate and are not connected to one another. The


trabeculae are not sharply defined and along their margins
the bone matrix streams out along the collagen fibers that
extend from the trabeculae into the neighboring stroma.
Under polarizing microscope irregular birefringent fibers
of immature or woven bone can be demonstrated. The
bone formed is metaplastic in nature thus the trabeculae
are not seen to be surrounded by osteoblasts. This form of
metaplasia is called a fibro-osseous metaplasia. Older
lesions may show lamellar maturation. At the periphery of
the lesion pre-existing host lamellar bone may be seen
without a clear demarcation between the lesion and the
host bone. The fibrous stroma comprises immature appearing small, slender spindle cells in loose and whorled
arrangement. Giant cells are usually not seen in lesions of
fibrous dysplasia but if seen are usually associated with the
pre-existing mineralized tissue. Presumably, they are
responsible for spread of the lesion.
The microscopic features of macules show excessive deposition of melanin, despite a normal number of melanocytes.

Histopathologic features

Serum calcium and phosphorus levels are normal. The serum


alkaline phosphatase levels may be elevated, roughly corresponding to the extent of the bone lesions. The levels
do not increase as seen in Pagets disease. Urinary hydroxyproline, specific index of bone collagen resorption, can
be elevated. In patients with McCuneAlbrights syndrome
the various endocrinopathies are associated with elevations of circulating hormones depending on which glands
are affected. High levels of growth hormone, prolactin,
and thyroid hormones and, less commonly, testosterone,
adrenocorticosteroids and parathyroid hormone have
been reported. In patients with rickets or osteomalacia,
hypophosphatemia and hyperphosphaturia are usually
present.

Grossly, the tissue is calcified, firm, gritty or granular. The


characteristic microscopic features of fibrous dysplasia
comprises a fibrous stroma in which spicules of woven
bone are found. The woven bone is present in the form of
irregular shaped trabeculae which can be resembled to
Chinese script writing (Figure 4). The bone trabeculae tend
Figure 3

Laboratory investigations

Figure 4

Computed tomographic image showing expansion of the


cortical plate and invasion of the maxillary sinus in fibrous
dysplasia. Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

The irregular (Chinese letter-shaped) trabeculae of bone in


fibrous dysplasia. Courtesy: Department of Oral Pathology,
MCODS, Mangalore

575

Section VII System Review

Management and prognosis


In most cases, the disease tends to stabilize and essentially
stops growing when skeletal maturation is reached. Small
lesions, particularly in mandible can be removed by complete resection. However diffuse and larger lesions preclude
their removal without extensive surgery. Cosmetic deformity, with associated psychological problems or functional
deformity may require surgical intervention. Re-growth
of the lesion is seen in 2550% of the patients after a
shave-down procedure. Re-growth after surgical procedures appears to be more common in younger patients
suggesting that surgical intervention should be delayed as
long as possible.
Malignant change in brous dysplasia, usually an
osteosarcoma rarely has been reported. This risk increases
in patients who receive radiation therapy. Thus radiation
therapy is denitely contraindicated in brous dysplasia.
Patients should be kept under long-term follow-up to rule
out any malignant changes. Patients with brous dysplasia do not have any complications associated with the
routine dental care.

BONE DISEASES
The bones of the facial skeleton particularly the maxilla
and mandible are affected by various diseases. These diseases present with a myriad of clinical features and characteristic oral manifestations. This section will attempt to
highlight common bone diseases affecting the maxillofacial
skeleton.

Osteogenesis Imperfecta
Osteogenesis imperfecta has also been referred to as
brittle bone disease, Vrolik syndrome and EkmanLobstein
syndrome.
Osteogenesis imperfecta is an inherited disorder of the
connective tissue having an autosomal dominant pattern
of inheritance. However, autosomal recessive and nonhereditary types have also been known to occur. The condition is characterized by fragile bones that tend to break
easily, often from the mildest of trauma.
Pathophysiology
The primary pathology in osteogenesis imperfecta is the
disturbance in the synthesis of type I collagen (predominant
protein of the extracellular matrix of most tissues). In bone,
this defect of extracellular matrix causes osteoporosis. The
affected bones become weak and fragile thereby making
them susceptible to fracture. Type I collagen is also a
major constituent of dentin, sclerae, ligaments, blood vessels and skin; therefore, abnormalities of these structures
576

is also seen in individuals suffering from osteogenesis


imperfecta.
Mutations that interfere with expression of the collagen
gene, formation of the triple helix (amino acid sequencing),
or procollagen secretion, affect the structure and function
of collagen brils, resulting in osteogenesis imperfecta.
Electron microscopic studies in osteogenesis imperfecta
reveals a smaller diameter of the collagen bril and smaller
than normal apatite crystals when compared to that of normal individuals.
Mutations in COL1A1 gene on chromosome 17 and the
COL1A2 gene on chromosome 7 (genes that encode for the
synthesis and/or structure of type I collagen) may cause a
combination of production of abnormal collagen and
decreased production of normal collagen. The variability in
combinations results in the different phenotypic expressions
of osteogenesis imperfecta.
Milder forms of osteogenesis imperfecta are caused
primarily by the decreased production of normal collagen,
while more severe forms are caused primarily by the production of abnormal collagen. These abnormalities may be
dominantly inherited or the result of sporadic mutation.
Classification
Dominant or classical osteogenesis imperfecta Majority
of the cases of osteogenesis imperfecta (up to 90%) are
caused by a dominant genetic defect. These individuals
have a 50% chance of passing on the disorder to each of
his/her progeny. Though most children in the dominant
form inherit the disorder from a parent, some are born
with the dominant form of osteogenesis imperfecta even
though there is no family history of the disorder. In these
children, the genetic defect occurs as a result of a spontaneous mutation.
Recessive osteogenesis imperfecta It is believed that
approximately 1015% of cases of osteogenesis imperfecta
are caused by a recessive mutation. The parents do not have
the disorder but their genes are mutated. To inherit the
recessive condition the individual must receive a copy of
the mutation from both parents. If one parent has osteogenesis imperfecta because of a recessive mutation, 100%
of their children will be carriers of the recessive mutation.
Whether any of these children will have the condition will
depend on their inheritance from the other parent.
Based on the clinical features and molecular studies
osteogenesis imperfecta is currently divided into eight
types.
It is estimated that approximately 8590% of osteogenesis imperfecta are caused by a dominant mutation in
a gene coding for type I collagen. Osteogenesis imperfecta
Types I, II, III and IV belong to this category. Types V and
VI do not have a type I collagen mutation, but the genes
causing them have not yet been identied. Types VII and
VIII are inherited in a recessive manner.

Chapter 19 Bone Diseases and Fibro-osseous Lesions

Clinical features
Type I It is the most common and mildest form of osteogenesis imperfecta. These patients present with normal or
close to normal stature. They may have muscle weakness
and hypermobility of joints. Since the bones are fragile
they tend to fracture easily and most of the fractures occur
before puberty. Fragility of the walls of the blood capillaries may be seen. The patients may present with a triangular shaped face. Some authors describe the facies to be
similar to that of cleidocranial dysostosis. The skull may
be disproportionately large with a temporal bulge thereby
causing the ears to be pushed outward and forward. The
forehead is broad with frontal bossing giving rise to a
mushroom-shaped skull.
Hearing loss due to osteosclerosis, may be usually seen
in the 2nd and 3rd decades of life. These patients typically
present with blue, purple or gray tinted sclera (Figure 5).
The sclera in these individuals tends to be extremely thin,
therefore allowing the color of the underlying choroid to
be transmitted. Most of the patients have normal teeth
whereas some may present with opalescent brittle teeth.
Histologically collagen has normal structure but the quantity of the collagen present is usually less than normal.
Type II It is the most severe and lethal form of this condition. Most infants are still born or die shortly after birth.
The death may occur mostly due to respiratory distress or
intracerebral hemorrhage. It is estimated that almost 90%
of the infants do not live longer than a month. Severe bone
deformity and multiple fractures are evident. These individuals have a small stature with underdeveloped lungs.
Blue colored sclera is seen. The collagen that is formed is
insufficient in quantity and is of poor quality. Dentinogenesis imperfecta may be seen.
Based on the radiographic ndings of the long bones
and ribs, Type II osteogenesis imperfecta is subdivided into
groups A, B and C. Type IIA demonstrates broad and short

long bones with broad and beaded ribs. Type IIB shows
broad and short long bones with thin ribs that have little
or no beading. Type IIC group shows thin and longer long
bones with thin and beaded ribs.
Type III In Type III osteogenesis imperfecta the bones
are extremely fragile and hence have an increased tendency to fracture. Fractures are often present at birth.
These individuals are usually short statured. The sclera has
a bluish tint. It has been reported that the mortality rate is
generally higher at adolescence. Kyphoscoliosis causes
cardiopulmonary distress resulting in death. A barrelshaped rib cage is seen. The patients may have a triangular
face. Hearing loss can be seen; some patients may present
with brittle opalescent teeth. Histologically the collagen is
improperly formed.
Type IV Individuals suffering from Type IV osteogenesis
imperfecta may show mild to moderate bone fragility. It is
considered that the severity of this form of the condition
is in between the severity of Type I and Type III osteogenesis imperfecta. These individuals may present with a mildto-moderate bone deformity and a slightly shorter than
average stature. Bones are fragile and fractures are usually
present before puberty. The sclera is generally white (normal) in color. Some patients may present with a faint blue
tint. Triangular face and barrel-shaped rib cage is usually
seen. Teeth may be brittle and appear opalescent in some
patients. Hearing deficits may be encountered. Histologically there is improper formation of collagen.
Type V It has a dominant inheritance pattern. Individuals
of this form of the condition do not exhibit mutations in
type I collagen genes. It mimics the symptoms and signs of
Type IV osteogenesis imperfecta.
The site of fracture shows hypertrophic calluses. Radiographs of long bones reveal a radiodense band adjacent to
the growth plate. The sclera is white and teeth are normal.
The characteristic microscopic nding is the presence of
mesh-like pattern of bone.

Figure 5
Type VI This subtype of osteogenesis imperfecta mimics
the symptoms and signs of Type IV. It is believed to be
inherited as a recessive trait.
The characteristic sh scale appearance of bone under
a microscope is unique for this type of osteogenesis imperfecta. Blood investigations reveal minimally elevated levels of alkaline phosphatase.

Blue colored sclera. Courtesy: Department of Oral Medicine


and Radiology, KLE Institute of Dental Sciences, Bangalore

Type VII It is inherited in a recessive manner. It is


believed to originate from mutation to the cartilage associated protein (CRTAP) gene.
This type of osteogenesis imperfecta mimics Type IV or
lethal Type II. Infants may present with a small head and
round face. The sclera are white; other features include
short stature, short humerus and femur. Another typical
feature is a deformation of the hip joint (coxa vara).
577

Section VII System Review

Type VIII It is inherited in a recessive manner. It is


believed to be caused by the mutation of LEPRE1 gene. The
clinical features in this type are similar to those of osteogenesis imperfecta lethal Type II or Type III. However, infants
present with severe growth deficiency and white sclera.

of multiple joints usually with flexion deformities, with or


without pterygia or webbing at the joints involved) and
osteogenesis imperfecta.

Orofacial manifestations

Exercises such as walking, swimming and water therapy,


to strengthen bones and muscles are recommended.
Patients should be advised to refrain from smoking, alcohol consumption, excessive use of caffeine and use of steroids as these can accelerate the rate of bone depletion.
Bisphosphonates such as palmidronate have been used
successfully in managing osteogenesis imperfecta. It is
believed that palmidronate minimizes the rate of bone
loss. It can be administered intravenously in a dosage of
7.5 mg/kg/year at 46 month intervals.

Patients suffering from this condition can present with triangular facies as a result of the soft craniofacial bones
along with a large and thin calvarium.
Osteogenesis imperfecta can be associated with dentinogenesis imperfecta. The color of teeth affected by
dentinogenesis imperfecta may vary from blue to gray to
brown. The outer enamel may often chip off to reveal the
underlying soft dentin.
Other skeletal and dental disturbances noted are the frequent presence of a skeletal class III malocclusion (especially
in type III and type IV osteogenesis imperfecta) and anterior
and posterior crossbites.
Radiographic features
General radiographic findings The common feature in
all forms of osteogenesis imperfecta is osteoporosis. In the
milder forms of the disease, the bones exhibit thin cortices
and minimal fractures. However, in severe forms of the
disease the long bones are stunted and exhibit extensive
fractures. The skull is poorly mineralized and exhibits
wormian bones. Spinal deformities such as flattened spinal
bones (platyspondyly) and S-shaped scoliosis. Other characteristic features associated with osteogenesis imperfecta
include cod fish vertebrae, popcorn calcifications in the
metaphyseal-epiphyseal region of long bones, especially
of the knee and ankle caused due to repeated microfractures at the growth plate, basilar invagination or impression (projection of the tip of the odontoid process above
the McGregor line) and Tam OShanter skull (caused by
large and thin cranium with platybasia).
Radiographic findings specific to oral cavity Teeth may
have bulbous crowns constricting at the cervical portion
and stunted roots. The pulp chamber and radicular portion
of the pulp may be partially or totally obliterated.
Dental considerations
Since most patients especially in the younger age group
have high susceptibility for fractures, excessive force should
best be avoided during extraction of teeth. Tooth wear
may be managed esthetically with restorations or crowns.
Syndrome association
Datta and others (2005) reported a 34-week pre-term baby
suffering from Bruck syndrome, which is a combination of
arthrogryposis multiplex congenita (congenital contractures
578

Management

Osteopetrosis
Osteopetrosis is also known as marble bone disease
and AlbersSchnberg disease. It was first described by
AlbersSchnberg, a German radiologist in 1904.
Osteopetrosis is a rare disorder of bone that arises from
defective differentiation and function of osteoclasts and
reduced generation of superoxide by leukocytes. As the
osteoclasts fail to resorb bone, the bones become dense
and fragile. Bone fragility occurs because very few collagen bers connect osteons adequately and the remodeling
of woven bone to compact bone is defective. This, in turn,
will make bones vulnerable to fracture.
The actual incidence of osteopetrosis is unknown.
However, Beighton et al (1979) reported that the overall
incidence of osteopetrosis was approximately one case in
100,000500,000 population.
Pathophysiology
The gene for adult osteopetrosis has been mapped to chromosome 1p21 (Van Hul, 1997).
Whyte (1999) described few probable reasons for the
functional failure of osteoclasts such as abnormalities in
the osteoclast stem cell or its microenvironment, osteoblast
precursor cells or the mature heterokaryon or in the bone
matrix.
Other factors that may predispose to altered bone
resorption that may inuence osteoclastic activity include
synthesis of abnormal parathyroid hormone and defective
production of interleukin-2 (IL-2). Hofbauer (1999) reported
osteopetrosis in cathepsin K (cysteine protease important
for osteoclast function) decient mice.
Types
Three distinct clinical forms of osteopetrosis are recognized:
1.

Adult form of osteopetrosis (osteopetrosis tarda)autosomal dominant

Chapter 19 Bone Diseases and Fibro-osseous Lesions

2.
3.

Infantile form of osteopetrosis (osteopetrosis congenita)autosomal recessive


Intermediate form of osteopetrosis (marble bone
disease)autosomal recessive.

The other rare varieties of osteopetrosis are transient


infantile, lethal and post infectious.
Clinical features
Adult form of osteopetrosis The adult form of osteopetrosis is usually discovered later in life on radiographic
examination. It is believed to be asymptomatic in about
60% of the patients. The usual complaint could be related
to bone pain, fractures and osteomyelitis. The typical radiographic finding in osteopetrosis tarda is sclerosis of the
axial skeleton. The long bones are generally spared or
minimally affected.
The adult form has two subtypes:
1.
2.

Type I: Occurrence of fractures is rare, cranial nerve


compression, normal serum acid phosphatase levels.
Type II: Fractures are commonly seen, cranial nerve is
rarely compressed, high levels of serum acid phosphatase levels.

A prominent dental consideration is the susceptibility to


develop osteomyelitis following dental extractions. Other
oral findings include increased susceptibility to carious
lesions, delayed eruption of teeth and/or malformed teeth.
Osteopetrosis congenita It is a severe form in which the
patient suffers from osteopetrosis at birth or in the first few
years of life. This condition is usually fatal due to bleeding,
severe anemia or uncontrollable infection. The skeleton
reveals generalized sclerosis. Osteopetrosis results in severe
bone marrow failure. Subsequently hepatosplenomegaly is
seen to compensate for hematopoiesis. Involvement of the
cranial foramina results in blindness, deafness and hydrocephalus. The child shows extreme growth retardation.
Other orofacial features include frontal bossing, hypertelorism and paranasal sinus malformations. Like other
forms of osteopetrosis the jaws are susceptible to osteomyelitis following dental extractions.
Marble bone disease The intermediate form of osteopetrosis is not as severe as osteopetrosis congenita. In this
form of the disease, bone marrow failure is not seen. These
individuals have retarded growth and may present with
fractures in the 2nd decade of life. However, they may
show intracranial calcifications, macrocephaly and cranial
nerve deficits. These individuals also show increased susceptibility to infections.
Histopathologic features
The presence of remnants of mineralized primary spongiosa
that persists as islands of calcified cartilage within mature
bone is typical of osteopetrosis.

Other features of abnormal endosteal bone formation are


evident such as tortuous lamellar trabeculae replacing the
cancellous portion of bone, globular amorphous bone deposition in marrow spaces and osteophytic bone formation.
The number of osteoclasts may be increased, normal or
decreased, but there is no evidence of functional osteoclasts, as Howships lacunae are not visible.
In the adult form of osteopetrosis, there is increased
amount of osteoid. The osteoclasts are usually few in number
and they lack rufed borders. Occasionally, the osteoclasts
may be large in size and may be present in large number.
Presence of woven bone may be a common feature.
In the infantile form of osteopetrosis, osteoclasts are
usually abundant and found at the bone surfaces. Osteoclast
nuclei are especially numerous, but the rufed borders or
clear zones that characterize normal osteoclasts are absent
and brous tissue usually crowds the marrow spaces.
Radiographic features
There is generalized, homogeneous increase in density
throughout the skeleton. The increased density obscures
the trabecular pattern such that the cortical bone and cancellous bone cannot be differentiated. Long bones may
appear club-like or bone within bone (endobone).
The skull shows increased radiodensity, especially at
the base. Sinuses are small and not fully pneumatized. The
extremely radiopaque vertebrae may exhibit alternating
bands which is referred to as known as the rugger-jersey
sign. The pelvic bones show subcrestal sclerosis.
Radiographic findings of jaws and teeth
The maxilla and mandible exhibit increased radiodensity.
Owing to the increased radiodensity, internal structures such
as teeth and other normal anatomic landmarks are not
readily visible.
The increased density of bone compromises the vascularity thereby making the jaws susceptible to infections
(such as osteomyelitis).
Osteopetrosis may cause delayed eruption of teeth.
Other dental ndings include relatively thickened lamina
dura, premature loss of teeth and malformed teeth. Teeth
may be susceptible to carious lesions as they are poorly
calcied.
Management and prognosis
Infantile osteopetrosis if untreated will usually result in
death in the first few years of life due to bone marrow
failure.
The only cure for children with severe osteopetrosis is
allogenic hematopoietic stem cell transplantation.
Askmyr et al (2008) propose the possibility for gene
replacement therapy to manage osteopetrosis. In their article,
they describe that the hematopoietic stem cell-targeted
579

Section VII System Review

gene therapy in a mouse model of infantile malignant


osteopetrosis has reportedly shown to correct many signs
and symptoms of osteopetrosis.
Key (1995) conducted a 6-month trial to study the efcacy of recombinant human interferon gamma on osteopetrosis. In the study comprising 14 patients suffering from
severe osteopetrosis, they administered subcutaneous
injections of recombinant human interferon gamma-1b
(1.5 g/kg of body weight per dose) three times per week
6 months. There were no side effects reported. They concluded that long-term therapy with interferon gamma
increases bone resorption and hematopoiesis and improves
leukocyte function.
Corticosteroids have also been used in managing osteopetrosis, though it is not a preferred modality of treatment.
Steroids have known to increase the red blood cell mass and
platelet count, but they do not improve the bone mass.
In another independent study, children suffering from
osteopetrosis were administered 1,25-dihydroxy vitamin D.
The study showed no improvement in the clinical condition
of these children. However, bone biopsies showed evidence of increased osteoclastic bone resorption.
Key and others (1984) suggested that large doses of
calcitriol (up to 32 g/day) along with the use of calcium
decient diet will stimulate bone resorption by activating
the dormant osteoclasts.

Cherubism
Cherubism is a non-neoplastic hereditary bone lesion that
is histologically similar to central giant cell granuloma.
It affects the jaws of children bilaterally and symmetrically, producing the characteristic cherubic appearance.
Cherubism has also been referred to as familial or hereditary fibrous dysplasia, bilateral giant cell tumor and familial
multilocular disease.
Cherubism was rst described by Jones in 1933. He
termed it familial multilocular disease of the jaws. However, as the cystic nature of the condition was invalidated
Jones and others were the rst to use the term cherubism.
The word cherub originally designated a member of the
second order within the Christian celestial chorus. These
were creatures with severe, staring eyes (including eyes on
the wings and the body) and a wheel below the feet.
Angels constituted another order within the celestial chorus, and angels with childish, full-cheeked faces, often
gazing upward, were widely depicted in baroque art. Thus,
the term cherubism, is actually inappropriate for the disease, because the typical clinical picture does not resemble
a classical cherub but a baroque angel.
According to the WHO classication, cherubism belongs
to a group of non-neoplastic bone lesions affecting only the
jaws. It is a rare, benign condition with autosomal dominant inheritance, and it is one of the very few genetically
determined osteoclastic lesions in the human body.
580

Genetic basis
The locus for the cherubism gene is 4p16. The most reasonable conclusion from the linkage data obtained in a study
of four families by Tiziani and others is that the locus for
cherubism is located on the telomeric side of D4S1582.
Ueki et al detected point mutations causing amino acid
substitutions in the SH3-binding protein SH3BP2.
Clinical features
Cherubism appears to have 100% penetrance in males and
only 5070% penetrance in females. Although the condition is known to be hereditary, in some cases there has
been no detectable family history, and although it usually
occurs bilaterally, there have also been cases of unilateral
involvement, perhaps because of incomplete penetrance or
new mutations.
Typically, the jaw lesions of cherubism remit spontaneously when affected children reach puberty, but the reason
for this remission is unknown. The reduction in osteoclast
formation caused by sex steroids and the increase in plasma
concentrations of estradiol and testosterone at puberty
both suggest that the genetic defect responsible for the
localized increase in osteoclasts in cherubism is overridden
and normalized by the increased synthesis of sex steroids.
Affected children are normal at birth and are without
clinically or radiographically evident disease until 14 months
to 3 years of age. At that time, symmetric enlargement of
the jaws begins. Typically, earlier the lesion appears, the
more rapidly it progresses. The self-limited bone growth
usually begins to slow down when the patient reaches
5 years of age, and stops by the age of 1215 years. At
puberty the lesions begin to regress. Jaw remodeling continues through the 3rd decade of life, at the end of which
the clinical abnormality may be subtle.
The signs and symptoms depend on the severity of
the condition and range from clinically or radiographically
undetectable features to grotesquely deforming mandibular and maxillary overgrowth with respiratory obstruction
and impairment of vision and hearing. Cherubism was
reportedly fatal in one case, where aspiration occurred
because of the grotesque facial deformity.
The jaw lesions are usually painless and symmetric
swellings, having orid maxillary involvement (Figures 6
and 7). The lesions, which are rm to palpation and nontender, most commonly involve the molar to coronoid
regions, the condyles usually being spared, and are often
associated with cervical lymphadenopathy. Enlargement of
the cervical lymph nodes contributes to the patients fullfaced appearance and is said to be caused by reticuloendothelial hyperplasia with brosis. The lymph nodes become
enlarged before the patient reaches 6 years of age, decrease
in size after the age of 8 years, and are rarely enlarged
after the age of 12 years. Intraoral swelling of the alveolar
ridges may occur. When the maxillary ridge is involved,

Chapter 19 Bone Diseases and Fibro-osseous Lesions

Figure 6

Figure 7

Extraoral photograph of a 7-year-old girl with cherubism.


Reproduced with permission from editor, JCDA. Ongole R,
Pillai RS, Pai KM. Cherubism in siblings: a case report.
J Can Dent Assoc 2003;69(3):15054

the palate assumes a V shape. A rim of sclera may be visible beneath the iris, giving the classic eye to heaven
appearance.
Numerous dental abnormalities have been reported, such
as agenesis of the second and third molars of the mandible,
displacement of the teeth, premature exfoliation of the
primary teeth, delayed eruption of the permanent teeth,
and transpositions and rotation of the teeth. In severe
cases, tooth resorption occurs.
Although cherubism was initially described as a familial
disease affecting the jaws, cases without any apparent hereditary origin have been reported. In a few cases cherubism has
been described as being associated with other diseases and
conditions such as Noonans syndrome, gingival bromatosis, psychomotor retardation and obstructed sleep apnea.

Extraoral photograph of the girls 14-year-old brother


also suffering from cherubism. Reproduced with
permission from editor, JCDA. Ongole R, Pillai RS, Pai KM.
Cherubism in siblings: a case report. J Can Dent Assoc
2003;69(3):15054

In order to overcome the limitations of Arnotts classication, Kalantar Motamedi developed a different classication system, which addresses both the involvement and
aggressive behavior of the disease.

Radiographic staging
Arnott suggested the following grading system for the
lesions of cherubism:

Grade I (divided into five classes): Lesions of the mandible without signs of root resorption
Grade II (divided into three classes): Lesions of the
mandible and maxilla without signs of root resorption
Grade III (divided into five classes): Aggressive lesions
of the mandible with signs of root resorption
Grade IV (divided into three classes): Lesions involving the mandible and the maxilla and showing signs
of root resorption
Grade V: Massively growing, aggressive and extensively deforming juvenile cases involving the maxilla
and the mandible and which may include the coronoid
process and condyles.

Radiographic features

Arnotts staging was not exhaustive and some authors


found it difficult to stage their cases.

Cherubism is characterized by bilateral multilocular cystic


expansion of the jaws (Figures 8 and 9). Early lesions occur
in the posterior body of the mandible and the ascending
rami. Maxillary lesions may occur at the same time but
escape early radiographic detection because of overlap of
the sinus and nasal cavities. Displacement of the inferior
alveolar canal has been reported.

Grade I: Involvement of both mandibular ascending


rami
Grade II: Involvement of both maxillary tuberosities
as well as the mandibular ascending rami
Grade III: Massive involvement of the whole maxilla and
mandible except the coronoid process and condyles.

581

Section VII System Review

Figure 8

Orthopantomograph showing bilateral multilocular radiolucencies involving the mandible and displacement of teeth in
cherubism in a 7-year-old patient. Reproduced with permission from editor, JCDA. Ongole R, Pillai RS, Pai KM.
Cherubism in siblings: a case report. J Can Dent Assoc 2003;69(3):15054

Figure 9

Orthopantomograph showing bilateral multilocular radiolucencies involving the mandible and displacement of teeth in
cherubism in a 14-year-old patient. Reproduced with permission from editor, JCDA. Ongole R, Pillai RS, Pai KM.
Cherubism in siblings: a case report. J Can Dent Assoc 2003;69(3):15054

Destruction of the alveolar cavity may displace the


teeth, producing a radiographic appearance referred to as
oating tooth syndrome (Figure 10). With adulthood, the
cystic areas in the jaws become re-ossied, which results
in irregular patchy sclerosis. There is a classic (but nonspecic) ground-glass appearance because of the small,
tightly compressed trabecular pattern.
Histopathologic features
Histologic examination of the lesions usually reveals
numerous multinucleated giant cells. These multinucleated
cells show strong positivity for monoclonal antibody 23c6
582

and tartrate-resistant acid phosphatase, which is characteristic of osteoclasts. The collagenous stroma, which contains a large number of spindle-shaped fibroblasts, is
considered unique because of its water-logged, granular
nature.
The capillaries exhibit large endothelial cells and perivascular capillary cufng. The eosinophilic cufng is considered to be a characteristic feature of cherubism. However,
these deposits are not present in many cases, and their
absence does not exclude the diagnosis of cherubism.
Resolving lesions of cherubism show an increase in brous
tissue, a decrease in the number of giant cells and formation of new bone.

Chapter 19 Bone Diseases and Fibro-osseous Lesions

Figure 10

Orthopantomograph showing bilateral multilocular radiolucencies affecting the body and ramus of the mandible in cherubism.
The radiograph also shows the lower right second molar appearing to be floating. Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

Differential diagnosis

Treatment

Giant cell granuloma of the jaws, osteoclastoma, aneurysmal bone cyst, fibrous dysplasia and hyperparathyroidism
are considered in the differential diagnosis of cherubism.
Giant cell granuloma and osteoclastoma are histologically similar to cherubism. However, giant cell granuloma
is usually unilateral and usually affects patients between
20 and 40 years of age, whereas cherubism is a symmetric
lesion affecting children.
Osteoclastoma rarely occurs in the jaws, unlike cherubism.
Aneurysmal bone cyst may also exhibit giant cells, but
its main feature is a cavity lined with tissue other than
endothelium.
Both brous dysplasia and hyperparathyroidism contain
large numbers of osteoclasts. However, histologic examination of the classic form of brous dysplasia reveals trabeculae of immature bone resembling Chinese characters
within the proliferating stroma. These trabeculae are not
rimmed by osteoblasts. Furthermore, polyostotic brous
dysplasia rst presents in the 2nd or 3rd decade of life.
Hyperparathyroidism rarely affects the jaw in an isolated manner. Its histologic features differ from those of
cherubism in which it does not contain the mononuclear
stromal cell population that is characteristic of the latter.
Finally, peritrabecular brosis is a feature of hyperparathyroidism but not cherubism. Serum concentrations of
parathyroid hormone and calcium also help to distinguish
these lesions. Levels of serum alkaline phosphatase are
generally elevated in cases of brous dysplasia. In cases of
hyperparathyroidism, levels of serum calcium are elevated,
levels of serum phosphorus are decreased and levels of
serum alkaline phosphatase are generally within normal
levels.

The condition is self-limiting and generally regresses


by puberty. Surgery to correct the jaw deformities of
cherubism is rarely indicated. If necessary, surgery is
usually undertaken after puberty or when severe functional and esthetic problems are reported. Although exacerbation has sometimes been reported after surgery, it is
believed that surgery ultimately accelerates the involution
process.
Liposuction has been used to change the contour of the
jaws in a patient with cherubism. The procedure involves
removal of the bro-osseous tissue (consistency of rm
Jell-o). This consistency of the tissue makes the removal
difcult with bone ronguers and curettes. A blunt suction
lipectomy cannula is used to curette the abnormal tissue
and then aspirated by a high-suction apparatus.
Radiation has been used successfully, but it is discouraged because of possible retardation of jaw growth as
well as the risks of osteoradionecrosis and induction of
malignancy.
The treatment of choice is curettage, but equally good
results have been obtained with simple contouring to produce a more cosmetically acceptable appearance.
Southgate and others (1998) proposed the possibility
of managing cherubism with calcitonin. de Lange et al
(2007) report a case of cherubism treated with calcitonin.

Infantile Cortical Hyperostosis


Infantile cortical hyperostosis was first described by Caffey
(1945) and Silverman. It is also known as Caffeys disease,
CaffeySilverman syndrome, familial or sporadic infantile
cortical hyperostosis.
583

Section VII System Review

It is a self-limiting, inammatory process with unknown


etiology characterized by hyperostosis or thickening of
cortices of various bones in the skeleton. Some authors
believe that it is transmitted as an autosomal dominant
trait with incomplete penetrance. Other proposed etiological factors include a primary arterial abnormality and an
allergic phenomenon.
Clinical features
As the name suggests the condition is first noticed at birth
or in the first few months of life. It has been reported that
the average age of onset varies from about 7 to 11 weeks.
Infants are usually very irritable and present with tender,
deep seated and rm swellings. The swellings are evident
on the scalp, face, neck, thorax and extremities overlying
the affected bones. Swellings in the mandible may be seen
in the ramus and angle of the mandible.
Hyperostoses of various bones of the skeleton are seen.
The mandible and clavicular bones are reported to be most
commonly affected. However, the ribs, skull and long
bones have been reportedly involved.
Other associated clinical features that have been reported
in literature include facial nerve palsy (Challapalli et al,
1998) and Hotlzman (1972) reported Erbs palsy (form of
brachial plexus palsy in which there is paralysis of the
muscles of the upper arm and shoulder girdle) in a patient
with infantile cortical hyperostosis affecting the scapula.
Histopathologic features
Initial stages of the condition show periosteal and soft
tissue inflammation. In the subsequent stages thickening
of the periosteum and immature lamellar bone beneath the
periosteum is seen.
However, in the advance stage of the disease, no signs
of inammation or subperiosteal changes are evident.
Hyperplasia of the lamellar cortical bone is appreciated.
Laboratory findings
Though laboratory findings are not specific for infantile
cortical hyperostosis, elevated erythrocyte sedimentation
rate and serum alkaline phosphatase levels are evident.
Some patients exhibit leukocytosis and anemia. Kumar
et al (2008) reported a patient with Caffey disease having
raised immunoglobulins (IgG and IgM) and thrombocytosis.
Radiographic features
Radiographic evaluation plays an important role in diagnosing infantile cortical hyperostosis. The long bones, clavicle and mandible are most frequently involved. These
bones initially reveal periosteal bone formation. With
time, the periosteal bone density increases and integrates
584

with the underlying cortical bone. Over time the bone


undergoes remodeling to assume normal morphology.
The mandible (unilaterally or bilaterally) is affected in
almost every patient. The cortices exhibit thickening and
sclerosis.
Bykov and others (2003) describe a characteristic radiotracer uptake in the mandible in bone scan of a child
suffering from localized mandibular Caffey disease. They
described the nding as bearded infant appearance.
Management
Caffey disease is almost always self-limiting. It usually
regresses without any complications by about 9 months.
Literature review shows use of corticosteroids and NSAIDs to
manage symptoms and signs of pain and inflammation. Other
drugs that have been used with some success are prostaglandin inhibitors such as naproxen and indomethacin.

Idiopathic Osteosclerosis
Idiopathic osteosclerosis has also been termed dense bone
island and enostosis.
It is believed that enostosis is a counterpart of exostoses
that occur in the inner surface of the cortical plates within
the cancellous bone. It represents a focus of mature compact
(cortical) bone within the cancellous bone (spongiosa).
The etiology for their occurrence is unknown. These are
asymptomatic, benign and usually found on routine radiographic investigations. Greenspan (1995) in a review of
enostosis described that enostosis is probably congenital or
developmental in origin and represents failure of resorption
during endochondral ossication.
Characteristic features
Idiopathic osteosclerosis have known to occur anywhere
in the skeleton. However, the sites that are commonly
involved are the pelvis, femur, other long bones, spine and
the mandible.
McDonnell (1993) in a review of 107 patients reported
that the average age at which idiopathic osteosclerosis
was discovered was 36 years and women exhibited enostosis twice as much as men. Mandible was most commonly
affected. However, he reported the presence of enostosis
in the maxilla in a few individuals. The common site of
occurrence is the mandibular rst molar region. Almost
10% of the enostosis occurring in the mandibular molar
region tend to resorb the roots of the mandibular rst molar.
The typical radiographic appearance is usually a solitary
radiopacity with relatively ill-dened or diffuse border.
However, occasionally the internal structure of the sclerotic
area may show variable radiopacity (Figure 11).
Kawai et al (1996) reported a gigantic dense bone island
of the jaws. The dimensions of these large enostoses

Chapter 19 Bone Diseases and Fibro-osseous Lesions

measured between 2.5 and 7 cm on an orthopantomograph.


They concluded that these gigantic dense bone islands
were simply larger versions of the dense bone islands seen
routinely.
Greenspan and Stadalnik (1995) reported that the characteristic ndings on a plain radiograph were a homogeneously dense, sclerotic focus in the cancellous bone with
distinctive radiating bony streaks (thorny radiation) that
blend with the trabeculae of the host bone to create a
feathered or brush-like border (Figure 12).

Figure 11

Bone islands are usually cold on bone scintigraphy.


However, one should be aware of the fact that some harmless bone islands can mimic aggressive lesions on a bone
scan.
No treatment is required. The clinician should differentiate these dense bone islands from other bone pathologies
that may require active treatment.

Gorhams Disease
Gorhams disease is also called BreschetGorham syndrome, Gorhams osteolysis, Gorhams syndrome, Gorham
Stout syndrome, massive osteolysis, vanishing bone
disease and phantom bone disease.
Gilbert Breschet, Lemuel Whittington Gorham and
Arthur Purdy Stout were the rst few people who described
this condition. However, JBS Jackson in 1838 published
the rst case report. Subsequently Gorham and coworkers
(1954) and Gorham and Stout (1955) reported patients suffering from massive osteolysis.
Gorhams disease is a rare condition characterized by
proliferation of vascular channels that result in destruction
and resorption of the osseous matrix.
Etiopathogenesis

Cropped orthopantomograph revealing small radiopaque foci


approximating the apices of the mandibular first premolar and
second molar. Courtesy: Department of Oral Medicine and
Radiology, MCODS, Mangalore

In this condition, the normal bone is replaced by an


aggressively expanding, non-neoplastic vascular tissue.
The aggressively proliferating neovascular tissue causes
massive bone loss. In a study by Graham and Stout, they
showed an association between vanishing bone disease
and the presence of hemangiomatous or lymphangiomatous tissue. However, they were not able to demonstrate
osteoclasts in the region of bone resorption.

Figure 12

Orthopantomograph revealing enostoses in relation to the mandibular right second molar, second premolar and mandibular left
first premolar. The radiopaque foci are homogeneously dense and blend into the normal trabecular bone pattern producing a
brush like border. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

585

Section VII System Review

Many other investigators however demonstrated osteoclasts in the lytic front of the lesion. The role of osteoclasts is
supported by the fact that the use of calcitonin and bisphosphonates (inhibitors of osteoclastic activity) to treat patients
suffering from Gorhams disease arrests bone resorption.
Devlin and others (1996) proposed that interleukin-6
(IL-6) can be a potential mediator of the massive osteolysis.
They found that the levels of cytokine IL-6 increases almost
by seven times when compared to the levels in a normal
patient.
They believe that there are multiple sources of interleukins such as the blood vessels or dilatation of the vascular
marrow or the osteoclasts or cells in the bone marrow
microenvironment, including monocytes, broblasts, and
lymphocytes are potential sources of IL-6.
Clinical features
Gorhams disease is usually discovered in the first 4 decades
of life. However it may affect any age group and exhibits
no sex predilection.
The disease commonly affects the pelvis and shoulder.
Other sites that are affected are the scapula, clavicle, maxillofacial skeleton, ribs, spine, skull and the bones of the
extremities.
Severe complications include paraplegia, when the spine
is involved and respiratory difculty when the thorax
involved.
It is believed that the maxillofacial skeleton in involved
in about 25 to 30% of the patients. Deformed mandible or
maxilla causes malocclusion, mobility of teeth and occasionally results in pathological fracture.
Classification of idiopathic osteolysis
(Hardegger et al, 1985)
Type 1 Hereditary multicentric osteolysis with dominant
transmission. Usually seen between the age of 2 and 7 years.
Associated with spontaneous pain and swelling beginning
in the hands and feet. Carpotarsal osteolysis occurs over
the period of a few years. The progression ceases normally
in adolescence.
Type 2 Hereditary multicentric osteolysis with recessive
transmission similar to type 1, but may be associated with
severe generalized osteoporosis.
Type 3 Non-hereditary multicentric osteolysis with
nephropathy. It appears in childhood. There is a gradual
disappearance of the carpus with the tarsal bones involved,
but to a less degree. Proteinuria is seen. Death occurs usually due to renal failure and malignant hypertension.
Type 4 Gorhams massive osteolysis (GorhamStout syndrome). Monocentric occurrence in any part of the skeleton may start at any age. Normally hemangiomatous tissue
is found in the osteolytic region. It has neither a hereditary
586

pattern nor an associated nephropathy. The disease is


benign and the osteolysis usually stops after a few years.
Type 5 Winchester syndrome with autosomal recessive
transmission. Rare childhood carpotarsal osteolysis in association with contractures, shortness of stature, skin lesions,
corneal clouding and osteoporosis without nephropathy.
Diagnosis and investigations
The typical radiographic features will help in definitive
diagnosis of Gorhams disease. Laboratory tests are generally not diagnostic and usually the blood tests are within
normal limits. However, the serum alkaline phosphatase
level may be slightly elevated.
Plain radiographs, bone scans, CT and MRI can be used
to evaluate the osteolysis. The initial changes include radiolucent foci in the medullary portion of the bone with illdened margins. As the disease progresses these foci
coalesce together and involve the cortical plates and subsequently large portion of bone undergo dissolution or disappear. Orthopantomographs may reveal thinned-out
cortical plates and loss of lamina dura.
Histologic features
Histologically, proliferation of thin walled vessels is seen.
As the disease advances, extensive osteolysis is seen.
Subsequently the osseous tissue is replaced by fibrous tissue.
Management and prognosis
The prognosis of massive osteolysis is relatively good
unless vital structures are involved. Generally massive
osteolysis has poor prognosis when the spine and viscera
are affected. The major cause for mortality or morbidity in
Gorhams disease is the development of chylothorax (presence of lymphatic fluid in the pleural space) due to direct
extension of the dilated lymphatic vessels into the pleural
cavity.
Though various treatment modalities have been used in
the management of massive osteolysis, no single treatment
modality has proven to be effective in controlling the disease process.
Various non-surgical methods have been tried such as radiation therapy (4045 Gy in 2 Gy fractions), anti-osteoclastic
drugs (bisphosphonates) and alpha-2b interferon.
Surgical management includes resection of the lesion
followed by reconstruction using bone grafts. Surgical defects
can also be cosmetically masked with prostheses.

Pagets Disease of Bone


Pagets disease was first described by Sir James Paget in
1877. He called this condition osteitis deformans as he
believed it was an inflammatory bone condition. Rhodes
and Jawad suggested that as the pathology is now known

Chapter 19 Bone Diseases and Fibro-osseous Lesions

to be a disorder in bone turnover and not an inflammatory


condition, the term osteodystrophia deformans is more
appropriate needs wider recognition.
Pagets disease of bone is characterized by excessive
osteoclastic bone resorption in a focal area that is accompanied by an increased osteoblastic bone deposition. This
abnormal resorption and deposition of bone results in
weakened and distorted architecture of bone.
Etiology and pathophysiology
The etiology of Pagets disease is still unknown. Some of
the well accepted causes include viral infection and genetic
predisposition.
Helfrich and Hockling (2008) describe that the disease
has a genetic basis and mutations in SQSTM1 gene have
been associated with familial and sporadic disease in up to
40% of cases. SQSTM1 gene encodes sequestosome 1,
also known as p62, which is an ubiquitin-binding protein
that is involved in the IL-1, TNF and RANKL signaling
pathways.
In Pagets disease, osteoclast precursors have also been
shown to be hyperresponsive to the RANK ligand (RANKL),
a member of the tumor necrosis factor-alpha superfamily,
which promotes osteoclast genesis. One possibility is that
increased expression of RANKL contributes to the localized
nature of the disease.
Macrophage-colony stimulating factor (M-CSF) may play
a role in Pagets disease. M-CSF is a growth factor produced by many cells, including osteoblasts and marrow
broblasts. Signicantly high levels of M-CSF have been
found in patients with untreated Pagets disease.
Several genetic theories also suggest that human leukocyte antigen (HLA) on chromosome 6 and the gene on
chromosome arm 18q may play important roles in Pagets
disease.
The other popular hypothesis for the etiology of Pagets
disease is the action of slow virus (slow viruses are those
that produce diseases with extended or prolonged incubation
periods).
The measles virus messenger RNA sequences have been
found in osteoclasts and other mononuclear cells of pagetic bones. Canine distemper virus nucleocapsid antigens
have also been found in osteoclasts from patients with
Pagets disease. According to this hypothesis, bone marrow
cells (the progenitors of osteoclasts) are infected by a virus
that causes an abnormal increase in osteoclast formation.
Progression of disease
The progression of Pagets disease passes through three
phases, namely, the lytic phase, mixed or intermediate phase
and the sclerotic phase.
In the lytic phase, there is increased bone resorption.
There is increased number of osteoclasts at the site of
resorption. These osteoclasts have typically multiple nuclei

(almost around 100 nuclei compared to ve to ten in normal osteoclasts).


In the intermediate phase, as the bone is rapidly resorbed,
there is an increased amount of bone formation with numerous osteoblasts which are morphologically normal. The new
bone formed is abnormal with the collagen bers being
laid down in a haphazard manner.
In the sclerotic phase bone formation occurs at a rapid
pace. The bone thus formed is disorganized (woven bone)
which is structurally weak. Fibrous connective tissue and
blood vessels invade the woven bone leading to a state
of hypervascularity of the bone. As time progresses there
is diminished hypercellularity resulting in the formation
of a pagetic bone. This state is referred to as burnt-out
Paget disease.
Clinical features
Pagets disease of bone affects individuals over the 4th decade
of life. The incidence increases with the advancing age. It is
believed that males are twice as more likely to be affected
than females. It is common in Europe, North America,
Australia and New Zealand and almost always affects whites.
Pagets disease is rare among Asians and Africans.
A series of articles by Joshi et al (2006), Anjali et al
(2006), Bhadada et al (2006) studied the prevalence and
presentation of Pagets disease in various parts of India.
They reported the mean age at which the condition was
diagnosed was in the 5th decade. The male-to-female ratio
of occurrence was 2.5:1.
Pagets disease follows a chronic course. It is estimated
that about 80% of the patients are asymptomatic and the
disease is recognized on routine radiographic examinations.
Though the disease affects multiple bones, almost 17%
are unifocal (monostotic). The common bones that are
involved are the bones of the axial skeleton (spine, pelvis,
sacrum, femur and the skull).
The common signs and symptoms are bone pain,
deformed bones, neurological decits secondary to compression of the neural tissues. Other patients present with
a range of symptoms that may include pathologic fractures, congestive heart failure, hearing loss (compression
of eighth cranial nerve), and dysesthesias and weakness
from nerve root compression.
Patients present with bowed legs and associated abnormalities in the gait. Some authors describe the gait as
waddling or simian gait. Spinal deformities such as spinal
stenosis or kyphosis are seen.
Some individuals exhibit increased size of the skull with
or without frontal bossing and enlargement of the middle
third of the face, mimicking the face of a lion (leontiasis
ossea). Patients generally nd the need to change hats to
accommodate the growing size of the head.
Pathologic fractures are common in Pagets disease.
However, the healing is normal.
587

Section VII System Review

Oral manifestations
The maxilla and mandible can be affected. It is estimated
that the maxilla is almost twice as commonly affected than
the mandible. The involved jaw will be enlarged. Enlarged
maxilla will cause widening of the alveolar ridge and flattening of the palatal vault. Spacing between teeth may be
a secondary complication.
In advanced cases, the lips fail to cover the enlarging
jaws resulting in an open mouth state.
Laboratory investigations
Patients with Pagets disease may demonstrate very high
levels of serum alkaline phosphatase (helps to estimate
bone formation), especially when multiple bones are affected.
It is believed that the total alkaline phosphatase levels
have only 78% sensitivity of detecting Pagets disease.
Therefore, bone specific alkaline phosphatase levels are
more accurate.
However, serum calcium and serum phosphorus levels are
normal. Other investigations that can help in the identication of the extent and severity of bone turnover include
estimating levels of deoxypyridinoline and N-telopeptide
of type I collagen (help in estimating amount of bone
resorption). Urinary excretion of deoxypyridinoline and
N-telopeptide are elevated. Alpha-alpha type I C-telopeptide
fragments are sensitive markers of bone resorption for assessing disease activity and monitoring treatment outcome.
Radiographic features
The radiographic findings in Pagets disease depend on the
phase of the disease. Radiographs may exhibit areas of
osteolysis and areas of bone deposition or an intermediate
phase.
There are very unique radiographic features of Pagets
disease such as osteoporosis circumscripta, blade of
grass lesion, brim sign, framed vertebrae and cotton-wool
appearance.
Osteolytic zones in the skull represented by large circumscribed radiolucent areas are referred to as osteoporosis circumscripta (usually seen in the frontal and occipital
bones). In the intermediate phase, as bone deposition occurs,
areas of patchy sclerosis are seen in the skull and the jaws,
giving rise to the cotton-wool appearance. Hypercementosis
and loss of lamina dura around the roots of teeth is usually seen in Pagets disease. Rarely, root resorption may
be seen.
Long bones of the skeleton reveal a V-shaped pattern
that divides the healthy bone from its pagetic counterpart.
This unique nding is termed blade of grass lesion. Thickening of the iliopectineal line in the pelvic bone is termed
brim sign. Enlargement of the vertebral bodies with thickened cortices and vertical striations gives rise to the appearance of framed vertebrae.
588

On radionuclide imaging, the radiopharmaceutical is


markedly taken up by the pagetic bone. Extensive involvement of the mandible may occasionally reveal the uptake
of the radiopharmaceutical from condyle to condyle giving
rise to the Lincolns sign or the black beard sign.
Histologic features
The histologic features depend on the phase of the disease
process. The pathognomonic feature in Pagets disease is the
presence of the basophilic resting and reversal lines which
are indicative of the junction between the resorptive and
formative phases of bone that results in the appearance
of mosaic pattern or jigsaw puzzle pattern of bone. The
bony trabeculae will reveal prominent osteoblastic and
osteoclastic activity.
Dental considerations
During the active phases of the disease process, invasive
oral surgical procedures may result in extensive bleeding
due the vascularity of the diseased bone. Hypercementosis
of teeth may make dental extractions difficult. Patients on
treatment with bisphosphonates are more likely to develop
chemo-osteonecrosis even with minimal trauma. Dental
extractions should be best avoided during the treatment.
Similarly, in the advanced phases of the disease, the bone
is susceptible to infections and pathologic fracture.
Patients may require frequent replacement of oral
prosthesis to accommodate for the ever increasing size of
the jaws.
Management
In symptomatic patients, bone pain can be managed with
NSAIDs. The drugs routinely used are calcitonin (osteoclast
inhibitor) and bisphosphonates (anti-resorptive agents).
These drugs minimize the bone turnover rate.
New generation bisphosphonates such as pamidronate,
etidronate, tiludronate, alendronate and risedronate are
preferred over calcitonin.
The recommended dosages of these drugs are etidronate (400 mg/day for 6 months), pamidronate (single IV
infusion of 60 mg to a maximum of 90 mg per day for
34 days diluted in saline or glucose solution for 46 hours),
alendronate (given orally 2040 mg/day for 6 months),
tiludronate (400 mg/day for 3 months) and risedronate
(30 mg/day for 2 months). All patients treated with
bisphosphonates should be given calcium and vitamin D
supplements.
Keating and Scott (2007) described the efcacy of
zoledronic acid, a third generation, nitrogen containing
bisphosphonate in the management of Pagets disease.
They describe that a single intravenous dose of zoledronic
acid 5 mg is effective and well tolerated in the treatment
of Pagets disease of bone. A single IV dose of zoledronic

Chapter 19 Bone Diseases and Fibro-osseous Lesions

acid was associated with a signicantly higher therapeutic response rate and a more rapid reduction in bone
turnover than that achieved with 60 days of oral risedronic acid. Moreover, biochemical remission was sustained after 24 months of follow-up in zoledronic acid
recipients.
Cytotoxic drug such as mithramycin (plicamycin) has
also been tried where the disease is refractory to bisphosphonates. However, it is seldom used these days.

Surgical management may be required mainly for decompression of the nerves.


Prognosis
It is believed that about 1% of the patients develop osteosarcoma as a complication of Pagets disease. Benign and
malignant giant cell tumors have also known to occur in
these patients.

589

CHAPTER

20

Autoimmune Disorders
Balaji Rao B, Sumanth KN

Concepts of Immunity and Autoimmunity

Sjgrens Syndrome
Mikuliczs Disease (Benign Lymphoepithelial Lesion)
Aphthous Stomatitis (Aphthous Ulcers, Canker Sores,
Recurrent Aphthous Stomatitis)
Giant Cell Arteritis
Periodontal Disease
Rheumatoid Arthritis

Systemic Autoimmune Diseases with


Orofacial Manifestations

Pemphigus
Pemphigus Vulgaris
Pemphigus Vegetans

CONCEPTS OF IMMUNITY AND


AUTOIMMUNITY
The human body has the ability to resist almost all types
of organisms or toxins that tend to damage the tissues and
organs. This capacity is termed immunity. A specific type of
immunity that arises from general processes, rather than
from specific disease organisms is called innate immunity.
In addition, the human body has the capability to develop
extremely powerful specic immunity against individual
invading agents such as lethal bacteria, viruses, toxins, etc.
This is called acquired immunity. Acquired immunity is
caused by special immune system that forms antibodies
and activated lymphocytes that attack and destroy specic
organisms or toxins.
Two basic forms of acquired immunity occur in the body.
In one of them the body develops circulating antibodies,
which are globulin molecules in the blood that are capable
of attacking the invading agent. This type of immunity is
called humoral immunity or B-cell immunity (because
B-lymphocytes produce the antibodies). The second type

590

Pemphigus Foliaceous
Brazilian Pemphigus
Pemphigus Erythematosus
Paraneoplastic Pemphigus
Bullous Pemphigoid
Cicatricial Pemphigoid

Epidermolysis Bullosa Acquisita

Systemic Lupus Erythematosus

Autoimmune Polyendocrinopathy
Candidiasis-Ectodermal Dystrophy

Diabetes Mellitus Type I (IDDM)

Systemic Sclerosis

Myasthenia Gravis

of acquired immunity is achieved through the formation of


large umbers of activated lymphocytes that are specically
designed to destroy the foreign agent. This type of immunity is called cell mediated immunity or T-cell immunity
(because the activated lymphocytes are T-lymphocytes).

Autoimmunity
Failure of the immune system to tolerate (antigen-specific
immunological unresponsiveness) self-tissues. It is a condition in which structural or functional damage is caused by
the action of immunologically competent cells or antibodies
against normal components of the body.
When the concept of autoimmunity came to be accepted
as a pathogenic mechanism, a large number of diseases
were suggested to have an autoimmune etiology, based
on the nding of autoantibodies in the patients. However,
autoantibodies have also been found in the serum or tissues of otherwise normal and healthy elderly individuals.
Autoantibodies are also formed following tissue injury and
may serve a role in the removal of the products of tissue

Chapter 20 Autoimmune Disorders

breakdown. This lead to the need to formulate criteria for


diagnosing autoimmune diseases.

orofacial region. Sumanth and Balaji Rao have proposed a


simpler classification of autoimmune diseases that affect
the orofacial region.

Diagnostic criteria for autoimmune disorders

1.

The first criterion for recognizing autoimmune disease was


given by Witebsky in 1957. This criterion was extended by
many authors. Robert H Waldman documented the following criteria:
1.

2.
3.
4.
5.

a.

Circulating or localized populations of cells sensitized to antigen, or products of immunologically


activated cells, active under physiologically conditions should be demonstrated, or
b. Circulating or localized populations of cells sensitized to antigen, or products of immunologically
activated cells, active under physiological conditions, should be present
Sensitizing antigen should be identified and
characterized
Antibodies or sensitized lymphocytes should be produced in vitro or in animals against the same antigen
Pathological events in vitro or in the experimental
animal should correspond to those in human disease
Transfer of disease from immunized to normal animal
by cells or serum.

Classification of autoimmune diseases


Fergusson (1995) categorized autoimmune diseases as
organ specific and non-organ specific.
1.

2.

Organ specific autoimmune diseases


a. Hashimotos thyroiditis
b. Primary myxedema
c. Thyrotoxicosis
d. Pernicious anemia
e. Autoimmune atrophic gastritis
f. Autoimmune Addisons disease
g. Type I diabetes mellitus
h. Goodpastures syndrome
i. Myasthenia gravis
j. Sympathetic ophthalmia
k. Autoimmune hemolytic anemia
l. Idiopathic thrombocytopenic purpura
m. Primary biliary cirrhosis
n. Chronic active hepatitis
o. Sjgrens syndrome
Non-organ specific autoimmune diseases
a. Rheumatoid arthritis
b. Dermatomyositis
c. Systemic sclerosis
d. Systemic lupus erythematosus (SLE).

Various classifications in literature do not necessarily


group autoimmune diseases that specifically affect the

2.

Autoimmune disorders affecting orofacial region predominantly


a. Sjgrens syndrome (GougerotSjgren syndrome)
b. Benign lymphoepithelial lesion (Mikuliczs disease)
c. Aphthous stomatitis
d. Periodontal disease
e. Giant cell arteritis (temporal arteritis)
Systemic autoimmune disorders with orofacial manifestations
a. Pemphigus
b. Bullous pemphigoid
c. Cicatricial pemphigoid
d. Epidermolysis bullosa acquisita
e. SLE
f. Bullous SLE
g. Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED)
h. Myasthenia gravis
i. Dermatomyositis
j. Systemic sclerosis
k. Idiopathic thrombocytopenic purpura.

Sjgrens Syndrome
(GougerotSjgren Syndrome)
Described in Chapter 11 (Diseases of Salivary Glands) on
page 265.

Mikuliczs Disease
(Benign Lymphoepithelial Lesion)
Described in Chapter 11 (Diseases of Salivary Glands) on
page 265.

Aphthous Stomatitis
(Aphthous Ulcers, Canker Sores, Recurrent
Aphthous Stomatitis)
Described in Chapter 7 (Vesiculobullous Disorders) on
page 174.

Giant Cell Arteritis


Giant cell arteritis is a relatively common form of large
vessel vasculitis occurring predominantly in elderly individuals. The mean age of onset is 70 years with a 2:1
female-to-male ratio. Temporal artery is the common
artery that is involved in cranial arteritis (Figure 1).

591

Section VII System Review

Figure 1

The prominent temporal artery in a patient suffering


from temporal arteritis. Courtesy: Dr C Stephen Foster,
The Ocular Immunology and Uveitis Foundation,
Cambridge, Massachusetts, USA

Muki proposed an autoimmune basis for giant cell arteritis because it occurred more frequently in patients with
other autoimmune disorders such as thyroid disease or
rheumatoid arthritis.
Clinical features

The temporal artery is extremely tender on palpation.


The individual may complain of deep aching or throbbing pain and burning sensation over the muscles.
The pain may radiate to the maxilla, mandible, neck or
face.
Diagnosis
The definitive diagnosis is based on temporal artery biopsy,
which demonstrates giant cell arteritis and elevated erythrocyte sedimentation rate.
Management
The condition once recognized should be treated aggressively
with corticosteroids. Approximately 50% of the patients who
have not been treated in time may develop blindness.

Periodontal Disease
For almost two decades the concept of autoimmune pathogenesis for periodontal disease was considered.
Alphonse et al (1981) have detected rheumatoid factor
by latex slide agglutination in subgingival plaque,

592

inamed gingival tissue, stimulated pooled saliva and


serum of patients suffering from chronic moderate periodontitis. They correlated the presence of rheumatoid
factors to the periodontal disease and concluded an autoimmune origin of the disease.
Ftis et al (1986) found increased levels of antibodies to
type I collagen in patients with periodontal disease than in
control subjects.
Hirsch et al (1988) used enzyme-linked immuno spot
test to enumerate antibody secreting cells to human collagen types IIV by cells isolated from gingival and
peripheral blood of individuals suffering from adult periodontitis. Analysis revealed the presence of high numbers
of cells that secreted antibodies to type I collagen when
compared to type III. They suggested that autoimmunity
may contribute to the pathogenesis of this common
disease.
Anusaksathien and Dolby (1991) postulated many possible explanations to explain the presence of autoantibodies in periodontal disease.
1.

2.
3.

4.
5.
6.

Enhanced presentation of self-antigens through increased


expression of the molecule associated with antigen
presentation, namely, Ia antigen.
Altered T helper or T suppressor cell function.
Polyclonal activation of cells which have the ability,
for reasons which may not be clear, to produce autoantibodies.
Idiosyncrasies of the antigen-idiotype network.
Bacterial or viral cross-reactivity with self-antigen
leading to the production of cross-reactive antibodies
Genetic predisposing factors.

Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder that may affect many tissues and organs
skin, blood vessels, heart, lungs and musclesbut principally
attacks joints, producing a non-suppurative proliferative
synovitis that often progresses to destruction of the articular cartilage and ankylosis of joints. Although the cause
for RA remains unknown, there is convincing evidence
that autoimmunity plays a pivotal role in its chronicity
and progression, likening this condition to other so-called
connective tissue diseases. RA can affect the TMJ.
Pathogenesis
It is currently believed that RA is triggered by the exposure of an immunogenetically susceptible host to an arthritogenic microbial antigen.
The involved mechanisms in the causation could be:
1.

Genetic susceptibility: Rosenberg and Nuki have


shown that 6580% of the individuals suffering from

Chapter 20 Autoimmune Disorders

2.

3.

4.

RA have human leukocyte antigen (HLA)-DR4 and


HLA-DR1 or both. Other haplotypes like DW4, DW10,
DW13, DW14 and DW15 have also been implicated.
Primary exogenous arthritogen: Roudier et al proposed EpsteinBarr virus as the primary microbial
agent for the causation of RA. Other microbial agents
like retroviruses, parvoviruses, mycobacteria, borrelia
and mycoplasma could also initiate the disease.
Autoimmune reaction: Warder in 1940 proposed
the presence of rheumatoid factor, which was the
first human autoantibody described in association
with RA.
Although T cells played a primary role in the
pathogenesis of RA, B cells were also involved. In
1993, Panayi reported that approximately 80% of
patients have rheumatoid factors which were directed
against Fc portion of IgG, present in serum and synovial fluid. The presence of rheumatoid factors in the
joints is believed to contribute to the inflammatory
reaction. Williams in 1996 observed that rheumatoid
factors showed principal specificity for structures on
C3 and C2 (Fc) domains of IgG, which thus defined
rheumatoid factor as an autoantibody associated
with RA.
Mediators of tissue damage: Panaji in 1993 reported
that the rheumatoid synovium was heavily infiltrated
with lymphocytes, most of which were CD4 helper
T cells. They generate cytokines, which in turn could
activate other immune cells and macrophages.

2.

3.

The changes of RA most useful for diagnosis are noted in


the hands and wrists. They include swan neck deformity,
ulnar deviation, dorsal interosseous muscle atrophy and
swelling of wrist.
Temporomandibular joint manifestations It is believed
that TMJ symptoms develop in more than one-third of the
patients during the first year of RA.
According to Tegellerg and Kopp (1987) and Votalia
(1964), the most characteristic clinical signs of RA affecting the TMJ were palpatory tenderness of the joint, crepitus from the joint and swelling in relation to the TMJ
region.
Almost 60% of the individuals present with bilateral
involvement of joints.
Severe RA involving the TMJ can result in a progressive anterior open bite due to bilateral destruction of mandibular condyles.
Hugh Ogus described a possible course of rheumatoid
involvement of the TMJ. He proposed that the TMJ
involvement progresses through three phases:
1.

Clinical features

2.

3.

It can occur at any age, but bimodal peaks are seen at


40 and 60 years of age.
Women are two-and-half times more likely than men
to develop disease.
Patients complain of polyarthralgias, fatigue and muscle aches.
Prolonged morning stiffness of joints.
Joints of the hands, feet, elbows, shoulders, knees and
TMJ are affected.
Within weeks of affliction, the involved joints become
tender and marked swelling is seen.
Low-grade fever, malaise, anorexia and weight loss is
seen.

1.

Joints that are usually affectedankles, cervical spine,


elbows, hips, knees, metacarpophalangeal joints, metatarsophalangeal joints, proximal interphalangeal joints,
shoulders, tarsal joints, temporomandibular joints and
wrists.

Active phase (acute symptoms, synovial effusion,


destruction of fibrocartilage and erosion of underlying bone)
Healing phase (remodeled and flattened articular
surface)
Secondary osteoarthrotic phase (marginal proliferations
and further destruction of the condyle, predominant
clinical finding of crepitus).

Radiographic features of rheumatoid arthritis


affecting the TMJ
1.

2.

Joint manifestations
Katz classified the joint manifestations as:

Unusually affected jointscarpometacarpal joints,


cricoarytenoid joint, sacroiliac joints and sternoclavicular joint.
Rarely affected jointsdistal interphalangeal joints,
lumbar spine.

3.
4.

Formation of new bone (marginal proliferation) was


described in 1975 by Hugh Ogus. It is reported that
the erosions of the articular surface were the most
important diagnostic finding of RA in other joints and
not the TMJ.
Subcondylar cystic destruction and severe destruction
of bone eventually lead to complete loss of condyle.
Such destruction will give the remaining condylar bone
the shape of the mouth piece of a flute.
Anterior open bite and reduced joint space (due to
destruction of articular cartilage).
The most characteristic radiographic signs of RA in
the TMJ are erosions of cortical outline and reduced
joint space (Figure 2) as proposed by Akerman et al
in 1988.

593

Section VII System Review

Figure 2

Erosions of the cortical outline of the condyle and reduced joint space. Courtesy: Department of
Oral Medicine and Radiology, MCODS, Mangalore

Kopps in 1995 stated that the radiographic diagnosis of


RA in TMJ was difficult. However, absence of radiographic
changes in the TMJ will not exclude the possibility of
early RA in TMJ.
Extra-articular manifestations of rheumatoid
disease
A. Systemic manifestations
1.
2.
3.
4.

Fever
Weight loss
Fatigue
Increased susceptibility to infections

1.
2.
3.
4.

Pleural effusions
Fibrosing alveolitis
Bronchiolitis
Caplans syndrome

G. Cardiac
1.
2.
3.
4.
5.

Pericarditis
Myocarditis
Endocarditis
Coronary vasculitis
Granulomatous aortitis

B. Musculoskeletal manifestations

H. Ocular

1.
2.
3.

1.
2.
3.
4.

Osteoporosis
Bursitis
Muscle wasting

C. Hematological manifestations
1.
2.
3.

Anemia
Thrombocytosis
Eosinophilia

Laboratory findings

1.
2.
3.

Visceral arteritis
Pyoderma gangrenosum
Digital arteritis

1.
2.
3.
4.

Cervical cord compressions


Compression neuropathies
Peripheral neuropathies
Mononeuritis multiplex

Episcleritis
Scleritis
Scleromalacia
Keratoconjunctivitis sicca

I. Amyloidosis.

D. Vasculitis

E. Neurological

594

F. Pulmonary

None of the multiple blood, synovial fluid or biopsy


studies is specific for RA.
These individuals exhibit increased ESR levels and
anemia.
50% of the patients show presence of antinuclear antibody (ANA).
80% of patients exhibit significant elevations of rheumatoid factor (not diagnostic).
Rheumatoid synovial fluid is generally cloudy and
tinged green.

Chapter 20 Autoimmune Disorders

Diagnosis
The diagnosis of RA is based on a carefully obtained history and a diligent physical examination to unravel subtle
signs of inflammation. One should strive to detect the condition as early as possible to prevent crippling deformities.
The American Rheumatism Association diagnostic criteria aid in clinical diagnosis. These criteria were designed
principally for research and literary purposes.
A. Classical rheumatoid arthritis This category requires
seven of the following criteria to match. In criteria 1 through
5, the joint signs or symptoms must be continuous for at
least 6 weeks.
1.
2.

Morning stiffness.
Pain on motion or tenderness in at least one joint
(observed by the physician).
3. Swelling (soft tissue thickening or fluid, not bony
overgrowth alone) in at least one joint (observed by a
physician).
4. Swelling (observed by a physician) of at least one
additional joint (symptom free period between the two
joint involvements may not be more than 3 months).
5. Symmetrical joint swelling (observed by a physician)
with simultaneous involvement of the same joint on
both sides of the body (bilateral involvement of proximal interphalangeal, metacarpophalangeal or metatarsophalangeal joints is acceptable without absolute
symmetry). Involvement of the terminal phalangeal
joint will also satisfy this criterion.
6. Subcutaneous nodules (observed by a physician) over
bony prominences, on extensor surfaces or in juxtaarticular regions.
7. Radiographic changes typical of RA (which must
include at least bony decalcification localized to or
most marked adjacent to the involved joints and not
just degenerative changes). Degenerative changes do
not exclude patients from any group classified as RA.
8. Positive agglutination testdemonstration of the
rheumatoid factor by any method which, in two
laboratories, has been positive in not over 5% of normal controlsor positive streptococcal agglutination
test (the latter is now obsolete).
9. Poor mucin precipitates from synovial fluid (with shreds
and cloudy solution).
10. Characteristic histologic changes in synovium with three
or more of the following marked villous hypertrophy,
proliferation of superficial synovial cells, often with palisading, marked infiltration of chronic inflammatory
cells (lymphocytes or plasma cells predominating)
with tendency to form lymphoid nodules, deposition
of compact fibrin either on surface or interstitially,
foci of necrosis.
11. Characteristic histologic changes in nodules show
granulomatous foci with central zones of necrosis,

surrounded by a palisade of proliferated macrophages,


and peripheral fibrosis and chronic inflammatory cell
infiltration, predominantly perivascular.
B. Definite rheumatoid arthritis This diagnosis requires
five of the above criteria. In criteria 1 through 5, the joint
signs or symptoms must be continuous for at least 6 weeks.
C. Probably rheumatoid arthritis This diagnosis requires
three of the above criteria and total duration of joint
symptoms must be at least 3 weeks.
D. Possible rheumatoid arthritis This diagnosis requires
two of the following criteria and total duration of joint
symptoms must be at least 3 weeks:
1.
2.
3.
4.
5.
6.

Morning stiffness
Tenderness or pain on motion (observed by a physician)
with history of recurrence or persistence for 3 weeks
History or observation of joint swelling
Subcutaneous nodules (observed by a physician)
Elevated erythrocyte sedimentation rate or C-reactive
protein
Iritis (of dubious value as a criterion except in the
case of juvenile RA).

Diagnostic criteria for local involvement of TMJ


The criteria for diagnosing TMJ involvement with RA were
given by Kopp in 1995.
1.
2.
3.
4.
5.
6.
7.
8.

Bilateral joint involvement


Tenderness to adaptation of lateral or posterior aspects
of the joint
Joint crepitus
Radiographic signs of erosions of the articular cortical
bone of the TMJ
Swelling over the TMJ (acute phase)
Temperature change in or over the TMJ. Increase in
the acute phase and decrease in the chronic phase
Anterior open bite
Abundance of polymorphonuclear leukocytes in the
joint fluid (acute phase) or mononuclear leukocytes
(lymphocytes and plasma cells, chronic phase)

The presence of four of those eight criteria should be able


to determine the local diagnosis.
Differential diagnosis
Differential diagnoses include ankylosing spondylitis,
psoriatic arthritis, Reiters syndrome, arthritis of chronic
inflammatory bowel disease, polytendinitis, osteoarthritis
and sarcoidosis.
Management
The successful management of RA lies in a comprehensive
multidisciplinary approach. Systemically administered
595

Section VII System Review

drugs, local injections of corticosteroids, physical therapy,


occupational therapy, psychosocial support, patient education, family involvement, surgical intervention and
vocational rehabilitation are all part of the routine daily
management program of patients with RA.

foliaceous. Oral mucosal involvement is of little consequence


in the foliaceous and erythematosus forms.

1.

Non-steroidal anti-inflammatory drugs Piroxicam


20 mg once a day, diclofenac 2575 mg twice a day,
naproxen 250500 mg twice a day, ibuprofen 400
800 mg four times a day or ketoprofen 5075 mg thrice
a day.
Remittive drugs used in the treatment of rheumatoid
arthritis
Antimalarials (chloroquine 250 mg, hydroxychloroquine 200 mg)one tablet twice a day followed by
once a day.
Gold parenterally (sodium aurothiomalate or urothioglucose)test dose of 10 mg followed by 2550 mg
weekly for 46 months.
Gold given orally (auranofin 3 mg)one tablet twice
a day
Methotrexate given orally (2.5 mg)one tablet thrice
a day, once or twice in a week
Penicillamine (125250 mg)initial dose of 250 mg
once a day, raised by 125 mg increments, every 68
weeks as tolerated if active arthritis persists, maximal
daily dose 1,500 mg.

Described in Chapter 7 (Vesiculobullous Disorders) on


page 174.

Physical and occupational therapy, surgery, occlusal splints,


occlusal adjustments, prosthetic treatment can increase
the patient comfort and help in mastication.

Described in Chapter 7 (Vesiculobullous Disorders) on


page 174.

2.

Pemphigus Vulgaris

Pemphigus Vegetans
Described in Chapter 7 (Vesiculobullous Disorders) on
page 174.

Pemphigus Foliaceous
Described in Chapter 7 (Vesiculobullous Disorders) on
page 174.

Brazilian Pemphigus (Fogo Selvagem)


Described in Chapter 7 (Vesiculobullous Disorders) on
page 174.

Pemphigus Erythematosus
(SenearUsher Syndrome)

Paraneoplastic Pemphigus

SYSTEMIC AUTOIMMUNE DISEASES WITH


OROFACIAL MANIFESTATIONS
PEMPHIGUS
It is an autoimmune disease involving the skin and the
mucosa and characterized by intraepidermal bullae formation. It is caused by antibodies directed as the intercellular
intercementing substances.
Classification

Pemphigus vulgaris
Pemphigus vegetans
Pemphigus foliaceous
Pemphigus erythematosus (SenearUsher syndrome)
Brazilian pemphigus (Fogo selvagem)
Benign familial chronic pemphigus (HaileyHailey
disease)
Paraneoplastic pemphigus.
Pemphigus vegetans is a variant of pemphigus vulgaris
and pemphigus erythematosus is a variant of pemphigus
596

Described in Chapter 7 (Vesiculobullous Disorders) on


page 174.

Bullous Pemphigoid
Described in Chapter 7 (Vesiculobullous Disorders) on
page 174.

Cicatricial Pemphigoid
Described in Chapter 7 (Vesiculobullous Disorders) on
page 174.

EPIDERMOLYSIS BULLOSA ACQUISITA


Epidermolysis bullosa acquisita (EBA) is a chronic subepidermal blistering disease associated with autoimmunity to
the collagen within the anchoring fibrils (type VII collagen) that are located at the dermalepidermal junction.
The rst diagnostic criterion was putforth by Raenigk
et al in 1971.

Chapter 20 Autoimmune Disorders

Figure 3

characteristically seen within the exural areas and skin


folds. Some patients may present with erythema and at
urticarial plaques in the absence of blisters.
About 10% of the patients exhibit severe mucous membrane involvement may present a picture clinically similar
to cicatricial pemphigoid with erosions and scarring in
the oral cavity, conjunctiva, upper esophagus and anus or
vagina.
Diagnostic criterion for EBA was proposed by Yaoita
et al (1981). This is still the most widely followed diagnostic
criterion. These criteria, with some updated modications
are as follows:
1.
2.
3.
4.

5.

Extensive erosions over the lower extremity and some


areas of healing with scar formation in epidermolysis
bullosa. Courtesy: Dr Ajit Auluck

1.
2.
3.
4.

A negative family and personal history for a previous


blistering disorder
An adult onset of eruption
Spontaneous or trauma-induced blisters that resemble
those of hereditary dystrophic epidermolysis bullosa
The exclusion of all other bullous diseases.

Clinical features
Epidermolyis bullosa acquisita may have at least three different clinical presentations: the classical presentation,
bullous pemphigoid like presentation and a cicatricial
pemphigoid like presentation.
The classical presentation is a non-inammatory, bullous disease with an acral distribution that heals with
scarring and milia formation. It is a mechanobullous disease marked by skin fragility. These patients have erosions, blisters and scars over trauma prone surfaces (back
of the hands, knuckles, elbows, knees, sacral area and toes)
(Figure 3).
A scarring alopecia and some degree of nail dystrophy
may be seen. The lesions heal with scarring and frequently
with the formation of pearl like, milia cysts within the
scarred areas.
The bullous pemphigoid like presentation is a widespread inammatory vesiculobullous eruption involving
the trunk, central body, skin folds and the extremities. The
bullous lesions are surrounded by inamed or urticarial
skin. The distribution of lesions like bullous pemphigoid is

Bullous disorder with the clinical spectra outlined above


No family history of a bullous disorder
A subepidermal blister by histologic examination
Deposition of IgG deposits within the dermal-epidermal junction (a positive direct immunofluorescence of
perilesional skin)
Junctional IgG deposits localized to the lower lamina
densa and/or sublamina densa zones of the basement
membrane when examined by direct immunoelectron
microscopy or indirect or direct salt split skin immunofluorescence and/or western blotting.

Histologic features
Routine histologic examination of lesion on skin obtained
from EBA patients show a subepidermal blister and a clean
separation between the dermis and the epidermis with
inflammatory infiltrate.
Immunologic parameters
Patients with EBA have IgG deposits within dermal
epidermal junction of their skin. This is detected by direct
immunofluorescence. IgG is the predominant immunoglobulin class, but deposits of complement IgA, IgM, factor B
and properdin may also be detected.
The localization of immune deposits within the dermal
epidermal junction of the skin of epidermal junction of the
skin of the patients is the gold standard for the diagnosis.

SYSTEMIC LUPUS ERYTHEMATOSUS


Systemic lupus erythematosus (SLE) is a systemic disease
affecting multiple organ systems that is characterized by
the presence of antibodies to nuclear antigens. Lupus is a
Latin word for wolf. It is called so because of the way it
eats away skin.
Types of lupus:
1.
2.
3.
4.

SLE
Discoid lupus erythematosus
Drug-induced lupus erythematosus
Lupus nephritis
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Section VII System Review

5.
6.

Subacute cutaneous lupus erythematosus


Neonatal lupus erythematosus.

Figure 4

Neonatal lupus erythematosus is a rare disease affecting


babies born to women suffering from SLE. Subacute cutaneous form is characterized by non-scarring skin lesions
on the areas of skin exposed to sunlight.
Epidemiology
Systemic lupus erythematosus is the most common connective tissue disease. The reported prevalence of SLE is 50.8 per
100,000 individuals above 17 years of age. The prevalence
of SLE in individuals in the age group of 1865 years is
about 1:1,000 in white women and 1:250 in black women.
In this age group, SLE is 10 times more frequent in females
than in males. Among children and elderly, SLE is only
twice as frequent in females than in males.
Etiology and pathogenesis
Genetic About 10% of the patients with SLE have a first
degree relative with the disease. Multiple HLA associations
have been reported, particularly for B8, DR2, DRW52,
DQW1 and DQW2. The null gene for C4 occurs more often
in patients with SLE in their families.
Environmental A significant exposure to sunlight
clearly precede the onset of the disease in about one-third
of the patients.

Maculopapular rash on the face and chest of a patient


suffering from SLE. Courtesy: Dr Ashok

2.

Medication Drugs that have been implicated in causing


SLE are categorized into:

High risk drugs (hydralazine, procainamide and


isoniazid)
Moderate risk to low risk drugs (quinidine, Dpenicillamine, carbamazepine, oral contraceptive pills).
Pathogenesis
The immune system is clearly abnormal in SLE. T cells do
not control the activity of the B cells, which produce a large
number of autoantibodies. Some of the autoantibodies
(anti-DNA) participate directly in the renal disease forming
immune complexes in the glomeruli. Other autoantibodies
form complexes with their antigens to lead to vasculitis.
At present, SLE is thought to be a disorder in which
genetic defects are present but not yet delineated. These
genetic defects lead to a defective homeostasis between
B cells and T cells. When the individual is challenged by
certain factors like ultraviolet light, infection or by an
unknown stimulus, the B cells become hyperactive leading
to a variety of autoantibodies.
Clinical features
1.

598

General manifestations Fever (low grade or spiking),


fatigue, weight loss and generalized malaise are general manifestations in patients suffering from SLE.

3.

4.

Cutaneous lesions Patients present with a typical erythematous rash over the malar region, which is popularly referred to as the butterfly rash. It is evident as
an erythematous and slightly edematous lesion located
on the cheeks, extending across the bridge of the nose
(Figure 4). It is generally the first manifestation of the
disease. It frequently occurs after exposure to sun. The
rash heals well without scarring or pigmentation.
Patients may also present with a pruritic maculopapular rash, which may resemble lesions of drug
eruption.
Joint manifestations About 95% of the patients show
joint involvement. Arthritis with pain on movement,
tenderness, or effusion is present in about 80% and
arthralgia is present in about 15% of the patients with
SLE. The proximal interphalangeal, knee, wrist and
metacarpophalangeal joints are most often involved.
Swan neck deformities occur in 15% of the individuals but unlike rheumatoid arthritis, no bony erosion
is seen.
Renal disease Renal involvement in SLE ranges from 29
to 53%. The WHO grading of type of renal lesions are
a. Type I: normal
b. Type II: mesangial hypercellularity and immune
deposits confined to mesangium. These patients
have mild proteinuria
c. Type III (focal proliferative lupus nephritis):
proteinuria, hematuria and occasionally nephrotic
syndrome

Chapter 20 Autoimmune Disorders

d. Type IV (diffuse proliferative nephritis): significant proteinuria, hematuria, renal insufficiency,


severe nephritic syndrome and hypertension may
be present
e. Type V (membraneous nephritis): significant proteinuria, hematuria and nephritic syndrome.
5. Cardiopulmonary manifestations The most common
symptom is pleuritic chest pain, which is present
in about 40% of the patients. Pleural effusions are
rarely evident. The common cardiac manifestation
is pericarditis which occurs in about 25% of the
patients.
6. Nervous system manifestations Approximately 14% of
the patients exhibit peripheral neuropathy and mixed
sensory motor disturbances. GuillainBarre syndrome
may occasionally be present. Grand mal seizures are
seen in about 15% of the patients in the early stages
of the disease. Organic brain syndromes are characterized by impaired orientation, perception, memory
and intellectual function.
CSF studies revealed significant elevation of protein levels and WBC count in 32% of the cases.
7. Gastrointestinal manifestations Nausea, vomiting and
anorexia are present in about 20% of the patients.
Dysphagia may be present and is usually associated
with Raynauds phenomenon. Hepatomegaly occurs
in about 30% of the patients and splenomegaly is
seen in 20% of the patients and is usually not associated with hemolytic anemia.
8. Ocular manifestations Approximately 15% of the
patients exhibit conjunctivitis and episcleritis. Rarely
occlusion of the central retinal artery may be seen.
Blindness from retinal arteritis may ensue.
9. Hematologic abnormalities One or more hematologic abnormalities are present in nearly all patients
of SLE. Most common is a mild to moderate normocytic normochromic anemia. Hemolytic anemia and
reticulocytosis occur in only 10% of the patients.
Leukopenia with WBC counts less than 4,000/l. Mild
thrombocytopenia is present in 1/3rd of patients
with SLE.
Circulating anticoagulant in SLE produces a slight
prolongation of the thromboplastin time or partial
thromboplastin time. Bleeding and clotting times are
normal. In contrast, antibodies directed against factors
VII, IX and XII may prolong bleeding times and result
in clinically significant state of anticoagulation.
10. Salivary gland manifestation Acute enlargement of one
or both parotid glands occurs occasionally in patients
with SLE. The swelling may be painful and usually
returns to normal as the systemic disease is controlled.
The enlargement may be associated with the presence
of Sjgrens syndrome.
11. Oral manifestations Oral manifestations of SLE were
first described by Bazin in 1861. Monash in 1931

Figure 5

White plaque with dark reddish purple margins on the palate


in a patient with SLE. Courtesy: Dr Ashok

examined 22 patients with SLE and reported that 50%


had oral lesions. The most common sites affected by
SLE are buccal mucosa, lips and palate.
The typical intraoral lesions are multiple white plaques
with dark, reddish purple margins (Figure 5). Hyperemia
and edema are marked, increasing the tendency for bleeding and superficial ulceration. The prevalence of ulceration (most commonly reported oral manifestation of SLE)
has been reported to be between 7 and 41%.
Rhodes and Johnson in 1989 reported xerostomia,
angular cheilitis, mucositis, glossitis, dental caries, periodontitis, dysphagia and glossodynia as the oral manifestations of SLE.
Laboratory investigations
1.

2.

Presence of ANA: A wide spectrum of autoantibodies


may be found in patients with SLE. ANA are usually
detected for screening purposes by the indirect fluorescence antibody technique. ANA are positive in
nearly all patients with SLE who have clinical evidence
of active disease. But the diagnosis of SLE should
never be made in a patient with a positive ANA and
absence of multisystem disease.
Polyclonal hypergammaglobulinemia is common in
patients with SLE. Serum complement levels are generally decreased in active SLE, especially in patients
suffering from active nephritis.
599

Section VII System Review

3.

4.

Rheumatoid factor: Approximately 18% of the patients


exhibit rheumatoid factor in conjunction with nonerosive deforming arthritis.
Lupus erythematosus (LE) cell phenomenon: A specific test for the disease was established with the discovery of the LE cell inclusion phenomenon by Hargraves
and associates in 1969. In this test, blood serum from
a suspected person is added to the buffy coat of normal
blood. If the patient is suffering from SLE, typical LE
cells will develop. The LE cell phenomenon consists of
a rosette of neutrophils surrounding pale nuclear
mass apparently derived from a lymphocyte.

Autoimmune polyendocrinopathycandidiasisectodermal
dystrophy (APECED) is a rare condition which requires at
least two of the following conditions to make the diagnosis: hyperparathyroidism, Addisons disease and chronic
mucocutaneous candidiasis.
Porter et al (1995) and Perniola et al (1998) described
developmental defects of teeth and oral candidiasis as the
characteristic oral ndings in these individuals.

LE cells are rarely found in discoid lupus erythematosus.

Clinical features

Management

1.
2.

The basis of treatment is the use of corticosteroids, given


in a dose adequate to control the multisystem disease and
to return the anti-DNA antibodies and complement levels
to normal.
Depending on the severity and nature of the disease
the dose of corticosteroids can vary from 10 mg to 1 g
intravenously per day.
In patients with repeated exacerbations of the disease
at moderately high doses of corticosteroids, azathioprine
may be useful to allow the patient to be maintained on
lower doses of corticosteroids. Antimalarial drugs are useful in patients with skin abnormalities, alopecia or mucosal ulcers. In the recent times, severe and unresponsive
cases have been managed successfully with plasmapheresis or leukapheresis.
Dental considerations
1.

2.

3.

4.

Platelet count estimation may be required prior to any


oral surgical procedure, to evaluate the severity of
thrombocytopenia.
Bacterial endocarditisLibmanSacks vegetations may
be found under mitral valve leaflets in SLE. These
vegetations rarely affect function but can lead to bacterial endocarditis. Patients with SLE have to be considered for antibiotic prophylaxis before dental treatment
that is likely to cause bacteremia.
According to Roura et al (1991), drugs that have a photosensitizing potential like penicillin, sulfonamides
and NSAIDs should be used judiciously as they tend to
exacerbate SLE.
SLE patients are susceptible to shock and infection as
they are medicated with adrenal suppressing doses of
corticosteroids or cytotoxic drugs.

Prognosis
Literature review reveals a 5-year survival rate in almost
95% of the patients of SLE. However, these patients need
to be constantly medicated with the lowest possible doses
of corticosteroids.
600

AUTOIMMUNE POLYENDOCRINOPATHY
CANDIDIASISECTODERMAL DYSTROPHY

3.
4.

Girls are more commonly affected.


Hypoparathyroidism is the most common endocrinopathy that is seen. However, addisonian adrenocortical
hypofunction, autoimmune thyroid disease, vitiligo,
diabetes mellitus and other autoimmune disorders can
also be associated with APECED.
Oral manifestations include pseudomembranous candidiasis and recurrent angular stomatitis.
Enamel hypoplasia may be seen secondary to hypoparathyroidism, usually affecting permanent dentition,
reflecting the early postnatal onset of autoimmune
hypoparathyroidism.

Management
APECED management requires antifungal therapy and the
management of endocrinopathy.

DIABETES MELLITUS TYPE I (IDDM)


Diabetes mellitus is a clinical syndrome characterized by
hyperglycemia due to absolute or relative deficiency of
insulin.
Among the various types of diabetes, insulin-dependent
diabetes mellitus (IDDM) has an autoimmune basis.
Edwards et al in 1995 proposed the following explanations as evidence to suggest autoimmune etiology for
IDDM:
1.
2.
3.
4.
5.

HLA-linked genetic predisposition


Association with other autoimmune disorders
Circulating islet cell cytoplasmic and surface, insulin
autoantibodies in new patients.
Mononuclear cell infiltration of pancreatic islets resulting in selective destruction of insulin secreting cells.
Recurrence of insulinitis and selective destruction of
insulin-secreting cells in pancreatic grafts.

Dental considerations
Median rhomboid glossitis is considered as a specific
pathognomonic oral manifestation associated with diabetes.

Chapter 20 Autoimmune Disorders

However, various oral conditions are worsened in a diabetic individual such as gingivitis and periodontal diseases, oral candidiasis, delayed socket healing after extraction and burning tongue.
Specific considerations pertaining to dental treatment
1.

2.
3.

Local anesthetics without epinephrine should be used


because even minimal doses of epinephrine can elevate
blood glucose concentration. Reduced blood supply in
diabetics due to atherosclerosis may be accentuated further by vasoconstriction activity of epinephrine and
can lead to dry socket.
Complicated dental procedures are best delayed in
uncontrolled diabetics.
Post-surgical infections are common in uncontrolled
diabetics. This can be managed with appropriate
antibiotics.

seen. The characteristic claw-like deformity of fingers is


seen due to flexural contractures and resorption of terminal phalanges (Figure 7). Some patients present with neuralgia or paresthesia.
Dermal involvement can be divided into three distinct
phases:
1.
2.
3.

Edematous phase (stiff, puffy fingers)


Indurative phase (hard, tight, hidebound)
Atrophic phase (softened skin, burned out).

Figure 6

However, all types of routine dental treatment may be performed safely in the dental setting in individuals whose
blood glucose levels are under control.

SYSTEMIC SCLEROSIS
Systemic sclerosis can be described as chronic, progressive
dermatosis characterized by board-like hardening and
immobility of the affected skin, with visceral involvement,
especially of lungs, esophagus, kidneys and heart. It is characterized by alterations of the microvasculature, disturbances of the immune system and by massive deposition of
collagen. Curzio in 1973, published the first detailed description of a scleroderma-like disease. A variant of systemic
sclerosis is termed acrosclerosis, which is a combination of
Raynauds phenomenon and scleroderma affecting the
extremities.
Epidemiology

Linear ribbon-like marking on the forehead resembling


mark produced by blow of a saber in systemic sclerosis.
Courtesy: Dr Ajit Auluck

Figure 7

The annual incidence of systemic sclerosis is approximately


612 patients per one million individuals. Individuals
between the 3rd and 5th decades of life are mostly affected.
Females are affected seven times more than males.
Types of systemic sclerosis
1. Localized form
a.

b.

Circumscribed morphea form (yellowish-white patches


on the skin surface surrounded by a violaceous halo
of varying size and shape).
Linear en coup de sabre form (linear ribbon-like
markings that resemble marks produced by blow of a
saber are seen) (Figure 6).

In the initial stages, indurated edema of skin followed by


fixation of epidermis to the deeper subcutaneous tissues is

Claw-like deformity in systemic sclerosis.


Courtesy: Dr Ajit Auluck

601

Section VII System Review

2. Diffuse form Diffuse form of systemic sclerosis is


characterized by fibrosis of internal organs with loss of
smooth muscle and loss of visceral function. More than
50% of the patients exhibit involvement of the gastrointestinal tract (mainly distal esophagus) resulting in dysphagia. Lung involvement results in dyspnea and hypoxia, due
to interstitial inflammation and fibrosis. Involvement of
the kidney and heart results in renal and cardiac failure
respectively. Occasionally, soft tissue calcifications may
also be seen.

Orofacial manifestations

Figure 8

Mask-like appearance of the face (due to loss of skin


folds) (Figure 8).
Alae of the nose will gradually atrophy to produce the
characteristic mouse-like facies.
Fibrosis of the buccal mucosa may be seen.
Tongue and lips may turn rigid.
Mucogingival periodontal problems (loss of attached
gingiva, gingival recession) are seen.
Mouth opening is significantly reduced, giving rise to
a purse string appearance to the mouth.
Involvement of the minor salivary glands may mimic
signs and symptoms of Sjgrens syndrome.
Some patients may complain of pain, paresthesia, or
hyperesthesia along the course of the trigeminal nerve.

Radiographic features

Mask-like facies in progressive systemic sclerosis.


Courtesy: Dr Ajit Auluck

The most commonly seen radiographic finding in


patients is the resorption of the terminal phalanges of
the hand and the distal portions of the radius and ulna.
Generalized widening of the periodontal ligament
space (two to four times the normal width) is seen in
1037% of the patients. In comparison to anterior
teeth, widening of periodontal ligament space is more
marked in the posterior teeth (Figure 9).
Resorption of the mandible in patients suffering from
scleroderma was first reported by Taveras in 1959.
Literature review reveals that the incidence of mandibular resorption varies from 10 to 33%. The sites that are
resorbed include the condyle, coronoid process, ascending ramus, posterior border of the ramus and the angle
of the mandible. The sites of resorption predispose
to pathological fractures, osteomyelitis, trigeminal

Figure 9

Generalized widening of periodontal ligament space in systemic sclerosis. Courtesy: Dr Ajit Auluck

602

Chapter 20 Autoimmune Disorders

neuropathy (associated with severe pain) and apertognathia.


Diagnosis
The diagnosis of systemic sclerosis is made by the presence
of the characteristic clinical and radiographic features.
However, some non-specific serological changes such as the
presence of antinuclear antibodies and rheumatoid factor
are seen.
Syndromes associated with systemic sclerosis
CREST syndrome was originally called Thibierge
Weissenbach syndrome in honor of two French physicians
who described this condition in 1910. Winterbauer renamed
this syndrome as CREST syndrome in 1964.
CREST syndrome is a combination of calcinosis cutis,
Raynauds phenomenon, esophageal hypomobility, sclerodactyly and telangiectasia.
Dental considerations
All forms of dental treatment can be safely carried out in
these patients. However, since the mouth opening gradually reduces, mouth opening exercises, use of increased
number of tongue blades between posterior teeth to stretch
facial tissues and bilateral commissurotomy are done to
manage these patients.
These patients can be instructed to practice good oral
hygiene practices as the gradual reduction in mouth opening will hinder maintenance of oral hygiene.
Course and prognosis
The prognosis is better when there are only dermal manifestations. Involvement of internal structures has an unfavorable prognosis. On an average the 5-year survival rate
is about 70%.

it involves muscles that control facial expression, chewing


and swallowing. In advanced stages, respiratory muscles
are affected leading to acute respiratory failure.
Epidemiology
It affects approximately 2 out of every 100,000 people and
can occur at any age. It is most common in women
in the 2nd and 3rd decades of life. In men, the condition
usually develops between 6th and 8th decades of life.
Types of MG
Generalized MG: Approximately 85% of the patients
develop generalized form of this condition within 1 year of
the onset of the disease. Patients report progressive weakness in the trunk, arms and legs.
Ocular MG: Muscles that control eye movements are typically affected. Approximately 1015% are affected by this
condition.
Congenital MG: Inherited condition caused by genetic
defect, develops at birth or shortly after birth.
Transient neonatal MG: It occurs in infants born to mothers who have MG. Around 1020% of the neonates develop
this condition. It occurs due to transfer of maternal antiAChR antibodies through the placenta to the newborn
reacting with the AChR of the neonate.
Etiology
The exact cause of MG is still unknown. Females and individuals with certain HLA have a genetic predisposition to
autoimmune diseases. It is proposed that there is a dysregulation of the immune system. Sensitization to a foreign antigen that has cross-reactivity with the nicotinic
ACh receptor has been proposed as etiology for MG.
Clinical features
1.

MYASTHENIA GRAVIS
The term myasthenia gravis (MG) was coined by combining two Greek words for muscle and weakness to form the
word myasthenia and adding the Latin word gravis, which
means severe. The autoimmune etiology for MG was proposed for the first time in 19591960 by two independent
workers, Simpson and Nastuck.
Myasthenia gravis is an autoimmune disorder of the
neuromuscular junction, in which autoantibodies are
directed toward acetylcholine receptors (Ac in the motor
end-plate units of skeletal muscle, resulting in a progressive fatigability of the skeletal muscle. In the initial stages,
extraocular muscles are affected. As the disease progresses

2.
3.

4.

5.
6.
7.
8.

Patients face may appear expressionless due to the


weak and slack facial muscles.
Inability to hold the head upright.
Mandibular movements are sluggish and slack. Patient
may have to support his/her mandible with a finger.
The patients mouth may remain open all the time.
Patient is said to have a snarling face when he/she try
to smile. When the patient attempt to smile, the corners
of the mouth are not drawn up and outward, and the
levator muscles expose the canines.
Gag reflex is often absent, and such patients are at risk
for aspiration of oral secretions.
Dysphagia is seen because of the weakness of the
muscles associated with chewing and swallowing.
Patient may complain of nasal regurgitation.
Patients voice may acquire a nasal quality.
603

Section VII System Review

9.

In severe cases patient is unable to clear bronchial


secretions which may predispose to pneumonia.
10. Ptosis is seen in almost all patients. Patients have
difficulty in eye closure. Characteristically, pupils are
unaffected in MG.
Diagnostic tests
Myasthenia gravis can be diagnosed with tests like edrophonium test, ice-pack test, test to assess eyelid twitch
response, anti-AChR antibody test, anti-MuSK antibodies,
electrophysiological tests (repetitive nerve stimulation test
and single fiber electromyography), CT/MRI of chest (to
screen for associated thymic tumors). Patients should also
be evaluated for diseases associated with MG such as thyroid disease, diabetes mellitus, rheumatoid disease, pernicious anemia, systemic lupus erythematosus, sarcoidosis,
Sjgrens disease and polymyositis.
Simple tests that can be performed in a dental
setting
Ice-pack test Patients having ptosis secondary to MG will
improve when an icepack is applied to the eyelid. However,
ptosis secondary to other conditions will not improve on
application of icepack.
Eyelid twitch response It is also referred to as Cogans
lid twitch. Patient is instructed to gaze downward for

604

1020 seconds. After 20 seconds the patient is advised to


bring his/her gaze to the normal position. In patients suffering from MG, the upper eyelid elevates and may either
slowly begin to droop or twitch several times before assuming a stable position. This phenomenon is brought about
by rapid recovery and easy fatigability of muscles. However, this test can be positive in patients with brain stem
or ocular disorders.
Management of MG
The current management of MG includes the use of anticholinesterase drugs for temporary improvement of neuromuscular transmission, removal of anti-AChR Abs by plasma
exchange or specific immunoadsorption procedures, use of
non-specific immunosuppressants or immunomodulators
to curb the anti-AChR response, and thymectomy.
MG when not treated with adequate dosage of medication can present with myasthenic crisis and when treated
with excessive medication can exhibit cholinergic crisis.
Myasthenic crisis may cause bronchospasm with
wheezing, cyanosis and in extreme conditions respiratory
failure can occur.
Cholinergic crisis may be associated with miosis and
SLUDGE syndrome, which is characterized by salivation,
lacrimation, urinary incontinence, diarrhea, gastrointenstinal upset, hypermotility and emesis.

CHAPTER

Granulomatous Diseases
Adel Kauzman, Iona Leong

21

Tuberculosis

Foreign Body Granulomas

Leprosy (Hansens Disease)

Wegeners Granulomatosis

Syphilis

Sarcoidosis

Deep Fungal Infections

Orofacial Granulomatosis

Blastomycosis
Histoplasmosis
Aspergillosis
Zygomycosis (Mucormycosis, Phycomycosis)

Crohns Disease (Regional Ileitis, Regional


Enteritis)

Granulomatous diseases are a heterogeneous group of disorders that are characterized by a specific pattern of chronic
inflammation called granulomatous inflammation, in which
granulomas are formed. Granulomas usually develop as a
result of a cell-mediated hypersensitivity reaction to a
non-degradable antigen. The clinical significance of a histological finding of granulomatous inflammation is that this
type of inflammation is associated with a relatively limited
number of conditions.
A granuloma is a focal aggregate of inammatory cells,
composed predominantly of epithelioid macrophages,
which may be surrounded by a rim of lymphocytes and/or
plasma cells. Epithelioid macrophages resemble epithelial
cells, having abundant pale pink cytoplasm, vesicular and
oval nuclei and indistinct cell borders (Figure 1). Some
activated macrophages may fuse to form multinucleated
giant cells which may be located within the center or
periphery of the granuloma (Figure 2). In Langhans type
giant cells the nuclei are arranged in the periphery, often in
the shape of a horseshoe. The nuclei of foreign body type
giant cells are arranged haphazardly in the cytoplasm.
Some granulomas may show central areas of necrosis.
Caseous necrosis, in which the dead tissue is soft and dry
and resembles cheese, is classically associated with tuberculosis. Long-standing granulomas may be surrounded by
a rim of brous connective tissue and broblasts.
Granulomas can be classied as immune or foreign body
type. Foreign body type granulomas develop in response to
inert endogenous or exogenous foreign material (Table 1).

Figure 1

Photomicrograph of a granulomatous inflammatory reaction


showing multiple granulomas surrounded by lymphocytes.
Each granuloma is composed predominantly of epithelioid
macrophages and multinucleated giant cells. Epithelioid
macrophages show abundant pale pink cytoplasm,
vesicular and oval nuclei and indistinct cell borders.
(Hematoxylin and eosin, original magnification 200)

Immune-mediated granulomatous inammation represents


a form of delayed type (cell-mediated) hypersensitivity
reaction and may be secondary to specic types of bacterial, fungal and parasitic infections. Immune granulomas
605

Section VII System Review

TUBERCULOSIS

Figure 2

Photomicrograph showing a multinucleated giant cell


in the center of a granuloma. The nuclei of the giant cell are
arranged in the periphery of the cytoplasm. (Hematoxylin and
eosin, original magnification 250)

Table 1

Granulomatous diseases that may affect the oral tissues

Infections
Bacterial
Tuberculosis
Leprosy
Syphilis
Others

Foreign body

Diseases of unknown
etiology

Silica
Beryllium
Talc
Suture material
Starch

Wegeners granulomatosis
Sarcoidosis
Orofacial granulomatosis
Crohns disease

Fungal
Blastomycosis
Histoplasmosis
Aspergillosis
Zygomycosis
Others
Parasitic
Leishmaniasis
Schistosomiasis

are mostly seen with mycobacterial and fungal infections


because the infectious organisms typically have antigens
which are poorly degraded by macrophages. Antigen
exposure initiates a cell-mediated immune response,
resulting in activated CD4 T lymphocytes of the Th1 type
which secrete cytokines such as interleukin (IL)-2, IL-12,
interferon (IFN)-, and tumor necrosis factor (TNF)-. The
cytokines stimulate activation of macrophages to form
granulomas. Some immune-mediated granulomatous diseases are of unknown etiology (Table 1).
606

Tuberculosis is a common worldwide infection caused by


bacteria belonging to the Mycobacterium tuberculosis
complex. Although tuberculosis usually affects the lungs, it
may also involve other organs in up to one-third of cases.
Initial infection, also known as primary infection, is followed
by a long latency period characterized by absence of symptoms in most individuals. Latent infection progresses to
active disease in a minority of individuals, due to reactivation or exogenous re-infection with a second strain of
M. tuberculosis. Therefore infection must be distinguished
from active disease. Active tuberculosis caused by drugsusceptible strains is curable if properly treated, but may
be fatal within 5 years in more than half the cases if
untreated.
The M. tuberculosis complex includes M. tuberculosis,
the most frequent and important agent of human disease.
M. bovis is transmitted by unpasteurized milk and is the
cause of a small percentage of cases in developing countries. M. tuberculosis is an aerobic, non-spore-forming,
rod-shaped bacterium. The organism is classied as an
acid-fast bacillus because the high mycolic acid and lipid
content in the cell wall prevents decolorization by acid
alcohol with acid-fast stains such as the commonly used
ZiehlNeelsen stain.
Tuberculosis is a disease of poverty associated with
overcrowding and undernutrition. Other risk factors for
tuberculosis include human immunodeciency virus (HIV)
infection, diabetes, smoking, excessive alcohol consumption, end-stage renal failure, and therapy with tumor
necrosis factor antagonists and corticosteroids.
Based on World Health Organization (WHO) estimates,
approximately two billion people or one-third of the worlds
total population were infected with M. tuberculosis in 2010,
with 1.4 million deaths caused by tuberculosis yearly.
Tuberculosis occurs world-wide, but the majority of cases
occur in low-income countries and in countries with emerging economies. The developing countries of Africa and Asia
have the highest prevalence of tuberculosis, with the most
cases occurring in India, China, South Africa, Indonesia and
Pakistan. Tuberculosis is uncommon in North America and
Europe, where it occurs predominantly in HIV-infected
persons, immigrants from high-prevalence countries, disadvantaged and marginalized populations. Although
intense efforts at disease control have resulted in stabilization or decreasing incidence of tuberculosis in most countries, there has been a rapid increase in Africa related to
the spread of the HIV epidemic.
Pathogenesis
The disease is usually transmitted by the airborne spread
of droplet nuclei produced by patients with infectious pulmonary tuberculosis. Droplets aerosolized by coughing,

Chapter 21 Granulomatous Diseases

sneezing or speaking are inhaled. Thus transmission of


infection is enhanced by crowded conditions in poorly ventilated rooms and prolonged, close contact with patients
with active tuberculosis. Inhaled bacilli reaching the alveoli
are ingested by non-specifically activated alveolar macrophages, which may contain the bacillary multiplication or
be killed by the multiplying bacilli. Chemotactic factors
released by lysed macrophages attract non-activated monocytes from the bloodstream to the site. These initial stages
of infection are usually asymptomatic.
Specic immunity develops about 24 weeks after
infection. Large numbers of activated macrophages accumulate at the site of the primary lesion, forming granulomas
or tubercles. Granuloma formation is mediated by cytokines
released by alveolar macrophages, including TNF-. This
delayed-type hypersensitivity reaction to bacillary antigens
destroys macrophages and causes necrosis in the center of
the tubercles. The necrotic material resembles soft cheese,
hence the designation caseous necrosis. Its low oxygen
tension and low pH inhibit growth of M. tuberculosis. Viable
organisms may however remain dormant within the macrophages or in the necrotic material for years or even
throughout the patients lifetime. Some tubercles in the lung
parenchyma and hilar lymph nodes may heal by brosis
and calcication, while others undergo further evolution.

Figure 3

Gross appearance of Ghon lesion in the lung of a patient


with a history of healed primary pulmonary tuberculosis.
It presents as a calcified spherical mass

Figure 4
Clinical features
Tuberculosis is classified as pulmonary or extrapulmonary.
Pulmonary tuberculosis can be primary or secondary.
Primary pulmonary disease results from an initial infection with M. tuberculosis in previously unexposed individuals and is usually asymptomatic. The lesion is usually
peripheral and localized to the middle and lower lung
zones and is accompanied by hilar or paratracheal lymphadenopathy. In most cases, the lesion heals spontaneously
and may later be evident as a small calcified nodule (Ghon
lesion) (Figure 3). Approximately 510% of patients progress directly from initial infection to active disease, usually
because of an existing state of immunosuppression. This is
especially seen in children and in persons with impaired
immunity, such as those with malnutrition or HIV infection. The initial lesion enlarges, cavitates, invades and
destroys bronchial walls and blood vessels. Large numbers
of bacilli spread into the airways and the environment
through expectorated sputum. Patients may develop pleural effusion and progressive primary tuberculosis.
Hematogeneous dissemination may result in fatal miliary
tuberculosis (Figure 4) or tuberculous meningitis.
Secondary pulmonary tuberculosis, also known as postprimary disease, is usually due to endogenous reactivation
of latent infection. Triggers for reactivation include immunosuppression, especially AIDS, malnutrition and vitamin D
deciency. The disease usually occurs in the apical and
posterior segments of the upper lung lobes, where the high

Gross appearance of miliary tuberculosis in the lung

oxygen tension favors mycobacterial growth. The extent


of lung involvement varies greatly, from small inltrates
to extensive cavitatory disease. Massive involvement of
the lungs, with coalescence of lesions, produces tuberculous pneumonia. The result may be death, spontaneous
607

Section VII System Review

Figure 5

Panoramic radiograph of a patient with a history of tuberculosis showing calcified cervical and submandibular lymph nodes

remission or chronic disease with a progressively debilitating course (consumption). Individuals with chronic disease
continue to discharge tubercle bacilli into the environment.
Symptoms and signs are often non-specic and insidious
early in the course of secondary pulmonary tuberculosis,
consisting mainly of fever, night sweats, weight loss,
anorexia, general malaise and weakness. Cough eventually develops in most individuals, often initially non-productive and subsequently accompanied by the production
of purulent sputum. The sputum may be blood-streaked
due to blood vessel involvement.
Virtually any organ system may be affected by extrapulmonary tuberculosis, but the most commonly involved
sites are the lymph nodes, pleura, genitourinary tract, bones
and joints, meninges, peritoneum, pericardium, and the
head and neck region. In the head and neck, tuberculosis can
involve the larynx, middle ear, nasal cavity, nasopharynx,
oral cavity, parotid gland, esophagus and spine. As a result
of hematogeneous dissemination in HIV-infected individuals, extrapulmonary tuberculosis is seen more commonly
nowadays than in the past.
Lymph node tuberculosis (tuberculous lymphadenitis)
is the most common form of extrapulmonary tuberculosis
and is especially common in HIV-infected persons. It usually
presents as painless swelling of the lymph nodes, most
commonly at cervical and supraclavicular sites (scrofula).
Lymph nodes are usually discrete in early disease but may
develop caseous necrosis and form stulas through the overlying skin draining caseous material. Involved nodes may
radiographically appear calcied (Figure 5). Pulmonary
tuberculosis is unusual in patients with scrofula.
Oral manifestations
The most common manifestation of tuberculosis in the oral
cavity is a chronic painless ulcer. Less frequently tuberculous lesions present as nodular, granular or rarely firm
608

leukoplakic areas. Most oral lesions represent secondary


infection from the initial pulmonary lesions, either from
hematogeneous spread or from exposure to infected sputum. Secondary oral lesions usually occur on the tongue,
palate and lip.
Primary oral tuberculosis without pulmonary involvement is rare. It usually involves the gingiva, mucobuccal fold
and areas of inammation adjacent to teeth or in extraction
sites. Primary oral lesions are frequently accompanied by
enlarged regional lymph nodes. Tuberculous osteomyelitis
has been reported in the jaws and appears as ill-dened
areas of radiolucency.
Histopathologic features
Affected tissues show multiple granulomas called tubercles
which consist of aggregates of epithelioid histiocytes, lymphocytes and Langhans multinucleated giant cells (Figure 1).
The tubercles often show central caseous necrosis (Figure 6).
Special stains such as ZiehlNeelsen or other acid-fast
stains are required to demonstrate the bacteria (Figure 7).
Because of the relative scarcity of bacilli within tissue,
organisms may not be successfully demonstrated in all
cases, and a negative result therefore does not completely
eliminate the possibility of tuberculosis.
Granulomas may be absent or poorly formed in people
with poor immune responses, especially those infected
with HIV.
Diagnosis and laboratory findings
A presumptive diagnosis of active tuberculosis is commonly made on the finding of acid-fast bacilli on microscopic examination of a diagnostic specimen such as a tissue
biopsy or a smear of expectorated sputum. Definitive diagnosis requires the isolation and identification of M. tuberculosis from a diagnostic specimen, usually sputum in a

Chapter 21 Granulomatous Diseases

Figure 6

Photomicrograph of a caseating granuloma from a


tuberculous lesion. The center of the granulomas shows
caseous necrosis. Multinucleated giant cells and lymphocytes
are seen in the periphery of the granuloma. (Hematoxylin and
eosin, original magnification 5)

Figure 7

Photomicrograph showing a positive Ziehl-Neelsen


stain in a case of pulmonary tuberculosis.
(ZiehlNeelsen, original magnification 400)

patient with productive cough. Specimens are cultured on


egg- or agar-based medium and incubated at 37C under 5%
CO2. The organisms grow slowly in culture and 48 weeks
may be required before growth is detected.
Automated liquid culture systems are faster and show a
greater yield than solid media-based systems.
New automated molecular tests such as XpertMTB/RIF
which is a nucleic acid amplication test allow rapid diagnosis not only of tuberculosis, but also of multidrug-resistant
tuberculosis (MDR-TB).

Due to inconsistent results and high rates of falsenegative and false-positive results, serological tests for the
diagnosis of active tuberculosis are not recommended.
Screening for latent M. tuberculosis infection can be
performed with skin testing with puried protein derivative (PPD). However, the test is of limited value in the
diagnosis of active disease because of its low sensitivity
and specicity. False-negative reactions are common in
immunosuppressed patients and in those with overwhelming tuberculosis. Positive reactions are elicited from individuals who have been infected with M. tuberculosis but
do not have active disease and from persons sensitized by
non-tuberculous mycobacteria or Bacille CalmetteGurin
(BCG) vaccination.
The gold standard for identifying M. tuberculosis
infection is an interferon- release assay which measures
interferon- titers released by T cells in response to stimulation with certain TB-speic antigens, such as ESAT-10
and CFP-10.
Management protocols and prognosis
Because of drug resistance, cure of tuberculosis requires
prolonged concomitant administration of at least two agents
to which the organism is susceptible. Four major drugs are
considered as first-line treatment agents: isoniazid, rifampin
(rifampicin), pyrazinamide and ethambutol. Second-line
drugs include streptomycin, kanamycin, amikacin, capreomycin, ethionamide, cycloserine, para-aminosalicylic acid
and fluoroquinolone antibiotics such as ofloxacin. Secondline agents are used in patients resistant to first-line therapy, because of their lower efficacy and higher toxicity.
Infectious cases should be diagnosed rapidly and appropriately treated until cure. The development of drug-resistant tuberculosis is primarily the result of monotherapy or
failure of the healthcare provider to prescribe at least two
drugs to which the tubercle bacilli are susceptible. Resistance
occurs also if the patient fails to take properly prescribed
therapy. Multidrug-resistant tuberculosis (MDR-TB) is a
form of tuberculosis that does not respond to the standard
drug treatment, i.e. the two main rst-line drugs: isoniazid
and rifampicin. The term extensive (extreme) drug resistant
tuberculosis (XDR-TB) has been used to describe a form of
MDR-TB resistant to any uoroquinolone and one of three
injectable aminoglycosides (capreomycin, kanamycin and
amikacin).
Strategies for prevention and disease control include
BCG vaccination and treatment of persons with latent tuberculosis infection who are at high risk of developing active
disease, such as those infected with HIV, close contacts of
persons with known or suspected active tuberculosis, persons
with medical risk factors associated with reactivation of
tuberculosis, medically underserved and low-income populations, alcoholics, injection drug users, persons with abnormal chest radiographs compatible with past tuberculosis,
609

Section VII System Review

and residents of long-term care facilities. BCG vaccine is


recommended for routine use at birth in countries with
high tuberculosis prevalence. However, general use of BCG
may not be recommended in countries with low risk of
transmission due to the wide variation in efcacy of the
vaccines available.

LEPROSY (Hansens Disease)


Leprosy is a chronic granulomatous disease affecting the
skin and peripheral nerves caused by Mycobacterium
leprae. Impairment of nerve function results in major disabilities which have physical, social and psychological
consequences and are the basis of the stigmatization historically associated with the disease. M. leprae is an acidfast-staining, gram-positive, obligate intracellular bacillus
with tropism for macrophages and Schwann cells. The
organism grows preferentially in areas of lower temperature, which is why the skin seems to be a target site for
infection. M. leprae does not grow in culture media. Animal
reservoirs of M. leprae include the nine-banded armadillo
(due to its low core body temperature), mice footpads and
some non-human primates.
According to the WHO, about 720,000 new cases of
leprosy are reported each year, and about two million persons suffer from leprosy-related disabilities. The disease is
endemic in several developing tropical countries, including
India (which accounts for the majority of reported cases
worldwide), Brazil, Myanmar, Madagascar and Mozambique.
More than 80% of all new cases are reported in these geographic locations. Moreover, geographic and ethnic differences in disease distribution are noted within each of these
countries. In contrast to other mycobacterial infections,
leprosy does not seem to be more frequent in patients
infected with HIV, and co-infection with HIV and M. leprae
does not appear to alter the course of either disease.
Pathogenesis
The precise mechanism of transmission of leprosy is still
unknown. Leprosy is not very contagious and has low
infectivity. Leprosy is not spread by touching, and exposure to the microorganism rarely results in clinical disease.
Transmission seems to require frequent and prolonged
contact with an infected person and there is an eight-fold
increased risk of disease development in household contacts. Disease transmission is thought to occur by inhalation of bacilli-laden aerosols from lesions in the respiratory
tract. The inhaled microorganisms are disseminated by
alveolar macrophages to different body organs. Growth
occurs mainly in cooler body sites, such as the skin, mucosa
and peripheral nerves. The incubation period between
exposure to the M. leprae and disease development is very
610

long, and is thought to be between 3 and 5 years, with a


range of a few months to 30 years.
Interactions between host genetic factors and the microorganism determine the clinical pattern of the disease.
Some genes control the overall susceptibility and resistance of the individual to the disease (innate resistance),
while HLA-associated genes inuence the ability and the
pattern of the immune response mounted against the
microorganism (through the function of T lymphocytes
and antigen-presenting cells).
Tuberculoid and lepromatous leprosy represent the two
main clinical patterns of the disease situated at either end of
a spectrum with borderline forms situated along this spectrum. Tuberculoid leprosy is seen in patients who are able
to mount a vigorous immune response to the mycobacterium,
and is characterized by low bacillary counts (paucibacillary
leprosy), few skin lesions and involvement of a small number of nerve trunks. It shows a predominant Th1 cytokine
response with high levels of IL-2, IL-12, IFN- and TNF-.
Lepromatous leprosy is characterized by a limited cellular
immune response, uncontrolled bacillary proliferation within
host macrophages (multibacillary leprosy), diffuse skin
lesions and extensive involvement of peripheral nerves. In
this form, there is a defective Th1 or a dominant Th2 cytokine response. High levels of IL-4, IL-5 and IL-10 are
detected in these lesions. Most patients, however, fall into
a broad borderline category between these two ends of
the spectrum, and are classied as borderline-tuberculoid,
mid-borderline (or dimorphous) and borderline-lepromatous.
These forms are clinically unstable, and affected patients
can experience a shift of the disease toward any end of the
spectrum.
Clinical features
Leprosy is twice as common in males as in females, especially after puberty. The age at diagnosis varies between 10
and 20 years. Leprosy can affect the skin, peripheral nerves,
eyes and bone. Peripheral nerve lesions can cause numbness and weakness, which results in traumatic injuries to
affected organs.
Tuberculoid leprosy, which corresponds to the paucibacillary form of the disease, presents initially on the skin
as hypopigmented, well-demarcated macules that enlarge
slowly and develop elevated margins. The number of lesions
is usually limited. Loss of dermal appendages (hair follicles and sweat glands) also is seen, especially in fully
developed skin lesions. Nerve involvement occurs early in
the course of the disease and sensory, motor and autonomic
nerves are affected, with resulting hypoesthesia, muscle
weakness and anhidrosis. Involved nerves are enlarged and
can be visible clinically. Some patients can present with
severe painful neuritis. Sensory loss in the hands and feet
often leads to severe trauma and burns. When the facial
nerve is affected, patients can experience lagophthalmos

Chapter 21 Granulomatous Diseases

(inability to close eyelids completely) and facial paralysis.


When the ophthalmic branch of the trigeminal nerve is
involved, anesthesia of the cornea and conjunctiva can
increase the risk of corneal trauma and ulceration. These
ocular lesions can result in blindness.
Lepromatous leprosy, which corresponds to multibacillary form of leprosy, shows extensive, symmetric and bilateral
skin lesions. The skin of the face is commonly affected,
becoming thickened and corrugated. Earlobes become pendulous and the lateral portions of the eyebrows are lost.
Involvement of the nose causes nasal stufness and nasal
bleeds, while perforation of the nasal septum results in
saddlenose deformity. Nerve involvement is less prominent
in lepromatous leprosy.
Leprosy reactions are acute inammatory complications presenting as medical emergencies during the course
of the disease. These can occur in untreated patients, but
may often represent a complication of therapy.
Oral manifestations
Oral lesions are not common in patients affected by leprosy, nor are they considered pathognomonic of the disease. Their prevalence ranges from 0 to 60% of cases. This
may decrease further with recent advances in therapy. Oral
lesions seem to be more frequent in the lepromatous form
of the disease and include papules, plaques, nodules, nonspecific erosions and ulcerations involving the tongue,
buccal mucosa and palate.
A triad of changes affecting the facial bones and termed
facies leprosa was described through archaeological studies.
It consists of atrophy of the anterior nasal spine, atrophy
and recession of the maxillary alveolar process, and endonasal inammatory changes. The alveolar destruction limited to the maxillary anterior region can result in loosening
and loss of teeth in the area. Granulomatous inammation
of the nasal cavity can result in palatal perforation and
oronasal communication.
In lepromatous leprosy, M. leprae can infect the dental
pulp and cause pulp necrosis. The microorganisms can
accumulate within myelinated nerves in the pulp. Infected
macrophages can be seen around capillaries. The resulting
vascular damage may cause a reddish discoloration of the
tooth.
Histopathologic features
Tuberculoid leprosy demonstrates well-developed noncaseating granulomas composed of histiocytes, lymphocytes and giant cells. Acid-fast bacilli are absent or difficult
to find. Peripheral nerves become enclosed within and are
destroyed by the granulomas. Tuberculosis, sarcoidosis and
other granulomatous inflammatory reactions may show
similar microscopic features and must be excluded by
clinical and laboratory investigations.

In lepromatous leprosy, sheets of foamy macrophages


called lepra cells are seen in the dermis. These cells contain
very large numbers of acid-fast bacilli, best demonstrated
with the Fite method. Well-formed granulomas are rare in
lepromatous leprosy.
Diagnosis and laboratory findings
The diagnosis of leprosy is based on a positive history of
prolonged contact with a known infected person, living in
endemic areas of the disease, clinical presentation and
laboratory findings. Important diagnostic signs include:
(i) hypopigmented or reddish patches with definite loss of
sensation, (ii) thickened peripheral nerves, and (iii) acidfast bacilli on skin smears or biopsy material.
Skin smears obtained to detect the microorganism are
highly specic, but not very sensitive, because bacilli may
not be identied in tuberculoid leprosy. This test is not
used routinely as a diagnostic aid because laboratory services are not readily available. Intradermal injection of
heat-killed M. leprae (lepromin test) has no diagnostic
utility in individual cases. A positive lepromin test reects
the ability of a person to develop a granulomatous response
to the microorganism, but does not indicate infection
with, or exposure to M. leprae. Major advances in the
laboratory diagnosis of leprosy were made by the development of genetic probes and polymerase chain reaction
(PCR) that can identify M. leprae DNA in clinical specimens. These molecular techniques are highly sensitive and
specic, but are not currently used in clinical practice, in
part due to the complexity of the procedures. The gold
standard for the diagnosis of leprosy is a full thickness
skin biopsy obtained from the advancing margin of an
active lesion.
Management protocols and prognosis
The WHO recommends prolonged multidrug therapy for
leprosy to overcome the problem of drug-resistant M. leprae. Paucibacillary leprosy is treated with dapsone and
rifampin while multibacillary leprosy is treated with a
regimen of dapsone, rifampin and clofazimine. The duration of treatment varies depending on the form of the disease. Other multidrug protocols with varying periods of
treatment are currently being tested.
Complications of leprosy include crippling of the hands
and feet, facial deformities and blindness. Recovery
from neurologic impairment is limited. Leprosy reactions,
which can occur during treatment, require special and
emergency care.
No highly effective vaccine has yet been developed against
leprosy, but there is evidence of a protective effect of BCG
vaccine. The efcacy of this vaccine ranges between 20 and
80% in different trials. Other vaccines are being tested
including BCG with heat-killed M. leprae.
611

Section VII System Review

SYPHILIS
Syphilis, also known as lues, is a chronic sexually transmitted disease caused by Treponema pallidum. The disease
has diverse clinical presentations and is characterized by
periods of active disease and latency.
The causative agent of syphilis, T. pallidum subspecies
pallidum, hereafter referred to as T. pallidum, is a microaerophilic spirochaete which cannot be grown in vitro.
The only known natural host for T. pallidum is the human.
The genome has been fully sequenced and is small, rendering T. pallidum an obligate parasite with limited metabolic capabilities. Other pathogenic treponemes also can
cause disease in humans, such as yaws and pinta.
Syphilis occurs worldwide and usually is transmitted by
sexual contact or from mother to infant. T. pallidum can
be transmitted as a blood-borne infection, but this is infrequent. Syphilis is most common among the poor, those who
lack access to healthcare and in those with many sexual
partners. According to WHO estimates, approximately
12 million new cases of venereal syphilis occurred in 1999,
most of them in developing countries. Congenital syphilis
is a leading cause of perinatal and neonatal death in many
of these countries. In North America and western Europe,
syphilis is less common and disproportionately affects minority populations, men who have sex with men, and persons
using cocaine and other drugs. The individuals at highest
risk for syphilis also are at increased risk for HIV infection,
and the two frequently coexist, as syphilis facilitates the
transmission of HIV.
Pathogenesis
T. pallidum rapidly penetrates intact mucous membranes
or microscopic abrasions in skin. It then enters the lymphatics and blood to produce systemic infection. Despite
induction of a strong humoral and cell-mediated immune
response, T. pallidum is able to survive in the untreated
human host for decades and may continue to be transmitted or cause end-organ damage. T. pallidum can be transmitted from a syphilitic woman to her fetus across the
placenta at any stage of pregnancy. The manifestations of
congenital syphilis are thought to be due to the immune
response of the host, rather than a direct toxic effect of the
pathogen.

612

with or without treatment. Because the ulcers are usually


painless and can occur at sites where they are not visible
or recognized, many individuals are not diagnosed at this
stage.
Hematogeneous dissemination of the pathogen in the
primary stage results in the manifestations of secondary
syphilis, approximately 68 weeks later. The most common manifestations of this stage are a maculopapular rash
affecting the ank, shoulder, arm, chest, back, hands and
soles of feet. A generalized non-tender lymphadenopathy
also is present. Less common features of secondary syphilis
are mucous patches, condyloma lata, alopecia, meningitis,
myalgia, ocular complaints, hepatic, pulmonary and neurologic involvement. The secondary lesions resolve, with
or without treatment, and the infection enters a latent stage
in which there are no clinical manifestations. Transmission
of syphilis is by lesion contact and occurs through individuals with the primary or secondary stages of the disease.
After many years, approximately one-third of individuals with latent syphilis progresses to tertiary syphilis, which
is characterized by cardiovascular disease, neurosyphilis
or gummas. Cardiovascular syphilis is the result of endarteritis obliterans of the vasa vasorum which provides the
blood supply to large vessels, leading to aortitis, aortic
regurgitation, aortic aneurysm or coronary ostial stenosis.
Neurosyphilis may take the form of general paresis, insanity and tabes dorsalis. Nearly all direct mortality is due to
cardiovascular or neurologic complications and is seen in
a relatively small proportion of patients, years after infection. Gummas are foci of granulomatous inammation which
may occur in any tissue and present as nodular ulcerative
lesions. The most commonly involved sites include skin and
skeletal system, mouth and upper respiratory tract, larynx,
liver and stomach.
In pregnant women, syphilis may lead to stillbirth,
spontaneous abortion or congenital infection of the neonate. Features of early congenital syphilis include rhinitis,
mucocutaneous lesions, periostitis, hepatosplenomegaly,
lymphadenopathy, anemia, jaundice, leukocytosis and
thrombocytopenia. Later features of congenital syphilis
are seen at least 24 months after birth and include the
hutchinsonian triad of interstitial keratitis of the cornea, sensorineural hearing loss, and the dental anomalies described
below.

Clinical features

Oral manifestations

Untreated syphilis is a chronic illness which is traditionally divided into primary, secondary and tertiary stages. In
the primary stage a chancre appears at the site of inoculation about 21 days post-infection. The chancre begins as a
painless papule that becomes ulcerated. Primary lesions
most commonly occur on the genitalia and are frequently
accompanied by regional lymphadenopathy. The primary
lesion usually resolves spontaneously within 46 weeks,

Although the oral cavity is the most common extragenital


site of infection, oral manifestations of syphilis are rare.
Primary syphilis results from orogenital or oroanal contact
with an active lesion and typically manifests as a solitary
ulcer (chancre) with indurated margins on the lip, tongue
or palate. The ulcer is usually deep, and is accompanied by
cervical lymphadenopathy. The chancre usually heals spontaneously within 710 days.

Chapter 21 Granulomatous Diseases

In secondary syphilis, maculopapular and nodular mucosal lesions are common. Supercial mucosal erosions, called
mucous patches, may be seen on the lips, oral mucosa,
tongue, palate and pharynx. The mucous patches are typically painless, oval to crescentic erosions, surrounded by a
red periphery. Snail track ulcers are serpiginous lesions
that may arise de novo, or form by coalescence of a number of mucous patches. Condylomata lata are broad-based
verrucous plaques which can be seen in secondary syphilis
of the oral cavity.
The oral manifestations of tertiary syphilis are mostly due
to gumma formation. Gummas are caused by endarteritis
obliterans and tend to involve the hard palate, tongue or
lower alveolus. The gummas form swellings which may
coalesce to form serpiginous lesions and eventually ulcerate,
resulting in bone destruction, palatal perforation and oronasal stula. Intraosseous gummas appear as ill-dened
radiolucent lesions. Interstitial glossitis is rare and is the
result of contracture of the tongue musculature after healing
of a gumma. An association between interstitial glossitis
and oral squamous cell carcinoma of the tongue has been
suggested, but this may be due to the carcinogenic agents
formerly used to treat syphilis (arsenicals and heavy metals)
rather than the infectious agent. Tertiary syphilis can also
give rise to both unilateral and bilateral trigeminal neuropathy and facial nerve palsy.
Oral manifestations of congenital syphilis include
Hutchinson teeth which are screwdriver-shaped incisors that
may show notching of the incisal edge. Mulberry molars
have multiple poorly developed cusps. The facies of patients
with congenital syphilis show frontal bossing, saddle nose,
and poorly developed maxillae. Rhagades are linear scars at
the angles of the mouth caused by secondary bacterial infection of a facial rash occurring in early congenital syphilis.
Histopathologic features
Primary and secondary syphilis are characterized by dense
plasma cell infiltrates, especially in a perivascular distribution, and by capillary endothelial proliferation and obliteration of small blood vessels. However, the microscopic
features are not specific for syphilis. Plasma cells are common in oral biopsies, especially those taken from the gingiva.
The WarthinStarry method is a silver impregnation technique which can be used to demonstrate T. pallidum, but
the stain is not specific and may label other spirochaetes
which inhabit the oral cavity. Gummas are composed of
aggregates of epithelioid and giant cells, forming granulomas,
usually with a prominent plasma cell infiltrate. T. pallidum
is rarely demonstrated in gummas.
Diagnosis
The diagnosis of syphilis is usually based on clinical signs
and symptoms and serologic tests. T. pallidum cannot be
detected by culture. Dark-field microscopic examination of

exudate is of limited value in oral lesions because other commensal Treponema species found in the human mouth can
be confused with T. pallidum. There are two types of serological tests for syphilis: treponemal and non-treponemal.
Commonly used non-treponemal tests include the rapid
plasma reagin (RPR) and venereal disease research laboratory (VDRL) tests. The non-treponemal tests measure IgG
and IgM directed against the cardiolipinlecithincholesterol antigen complex and are used for screening or for
quantification of serum antibody. Treponemal tests are used
for confirmation of reactive non-treponemal results and
include fluorescent treponemal antibody-absorbed (FTAABS) test and T. pallidum particle agglutination assay
(TPPA). The treponemal tests are qualitative tests and are
not used in assessing treatment responses.
Treatment
Parenteral long-acting penicillin G is the drug of choice
for all stages of syphilis. Resistance to penicillin has not
been described. Other antibiotics effective against syphilis
include the macrolides such as erythromycin and azithromycin, as well as tetracycline antibiotics, such as tetracycline and doxycycline. Unfortunately, with increased use
of azithromycin for many infections, there has been an
increased prevalence of macrolide-resistant T. pallidum.
Vaccines are not available for this disease. Testing for HIV
status in affected patients is also recommended.

DEEP FUNGAL INFECTIONS


Fungal infections or mycoses usually are superficial and
involve the skin, hair, nails and mucous membranes. In
some cases, especially in immunocompromised patients,
disseminated or deep fungal infections can cause extensive
tissue destruction. In immunocompetent hosts, deep fungal
infections can heal or remain latent for prolonged periods
of time. Many fungal infections can initiate a granulomatous
inflammatory response in the host as discussed below.

Blastomycosis
Blastomycosis is caused by Blastomyces dermatitidis, a
dimorphic fungus that grows in soil and decaying wood.
The organism is endemic in some parts of the United States
and Canada, but infections are also seen in Mexico, MiddleEast, Africa and India. Infection occurs through inhalation
of the conidiae (asexual spores). In the lungs at body temperature, the conidiae are transformed into yeasts that
multiply through budding. Yeasts represent the pathogenic
forms of the organism. The infection usually is contained
in the lungs and most patients are either asymptomatic or
develop mild non-specific flu-like symptoms. In some
patients, hematogeneous spread can occur.
613

Section VII System Review

Figure 8

Photomicrograph showing Blastomyces dermatitidis. The


organism appears as round yeast with thick refringent cell
wall. (Hematoxylin and eosin, original magnification 200)

Three clinical forms of blastomycosis are recognized:


pulmonary blastomycosis, disseminated blastomycosis and
cutaneous blastomycosis which is very rare. Pulmonary
disease can be acute or chronic. Acute pulmonary blastomycosis presents clinically with productive cough, chest
pain, dyspnea, fever and night sweats. Chronic pulmonary
blastomycosis can be mistaken for tuberculosis, sarcoidosis, or even malignancy. Oral involvement is rare and can
present as ulcers or exophytic mucosal lesions. The clinical differential diagnosis includes oral squamous cell carcinoma and biopsy usually is needed to exclude this
possibility.
The diagnosis of blastomycosis is based on the identication of B. dermatitidis in a tissue biopsy or a cytological
smear of an infected body uid. The organism appears as
a round yeast cell which divides by broad-based budding.
It has a thick, refringent cell wall (Figure 8). Biopsy from
lesional tissue shows a mixed acute and granulomatous
inammation. Special stains such as periodic acid-Schiff
(PAS) (Figure 9) and methenamine silver (Figure 10) can be
used to identify the organism in tissue samples. Skin or
mucous membrane lesions show marked pseudo-epitheliomatous hyperplasia. Diagnosis can be conrmed by culture as well, but this may take several weeks. Highly
specic and sensitive DNA probes can be used to identify
the organism, a few days after culture.
Treatment is based on the severity of the disease. Patients
with mild to moderate illness are treated with itraconazole.
Those with severe disease, meningeal lesions and immunocompromised patients are managed with amphotericin B.

Histoplasmosis
Histoplasmosis is caused by Histoplasma capsulatum, a
dimorphic fungus found in soil contaminated with bird or
614

Figure 9

Periodic acid-Schiff (PAS) stain showing Blastomyces


dermatitidis in the lung of a patient who died of disseminated
blastomycosis. (Original magnification 400)

Figure 10

Methenamine silver stain of the same case shown in


Figure 9. Note the broad-based budding of the yeast.
(Original magnification 400)

bat droppings, and hence rich in nitrogen. The organism is


endemic in some areas of the United States, especially
in the Mississippi and Ohio River Valleys. It can also be
seen in other parts of the world, including central America,
Asia and some Mediterranean countries. Disease occurs
through inhalation of the microconidia, the infectious
form of the fungus. Macrophages, the main target of infection, can be destroyed by the intracellular multiplication
of the pathogen.

Chapter 21 Granulomatous Diseases

The severity of the disease is proportional to the amount


of inhaled spores and to the integrity of the immune response
of the host. Therefore, immunocompromised patients, such
as those with AIDS, organ transplant recipients, and those
with hematological malignancies may develop disseminated histoplasmosis, with involvement of extrapulmonary
sites.
Acute pulmonary infection presents with fever, dyspnea, productive cough and anterior chest discomfort.
Granuloma formation and coagulative necrosis can result
in cavitation of lung tissues. Healing of the granulomatous lesions can cause brosis and concentric calcications. A chronic progressive form of histoplasmosis
exists as well and resembles tuberculosis clinically. The
most common form of histoplasmosis, however, is an
asymptomatic pulmonary infection or a mild respiratory
illness.
Oral involvement is seen mainly in disseminated disease in the form of ulcers, red or white lesions. Oral ulcers
secondary to histoplasmosis may resemble squamous cell
carcinoma or tuberculous ulcers.
The diagnosis of histoplasmosis is based on culture,
identication of the organism in tissue samples, and serologic tests. Growth of the organism in culture can take
several weeks. More rapid identication can be achieved
with specic DNA probes. Microscopic examination of
lesional tissue can show granulomas and multinucleated
giant cells or a diffuse, mixed inammatory inltrate dominated by macrophages. Special stains conrm the presence of small, uniform and oval budding yeast.
Treatment is based on the severity of the disease.
Mild-to-moderate forms of histoplasmosis are treated with
itraconazole, while disseminated disease and immunocompromised patients require treatment with amphotericin B.

Aspergillosis
Aspergillosis is a fungal infection caused by members of
the Aspergillus species which are ubiquitous saprophytic
molds growing on organic matter. Sporulation of the mold
produces large numbers of conidia that can be inhaled by
humans without adverse consequences in the majority of
cases. In some patients, the inhaled organisms can cause
allergic fungal sinusitis, allergic pulmonary aspergillosis
or asthma. A mass of fungal hyphae, called aspergilloma,
can form in the sinuses or the lungs of patients suffering
from cavitary tuberculosis, bronchiectasis or lung abscesses.
Immunocompromised patients, such as individuals with
AIDS, bone marrow or organ transplant recipients, and
patients with hematological malignancies, can develop
invasive disease, where primary disease of the lungs is followed by widespread hematogeneous dissemination and
multiple organ involvement.
Aspergillus fumigatus and A. avus are the most common species to cause human aspergillosis. A. fumigatus is

Figure 11

Aspergillosis of the maxillary sinus in an


immunocompromised patient. Note the septate hyphae
that branch at acute angles. (Hematoxylin and eosin,
original magnification 400)

responsible for the majority of invasive infections in


immunocompromised patients.
Diagnosis of aspergillosis is based on the clinical signs
and symptoms, individual patient risk, culture and histopathology. Microscopically, multiple septate hyphae,
34 m in diameter, with a tendency to branch at acute
angles and with occasional fruiting bodies can be seen
(Figure 11). Aspergillus has a tendency to invade blood
vessels, which explains the presence of areas of hemorrhage and infarction in involved tissues. A non-caseating
granulomatous inammatory response with giant cells can
be seen in immunocompetent patients. It can be intense
enough to cause pressure necrosis of adjacent bone.
Until recently, amphotericin B and itraconazole were
the standard therapeutic regimen for patients with invasive aspergillosis. A recent trial showed that voriconazole
is more effective in these cases and is associated with better survival and fewer side effects. Patients with allergic
fungal sinusitis may require surgical debridement, systemic
antifungal treatment and systemic or topical steroids.
Aspergilloma requires surgical debridement.

Zygomycosis (Mucormycosis, Phycomycosis)


Zygomycosis is a fungal infection caused by zygomycetes,
especially those belonging to the order of Mucorales. The
Rhizopus species and the Mucor species belonging to the
Mucoraceae families of Mucorales are the most common species causing human zygomycosis. Rare human infections can
be caused by the enthomophthorales order of zygomycetes.
Mucorales fungi are ubiquitous and can grow on organic
matter including bread, fruits, vegetables and soil. They produce abundant spores that can be spread in the environment
615

Section VII System Review

Figure 12

FOREIGN BODY GRANULOMAS


A number of foreign materials of endogenous or exogenous
origin, which cannot be phagocytosed by macrophages
because of their size or composition, can induce a granulomatous inflammatory response in tissues. Examples include
silica, beryllium, glass, talc, starch, suture material, and a
large number of dental materials, such as pumice, gutta
percha, endodontic sealers, and some impression materials.
Some endogenous substances such as hair, keratin, amyloid and calcifications can also induce granulomatous
inflammation in tissues. Macrophages accumulate in the
site, become activated, and differentiate into epithelioid
cells. Some of the macrophages fuse to form foreign body
giant cells. Granulomas form and envelop the foreign
material, which may be seen in the cytoplasm of some
macrophages and giant cells.

Zygomycosis of the mandible in a patient undergoing


chemotherapy. The photomicrograph shows multiple
broad, thin-walled, aseptate hyphae that tend to branch
irregularly or at right angles. (Hematoxylin and eosin,
original magnification 400)

and inhaled by humans. Infection rarely occurs in


immunocompetent patients. The most common underlying
risk factors for zygomycosis are uncontrolled insulindependent diabetes mellitus (IDDM) with metabolic acidosis, immunosuppressive treatment, prolonged systemic
corticosteroid use, solid-organ and hematopoietic stem
cell transplantation, persistent neutropenia and ironchelating treatment.
The most common human manifestation of this infection is rhinocerebral zygomycosis that affects the nose,
maxillary sinus, midface with frequent extension into the
brain. Sinonasal disease causes nasal obstruction, rhinorrhea,
facial pain and facial swelling. Oral mucosal involvement
presents with ulceration. Typically, the base of the ulcer is
black and massive tissue destruction and necrosis can be
seen in untreated patients.
The diagnosis of zygomycosis relies on the identication of the broad, thin-walled, irregularly-branching and
mostly aseptate hyphae in affected tissues. Branching
occurs at right angles (Figure 12). The organism has high
afnity for blood vessel invasion, which explains the massive tissue infarction and necrosis observed clinically and
microscopically.
Treatment of zygomycosis necessitates management of
the underlying medical condition, use of effective antifungal treatment and surgical debridement. Amphotericin B is
the treatment of choice. Posaconazole seems to provide
encouraging results, especially in prophylaxis. Debridement
is necessary because antifungal treatment cannot reach
infected tissues, and correction of the surgical defects is
needed once active disease is controlled.
616

Clinical features
The clinical manifestations of foreign body reactions are
usually non-specific and vary from a localized mass to
superficial erosions and ulcerations. In the oral cavity, the
gingiva seems to be the most common site of involvement
and the condition has been termed granulomatous or foreign body gingivitis. Dental materials are the most common causative factors in these cases, but other substances
including hair and nails have been reported. The condition
presents clinically as a localized change in gingival color,
ulceration or diffuse gingival erythema. Lesions start at
the interdental papilla and extend laterally. An important
diagnostic clue is that the condition does not regress with
improvement of oral hygiene measures.
Histopathologic features
Biopsy material from the gingiva can show granulomas and
foreign body giant cells in the absence of microorganisms.
The foreign substance can be identified in hematoxylin
and eosin stained sections (Figure 13) or by polarized light
microscopy. Energy-dispersive radiographic microanalysis
can help confirm the presence of foreign material in tissue
sections and identify its nature. In the absence of identifiable foreign material, other causes of granulomatous
inflammation have to be investigated. In some cases, the
inflammatory response is lichenoid in appearance and the
foreign body is too small to be identified microscopically.
A diagnosis of lichen planus can therefore be rendered,
but the lesions will not respond to conventional treatment
of lichen planus.
Management protocols and prognosis
The treatment of foreign body reactions includes the elimination of the offending agent and excision of involved
tissues. This results in adequate clinical response in the

Chapter 21 Granulomatous Diseases

Figure 13

The role of genetic factors is suggested based on disease


association with distinct HLA alleles. Other genes involved
in controlling the immune response can play a role in disease pathogenesis as well.
Granulomatous vasculitis of the upper airways and lungs
suggests that the disease may represent a cell-mediated
reaction to an inhaled antigen of bacterial, viral or environmental origin. Chronic nasal carriage of S. aureus has
been linked to the initiation and relapse of WG through a
number of molecular mechanisms implicating B cells,
T cells and neutrophils.
Clinical features

Photomicrograph of a foreign body reaction following


reconstructive surgery in the temporomandibular joint
showing a large number of multinucleated giant cells
engulfing a foreign material. Typical granulomatous
inflammation was seen elsewhere in the specimen.
(Hematoxylin and eosin, original magnification 100)

majority of cases. If a diagnosis of granulomatous gingivitis


is made in the absence of an identifiable foreign material,
the patient should be investigated for other causes of
granulomatous inflammation.

WEGENERS GRANULOMATOSIS
Wegeners granulomatosis (WG) is a systemic autoimmune
disease that is invariably fatal if left untreated. The disease
may occur in generalized and limited forms, and consists
of the classical triad of (i) necrotizing granulomatous
inflammation involving the upper respiratory tract, the
lower respiratory tract, or both, (ii) necrotizing glomerulonephritis, and (iii) systemic vasculitis involving small to
medium-sized vessels (capillaries, venules, arterioles, or
arteries).
WG is an uncommon disease, with an estimated prevalence of 3.0 per 100,000 persons in the United States. It is
more common in whites than in blacks and affects both
sexes equally. The mean age at onset is approximately
40 years, but the disease can occur at any age, with 15%
of cases occurring in patients younger than 19 years.
Etiology and pathogenesis
The etiology of WG has not been fully elucidated. Genetic
factors, exposure to environmental antigens such as silica
and infection (in particular with Staphylococcus aureus)
seem to play an important role in disease pathogenesis.

WG affects mainly the upper and lower respiratory tracts.


In generalized WG, renal disease develops rapidly. Limited
WG refers to disease restricted to the respiratory system
without rapid renal involvement. In some cases, the disease
is restricted to the skin and mucosa. This has been termed
superficial WG.
Pulmonary involvement is seen in more than 80% of
patients who may present with cough, hemoptysis, dyspnea and chest discomfort. In asymptomatic patients, abnormal chest radiograph may be the only manifestation of the
disease. Renal disease develops in the majority of patients
(77%), and is the most common cause of morbidity and
mortality. Early glomerulonephritis presents with proteinuria, hematuria and red blood cell casts in urine. Disease
progression leads to renal failure, especially if no treatment
is administered. Active disease is characterized in general
by constitutional symptoms such as malaise, fever, night
sweats and weight loss. Other organs can be involved by the
granulomatous vasculitis, including peripheral and cranial
nerves, heart, eyes and skin.
Involvement of the head and neck region is very common in WG. The nasal cavity and paranasal sinuses are
affected in 6090% of the cases, with symptoms of nasal
obstruction, sinusitis and headache, purulent nasal discharge, epistaxis, and mucosal ulceration. Nasal septal
perforation can cause saddle nose deformity. The ears, the
eyes, the larynx and the oral cavity can be affected as well.
Eustachian tube blockage may result in persistent serous
otitis media. Laryngeal disease can result in subglottic stenosis which can lead to upper airway obstruction requiring
emergency tracheostomy. Salivary gland involvement is
uncommon, but has been reported in WG.
Oral manifestations
Oral involvement is quite common in WG and it may be
the first sign of the disease. Strawberry gingivitis, one of
the characteristic signs of WG, is thought to be an early
manifestation of the disease, occurring before renal involvement. Clinically, strawberry gingivitis appears as hyperplastic granular and friable gingival lesions with multiple
surface petechiae. The buccal surface of the gingiva is more
617

Section VII System Review

frequently involved. The process originates in the interdental papillae and extends laterally to involve the rest of
the gingiva. Periodontal bone loss has been described and
can result in tooth mobility and extraction. Non-healing
of extraction sockets is possible. Oral ulcers affecting any
mucosal surface can be seen in WG, but are non-specific
and seem to develop at an advanced stage of the disease,
usually after renal involvement occurs. Necrosis and ulceration of the palate can be seen.
Histopathologic features
Wegeners granulomatosis is characterized microscopically by granulomatous inflammation, geographic necrosis and vasculitis. The granulomas are ill-defined, surround
areas of necrosis, and are not as compact and as defined
as those seen in tuberculosis and sarcoidosis. In lung biopsies, areas of necrosis are surrounded by a shell of fibroblastic, inflammatory and giant cells, producing palisading
granulomas. The inflammatory infiltrate can be dense,
mixed, and non-specific and overshadow the underlying
pathology. Special stains do not show microorganisms and
foreign body cannot be identified by polarizing light
microscopy. Affected vessels show a transmural inflammatory reaction, with focal or diffuse polymorphonuclear
infiltrates causing vessel wall destruction and fibrin deposition within the walls and the lumen. The necrosis seen
seems to be secondary to the vasculitis.
Oral mucosal biopsies show an inammatory inltrate
composed mainly of neutrophils and eosinophils that occasionally form microabcesses. Giant cells are common and
ill-dened granulomas can be seen. Vasculitis is less prominent in mucosal biopsies from the head and neck region,
including the mouth, mainly due to the small size of these
biopsies and lack of larger vessels in mucosa. Strawberry
gingivitis shows pseudoepitheliomatous hyperplasia and a
prominent vascular component associated with red blood
cell extravasation.
Diagnosis and laboratory findings
The diagnosis of WG is based on history, clinical presentation, laboratory test results and microscopic findings of
necrotizing granulomatous vasculitis in a biopsy specimen.
Laboratory tests show an elevated erythrocyte sedimentation rate (ESR), high C-reactive protein, leukocytosis and
thrombocytosis. Renal involvement can result in urinary
sediment, erythrocyturia, proteinuria and high serum creatinine levels. Chest radiographs and computerized tomography can confirm the presence of pulmonary infiltrates or
nodules. Detection of c-ANCA by indirect immunofluorescence and confirmation of the specificity of ANCA against
proteinase-3 (PR3-ANCA) by ELISA yields a specificity of
99% and a sensitivity of 73% in the diagnosis of WG.
Identification of c-ANCA is an adjunctive test, as false positive results can be seen in some infectious and neoplastic
618

diseases. Furthermore, a negative c-ANCA titer does not


exclude the diagnosis of WG. Changes in ANCA titers
appear to reflect disease activity and rising titers can predict
relapse in treated patients although this is not a consistent
finding.
Management protocols and prognosis
Wegeners granulomatosis is typically treated with longterm cyclophosphamide given in oral doses together with
glucocorticoids which produces rapid and marked improvement in the majority of patients. Recently, it was shown
that rituximab can play a role in the induction of remission. Less toxic drugs such as azathioprine, methotrexate
and leflunomide can be used to maintain remissions.
Approximately half of remissions are followed with one
or more relapses, and many patients develop some degree
of morbidity either from irreversible features of their disease or from the toxic side effects of treatment. Patients may
suffer from varying degrees of renal insufciency or impaired
upper respiratory tract function. Cyclophosphamide-related
toxicities include cystitis, bladder cancer, myelodysplasia
and infertility. Diabetes mellitus, cataracts, infectious complications and osteoporosis are some of the glucocorticoidassociated side effects.

SARCOIDOSIS
Sarcoidosis is a relatively common multisystem immunemediated disease primarily affecting the lungs and lymphatic systems. It is characterized by the presence of
non-caseating granulomas in affected organs. The etiology of sarcoidosis is unknown, but familial, spatial (e.g.
among people in the same household), seasonal and occupational clustering of the disease have been reported, suggesting multiple underlying factors, including genetic
predisposition, infectious agents and environmental exposures. Possible microbial triggers include mycobacterial
and propionibacterial organisms, with the mycobacterial
catalase-peroxidase (mKatG) protein as a potential candidate antigen. Sarcoidosis likely develops from an exaggerated cellular immune response (acquired, inherited or both),
to a limited class of persistent antigens or self-antigens.
Space-occupying granulomas form from the accumulation
of mononuclear inflammatory cells, mostly CD4 Th1 lymphocytes and mononuclear phagocytes in affected organs.
Organ dysfunction and tissue injury result from physical
distortion of the tissue by the granulomas.
Sarcoidosis is found throughout the world, but is most
prevalent in United States and Scandinavian populations.
In the United States there is a three-fold to ve-fold increased
incidence in blacks compared to whites. Geographic, ethnic and genetic factors are linked to the specic clinical
characteristics of patients with sarcoidosis. Blacks are more

Chapter 21 Granulomatous Diseases

likely to have severe musculoskeletal or constitutional


symptoms on presentation, while whites appear to have
higher rates of asymptomatic disease, disease limited to
the chest and erythema nodosum.

Figure 14

Clinical features
Sarcoidosis is more common in young and middle-aged
adults, with approximately 75% of the cases in individuals
younger than 40 years. Females appear to be slightly more
susceptible than males. Sarcoidosis has a variable clinical
presentation and course, and can affect many organs and
tissues, but the lungs are most commonly affected. Unlike
many lung diseases, sarcoidosis favors non-smokers. Other
organ systems that may be affected by sarcoidosis include
the heart, liver, spleen, bones, skin, eyes, lymph nodes,
parotid glands, and uncommonly, the oral cavity. The
majority of patients with sarcoidosis are asymptomatic,
with the disease being discovered on routine chest radiographs. Symptomatic sarcoidosis may develop abruptly
over a period of a few weeks. Less frequently sarcoidosis
arises insidiously over months or years without significant
symptoms. Symptomatic patients usually present with
respiratory and skin manifestations or with constitutional
and non-specific symptoms such as fever, night sweats,
fatigue and malaise. Dry cough, dyspnea and chest pain
are frequent respiratory complaints. Cutaneous manifestations occur in approximately 25% of patients and include
erythema nodosum and lupus pernio. Erythema nodosum
are scattered tender erythematous nodules occurring frequently on the lower legs, while lupus pernio represents
chronic, violaceous lesions involving the face, limbs, back
and buttocks. Ocular symptoms may be due to anterior
uveitis or lacrimal gland involvement resulting in keratoconjunctivitis sicca. Two distinctive clinical syndromes
are associated with acute sarcoidosis. Lfgren syndrome, a
form of acute sarcoidosis usually found in white females,
consists of erythema nodosum, bilateral hilar lymphadenopathy and arthralgia. Heerfordt syndrome (uveoparotid
fever) is characterized by parotid enlargement, anterior
uveitis, facial paralysis and fever.
Oral manifestations
Excluding salivary gland and lymph node involvement,
oral manifestations of sarcoidosis are uncommon, and the
disease is typically diagnosed before oral symptoms appear.
Sarcoidosis may involve any oral mucosal site, most commonly buccal mucosa, followed by gingiva, lips, floor of
mouth, tongue and palate. The lesions most commonly present as submucosal masses, which may vary in color from
normal to brownish-red or violaceous or they may be hyperkeratotic. Sarcoidosis of the major and minor salivary
glands may result in xerostomia. Sarcoidosis can cause
bilateral enlargement of the major salivary glands which,
in conjunction with xerostomia and keratoconjunctivitis

Photomicrograph of a granulomatous inflammatory


lesion involving the lung of a patient with sarcoidosis.
Well-formed non-caseating granulomas are noted and
are surrounded by a rim of lymphocytes. (Hematoxylin
and eosin, original magnification 200)

sicca, can mimic Sjgrens syndrome. Intraosseous lesions


are less common than soft tissue lesions, accounting for
approximately one-fourth of all reported intraoral cases.
Either jaw may be affected. Intraosseous lesions typically
appear as non-expansile ill-defined radiolucent areas which
may be accompanied by tooth mobility due to alveolar
bone loss.
Histopathologic features
Lesions of sarcoidosis consist of tightly clustered aggregates of epithelioid histiocytes surrounded by a rim of lymphocytes (Figure 14). Multinucleated giant cells of the
Langhans type or foreign body type are intermixed with
the histiocytes. Necrosis is typically absent (Figure 15). The
giant cells may contain laminated calcified structures called
Schaumann bodies or stellate inclusions known as asteroid
bodies. Special stains for fungal and bacterial organisms
are negative. Polarizable, dissolvable and pigmented foreign
materials are not detectable.
Diagnosis and laboratory findings
The diagnosis is based on clinical and radiographic findings, histopathologic evidence of non-caseating epithelioid granulomas, and exclusion of other known causes of
granulomatous inflammation. Chest radiographs may show
bilateral hilar lymphadenopathy, diffuse parenchymal infiltrates, or both, and 90% of patients have abnormal chest
619

Section VII System Review

Figure 15

The overall prognosis of sarcoidosis is good. Spontaneous resolution is common and in most patients symptoms
resolve spontaneously within 2 years without treatment.
Poor prognostic indicators include chronic disease, older age
at onset, black race, lupus pernio, neurosarcoidosis, cardiac
involvement and advanced pulmonary disease. Approximately 410% of patients die of progressive respiratory,
central nervous system or cardiac involvement.

OROFACIAL GRANULOMATOSIS

Photomicrograph of sarcoidosis showing absence of necrosis.


Scattered giant cells are noted within the granulomas.
(Hematoxylin and eosin, original magnification 100)

radiographic findings sometime during the course of their


disease. Lung function abnormalities typically found include
decreased lung volumes and diffusing capacity. Elevated
serum angiotensin-converting enzyme (ACE) levels support
the diagnosis of sarcoidosis, but this test lacks sensitivity
and specificity. Elevated serum calcium concentration and
urinary calcium level may be found. The Kveim test, a skin
test for sarcoidosis involving intradermal injection of
human spleen extract of sarcoid tissue, is no longer used
because of concerns of transmission of infectious diseases.
Minor salivary gland biopsy may be helpful in suspected
cases of sarcoidosis, with success rates between 19% and
58%. However, parotid biopsy provides a better diagnostic
yield, with confirmation of sarcoidosis reported in 93% of
patients following this procedure.
Management protocols and prognosis
The diagnosis of sarcoidosis usually is followed by a
3- to 12-month period of observation to define the general
course of the disease. Immediate medical treatment is indicated for patients with neurological, cardiac, severe ocular,
advanced pulmonary and disfiguring cutaneous disease, as
well as persistent hypercalcemia. The standard treatment
for sarcoidosis is systemic corticosteroids. Other immunosuppressive and immunomodulating drugs including tumor
necrosis factor antagonists, have been used, but definitive
evidence of their efficacy is lacking. Xerostomia secondary to sarcoidosis of the major salivary glands predisposes
patients to caries, periodontal disease and candidiasis, necessitating preventative measures, salivary stimulants, topical
fluoride and antifungal medications. Systemic corticosteroid therapy can result in adrenal suppression requiring
special precautions before oral surgical interventions.
620

Orofacial granulomatosis (OFG) is a clinical and pathologic term introduced by Wiesenfeld in 1985 to describe
a group of conditions affecting the oral and maxillofacial region, and characterized microscopically by noncaseating granulomatous inflammation. The spectrum of
OFG includes cheilitis granulomatosa (CG) of Miescher,
MelkerssonRosenthal syndrome (MRS), Crohns disease,
sarcoidosis and other granulomatous inflammatory conditions that could affect this region. Some cases of OFG can
develop secondary to a chronic dental infection or to a
contact hypersensitivity reaction while others appear to be
idiopathic. A preliminary diagnosis of OFG should be followed by a thorough clinical and laboratory investigation
to identify and treat any possible underlying local or systemic disease and thus idiopathic OFG is a diagnosis
acquired by exclusion.
The etiology of OFG is unknown and the disease is
thought to represent an abnormal immune reaction. Infection, allergy and genetic predisposition have been suggested. Monoclonal lymphocytic expansion, which may be
secondary to chronic antigenic stimulation, has been identied in OFG. Cytokine production by the monoclonal lymphocytic proliferation could stimulate granuloma formation.
The spectrum of OFG encompasses cheilitis granulomatosa (CG) of Miescher and MelkerssonRosenthal syndrome (MRS). Systemic conditions such as tuberculosis,
Crohns disease, sarcoidosis and other granulomatous
inammatory conditions could present with granuloma
formation in the oral and maxillofacial region.
Clinical features
The most consistent finding in OFG is a painless, persistent
diffuse swelling involving one or both lips (macrochelia).
The swelling can be unilateral or involve the whole lip
(Figure 16). In the early phases of the disease, the swelling
is usually soft, intermittent and recurrent. Later, the swelling becomes permanent and fibrotic. Generalized edema,
erythema and non-specific erosions and ulcerations may
be seen in the mouth. Gingival swelling can be seen in some
cases. Some patients develop swelling elsewhere in the face,
with or without lip involvement, making the diagnosis
more difficult. Other reported manifestations of OFG include

Chapter 21 Granulomatous Diseases

Figure 16

Diffuse lip swelling in a patient with orofacial granulomatosis.


Slight erythema was noted on the facial skin

fissures of the tongue, taste alterations, decreased salivary


production and a cobblestone appearance of the buccal
mucosa.
When the swelling is limited to the lips, the term CG is
used by some clinicians and when it is associated with a
ssured tongue and a history of recurrent facial paralysis
a diagnosis of MRS can be applied. It is better, however, to
limit the use of these terms since they are considered
as subsets of OFG rather than specic disease entities. It is
also useful to use terms such as OFG in the context of
Crohns disease or sarcoidosis, OFG secondary to contact
hypersensitivity reaction, or idiopathic OFG to standardize
terminology.
Histopathologic features
Orofacial granulomatosis is characterized by the presence
of non-caseating epithelioid granulomas, usually with
multinucleated giant cells (Figure 17). The granulomas may
be concentrated around blood vessels, or they may be scattered in the connective tissue and lamina propria. Sometimes,
minor salivary gland involvement can be seen. A perivascular lymphocytic infiltrate with marked dilation of lymphatic
channels and marked edema of the superficial lamina propria is seen in some cases, and can be useful when typical
granulomas are absent. Acid-fast bacilli and fungal organisms cannot be identified with special stains and foreign
material is not seen with polarized light microscopy.

Figure 17

Photomicrograph of a buccal mucosal biopsy showing


multiple non-caseating epithelioid granulomas with
multinucleated giant cells. An intense lymphoplasmocytic
infiltrate is associated with the granulomas. (Hematoxylin
and eosin, original magnification 100)

exclusion of possible causes of granulomatous inflammation should be followed by a systematic work-up, including
clinical, laboratory and radiographic investigations, to
rule out underlying local or systemic disease.
All oral foci of infection should be identied and
treated. Elimination diet and patch testing against potential allergens such as food additives, cosmetics, fragrances
and dental hygiene products should be performed if contact hypersensitivity reaction is suspected. Chest radiographs and serum levels of angiotensin-converting enzyme
can be obtained to screen for evidence of sarcoidosis.
Complete blood count, ESR, and serum levels of folic acid,
vitamin B12, and iron are useful in patients with unusual
gastrointestinal manifestations. These patients also should
undergo specialized gastrointestinal examination to assess
for Crohns disease. If this investigation is negative, it can
be repeated later, especially if clinically indicated and in
younger patients with OFG as these patients are more
likely to have concomitant intestinal disease. Tuberculin
test and chest radiographs should be performed even if
acid-fast stains were negative on histology to exclude
tuberculosis.
Management protocols and prognosis

Diagnosis and laboratory findings


Special stains, such as the PAS stain, Grocott methenamine silver stain, ZiehlNeelsen and Gram stain applied to
the lesions of OFG do not show fungal or specific bacterial
organisms. Foreign body is not demonstrable within the
lesions with polarized light microscopy. The microscopic

Intralesional corticosteroid injection is the treatment of


choice in OFG. The response to intralesional treatment is
usually fast, but relapses are common, and therefore
repeated injections are needed. Systemic corticosteroids
are effective, but their long-term use is limited by the
recurrent and chronic nature of the disease and by their
621

Section VII System Review

serious side effects. Other therapeutic measures have been


used with variable success, including hydroxychloroquine,
methotrexate, clofazimine, metronidazole, minocycline alone
or in combination with oral prednisone, thalidomide, dapsone and danazol. One study showed that the impact of
dietary manipulation in patients suffering from OFG can
be significant, especially in the presence of oral mucosal
inflammation. Other investigators reported improvement
of oral manifestations upon removal of amalgam restorations, but this has not been reproduced in controlled studies. Surgical intervention (cheiloplasty) is performed when
the response to medical treatment is weak and in severely
disfiguring cases. It is not a first-line therapy because of
the high risk of recurrence.
The treatment of OFG is difcult and often disappointing due to the chronic nature of the disease and the high
risk of recurrence. Identifying the underlying causative factor
is not feasible in many cases, which increases the risk of
recurrence. Spontaneous remissions have been reported
but do not seem to be very common.

CROHNS DISEASE (Regional Ileitis, Regional


Enteritis)
Etiology and pathogenesis
Crohns disease is a chronic, relapsing, immunologically
mediated inflammatory bowel disorder. Its etiology and
pathogenesis have not been clearly defined. Crohns disease
is thought to be due to an inappropriate acquired T-cell
immune response to certain commensal enteric bacteria
developing in genetically susceptible hosts. Environmental
factors seem to play a role in disease pathogenesis as well.
T cells implicated in Crohns disease are primarily activated CD4 Th1 lymphocytes which secrete cytokines
such as IL-12, IFN- and TNF. Although Crohns patients
show loss of tolerance to enteric commensal bacteria, no
specific infectious etiology has been identified. The role of
environmental triggers such as smoking, use of antibiotics
and non-steroidal anti-inflammatory drugs (NSAIDs), stress
and infection is not well understood, but these factors
appear to play a role in precipitating the onset or the reactivation of disease. Evidence for hereditary factors in the
pathogenesis of Crohns disease includes a concordance
rate of approximately 50% in monozygotic twins and an
increased risk of the disease in relatives of patients with
Crohns disease.
Genes associated with innate immunity, such as
NOD2 (nucleotide-binding oligomerization domain 2) and
ATG16L1 (autophagy-related, 16-like) genes, have been
implicated in Crohns disease. NOD2 is an intracellular
protein that senses bacterial products and activates components of the innate immune system. Other genetic loci
linked to Crohns disease include several genes involved in
622

endoplasmic reticulum and metabolic stress, regulation of


adaptive immunity and inammation.
The role of genetics in disease development is actively
investigated and susceptibility genes such as NOD2/CARD15,
IL23R, ATG16L1 and others have been identied. Of these,
the NOD2/CARD15 gene (caspase recruitment domain family member 15) is the most replicated and understood. It
plays a role in regulating innate immune responses, bacterial killing, immune responses to endogenous microbial
antigens and epithelial function. NOD2 (nucleotide-binding oligomerization domain containing 2) is an intracellular protein that senses bacterial products and activates
components of the innate immune system.
Clinical features
Crohns disease is more prevalent in western countries than
in developing countries and is more prevalent in northern
regions compared to southern regions. Urban areas have a
higher prevalence of Crohns disease than rural areas. The
disease frequency is highest in Ashkenazi Jews. Higher
economic status and active smoking increase the risk for
Crohns disease. The peak age of onset is between 15 and
30 years, and a second peak occurs between the ages of
60 and 80. The male-to-female ratio is 1:1 to 1.8:1.
Crohns disease can affect any part of the gastrointestinal tract from the mouth to the anus, with the terminal
ileum being involved in the majority of patients. Symptoms
commonly include long-standing diarrhea, abdominal pain,
weight loss, and some patients may experience non-specic
symptoms such as malaise, anorexia or fever. Transmural
inammation (inammation affecting all layers) of the gut
may result in ssures, abscesses, stulas, thickening of the
bowel wall and limited distensibility. Aphthous-like supercial ulcerations can be seen. These can fuse longitudinally
and transversely around normal tissue to produce a cobblestone appearance of the bowel mucosa.
Extraintestinal manifestations are relatively common
and include dermatologic conditions such as erythema
nodosum, pyoderma gangrenosum, pyodermatitis vegetans,
and Sweet syndrome, a neutrophilic dermatosis. Rheumatologic manifestations include asymmetric polyarticular
migratory polyarthritis most often affecting the large
joints of the upper and lower extremities, and ankylosing
spondylitis. Ocular complications include conjunctivitis,
anterior uveitis/iritis and episcleritis.
Oral manifestations
Oral lesions of Crohns disease can vary and be relatively
non-specific. These do not necessarily reflect intestinal
disease activity. Oral involvement can occur at any time
during the course of the disease and may precede gastrointestinal manifestations in as many as 30% of the cases.
Findings include diffuse or nodular swelling of the oral
and perioral tissues, a cobblestone appearance of the oral

Chapter 21 Granulomatous Diseases

Figure 18

A linear ulcer in the upper left vestibule of a young


patient with Crohns disease

Figure 20

Clinical appearance of pyostomatitis vegetans, presenting


diffuse erosive and erythematous lesions involving the labial
mucosa, the gingiva and the vestibule

Figure 19
Figure 21

Diffuse hyperplastic gingivitis in the same patient


shown in Figure 18. Biopsy confirmed the presence
of non-caseating granulomas

mucosa and deep linear ulcers involving the buccal vestibule (Figure 18). Aphthous ulcers can be seen, but their
significance in Crohns disease is uncertain, as they occur
as frequently in the general population and in the same
age group affected by Crohns disease. Other reported
oral manifestations include fibroepithelial hyperplasia,
granulomatous gingivitis (Figure 19), angular cheilitis,
persistent submandibular and superficial cervical lymphadenopathy, and metallic dysguesia. Less than 1% of
patients with Crohns disease may develop diffuse stomatitis, with some cases caused by Staphylococcus aureus,
and others being non-specific. A rare condition called
pyostomatitis vegetans may be associated with Crohns disease. Pyostomatitis vegetans is usually seen on the buccal,
labial mucosa, soft palate, ventral tongue and facial gingiva

Photomicrograph of a gingival biopsy from the patient


shown in Figure 19 demonstrating multiple non-caseating
granulomas with a large number of multinucleated giant cells.
(Hematoxylin and eosin, original magnification 100)

and is characterized by the development of multiple yellowish, serpiginous pustules on erythematous oral mucosa
(Figure 20). The pustules often rupture, leading to erosions
and fissuring.
Histopathologic features
In the bowel, Crohns disease is characterized by transmural non-necrotizing granulomatous inflammation. Oral
lesions show non-necrotizing granulomas in the submucosa
similar to those seen in OFG (Figure 21). The severity of the
granulomatous inflammation may vary tremendously from
623

Section VII System Review

patient to patient and from various sites in the same


patient. Therefore, a negative biopsy at one site and time
may not necessarily rule out a diagnosis of Crohns disease. Special stains should be performed to rule out the
possibility of deep fungal or mycobacterial infection.
Diagnosis
A single gold standard for the diagnosis of Crohns disease is
not available. The diagnosis is confirmed by clinical evaluation and a combination of endoscopic, histopathologic,
radiographic and biochemical investigations. Serological
tests for anti-Saccharomyces cerevisiae antibodies/perinuclear
ANCA (ASCA/ANCA) have a high specificity for the diagnosis of Crohns disease if the pattern is positive (ASCA/
ANCA). High serum levels of C-reactive protein are useful for assessing a patients risk of relapse and may correlate with disease activity.
Management and prognosis
Current therapeutic options include anti-inflammatory and
immunosuppressive medications, such as sulfasalazine,
5-ASA agents, prednisone, budesonide, azathioprine and
6-mercaptopurine. Anti-TNF therapies such as infliximab,
adalimumab and certolizumab are effective against Crohns
disease as they block TNF, a key inflammatory cytokine
and mediator of intestinal inflammation. Antibiotics, especially metronidazole and ciprofloxacin, are used for their
anti-inflammatory and anti-infectious properties. Surgery
is required for most patients and is related to the duration
of disease and site of involvement. Oral Crohns disease

624

shows a variable and unpredictable response to topical


and systemic glucocorticoid therapy. Topical treatment
may yield remission in almost 50% of patients and should
be used as first-line therapy in patients with asymptomatic
intestinal disease, while intra-lesional corticosteroids and
systemic treatment should be considered when topical
treatment fails to control symptoms. Crohns patients have
an increased risk of colorectal cancer, non-Hodgkins lymphoma, squamous cell carcinoma of the skin and small
bowel cancer.
The management of Crohns disease is based on controlling acute ares followed by maintenance of clinical
remissions. This is achieved by the use of corticosteroids
as rst-line therapy followed by immunosuppressive drugs
such as azathioprine, 6-mercaptopurine and methotrexate
for maintenance. Sulfasalazine and 5-ASA can be used to
maintain remissions or for the treatment of mildly active
disease, but their role is questioned and considered to be
modest. Budesonide, a locally active steroid with limited
systemic activity, can be used as single agent or in combination therapy to induce remissions in mild and localized
ileocaecal disease. Its role in maintenance is questioned.
TNF antagonists such as iniximab and adalimumab seem
to be extremely effective against Crohns disease as they
induce and maintain mucosal healing and reduce surgery
and hospitalization rates. However, in current treatment
protocols, they are reserved for patients resistant to steroids and immunosuppressors as well as for those with
severe stulizing disease. This concept is challenged and
use of TNF antagonists is tested for the treatment of early
Crohns disease and for the maintenance of remissions.

CHAPTER

Sexually Transmitted
Diseases
Praveen BN, Nagaraj A, Ravikiran Ongole

22

Fellatio Syndrome

Condyloma Acuminatum

Traumatic Lesions of Lingual Frenum

Oropharyngeal Gonorrhea

Syphilis or Lues

Oropharyngeal Chlamydial Infection

Human Immunodeficiency Virus Infection

Oropharyngeal Trichomonal Infection

Intraoral Molluscum Contagiosum

Sexually transmitted diseases (STDs) or sexually transmitted


infections (STIs) or venereal diseases are infections that
can be transferred from one person to another through sexual contact.
Sexually transmitted diseases have been a part of
human existence from ages. However, in the last couple of
decades with changing sexual practices among heterosexual and homosexual individuals, the incidence of STDs
have exponentially increased.
Moreover, with the emergence of various multidrug
resistant strains of pathogens, newer spectra of diseases
such as acquired immunodeciency syndrome (AIDS) and
the evidence of venereal spread of various pathogens, the
need to prevent, recognize these diseases and manage them
effectively is important.
According to the statistics of the Centers for Disease
Control and Prevention (CDC), approximately 19 million
STD cases are reported annually in the United States. Among
these 19 million cases about 50% of these are seen in people
in the age group of 1524 years.
It is believed that there are more than 25 diseases that
are transmitted through sexual activity. The most common
STDs are HIV, chlamydia, gonorrhea, syphilis, genital herpes,
human papillomavirus, hepatitis B, trichomoniasis and bacterial vaginosis.
As most of these venereal diseases have characteristic
oral ndings, the oral physician needs to keep abreast of the
latest updates about the whole range of clinical manifestations of these diseases.
This chapter will deal with common STDs associated
with oral manifestations.

FELLATIO SYNDROME
It is described as submucosal hemorrhage secondary to
repetitive negative pressure and/or blunt trauma associated with fellatio (Terezhalmy et al, 2000).
These oral lesions are typically found in sexually active
adults. However, presence of such lesions in children may
be associated with sexual abuse.
Clinical features
The submucosal hemorrhages are characteristically seen at
the junction of the soft and hard palate without involvement of the uvula, pharyngeal wall or other oropharyngeal
structures.
These lesions may appear bilaterally as solitary lesions,
occasionally connected hemorrhagic bridge. They may also
appear as a well-dened band of ecchymosis stretching
across the soft palate.
These non-ulcerated hemorrhagic areas are painless and
do not blanch on palpation.
Diagnosis and differential diagnosis
A good personal history will help in the diagnosis. However,
other conditions that may mimic such lesions are frequent
use of drinking straws, habit of sucking on candies (produces negative pressure), petechiae secondary to forceful
sneezing, vomiting or coughing, upper respiratory tract
infections, blood dyscrasias, infectious mononucleosis, nasopharyngeal tumors and anticoagulant or antithrombotic
medications.
625

Section VII System Review

Management
Patient should be made aware of the nature and cause of
the lesion. Hemorrhagic diathesis should be considered when
the lesions do not subside in about 10 days time following
cessation of the habit.

TRAUMATIC LESIONS OF LINGUAL FRENUM


Lesions on the lingual frenum are usually seen in individuals
who practice cunnilingus (tongue projected into the vaginal
area). During such tongue thrusting, the ventral surface of
the tongue and particularly the lingual frenum rubs against
the incisal edges of the mandibular anterior teeth.
Clinical features
Patient may complain of pain and soreness in relation to
the ventral surface of the tongue. On clinical examination,
the ventral surface of the tongue and the lingual frenum may
exhibit an ulcerative lesion usually covered by a fibrinous
exudate. The ulcer is typically bounded by an erythematous
halo. In chronic cases irritation fibroma may be evident on
the lingual frenum.
Management
In most patients the ulcer will resolve in about a weeks
time. Topical anesthetic agent can be prescribed for symptomatic relief. Irritation fibroma will have to be surgically
excised.

SYPHILIS OR LUES
Syphilis is a chronic venereal infection caused by fragile
spirochete Treponema pallidum.
The term syphilis was coined by the Italian physician and
poet Girolamo Fracastoro (1530). Other names which have
been used in literature are French disease, Italian disease,
Christian disease, British disease, lues venerea and Cupids
disease. In the 16th century syphilis was recognized as
Great Pox in Europe.
Diseases caused by other species of Treponema include
Yaws (caused by T. pertenue), Pinta (caused by T. carateum)
and bejel (endemic syphilis, caused by T. endemicum).
The major source of transmission of syphilis is by sexual
contact (acquired). The other modes of transmission include
transplacental spread (congenital/neonatal) or accidental
inoculation of the causative organism (non-sexual modes
of transmission).
T. pallidum is a delicate fastidious spirochete whose
only natural hosts are humans. It is of 1015 m in length
and 0.2 m in thickness, tapering ends and possesses
1015 spirals. It has a graceful to and fro and angulating
626

movement under dark-eld microscopy in a wet preparation. Organisms can be demonstrated in tissue/tissue uids
by silver staining and immunouorescence. Pathogenic
T. pallidum (Nicholas strain) has not yet been able to culture but organisms can be maintained in rabbits testicular
tissue with retaining its pathogenicity. In refrigerated blood
the organisms die within 5 days and can be easily killed
with soap and water.
Pathogenesis
The organisms gain entry through mucous membrane or
abraded skin during sexual contact. It is estimated that only
about 50% of people who come in contact develop syphilis.
It is believed to be due to the presence of local factors and
immobilins in the blood which immobilize T. pallidum.
Incubation period varies from 9 to 90 days.
Natural immunity to syphilis does not occur in humans
and vascular changes appear to be more signicant, characterized by endarteritis and periarteritis. Fibroblastic proliferation leads to brosis and scar formation.
Clinical features
Primary syphilis Primary syphilis is typically acquired
via direct sexual contact with the infectious lesions of a
person with syphilis. Approximately 1090 days after the
initial exposure (average 21 days), a skin lesion appears at
the point of contact, which is usually the penis, vagina or
rectum, but can occur anywhere on the body.
It is estimated that only about 2% of the primary lesions
are evident on extragenital sites such as the rectum, ngers,
lips, tongue, palate, tonsils, nipple and chin.
Lee et al (2006) reported a case of syphilitic chancre
presenting as a solitary nodule of the nipple. Primary lesions
on the ngers usually result from contact with genital lesions
during sexual foreplay or as an occupational exposure
in physicians and nurses as a result of direct contact with
infectious ulcers in their patients. Little (2005) suggested
that syphilis can be spread by direct contact with mucosal
lesions of primary and secondary syphilis or blood and
saliva from infected patients.
This lesion, called a chancre, is a rm, painless ulceration localized at the point of initial exposure to the spirochete. The chancre begins as a papule that subsequently
ulcerates. The chancre may persist for 38 weeks and usually heals spontaneously. Localized lymphadenopathy may
be evident.
The oral primary syphilitic lesion (chancre) like elsewhere
in the body, is generally seen after about 3 weeks after the
exposure at the site of inoculation of the virus. Initially a
papule is formed which subsequently ruptures to form a
painless ulcer. The ulcer is generally punched out and may
be indurated. Regional lymphadenopathy is usually a characteristic feature. The chancre resolves in about 4 weeks
leaving a scar.

Chapter 22 Sexually Transmitted Diseases

Secondary syphilis Though it is often believed that the


secondary lesion of syphilis appears about 2 months after
the primary lesion has healed, an estimated 30% of the individuals may present a chancre along with the secondary
lesion.
The secondary lesions of syphilis affect the skin, liver,
kidneys, genitalia, oral mucosa, eyes, ears and bones.
Skin rashes may be seen which may have varied presentations such as papules, macules and pustules. These lesions
are typically copper colored and sometimes referred to as
raw-ham colored lesions. The palms and soles are commonly affected. These lesions are generally not pruritic.
It is estimated that about 510% of the patients present
with patchy or moth-eaten appearance alopecia.
Systemic signs and symptoms associated with secondary
syphilis include malaise, prostration, cachexia, low-grade
fever (seldom exceeding 100F), headache, asymptomatic
meningitis, cranial nerve palsies (nerves II to VIII), painless
lymphadenopathy, vague bone pain, jaundice, syphilitic
hepatitis, proteinuria, nephrotic syndrome, rapidly progressive glomerulonephritis, renal failure and ulcers affecting
the antral and pyloric areas of the stomach.
Ophthalmic signs and symptoms include episcleritis,
scleritis, interstitial keratitis, posterior uveitis, papillary
abnormalities and optic nerve involvement.
Patients can also complain of bilateral tinnitus and
deafness. Genital mucosa reveals the presence of macules,
papules, ulcers or condylomata. These lesions usually resolve
in about 3 weeks.
It is estimated that about 30% of the patients with secondary syphilis present with oral mucosal involvement.
Secondary syphilis in the oral mucosa can exhibit two characteristic features: mucous patches and maculopapular
lesions. Occasionally nodular lesions may be seen.
A severe generalized form of secondary syphilis is
referred to as ulceronodular disease (lues maligna). This form
of syphilis is characterized by fever, headache and myalgia,
followed by a papulopustular eruption that rapidly transforms into necrotic, sharply demarcated ulcers with hemorrhagic brown crusts on the face and scalp. The incidence
of lues maligna in AIDS patients is high.
Intraorally crateriform or shallow ulcers are seen on the
gingivae, palate or buccal mucosa, with multiple erosions
on the hard and soft palates, tongue and lower lip.
Mucous patches
Mucous patches are evident as oval or crescent-shaped
erosions or shallow ulcers of about 1 cm diameter, covered
by a grayish-white pseudomembrane surrounded by an
erythematous halo.
These may be seen bilaterally on the mobile surfaces of
the mouth. However, the gingiva, hard palate, tonsils and
pharynx may be involved. At the commissures, the mucous
patches may appear as split papules, while on the distal

and lateral aspects of the tongue, they tend to ulcerate or


manifest as irregular ssures. The mucous patches may
coalesce to give rise to, or arise de novo as serpiginous
lesions, which are popularly referred to as snail track ulcers.
Maculopapular lesions
The macular lesions are seen on the hard palate as flat-toslightly raised, firm, erythematous lesions.
The papular lesions are seen as erythematous, raised,
rm round nodules with a gray center that may ulcerate.
The papules may be evident at the commissures and condyloma lata (papillary outgrowths) on the buccal mucosa.
Nodular disease
Occasionally lesions of secondary syphilis present as nodules.
These lesions may mimic keratoacanthoma or squamous cell
carcinoma when they occur on the vermillion border of
the lip. These nodular lesions are usually seen on the face,
mucous membranes, palms of the hands and soles of the feet.
Latent syphilis Latent syphilis is defined as having serologic proof of infection without signs or symptoms of
disease.
Latent syphilis is further classied as early or late. Early
latent syphilis is dened as having syphilis for 2 years
or less from the time of initial infection without signs or
symptoms of disease. Late latent syphilis is infection for
more than 2 years but without clinical evidence of disease.
Early latent syphilis is considered more infectious than
the late latent syphilis.
Tertiary syphilis The evidence of the tertiary stage of
syphilis may occur anywhere from a year of the primary
infection to about 10 years. The pathognomonic feature of
this phase is the presence of gummas. These soft masses of
inflammation (granulomas) can occur anywhere in the
body. Other clinical manifestations of tertiary stage of
syphilis include neuro- and cardiovascular syphilis.
Neurologic complications include generalized paresis of
the insane or general paresis (chronic dementia along with
progressive personality changes and memory loss). Other
neurologic manifestations are hyperactive reexes and
Argyll Robertson pupil (small and irregular pupils constrict in response to focusing the eyes, but not to light) and
tabes dorsalis (locomotor ataxia).
Cardiovascular complications include syphilitic aortitis,
aortic aneurysm and aortic regurgitation. Syphilitic aortitis
can cause de Mussets sign (bobbing of the head). Trophic
lesions such as Charcots joints and distal extremity neuropathic perforating ulcers are seen in some patients.
Oral manifestations
Gumma formation, syphilitic leukoplakia and neurosyphilis are the oral manifestations seen in the tertiary stage of
syphilis.
627

Section VII System Review

The initial gummatous lesion is evident as a painless


swelling that commonly occurs on the hard palate and
tongue. However, occasional reports of the gumma occurring
on the lower alveolus, parotid gland and soft palate have
been described. These swellings subsequently ulcerate.
Gumma on the palate may cause palatal perforation and
formation of an oronasal stula formation. Radiographically,
gumma involving bone show ill-dened destruction of bone
mimicking malignant lesions. These gummatous lesions
heal by scarring over a period of time.
Gumma involving tongue is referred to as interstitial
glossitis. The tongue appears irregular, enlarged and lobulated. Occasionally, papillary atrophy may be appreciated
on the dorsal surface of the tongue resulting in a condition
termed luetic glossitis.
Syphilitic leukoplakia
Syphilitic leukoplakia appears as a homogeneous white
patch on the dorsum of the tongue. Some studies have
shown that the prevalence of syphilis in patients with
squamous cell carcinoma of the tongue was about 60%.

Neurosyphilis
Tertiary syphilis can cause unilateral and bilateral trigeminal neuropathy and facial nerve palsy. It is also believed
that syphilitic osteomyelitis may give rise to trigeminal
neuropathy.

Congenital Syphilis
Congenital syphilis or prenatal syphilis is caused when
T. pallidum is transmitted to the offspring by an infected
mother. T. pallidum crosses the placenta only after the
16th week of intrauterine life.
Untreated mothers can drastically affect the status of the
offspring. Most of the pregnancies result in spontaneous
abortion, stillbirth, premature delivery or perinatal death.
Prematurity and low-birth weight have also been reported.
Kassowitzs law is an empirical observation used in
context of syphilis. It states that greater the duration between
infection of mother and pregnancy, better is the outcome
for the infant. Better outcome includes lesser chances of
stillbirth and of developing congenital syphilis.
The rate of vertical transmission in untreated women is
70100% for primary syphilis, 40% for early latent syphilis
and 10% for late latent disease.
These statistics show very clearly that the longer the
interval between infection and pregnancy, the better is the
prognosis for the newborn.
Based on the time of presentation of the signs and
symptoms, the clinical manifestations can be categorized
as early manifestations (occurring in the rst 2 years of
life) and late manifestations occur after 2 years of age.
628

Early manifestations The earliest clinical finding is persistent rhinitis. Other associated findings include hepatomegaly, splenomegaly, glomerulonephritis and nephrotic
syndrome.
Palms and soles of these neonates show erythematous
maculopapular rashes or vesiculobullous lesions. Generalized lymphadenopathy is evident. Bone lesions such as
osteochondritis and osteomyelitis.
Late manifestations Hutchinsons triad (interstitial keratitis, peg-shaped upper incisors, and eighth cranial nerve
deafness), saber shins, irregular thickening of the sternoclavicular portion of the clavicle (Higoumenakis sign), flaring scapulas, mental retardation and hydrocephalus are the
late manifestations of syphilis.
Bilateral hydrarthrosis (Cluttons joints) and neurosyphilis are other common late manifestations of syphilis.
Orofacial manifestations in congenital syphilis Localized periostitis of the frontal and parietal bones is manifested as frontal bossae of parrot. Appearance of the
Olympian row is seen when the supraorbital region is
involved.
Inammation of the nasal mucosa may destroy the
underlying bone and cartilage, perforate the nasal septum
and manifests as saddle nose.
A short maxilla along with the saddle nose may present
as concave or shallow-dish appearance of the middle third
of the face. A relative mandibular prognathism results in a
bulldog jaw.
Other oral changes include high palatal arch. The dental
anomalies of congenital syphilis only arise in teeth in which
calcication occurs during the rst year of life, namely,
the permanent incisors and rst molars.
Hutchinsons teeth are short, barrel-shaped or peg-shaped
widely spaced central incisors. Other ndings include
notching of incisal edges. The incisors have a screwdrivershaped morphology (convergence of the lateral margins
toward the incisal edge). Mulberry molars, hypocalcication of enamel and presence of rhagades extending from
the angle of the mouth are other prominent features. Occasionally, atrophic glossitis and facial neuropathies may
be seen.
Diagnosis
Along with the typical history and clinical picture of
syphilis, serological tests are necessary for an accurate
diagnosis.
Dark-eld microscopy has been used extensively for
the diagnosis of primary syphilis. However, it cannot differentiate T. pallidum from the other treponemal species.
Serological tests can be used effectively to diagnose
secondary, latent and tertiary syphilis. The serologic tests
include non-treponemal tests (Venereal Disease Research
Laboratory [VDRL] test and the Rapid Plasma Reagin [RPR]

Chapter 22 Sexually Transmitted Diseases

test) and treponemal tests (serum uorescent treponemal


antibody absorption test [FTA-ABS] and microhemagglutination test for T. pallidum [MHA-TP]).

5.

Management

6.

Parenteral penicillin G is the drug of choice for the


treatment of all stages of syphilis. Patients allergic to penicillin can be treated with doxycycline, tetracycline or
erythromycin.

HUMAN IMMUNODEFICIENCY VIRUS


INFECTION
In 1981, homosexual men with symptoms of a disease that
now are considered typical of the AIDS were first described
in Los Angeles and New York by the CDC. In 1983, researchers in the United States and France described the virus that
causes AIDS, now known as the human immunodeficiency
virus (HIV) and belonging to the group of viruses called
retroviruses. It is estimated that about 33.2 million people
are affected by AIDS worldwide.
Modes of transmission
HIV is transmitted through direct contact of a mucous membrane or the bloodstream with a body fluid containing HIV,
such as blood, semen, vaginal fluid, preseminal fluid and
breast milk. The transmission of HIV can result from vaginal, anal or oral sex, infected needles, blood transfusion,
maternal-fetal transmission during pregnancy, birth and
breast feeding.
Sexual mode of transmission
It is estimated that the transmission through sexual contact
accounts for 7585% of all HIV infections. Sexual transmission occurs with the contact between sexual secretions
of one person with the rectal, genital or oral mucous
membranes of another.
Some facts about sexual mode of transmission
1.
2.

3.
4.

Unprotected receptive sexual acts are riskier than


unprotected insertive sexual acts.
Anal sex is the most efficient means of sexual HIV
transmission compared to vaginal intercourse or oral
sex (the rectal mucous membranes seem to have more
receptors to bind HIV and the tissue is more easily
traumatized).
HIV can be transmitted through both insertive and
receptive oral sex.
The risk of HIV transmission from exposure to saliva
is considerably smaller than the risk from exposure to
semen.

7.

Other STIs increase the risk of HIV transmission and


infection, because they cause the disruption of the
normal epithelial barrier by genital ulceration and/or
microulceration.
HIV transmission through oral exposure to semen or
vaginal fluids have been documented. Fellatio (mouth
to penis contact) and cunnilingus (mouth to vulva contact) cannot be considered to be totally safe practices.
Transmission appears to be highest during the early
and late stages of HIV when the viral load is at its peak.

HIV and AIDS are described in detail in Chapter 4 on


Bacterial, Viral and Fungal Infections.

INTRAORAL MOLLUSCUM CONTAGIOSUM


Molluscum contagiosum is a DNA poxvirus that generally
affects the skin or mucous membranes. Juliusburg (1905)
discovered the viral nature of this condition. Molluscum
contagiosum has also been known as epithelioma contagiosum and dimple wart.
Molluscum contagiosum is primarily caused by MCV-1
and MCV-2 (molluscum contagiosum virus subtypes 1
and 2).
The virus is transmitted by direct contact and autoinoculation. Upon entering the host cell the virus replicates
in the cytoplasm of epithelial cells producing cytoplasmic
inclusions and cause enlargement of the infected cells.
Molluscum contagiosum is more common in patients who
are on steroid therapy or in those who have atopic dermatitis, immunodeciency or lymphoproliferative disorders.
Clinical features
The infection affects both adults and children. In children,
the transmission is via non-sexual skin contact whereas in
young adults it occurs as an STD. In children, the lesions are
generally seen on the face, trunk, extremities (especially in
the axillae), and sometimes on the mucous membranes of
the lips, tongue and buccal mucosa. In adults, involvement of the pubic, genital and perineal areas is common.
The typical lesion is an umbilicated or waxy papule
associated with itching and pain. Some patients develop
eczema around the papule.
The papules are esh-colored and occasionally
yellowish-white in color. These papules can occur as solitary lesions and sometimes several in number. These are
generally about 25 mm in diameter. Large sized lesions
(5 mm) and a greater number of lesions (30 in number)
are usually seen in AIDS patients.
Oral manifestations
Oral lesions are rarely encountered in molluscum contagiosum. These lesions mimic the skin lesions.
629

Section VII System Review

The common sites of involvement include the lips,


buccal mucosa, hard palate, retromolar area and tongue.
Fornatora et al (2001) described a rare case of molluscum
contagiosum occurring on the gingiva.
Histologic features
Hematoxylin and eosin-stained biopsy sections reveal
thickening (almost six times more than normal) and downgrowth of epithelium. Presence of intracytoplasmic inclusion bodies (molluscum bodies or HendersonPatterson
bodies) is typical of molluscum contagiosum.
Alternatively, smears taken from scrapings of the lesion
show inclusion bodies when stained with Papanicolaou,
Wright, Giemsa or Gram stain.
An advanced technique to identify the antigen of MCV
by uorescent antibody technique may be employed.
Management
Most of the lesions are self-limiting and usually resolve in
about 912 months. The goal of the treatment is to limit
the transmission and autoinoculation.
Topical application of cantharidin, podophyllin or tretinoin cream may be benecial.
Cryotherapy with liquid nitrogen is a popular management strategy. Surgical excision of the lesion is also an
accepted treatment modality.
Antiviral medications such as ritonavir, zidovudine
have been used to manage the molluscum contagiosum in
immunocompromised individuals.

CONDYLOMA ACUMINATUM
Condyloma acuminatum commonly termed genital or venereal wart occurs commonly on external genitalia; however,
oral lesions can occur either through orogenital sex or by
auto-inoculation of genital lesions. Condyloma acuminatum is caused by human papilloma virus types 6, 11 and
16. Condylomata acuminata are now thought to be one of
the four most common STDs.
Clinical features
Typical lesions are evident as solitary or multiple papular
eruptions. These eruptions are usually flesh colored and
appear pearly, filiform, fungating, cauliflower or plaque like.
The most commonly affected areas are the penis, vulva,
vagina, cervix, perineum and perianal area. Rarely, mucosal lesions in the oropharynx, larynx and trachea have
been reported.
Oral manifestations
The typical oral lesions of condyloma acuminatum are minute, multiple pink colored nodules which tend to coalesce
630

to form bulbous/papillomatous lesions. These papillomatous


lesions can affect any part of the oral cavity. The common
sites of involvement are the dorsal surface of the tongue,
palate, alveolar ridge, buccal mucosa and gingiva.
The nodules proliferate and coalesce to form soft, red
or dirty gray, sessile or pedunculated papillary growths.
Lesions develop rapidly to form discrete single or extensive clusters of granular or cauliower-like neoplasms.
Diagnosis
Diagnosed indirectly by cytology, biopsy or the appearance of white areas after the application of acetic acid
(acetowhitening).
The affected area is wrapped with a gauze piece soaked
with 5% acetic acid for 5 minutes. A magnifying lens (10)
or a colposcope can be used to visualize the warts which
appear as minute white colored papules.
A more denitive diagnosis can be made by detecting
the viral nucleic acid or capsid protein.
Management
Podophyllin (cytotoxic agent) is the drug of choice. Alternatively, topical trichloroacetic acid and 5-fluorouracil can
be used. Surgical modalities include the use of cryotherapy and carbon dioxide laser ablation.

OROPHARYNGEAL GONORRHEA
Gonorrhea is a caused by Neisseria gonorrheae. The disease is characterized by purulent inflammation of mucous
membrane surfaces.
Clinical features
The bacterial infection spreads through sexual contact.
Gonococcal infections are 1.5 times more common in men
than in women. It is usually seen in sexually active adolescents and young adults. Like most STDs, the presence of
gonorrhea in a child can be considered as an indicator for
sexual abuse of the child.
Men may present with urethral discomfort, dysuria and
purulent discharge. Other notable feature is epididymitis.
Women may complain of thin, purulent and mildly
odorous discharge from the vagina. Another important
complication of gonorrhea in women is pelvic inammatory disease (PID). PID indicates that the offending organism has ascended to involve the endometrium, fallopian
tubes, ovaries and peritoneum. PID is characterized by midline mild or severe pain and cramps.
Right upper quadrant pain from perihepatitis (Fitz
HughCurtis syndrome) may occur following the spread of
organisms upward along peritoneal planes.
Occasionally rectal discharge, bloody stools and pruritus
may be evident.

Chapter 22 Sexually Transmitted Diseases

Many of the patients may suffer from dysphagia secondary to pharyngitis.


An extensive form of gonorrhea, disseminated gonorrheal infection (DGI) is seen in some patients. The disseminated form is characterized by joint or tendon pain
(gonococcal arthritis), skin rash, gonococcal meningitis
and gonococcal endocarditis.

Oral manifestations

Oral manifestations

Diagnosis

In the initial stages of the infection, patients may complain of burning sensation, drying of the mouth and foul
breath.
This phase may be followed by the evidence of painful
ulcers usually seen on the lips, gingival, tongue, palate
(hard and soft) and the tonsillar regions.
The ulcers are typically punched out in the interdental
gingiva. The tongue may exhibit papillary atrophy. The
ulcers are usually covered by grayish-white or yellowishwhite pseudomembrane. Pharyngitis is a characteristic
feature.
Regional lymphadenopathy may be evident. In some
patients, the TMJ may be affected (gonococcal arthritis of
TMJ).

Cultures are usually difficult to obtain and expensive.


However, direct immunofluorescent antibody and enzyme
immunoassay can be used. Alternatively, PCR can be
used.

Diagnosis
The evidence of gram-negative diplococci in a Gram stained
smear of exudates from the gonococcal lesions is suggestive of N. gonorrheae infection.

Patients may present with pharyngitis. The oral mucosa


appears intensely erythematous. However, painless mucositis is the characteristic feature. Lips, buccal mucosa, floor
of mouth, tongue, tonsillar regions and uvula are the common sites affected. Occasionally, cervical lymphadenopathy
may be present.

Management
The drugs of choice are doxycycline or azithromycin with
ofloxacin.

OROPHARYNGEAL TRICHOMONAL
INFECTION
Trichomonas vaginalis is the causative agent of trichomoniasis. It is a parasitic protozoan with humans as the only natural host. It infects the squamous epithelium of the genital
tract. Incubation time is generally between 4 and 28 days.
It is believed that T. vaginalis infections are a marker for
high risk sexual behavior as they are generally associated
with other STDs, especially gonorrhea.

Management
Oropharyngeal gonorrhea is best managed with intramuscular injection of ceftriaxone. Other drugs that have been
used effectively include cefixime and ciprofloxacin.

OROPHARYNGEAL CHLAMYDIAL
INFECTION
Chlamydial infection is caused by Chlamydia trachomatis,
an obligate intracellular bacterium that infects the urethra,
epididymis, uterus and cervix. The bacterium is usually
spread through sexual activity.
However, it can also spread vertically to cause pneumonia and conjunctivitis in neonates.
Chlamydial infection is usually seen in the 2nd and 3rd
decades of life.
Clinical features
Women may present with dysuria, vaginal bleeding, vaginal discharge and lower abdominal pain. Men may exhibit
dysuria, rectal and/or urethral discharge and proctitis.

Clinical features
Women complain of foul smelling, frothy vaginal discharge. However, the pathognomonic sign is the presence
of strawberry cervix or colpitis macularis on colposcopy.
Patients may also complain of lower abdominal pain and
dysuria. However, some patients may remain asymptomatic.
Male patients may remain asymptomatic or present
with urethritis.
Oral manifestations
The characteristic feature is strawberry-like inflammation
of the oral mucosa secondary to vasodilation. The mucosal
surface may show presence of exudate.
Diagnosis
The gold standard for diagnosing trichomonads is by culture. The Diamonds medium is the ideal medium for this
procedure.
Few simple diagnostic tests that may be used are the
immediate examination of a wet slide and whiff test.
The easiest method to visualize motile trichomonads
is by placing a small amount of vaginal discharge on a
631

Section VII System Review

microscope slide and mixing with a few drops of saline


solution within 20 minutes of obtaining the sample. The
slide is then examined under a microscope at low or
medium power. The presence of agellated, pyriform protozoa indicates a positive result.
Alternatively, several drops of 10% potassium hydroxide
are mixed with a sample of vaginal discharge. Presence

632

of a strong shy odor is indicative of a positive result.


This test is referred to as the whiff test or amine odor test.
Management
Metronidazole and tinidazole are the drugs of choice. The
recommended dose is 2 g orally in a single dose.

CHAPTER

Nutritional and Metabolic


Disorders
Shubha Sairam, Praveen BN

Nutritional Requirements of Indians

Carbohydrates

Proteins

Lipids

Vitamins
Vitamin A
Vitamin D
Vitamin K
Vitamin C
Vitamin B Complex

Nutriology as per Dorlands Medical Dictionary is the science of nutrition. It is the science of how the body utilizes
food to meet requirements for development, growth, repair,
and maintenance. Nutrients are biochemical substances that
can be supplied only in adequate amounts from an outside
source, usually from food.
The relationship between nutrition and oral health is
multifaceted. Nutrition has both local and systemic
impacts on the oral cavity. While diet and eating patterns
have a local effect on the teeth, saliva and soft tissues, the
systemic impact of nutrition also has considerable implications and it too merits assessment as a component of
comprehensive care. The systemic effect is the impact of
the nutrients consumed as they assume their biological
functions in relation to the development and maintenance
of the extra- and intraoral structures and secretions. The
oral cavity is often one of the rst sites where nutrient
deciencies can be clinically noted.
Clinical manifestations of nutrient deciencies can
have a signicant impact on the function of the oral cavity. Functional properties of the oral cavity include taste,
salivation, mastication and swallowing food. Any alterations in the structure and function of the oral cavity may
compromise intake and contribute to the development of a
nutrient-deciency state. When the associated oral structures are affected, these alterations may be compounded

23

Metabolic Disorders
Lysosomal Storage Diseases
Lipoid Proteinosis
HandSchullerChristian Disease or Multifocal
Eosinophilic Granuloma
LettererSiwe Disease

Lipid Reticuloendothelioses
Gaucher Disease
NiemannPick Disease

even further, leading to subsequent inadequate dietary


intake and compromised nutritional status.
There are six classes of nutrients: water, carbohydrates,
proteins, fats, minerals and vitamins. Nutrients work
together and interact in complex metabolic reactions.
Proteins, carbohydrates and fats provide energy for body
needs. However, the body cannot use this energy without
adequate amounts of vitamins and minerals.

NUTRITIONAL REQUIREMENTS OF INDIANS


Energy requirement is defined as the amount that will balance the energy expenditure of the individual (as determined by body size and composition and level of physical
activity) consistent with long-term good health. This
intake will allow for the maintenance of economically
necessary and socially desirable physical activity. In children and pregnant/lactating women, the energy requirement will include energy needed for deposition of tissue
and secretion of milk at the rate consistent with good
health. All estimates of requirement are based on habitual
intakes though these are expressed as daily intake.
Recommended dietary allowance (RDA) is the amount of
selected nutrients considered adequate to meet the known
633

Section VII System Review

nutrient needs of healthy people. The Canadian equivalent


is the recommended nutrient intakes (RNIs). The energy
needs of men and women for different activity levels
computed on the basis of recommendations made by a
Joint Expert Consultation of the World Health Organization
(WHO)/Food and Agricultural Organization (FAO)/United
Nations University (UNU) in 1985 and by an Expert
Committee constituted in 1988 by the Indian Council of
Medical Research (ICMR) are as shown in Tables 1 and 2.
The ICMR's RDA is higher than those recommended by the
WHO/FAO/UNU.
For computing RDA, the ICMR has taken body weight
of reference man as 60 kg and that of woman as 50 kg.
Average weight of Indian men is 52 kg and women 44 kg.
For children and adolescents, weight for age from National
Center for Health Statistics (NCHS), USA/well-to-do Indian
children have been utilized by ICMR for deriving the RDA
so that energy intake enables optimum growth. However, as
in adults, majority of children and adolescents weigh substantially less and hence their energy requirement is lower.

CARBOHYDRATES
Carbohydrates have been the major sources of energy
since the dawn of history and furnish up to 90% of energy
needs. Carbohydrates provide about 4 kcal/g. The average
adult stores about 300 g of carbohydrate in the liver and
muscle tissue as glycogen.

Mainly provides fuel for the body, especially the central nervous system.
Adequate consumption has a protein sparing function,
i.e. proteins consumed are used for anabolic function
rather than as an energy source.
In the absence of carbohydrates, fat metabolism is
incomplete and leads to formation of ketone bodies.
Carbohydrates are required for the formation of structural
components such as cartilage, nervous tissue and bone.

Sex

Sources
Grains (wheat, corn, rice, oats, rye, barley, buckwheat and
millet) provide complex carbohydrates and starches. Vegetables, especially root and seed varieties (potatoes, sweet
potatoes, beet and peas) contain considerable amounts of
starch. Milk is a good source of lactose. Dietary fiber can be
obtained from whole grain breads and cereals and legumes.
Dental considerations
For decades, dietary carbohydrates have one of the major
constituents incriminated in the causation of caries. The
occurrence of caries depends upon the frequency of consumption, chemical constitution, route of administration,
and physical properties of carbohydrates.
Sugar substitutes have been claimed to be non-cariogenic
due to their inability to act as substrates for the enzyme
glucosyltransferase. Xylitol is one such commonly used
sugar substitute. It has been found to be non-cariogenic.
Some studies also show that chewing xylitol gum has
Recommended dietary allowance of infants and
children

Age of infant

Energy (kcal)

Weight (kg)

36 months*

700

69 months*

810

8.5

912 months*

950

9.5

6 months

583

5.4

612 months

844

8.6

Source: *WHOIFAO/UNO (1985); ICMR (1988).

ICMR's recommended dietary allowance for energy


Ref. body
weight (kg)

Actual body
weight (kg)

Man

60.0

Woman

50.0

Energy RDA
Activity
category

For ref. body


weight

For actual
body weight

Percentage
difference

52.0

Sedentary
Moderate
Heavy

2,425
2,875
3,800

2,115
2,492
3,293

13
13
13

44.0

Sedentary
Moderate
Heavy

1,875
2,225
2,925

1,740
1,958
2,594

12
12
11

Source: Dr BS Narasinga Rao-Gopalan Oration (2001).

634

Carbohydrates are required for the formation of nonessential amino acids.


Non-starch polysaccharides constitute dietary fibers
that are required to prevent constipation, reduce blood
cholesterol and give satiety.
It is recommended that 5560% of total energy intake
should be obtained from carbohydrates.

Table 2

Functions

Table 1

Chapter 23 Nutritional and Metabolic Disorders

cariostatic properties. Other sugar substitutes, sorbitol,


aspartame, sucralose have been found to have a negligible
effect on the development of caries.

PROTEINS
Second to water, proteins are the most abundant substances in the body. The structural units of proteins are
amino acids. Of the 20 amino acids present in nature, nine
are considered essential, i.e. these are to be supplied by
the diet.
Functions

Generation of new body tissues


Repair of body tissues
Production of enzymes, hormones, immunoglobulins
Regulation of fluid balance
Transport of insoluble fats
Provide energy4 kcal/g.

Sources
Meat and milk food groups provide most of the dietary
proteins. Soy is also a good source of proteins.

Dental considerations
During tooth development, mild-to-moderate protein deficiency results in smaller molars, chemical alterations of
the exposed enamel surface, significantly delayed eruption
and retardation of mandibular development. Smaller salivary glands develop resulting in decreased salivary flow.
This saliva has a different protein, amylase and aminopeptidase activity, thereby compromising its immune function.
Delayed eruption and decreased salivary flow lead to
increased incidence of dental caries. Epithelium, connective
tissue and bone may be poorly developed. Insufficient
intake of protein results in negative nitrogen balance,
decreased levels of secretory IgA. This leads to a lowered
resistance to infections, reduced ability to withstand the
stresses of injury or surgery, and prolonged recovery time.
PEM may be a major reason for the occurrence of necrotizing ulcerative gingivitis (NUG) and noma.

LIPIDS
Lipids provide more energy per gram than either carbohydrates or proteins and are an essential component of tooth
enamel and dentin.
Chemistry and sources

Deficiency
Protein energy malnutrition This term covers the spectrum of clinical conditions seen in undernutrition. The two
clinical forms of protein energy malnutrition (PEM)
include kwashiorkor and marasmus.
Kwashiorkor occurs when a child is fed on a diet with
very low protein content relative to energy. This results in
a high level of plasma insulin and low levels of plasma
cortisol. This hormonal pattern leads to an uptake of
amino acids in muscle, diverting these from liver, leading
to decreased albumin synthesis and therefore edema.
Thus a child with kwashiorkor shows apathy, lethargy
and severe anorexia. There is generalized edema, muscle
wasting in shoulders and upper arms. The child may have
a moon face. Potbelly due to weakness of abdominal
muscles occurs. Skin changes in the form of thickening,
cracking and areas of denudation occur. Hair changes
color and becomes sparse.
Marasmus occurs when there is inadequate food intake
resulting in energy deciency. This leads to low insulin
and high plasma cortisol levels. This results in amino acids
being released from muscles making them available for
protein synthesis.
A child with marasmus presents with no subcutaneous fat
and wasted muscles. The body weight is severely reduced.
There is no edema, and skin and hair changes are mild or
absent.
Studies have shown that the incidence of PEM among
Indian children could be as high as 51.670%.

The structural units of lipids are fatty acids. Saturated fatty


acids contain only single bonds. Examples include palmitic and stearic acids found in animal fat, butter, coconut
oil, chocolate, etc.
Monounsaturated fatty acids contain only one double
bond. The most abundant of these is oleic acid found in
olive, peanut oil and animal products.
Polyunsaturated fatty acids (PUFAs) contain two or
more double bonds. Three PUFAs that are considered to be
essential fatty acids include linoleic, linolenic and arachidonic acids. These are found in safower, soybean, sh
and corn oils, nuts and seeds.
Decient consumption of fats leads to loss of weight.
Deciency of linoleic acid leads to growth retardation,
skin lesions, and reproductive failure.
Over consumption of fats leads to excessive fat stores
and obesity. Other conditions related to fat consumption
include diabetes mellitus, hyperlipidemia, fatty inltration
of liver, and certain types of cancer.
Dental considerations
Epidemiological and laboratory studies indicate that fats
have a cariostatic effect. Dietary fats probably have local
rather than systemic influence. Hypotheses for anticariogenicity include:
1.

Some fatty acids, such as oleic acid act as growth factors for lactobacilli, others, such as lauric acids inhibit
the growth of streptococci.
635

Section VII System Review

2.

Long-chain fatty acids may decrease the dissolution


of hydroxyapatite by acids.
Oral food retention decreases with increased fat intake.
Fats may lubricate the tooth and prevent acid penetration into enamel.
Fats may produce a film on food particles and prevent
partial digestion of food particles in the mouth.
Dietary fat delays gastric emptying, enhancing fluoride
absorption and increasing tissue fluoride concentration.

Characteristics of fat-soluble vitamins: These are soluble


in fats or fat solvents. Chemically, these are organic substances and do not contain nitrogen. These are absorbed in
the intestines in the presence of bile. These are fairly stable
to heat, as in cooking. Larger amounts of these vitamins
can be stored in the body and for long periods of time. Thus,
symptoms of deficiencies appear late. Increased intake may
lead to toxicity.

The growth and differentiation of epithelial cells


throughout the body is especially affected by vitamin A
deciency. In addition, goblet cell numbers are reduced in
epithelial tissues and as a consequence, mucous secretions
(with their antimicrobial components) diminish. Cells lining protective tissue surfaces fail to regenerate and differentiate, hence they atten and accumulate keratin. Both
factorsthe decline in mucous secretions and loss of cellular integrityreduce the bodys ability to resist invasion
from potentially pathogenic organisms. Pathogens can also
compromise the immune system by directly interfering
with the production of some types of protective secretions
and cells. Classical symptoms of xerosis (drying or nonwettability) and desquamation of dead surface cells as
seen in ocular tissue (i.e. xerophthalmia) are the external
evidence of the changes also occurring to various degrees
in internal epithelial tissues.
Current understanding of the mechanism of vitamin A
action within cells outside the visual cycle is that cellular
functions are mediated through specic nuclear receptors.
Binding with specic isomers of retinoic acid (i.e. all-transand 9-cis-retinoic acid) activates these receptors. Activated
receptors bind to DNA response elements located upstream
of specic genes to regulate the level of expression of those
genes. These retinoid-activated genes regulate the synthesis of a large number of proteins vital to maintaining normal physiologic functions. There may, however, be other
mechanisms of action that is as yet undiscovered.

Vitamin A

Dietary sources

Vitamin A (retinol) is an essential nutrient needed in small


amounts by humans for the normal functioning of the visual
system; growth and development; and maintenance of
epithelial cellular integrity, immune function, and reproduction. These dietary needs for vitamin A are normally
provided as preformed retinol (mainly as retinyl ester) and
provitamin A carotenoids or -carotene.

Preformed retinal is found in milk, cheese, butter, eggs,


meat, cod liver oil and liver. -Carotene is also present in
yellow, orange and green leafy vegetables (spinach,
turnip greens, broccoli).
To express the vitamin A activity of carotenoids in diets
on a common basis, a Joint FAO/WHO Expert Group in
1967 introduced the concept of the retinol equivalent (RE)
and established the following relationships among food
sources of vitamin A:
1 g retinol  1 RE
1 g -carotene  0.167 g RE
1 g other provitamin A carotenoids  0.084 g RE.

3.
4.
5.
6.

VITAMINS
Vitamins are catalysts for all metabolic reactions using
proteins, fat and carbohydrates for energy, growth and cell
maintenance. Vitamins are vital to life, but are required in
minute amounts.
Vitamins are classied as fat solublevitamins A, D, E, K
and water solublevitamins B, C.

Functions
Vitamin A functions at two levels in the body: the first is
in the visual cycle in the retina of the eye; and the second
is in all body tissues where it systemically maintains the
growth and soundness of cells.
In the visual system, carrier bound retinol is transported
to the retina. Rhodopsin, the visual pigment critical to
dim-light vision, is formed in rod cells after conversion of
all-trans-retinol to retinaldehyde, isomerization to the
11-cis-form, and binding to opsin. Alteration of rhodopsin
through a cascade of photochemical reactions results in
the ability to see objects in dim light. The speed at which
rhodopsin is regenerated is related to the availability of
retinol. A decient intake of vitamin A thus leads to night
blindness.
636

Older literature describes the International Unit of vitamin A.


This may be converted to RE as depicted in Table 3:
1 IU retinol  0.3 g retinol
1 IU -carotene  0.6 g -carotene
1 IU retinol  3 IU -carotene.
Deficiency
Vitamin A deficiency leads to xerophthalmia and night
blindness due to degeneration of epithelial cells. Xeroderma
can also occur. Mild deficiency may be related to a
depressed immune response.

Chapter 23 Nutritional and Metabolic Disorders

Table 3

Estimated mean requirement and safe level of


intake for vitamin A

Group

Mean requirement
(mg RE/day)

Infants and children


06 months
712 months
13 years
46 years
79 years

Recommended safe
intake (mg RE/day)

180
190
200
200
250

375
400
400
450
500

330400

600

270
300

500
600

300
300

600
600

Pregnant women

370

800

Lactating women

450

850

Adolescents
1018 years
Adults
Females
1965 years
65 years
Males
1965 years
65 years

Source: Vitamin and mineral requirements in human nutrition, WHO.

Dental considerations
Vitamin A is necessary for growth of both soft tissue and
bone. It is required for resorption of old bone and synthesis of new bone, formation of ameloblasts, odontoblasts,
and maintenance of the integrity of epithelial tissues.
Severe deciency of vitamin A may result in enamel
hypoplasia and defective dentin formation in developing teeth. Odontoblasts lose the ability to arrange themselves in normal parallel linear formation leading to
altered dentin deposition. This further leads to degeneration and atrophy of ameloblasts. This results in enamel
hypoplasia characterized by defects in enamel matrix and
incomplete calcication.
Clinical applications
Carotenoids possess antioxidant properties and are very efficient in scavenging singlet oxygen and peroxyl radicals.
These free radicals are known to damage the structure and
function of cell membranes. Thus a diet rich in antioxidants
is associated with a lower risk of cancer and heart disease.
Stich and colleagues gave large quantities of -carotene
and sometimes vitamin A to chewers of betel quids in Kerala,
India, and to Canadian Inuits with pre-malignant lesions
of the oral tract and witnessed reductions in leukoplakia
and micronuclei from the buccal mucosa.
However, the amount of supplements used in these studies have been large and hence, not advisable other than
increasing consumption of fruits and vegetables.

Retinoids have been used in oral precancer, cancer and


immunologically mediated diseases such as lichen planus.
Retinoids have a potent growth inhibiting effect on cancer
in vivo and in vitro. They can induce apoptosis and regulate the function of the immune system. On this basis, retinoids have been used as chemopreventive agents in oral
squamous cell carcinoma (SCC). However, clinical trials of
retinoids have not yielded signicant results. Retinoids
have been used in the treatment of oral leukoplakia, and
has been shown to cause temporary remission, but also
causes toxicity. Retinoids have been used as an adjunctive
treatment in the management of oral lichen planus.
Retinoids eliminate reticular and plaque-like lesions but
these recur following withdrawal of therapy.
Toxicity
Because vitamin A is fat soluble and can be stored, primarily in the liver, routine consumption of large amounts
of vitamin A over a period of time can result in toxic symptoms, including liver damage, bone abnormalities and joint
pain, alopecia, headaches, vomiting, and skin desquamation. Other clinical symptoms include diplopia, alopecia,
dryness of mucous membranes, reddened gingiva, thinning
of epithelium, cracking and bleeding lips, and increased
activity of osteoclasts. Overconsumption of -carotene leads
to hypercarotenemia and yellow pigmentation of skin.

Vitamin D
Functions
Vitamin D is required to maintain normal blood levels of
calcium and phosphate, which are in turn needed for the
normal mineralization of bone, muscle contraction, nerve
conduction and general cellular function in all cells of
the body. Vitamin D achieves this after its conversion to
the active form 1,25-dihydroxy vitamin D (1,25-(OH)2D),
or calcitriol. This active form regulates the transcription
of a number of vitamin D-dependent genes that code for
calcium-transporting proteins and bone matrix proteins.
Vitamin D also modulates the transcription of cell cycle
proteins, which decrease cell proliferation and increase
cell differentiation of a number of specialized cells of the
body (e.g. osteoclastic precursors, enterocytes, keratinocytes). This property may explain the actions of vitamin D
in bone resorption, intestinal calcium transport and skin.
Sources
The most physiologically relevant and efficient way of
acquiring vitamin D is to synthesize it endogenously in the
skin from 7-dehydrocholesterol by sunlight (UV) exposure.
In most situations, approximately 30 minutes of skin exposure (without sunscreen) of the arms and face to sunlight can
provide all the daily vitamin D needs of the body (Table 4).
637

Section VII System Review

Table 4

Recommended nutrient intakes (RNIs) for vitamin D

Group

RNI (mg/day)

Dental considerations

Infants and children


06 months
712 months
13 years
46 years
79 years

5
5
5
5
5

Adolescents
1018 years

Adults
1950 years
5165 years
65 years

5
10
15

Pregnant women

Lactating women

Units: For vitamin D, 1 IU  25 ng, 40 IU  1 mg, 200 IU  5 mg, 400 IU 


10 mg, 600 IU  15 mg, 800 IU  20 mg.
Source: Vitamin and mineral requirements in human nutrition, WHO.

Skin synthesis of vitamin D may be inuenced by:

Latitude and seasonboth influence the amount of UV


light reaching the skin
The aging processthinning of the skin reduces the
efficiency of this synthetic process
Skin pigmentationthe presence of darker pigments in
the skin interferes with the synthetic process because
UV light cannot reach the appropriate layer of the skin
Clothingvirtually complete covering of the skin for a
medical, social, cultural or religious reasons leaves
insufficient skin exposed to sunlight
Sunscreen usewidespread and liberal use of sunscreen, though reducing skin damage by the sun, deleteriously affects synthesis of vitamin D.

It is recommended that individuals not synthesizing vitamin D should correct their vitamin D status by consuming
the amounts of vitamin D appropriate for their age group.
Other food sources include cod liver oil, catsh, salmon,
turnip greens, tuna, milk, egg yolk and butter.
Deficiency
Rickets is a clinical syndrome that occurs when there is a
deficiency of vitamin D in the growing skeleton. Infants with
rickets exhibit delayed development and muscle hypotonia, craniotabes (small non-calcified areas in skull bones),
bossing of frontal and parietal bones, swelling of the rib
costochondral junctions (rickety rosary). Severe rickets may
be associated with hypocalcemic tetany, giving rise to laryngeal stridor when the vocal cords are affected.
Vitamin D deciency in the adults is termed osteomalacia. Osteomalacia is characterized by bone pain, pathologic
638

fractures. Muscle weakness and a waddling gait may be


present.

Patients with rickets also have involvement of alveolar bone


resulting in its weakening. Patients with severe vitamin D
deficiency develops enamel hypoplasia. This is characterized
by pitting of surface enamel. These surfaces are prone to
adherence of plaque. However, studies of susceptibility to
caries among these teeth reveal conflicting results.

Vitamin K
Vitamin K is an essential fat-soluble micronutrient. Thus far,
the only unequivocal role of vitamin K in health is in the
maintenance of normal coagulation. The vitamin K-dependent
coagulation proteins are synthesized in the liver and comprise factors II, VII, IX and X, which have a hemostatic role
(i.e. they are procoagulants that arrest and prevent bleeding), and proteins C and S, which have an anticoagulant
role (i.e. they inhibit the clotting process). Despite this
duality of function, the overriding effect of nutritional
vitamin K deficiency is a bleeding tendency caused by the
relative inactivity of the procoagulant proteins.
Chemistry and function
Vitamin K is the family name for a series of fat-soluble
compounds which have a common 2-methyl-1,4-naphthoquinone nucleus but differ in the structures of a side chain
at the 3-position. These are synthesized by plants and bacteria. In plants, the only important molecular form is phylloquinone (vitamin K1). Bacteria synthesize a family of
compounds called menaquinones (vitamin K2).
The biological role of vitamin K is to act as a cofactor
for a specic carboxylation reaction that transforms selective glutamate (Glu) residues to -carboxyglutamate (Gla)
residues. The reaction is catalyzed by a microsomal enzyme,
-glutamyl, or vitamin K-dependent carboxylase.
Dietary sources
Phylloquinone is distributed ubiquitously throughout the
diet, and the range of concentrations in different food categories are very wide. In general, the relative values in
vegetables confirm the known association of phylloquinone with photosynthetic tissues, with the highest values
being found in green leafy vegetables. The next best sources
are certain vegetable oils (e.g. soybean, rapeseed and
olive); other vegetable oils, such as peanut, corn, sunflower and safflower. Menaquinones seem to have a more
restricted distribution in the diet than does phylloquinone.
Menaquinone-rich foods are those with a bacterial fermentation stage.
Intestinal microora synthesize large amounts of
menaquinones, which are potentially available as a source

Chapter 23 Nutritional and Metabolic Disorders

of vitamin K. Most of these menaquinones are present in


the distal colon. It is noteworthy that menaquinones with
very long chains are known to be synthesized by members
of the anaerobic genus Bacteroides.
It is commonly held that animals and humans obtain a
signicant fraction of their vitamin K requirement from
direct absorption of menaquinones produced by microoral synthesis, but conclusive experimental evidence documenting the site and extent of absorption is lacking. The
most promising site of absorption is the terminal ileum,
where there are some menaquinone-producing bacteria as
well as bile salts. However, the balance of evidence suggests
that the bioavailability of bacterial menaquinones is poor
because they are for the most part tightly bound to the
bacterial cytoplasmic membrane and also because the largest pool is present in the colon, which lacks bile salts for
their solubilization (Table 5).
Deficiency
Primary deficiency of vitamin K is uncommon, but may
occur due to impaired fat absorption in celiac disease, sprue,
ulcerative colitis and jaundice. The gut remains sterile for
the first few days after birth and hence newborns may suffer from vitamin K deficiency. Deficiency also occurs secondarily following antibiotic therapy.

Table 5

Recommended nutrient intakes (RNIs) for vitamin K

Group

RNIa (mg/day)

Infants and children


06 months
712 months
13 years
46 years
79 years

5b
10
15
20
25

Adolescents
Females, 1018 years
Males, 1018 years

3555
3555

Adults
Females
1965 years
65 years
Males
1965 years
65 years

55
55
65
65

Pregnant women

55

Lactating women

55

The RNI for each group is based on a daily intake of approximately 1 mg/kg

body weight of phylloquinone. bThis intake cannot be met by infants who


are exclusively breast-fed. To prevent bleeding due to vitamin K deficiency,
it is recommended that all breast-fed infants should receive vitamin K
supplementation at birth according to nationally approved guidelines.
Source: Vitamin and mineral requirements in human nutrition, WHO.

Dental considerations
Oral manifestations of vitamin K deficiency include gingival bleeding, petechiae and ecchymoses. Bleeding on brushing occurs when prothrombin levels fall below 35% and
spontaneously when the levels fall below 20%.
Characteristics of water-soluble vitamins: These are
water-soluble organic substances. The B vitamins also
contain nitrogen. These vitamins are readily absorbed in
the jejunum. The body stores very small quantities of each
of these vitamins and hence, daily intake is important.

Vitamin C
Vitamin C (chemical names: ascorbic acid and ascorbate)
is a six-carbon lactone which is synthesized from glucose
by many animals. Vitamin C is synthesized in the liver in
some mammals and in the kidney in birds and reptiles.
However, several species including humans are unable to
synthesize vitamin C. When there is insufficient vitamin C
in the diet, humans suffer from the potentially lethal deficiency disease scurvy.
Functions
Vitamin C is an electron donor (reducing agent or antioxidant), and probably all of its biochemical and molecular roles can be accounted for by this function.
Dietary sources
Ascorbate is found in many fruits and vegetables. Citrus
fruits and juices are particularly rich sources of vitamin C
but other fruits including cantaloupe and honeydew melons, cherries, kiwi fruits, mangoes, papaya, strawberries,
tangelo, tomatoes and water melon also contain variable
amounts of vitamin C. Vegetables such as cabbage, broccoli, Brussels sprouts, bean sprouts, cauliflower, mustard,
greens, red and green peppers, peas and potatoes are also
important sources of vitamin C (Table 6).
Deficiency
Deficiency of vitamin C leads to scurvy, which can manifest
in as little as 20 days. From the 15th century, scurvy was
dreaded by seamen and explorers forced to subsist for months
on diets of dried beef and biscuits. Scurvy was described by
the Crusaders during the sieges of numerous European cities,
and was also a result of the famine in 19th century Ireland.
Three important manifestations of scurvy, namely, gingival changes, pain in the extremities, and hemorrhagic
manifestations precede edema, ulcerations, and ultimately
death. Skeletal and vascular lesions related to scurvy probably arise from a failure of osteoid formation. In infantile
scurvy, the changes are mainly at the sites of most active
bone growth; characteristic signs are a pseudoparalysis
639

Section VII System Review

Table 6 Recommended nutrient intakes (RNIs) for vitamin C

Vitamin B Complex

Group

Vitamin B1Thiamine

RNI (mg/day)

Infants and children


06 months
712 months
13 years
46 years
79 years

25
30
30
30
35

Adolescents
1018 years

40

Adults
1965 years
65 years

45
45

Pregnant women

55

Lactating women

70

Sources

Source: Vitamin and mineral requirements in human nutrition, WHO.

of the limbs caused by extreme pain on movement


and caused by hemorrhages under the periosteum, as
well as swelling and hemorrhages of the gums surrounding erupting teeth. In adults, one of the early principal
adverse effects of the collagen-related pathology may be
impaired wound healing. Vitamin C deciency can be
detected from early signs of clinical deciency, such as
the follicular hyperkeratosis, petechial hemorrhages, swollen or bleeding gums and joint pain, or from the very
low concentrations of ascorbate in plasma, blood or
leukocytes.
Dental considerations
One of the earliest manifestations of scurvy is gingivitis
leading to periodontitis and resulting in tooth mobility and
loss of teeth. However, vitamin C deficiency per se does
not lead to gingivitis. Gingivitis is caused by bacterial
plaque. Vitamin C deficiency may aggravate the gingival
response to plaque and worsen the edema, enlargement
and bleeding.
Acute vitamin C deciency results in edema and hemorrhage in periodontal ligament, osteoporosis of alveolar
bone, tooth mobility and degeneration of collagen bers.
Vitamin C deciency accentuates the destructive effect of
gingival inammation on the underlying periodontal ligament and bone. Vitamin C inuences the metabolism of collagen in the periodontium, affecting the ability of the tissue
to regenerate and repair itself.
Scurvy also leads to changes in teeth in the form of
hypoplastic teeth. Vitamin C deciency leads to the atrophy of ameloblasts and odontoblasts leading to a disruption in their orderly polar arrangement. Thus, dentin formed
resembles osteodentin, with a lack of parallel arrangement
of dentinal tubules. Severe deciency of vitamin C leads to
hypercalcication of predentin.
640

It functions as a coenzyme, thiamine pyrophosphate (TPP)


in the metabolism of carbohydrates and branched-chain
amino acids. It is required for the normal functioning of the
brain, nerves, muscles and the heart. Carbohydrate metabolism is impossible without thiamine.

Whole grains, nuts, legumes, pork are good sources of


thiamine.
Deficiency
Intake of polished rice, alcoholism and ingestion of raw
fish lead to the deficiency of thiamine.
Mild deciency of thiamine leads to depression,
anorexia, fatigue and inability to concentrate. Hence, this
vitamin has also been called as morale vitamin.
Severe deciency leads to beriberi. Beriberi occurs in
two forms: wet and dry. Dry beriberi is characterized by
impairment of sensory and motor function and muscle wasting. Wet beriberi presents with edema, cardiac enlargement
and tachycardia.
WernickeKorsakoff syndrome occurs in the deciency
of thiamine and is characterized by nystagmus, ataxia and
mental confusion in alcoholics.
Dental considerations
Tongue changes in the form of an enlarged, flabby, red
and edematous appearance with enlargement of fungiform
papillae have been associated with thiamine deficiency.
The gingiva becomes inflamed and presents with an old
rose color (Table 7).
Vitamin B2Riboflavin
Riboflavin is a flavoprotein and is part of the oxidation
chain in the mitochondria, acting as a coenzyme in oxidationreduction reactions. It is required for the metabolism of
carbohydrate, proteins and fat. It is also required for the
maintenance of mucous membranes (Table 8).
Sources
Milk and milk products, grains, meat, poultry and fish.
Deficiency
Riboflavin (vitamin B2 ) deficiency results in the condition
of hypo- or ariboflavinosis. As riboflavin deficiency almost
invariably occurs in combination with a deficiency of other
B complex vitamins, some of the symptoms (e.g. glossitis and
dermatitis) may result from other complicating deficiencies.

Chapter 23 Nutritional and Metabolic Disorders

Table 7 Recommended nutrient intakes (RNIs) for thiamine


Group

RNI (mg/day)

Dental considerations

Infants and children


06 months
712 months
13 years
46 years
79 years

0.2
0.3
0.5
0.6
0.9

Adolescents
Females, 1018 years
Males, 1018 years

1.1
1.2

Adults
Females, 19 years
Males, 19 years

1.1
1.2

Pregnant women

1.4

Lactating women

1.5

Source: Vitamin and mineral requirements in human nutrition, WHO.

Table 8

resection of the small bowel, and decreased gastrointestinal


passage time.

Recommended nutrient intakes (RNIs) for riboavin,


by group

Group

RNI (mg/day)

Infants and children


06 months
712 months
13 years
46 years
79 years

0.3
0.4
0.5
0.6
0.9

Adolescents
Females, 1018 years
Males, 1018 years

1.0
1.3

Adults
Females, 19 years
Males, 19 years

1.1
1.3

Pregnant women

1.4

Lactating women

1.6

Source: Vitamin and mineral requirements in human nutrition, WHO.

The major cause of hyporiboavinosis is inadequate


dietary intake as a result of limited food supply, which is
sometimes exacerbated by poor food storage or processing.
Children in developing countries will commonly demonstrate clinical signs of riboavin deciency during periods
of the year when gastrointestinal infections are prevalent.
Decreased assimilation of riboavin also results from
abnormal digestion, such as that which occurs with lactose
intolerance. This condition is highest in African and Asian
populations and can lead to a decreased intake of milk, as
well as an abnormal absorption of the vitamin. Absorption
of riboavin is also affected in some other conditions, for
example, tropical sprue, celiac disease, malignancy and

Oral symptoms are a prominent feature of riboflavin deficiency. These are characterized by angular cheilitis and
glossitis.
In the initial stages, there is a reddish appearance of the
tip and lateral margins of the tongue. The tongue appears
to be coarsely granular due to atrophy of liform papillae
and swelling of fungiform papillae. Severe cases lead to
atrophy of all papillae causing the tongue to appear smooth
and glazed. Riboavin deciency also leads to increased
vascularization causing the tongue to appear magenta in
color.
Angular cheilitis initially presents as pallor of the lips
at the angles of the mouth. This is followed a few days
later by reddening of lips due to the desquamation of the
epithelium and ssuring at the angles of the mouth. There
may be only one or multiple ssures. These ssures develop
a yellow crust, which can be removed without bleeding.
If the deciency is not treated, the ssures become deep
and may bleed and become painful. Secondary infection
with oral and/or skin microorganisms may occur. The
incidence of the orolingual and dermal lesions in India is
high about 510%, particularly in pregnant women and in
school-going children.
Angular stomatitis, however, may be associated with
iron deciency anemia. Angular cheilitis, however, is
often associated with fungal infections, lip-sucking and
dehydration.
Patients with riboavin deciency also reveal a scaly,
greasy dermatitis of the alae of nose and nasolabial folds.
Corneal vascularization, supercial and interstitial keratitis have also been reported in ariboavinosis. Impairment
of psychomotor performance tests in riboavin deciency
has been reported to occur since physical work increases
riboavin requirement. Riboavin deciency has also been
implicated in the etiology of cataract.

METABOLIC DISORDERS
Lysosomal Storage Diseases
Lysosomes are subcellular organelles containing specific
hydrolases that allow targeted processing or degradation
of proteins, nucleic acids, carbohydrates and lipids. There
are more than 40 different types of lysosomal storage
diseases.
Metabolic diseases can be categorized as:
1.
2.
3.

Disorders of protein metabolism


Disorders of carbohydrate metabolism
Disorders of lipid metabolism
641

Section VII System Review

Disorders of Protein Metabolism


Amyloidosis It is a rare disease characterized by the
deposition of an insoluble extracellular fibrillar protein in
various tissues of the body. This protein called amyloid is
not a single entity, but has three major and several minor
biochemical forms. The major biochemical forms include
AL (amyloid light chain), derived from plasma cells; AA
(amyloid-associated) protein synthesized by liver; and A
amyloid found in the cerebral lesion of Alzheimer's disease. The characteristic physical nature of amyloid is its
crossed -pleated sheet conformation as demonstrated by
X-ray crystallography and infrared spectroscopy.
Classification Amyloidosis can be primary systemic,
secondary systemic, localized, myeloma-associated or
hereditary-familial. These categories constitute 56%, 8%,
9%, 26% and 1% of cases respectively. The primary systemic
form affects mainly mesenchymal tissues such as the heart,
tongue, and gastrointestinal tract and is characterized by
the deposition of AL amyloid. The secondary form is however associated with destructive chronic inflammatory diseases such as tuberculosis, leprosy, rheumatoid arthritis,
ankylosing spondylitis and osteomyelitis and is characterized by the deposition of AA amyloid. This form affects
primarily the kidneys, adrenals, liver and spleen. About
12% of myeloma patients develop amyloidosis. Various
heredofamilial types have been reported including familial
Mediterranean fever and transthyretin-related amyloidosis
(ATTR) type.
Clinical features Generally, peak age incidence is in the
fifties, with a male-to-female ratio of 2:1 and no racial
bias. Clinical manifestation depends on the organ or site
of involvement and the severity of involvement. Its manifestations range from asymptomatic deposition to serious
clinical impairment to even death. Initial symptoms include
fatigue, weakness and weight loss. Later, the disease may
manifest as renal disease, hepatomegaly, splenomegaly or
cardiac abnormalities.
Oral considerations Oral manifestations of systemic
amyloidosis have been well documented. The tongue is the
most frequently reported location of intraoral amyloid
deposition. Macroglossia commonly develops, and difficulty with speaking and chewing may ensue. Dental indentations of the lateral borders of the tongue may be evident
owing to pressure against the teeth. Other sites in the oral
cavity that may have amyloid deposition include the buccal mucosa, palate, gingiva and floor of the mouth. A rare
instance of amyloid deposition of amyloid in the parotid
gland has been reported.
In the absence of clinical symptoms, oral tissues have
been advocated for biopsy to detect amyloid deposition.
Oral biopsy sites that have demonstrated presence of amyloid are numerous, including the gingiva, parotid gland,
minor salivary glands of the lower lip and buccal mucosa.
642

Investigations A diagnosis of amyloidosis is first made


on the basis of clinical suspicion; a tissue biopsy is used to
establish a definitive diagnosis. Biopsy followed by Congo
red staining is considered the gold standard for diagnosis.
Amyloid shows an apple-green birefringence when viewed
with polarized light microscopy. Biopsy is generally from
the organ suspected to be involved. Gingival biopsy may
be taken in generalized amyloidosis. After the sample has
yielded a positive result, the type of amyloidosis must be
determined. Immunofixation electrophoresis of serum or urine
will enable the detection of monoclonal immunoglobulins
or light chains in 90% of patients with AL amyloidosis.
In patients whose light chains are not detected, a bone marrow biopsy can be used to detect the clonal dominance of
plasma cells by immunohistochemical staining techniques.
If no evidence of plasma cell dyscrasias is noted, other types
of amyloidosis should be considered, such as the hereditaryfamilial type. Patients suspected of having AA amyloidosis
should undergo immunohistochemical staining of their
serum for the detection of the AA protein.
Treatment The treatment of amyloidosis is directed both
toward the affected organ and the specific type of the disease. Nephrotic involvement may necessitate the need for
diuretics and dialysis, and cardiac involvement may dictate the need for diuretics as well. Colchicine, intermittent
oral melphalan, prednisone, vincristine and adriamycin, in
combination with dexamethasone have met with considerable success. Treatment with high-dose intravenous
melphalan with autologous blood stem cell support results
in complete remission of the plasma cell dyscrasia. Renal
transplantation is extremely successful in providing dramatic symptom relief for patients with dialysis-related
amyloidosis. The definitive therapy for ATTR amyloidosis
is liver transplantation.
Prognosis The prognosis for patients with generalized
amyloidosis is poor if left untreated. The disease is rapidly fatal within 13 years of diagnosis. Diagnosis is mostly
made at postmortem; the 5-year survival rate has been put
at 20%. Prognosis of secondary amyloidosis depends on the
control of the underlying condition. Patients with myelomaassociated amyloidosis have a poorer prognosis.
Porphyria The term porphyria' is derived from the
Greek word porphuros, meaning purple pigment, after
the purple-red urine that some patients produce during an
acute attack.
Porphyrias are a group of inherited or acquired disorders of certain enzymes in the heme biosynthetic pathway
(also called porphyrin pathway).
Porphyrias can be categorized into acute porphyria and
cutaneous porphyria.
Acute porphyrias are further subdivided into acute
intermittent porphyria, hereditary coproporphyria, variegate porphyria and ALA dehydratase-decient porphyria.

Chapter 23 Nutritional and Metabolic Disorders

Cutaneous porphyria is divided into congenital erythropoietic porphyria (Gunthers disease), porphyria cutanea
tarda and erythropoietic protoporphyria.
Clinical features
Acute intermittent porphyria It is an autosomal dominant disorder caused by the deficiency of uroporphyrinogen I synthetase. Acute attacks in this disease are triggered
by alcohol consumption, tobacco use, stress and hormonal
changes such as in luteal phase of menstrual cycle and
pregnancy. Men and women are equally affected. The
symptoms of the disorder are frequently manifested after
puberty.
In acute episodes the urine turns purple-red following
exposure to sunlight. Acute attacks are characterized by
nausea, vomiting, malaise, myalgia and chest pain. Some
individuals may present with depression, confusion, hallucinations and seizures. Severe forms of the condition
may result in respiratory paralysis.
Downey (1992) reported a patient who complained of
severe abdominal pain, seizures, diarrhea, drooling of saliva
associated with a metallic taste immediately after placing
a xed partial denture containing pallidum (76%), copper
(10%) and gold (2%). The symptoms subsided on removing
the denture. This patient was diagnosed as suffering from
acute intermittent porphyria.
Acute intermittent porphyria can be diagnosed by the
qualitative assessment of urine for porphobilinogen.
Hereditary corpoporphyria It is the rarest form of acute
porphyria characterized by the deficiency of enzyme corpooxidase. It is an autosomal dominant condition which is
usually more common in women. The trigger factors are the
same as that of the acute intermittent porphyria. However,
acute attacks are less common and less severe.
The clinical symptoms are the same as that of the acute
intermittent type. These patients may exhibit cutaneous
photosensitivity.
Elevated levels of coproporphyrins in stool analysis is
diagnostic of hereditary corpoporphyria.
Variegate porphyria The term variegate' is used to
describe the variety of clinical manifestations that this form
of porphyria exhibits. It can manifest as an acute form, cutaneous form, both or occasionally appear clinically latent.
Protocoproporphyria hereditaria or South African porphyria (widely prevalent in the white population of South
Africa) are other names by which variegate porphyria is
known.
Vareigate porphyria is diagnosed based on the marked
increase in the levels of protoporphyrin in stool.
ALA dehydratase-deficient porphyria It is an acute
form of porphyria whose pattern of inheritance is still not
known. The clinical presentation mimics that of acute
intermittent porphyria.

Congenital erythropoietic porphyria Congenital erythropoietic porphyria or Gunthers disease is a rare autosomal
recessive disorder that usually presents with marked skin
photosensitivity, hypertrichosis, blistering, scarring, milia
formation and dyspigmentation of the photo-exposed areas.
The enzyme URO-3-synthetase is decient. It typically
begins in infants or young children.
Sun-exposed regions of the body such as the hands, neck
and face may exhibit vesicular or bullous lesions. These vesicles subsequently rupture and heal with scar formation.
Owing to its physical afnity to calcium phosphate, porphyrin binds to teeth, nails and bones. Both the deciduous
and permanent dentition appear red or brown in color
(erythrodontia).
Porphyria cutanea tarda It is an autosomal dominant
disorder and the most common of all the porphyrias. It is
caused by the deficiency of URO-decarboxylase.
Alcohol consumption, hepatitis C and medications such
as iron supplements and hormonal replacements can predispose to porphyria cutanea tarda.
Cutaneous photosensitivity is the most striking feature.
Exposure to sun leads to the formation of vesicles and bullae which subsequently heal forming crusts. These individuals may exhibit hyperpigmentation and hirsutism.
Erythropoietic protoporphyria It is an autosomal dominant disorder caused by the deficiency of ferrochelatase.
The striking feature of this type of porphyria is the development of cutaneous manifestations of pain, redness, itching and burning sensation within a few minutes of sun
exposure. Thickening of the skin and nail deformities are
seen in chronic cases. Unlike other forms of porphyria
hyperpigmentation and hirsutisms are rare.
Orofacial manifestations and dental
considerations
Individuals suffering from cutaneous porphyria may present with long eyelashes, bushy eyebrows and facial hair
(facial hirsutism).
Oral mucosa is very vulnerable even to the mildest trauma
due to the accumulation of porphyrin precursors. Intraoral
erosions and bullae may be seen.
Patients suffering from congenital erythropoietic porphyria
(CEP) may exhibit pallor of the oral mucosa. Occasionally,
the alveolar mucosa may appear bluish purple owing to
the discolored underlying alveolar bone.
Deciduous dentition of CEP patients may appear deep
red-brown in color. Permanent teeth may not be severely
discolored. The cervical regions of teeth are more intensely
discolored compared to the occlusal region. These discolored teeth tend to uoresce with Woods light (near UV
light of 365 nm wavelength).
It is believed that the concentration of porphyrin is higher
in the dentin compared to the enamel.
643

Section VII System Review

Fayle and Pollard (1994) reported that the enamel


showed marked thinning in a 4-year-old child suffering
from CEP. They believed that the thinning of enamel can
increase the caries risk in these individuals.
Use of carbohydrate in the management of acute porphyria can cause extensive periodontal disease and high
caries incidence.
Oral B carotene which is used to improve tolerance to
light in CEP and erythropoietic protoporphyria patients
can induce carotenemia, leading to yellowish-orange discoloration of the oral mucosa and tongue.
As heavy metals can provoke an acute episode of porphyria, dental amalgam has been recommended to be
avoided in these patients.
Light in the operation theatre have known to cause
burns in some patients. Hence, the light on the dental chair
should be considered a potential hazard to these patients.
It is advisable to use lters that remove light in the wavelength of 400550 nm.
Various medications that can be used and those that
have to be avoided are listed in Table 9.

Disorders of Carbohydrate Metabolism


Mucopolysaccharidoses (MPS) These are normal components of the cornea, cartilage, bone, connective tissue
ground substance and the reticuloendothelial system.
MPS are characterized by the storage of mucopolysaccharides in various tissues. Theses are caused by the deficiency
of the enzymes required for their degradation. The overall
prevalence of MPS is about 1 in 25,000. The variants of
MPS have been classified as types I through VII. Of these,
Table 9 Drug recommendations in patients suffering from
porphyria

644

Safe drugs
(commonly used)

Contraindicated drugs
(commonly used)

Acetaminophen

Alcohol

Acetyl salicylic acid

Clindamycin

Acyclovir

Diclofenac

Amoxicillin

Erythromycin

Amphotericin B

Lidocaine

Bupivacaine

Mepivacaine

Codeine

Miconazole

Dexamethasone

Prilocaine

Gentamicin

Pyrazolones

Ibuprofen

Carbamazepine

Iron

Phenytoin sodium

Nitrous oxide

Dapsone

Penicillins

Sulfonamides

Streptomycin

Oral contraceptives (some)

MPS I or Hurler syndrome is the most common. All of


them are inherited as autosomal recessive traits except
MPS type IIHunter syndrome, which is inherited as an
X-linked trait.
Mucopolysaccharidosis I (MPS I) It is caused by deficient or absent activity of the lysosomal hydrolase-Liduronidase. This enzyme is responsible for the degradation
of heparan sulfate and dermatan sulfate, and a deficiency
in the enzyme leads to accumulation of these substances
in various tissues.
MPS I includes three subtypes:

MPS I-H (Hurler syndrome): The most severe form in


which the onset is in infancy.
MPS I-H/S: The intermediate form, characterized by mental retardation and other features of Hurler syndrome.
MPS I-S (Scheie syndrome): The least severe form
having its onset in adulthood and presenting no features of mental retardation.
Hurler syndrome (Gargoylism) The worldwide incidence
of MPS I-H has been reported to be 1:100,000. The chromosomal abnormality in this syndrome has been mapped
to 4p16.3.
Clinical features The disease becomes apparent in the
first 2 years of life, progressing in childhood. Death usually occurs before the 2nd decade of life, unless affected
patients are treated by bone marrow transplantation.
Patients are characterized by dwarfism, mental retardation,
skeletal malformations, hernias, cardiac disease and systemic hypertension, hepatosplenomegaly and flexion contractures. The facial features are characteristic, with patients
having a large head, prominent forehead, a broad saddle
nose, hypertelorism, puffy eyelids and an open mouth.
The oral and dental ndings of MPS I-H include hyperplastic gingiva, macroglossia, high-arched palate, short mandibular rami with abnormal condyles, spaced hypoplastic
peg-shaped teeth with retarded eruption; and localized dentigerous cyst-like radiolucencies. Gingival hyperplasia has
been reported in some patients. Guven et al reported that
MPS I-Haffected dentin was characterized by extremely
narrow dentinal tubules, whose direction followed an irregular wave-like pattern. The enameldentin junction had
microgaps, and the enamel displayed irregular arrangement
of prisms. There was a decrease in the protein content of
enamel and dentin.
The mucopolysaccharides accumulate in broblasts, giving them an appearance of clear or gargoyle cells, and
hence the term gargoylism. Elevated levels of mucopolysaccharides are found in urine.
Mucopolysaccharidosis II (Hunter syndrome) The biochemical cause of Hunter syndrome is a deficiency in the
activity iduronate-2-sulfatase and is characterized by the
deposition of dermatan sulfate and heparan sulfate in tissues.

Chapter 23 Nutritional and Metabolic Disorders

It has an estimated prevalence of 1 in 170,000 male live


births. Its prevalence among Ashkenazi and Oriental Jews
is reported to be approximately twice that reported in other
populations. Hunter syndrome is an X-linked, recessive
inherited disease that affects males nearly exclusively. The
gene responsible for the syndrome is located at Xq28.
Clinical features In its severe form, clinical features
appear between 2 and 4 years of age in the form of severe
mental impairment. Death usually occurs in the 1st or 2nd
decade of life, following obstructive airway disease and/or
cardiac failure. The disease may have a slightly later onset,
with minimal neurologic dysfunction. These patients have
normal intelligence and survive into adulthood.
Clinical features include coarsening of facial features,
broad noses with ared nostrils, prominent supraorbital
ridges, large jaws, and thick lips, enlarged protruding tongue.
Mobility is restricted because of joint stiffness and contractures. The skeletal ndings of Hunter syndrome are collectively known as dysostosis multiplex. Corneal clouding
is not a feature of Hunter syndrome. There may be progressive hearing loss, sleep apnea, hepatosplenomegaly, valvular heart disease, progressive airway obstruction, and
distinctive skin lesions, described as ivory-white papules
that are 210 mm in diameter, often coalescing to form
ridges. Diagnosis is established by measurement of urine
mucopolysaccharide levels and enzyme activity.
Mucopolysaccharidosis III (Sanfilippo syndrome) It is
characterized by the deposition of heparan sulfate in tissues. Based on the deficient enzyme, this syndrome is classified into four subtypes A, B, C and D. The incidence of
the combined MPS III subtypes has been estimated at 1 in
24,000 births to 1 in 66,000 with MPS III A being the most
common subtype. MPS III A is characterized by the deficiency of heparan-N-sulfatase, MPS III B by N-acetyl-glucosaminidase, MPS III C by acetyl-CoA-glucosaminide
N-acetyltransferase deficiency, and MPS III D by the deficiency of N-acetylglucosamine-6-6-sulfate sulfatase.
Clinical features Symptoms begin in late infancy with
various patterns of neurodegeneration resulting in severe
mental retardation characterized by rapid loss of social
skills with aggressive behavior and hyperactivity, and disturbed sleep patterns. In profoundly affected patients,
delayed speech development is often noticed at 2 years of
age. Hirsutism, coarse facies and diarrhea are found. Mild
hepatosplenomegaly and mild skeletal disturbances may
be found. Diagnosis depends on enzymatic analysis and
heparan sulfaturia.
Mucopolysaccharidosis IV (Morquio syndrome) This
syndrome is characterized by the deposition of keratan
sulfate and chondroitin-6-sulfate in tissues. It is subclassified into Morquio type A, characterized by the deficiency
of N-acetyl galactosamine; and Morquio type B, caused by
the deficiency of -galactosidase.

Clinical features The syndrome is characterized by severe


skeletal changes including hypoplasia of odontoid process,
short neck, pectus craniatum, kyphoscoliosis and dwarfism.
Other findings include laxity of joints, neurosensory deafness and corneal clouding. Mental retardation is absent.
Characteristic dental ndings are found in MPS IV A,
but not in MPS IV B. These have been described as mineralization disturbances of enamel leading to the appearance
of dull grayish to yellowish crowns, small teeth, severe
attrition, and pointed cusps. The enamel, however, had a
normal radiodensity. Damage to TMJ has been reported in
the form of irregularity of cortical bone of the head of condyle, possibly aggravated by severe attrition of teeth.
Diagnosis of the disease is by the estimation of keratan
sulfate levels in urine and plasma.
Mucopolysaccharidosis V: absent Mucopolysaccharidosis VI (MaroteauxLamy syndrome). It occurs due to a
deciency of arylsulfatase B (N-acetylgalactosamine-4sulfatase), which results in the accumulation of dermatan
sulfate within lysosomes. An incidence of 1:100,000 to
1:1300,000 has been reported.
Clinical features Patients suffering from Maroteaux
Lamy syndrome have similar somatic features resembling
those of the other mucopolysaccharidoses, but distinguished by the presence of normal intelligence, prominent
metachromatic inclusions in leukocytes and a deficient
activity of arylsulfatase B. Characteristic features of this
disease include growth retardation, hernias, a large deformed
head, typical facies, a short neck and spinal abnormalities.
Hepatosplenomegaly results from mucopolysaccharide
deposits in several organs. Severely affected MPS VI patients
are usually diagnosed in infancy or early childhood and the
condition usually results in death in the 2nd decade of life.
Death is usually a result of either respiratory tract infection
or cardiac disease, which are caused by the deposition of
mucopolysaccharides.
The craniofacial features in this syndrome are similar
to Hurler syndrome. The head is large, with a prominent
forehead, often marked supraorbital ridges and temporal
bulge. Rhinitis with rhinorhea is common and corneal
opacity is also observed. At rest, the mouth is open and the
enlarged tongue tends to protrude. The teeth have been
reported as being short or stubby, misshapen, malformed,
peg-shaped, poorly formed, abnormal, poorly calcied,
and hypoplastic. Usually there is an anterior open bite
relationship in association with macroglossia. Localized
radiolucent areas resembling dentigerous cyst-like follicles are also reported in MaroteauxLamy syndrome. The
margins of the radiolucencies are usually smooth and
clearly dened. These radiolucencies are caused by accumulation of mucopolysaccharides in the tissues.
Mucopolysaccharidosis VII (Sly syndrome) It is caused
by a deficiency in the enzyme -glucuronidase. This
645

Section VII System Review

results in the accumulation of heparan sulfate and dermatan


sulfate in tissues.
Clinical features The syndrome is highly variable, with
clinical presentation ranging from severe lethal hydrops
fetalis to mild forms with survival into adulthood. Sewell
et al suggested that MPS VII comprises three main clinical
groups: an early severe lethal form, an intermediate form
with slight organomegaly and moderate skeletal anomalies and a very mild form in which patients present later
and show longer survival. Most patients show hepatosplenomegaly, and skeletal anomalies such as disproportionate dwarfism, sternal protrusion, kyphosis, scoliosis,
and a broad-based gait. Craniofacial dysmorphism characterized by epicanthus, anti-mongoloid eyelids, short nose
with anteversion of the nostrils, macroglossia, and coarse
facies may be seen. A variable degree of mental impairment and delayed speech is present.
Management of mucopolysaccharidoses Methods of
replacing the enzyme missing in MPS have included
bone marrow transplantation, human amnion membrane
implantation, fibroblast transplantation, serum or plasma
infusion, white blood cell infusions, gene therapy, intraperitoneal implantation of myoblasts overexpressing I2S
and enzyme replacement therapy. Future prospects include
gene therapy, newborn screening and prenatal screening.

Lipoid Proteinosis
Lipoid proteinosis also known as hyalinosis cutis et mucosae or UrbachWiethe disease. It is transmitted as an autosomal recessive disorder. Lipoid proteinsosis is characterized
by generalized thickening and scarring of the skin, mucosae and occasionally some viscera secondary to diffuse
deposition of a hyaline-like substance.
Recent studies have shown that lipoid proteinosis is
caused by the mutations in a glycoprotein (extracellular
matrix protein 1) that is expressed in various tissues. The
mutation was mapped to a locus on chromosome 1q21.
Clinical features
Deposits in the vocal cords may manifest as inability of
babies to cry at birth and hoarseness of voice from early
infancy or childhood.
The skin characteristically shows whitish, moniliform
papules on the eyelids (blepharosis moniliformis, eyelid beading), and yellowish or waxy papules or nodules on the lips,
knuckles, hands, knees, elbows, axillae and the perineal
regions.
Occasionally, the face may exhibit vesiculobullous eruptions which later form scars. Patchy alopecia has also been
reported.
Other features include dyspnea, dysphagia, corneal opacities and glaucoma. Calcications of intracerebral parasellar or hippocampal gyri may be associated with epilepsy,
646

mental retardation and neuropsychiatric illnesses. Intestinal


bleeding has been reported following hyaline deposits in
the small bowel.
Oral manifestations
The oral mucosa appears thickened and nodular. The sites of
involvement are the labial, buccal and palatal mucosa, posterior tongue, uvula, tonsillar region and lingual frenulum.
The typical oral lesions are seen as yellowish-white
papules or plaques.
Involvement of the lingual frenum causes difculty in
tongue protrusion. Macroglossia and wood-hard tongue
are other characteristic features. Lips may be enlarged,
nodular and may exhibit ssuring.
Occasionally, patients may report dry mouth secondary
to inltration and obstruction of the parotid duct by the
hyaline material. Gingival hyperplasia has also been
reported.
Oezarmagan et al (1993) in their report of lipoid proteinosis in two sisters, describe the ndings of overretention of deciduous teeth and oligodontia.
Radiographic features
Bean-shaped radiopacities in the temporal lobe or hippocampus on skull radiographs are typical findings in lipoid
proteinosis.
Histopathologic features
On histopathologic evaluation the hyaline deposits exhibit
positivity for periodic acid-Schiff (PAS) and Congo red.
However, the material is diastase resistant.
Ultrastructural features include concentric rings of
excess basement membrane surrounding blood vessels,
and irregular reduplication of lamina densa at dermoepidermal junction resulting in onion-skin appearance.
Dyer et al (2006) studied the lesional epidermis, cultured
monolayer keratinocytes and raft keratinocyte cultures
from blistering lesions of a child with lipoid proteinosis.
Their ultrastructural studies showed the dissociation
of relatively intact desmosomes from keratinocytes, with
desmosomes which were free-oating in the intercellular
spaces or attached by thin strands to the cell membrane.
They suggest that these free-oating desmosomes could
be a result of an inherent defect in keratinocyte adhesion.
Management
Lipoid proteinosis to date has no definitive treatment. However, Wong and Lin (1988) successfully used oral dimethyl
sulfoxide in a 41-year-old man. They initially used a dose
of 40 mg/kg/day, which was subsequently increased progressively to 60 mg/kg/day. In their follow-up after 3 years
of treatment, the patients skin lesions, hoarseness of voice
and abnormal esophageal function improved to a great

Chapter 23 Nutritional and Metabolic Disorders

extent. The only side effect they encountered was the


garlic-like smell on the patients breath.
Intralesional heparin and ketretinate have also been used
with limited success. Other treatment options used include
CO2 laser surgery of vocal cords and beaded eyelid papules, and dermabrasion of skin for aesthetic and functional
reasons.
In severe forms of the condition, resulting in respiratory
embarrassment, tracheostomy is performed.

Disorders of Lipid Metabolism


Non-lipid reticuloendothelioses It involves diseases such
as unifocal eosinophilic granuloma, multifocal eosinophilic
granuloma (HandSchullerChristian disease) and Letterer
Siwe disease. These diseases are collectively referred to as
histiocytosis X disease.
Histiocytosis X is the term used to describe a group
of conditions affecting the reticuloendothelial system.
Lichtenstein in 1953 coined the term histiocytosis X. It is
a non-neoplastic lesion of unknown etiology characterized by an intense proliferation of histiocytes along with a
number of eosinophilic leukocytes, neutrophilic leukocytes, lymphocytes, plasma cells and multinucleate giant
cells.
However, this term has now been changed to Langerhans
cell histiocytosis (LCH) by Risdall et al (1983), as these
diseases are known to involve Langerhans cell precursors.
Eosinophilic granuloma is considered to be the chronic
localized form of LCH which also includes HandSchuller
Christian disease (the chronic disseminated form) and
LettererSiwe disease (the acute disseminated form).
Radiographic features of histiocytosis X Dagenais et al
(1992) described the characteristic radiographic features of
histiocytosis X. They reported that seven characteristics,
either alone or in combination, are useful in the identification of histiocytosis X. These include the appearance of
solitary intraosseous lesions, the multiplicity of alveolar
bone lesions, the scooped-out effect in the alveolar process, the well-defined periphery, sclerosis in the alveolar
bone lesions, periosteal new bone formation and slight
root resorption.
Eosinophilic granuloma It affects men twice as more
than women. It is usually seen in young adults. The condition may have varied presentations. Some patients may
complain of pain whereas in some others it may be incidentally evident on routine radiographic evaluation.
It is believed that oral involvement is usually associated
with pain, swelling, mucosal ulcerations and gingival
inammation. Ardekian et al (1999) in their study found
that 44% of patients complained of pain and about 48%
also complained of swelling in the affected area. The bones
that are commonly affected are the skull bones, mandible,
ribs, femur, humerus and pelvis. However, the bones of the

hand and feet are usually spared. Mandibular posterior


region is usually the site to be affected.
Radiographic features Alveolar bone may show irregular radiolucent lesions. Larger lesions may cause destruction of the cortical plate resulting in pathological fracture.
However, lesions within the mandible appear as
well-dened radiolucent areas mimicking cysts.
These varied radiographic appearances of eosinophilic granuloma can be mistaken for odontogenic cyst,
osteomyelitis or a malignancy.
Management The currently accepted methods of managing eosinophilic granuloma include surgical curettage,
low dose radiation (not more than 10 Gy) and chemotherapy used alone or in combination.

HandSchullerChristian Disease or Multifocal


Eosinophilic Granuloma
The condition was named after Henry Asbury Christian,
Alfred Hand Jr and Artur Schller.
It is a chronic form of eosinophilic granuloma characterized by disseminated form of skeletal and extraskeletal
(soft tissue) lesions.
Clinical features
Facial asymmetry secondary to involvement of the facial
bones is a characteristic feature. Patients may complain of
pain, swelling and progressive facial asymmetry.
Ribs, vertebrae, femur and pelvis are other bones that are
commonly affected. It is believed that about 25% of the
patients present with the classical triad of signs and symptoms that include punched-out radiolucent areas in the
skull on a radiograph, exophthalmos and dwarsm, infantilism or polyuria.
Oral manifestations
The oral manifestations in these patients may mimic manifestations of advanced periodontitis such as halitosis, gingival inflammation with purulent discharge, spontaneous
exfoliation of teeth and extensive loss of alveolar bone.
Other symptoms include loss of taste sensation and oral
mucosal ulceration or soreness.
Radiographs may reveal displacement of teeth, and
sometimes teeth oating in air appearance may be appreciated. Bone scan may help in identifying multifocal disease. The bone destruction may be round, oval or irregular,
occasionally with a periosteal reaction
Diagnosis
Radiographic features, histopathologic features and
laboratory investigations are sufficient to diagnose this
condition.
647

Section VII System Review

Histologically the lesion progresses through the phase


of proliferative histiocytic phase, vascular granulmatous
phase, diffuse xanthomatous phase (abundance of foam
cells), and nally the brous or healing phase.
Laboratory studies reveal normal serum cholesterol
level and an elevated tissue cholesterol level.
Management
Surgical curettage or excision is the ideal mode of treatment. Lesions that are not amenable to surgery can be
irradiated or drugs such as vinblastine or cyclophosphamide can be used.
However, almost 50% of the patients exhibit spontaneous remission over a period of time.

LIPID RETICULOENDOTHELIOSES
Gaucher Disease
Gaucher disease is a rare autosomal recessive disorder
characterized by defective function of the catabolic
enzyme -glucocerebrosidase, leading to an accumulation
of its substrate, glucocerebroside, in the mononuclear
phagocyte system, lymph nodes, bone marrow; Kupffer
cells in the liver; osteoclasts in bone; microglia in the central nervous system; alveolar macrophages in the lungs;
and histiocytes in the gastrointestinal tracts, genitourinary
tracts, and the peritoneum. Cells with this deposition are
termed Gaucher cells.
Classification

LettererSiwe Disease
It is named after Erich Letterer and Sture August Siwe.
Unlike the other forms of Langerhans cell histiocytosis,
LettererSiwe disease is an acute disease and almost
always seen in infants. It usually runs a short course and
ends fatally.
Clinical features
In LettererSiwe disease, recurrent pyoderma-like lesions
with crusting and scaling, vesicopustular and purpuric
eruption occurs in crops over the face, scalp and trunk,
resembling seborrheic dermatitis.
Oral manifestations
In most of the cases, oral manifestations may not be
appreciated owing to the rapid course of the disease.
However, mucosal ulceration associated with hemorrhage,
gingival inflammation, extensive loss of the maxilla and
mandible and spontaneous exfoliation of teeth may be
seen.
Diagnosis
Tzanck smear of the vesicopustules shows pale histiocytes
which can be used as a rapid screening test.
Skin biopsy shows a proliferative reaction with extensive upper dermal inltration and epidermal invasion
with histiocytes, some of which are atypical, along with
erythrocytes.
Typically foam cells and brosis are appreciated
histologically.

There are three clinical variants caused by distinct allelic


mutations. Type I, also called as chronic non-neuronopathic
form, accounts for 99% of cases of Gaucher disease and
has an incidence of 1:100,000 in general population. It is
most common among Ashkenazi Jews and is compatible
with long life. Type II is termed acute neuronopathic form
and is highly lethal. Type III, termed chronic/subacute
neuronopathic form has a course intermediate between
types I and II.
Clinical features
Type I is characterized by the absence of neurologic symptoms. Patients may present with hepatosplenomegaly, leukopenia and thrombocytopenia due to marrow replacement
and cortical erosion. Extensive skeletal disease and pathologic fractures may be seen.
Neurologic symptoms (in types II and III) include convulsions, dementia, ocular muscle apraxia, mental retardation
and myoclonus.
Oral manifestations
Oral mucosa has a yellow pigmentation and presents petechiae. Jaw involvement is often asymptomatic and may be
detected on routine dental radiographs. Generalized osteopenia, loss of trabecular structure, effacement of lamina
dura, displacement of mandibular canal, pseudocystic radiolucent lesions and apical root resorption of teeth adjacent
to lesions have all been reported. Involvement of maxillary sinus has been reported in a few cases. Delayed eruption has been reported in more than 50% of cases.
Diagnosis

Management and prognosis


The prognosis of this condition is very poor. It is believed
that the presence of purpura is a lethal sign. Chemotherapy
is usually the only mode of treatment.
648

Bone marrow aspiration or biopsy of liver and spleen


reveal the presence of Gaucher cells, which appear as large
cells having abundant granular, or fibrillary blue-gray
cytoplasm with a wrinkled tissue paper-like appearance

Chapter 23 Nutritional and Metabolic Disorders

with abundant lightly PASpositive fibrillary material in


the cytoplasm. The level of glucocerebrosidase in leukocytes or cultured fibroblasts is also helpful in diagnosis.
Prognosis and treatment
The infantile form (type II) of Gaucher disease may lead to
early death. Most affected children die before the age of
5 years. Type I of Gaucher disease requires close medical
follow-up with periodic assessment. With the availability
of recombinant enzyme, most patients with the adultchronic form can look forward to normal or near-normal
life expectancy. Enzyme replacement therapy with a
recombinant glucocerebrosidase known as imiglucerase
(Cerezyme) given intravenously is the mainstay of treatment for Gaucher disease. Hepatosplenomegaly, anemia
and thrombocytopenia usually improve within 6 months.
Unfortunately, it is not effective on neurologic symptoms,
because it does not cross the bloodbrain barrier. Future
treatments may include gene therapy and intervention
with chemical chaperones.

NiemannPick Disease
It is characterized by the deficiency of the enzyme, sphingomyelinase, and accumulation of sphingomyelin in tissues.
Classification
It can be classified into two categories based on biochemical and molecular criteria. The first category includes types
A and B, the second, type C.
Clinical features
The organs most commonly involved are spleen, liver,
bone marrow, lymph nodes and lungs. The entire central
nervous system also becomes involved. The patient presents with massive visceromegaly and severe neurologic
deterioration.
Diagnosis is achieved by the estimation of sphigomyelinase activity in leukocytes or cultured broblasts.
Prognosis is poor and affected infants die before the
age of 3 years. Antenatal diagnosis is possible.

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SECTION

Forensic Dentistry

VIII

24

Clinical and Radiological Perspective

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CHAPTER

Clinical and Radiological


Perspective
Ashith B Acharya

Introduction, History and Relevance

Incinerated Teeth
Postmortem Pink Teeth
Tongue Hemorrhage

Social Profiling

Identifying the Edentulous


Denture Marking Systems
Palatal Rugae in Identification

Craniofacial Identification
Cranial Suture Pattern
Frontal Sinus Configuration
Skull-Photograph Superimposition
Challenges in Superimposition
Three-Dimensional Digital Superimposition

INTRODUCTION, HISTORY AND RELEVANCE


Forensic odontology is the branch of dentistry which deals
with the law. The last half-century has seen forensic dentistry make tremendous progress globally, both in terms
of research as well as application in routine casework.
Forensic odontology primarily involves identification.
Right through history, the human dentition has been used
several times in identifying individuals. Harvey (1973) has
traced one of the earliest recorded incidences of dental
identification to 66 AD, when the severed head of the wife
of Roman emperor Nero was identified by a rival from her

Bite Mark Procedures


How Does a Bite Mark Look?
Type of Injury
Site of Injury
Differential Diagnosis of Human Bite Marks
Bite Mark Investigation
Collecting Bite Mark Evidence
Demographics of the Case
Visual Examination and Documentation
Photographs
Saliva Swab
Obtaining Dental Evidence from a Suspect
Analyzing and Comparing Bite Mark Evidence
Conclusions of Bite Mark Analysis

Postmortem Alterations to Teeth and Oral


Tissues

Age Estimation Methods


Clinical Methods of Age Assessment
Radiographic Methods for Age Assessment
Estimating Age in Children and Adolescents
Third Molars in Age Estimation
A Combined Clinical and Radiographic Method
Estimating Age in Adults

Challenges in Postmortem Examination


Rigor Mortis
Incineration
Jaw Resection
Tooth Colored Restorations

Facial Approximation
Clay Modeling
Computer-assisted Approximation

Dental Identification
What is Identification?
Importance of Teeth in Postmortem Identification
Principle of Dental Identification
Dental Identification Procedure

24

Lip Print Investigation

black anterior tooth. In 1193 AD the Maharaja of Kannauj,


Jai Chandra Rathor, was recognized by his false teeth following death in a battle. The English duke Charles of
Burgundy, who also died in a battle in 1477 AD, was identified from his dental features courtesy, the court physician
who recognized two recently extracted teeth (Furness,
1972). Paul Revere is credited as being the first dentist to
identify a person from dental features (Luntz, 1970). He
identified a friendwho died in the American Revolution
in 1775from a silver and ivory bridge prepared by him.
Subsequently, intermittent cases of forensic dental
identication in 19th century Europe and America have
653

Section VIII Forensic Dentistry

been reported (Pedersen, 1965). However, Gustafson (1962)


believed that the role of forensic odontology in human identication came to prominence toward the end of the 19th
century after two major res in Europe: the rst occurred
in 1881 when the Ring Theatre in Vienna was destroyed
during a performance with 449 casualties; and the second
the Charity Bazaar re in Paris in 1897resulted in 127
deaths. In both tragedies, dental features were used for
identication. According to Harvey (1973), one of the
dentists who assisted the identications in Paris was a
Cuban named Oscar Amoedo. In 1898, he authored one of
the rst books on forensic odontology, Lart Dentaire en
Medicine Legale, and is considered a pioneer of modern
forensic dentistry. It is noteworthy that Yasutami Kojimahara
of Japan had published a similar work titled Dental
Jurisprudence a few years earlier in 1894 (Suzuki, 1996).
The routine use of dental evidence in human identication
gained impetus during the 1950s and 1960s, and forensic
dentistry gained organized status in 1972 with the formation of the International Organization for Forensic OdontoStomatology (IOFOS).
With the evolution of criminal investigation in the
industrialized world, scientic methods of detecting both
the victim and culprit in a crime concurrently developed.
Fingerprinting was one such methodthe dermal ridges on
our ngers are so unique even twins do not share an identical pattern. The human dentition is considered to be as
unique to an individual as ngerprints are. The adult dentition normally consists of 32 teeth of which some may be
missing, decayed or treated. Effects of various environmental factors such as uorosis may also manifest in the teeth.
Hence, it is extremely rare to have two identical dentitions,
and this concept makes use of identifying the deceased.
Moreover, teeth are one of the most durable parts of the
body and can withstand physical, chemical and biological
insults. As a result, teeth can be used to build the prole of
skeletal remains. For example, race and sex differences in
tooth morphology are known to occur; age estimation using
tooth eruption, calcication and histological methods is frequently applied. Dental age estimation gained prominence
following a case in Britain in 1935, where the age of two
badly mutilated bodies was estimated from the calcication of third molars (Taylor, 1963). This contributed to the
eventual identication of the bodies using photographic
superimposition. In an age when heightened social, emotional and legal importance is placed on identifying the
dead, dental identication methods has great relevance.
Apart from identication, forensic odontology is applied
in the investigation of crimes where traces of the teeth, such
as bite marks, are observed. The ability to match a bite mark
to the uncommon arrangement of the dental arch can prove
important in investigating sex crimes and violent ghts.
It is interesting to note that as early as the 6th century AD,
the Indian sage Vatsy a yana had recognized the prevalence
of bites during love-making. Consequently, he devoted an
654

entire chapter to love bites, with its detailed classication,


in the treatise Kama Sutra. The unique arrangement of the
dental arch was recognized in medieval Britain during the
reign of William I (10271087 AD), green wax seals with
the impression of the kings teeth were implanted on state
documents to avoid falsication and indicate the authenticity of the seal.
The use of bite marks as evidence in court can be traced
back to 1692 in the United States. Harvey (1973) cites a
1906 case where a burglar was convicted in Britain because
his dental models t the marks left in cheese found at the
crime scene which was probably the rst successful conviction based on bite mark evidence in Europe. Subsequently
there have been numerous cases that made use of bite
marks but, with varying degrees of success. Therefore, bite
marks remained a contentious area of forensic sciences.
However, over the latter half of the 20th century, bite mark
procedures have greatly advanced and it is now routinely
used in court proceedings of Europe, America and Asia
Pacic. Its objective application as evidence in crime can
have far reaching implications for the society in general
and criminology in particular.
The potential of teeth as legal evidence has rendered
forensic dentists as an integral part of the forensic team of
experts. Interest in the subject is not only conned to specialist forensic dentists but also oral physicians and radiologists, oral pathologists, pedodontists, prosthodontists and
forensic medical professionals. This chapter attempts to
address relevant clinical and radiological aspects of forensic odontology and it is intended to further stimulate the
readers inquisition in this fascinating area.

DENTAL IDENTIFICATION
What is Identification?
Identity refers to the characteristics by which a person
may be recognized (Acharya and Taylor, 2003) and identification is the establishment of a persons individuality.
Accurate identification of the dead is required both for
legal and humanitarian reasons (Brown, 1984). It enables
the settlement of insurance and property, permits remarriage of the surviving spouse and facilitate last rites of the
body in accordance with appropriate religious customs.
Haglund and Morton (1994) believe that a majority of
individual identifications in forensic settings are nonproblematic since most individuals die in the company of
family and friends. These deaths may occur at home or in
a hospital, allowing visual identification. However, in cases
where the body is burned, traumatized or decomposed,
visual identification can prove unreliable. Hence, Sopher
(1972) believes that visual recognition and use of personal
effects are the least dependable methods of identification
in such circumstances. Therefore, the safest option is for

Chapter 24 Clinical and Radiological Perspective

the forensic expert to analyze physical features present in


the body.

Importance of Teeth in Postmortem Identification


Every individual has a variety of physical features that
include built, height, epidermal ridges and dental characteristics. Most of these, however, are prone to change over
an individuals lifetime. Epidermal ridges (which produce
fingerprints) are exceptions but, like other soft tissues, are
susceptible to postmortem decomposition. Teeth are considered as the hard tissue analog to fingerprints and gain
importance in identification as the time period since death
increases. Although teeth are susceptible to disease during
life, they are the most durable part of the body after death.
Apart from teeth being relatively resistant to postmortem
change, practically all materials used by the dentist are also
resistant to postmortem destruction. Therefore, the use of
dental evidence is considered essential for establishing identity in traumatized, decomposed and incinerated remains.

Principle of Dental Identification


The underlying principle of dental identification is that
combinations of dental characteristics are never the same
in any two individuals. Several authors believe that the
human dentition is unique (Johanson and Lindenstam,
1961; Keiser-Nielsen, 1977; Fellingham et al, 1984; Phillips
and Scheepers, 1990). Human beings normally have 32
permanent teeth which vary in morphology and arrangement. Although teeth are relatively resistant to environmental factors and postmortem proteolysis, during life they are
susceptible to disease such as caries. As a result, teeth may
have undergone treatment in the form of fillings, crowns,
etc. Those teeth that cannot be restored may have been
extracted and, thus, missing from the oral cavity. According
to Keiser-Nielsen (1977), the number of combinations 16
missing teeth can produce is approximately 60 crore.
Sixteen filled teeth produce a similar combination. Four
missing and four filled teeth combined can produce about
70 crore combinations. Every tooth has five surfaces and
taking the 160 tooth surfaces individually would produce
astronomical variations. In addition to the features visible
on oral examination, radiographs reveal distinct shape and
outline of various restorations of the crown and root and
anatomic features of the teeth and bone (Sopher, 1972).
Hence, the permutations resulting from observing the teeth
clinically and radiographically would be phenomenal. It
has been calculated that there are 1.8  1019 possible combinations of 32 teeth being intact, decayed, missing or filled
(Fellingham et al, 1984). Therefore, dental identity can be
considered as the sum total of all characteristics of teeth
and associated structures which, while not individually
unique, equal a unique totality (Acharya and Taylor, 2003).

Dental Identification Procedure


Having ascertained the value of teeth in identification and
the principle for the same, one can proceed with the procedure. Dental identification may be required in establishing
the identity of a single person, a small group of individuals or in large fatalities such as accidental or natural disasters. The method for the different scenarios is essentially
the same and is addressed together in the following columns
although, considering the magnitude of the latter, the
approach may vary. The identification procedure includes
a number of steps, namely:
1.
2.
3.
4.
5.

On-site evidence recovery


Postmortem dental examination and radiography
Obtaining dental records
Comparing post- and antemortem data
Preparing the identification report and conclusion

On-site evidence recovery


To begin with, it is essential to collect all dental evidence
from the dead body (Haglund and Morton, 1994). This may
require the dentists presence at the site where the dead body
is recovered (Brown, 1984). Dental evidence present at the
site where the body was found may be overlooked and not
recovereddecomposition and skeletonization often leads
to loosening of teeth and the anterior teeth, which have conical roots, may get dislodged. Oliveira and associates (2000)
and uric and coworkers (2004) have reported that incisors, especially maxillary, are most prone to getting lost postmortem. Incinerated bodies have fragile bones and teeth,
which can easily be mishandled by an untrained individual;
trauma may result in scattering of dental evidence around
a large area. Acharya and Taylor (2003) have found that the
inability to recover complete and intact postmortem dental data can undermine successful identification. Therefore,
to maximize success, one must try to recover all dental
evidence that may be present at the site. Hence, care must
be taken to document and photograph the scene at which
the body is recovered; a forensic odontologist should be
present to ensure proper search and recovery of all material
of dental significance needed for identification.
Postmortem dental examination and radiography
The postmortem dental examination is usually conducted in
a mortuary. Case numbers allotted to the body should be
verified and entered in the modified Interpol postmortem dental odontograph, also referred to as the pink form (Figure 1)
before the commencement of examination. A visual appraisal
of the body may enable preliminary assessment of the ethnicity, gender and approximate age of the victim. The
body bag used to transport the deceased should be thoroughly searched for dislodged teeth or dental appliances.
Postmortem dental examination is similar to routine
examination of the oral cavity. All oral and dental features,
655

Section VIII Forensic Dentistry

Figure 1

Modified Interpol postmortem form

including intact and missing teeth, caries and other pathology, restorations, attrited and rotated teeth should be carefully charted on the postmortem form. This will be the
basis for later comparison and verification. Brown (1984)
suggests that postmortem examination should be undertaken by dentists working in pairsone examining and
the other recording. The roles are then reversed and the
procedure repeated as an added check. Any dental
evidence missing should be reported to the forensic
pathologist or accompanying law enforcement personnel.
Subsequent dental evidence recovered must be labeled
properly.
656

The dental examination must be complemented with postmortem dental radiography as this will reveal what cannot
be observed clinically. Radiographic lms may be stabilized
in the mouth using readily available materials such as gauze
or cotton rolls. Whenever possible, postmortem radiographs
should be taken to replicate the type and angle of the antemortem radiographs (Goldstein et al, 1998). According to
these authors, if the difference in horizontal angulation
between the ante- and postmortem radiographs is more than
10, comparison will not facilitate identication. However,
changes in the vertical angulation or the focal point-lm
distance do not affect the outcome of comparison. Pretty and

Chapter 24 Clinical and Radiological Perspective

Sweet (2001) have suggested that ante- and postmortem


radiographs could be marked using a rubber-dam punch to
differentiate the twoone hole for antemortem lms and
two holes for postmortem lms. The exposure time may
need to be increased or decreased respectively in bloated
bodies recovered following drowning and in skeletal remains.

Therefore, the authors examined whether radiographs with


no restorations could be used in postmortem identification. Their results indicated that dental anatomy observable on the radiographs, especially root morphology and
alignment, facilitated correct identification in more than
85% of cases.

Obtaining dental records

Identification report and conclusion

Dental records contain information on treatment and dental status of a person during life. These antemortem records
can be obtained from the local dentist, specialist or hospital records. Whenever possible, the original records should
be examined. Records include hand-written dental charts,
radiographs, study casts and photographs. An individual
may have visited more than one dentist for therapy and
multiple dental records may exist. Relevant information
from the dental records should be transcribed onto the
modified Interpol antemortem odontograph (the yellow
form) (Figure 2).
Contribution of dental records in successful identication
depends on the availability of original records, their completeness and quality (Acharya and Taylor, 2003). By maintaining good dental records, dentists reect their awareness
and responsibility to forensic identication (note: quality
dental records are also important as a counter to malpractice lawsuits). It is also important that these records are
relatively recentrecords made for a 6-year-old child may
not be useful 20 years later in adulthood.

Subject to the availability of adequate postmortem data


and quality antemortem records, Haglund and Morton
(1994) have stated that the comparison and eventual
dental identification are straightforward and routine.
These authors believe that the quality and quantity of
information required for establishing positive dental
identification has not been established. In fingerprinting,
differences in the ante- and postmortem data rule out a
positive match. This concept, however, does not apply to
dental identification as long as the inconsistencies are
explainable. For example, the postmortem data may
reveal a restoration on a tooth but the dental records indicate that the same tooth is intact. This difference, however, can be explained since the restoration may have
been placed on a date after the last available dental
record. On the other hand, if the postmortem data shows
an intact tooth but the same tooth is indicated as being
restored in the dental record, this would probably suggest
a mismatch. Having compared the ante- and postmortem
data, one should address whether the similarities are significant and the differences can be explained. Based on
this, a range of conclusions can be reached which have
been modified below from McKenna (1986), Silverstein
(1995) and Acharya and Taylor (2003).

Comparing the dental data


The comparison of known antemortem data with the
obtained postmortem data is called comparative identification. Sholl and Moody (2001) have stated that the basic
principle of any method of identification is to determine
that individual characteristics observed postmortem are congruent with those known to have been present in life. Once
the postmortem findings and antemortem records are available, the data can be compared. Comparison should be
qualitative rather than quantitative in nature; it must also be
systematic and methodical. Features compared include dental restorations, pathology, crown, root and pulp anatomy,
associated bony structures, artifacts and dental anomalies.
An individual with multiple dental treatment and uncommon
dental features has a better probability of being identified
than someone with no extraordinary dental characteristics.
Radiographic morphology in dental identification
Presence of restorations are an important component of
comparative dental identification. Sholl and Moody (2001)
have suggested that the incidence of restorative work
among younger age groups in Europe and North America
appears to be declining, probably a long-term benefit of
fluoridation and improved oral hygiene. Hence, there may
be the necessity to rely on other features of the dentition.

Positive identification This indicates that the ante- and


postmortem data match each other with no unexplainable
differences. The identity is proven beyond reasonable doubt
and should include radiographic support.
Probable identification The ante- and postmortem data
have a high level of concordance but a lack of quality
information precludes positive identification. Explainable
differences may exist between the two sets of data and
radiographic support is, usually, not available.
Possible identification The ante- and postmortem data
are in agreement but the available information is insufficient both in terms of quantity and quality. The available
information neither permits a definitive identification nor
enables the identity to be excluded.
Insufficient evidence The available ante- and/or postmortem information are insufficient to form the basis for a
conclusion.
Excludes identity The ante- and postmortem data are
clearly inconsistent; the data contain unexplainable differences that comprehensively indicate a mismatch.
657

Section VIII Forensic Dentistry

Figure 2

Modified Interpol antemortem form

It is necessary for the forensic odontologist to be absolutely certain for an identication to be positive. One also
needs to remember that any attempt at establishing identity
is addressed to the legal authorities. Hence, the report and
conclusion should be as denitive and clear as possible.
Digital radiography in dental identification Traditional
methods of radiography involve the use of film. The advent
of digital radiography over the past decade, which replaces
the radiographic film with an image capturing sensor,
658

presents certain advantages to forensic investigation. Since


the images can be viewed immediately after exposure, the
operator has the choice to either accept or reject the image
depending on its quality. Further, postmortem images may
be retaken to replicate the antemortem radiographic position and angulation. This could be particularly relevant
in postmortem settings where access to radiographic processing may be unavailable or the ability to retake the
radiographs of the decedent at a future date is unlikely.

Chapter 24 Clinical and Radiological Perspective

Hanaoka and colleagues (2001) have successfully used the


technology in postmortem dental identification and predicted its routine application in the future. They have stated
that receiving, sending and storing digital radiographs
through computer networks is effortless. According to
Hubar and Carr (1999) and Du Chesne and associates (1999),
the radiographic image may be enlarged, rotated and its
brightness and contrast modified. Several images may be
viewed together which allow convenient comparison of
ante- and postmortem images. Subtle features difficult to
visualize on conventional radiographs such as trabecular
bone patterns are seen with greater detail digitally and
may further help to corroborate identification of a decedent (Hubar and Carr, 1999). However, manipulations
which distort the structures visible on the radiograph by
changing their angular relationship are not admissible by
the courts of law (Du Chesne et al, 1999). Hence, these
authors have stated that it must not be the objective of
postmortem radiology to manipulate the images to such an
extent that optimal or even misleading results are presented.
While it is reasonable to expect forensic experts to avoid
such alterations on postmortem radiographs, one cannot
be so sure about antemortem digital images. Therefore, the
conclusions based on comparison of post- and antemortem
digital radiographs may be brought into question by the
courts of law, which will probably give greater weight to
documentary evidence such as conventional radiographic
films than electronic data files.

CHALLENGES IN POSTMORTEM
EXAMINATION
Examining dental remains may be challenging in cases of
rigor, incineration and other circumstances. Described
below are some techniques to overcome difficulties, as well
as precautions to be taken while using them.

Rigor Mortis
Limited opening of the mouth due to severe postmortem
rigor will affect dental examination since access to the
oral cavity is limited and viewing the dentition is impaired.
In such cases, where the muscles are extremely rigid, the
mouth will have to be forced open. The use of trismus
screws (made from acrylic) for obtaining initial opening in
the anterior dentition followed by Fergusson or Heister
mouth gags to increase jaw separation at the posterior
region has proven useful in the authors experience.
However, one must be careful not to fracture the teeth.
Nakayama and coworkers (2001) have advocated an intraoral approach for myotomy of the temporalis muscle. They
contend that mouth opening demands relaxation of the
temporalis and, hence, its myotomy will facilitate easy

dental examination. Their method prescribes an intraoral


incision to expose the coronoid process followed by the
insertion of a curved Cooper type scissors through
the incision to dissect temporalis fibers that are inserted to
the top of the coronoid process (Figure 3A, B). The deep
fibers, which may also insert to the mandibular notch, are
drawn forward with a channel retractor for dissection
(Figure 3C, D). The myotomy is carried out on both the left
and right sides.

Incineration
Due to the fragility of dental tissues consequent to fire, it
is essential to maintain their integrity during examination
of charred human remains. According to Delattre (2000),
charred dental remains are by nature rather delicate and
can crumble if not handled cautiously. The color of the teeth,
apparently, gives an indication of its relative fragility
blackened teeth are less fragile than those that are ashen
gray (the appearance of incinerated teeth is described later
in this chapter). The lips and cheek may contract in prolonged or intense fire and withdraw exposing the anterior
teeth. As a result, these teeth are the most exposed to fire
and the enamel and dentin on their anterior surface can
simply crack off when touched. To prevent the loss of tooth
structure, Mincer and associates (1990) have listed a variety of materials that can stabilize incinerated teeth. They
endorse clear acrylic spray paint and cyanoacrylate glue
as the best agents since these are readily available, economical, portable, permeate the teeth well and set fast.
However, in their study, not all specialists surveyed considered reinforcing incinerated teeth essential. Many felt
problems could be circumvented by very careful handling
of the teeth or photographing the teeth prior to handling.
Intraoral radiography without jaw opening can be accomplished by removing the tongue through the floor of the
mouth and inserting the films through the opening. This
has been referred to as the tunneling technique by
Griffiths and Bellamy (1993), who have also suggested the
use of material such as bubble plastic or a sheet of foam to
protect the fragile skeletal and dental remains during
transportation.

Jaw Resection
Depending on the circumstances of death and condition of
the body, the forensic dentist can decide to cut open the soft
tissue of the cheek to reach the teeth, or remove the jaws
entirely. Resected jaws are easier to examine and radiograph.
However, such invasive procedures can pose obstacles,
especially when the body needs to be viewed by relatives.
Furthermore ethical and legal hurdles may be faced.
Therefore, one must consider jaw resection as a last option
and obtain prior permission from the forensic pathologist.
659

Section VIII Forensic Dentistry

Figure 3
A

(A, B) Intraoral approach for myotomy: when the temporalis is attached to the top of the coronoid process, myotomy is
accomplished with scissors only; (C, D) in case the temporalis is attached both to the coronoid and mandibular notch,
a channel retractor is inserted to draw forward the deep end of the muscle to facilitate dissection. (Reprinted from Nakayama Y,
Aoki Y, Niitsu H, et al (2001), Forced oral opening for cadavers with rigor mortis: two approaches for the myotomy on
the temporal muscles, Forensic Science International, Vol. 118, pp. 3742, with permission from Elsevier)

Tooth Colored Restorations

Incinerated Teeth

Tooth colored restorations such as composites and glass


ionomers may be missed during examination. These can be
disclosed using dyes such as mercurochrome or tinted benzalkonium chloride, which are applied on the teeth with
cotton swabs. However, using dyes may leave the oral cavity stained and messy (Clark and Meeks, 1989). Therefore,
Carson and colleagues (1997) have suggested the use of commercially available alternative light sources. They discovered
that tooth colored restorations are best revealed at wavelengths of 415530 nm. This range of wavelength also
revealed restorations when the teeth were burnt, although
standard UV light (350 nm) may have more practical value
in fire-damaged bodies.

The identification and recovery of burnt teeth subsequent to


accidents, arson or terrorist activitieswhere human remains
may only be recovered in partscan assist in establishing the
origin of the remains and help reconstruct the scene.

POSTMORTEM ALTERATIONS TO THE TEETH


AND ORAL TISSUES
While teeth are known for their relative postmortem stability, their appearance may be altered, and this can provide
clues about the circumstances of death.
660

Crown
Muller and associates (1998) have undertaken one of the
few detailed works on changes that teeth undergo when
exposed to high temperatures. They observed that enamel
shows crazing (fine surface cracks) at 150C but retained
its normal color although at 200C, enamel loses its gloss.
Further increase in temperature causes more crazing
initially over the neck, then more coronallyfollowed by
a few frank cracks.
Initial separation of enamel from dentin occurs at 400C
and the enamel shell separates totally at 450C. At 500C,
Harsnyi (1975) has observed deep longitudinal furrows on
the crown which almost divide it into several pieces. At this
temperature, the pulp chamber and root canal are preserved
and not narrowed. Above 500C, the crown undergoes

Chapter 24 Clinical and Radiological Perspective

fragmentation and consistently becomes smaller with further rise in temperature. The narrowed cavities of the pulp
chamber and root canal are recognizable even at 1,100C.
The coronal dentin is exposed at 450C (following total
separation of the enamel shell). Cracks appear at 600C with
disintegration from 800C onward. While enamel is converted to powder, dentin is not. This has been attributed to
hypermineralized pretubular zone of the dentin. Myers
and colleagues (1999) believe that the mineral content of
dentin, located within its organic matrix composed of type I
collagen, helps stabilize the collagen against thermal denaturation and shrinkage. The color changes in the crown
and root at different temperatures has been demonstrated
by Muller and associates (1998) (Table 1). However, these
authors have cautioned that in real-life scenarios, it may be
much more difcult to observe the color changes since teeth
found at the site of re need to be carefully cleaned. They
added that the presence of a supercial metallic layer,

resulting from the dry distillation of organic matter, can


lead to observational errors.
Root
The root shows a light yellow color at 150C and exhibits
a calcinated appearance at 300400C when exposed directly
without protection of the alveolar bone. Further rise in
temperature displays crazing of the coronal one-third of
the root. This progresses to the apical part at a temperature
beyond 800C and the root begins to fragment at 900C.

Root

Off-white to light yellow

200

Crown

Dull, light brown surface

300

Crown

Light brown to grayish with dark brown


spots

Root

Black

Crown

Dark brown/gray

Root

Shiny black

Crown

Enamel is dark brown or gray; dentin is


gray

Root

Gray/brown

Effects of temperature on restorative materials Like


teeth, restorative materials used in treatment are equally
resistant to the effects of high temperature. According to
Rossouw and associates (1999), composites, compomers
and glass ionomers can withstand 250500C for a short
time but, beyond 5 minutes their compressive strength is
reduced to almost zero. Hence, they need to be handled
very carefully. Compomers (14.3%) and glass ionomers
(18.6%) have higher volume shrinkage when compared to
composites (610%). This means that the former restorative materials may get dislodged, especially from the
buccal and lingual preparations. Most tooth colored
restorative materials turn grayish-black at the aforementioned temperatures. Their change in color means that it is
difficult to spot them visually. However, the radiodensity
is not altered and, therefore, they can be viewed on radiographs. Metallic restorative materials melt and distort at
different temperatures: gold alloys melt at 9151,090C;
silver amalgams range depends on the mercury content
(some amalgams may resist up to 870C). Porcelain denture teeth have been cited as resisting temperatures as
high as 900C (Taylor et al, 2002); however, acrylic denture material depolymerizes to monomer at 450C.

Crown

Dark gray enamel and blue-tinted gray


dentin

Postmortem Pink Teeth

Root

Blue-tinted gray with white spots

Crown

Dark gray enamel and blue-tinted white


dentin; the cusp tips are blue

Root

Blue-tinted white or white only

Crown

Dark gray enamel with white spots;


white dentin

Root

White with gray spots

Crown

White dentin

Root

White with dark gray or black spots at CEJ

Crown

White dentin

Root

White with pink tinge at apex

Crown

Chalky white

Root

Chalky white

Crown

Chalky white

Root

Chalky white

Table 1 Color changes in burned teeth


Temperature (C)
150

400
500

600

700

800

900
1,000
1,100
1,150

Appearance
Crown

Normal color and shiny appearance

Source: Modified from Muller and associates (1998).

Pink colored teeth are encountered on occasions during


postmortem dental examinations. This intrinsic pigmentation is believed to be associated with victims of sudden
death (Padayachee, 1988). Van Wyk (1989) cites a number
of studies which suggest that the phenomenon requires
increased blood supply to the pulp. This may be the result
of raised venous pressure caused by an event such as
strangulation (Whittaker et al, 1976) although van Wyk
(1988) could not correlate the cause of death or the time
since death to the presence of pink teeth. Padayachee
(1988) has stated that pink teeth show conspicuous bleeding in the dental pulp and the resultant pigmentation is
thought to be due to an increased pressure in the pulpal
circulation. The phenomenon of postmortem pink teeth is
believed to be analogous to postmortem lividity produced
by the flow of blood into a dependent part of the body
after death (Whittaker et al, 1976; van Wyk, 1987).
According to van Wyk (1988), the blood vessels in the
661

Section VIII Forensic Dentistry

pulp become distended due to pooling of blood. The red


cells undergo hemolysis followed by autolysis of the blood
vessel walls and release of pigment in solution which diffuses into the dentinal tubules. The degree of dentinal
staining varies and van Wyk (1988) concludes that teeth
appear pink clinically only when the dentin is stained
extensively. The pigment responsible for the pink discoloration is undegraded hemoglobin (van Wyk, 1989).

Tongue Hemorrhage
Hemorrhage of the tongue can be observed associated with
strangulation deaths. Bockholdt and Maxeiner (2002) consider tongue hemorrhage to be the result of either cranial
congestion, compression by the dental arches or the hyoid
bone pressing onto the base of the tongue following neck
compression. These authors have reported tongue hemorrhage in 71% of homicidal strangulations, 19% of which were
the result of biting caused by compression of the tongue
between the teeth. However, tongue injury was observed
in only 5% of suicidal strangulations. A protruded tongue,
compressed between the jaws, is observed in a significant
number of suicidal hangings although the number of grossly
visible tongue bites with hemorrhages is small; a similar
small number of internal hemorrhages restricted to the tip
or anterior part of the tongue (development during a protrusion of the tongue in the course of the hanging agony)
are evident. However, extensive internal hemorrhages in
suicidal strangulations should be treated with some degree of
cautionBockholdt and Maxeiner (2002) have cited reports
of internal tongue hemorrhage in victims who were first
strangulated and then hung by the killer (simulated suicide), i.e. extensive internal tongue hemorrhage could indicate a presumed sucide as being a homicide. But they may
also be the result of highly atypical suicidal strangulation.

SOCIAL PROFILING
According to van Wyk (1976), information about habits and
occupational antecedents can be obtained from the dentition.
This can provide valuable information on the persons social
background and prove useful in identification. Based on
personal observation and epidemiological studies, van Wyk
(1976) categorized such features as: (i) lesions of the teeth
only, (ii) lesions of the teeth and soft tissues, and (iii) lesions
of the soft tissues only. This section, however, will emphasize on the lesions of the teeth, since they are more likely
to survive postmortem vagaries than soft tissues.
According to Gustafson (1966), grooving of the upper
anterior teeth may be encountered in cobblers, carpenters
and electricians. Such a groove commonly results from the
habit of opening hairpins with an upper central incisor
the constant abrasion of the metal pin against the tooth
edge eventually leaves a shallow groove. Among pipe
662

smokers, a typical elliptical type of attrition of the anterior


teeth corresponding to the pipe stem is visible. In musicians also, specic form of attrition on the anterior teeth
caused by a musical instruments mouthpiece can be seen.
Padayachee (1988) has highlighted certain forms of occupational staining, e.g. extrinsic staining in industrial
workers has been attributed to exposure to metals and
their salts. He also cited black/gray pigmentation of teeth
in anemics taking liquid iron supplements.
Sociocultural practices such as betel nut chewing prevalent in India also result in characteristic brown deposits
on the teeth (Padayachee, 1988). On the other hand, van
Wyk (1976) draws attention to an unusual sociocultural
custom among a particular group of people from South
Africathe deliberate extraction of the maxillary incisors,
especially in females, to facilitate oral sex.
Probably more unusual is a purported case of selfextraction of the teeth among drug abusers reported by
Pretty and Hall (2004). These authors have suggested that
dentists should consider self-injury as an explanation for
intra- and peri-oral injuries of unknown origin. They add
that the presence of extraction sockets due to self-mutilation
could be a nding in mentally imbalanced individuals or
among those with an altered state of mind resulting from
drug abuse. Bcart and coworkers (1997) have reported
that heroin users have a greater incidence of decayed
teeth, especially atypical carious lesions on the labial/buccal surfaces. These lesions may appear larger, darker and
less painful than usual cervical caries, convincing some
authors to consider them as a pathognomonic sign of drug
addicts (Lowenthal, 1967; Colon, 1972). Pretty and Sweet
(2001) cited a number of studies that also indicate the
presence of dental erosions in drug abusers and alcoholics.
Cattaneo and coworkers (2003) have detected morphine
and codeine in the teeth of skeletal remains found 2 years
after death. They believes that such ndings suggestbut
do not provea drug related death. This not only throws
light on the social antecedents of the unidentied individual but also gives clues to the circumstances surrounding
the death (e.g. drug overdose).

IDENTIFYING THE EDENTULOUS


Borrman and coworkers (1999) have cited studies that project
an increase in the percentage of elderly around the world in
the coming decades. While the percentage of edentulousness
among this group may decrease, the number of edentate individuals may actually remain the same or even increase. From
a forensic odontology point of view, problems arise when
attempting to identify edentulous cases. The absence of a
dental combination may render conventional comparative
identification of little use. In fact, it is believed that most problems in postmortem identification are encountered in complete denture cases (Gustafson, 1966). The denture, however,

Chapter 24 Clinical and Radiological Perspective

can be a crucial piece of evidence in identifying the edentulous as they remain intact or only slightly damaged following
traumatic accidents. Dentures may have been fabricated to
replicate an individuals dentition. For example, Taylor and
coworkers (2002) were able to positively identify an individual based on, among other evidences, distinct features of a
maxillary denture which contained a midline diastema and
gold inlays on two of the teeth (Figure 4). In addition, the type,
size and shape of teeth used in the denture can be used for
identification. This, however, warrants detailed dental records.
Therefore, use of denture-marking systems may be more practical; comparison of palatal rugae may also hold some use.
Figure 4

Characteristic features in a maxillary denture. (Reprinted from


Taylor PTG, Wilson ME, Lyons TJ (2002), Forensic odontology
lessons: multishooting incident at Port Arthur, Tasmania,
Forensic Science International, Vol. 130, pp. 17482,
with permission from Elsevier)

Denture Marking Systems


A widely recommended technique for identifying the edentulous is to mark dentures with the individuals name and/or
a personal number. Markers such as printed onion skin paper
and adhesive labels, electronically inscribed clear laminated tape, photochemically etched microchips (Figure 5)
or typewriter-punched stainless steel bands can be placed
either in the tissue surface during trial packing or in the
polished surface after processing (Borrman et al, 1999). The
materials and the mode of imprint should be strong enough
and preferably resistant to high temperatures expected in
a fire. Moreover the marker should not compromise the denture strength. However, these forms of markingswhere
identity can be revealed easily and publiclymay raise privacy issues. Hence, Rtzscher and associates (1999) have
suggested writing and reading personal data on a microchip by means of a handheld electronic scanner. This personal information pertaining to the individual cannot be
directly viewed but may be accessed using specific computer
hardware and software. Issues of privacy notwithstanding,
marking a denture enables a simple mean to identification
when other methods are unavailable. However, Borrman and
coworkers (1997) highlighted that the denture per se does
not prove identity since it is not a fixed appliance but it is
a significant link in a chain of evidence of personal identity.

Palatal Rugae in Identification


Since denture marking is still an uncommon practice,
alternatives for identifying the edentulous need to be
explored. The use of palatal rugae pattern could prove useful for this purpose. The rugae on the maxilla or maxillary

Figure 5
A

Denture marking microchip with inscription (A) and the microchip incorporated in a maxillary denture (B).
(Reprinted from Rajan M, Julian R (2002), A new method of marking dentures using microchips, Journal of Forensic
Odonto-Stomatology, Vol. 20, No. 1, pp. 15, with permission from authors)

663

Section VIII Forensic Dentistry

denture of the deceased can be compared to previous dentures recovered from the decedents home, or plaster models that may be available with the dentist or laboratory
technician. Palatal rugae are well protected by the orofacial tissues in fires and traumatic accidents. In a recent
pilot study, Muthu, Subramanian and colleagues (2005)
have found that rugae were unaltered in 93% of victims of
third-degree burns; they also discovered that the rugae
withstood decomposition and were recognizable in more
than 80% of the cases. Furthermore, rugae patterns are
unique to an individual and can be used in identification
Limson and Julians study (2004), which obtained highpercentage accuracy in identifying individuals in a simulated ante- and postmortem comparison of the palatal
rugae, bears reasonable testimony to this premise. These
authors employed a softwareRUG FP-ID Matchfor the
comparison. First, rugae outlines on the casts were demarcated using a graphite pencil and photographed. The
image was transferred to a computer where the medial and
lateral ends of the rugae were marked manually (Figure 6).
Based on the principle commonly employed in fingerprint
analysis, the software compared the marked points
between ante- and postmortem cast images to ascertain a
match.

CRANIOFACIAL IDENTIFICATION
In cases where comparative dental identification is not
possible due to reasons such as unavailability of dental
Figure 6

records or unidentified skeletal remains, craniofacial


methods of identification may be applied. The utility of
these methods is variable and may result in establishing
the identity of the deceased or providing broad clues.

Cranial Suture Pattern


The cranial sutures are seam-like joints of bone exclusive to
the skull. As the cranial bones grow and meet, the margins
become highly complex and irregular. In a study of ectocranial suture patterns on 320 skulls, Sekharan (1985) observed
that their configuration differed in every individual (Figure 7),
including twins. He categorized the suture patterns into serrated (saw-like junctions), denticulate (characterized by small
tooth-like projections), squamous, limbous and plane types.
For example, the sagittal, lambdoid and coronal sutures on
the cranial vault can be divided into a number of subdivisions and within these subdivisions one may appreciate serrations and denticulations. Therefore, the patterns produced
by cranial sutures are highly variable and individualistic and
may be used in identification. To accomplish this, however,
antemortem radiographs of the lateral and anteroposterior
view (preferably Townes view) should be available. Sekharan
(1985) observed that the suture patterns, which are visible in
the majority of such radiographs, can be compared with
sutures on forensic skull specimens in situ. Alternatively, he
suggests taking postmortem radiographs and comparing the
suture pattern on these to those on the antemortem radiograph. However, the cranial vault reaches adult dimensions at about 7 years of age. Therefore, one needs to be
cautious while comparing postmortem radiographs of an
adult to those taken during childhood. Recently, Rogers
and Allard (2004) have pointed to the success of viewing
sutures on computerized tomography (CT) scans and recommend this technology over conventional radiography.

Frontal Sinus Configuration

Characteristic points are plotted manually on the rugae


pattern image. (Reprinted from Limson KS, Julian R (2004),
Computerized recording of the palatal rugae pattern and
an evaluation of its application in forensic identification,
Journal of Forensic Odonto-Stomatology, Vol. 22, No. 1,
pp. 14, with permission from authors)

664

The frontal sinuses are irregular shaped, pneumatic cavities


located along the inferior aspect of the frontal bone, deep
to the superciliary arches (Harris et al, 1987). Although absent
or insignificant at birth, it increases in size and complexity with age and attains maximum size by about 20 years
(Schuller, 1943). In fact, Schuller (1943) is attributed having
stated that the radiographic appearance of these sinuses
show individual variation. In a pilot study, Harris and
associates (1987) have also observed that no two frontal
sinuses were alike in terms of height, width and number
of edge loculations, but Schuller (1943) has warned that
certain diseases and disorders may alter the size and shape
of the sinuses. For example, acromegaly renders the
sinuses extremely large while sinusitis can also cause some
changes. Moreover, the sinus walls become thinner in old
age and look larger (Nambiar et al, 1999), although these
changes are minor (Kullman et al, 1990).

Chapter 24 Clinical and Radiological Perspective

Figure 7
A

Cranial suture pattern of different skulls. (Reprinted from Sekharan PC (1985), Identification of skulls from its suture pattern,
Forensic Science International, Vol. 27, No. 3, pp. 20514, with permission from Elsevier)

The radiograph which best reveals frontal sinuses is the


anteroposterior view (especially occipitomental view), a
record which may be available on occasion. Depending on
the condition of the postmortem remains, radiographs from
several views with different angulations and densities may
need to be taken for proper comparison with antemortem
radiographs (Nambiar et al, 1999).
Schuller (1943) attempted to describe frontal sinus conguration and dened seven characteristics:
1.
2.
3.
4.
5.
6.
7.

Septum and its deviation


Upper border (scallop, arcades)
Partial septum
Ethmoidal and supraorbital extensions
Height from planum
Total breadth
Position of sinus midline.

Yoshino and coworkers (1987) have provided a simpler


classification of the frontal sinuses based on the size,

shape, symmetry and septa. However, these categories


may hold little practical value since investigators resort to
simple visual comparison of radiographs placed side-byside or superimposed. Harris and associates (1987) have
suggested tracing the sinus outlines visible on radiographs
onto orthodontic tracing paper for comparison although,
Kullman and coworkers (1990) obtained near 100% accuracy
in a study that compared simulated ante- and postmortem
radiographs per se. The latter also state that successful comparison is not influenced by the experience of the observer.
The frontal sinuses have been used to establish identity
in numerous cases and it has seen an increase in its use
and acceptance among forensic anthropologists and radiologists (Christensen, 2004). However, successful identication using frontal sinuses is contingent to standard
methods of comparison including uniform angulation and
orientation of radiographs taken ante- and postmortem
and substantial empirical evidence pertaining to their
uniqueness.
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Section VIII Forensic Dentistry

Skull-Photograph Superimposition
Superimposing the facial photograph (of the suspected
deceased) and skull was first successfully put to use in a
criminal case by Glaister and Brash (1937). They superimposed antemortem photographic negatives of the heads of
two homicide victims to the respective postmortem skull
radiographs and obtained positive identification. Since the
anterior dentition may be visible on many personal photographs, the use of tooth size, shape, angulations may be of
particular relevance in superimposition. However, adjustments need to be made to orient the ante- and postmortem
images. It is advisable to use superimposition as a corroborative tool, rather than the sole method, for identification.
Actually, it may have more value in exclusion rather than
identification per se. Nevertheless, it gains prominence in
the Indian context since research and case work have been
reported on a regular basis. The infrequent availability of
quality dental records has probably encouraged its use in
forensic identification. It includes photographic superimposition, video superimposition and newer digital techniques.

Camera-object distance: Differences in the focal lengths


of camera lens can alter the contour of high-curvature
areas on the face
Scaling factors: Appropriate magnification of the photograph may be essential to obtain equivalence in size
vis--vis skull specimen.
Figure 8

Photographic superimposition
The conventional superimposition method, photographic
superimposition utilizes antemortem photographs, radiographs or portraits (Nickerson et al, 1991) for comparison
with the skull specimen at hand. The skull is photographed
and its tracing laid over that of the antemortem photograph.
The superimposed images are carefully studied to determine
how closely the skull and face fit each other. The general size
and shape of the skull and bony landmarks such as the orbits,
nasal cavity, dentition, etc. are used to indicate the proximity
of the fit. The facial soft tissue thickness should also be considered during superimposition. Recently, Bilge and coworkers
(2003) have reported a case where identification was established by superimposing a photograph of an unidentified skull
with the antemortem photograph (Figure 8) using commercially available software such as Adobe Photoshop. They
state that the photo-to-photo superimposition technique
is quite a supportive system for positive identification, especially when the questioned person displays uncommon features, and good quality photographs are achieved.
As an aid to enhance the success of photographic
superimposition, Jayaprakash and colleagues (2001) have
suggested that the skull surface details be studied carefully
and correlated to that of the face photograph before drawing a conclusion. The similarity between the dry skulls and
photographs with respect to, for example, the frontal eminence or nasal bone morphology (Figures 9 and 10) can
be correlated adding due weight to the superimposition.
Nevertheless, a number of practical problems may undermine the outcome of photographic superimposition:

666

Angular positioning: The skull and the facial image


should have reasonably equal horizontal and vertical
angulations

Superimposition of the putative deceaseds photograph and


skull. (Reprinted from Bilge Y, Kedici PS, Alako YD, et al
(2003), The identification of a dismembered human body:
a multidisciplinary approach. Forensic Science International,
Vol. 137, No. 23, pp. 1416, with permission from Elsevier)

Figure 9
A

(A) Broad and raised nasal ridge and nasomaxillary


notches in a male skull and (B) the nasal morphology in
the corresponding face photograph. (Reprinted from
Jayaprakash PT, Srinivasan GJ, Amravaneswaran MG (2001),
Cranio-facial morphoanalysis: a new method for enhancing
reliability while identifying skulls by photo superimposition,
Forensic Science International, Vol. 117, pp. 12143, with
permission from Elsevier)

Chapter 24 Clinical and Radiological Perspective

Figure 10
A

image and anatomical landmarks such as the glabella,


nasion, ectocanthion and maxillary dentition compared to
determine the fit of the images. The authors claim gains in
terms of image restoration and enhancement and nearoptimal superimposition as potential advantages of this
technique.

Challenges in Superimposition

(A) Narrow, prominent and wavy nasal ridge, conspicuous


nasomaxillary notches and asymmetric bulge in the lateral
aspects of the nasal ridge in a male skull and (B) the nasal
morphology in the corresponding face photograph. (Reprinted
from Jayaprakash PT, Srinivasan GJ, Amravaneswaran MG
(2001), Cranio-facial morphoanalysis: a new method for
enhancing reliability while identifying skulls by photo
superimposition, Forensic Science International, Vol. 117,
pp. 12143, with permission from Elsevier)

One of the challenges to proper superimposition is to obtain


life-sized enlargement of the photograph to the corresponding skull. The presence of an object of known size on the
photograph is helpful in reaching this end. However, in its
absence, a number of reference points have been suggested.
Sekharan (1971) has recommended measuring the distance
between various anatomical landmarks (gonion, nasion,
menton, etc.) independently on the skull and photograph.
Their ratio are calculated and compared between the skull
and photograph for concordance. However, the use of teeth
to achieve life-sized enlargement may be more reliable.
Teeth are the only craniofacial components visible clinically during life and may be evident on antemortem photographs where the subject is smiling. Hence, dental features
on the photograph, such as the outlines of teeth or intercanine width, can be compared to the same on the skull to
obtain a 1:1 magnication (McKenna et al, 1984).

Video superimposition
The advent of videography led to improvements in conventional still photography superimposition. Video superimposition usually makes use of two video cameras, one
focussing on the skull and another on the antemortem
photograph. The resulting images are mixed into one
composite image (Nickerson et al, 1991) using image mixing devices. The advantage of video superimposition over
photographic superimposition is that the skull can be
placed on a flexible mounting device and its angular position and distance from the camera adjusted according to
the position of face on the photograph. In addition, image
mixers enable added advantage of fade-in and fade-out,
and vertical and horizontal sweep mechanisms. This
allows different images to be progressively superimposed
upon each other.

FACIAL APPROXIMATION

Three-Dimensional Digital Superimposition

According to Phillips and coworkers (1996), facial approximation is a combination of art and science in which a 3D
representation of the facial features is produced using the
skull as foundation. These authors have described the following steps to manually approximate a face: first, one
needs to make an assessment of the ethnicity, sex and age
using the skull bones and teeth. This information can add
value to, and assist in, the approximation. The mandible is
articulated with the skull and jaws and the soft tissue profile is drawn around the underlying bone using average
facial tissue thickness; the nasal profile can be constructed

The use of three-dimensional (3D) superimposition imaging techniques has been suggested by Nickerson and
coworkers (1991). The antemortem photograph is digitized
to produce a two-dimensional (2D) image whereas the
skull is laser-scanned to produce a 3D image. The 2D digitized facial image is mapped onto a polygona process
known as texture mapping. The texture-mapped image
can be manipulated as easily as the 3D skull model. This
texture-mapped image is then projected onto the 3D skull

When virtually no information is available on the identity


of skeletal remains, an attempt at reconstructing the face
from the skull may be considered. Since such a reconstruction usually results in an approximate reproduction of the
target face, the term facial approximation is believed to be
more appropriate. Facial approximation is used as a technique of last resort for identifying individuals in forensic
cases. It can involve 2D sketches using the artists perception
or, as described in the next section, 3D methods which use
clay modeling techniques and computer-generated images.

Clay Modeling

667

Section VIII Forensic Dentistry

at this stage using a cephalograph. The skull cavities (orbits,


nasal fossa, etc.) are blocked with modeling wax and an
impression of the entire skull is made using rubber-base
impression material. The cast is poured in plaster and reference points marked on it; shallow holes are then drilled at
these points. Thin dowel sticks are placed in the holes to
indicate the thickness of facial tissues at these points. The
muscles of facial expression and mastication are reproduced on the plaster cast using modeling clay. Once the
basic face is sculpted, finishing touches such as wrinkles,
hair pattern, eyes, etc. are added. The authors claim that
artistic creativity developed during the method may result
in a more life-like reproduction of the face. However, the
method has a variable success rate, is subjective and, at
best, merely replicates certain facial features which may
be characteristic (Phillips et al, 1996).

Computer-assisted Approximation
Vanezis and associates (2000) have developed a computerassisted 3D facial approximation technique. To begin with,
the defects and natural orifices of the skull are covered
with cotton and the skull placed on a turn-table. The table
is rotated 360 and scanned under a low-intensity laser
beam. This results in the production of 200250 skull profiles which are fed to a computer system to enable viewing
of a 3D skull image (viewing is achieved by means of a
Facial Reconstruction software). The same software is then
used to mark landmarks on the skull image at which the
facial depth has been previously determined (Figure 11).
From a database of facial templates, a face is chosen
which has average features and matches the skull anthropologically; landmarks corresponding in location to those
of the skull are placed on the face (Figure 12). The facial
template is then carefully placed on the skull image so that

the landmarks of the face lie on top of those of the skull;


soft tissue thickness is selected to give the face a thin,
medium or fat appearance. The computer is now ready
to fit the face over the skull which is achieved using a
3D transformation termed warp, resulting in an approximated face (Figure 13). A limitation of this method is that
it relies on the operators ability to select the average
facial templatea procedure that may be inaccurate and
prone to bias. To overcome this, Claes and associates
(2006) have recently developed a facial template that is
based on the features of 118 individuals. This would be a
more realistic average, although the database could be
further expanded. Certain advantages of the computerbased approximation over clay modeling include:

A plaster cast of the skull need not be prepared.


Therefore, it circumvents potential damage to the skull
arising from impression making (Vanezis et al, 2000).
Faster, easier and more efficient generation of approximations (Vandermeulen et al, 2006).
Superimposition of the skull and approximated face
allows the operator to assess soft tissue to skull alignment
and check for any obvious errors (Vanezis et al, 2000).
Multiple approximations, that can take into account
differences in facial appearance due to subject-specific
attributes such as race, gender, age and body mass
index, is possible (Claes et al, 2006; Vandermeulen
et al, 2006).
Facial approximation is by no means a definitive form of
identification, rather a means to it. It can be difficult to
obtain facial models which reflect the exact likeness of a
missing person. However, an image approximated may be
published or broadcast in the media to revive the publics
memory about a victim and obtain further leads. As
Vanezis and associates (2000) point out, the purpose of

Figure 11
A

Views of digitized image of the skull with landmarks in position. (Reprinted from Vanezis P, Vanezis M,
McCombe G, et al (2000), Facial reconstruction using 3D computer graphics, Forensic Science International,
Vol. 108, pp. 8195, with permission from Elsevier)

668

Chapter 24 Clinical and Radiological Perspective

Figure 12
A

Anthropologically matching facial template with landmarks in position. (Reprinted from Vanezis P, Vanezis M,
McCombe G, et al (2000), Facial reconstruction using 3D computer graphics, Forensic Science International,
Vol. 108, pp. 8195, with permission from Elsevier)

Figure 13
A

The facial template has been warped on the skull-image to produce an approximated face. (Reprinted from Vanezis P,
Vanezis M, McCombe G, et al (2000), Facial reconstruction using 3D computer graphics, Forensic Science International,
Vol. 108, pp. 8195, with permission from Elsevier)

facial approximation is to trigger the recognition process


to see whether a name can be put to a face. Once this is
achieved, one can proceed to a more definitive identification using comparative antemortem data.

histologic age has been presented elsewhere (Acharya and


Sivapathasundharam, 2006). In this chapter, a few clinical
and radiographic methods for dental age estimation are
described.

Clinical Methods of Age Assessment

AGE ESTIMATION METHODS


.
Krogman and Iscan (1986) considered age, sex, population affinity and stature to be the four essential parameters in identification of the deceased when no clue is
available. The dentition can reveal the first three of these
parameters. An overview of estimating sex, ethnicity and

Estimating age by observing the teeth clinically is a convenient and economical method. In clinical set-ups, the
age of children is routinely estimated by examining the
type of tooth that has emerged into the oral cavity
although, this method falls short of scientific credibility. A
more objective clinical count of the number of erupted
teeth has also been developed for assessing age in young
669

Section VIII Forensic Dentistry

individuals (Foti et al, 2003), which is described later. In


adults, however, where all the teeth have emerged other
parameters, such as dental attrition, may be utilized.
Dental attrition
According to Solheim (1988), dental attrition has been
used to assess age in archeological and forensic contexts.
An advantage of using attrition in age estimation is that it
is one of the few regressive changes of the teeth that can
be clinically examined. However, the degree of attrition in
modern humans may have reduced as a result of diet that
comprises processed food. Moreover, attrition can be aggravated in certain pathological conditions such as bruxism.
Solheim (1988) assessed attrition in different types of teeth
by measuring the surface area, length of the crown and
certain other criteria, and observed a weak correlation with
age. He further developed multiple regression formulas
which showed that attrition may best be applied for age
assessment using the premolars. However, the author adds
that age estimates from attrition should be based on
examination of several teeth or the entire dentition.

Table 2

Tooth-calcication stages and their coded symbols

Stage

Coded symbol

Initial cusp formation

Ci

Coalescence of cusps

Cco

Cusp outline complete

Coc

Crown 1/2 complete

Cr

Crown 3/4 complete

Cr

Crown complete

Crc

Initial root formation

Ri

Initial cleft formation

Cli

Root length 1/4 complete

Root length 1/2 complete

Root length 3/4 complete

Root length complete

Rc

Apex 1/2 closed

Apex completely closed

Ac

Source: Modified from Moorrees et al (1963).

Demirjians method

Radiographic Methods for Age Assessment


Gleiser and Hunt (1955) first stated that the calcification
of a tooth may be a more meaningful indication of somatic
maturation than is its clinical emergence. Calcification is
a continuous process which can be assessed from radiographs. This relies on stages of tooth formation ranging
from the actual formation of crypt to the fully mature
tooth. There is a continuous change in the shape and size
of the teeth with each tooth following the same sequence.
The radiographic appearance of the teeth may be used for
age estimation even after tooth development is complete,
e.g. deposition of secondary dentin can be viewed indirectly in terms of the size of the pulp chamber.

Estimating Age in Children and Adolescents


Moorrees method
Moorrees and colleagues (1963) categorized permanent
tooth calcification into 14 stages (Table 2). The developing
tooth is compared to a chart and an appropriate development stage assigned. The selected stage is compared to
chronological age-conversion charts. The charts are composed of segments, one for a specific tooth, in which the
chronology of its development is recorded graphically by
horizontal bars for each stage. On the horizontal bar, the
mean age of attainment of that stage and the range (1 and
2 SD) are indicated. A scale is provided at the top and
bottom of the chart for indicating chronological age. The
assessment of tooth formation is recorded by ticking the
appropriate stage for a particular tooth.
670

Demirjian and coworkers (1973, 1976) developed a method


of age estimation which, over the years, has become the
most widely used technique to assess age from the dentition
of children and adolescents. The method utilized seven permanent mandibular teeth on the left side (incisor to second
molar) and did not make use of the third molar. Consequently, it was not applicable to individuals older than 16
years (since the second molar is fully developed by this
age). A recent modification of the method (Chaillet and
Demirjian, 2004) incorporated the third molars allowing
its application to just over 18 years of age. In addition,
the development of each tooth was divided into 10 stages,
instead of the original eight. These stages were numbered
0 (no visible tooth calcification) to 9 (complete closure of
the root apex). Each of the eight teeth on the radiograph is
compared to a chart that contains a diagrammatic representation of the 10 stages and assigned an appropriate developmental stage (any one of 09). Next, corresponding to the
developmental stage, a maturity score is allotted to each
tooth. The maturity score assigned for the eight teeth are
added and a total maturity score obtained. The total maturity score (S) is substituted in regression formulas and the
chronological age derived. Owing to differences in dental
development in males and females, different formulas for age
estimation were developed. In females the formula used is:
Age  (0.0000615  S3) (0.0106  S2)(0.6997  S)
9.3178
In males, the formula used is:
Age  (0.000055  S3) (0.0095  S2)(0.6479  S)
8.4583

Chapter 24 Clinical and Radiological Perspective

The estimated age should accommodate an age range of


 2.65 years for females and  2.28 years for males. While
the method is convenient to use and applied extensively, it
has a few limitations:

Demirjians 8-teeth method was recently tested on an


Indian sample (n  100) by Rimal and Sumanth (2006)
who revealed that the method underestimated age by
1.14  0.34 years. This reinforces long-held observations
that the accuracy of the method varies from one population to another, possibly due to regional variations in
tooth development. Demirjians method was developed on
children of French ancestry and will need local modifications on large samples if it is to be reasonably reliable in
the population to be tested.

respects and not an ideal development marker however, in


the absence of other biological indicators of age in the lateteens and early adulthood, they are used to estimate age
(Mincer et al, 1993). Arany and associates (2004) have
adapted Demirjians developmental stages exclusively to
the third molar and assessed if its calcification can be used
to estimate ages with legal implications (e.g. 14, 16 and 18
years). They calculated a ~97% probability that an individual is at least 14 year old if the root length  crown
height (Demirjians Stage 7); ~93% probability of 16-years
if the root development is complete but apex patent
(Demirjians Stage 8); and ~98% probability of 18-years
if the root apex is closed (Demirjians Stage 9). The latter
has important implications in India and other countries
since 18 years is the age of majority, and the consequent
change in legal outlook toward a persons rights and actions.
Interestingly, third molar develops faster in males, which
is in contrast to the earlier development of all other teeth
in females. One must remember that the probabilities
described above are based on a study on the Japanese and
can vary in different populations.

Open apices method

A Combined Clinical and Radiographic Method

If a tooth is missing, the method may not be used


(unless the tooth is present on the right side).
The 10 developmental stages may not describe the entire
gamut of stages of tooth development.
Choosing a tooth developmental stage may have inherent subjectivity.

A recent age estimation method suggests measuring the


open apices of developing permanent teeth (Cameriere et al,
2006). This method also examined seven mandibular teeth
on the left side, probably to test its effectiveness in age
assessment vis--vis Demirjians original method (1973,
1976). For assessing age, orthopantomographs are digitized
using a flat-bed scanner and the images measured with the
aid of the software Adobe Photoshop. Since measurements
of the open apexes may be influenced by factors such as
radiographic magnification and angulation errors, the ratio
of each tooth apex in terms of the respective tooth length
was obtained. A multiple linear regression equation was
developed from these ratio which estimated age, on the
average, to within 0.04 years of the actual age. The highprecision level in age estimation has been verified by Rimal
and Sumanth (2006) in an Indian sample where, chronological age was marginally underestimated (0.32 years). Accuracy
of the method notwithstanding, the relative effort involved
in measuring the apices and tooth length may preclude its
widespread use, and it is unlikely to replace the acceptance
enjoyed by Demirjians method in the near future.

Third Molars in Age Estimation


With the completion of development of all teeth by about
16 years, the third molars remain the only tooth that continues to develop. Consequently, radiographic evaluation of
third molars is one of the two parameters for age estimation in adolescents and young adults (Arany et al, 2004),
the other being morphological examination of skeletal features. The third molar is the most variable tooth in many

To facilitate clinical age assessment, Foti and coworkers


(2003) have suggested a method which utilizes the number
of erupted teeth. In addition, they also give provision for
using tooth calcification visible on radiographs. Using multiple regression analysis, they presented formulas for age
estimation for different clinical and forensic scenarios. For
example, when the teeth are visible clinically as well as radiographs are available for observing the calcifying tooth germs,
the following formula is recommended:
Age  16.088  (0.226  number of erupted permanent
upper 1st molars)  (1.564  number of erupted
permanent upper 2nd molars)  (0.832  number of
erupted upper 3rd molars)  (0.912  number of erupted
lower 3rd molars)  (1.699  number of tooth germs on
radiographs excluding 3rd molar germs).
There may be instances when partial skeletal remains,
e.g. only the mandible, are recovered and one may need to
estimate the age based solely on clinically visible teeth.
The formula for estimating age from a mandible in such a
scenario is:
Age  9.726  (0.571  number of erupted deciduous
lower incisors)  (0.378  number of erupted permanent
lower canines)  (0.579  number of erupted lower
premolars)  (1.056  number of erupted permanent
lower 2nd molars)  (2.236  number of erupted lower
3rd molars).
Using this method, the authors claim reasonable accuracy in age estimation comparable to those obtained with
Demirjians method. While the technique is promising,
671

Section VIII Forensic Dentistry

it is as yet untested and needs to be validated on diverse


populations.
The accuracy of dental aging is not uniform from birth to
maturity. Age estimation in younger ages tends to be more
accurate since more teeth are calcifying and the intervals
between morphologic stages are shorter and more precise;
in older children, the biological variation increases considerably (Hgg and Matsson, 1985). These authors have
reported an age range of 12 months in younger children
while the same increases to 20 months in older children.
Moreover, the diversity in the rate of dental development
among children and adolescents of different populations
undermines accuracy of the preceding age estimation methods. Development of population-based dental development
standards could render the age estimates more acceptable.

Figure 14
T
P

Estimating Age in Adults


In adults, the teeth are completely developed and one cannot
rely on tooth emergence or stages of calcification for assessing the age. Traditionally, histological methods have been
used for estimating age in this group, most notable of these
being Gustafsons pioneering work (1950) and its subsequent
modification by Johanson (1971). A major disadvantage of
these methods, however, is the necessity to extract and section the teeth. While this may be practical in dead individuals, it is neither possible nor ethical among living adults.
Kvaals radiographic method
A method developed by Kvaal and associates (1995) sidesteps the necessity for extracted teeth in adult age estimation. Their method used the tooth, root and pulp size
measurement of six teeth (maxillary central and lateral incisor and second premolar; mandibular lateral incisor,
canine and first premolar) observed on periapical radiographs. The measurements included several length and
width ratio (Figure 14) such as pulp/root length (P), pulp/
tooth length (R), tooth/root length (T), pulp/root width at
CEJ (A), pulp/root width at mid-root level (C), pulp/root
width at mid-point between levels A and C (B), mean value
of all ratio excluding T (M), mean value of width ratio B
and C (W), mean value of length ratio P and R (L). These
ratio were used to compensate for magnification and angulation errors of teeth on the radiograph. When six teeth
(right or left side) from both jaws are available, the following regression formula can be used:
Age  129.8  316.4  (M)  66.8  (W L).
The length measurements may be recorded using a calliper
however, the widths need to be measured using a stereomicroscopean equipment that may not be available routinely in Indian dental set-ups. Hence, applying this method
on digitized radiographs and measuring the teeth on a computer monitor with accompanying software tools may be
more convenient. Kolltveit and colleagues (1998) first tested
672

Diagram showing measurements made on the radiograph of


each tooth. The ratio of these lengths and widths were used
in age assessment. (Reprinted from Kvaal SI, Kolltveit KM,
Thompsen IO, et al (1995), Age estimation of adults from
dental radiographs, Forensic Science International, Vol. 74,
pp. 17585, with permission from Elsevier)

the efficacy of the method on digitized radiographs and


obtained lower correlation with age. However, more recently,
Bosmans and coworkers (2005) have obtained accurate age
estimates on digital orthopantomographs. Further testing
on conventional and digital radiographs in different population groups will reinforce the validity of this method.

BITE MARK PROCEDURES


Dental identification makes use of the randomness of intact,
diseased, restored and missing teeth. Bite mark investigation, on the other hand, uses the configuration of teeth to
establish the identity of a biter. The size, shape, angulation
and pattern of the biting edges of the anterior teeth in the
upper and lower dental arches can be arranged in 1.36  1026
different ways (Rawson et al, 1984). But the dynamics
involved during production of bite markssuch as movement
of the biters jaw, movement of the victim and flexibility of
the bitten tissuerenders the appearance of the mark highly
variable (Figure 15) and the presumed uniqueness of the dentition may not be depicted on the mark (Pretty, 2006a).
Therefore, investigating bite marks, perhaps, provides the
greatest challenge to forensic odontologists (Brown, 1985).
Bite marks have been described as marks made by the
teeth either alone or in combination with other mouth parts
(MacDonald, 1974). Bite marks may be caused by humans

Chapter 24 Clinical and Radiological Perspective

Figure 15
A

Two distinct bite marks (A, B) on the back of a victim made by the same dentition. In both photographs, mandibular arch mark is
further from the scale. (Reprinted from Sheasby DR, MacDonald DG (2001), A forensic classification of distortion in human
bitemarks, Forensic Science International, Vol. 122, pp. 758, with permission from Elsevier)

or animals; these may be on tissue, edible items or objects.


Biting is considered to be a primitive type of assault and
results when teeth are employed as a weapon of attack,
dominance or self-defense. As a result, bite marks are usually associated with sex crimes and violent ghts. Hence,
matching a bite mark to a suspects dentition may enable
law enforcers to implicate the suspect in the crime.

How Does a Bite Mark Look?


Features of a bite mark
The human bite mark may be identified by its gross, class
and individual features (Sweet, 1995):
Gross features Grossly, a bite mark usually appears as a
circular or elliptical mark with a central ecchymosed area.
The circular/elliptical mark is caused by the dental arches
while the central area of ecchymosis is apparently due to
sucking action or negative pressure created by the mouth.
Class features The marks produced by different types of
teeth are usually distinct allowing one to differentiate the
tooth class. For example, incisors produce rectangular, canines
triangular and premolars spherical-shaped patterns.
Individual features Class features may, in turn, have
characteristics such as rotations, fractures, etc. Such features are known as individual features and render the bite
mark distinct.

Type of Injury
A bite mark may appear as an indentation, contusion, abrasion, laceration or avulsion. Initially, compression of the skin

surface as a result of tooth pressure during a bite causes


indentations. Indentations, while ideal for collecting as evidence and subsequent analysis, seldom persist for long durations unless the victim is deceased. Owing to the elastic nature
of skin, indentations soon disappear and the skin regains
its original contour. This is followed by a brief period
of edema over the bitten area, which usually obscures the
bite mark completely. Once the edema subsides, subcutaneous bleeding becomes apparent. These are referred to as
contusions or bruises and are the most common presentation of bite marks. These appear as reddish/purplish discoloration on the skin surface, a result of blood escaping into
the subcutaneous tissue from ruptured vessels. With increased
intensity of the bite, there may be abrasions and lacerations
of the skin. The most extreme form of bite mark injury is
avulsion, where part of the tissue is bitten off. However, the
forensic significance of a bite mark does not necessarily
increase with the severity of the injury. Pretty (2006b) has
proposed a bite mark severity and significance scale to assist
forensic dentists in determining how valuable a bite mark is
as forensic evidence. The proposed index has two partsa textbased index (Figure 16) and a pictorial guide (Figure 17). As
illustrated in these figures, well-defined bruising and lacerations are usually best suited for forensic investigation.

Site of Injury
Bite marks may be found on any part of the body (Pretty
and Sweet, 2000). However, females are bitten most often
on the breast followed by the arms, legs and thighs while
males are bitten on the arm, hands/fingers and the back.
Interestingly, many of the male victims received bites during the course of a crime committed by them, i.e. they were
bitten by their victims, probably in self-defense.
673

Section VIII Forensic Dentistry

Figure 16
1. Very mild bruising, no individual tooth marks present,
diffuse arches visible, may be caused by something other
than teethlow forensic significance

Increasing severity

2. Obvious bruising with individual, discrete areas associated with teeth, skin remains intactmoderate forensic
significance
3. Very obvious bruising with small lacerations associated
with teeth on the most severe aspects of the injury, likely
to be assessed as definite bite markhigh significance
4. Numerous areas of laceration, with some bruising,
some areas of the wound may be incised. Unlikely to
be confused with any other injury mechanisma high
forensic significance

High
forensic
significance

5. Partial avulsion of tissue, some lacerations present indicating teeth as the probable cause of the injurymoderate
forensic significance
6. Complete avulsion of tissue, possibly some scalloping
of the injury margins suggested that teeth may have
been responsible for the injury may not be an obvious
bite injurylow forensic significance

The bite mark severity and significance scale. (Reprinted from Pretty IA (2006), The barriers to achieving an evidence base for
bitemark analysis, Forensic Science International, Vol. 159S, pp. S11020, with permission from Elsevier)

Differential Diagnosis of Human Bite Marks


Grey (1989) has reported a case where defibrillator paddles
used in resuscitation caused artifacts that resembled
bite marks. He urges caution while investigating what may
appear as a bite mark to the casual eyethings are not
always what they seem to be; care must always be taken not
to misinterpret findings. Other bite mark-mimicking injuries may be caused by:

Hair curling iron


The ends of a pipe
Jewellery
Shoe heel.

These, however, are usually differentiated from true bite


marks by the absence of class characteristics.

Bite Mark Investigation


Any attempt at bite mark investigation should begin with
the following questions (Drinnan and Melton, 1985; Sweet,
1995):

674

Is the injury a bite mark?


If a bite, was it caused by human teeth?
Was it caused by an adult or a child?

Does the age of the bite mark correspond to the time


and type of crime?
Are there unique, individual characteristics in the bite
mark?
Can these characteristics be compared to the teeth of
the suspect?
Once these questions have been answered satisfactorily,
one may proceed with the next stepcollecting bite mark
evidence.

Collecting Bite Mark Evidence


When a suspected case of bite mark is presented, immediately report it to the law enforcement agency and collect
necessary evidence. However, the primary concern is
patient careat no time should collection of bite mark evidence interfere with timely patient treatment. This is especially important since Pretty and associates (1999) have
reported that human bites have a great potential for infection (including HIV, hepatitis B and syphilis), particularly
when the bite injury presents as an abrasion or laceration.
Drawing from the experience and suggestions of accredited forensic dentists, the American Board of Forensic
Odontology (1995) has suggested the following protocol
for bite mark evidence collection.

Chapter 24 Clinical and Radiological Perspective

Figure 17
A

Visual index of the bite mark severity and significance scale. (Reprinted from Pretty IA (2006), The barriers to achieving an
evidence base for bitemark analysis, Forensic Science International, Vol. 159S, pp. S11020, with permission from Elsevier)

Demographics of the Case

Visual Examination and Documentation

Vital information pertaining to the case should be noted


first, e.g. name, age and sex of the victim; case number,
date of examination and name of the examiner(s).

Visually examine the bite mark and document the following:

Location, shape, color and size


Type of injury
675

Section VIII Forensic Dentistry

Contour, texture and elasticity of the bite site


Differences between upper and lower arches, and
between individual teeth

Note: If the victim is dead, examine the bite mark prior


to autopsy (Brown, 1985).

Photographs
High-quality photographs provide a permanent record of
the bite mark appearance. No time should be lost in
obtaining photographs as the injury rapidly changes
appearance due to healing in living victims or postmortem change in the deceased. Color and black-and-white
photographs may be taken using off-angle light source.
Orientation and close-up photographs (Figure 18) should
be taken: orientation photographs depict the location of
the bite mark on the body; close-up photographs of the
bite mark should be made with a rigid reference scalea
ruler, such as the ABFO No. 2 scale, should be placed on
the same plane as the bite mark. The entire scale and bite
mark must be visible on the photograph. A second closeup photograph depicting the bite mark without the scale
can be made to indicate that no portion of the mark has
been concealed by the scale. The camera should be positioned directly over the injury site with the long axis of the
lens perpendicular to the surface of the bitten skinthis
decreases perspective distortion of the image due to offangle camera position (Sweet and Pretty, 2001). If the bite
is on a curved surface and the upper and lower arch marks
are widely spaced, separate photographs of each mark

should be taken. In case of a living victim, photographs can


be repeated every 24 hours for 34 days to record progressive changes in the pattern of bruising (Brown, 1985).

Saliva Swab
It is reasonable to assume that a bite cannot be inflicted
without leaving saliva behind. Saliva deposited in the bitten
area may be a source of cellular DNA, enabling a direct link
to the suspect. Care should be taken not to wash the bite
area before saliva swabbing. According to Clift and Lamont
(1974), the amount of saliva deposited in a bite mark is
about 0.3 ml, distributed over an area of 20 cm2. However,
by the time of evidence collection, the bite area may have
dried up. Therefore, a cotton swab moistened with distilled
or clean tap-water should be used for swabbing. This
rehydrates the dry cells in the bite area. The swab is held
vertical along its long axis making circular motion with
moderate pressure over the bitten surface. A second swab,
which is dry, is used to collect the moisture left on the skin
by the first swab and cells that remain. This constitutes the
double swab technique recommended by Sweet and associates (1997) and is supposed to yield higher amounts of
salivary DNA. Both swabs are then air-dried at room temperature for about 30 minutes. Following this, the swabs
should be placed in paper envelopes to facilitate continued
air circulation around the swab tips (Sweet and Pretty,
2001). These are labeled and stored under refrigeration.
The latter prevents degradation of salivary DNA and bacterial growth in case of delay in lab processing. A third
control swab may be taken from an anatomically similar

Figure 18
A

(A) Anatomical location of bite mark on victims left shoulder; (B) close-up photograph of the bite mark.
(Note: The use of flexible scales is not recommended for bite mark evidence collection and ABFO No. 2 scale (Figure 17)
is preferred). (Reprinted from Pretty IA (2006), The barriers to achieving an evidence base for bitemark analysis,
Forensic Science International, Vol. 159S, pp. S11020, with permission from Elsevier)

676

Chapter 24 Clinical and Radiological Perspective

location outside the bite area and bagged separately. Clark


(1992) has suggested that if the bite has occurred through
clothing, the clothes must also be swabbed. The use of
high-intensity alternative light source (such as UV light) to
locate stains from body fluids enable saliva traces to be
recovered even in the absence of visible bite marks. There
are some disadvantages to salivary DNA analysis, including the need for extensive laboratory equipment and
expertize, high cost and possible degradation of DNA.
Nevertheless, there is an increasing uptake of such technology among forensic dentists (Pretty, 2006a).
Note: Saliva swabs may also be collected according to
the recommendations of the testing laboratory.
Some important steps in managing bite mark cases:

Notify concerned legal authorities and consult a forensic


odontologist.
Record history and perform a detailed physical examination.
Obtain adequate records of the bite marks including:
Documentation
Photographs
Saliva swab.

Obtaining Dental Evidence from a Suspect


The bite mark evidence collected should be complemented
with dental evidence from the suspect who has purportedly caused the bite. Evidence must be obtained in the
presence of law enforcers, using a signed and witnessed
informed consent or a warrant; infection control and
asepsis must be adhered to. Begin by obtaining history of
any dental treatment subsequent to, or in proximity of, the
date of bite mark; follow it up with a detailed extra- and
intraoral clinical examination. Other evidence recovered
should include:

testimony that proves that the evidence has not been altered
or tampered with in any way since it was obtained. This is
necessary both to assure its admissibility in courts of law
and its probative value in preceding investigations.

Analyzing and Comparing Bite Mark Evidence


Ideally, bite mark analysis should begin with a qualitative
and quantitative analysis in situ. This should be followed
by the analysis of life-sized or enlarged photographs.
A separate qualitative and quantitative analysis of the
models and occlusal registrations of the suspects dentition can be performed at this stage. Rather than relying on
the number of teeth depicted in the mark, analyze uncommon characteristics such as presence or absence of a particular tooth, mesiodistal dimension of the teeth and dental
arch, rotation, fracture and diastema. Following this, one
may proceed with the comparison.
According to Sweet (1995), the protocol for bite mark
comparison is made up of two broad categories: (i) metric
analysis, and (ii) pattern association.
Metric analysis The measurement of specific features of
the bite mark and suspects dentition is known as metric
analysis. Measurements may be made on life-sized photographs of the bite mark and include:

Overall size of the mark


Intercanine distance
The length and width of the tooth
Spacing between tooth marks
Rotation from normal arch form.

A similar procedure is employed on the suspects dental


casts. The measurements thus obtained from the mark and
the cast are compared to one another. Simple instruments
like callipers may be used for the measurements. Recently,
computer-based measurements using software such as
Adobe Photoshop have also been used (Johansen and
Bowers, 2000). Metric analysis, however, must be applied
in conjunction with pattern association.

All evidence obtained must be labeled and stored appropriatelythe case number, date, time, place, as well as any
witnesses involved must be recorded at every step of evidence collection to maintain the chain of custody. In practical terms, a chain of custody is the documentation and

Pattern association Matching the conguration of the


bite injury to the arrangement of teeth on the suspects
dental cast is called pattern association. This can be done
by hand-tracing the incisal and occlusal edges of the suspects teeth on transparent acetate sheets and superimposing
these overlays on life-sized bite mark photographs. Sweet
and coworkers (1998) developed a computer-based technique to produce overlays, which was found to be the
most accurate tracing method (Sweet and Bowers, 1998).
Johansen and Bowers (2000) have elaborated on this technique to develop a digital method for bite mark comparison and newer methods have since been reported (Thali
et al, 2003) (Figure 19). The trend today appears to be moving toward the use of computer-based methods (Pretty,
2006a); nevertheless, standardization of the comparison

Photographs of the suspects teeth in occlusion and in


open bite
Maxillary and mandibular impressions made with rubber-base impression material or irreversible hydrocolloid
and models poured in dental stone. It is useful to pour at
least one additional cast of the suspect as backup
Bite registration on a sheet of wax may be obtained in
the absence of impressions
If saliva has been recovered from the bite mark,
swab should be obtained from the suspect for DNA
comparison.

677

Section VIII Forensic Dentistry

Figure 19

However, in a recent review of bite mark analysis,


Pretty (2006a) has warned against considering such a system of conclusion as an absolute interpretation of bite
mark evidence. He believes that existing research data on
physical bite mark comparison is not infallible and has
stressed that to prevent miscarriages of justice it is essential
that odontologists are highly trained, undergo prociency
testing and aim to collect biological evidence whenever
possible. Further, he adds that while presenting conclusions to the courts of law one must avoid overstating the
level of certainty and acknowledge the subjectivity of the
analysis.

LIP PRINT INVESTIGATION

A bite mark is compared to digitized casts of the suspect using


3D/CAD program. (Reprinted from Thali MJ, Braun M,
Markwalder TH, et al (2003), Bitemark documentation and
analysis: the forensic 3D/CAD supported photogrammetry
approach, Forensic Science International, Vol. 135, No. 2,
pp. 11521, with permission from Elsevier)

process is yet to be achieved and conclusion of the analysis is usually based on the experts level of personal experience and judgment (Rothwell, 1995).

Conclusions of Bite Mark Analysis


Levine (1982) has suggested three likely outcomes or conclusions to bite mark comparison, which has been modified
as follows:
Positive identification
There is reasonable dental certainty to indicate that the
bite mark has been produced by the suspects dentitionthis
implies that there are characteristic matches between the
bite mark dimensions/pattern and that of the suspects teeth.
Possible identification
The bite mark and the suspects dentition are consistent
although the suspects teeth could have made the bite mark,
there are no characteristic matches to be absolutely certain.
Excludes identification
The bite mark and the suspects dentition are not consistentfeatures on the bite mark indicate that the suspects
teeth have definitely not caused them.
*These grooves may traverse the lips completely or partially.
678

Lip printthe study of which is called cheiloscopycan


be important in crime investigation (Caldas et al, 2007).
According to Ehara and Marumo (1998), lipstick smears
are frequently encountered in forensic investigations as an
important form of transfer evidence. These researchers
have stated that lipstick smears on the suspects clothing
can indirectly prove a link between the suspect and a
female victim, and smears left on cigarette butts, glasses
or cups can prove a link between a suspect and a crime
scene.
Snyder (1950) is believed to have rst pointed out that
the lines and ssures on the lips have individual variations, much like ngerprints. Renaud (1972) examined lip
prints on 4,000 individuals and found them to be singular.
The uniqueness of lip grooves has also been conrmed by
Tsuchihashi (1974), who studied more than 1,300 lip prints.
These researchers and a few others studied lip prints using
similar classication, a composite of which is:
1.
2.
3.
4.
5.
6.

Vertical grooves*
Branched grooves*
Bifurcated grooves*
Intersected grooves
Reticular grooves
Other grooves (comma, ellipse, triangle, horizontal,
etc.)

Both Renaud (1972) and Tsuchihashi (1974) recorded the


lip pattern of an individual quadrant-wise, i.e. the lips
were divided into four quadrants, much like the dentition
a horizontal line dividing the upper and lower lip and a
vertical line along the sagittal plane dividing the lips into
right and left sides. Grooves in each quadrant of the lip
were recorded according to the above classification.
Suzuki and Tsuchihashi (1975) applied the classication
in two criminal cases, both of which enabled the exclusion
of the suspectsin effect proving the innocence of the

Chapter 24 Clinical and Radiological Perspective

Figure 20
A

(A) Invisible lip print prior to and (B) after developing with lysochrome powder. (Reprinted from Navarro E,
Castell A, Lpez JL, et al (2006), Criminalisitic, effectiveness of lysochromes on the developing of invisible
lipstick-contaminated lipmarks on human skina preliminary study, Forensic Science International,
Vol. 158, pp. 913, with permission from Elsevier)

suspected perpetrators, which is of equal importance as


proving the identity of criminals. These two cases investigated lip prints caused by the use of lipsticks that leave
behind a visible mark. More recently, however, the cosmetics industry has developed lipsticks that do no leave a
visible trace on contact with a surface (Segu et al, 2000).
Such colorless lip prints, too, can be visualized using
developing reagents such as metallic powders (Segu et al,
2000) or lysochromes (Navarro et al, 2006) (Figure 20).
However, developing lip prints on colored or multicolored
surfaces using these reagents may not prove useful due to
contrast problems (e.g. Sudan Blacka lysochrome powder of the same colormay not be useful in developing lip
prints on a black ceramic cup). Therefore, some authors
have advocated the use of uorescent reagents such as
Nile Red (Castell et al, 2005). This reagent can either be
used in powder form or in solution (0.1 mg Nile Red dissolved in 100 ml ethanol). The reagent powder or solution
is applied to the area of interest (with a brush or piece of
cloth, respectively) and visualized under UV or blue light.
The shape, outline and grooves of the lips were discernible
and the authors believe that it has value in identication.

However, further studies on whether the lip prints developed can be accurately compared to those of a suspect are
warranted. According to Tsuchihashi (1974), lip grooves
are on the zone of transition of the lips which, being
extremely mobile, are affected by the pressure applied by
the lips and their direction. Consequently, there is the possibility that lip prints of one individual may be mistaken
for anothers. However, the classication provided and
quadrant-based recording of the lip grooves will probably
render a successful comparison. The suggested method for
comparison is to examine lip prints closest to the mid-line
and then work laterally (Tsuchihashi, 1974). Whether lip
print evidence is admissible in court and can stand the
rigors of legal scrutiny is a matter of debate. According to
Ball (2002), there is very little science and research to support a methodology for collecting and comparing lip print
evidence which has gained acceptance within the forensic
community. Further research to verify the uniqueness of
lip prints, develop protocols for lip print investigation and
establish its accuracy in comparative analysis is essential,
without which it would fail to meet any scientic standards of reliability (Ball, 2002).

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PART

Oral Radiology

II

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SECTION

IX

Basics of
Radiology

25 Basics of Radiation Physics


26 Radiation Biology

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CHAPTER

Basics of Radiation Physics


Ravikiran Ongole

Pioneers in Dental Radiology

PIONEERS IN DENTAL RADIOLOGY


Wilhelm Conrad Rentgen (18451923)
Wilhelm Rentgen, the physicist from Germany is considered the father of diagnostic radiology. Rentgen discovered X-rays in 1895.
Personal life and early years
Wilhelm was born to a German father Friedrich Conrad
Rentgen and Dutch mother Charlotte Constanze on March
27th, 1845 in the small town of Lennep in Rhineland. When
Rentgen was 16 years old he enrolled in Utrecht Technical
School, Netherlands. In 1868, he obtained a diploma in
mechanical engineering from the Polytechnic School in
Zurich. Under the tutelage of AEE Kundt, Wilhelm studied
the properties of gases and obtained a doctoral degree in
1869. After obtaining his PhD, he worked as Kundts assistant at the University of Wrzburg and later elevated to the
post of an associate professor in theoretical physics. Wilhelm
married Anna Ludwig in 1872. She was the daughter of an
inn-keeper and 6 years elder to him. His wife died in 1919,
following a prolonged illness and Wilhelm died due to
intestinal cancer at the age of 73 years on February 10th,
1923. They were buried in Giessen.
Recognition and awards
The University of Wrzburg appointed Rentgen as professor of physics in 1888. Just 6 years later in 1894, he was
chosen as the Rector of the same university. After serving

Intraoral X-ray Units


Components of an Intraoral X-ray Machine
Filters and Collimators

Fundamentals of Radiation Physics


Radiation
Particulate Radiation
Electromagnetic Radiation
Ionizing and Non-ionizing Radiation
Production of X-rays
Properties of X-rays

25

Interaction of X-rays with Matter


Scattering
Absorption

the University of Wrzburg for 6 years as Rector, he took


over as Director of a new physical institute in the University
of Munich. For his outstanding work, Rentgen was
awarded an honorary MD degree by the University of
Wrzburg. He was awarded the Rumford Gold Medal from
the Royal Society (1896) and a gold medal from the
Franklin Institute of Philadelphia. He was honored with
the first Nobel Prize in Physics in 1901. The International
Union of Pure and Applied Chemistry (IUPAC) in honor of
Rentgen, named element number 111 as roentgenium (Rg)
in 2004.
Publications on X-rays
1.

2.
3.

On a New Kind of Rays, A Preliminary Communication. Journal of Wrzburg Physical-Medical Society,


December 28, 1985.
On a New Kind of Rays, Continued. Journal of
Wrzburg Physical-Medical Society, March 9, 1896.
Further Observations on a New Kind of Rays. Journal
of Prussian Academy of Science, March 10, 1897.

William Herbert Rollins (18521929)


William Herbert Rollins was an American scientist and
dentist. He was a pioneer in radiation protection and is
known as the father of radiation protection. It is believed
that he had published over 200 scientific articles regarding
the hazards of radiation. Rollins, although a practicing
dentist, also had a medical degree from Harvard Medical
School. He called X-rays X-light and documented them
685

Section IX Basics of Radiology

extensively in 1904. He is called the Forgotten Man of


dentistry. William Rollins proposed the use of filters to
remove the low energy X-rays from the primary beam and
introduced collimation. He recommended a long targetfilm distance to improve image quality. He pioneered the
sandwiching of the X-ray film between two intensifying
screens to increase the film speed. Dr Rollins advocated the
need to determine a safe and harmless dose of radiation. In
1901, he advocated the use of leaded glasses for radiation
personnel and a lead shield to cover all areas on the
patients body that were not being imaged. Rollins also felt
the need to construct a lead hood that would cover the
X-ray tube head.

Howard Riley Raper (18871978)


In 1909, Dr Howard Raper, was the first to introduce
radiology as a subject in the dental school. He also had
three other firsts to his creditfirst Professor of Radiology,
first academician to teach dental radiology and published
the first textbook dealing with oral radiology titled
Elementary and Dental Radiography, in 1913. In 1917, he
proposed the first model of angle meter used with a chart
of vertical angles for various teeth to avoid distortion.
In 1925, in co-operation with Eastman Kodak Company,
Dr Raper developed the bitewing technique for the detection of interproximal caries.

used to help him to mix materials and take the X-rays.


In 1986, Edmund Kells and Brown Ayres devised a technique
for radiographing the teeth and jaws. Dr Kells, in Dental
Cosmos, mentioned the importance of keeping the film and
object at right angles to the source using a film holder. In
1903, he introduced processing tanks and time-temperature processing. In 1909, Kells cut, wrapped and used rolltype photographic film.

Friedrich Otto Walkhoff (18601934)


Friedrich Otto Walkhoff was a Berlin dentist, a pioneer of
dental X-ray diagnostics and a dedicated fighter for civil
interests of dentists. It was barely 14 days after the
announcement of the discovery of roentgen rays that
Walkhoff wrapped a photographic glass plate in a routinely used rubber dam material and held it with his teeth.
He then laid still on the floor for an X-ray exposure that
lasted a full 25 minutes. This was considered the first dental radiograph. A year later, he managed to take extraoral
radiographs with an exposure time of 30 minutes.

Gordon Fitzgerald (19071981)


In the 1940s, Dr Fitzgerald designed the long cone for the
dental X-ray machine. He published four papers on long
cone technique in the Journal of American Dental Association between 1947 and 1950.

Weston A Price (18701948)


Weston Andrew Valleau Price was a dentist known primarily for his theories on the relationship between nutrition, dental health, and physical health. Dr Price, in 1897,
a founding member of the American Roentgen Ray Society,
designed and patented lead-lined gloves for protection
against X-ray burns, but placed his innovation in the public
domain instead of commanding fees from users. In 1900,
Price designed a celluloid-based dental film. In 1904, he
proposed two techniques for film positioning in the oral
cavity, namely, the paralleling technique and the bisecting
angle technique.

Frank Van Woert (18561927)


Dr Frank Van Woert is credited for his work on the use of
films, film holders and processing of films. He was the first
to use films as image receptors which were developed by
Kodak. He also engineered a metallic holder which could
be used to hold films. His other inventions include the
daylight film processing tank, an improved angle meter
for bisecting angle technique and an automated exposure
timer switch.

Franklin W McCormack
Edmund C Kells (18561928)
Edmund Kells was born in New Orleans, Louisiana, to a
dentist Charles E Kells. He became a dentist, researcher,
and inventor. His experiments caused the loss of most of
his left arm. In 1899, he set up the first X-ray laboratory
(The New Orleans X-Ray Laboratory) for radiographs and
fluoroscopic examinations. He demonstrated the radiograph of chest and hip, a bullet in the head and the measurement of a root canal. He hired the first acknowledged
dental assistantMalvina Cuera, before which, his wife

686

Franklin McCormack, an American medical X-ray technician, employed paralleling technique principles in intraoral radiography. He wrapped the film with a black paper
and used a flat metal plate to make the film packet rigid.
He was also known for using bite blocks and hemostat as
film holders to stabilize the film in the mouth.
Readers are encouraged to visit the website of the
roentgen museum for more information on the chronology of events in origin of radiology (http://www.roentgenmuseum.de).

Chapter 25 Basics of Radiation Physics

Particulate Radiation

Films and Processing of Films


1896:

The exposure time varied between 5 and


15 minutes and the processing time varied between 30 and 60 minutes
1913:
Hand-wrapped, moisture-proof, dental
packet containing two films
1919:
First machine-wrapped dental X-ray
film packet called Regular film (Kodak)
with emulsion on only one side
1920:
Film hangers were introduced
Early 1920s: Cellulose nitrate as base, emitted poisonous gases on burning
1924:
Radia-tized film (Kodak) with double
side emulsion
1924:
Non-flammable cellulose triacetate film
base
1940:
Ultra speed (improved Radia-tized film)
doubled the film speed of the 1924 film
Early 1960s: Polyester film base
1980s:
Ektaspeed film introduced by Kodak

FUNDAMENTALS OF RADIATION PHYSICS


Radiation
Radiation is the transmission of energy through space and
matter. There are two basic forms of radiation, namely,
particulate radiation and electromagnetic radiation.

Particulate radiation consists of a stream of atomic or subatomic particles that transmit kinetic energy by means of
their small masses moving at very high velocities. They may
carry a positive charge (alpha particles), negative charge
(beta particles) or no charge (neutrons). Examples of particulate radiation are alpha rays, beta rays and cathode rays.

Electromagnetic Radiation
There are two concepts to understand electromagnetic
radiation, namely, classical theory and modern quantum
theory. According to the classical theory, the flow of
energy at the universal speed of light through free space or
through a material medium is in the form of the electric
and magnetic fields that make up electromagnetic waves
such as radio waves, visible light, and gamma rays. In
such a wave, time-varying electric and magnetic fields are
mutually linked with each other at right angles and perpendicular to the direction of motion (Figure 1).
In terms of the modern quantum theory, electromagnetic radiation is the ow of photons (also called light
quanta) through space. Photons are packets of energy (h)
that always move with the universal speed of light. The
symbol h is Plancks constant, while the value of is the
same as that of the frequency of the electromagnetic wave
of classical theory. The spectrum of frequencies of electromagnetic radiation extends from very low values over the
range of radio waves, television waves, and microwaves to
visible light and beyond to the substantially higher values
of ultraviolet light, X-rays, and gamma rays.

Figure 1
Propagation vector

Electric field

Magnetic field

Electromagnetic spectrum

687

Section IX Basics of Radiology

Production of X-rays

Figure 2
1
10, 000

Measured in angstrom units

1
1000
1
100
1
10
1

X-ray radiography

10
100

Ultraviolet ray
Sun lamp

1000
10,000
100,000
1,000,000

Measured in meters

X-ray therapy

1
1000
1
100
1
10
1

Light ray
photography
Infrared ray
toaster
Microwave
oven

Radar

10
100
1000
10,000

Television

100,000
1,000,000

Radio

10,000,000
100,000,000

Various energy levels of the electromagnetic spectrum

Ionizing and Non-ionizing Radiation


Radiation has a wide range of energies that form the electromagnetic spectrum (Figure 2). The spectrum has two
major divisions:
1.
2.

Non-ionizing radiation
Ionizing radiation.

Radiation that has enough energy to move around atoms


in a molecule or cause them to vibrate, but not enough to
remove electrons, is referred to as non-ionizing radiation.
Examples of this kind of radiation include radio waves,
infrared, ultraviolet, visible radiation and microwaves.
Radiation that falls within the ionizing radiation range
has enough energy to remove tightly bound electrons from
atoms, thus creating ions.
688

X-ray photons are produced within the X-ray tube by


accelerating electrons with a high voltage and allowing
them to collide with a metal target. This collision results
in the production of X-rays by two basic mechanisms:
Bremsstrahlung radiation and characteristic radiation.
Bremsstrahlung radiation is the major source of X-ray
photons from the X-ray tube. Characteristic radiation contributes only to a small amount of X-ray photons that are
produced from the X-ray tube.
Bremsstrahlung radiation
It is also referred to as braking radiation or deceleration
radiation (Figure 3). Bremsstrahlung is derived from the
German words bremsen meaning to brake and strahlung
meaning radiation. The sudden braking of high speed
electrons at the target produces bremsstrahlung radiation.
When high speed electrons are directed toward the
tungsten target, they interact with the nuclei of the atoms
in the tungsten target in two ways, namely, direct hit and
near miss/wide miss.
Direct hit interaction In this interaction the high speed
electrons collide head on with the nuclei of the atoms in
the tungsten target. However, very few electrons display
such direct collisions. When such a collision takes place,
the total kinetic energy of the high speed electron is converted into a single X-ray photon whose energy is numerically equal to the energy of the high speed electron.
Near miss/wide miss interaction Majority of the interactions of the high speed electrons with the nuclei of the
atoms of the tungsten target are near/wide misses. Because
of the attractive force of the nucleus, the high speed negatively charged electrons are drawn toward the nucleus
(however, does not collide head on), resulting in the deflection of the electron from its original path. This results in
the electron losing some of its kinetic energy, which is
given out in the form of an X-ray photon. The closer the
high speed electron is drawn toward the nucleus greater
will be the stopping/braking effect and resultant energy of
the photon.
Characteristic radiation (Figure 4A, B)
Apart from the direct hit and near/wide misses many of
the high speed electrons interact with the electrons in the
outer orbit around the nucleus. This interaction causes
removal of the electron from its shell, thereby ionizing the
atom. The vacant site in the inner shell produced by the
displaced electron is quickly filled up by another electron
from an outer shell. When the displaced electron is replaced,
a photon is emitted with the energy equivalent to the difference in the two orbital binding energies.

Chapter 25 Basics of Radiation Physics

Figure 3
X-ray photon

Near miss

Direct hit

X-ray photon
High speed electron
Target
Bremsstrahlung radiation

Bremsstrahlung radiation. Courtesy: Dr Jaideep Shekhar

Figure 4
A

Characteristic radiation. (A) Interaction with inner shell electron. (B) interaction with outer shell electron.
Courtesy: Dr Jaideep Shekhar

Properties of X-rays
1.
2.

X-rays are forms of electromagnetic radiation.


They have short wavelength and hence exhibit great
penetrating power.
3. They travel at the speed of light (3 108 meters/second
or 186,000 miles/second).
4. They affect (produce images) photographic plates and
X-ray films.
5. They travel in straight lines in the form of waves.
6. X-rays are made up of small packets of energy called
photons or quanta.
7. They can ionize gases.
8. They cannot be focused using a lens.
9. They cannot be reflected, refracted or deflected by
magnetic or electric field.
10. They can penetrate opaque objects.
11. They follow the inverse square law.

12.
13.
14.
15.
16.
17.

18.

(Inverse square law: For a given beam, the intensity is


inversely proportional to the square of the distance
from the source).
They are invisible to eye and cannot be heard or smelt.
They exhibit properties of interference, diffraction and
refraction similar to visible light.
They produce an electric field at right angles to their
path of propagation.
They produce a magnetic field at right angles to the
electric field and path of propagation.
They do not require any medium for propagation.
X-rays can penetrate liquids, solids and gases. The
degree of penetration depends on quality, intensity
and wavelength of X-ray beam.
They are absorbed by matter, the absorption depends
on the anatomic structure of the matter and the wavelength of the X-ray beam.
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Section IX Basics of Radiology

Figure 5

Figure 6

Wall mounted intraoral radiographic unit

19. X-rays interact with materials they penetrate and


cause ionization.
20. When X-rays fall upon certain materials, visible light
will be emitted called fluorescence.
21. X-rays have the property of attenuation, absorption
and scattering.
22. They exhibit heating effect.
23. They can stimulate or destroy living tissues.
24. They have a germicidal or bactericidal effect.

Mobile intraoral radiographic unit mounted on


a stand with casters

Figure 7

Other biological effects of X-rays are discussed in Chapter 26


on Radiation Biology.

INTRAORAL X-RAY UNITS


Various types of dental X-ray (intraoral radiography) units
are available to suit the needs of the maxillofacial radiology
department.
Majority of the intraoral X-ray units are meant for wall
mounting (Figure 5) or simply xed to the oor. However,
mobile versions are also widely used. These mobile units
comprise of a standard intraoral X-ray unit mounted on
a stand with casters (Figure 6). These are referred to as
stand-type units. These units can be freely moved between
multiple operatories. A few dental clinics prefer the a ceiling mounted version of the X-ray unit.
The ideal location of the X-ray unit (Figure 7) is on
the wall right behind the patients head (12 oclock wall).
Alternatively, mounting the lateral wall is also acceptable
as this allows the X-ray unit to be shared between two
treatment rooms via a lead-lined pass through cabinet.
Over the last few years, portable handheld X-ray units
have gained popularity. These are battery operated (usually rechargeable NiCd), weighing 59 pounds (Figure 8).
Since these handheld devices can be taken from room to
690

Photograph depicting the X-ray unit mounted on the wall


behind the patients head

room, it eliminates the need for multiple X-ray units, and


these can be used effectively in remote rural areas. Studies
have shown that these systems help in reducing the number of repeat radiographs by 50% and are also twice as fast
in taking radiographs compared to the conventional dental X-ray units.
Another recent development in the dental X-ray systems is the use of direct current (DC) for X-ray generation.
Until relatively recently, many of the dental X-ray generators applied alternating current (AC) to the tube when
generating X-rays. Constant potential generators produce
a relatively constant stream of radiation and a greater percentage of higher energy useful radiation.
With an AC generator, voltage across the tube goes
from zero up to the maximum kilovolt peak (kVp), then

Chapter 25 Basics of Radiation Physics

back to zero. This produces X-ray photons of varying


energies. The lowest energy photons are ltered out, but
the average photon energy produced by an AC tube for a
given kVp is still lower than the average photon energy
produced by a constant potential tube at that same kV.
Lower energy photons are more readily absorbed by the
patient, so the more homogeneous beam of higher energy
photons produced by constant potential units may slightly
reduce patient exposure.
When using conventional lm, the lower average photon energy of an alternating current unit will produce
lms of higher contrast than a constant potential unit (for
a given kVp). However, constant potential units typically
operate at 60 or 65 kV compared to the 70 kVp of an alternating unit which brings the contrast levels closer to each
other. While most X-ray units operate at a single, xed kVp,
some models have a facility to vary the kVp settings.
In summary, AC and DC units are both capable of producing diagnostic images whether using conventional lm
or digital radiography. Constant potential units (DC) produce
Figure 8

lower contrast conventional lms compared to AC units


at any given kVp, but these units typically operate at a
slightly lower kV than AC units, which decreases this difference. Constant potential units may reduce patient exposure slightly and may produce more consistent exposures
at the very short exposure times associated with digital
radiography.

Components of an Intraoral X-ray Machine


The intraoral X-ray machine is made up of the following
parts:
1.
2.
3.

X-ray tube head (Figure 9A, B)


Control panel
Swivel arms for maneuverability.

X-ray tube head


It is made up of an evacuated (vacuumed) borosilicate
glass envelope, which encloses the anode and cathode,
power supply circuit, protective lead housing and insulating (coolant) oil between the glass envelope and the outer
protective housing (Figure 10).
Glass envelope (Figure 11) It is made of borosilicate
glass that is evacuated. The glass tube is evacuated in
order to:

Prevent collision of the electrons with gas molecules,


which might reduce their speed.
Prevent oxidation burn out of the tungsten filament.
Anode (Figure 12) The anode is positively charged. It
comprises of a tungsten target that is embedded in a copper stem.
Tungsten Tungsten is chosen as an ideal target material
because of the following reasons:
Portable handheld X-ray unit

It has a high atomic number (74)very efficient for


production of X-rays.

Figure 9
A

(A) X-ray tube head with a long cone. (B) X-ray tube with a short cone

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Section IX Basics of Radiology

Figure 10

4
5

10

11
12

7
9

13

14

15
1. Swivel arms
2. Yoke
3. External housing
4. Step down transformer
5. Step up transformer
6. Borosilicate glass housing
7. Cathode
8. Molybdenum focusing cup
9. Tungsten filament

17
16

10. Electron beam


11. Anode
12. Copper stem
13. Tungsten target
14. Aluminum filter
15. Collimator
16. Primary X-ray beam
17. Position indicating device

X-ray tubeschematic diagram. Courtesy: Dr Jaideep Shekhar

Figure 11

Low vapor pressureit helps in maintaining the vacuum in the tube at high temperatures during the operation of the machine.

The tungsten target is angulated at about 20 to the central


ray of the X-ray beam.
Copper stem The tungsten target is embedded in a copper stem. In order to compensate for the poor thermal conductivity of tungsten, the target is embedded in a copper
stem, which is a good conductor of heat. It carries away
the heat from the tungsten target thereby preventing tungsten from melting at high operating temperatures.
Cathode The cathode is negatively charged. It comprises
of a filament and focusing cup.
Borosilicate glass tube housing the anode and cathode

692

High melting point (3360C)it is a known fact that


almost 99% of the kinetic energy of electrons is converted to heat, therefore making it necessary for the
target to withstand high temperatures.

Filament The filament is made up of tungsten. The tungsten


filament is in the shape of a coil, which is about 1 cm in
length, and the coil of wire used is about 2 mm in diameter.
The coil is mounted on supporting rods that carry the power
supply to the filament. To produce X-rays, the filament is
heated to incandescence using current from a low voltage
source. The tungsten filament in turn gives out electrons at
a rate that is proportional to the temperature of the filament.

Chapter 25 Basics of Radiation Physics

Figure 12

Figure 13

Anode and cathode of the X-ray tube head

Focusing cup The filament lies in the focusing cup. The


focusing cup is made up of molybdenum. It is a negatively
charged concave reflector, which electrostatically focuses
the electrons into a narrow beam that is directed toward
the focal spot.
Power supply circuit The power supply circuit of the X-ray
tube head mainly consists of a step down transformer,
high voltage transformer and electrical insulating oil surrounding the transformers. The transformers are encased
in an electrically grounded metal housing. Other parts of
the power supply circuit are a filament current (mA) control switch and a kilovolts peak (kVp) selector dial.
Step down transformer It helps to reduce the voltage of
the incoming alternating current to about 10 volts. This is
controlled by the mA switch. The step down transformer
provides a low voltage current to heat the filament of the
X-ray tube.
High voltage transformer It helps in generating a high
potential difference between the anode and cathode, thereby
accelerating the electrons from the cathode toward the
anode to generate X-rays.
Electrical insulating oil This oil acts as a coolant as well
as an electrical insulator. The insulating oil aids in dissipation of heat produced by the X-ray tube.
Control panel (Figure 13)
Most of the intraoral machines available have the facility to
adjust the tube voltage and tube current. However, most of
the machines operate at fixed parameters. X-ray machines
used for taking intraoral radiographs are calibrated at
about 6065 kVp and 8 mA.
The exposure time is usually one parameter that the
dentist can control. The exposure time in most machines
can be adjusted from 0.1 to 3 seconds.

Control panel of an intraoral radiographic unit

Working mechanism of the X-ray machine


To ensure a sufficient rate of electron emission, the tungsten filament should be pre-heated to an optimum operating temperature. The timer circuit initially sends a current
through the filament for about half a second to heat
the filament and bring it to an optimum operating temperature. Once the filament is heated to an optimum temperature, the timer applies power to the high voltage
circuit.
However, it is not practical to keep the lament preheated continuously as it shortens the lifespan of the
tungsten lament. Accordingly, it is not advisable to leave
the X-ray machine switched on all through the working
hours.
Dissipation of heat from the X-ray machine It is understood that 99% of the electrons emitted, contribute to the
heat generated within the X-ray machine and only 1%
contribute to X-ray production.
Various methods are employed to dissipate heat from
the X-ray machine:
1.

2.
3.

4.
5.

The X-ray machine should be operated in an air


conditioned environment with the temperature about
1820C.
Presence of an insulating oil or coolant between the
X-ray tube and the outer protective housing.
Embedding the tungsten target in a copper stem.
Copper being a good conductor of heat carries away
the heat from the target.
Angulating the target to about 20 helps in minimizing the heat generated at the focal spot.
Using a rotating anode minimizes the heat generated
during the production of X-rays. A rotating anode
provides a large surface area at the focal spot thereby
aiding in the dissipation of heat.
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Section IX Basics of Radiology

Figure 14

components of the X-ray tube such as the borosilicate


glass envelope, insulating oil and the sealant that prevent
the leakage of the insulating oil, by way of design prevent
low energy X-ray photons to leave the X-ray tube housing. This inherent filtration is equivalent to 0.52 mm of
aluminum.
2. Added filtration Aluminum disks of various thicknesses as per the requirement are placed at the exit
portal.
3. Total filtration It is the sum of both the inherent filtration and added filtration. The amount of filtration required
is based on the tube voltage of the machine that is used.
The quantity of filtration required is expressed as half
value layer.

Photograph showing the aluminum filter at the far end


of the PID

Filters and Collimators


X-rays produced in the X-ray tube exit the glass envelope
through the exit port. Before the X-rays reach the object
to be imaged they pass through the filter and then the
X-ray beam is collimated and directed at the area of interest using the position indicating device (PID).
Filters
X-ray photons produced in the X-ray tube consists of
photons of various energy levels. It is a known fact that
photons of the maximum energy contribute to the production of the latent image on an image receptor system film
and photons of low energy contribute to exposure of the
patient. Studies have shown that the surface exposure levels reduce to about 20% when the X-ray beam is filtered.
Photons of low energy levels have a low penetrating
power and hence do not aid in the formation of an image
of diagnostic quality. It becomes necessary to prevent
photons of low energy and low penetrating power from
reaching the patient. This is achieved by using a lter at
the exit port of an X-ray tube (Figure 14).
Design: The filter is made up an aluminum disc. It selectively allows the passage of high-energy X-ray photons
and prevents the low energy X-ray photons from leaving
the X-ray tube. The aluminum disk is about 0.1 mm in
thickness.
Types of filtration
1. Inherent
2. Added
3. Total.
1. Inherent filtration As the name suggests it is the filtration offered by the design of the X-ray tube. Various
694

Half value layer It is the thickness of aluminum required


to reduce by half the number of X-ray photons passing
through it. For a machine operating between 3070 kVp,
total filtration should be about 1.5 mm and a machine
operating at 90 kVp the total filtration required is about
2.5 mm of aluminum.
Along with aluminum filters, rare earth materials like
erbium, yttrium and samarium have been used as filters. These filters used in conjunction with aluminum
filters further reduce the patient exposure. However, the
exposure time has to be increased by almost 50% and
the contrast, resolution and sharpness of the resultant
image is reduced.
Collimators
Collimator is a metallic barrier with a central aperture,
which is used to contain the size of the X-ray beam to the
required site of exposure. The collimator is generally made
up of a thick plate of lead (radiopaque substance). It is
desirable that the collimated beam should be contained
within a circle having a diameter of 7 cm or 2 inches.
Functions of the collimator
1. Reduces patient exposure by containing the size of
the X-ray beam to the site that has to be exposed.
2. Prevents scattered radiation from reaching the film,
that add to film fog and thereby degrading the diagnostic quality of the radiographic image.
Types of collimators
be classified as:
1.
2.
3.

Based on the shape collimators can

Rectangular collimators
Diaphragm collimators (Figure 15)
Tubular collimators.

A rectangular collimator (Figure 16) reduces the skin surface exposure by almost 60% compared to that of a diaphragm collimator.

Chapter 25 Basics of Radiation Physics

Figure 15

Figure 17

Coherent scatter
Compton scatter
Photoelectric
absorption

Interaction of X-rays with matter

Photograph of a diaphragm collimator with the


central aperture

Figure 18

Figure 16

Coherent scatter. Courtesy: Dr Jaideep Shekhar

Scattering
Coherent scatter

Rectangular collimator

INTERACTION OF X-RAYS WITH MATTER


The X-ray beams that exit out of the X-ray tube interact
with matter that they encounter. Such encounters result in
absorption of scattering of X-ray photons. It is believed
that almost 9% of the X-ray photons pass through matter
without any interaction.

Coherent scattering is also referred to as classic scattering.


It accounts for only about 8% of the total interactions of
X-rays with matter, therefore has a very small role in producing film fog.
When a low energy X-ray photon passes near an atoms
outer electron, it may not be absorbed but scattered without loss of energy. The incident photon interacts with the
electron by causing it to vibrate momentarily at the same
frequency as the incoming photon. Following this interaction, the incident photon ceases to exist (Figure 18).
The vibration causes the electron to radiate energy in
the form of another X-ray photon with the same frequency
and energy as in incident photon. This secondary photon is
emitted at an angle to the path of the incident X-ray photon.
Compton scatter

Types of Interaction (Figure 17)


Scattering
Coherent scatter
Compton scatter

Absorption
Photoelectric effect.

Compton scatter accounts for about 62% of the interactions of X-rays with matter. It occurs when a X-ray photon interacts with an outer electron. The incident photon
collides with the electron, which receives kinetic energy
and recoils from the point of impact. The incident photon
is deflected by its interaction and scattered from the site of
collision (Figure 19).
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Section IX Basics of Radiology

Figure 19

Compton scatter. Courtesy: Dr Jaideep Shekhar

Energy of the scattered photon equals energy of the


incident photon minus the kinetic energy gained by the
recoil electron plus its binding energy. Compton effect
results in loss of the electron, thus ionization of absorbing
atom. The scattered photons travel in any direction. On
reaching the lm, they cause lm fog.

Absorption
Photoelectric effect
Photoelectric effect accounts for about 30% of all the
interactions of X-rays with matter. It is characterized

696

Figure 20

Photoelectric absorption. Courtesy: Dr Jaideep Shekhar

by the absorption of X-rays by matter. It occurs when


incident photon collides with a bound electron in an
atom. During this interaction, the photon ceases to exist
(Figure 20).
The electron is ejected from its shell and becomes a
recoil electron (photoelectron). The kinetic energy of recoil
electron is equal to the energy of photon minus that required
to overcome the electron binding energy.
Photoelectric effect results in electron deciency, which
is instantly lled by an electron from outer orbit with
the release of characteristic radiation, which is absorbed
within the object.

CHAPTER

26

Radiation Biology
Shubhasini AR, Bhanushree R, Praveen BN

Effects on Living Systems

Molecular and Cellular Radiobiology

Deterministic and Stochastic Effects

Patient Exposure and Dose


Reducing Dental Exposure
Conducting the Examination
Protecting Personnel
X-ray Equipment Installation and Related Factors
Shielding
Radiation in the CT Suite

Deterministic Effects on Tissues and


Organs
Effects of Total Body Radiation
Effects of Radiation on Oral Tissues

Radiation Safety and Protection

Sources of Radiation
Natural Radiation
Man-made Radiation

X-rays were discovered in 1895, and since then, these rays


were applied in several fields such as physics, chemistry
and biology. In the beginning, people using these rays
were not aware of the biological effect of X-rays. X-ray
tubes were calibrated based on the erythema produced on
skin when the operator placed his hand in front of the
X-ray beam. There were numerous episodes of injury to
operators and patients. The first biological effects of X-rays
were reported in 1896 and included skin burns, epilation
and eye irritation. In 1906, two French radiobiologists,
Bergonie and Tribondeau described a law which states that
the radiosensitivity of a cell is directly proportional to its
reproductive activity and inversely proportional to its
degree of differentiation.
X-rays interact with atoms and molecules in the body
within pico to femto second (1013 to 1015 s) of exposure.
This reaction may occur directly on biological molecules
or indirectly through the action on water molecules. This
results in the formation of free radicals. Free radicals are
fragments of molecules which have unpaired electrons, and
hence high reactivity. They react with surrounding molecules and become stable by cross-linking or dissociation.
Thus, there is an alteration of cellular molecules which
further results in biological effects.

Dose and Risk in Radiography

Radiation Detection and Measurement


Personnel Dosimetry
Wearing the Dosimeter

Film Exposure and Processing

EFFECTS ON LIVING SYSTEMS


Living tissues may be affected by radiation in two ways
directly by the action on cellular molecules and indirectly
by the action on water. While direct effects account for
one-third of damages, indirect effects account for the
remaining two-thirds.
Direct effect X-rays interact with biological molecules
causing excitation and ionization. This results in the
breakage of chemical bonds in these molecules and results
in the formation of free radicals.
These reactions may be represented as follows:
X-ray photon RH R* H e,
where RH represents a biological molecule such as a carbohydrate and R* is a free radical formed after the loss of
an electron e. Both R* and H immediately react with other
biological molecules either by dissociation:
R* X Y*
or cross-linking:
R* S* RS

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Section IX Basics of Radiology

The altered molecules differ structurally and functionally


from the original molecules resulting in a biological change
in the irradiated tissues.
Indirect effect Water is the most abundant molecule in
living tissues and hence X-rays passing through the body
readily encounter water molecules. A series of complex
chemical reactions then occur in water and finally result
in the formation of highly reactive molecules. This is
termed radiolysis of water.
In the rst step, X-ray photons displace an electron resulting in the formation of positively charged water molecule.
X-ray photon H2O H2O e
This positively charged water molecule reacts with another
water molecule, thus:
H2O H2O H3O OH*
The free electron produced in the first reaction combines
with a water molecule:
e H2O H2O OH H*
The electron may also be dissolved in the solution to form
aqueous electron, eaq.
e eaq
X-ray photons may act directly on water molecules to
produce electronically excited water molecules, which in
turn breakdown to hydroxyl and hydrogen radicals:
X-ray photon H2O H2O* OH* H*
The end result of the radiolysis of water is the production
of OH*, H*, and eaq. All these are highly reactive radicals
and react readily with cellular molecules such as DNA and
lipids.
RH OH* R* H2O
RH H* R* H2
The hydrogen free radical combines with dissolved oxygen
to form hydroperoxyl free radicals:
H* O2 HO2*
These hydroperoxyl free radicals form hydrogen peroxide:
HO2* H* H2O2
HO2* HO2* H2O2 O2
These hydroperoxyl free radicals and hydrogen peroxide
react with biological molecules, alter them and cause cell
destruction.

MOLECULAR AND CELLULAR


RADIOBIOLOGY
Exposure of proteins to radiation leads to changes in their
secondary and tertiary structures although the primary
698

structure remains unaffected. Exposure of enzymes, however, has a cascading effect, since altered enzymes may not
perform their physiological actions, resulting in intracellular molecular alterations. These changes occur at radiation
doses much higher than that which causes cell death.
The nucleus is more often affected due to radiation, but
changes can occur in mitochondria on exposure to higher
doses of radiation. Mitochondria become swollen with disorganization of internal cisternae.

Radiation Effects in DNA


Radiation causes a wide range of lesions in DNA such as:

Single strand breaks


Double strand breaks
Base damage
ProteinDNA crosslinks
Proteinprotein crosslinks involving nuclear proteins
such as histones and non-histone proteins.

Most base damages, proteinDNA crosslinks and protein


protein crosslinks are usually minor damages which can be
repaired and probably play a minor role in carcinogenesis.
Single strand breaks are characterized by damage to a single strand of the helix of DNA and are repaired easily using
the intact strand as a template. However, double strand
breaks, characterized by damage to both strands at the
same site or in close proximity, are more difficult to repair.
Thus, they frequently result in cell death. Fortunately, these
are less common in occurrence. An exposure of 12 Gy to
a cell produces approximately more than 1,000 base damages, about 1,000 single strand breaks and only about 40
double strand breaks.
Cell cycle effects
Dividing cells participate in cell division which, although a
continuous process, can be described in the following
phases:

First Gap (G1) phase or phase characterized by division


of synthesis of organelles
Synthetic (S) phase characterized by division of DNA
Second Gap (G2) phase characterized by preparation
for mitosis
Mitotic (M) phase in which the actual cell division occurs.
Cells not undergoing division remain in G0 phase. Typical
cell division times are 1040 hours with the G1 phase taking
about 30%, S phase 50%, G2 phase 15% and M phase 5% of
the cell cycle time. There are checkpoints at the G1/S and
G2/M boundaries that monitor the accuracy of cell division.
Radiosensitivity differs throughout the cell cycle with
late S phase being most radioresistant, G2/M being most
radiosensitive and G1 phase taking an intermediate position. In G2/M phase, chromatin is tightly compacted and a
poor repair capacity. This explains the high radiosensitivity

Chapter 26 Radiation Biology

of this period. DNA synthesis is almost complete by late


S phase. Damage by X-rays at this phase can be repaired,
and thus the cell is radioresistant at this phase. DNA has an
open structure in G1 phase having a better repair capacity;
this makes G1 phase radioresistant.
Bystander effect
Cells close to irradiated cells but not themselves exposed
to radiation may also exhibit DNA damage and reduced survival. This phenomenon is termed bystander effect. This
may occur due to the damaging signals communicated by
irradiated cells through gap junctions, or through damaging molecules released into the surrounding medium.

DETERMINISTIC AND STOCHASTIC EFFECTS


Radiation exposure can lead to many harmful health effects.
Such effects were classified by International Commission on
Radiological Protection (ICRP) in 1990 into deterministic
and stochastic effects.
Deterministic effects Deterministic effects also called
tissue reactions, refer to those effects in which the severity of response is proportional to the dose. These effects,
usually cell killing, occur in all people when the dose is
large enough. Deterministic effects have a dose threshold
below which the response is not seen. Examples of deterministic effects include oral changes after radiation therapy.
Stochastic effects Stochastic effects also called cancer/
heritable effects, refer to those effects for which the probability of the occurrence of a change, rather than its severity, is dose dependent. Stochastic effects are all-or-none,
i.e. a person either has or does not have the condition. For
example, radiation-induced cancer is a stochastic effect
because greater exposure of a person or population to radiation increases the probability of cancer but not its severity.
Stochastic effects are believed not to have dose thresholds.
ICRP introduced another term detriment to measure the
harmful health effects of low-dose radiation to individuals
and their offsprings. The detriment in a population is dened
as the mathematical expectation of the induction of cancer
and hereditary damage caused by an exposure to radiation.
Detriment is a complex concept combining the probability,
severity and time of expression of radiation harm.

Deterministic Effects on Tissues and Organs


Cellular and tissue response
Based on the law of Bergonie and Tribondeau, cells may be
classified into five groups based on their radiosensitivity.
1. Vegetative intermitotic cells Early precursor cells of
blood cells and spermatogenic cells, and basal cells of oral

mucous membrane are all cells which divide regularly and


do not undergo differentiation. These cells are extremely
radiosensitive.
2. Differentiating intermitotic cells Intermediate precursors of blood cells, spermatocytes and oocytes, dividing
cells in inner enamel epithelium are cells that divide less
frequently and undergo some differentiation. These cells
are less radiosensitive than the first group.
3. Multipotential cells Connective tissue cells such as
fibroblasts, vascular endothelial cells, and mesenchymal
cells are cells that divide when there is a need for more
cells. These cells have an intermediate radiosensitivity.
4. Reverting post mitotic cells Cells such as acinar and
ductal cells of salivary glands, and parenchymal cells of
liver, kidney and thyroid are cells which are differentiated
and specialized in their function. These are divided infrequently and hence are usually radioresistant.
5. Fixed post mitotic cells Cells such as neurons, striated
muscle cells, epithelial cells close to the surface and erythrocytes are cells which are highly differentiated and are
incapable of division. These cells are most resistant to
radiation.
Effects of radiation on tissues
The effects of radiation treatment on normal tissues have
been divided into the following:

Early (or acute) responsewhen clinical symptoms are


seen within a few weeks of radiation treatment. This
response occurs in more radiosensitive tissues.
Late responsewhen clinical symptoms take many
months or years to develop. It occurs in organs where
parenchymal cells divide rarely.

Effects of Total Body Radiation


Acute radiation syndrome
It refers to the various effects on the health of an individual exposed to high doses of radiation. These effects present within 24 hours of irradiation and may last for months.
These have been classified into gastrointestinal, hematopoietic and neural/vascular presentations.
Prodromal symptoms of total body radiation include
nausea, vomiting, fever, headache, fatigue and a brief skin
erythema. These changes occur on exposure to minimum
dose of 1.5 Gy.
Hematopoietic syndrome It occurs after exposure to
27 Gy of radiation. It occurs due to the exposure to active
hematopoietic areas such as sternum and pelvis. This results
in destruction of the blood cell precursors, which in turn
leads to lower levels of peripheral blood cells. Circulating
blood cells themselves are not affected by radiation.
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Section IX Basics of Radiology

Granulocytes which have a short lifespan, are not replaced


by maturation of precursor cells. This predisposes to infections. As thrombocytes disappear in peripheral blood, bleeding ensues. As erythrocytes, which have a long lifespan,
disappear, anemia occurs.
Gastrointestinal syndrome It occurs after an exposure
of about 715 Gy. Exposure of the stomach and intestines
to radiation results in injury to the rapidly dividing basal
epithelial cells. This results in ulceration of the mucosa,
resulting in loss of plasma and electrolytes, bleeding, and
diarrhea. The normal microbial flora invades the mucosa
resulting in septicemia. The combined effects of gastrointestinal and hematopoietic syndromes result in death within
2 weeks.
Neurovascular syndrome It occurs after exposure to
more than 50 Gy of radiation. It is uniformly fatal and
death occurs in 1 or 2 days. It occurs due to extensive
injury to the central nervous system and the vascular system. There may be dizziness, headache, incoordination,
convulsions, and stupor.
Radiation effects in the developing embryo and
fetus
Cells and tissues in embryos and fetuses are more radiosensitive than adult cells. In the early fetus, radiation
exposure has an all-or-none effect, i.e. there is either spontaneous abortion or normal development. The most sensitive period for the occurrence of developmental anomalies
is between 18 and 45 days of gestation. The period of brain
development, from 8 to 15 weeks post conception is also
a very sensitive period. Radiation exposure during this
period may result in microcephaly and mental retardation.
Exposure after this period may result in general growth
retardation and an increased risk for childhood cancer.
However, all these changes occur after exposure to radiation
levels of about 1 Gy, whereas full mouth dental radiography
using a lead apron results in an exposure of just 0.25 Gy.
Radiation-induced heritable diseases
Radiation exposure to germ cells may result in chromosomal alterations which are heritable. The major genetic
effect of radiation is due to microdeletions, which refer to
the deletion of multiple, functionally unrelated but contiguous genes. These effects do not cause death of the individual but result in several malformations such as mental
and physical retardation and various malformations. These
diseases are rare. It has been estimated that the risk of these
multi-organ congenital disorders after exposure to 1 Gy is
approximately 0.1%.
Mechanism of radiation-induced cancer
Exposure to ionizing radiation is an established cancer risk
factor. Cancer risk has been described based on the linear
700

non-threshold hypothesis, according to which, at low doses


and dose rates, total radiation-related cancer risk is proportional to dose. The mechanism of carcinogenesis is thought
to be due to gene mutations. These may not be repaired
and the unrepaired genes may be transmitted to daughter
cells, which may lead to the development of cancer. It has
been suggested that radiation acts as both an initiator and
a promoter of carcinogenesis.

Effects of Radiation on Oral Tissues


One of the modalities used in the treatment of cancer is
radiotherapy. Irradiation of a high dose given to patients suffering from cancer in the orofacial region invariably exposes
the oral tissues. The source of radiation is usually gamma
rays from external source, while brachytherapy with inserted
radon or iodine-125 implants may occasionally be used.
The dose of radiation is about 50 Gy, given in divided doses
of 2 Gy/day.
This results in several effects which are described
below.
Mucositis
The basal layer of the oral mucosa consists of dividing
cells which are susceptible to radiation damage. Death of
these cells results in mucositis. Mucositis begins 1217 days
after initiation of radiotherapy.
Based on severity, mucositis has been classied into
four grades:
Grade 1 Begins at the end of first week of radiotherapy.
Characterized by the presence of white areas in the oral
mucosa due to hyperkeratosis. This stage is usually asymptomatic.
Grade 2 Occurs around the end of second week of radiotherapy. Small areas of ulceration are noted. Patient can
take a soft diet.
Grade 3 Severe mucositis characterized by large ulcers
covered by pseudomembrane. Patient has pain and difficulty in eating and can tolerate only liquid diet.
Grade 4 Even more severe mucositis characterized large
areas of ulceration covering almost the entire oral mucosa.
Patient can consume only liquids, or may need nasogastric
intubation.
Mucositis continues up to the completion of radiotherapy. After this, the mucosa heals and healing is complete
by 2 months. Later, the mucosa tends to become atrophic.
Xerostomia
Salivary glands are frequently in the path of radiation
and are exposed during radiotherapy. The parenchyma of
these glands is radiosensitive, which finally results in a
fibrosis of the gland. This results in a progressive decrease

Chapter 26 Radiation Biology

in salivary secretion, termed xerostomia. This decrease is


dose dependent and secretion reaches zero at about 60 Gy.
Patients complain of dry mouth and difficulty in swallowing. As lubricating properties of saliva are lost and its pH
decreases, demineralization of enamel begins.
Teeth Mature teeth are not affected by radiation, however, radiation doses as low as 400 cGy may retard the
development of incompletely formed teeth. Irradiation to
developing teeth may result in short roots, incomplete calcification, dilaceration, and delayed or arrested eruption.
Radiation caries It is a form of rampant caries that occurs
in individuals exposed to curative radiation. Radiation
causes a change in saliva by decreasing its secretion, lowering its pH, and reducing its buffering capacity. This
reduces the cleansing action of saliva on teeth and results
in accumulation of debris, demineralization, and finally,
rampant caries.
Three types of radiation caries have been described:
Type 1: The most common type. It is characterized by caries occurring around the teeth in the cervical
region. As caries deepens, there is amputation of
the crown.
Type 2: It is characterized by the initiation of caries on all
crown surfaces, eroding away the entire coronal
structure.
Type 3: The least common type. It is characterized by color
changes in dentin resulting in a diffuse blackening or dark brown discoloration of the crown.

radiation and have adequate knowledge regarding the


methods to minimize unnecessary exposure to radiation.
This section will attempt to highlight various measures to
protect the patient, radiation personnel and public from
the long-term hazards of diagnostic radiology.

Historical Events in Radiation Safety and


Protection

Osteoradionecrosis
It refers to the secondary infection of irradiated bone.
Radiation exposure to bone affects the vascularity of bone,
destroys osteoblasts and some osteoclasts. The normal
vascular bone marrow is converted to fatty and fibrous
marrow. Thus, the marrow tissue becomes hypoxic, hypovascular and hypocellular.
If secondary infection is then superimposed on irradiated bone, the bone readily undergoes necrosis. Infection
may occur from sequelae of caries, periodontitis, denturesore or a tooth extraction. Osteonecrosis is more common
in mandible than the maxilla, presumably because of the
rich vascular supply of maxilla, and also since the mandible is irradiated more frequently.
Thus, before the initiation of radiotherapy, the dental
status of a patient should be assessed. Any pre-existing
disease such as caries, periodontal disease, third molar
pathology, defective restoration, etc. should be treated.

RADIATION SAFETY AND PROTECTION


It is imperative that dental professionals as well as the
public are aware of the potential hazards of the ionizing

X-ray induced case of severe dermatitis was published in July 1896. The first dose limit of 10 rad
per day (or 3,000 rad per year) was recommended in
1902 based on fogging observed on a photographic
plate.
The destructive effect of X-rays on living tissues,
such as skin, blood forming-organs and reproductive organs was first evident by the animals studies
performed in 1903.
In 1928, the first formal radiation unitthe roentgen,
was adopted. In 1953 and 1954, the bone marrow
dose limit of 300 millirem (mrem) per week and skin
dose limit of 600 mrem per week was adopted by
ICRP and NCRP (National Council on Radiation
Protection and Measurements), respectively.
An annual occupational dose limit of 5 rem per year
was recommended by ICRP in 1957. A lifetime occupational dose limit of 235 rem for individuals in the
age group between 18 to 65 years and an annual
dose limit of 500 mrem per year to public was recommended by NCRP in 1958. The three parts of
dose controljustification, optimization and limitation was put forth by ICRP, in 1961 (Table 3).
The ALARA (As Low As Reasonably Achievable)
guidelines for radiologic protection for radiation
personnel, the maximum annual radiation dose limit
of 5 rem per year was recommended.
In 1980, ICRP limited the radiation exposure to 10 rem
over any 5-year period and 5 rem in any 1 year. The
public limiting dose as 100 mrem per year averaged
over any 5-year period.

SOURCES OF RADIATION (Table 1, Figure 1)


Radiation is the transmission of energy through space and
matter. It is natural and part of our lives. The radioactive
materials present naturally in the earths crust can be
encountered in the building construction materials, food
substances and the air we breathe. Muscles, bones, and
tissues of our own bodies contain naturally occurring
radioactive elements. It is estimated that about four-fifths
of the average annual radiation dose worldwide is the
contribution from natural radiation.
701

Section IX Basics of Radiology

Table 1

Average effective dose of ionizing radiation from


different sources

Source

Dose (Sv)

Natural
Cosmic

0.4

Terrestrial
External
Radon
Other

0.5
1.2
0.3
2.4

Total
Man-made
Medical (estimated)
Diagnostic X-ray
Nuclear medicine

2
0.5
0.08

Other consumer products


Other
Professional
Fallout
Nuclear fuel cycle
Dental radiology

0.01
0.01
0.01
0.01
2.5

Total

Cosmic sources
It is estimated that cosmic radiation accounts for about
8% of the annual total body exposure.
In different parts of the world the cosmic radiation varies
in dosage due to difference in altitude (radiation doubles for
every 6,000 feet) and magnetic eld. The sources of cosmic
radiation are protons, electrons, X-rays and gamma rays.
Terrestrial sources
Terrestrial sources originate from both external and internal
sources; external sources being soil and internal sources,
including radon and other nuclides that are inhaled or
ingested. Radon contributes 1.2 mSv to natural radiation
and the average whole body radiation from it is 228 mrem
per year. Potassium-40 and carbon-14 are two of the main
enlisted internal sources of radiation. The entrapment of
radioactive materials by the bodys own tissues through
the soil, water and air constitute about 11% of our total
annual exposure.

Man-made Radiation

Figure 1
Nuclear
medicine
4%

Consumer
products
3%

Other
1%

Cosmic rays
8%
Terrestrial
8%
Internal
sources
11%

Sources of radiation
exposure radon
54%
Medical X-rays
11%

Sources of radiation exposure

Natural Radiation
The natural background radiations are from three sources
cosmic radiation, terrestrial radiation and internal radiation.
The annual effective dose of radiation from cosmic and
terrestrial sources is about 2.4 millisieverts (mSv) worldwide. The average whole body radiation to an individual
from background radiation is estimated to be around
620 mrem.
702

Exposure to man-made radiation increases depending on


its usage; place of residence, lifestyle, pattern of house
construction, kind of traveling and smoking also affects
radiation exposure. People residing in the coastal regions
are more protected than airline crew due to the thick cover
of earths atmosphere.
Medical and dental diagnosis and treatment
Medical and dental X-rays account for an average of about
11% of our total annual exposure. But dental X-ray examinations account for less than 1% of the average annual
exposure from man-made exposures. Annually worldwide,
over one billion medical examinations and 300 million dental examinations are performed which include radiation
therapy, nuclear medicine and diagnostic medical exposure.
The average dose received from all medical exposures is
300 mrem which represents six-fold increase in average
medical exposures over the past 25 years. Half of the average
background medical exposure (147 mrem) is from computed
tomography (CT) examinations, a relatively new technology
that has significantly improved diagnostic imaging.
For a professional medical or dental radiologist, technologist or assistant, the occupational dose limit is 5,000 mrem
per year. For the non-medical or dental public, the dose
limit is 100 mrem per year.
Although the risk involved in dental radiography is
very less, it becomes imperative for the practitioner to avoid
even the smallest unnecessary dose of radiation in working area. For this, developing basic concepts on radiation
units and measurements and applying the same for safety
and protection measurement is indispensable (Table 2).

Chapter 26 Radiation Biology

Table 2

Radiation unit conversion factors


Radiation units of measurements

Unit of measure

Conversion equivalent

1 curie

3.7 1010 disintegrations/second

1 becquerel

1 disintegration/second

1 millicurie (mCi)

37 megabecquerel (MBq)

1 rad

0.01 gray (Gy)

1 rem

0.01 sievert (Sv)

1 roentgen (R)

0.000258 coulomb/kilogram (C/kg)

1 megabecquerel (MBq)

0.027 millicurie (mCi)

1 gray (Gy)

100 rad
1 joule/kilogram

1 sievert (Sv)

100 rem
1 Gy Wr

1 coulomb/kilogram (C/kg)

3,880 roentgen

For diagnostic and therapeutic purposes of a patient,


NO LIMIT has been set for the exposure.
Consumer and industrial products
Consumer products account for 3% of annual exposure
(0.10 mSv). To name a fewsmoke detectors, color television, domestic water supply, tobacco products, combustible fuel, dental porcelain, pocket watches are all included
in this group.
Other man-made sources
Workers in mining, milling, nuclear plants including
weapons are occupationally exposed to radiation. Among
these sources strontium-90 and iodine-131 are important.
Strontium-90, a beta emitter gets easily assimilated in bones
and teeth of children and young adults due to its chemical
similarity to calcium. Iodine-131, a gamma emitter gets
accumulated in the thyroid gland. Nuclear power contributes 0.01 mSv annual exposure.

DOSE AND RISK IN RADIOGRAPHY


The goal of health physics is prevention of deterministic
effects and reduction of stochastic effects by minimizing
the exposure of radiation workers and patients during
radiographic examinations. This is usually performed by
the government agency, regulatory bodies, advisory bodies or registered bodies by setting up regulations. This limits
the individuals who are occupationally exposed, patients
and general population, from unnecessarily being exposed
to radiation. This section deals with radiation dose, risk
and limitations in medical and dental radiography.

Dose limits
The regulatory bodies at the international and national
levels, namely, ICRP, its counterpart the NCRP in the United
States, and the Atomic Energy Regulatory Board (AERB) in
India have laid down recommendations for radiation safety
and protection to humans without limiting their beneficial
application. In spite of low dosage in dental radiography,
radiation should be minimized wherever practicable. The
efficacy of radiology department lies in wise choice of
investigative procedures which aims at reduced radiation
exposure and diagnostic accuracy.

Patient Exposure and Dose


Risk estimates
Man-made as well as naturally occurring radiation can
result in birth defects. Six out of one hundred live-births
can present birth defects from natural radiation. This fact
may be explained with the concept that the fetus which
has a rapid rate of development and a yet to be formed
immune mechanism is vulnerable to hazardous chemicals
and infections.
The severity of the complication exhibited by the fetus
depends on the radiation dose as well as the stage of growth
(particularly, specic organ defects) at the time of exposure. Severe birth defects including mental and physical
growth retardation can occur if a pregnant lady is exposed
to a radiation dose higher than 100 rem.
The ignorance period of radiation exposure to birth
defect will be between 812 weeks of gestation period, the
time matching with the non-conformity with pregnancy.
Small head size can result if the radiation received in the
womb is greater than 10 rad. If a dose of 25 rad is received
after 8 weeks of gestation period, mental retardation along
with a small head size is seen.
For public The whole bodys maximum permissible dose
is 100 mrem (1 mSv) in a year or the average dose for
5-year period should not exceed 100 mrem (1 mSv).
For occupational exposure The whole bodys maximum
permissible dose is 2 rem (20 mSv) and over 5 years should
not exceed 100 mSv. The effective dose should not exceed
30 mSv in any single year.

Reducing Dental Exposure


ICRP is a non-governmental, independent organization,
a registered charity, created in 1928 by International
Congress of Radiology, the primary body in protection
against the unwise usage of ionizing radiation in different
fraternity including medicine, dentistry, industry, nuclear
enterprise and also from naturally occurring radiation
sources.
703

Section IX Basics of Radiology

The reports and recommendations of ICRP are published


four times a year in the journal Annals of ICRP. The key
principles of ICRP are:

(American Dental Association) and FDA (Food and Drug


Administration) for dental radiographic examination which
include the following:

1. Principle of justification This means the situation


dependent alteration of radiation exposure should be beneficial for the receiver.

1.

2. Principle of optimization of protection This means to


follow ALARA principle for individual or mass radiation
protection.
3. Principle of application of dose limit This implies for
usage of radiation in different field area, the ICRP dose limit
recommendation should be followed with exception in medical fraternity and unexpected or urgent attention situations.
Patient selection criteria
Clinical examination is a must irrespective of the kind of
receptor and the imaging operating technique. Radiographic
exposure in an asymptomatic patient is non-evidence supportive. But in a symptomatic patient, the images should
be limited to diagnosis and treatment plan in addition to
adherence to published patient selection criteria by ADA

Dose limits
Application

Dose limits
Occupational

Effective dose

Annual equivalent dose


Lens of the eye
Skin
Hands and feet

20 mSv per year,


1 mSv in a year
averaged over a period
of 5 consecutive years
150 mSv
500 mSv
500 mSv

15 mSv
50 mSv

Effective doses from conventional dental imaging techniques in Sv


Examination

Effective dose (Sv)


1.5

Panoramic radiograph

2.724.3

Rem

Sievert

Cephalometric radiograph

Whole body

0.05

Maxillomandibular MSCT

2801,410

Individual organ or tissue other than


the lens of the eye

50

0.5

Lens of the eye

15

0.15

Skin

50

0.5

Typical doses from common diagnostic radiology procedures

Extremity

50

0.5

Examination

Estimated loss of life expectancy from health risks

MSCT: multislice CT.

Skull radiograph
PA chest radiograph

Health risk

704

Public

Intraoral radiograph

Annual allowable occupational dose


Part of the body

Consideration to be given to patients susceptibility to


dental caries and periodontal disease, growth and
development stage and other unambiguous status.

Estimate of reduced life


expectancy (average)

Cigarette smoking20 per day

6 years

Overweight (15%)

2 years

Alcohol ingestion

1 year

All kinds of accidents

1 year

Motor vehicle accidents

207 days

Home accidents

74 days

Drowning

24 days

Natural hazards (earthquake, lightning,


flood, etc.)

7 days

Medical radiation

6 days

Occupational exposure
0.3 rem/yr from age 18 to 65
1 rem/yr from age 18 to 65

15 days
51 days

Effective dose
(mSv)

Equivalent period of
natural background
radiation

0.18

2.6 weeks

0.029

3.4 days

Computed tomography: head

1 year

Computed tomography: chest

88

4 years

Barium meal

2.5 years

PA: posteroanterior.

Dose guidance levels for computed tomography for a typical


adult patient
Guidance levels of dose for diagnostic radiography for a typical
adult patient
Examination
Head

Multiple scan average dose (mGy)


50

Lumbar spine

35

Abdomen

25

Chapter 26 Radiation Biology

Effects resulting from acute whole body external exposure of radiation to men
025 r

25100 r

100200 r

200300 r

300600 r

600 or more

No detectable
clinical effects

Slight transient
change in
lymphocytes and
neutrophils

Nausea and
fatigue with
possible vomiting
above 125 r

Nausea and vomiting


on first day

Nausea, vomiting and diarrhea


in first few hours

Nausea, vomiting and


diarrhea in first few
hours

Latent period up to
2 weeks or perhaps
longer

Latent period with no definite


symptoms, perhaps as long as
1 week

Short latent period with


no definite symptoms in
cases during first week

Delayed effects
may occur

Disabling sickness
not common,
exposed individuals
should be able to
proceed with usual
duties

Reduction in
lymphocytes and
neutrophils with
delayed recovery

Following latent period


symptoms are mild:
loss of appetite,
malaise, sore throat,
pallor, petechiae,
diarrhea, moderate
emaciation

Epilation, loss of appetite,


general malaise and fever,
during second week followed
by hemorrhage, purpura,
petechiae, inflammation of
mouth and throat, diarrhea and
emaciation in the third week

Diarrhea, hemorrhage,
purpura, inflammation
of mouth and throat,
fever toward the end of
first week

Delayed effects
possible, but
serious effects on
average individual
very improbable

Delayed effect
may shorten life
expectancy in the
order of 1%

Recovery in likely
about three months,
unless complicated by
poor previous health,
superimposed injuries
or infections

Some death in 26 weeks,


possible eventual death to
50% of the exposed
individuals for about
450 r

Rapid emanciation and


death as early as the
second week with
possible eventual death
of up to 100% of
exposed individuals

r: Rads.

NCRP and ICRP radiation protection recommendations


Recommended annual limits for human exposure to ionizing radiation
Recommendation

NCRP

ICRP

Relative to stochastic
effects

50 mSv annual effective dose limit and (10 mSv)


(age [yr]) cumulative effective dose limit

50 mSv annual effective dose limit and 100 mSv in 5 years


cumulative effective dose limit

Relative to deterministic
effects

150 mSv annual equivalent dose limit to lens of eye


and 500 mSv annual equivalent dose limit to skin and
extremities

150 mSv equivalent dose limit to lens of eye and 500 mSv
annual equivalent dose limit to skin and extremities

Occupational dose limits

Non-occupational (public) dose limits


Relative to stochastic
effects

5 mSv annual effective dose limit for infrequent


exposure and 1 mSv annual effective dose limit for
continuous exposure

1 mSv annual effective dose limit and if higher, not to exceed


annual average of 1 mSv over 5 years

Relative to deterministic
effects

50 mSv annual equivalent dose limit to lens of eye,


skin and extremities

15 mSv annual equivalent dose limit to lens of eye and 50 mSv


annual equivalent dose limit to lens of eye, skin and extremities

Embryo/fetus

0.5 mSv equivalent dose limit per month after


pregnancy is known

2 mSv equivalent dose limit after the pregnancy has been


declared

Negligible individual dose

0.01 mSv annual effective dose

None established

2.
3.
4.

Radiographs based on sound professional judgment


on clinical diagnosis and treatment plan.
To avoid routine dental radiographs for all patients at
preset intervals.
Prescription of dental radiograph may be based on
clinical suspicion of oral disease secondary to medical
or dental history.

5.

6.

For a referred patient, the clinicians first option should


be to obtain all the previous medical and dental records
including radiographs from previous health care providers which help in comparing as well as future
investigations and treatment protocols.
For female patients under gestation period, it is best
to adhere to FDA selection criteria guidelines. In these
705

Section IX Basics of Radiology

7.

patients, to prevent the transmission of diseases from


mother to fetus through dental diseases and to diagnose and manage the same, dental radiographs become
obligatory.
Patients under treatment for head and neck malignancy,
no special consideration is necessary as the risk of developing oral diseases is of high rate rather than the
diagnostic usage of X-ray exposure for review patients.

Conducting the Examination


As the patient selection for radiographic examination is
justified, the choice and operation of the equipment, the
radiographic technique, processing and interpretation of
the image, will also have an impact on patient radiation
exposure. Conducting examination should be under protection beneficiary for both patient and the operator.
Choice of the equipment
A boon to the modern dental health care is to have
qualitative diagnostic radiographs which are preliminarily
as a result of good X-ray equipment with certain basic
requirement.
1. Control panel requirements
a. Warning signals incorporation: (i) during unauthorized usage, (ii) during X-ray emission
b. X-ray machine status indicators: should alert
(i) when energized to produce X-rays, (ii) when a
single control panel is controlling multiple X-ray
tubes, each X-ray tube should have a separate
indicator during ready for usage and one usage
at a time by interlock option.
2. Irradiation switch: Must be an intentional pressure operator. If cable mounted or wall mounted, the exposure
timer should be placed about 1012 feet away from
the X-ray tube.
3. Exposure parameters indicators: Indicators like electrical
meters are advisable for adjustable X-ray tube voltage, X-ray tube current and timer. For non-adjustable
indicatorspermanent markers or labels can be sufficient.
4. X-ray tube voltage: To operate the X-ray tube, the
minimum tube voltage should not be below 50 kilovolt peak (kVp). The actual kVp should not deviate 7%
the selected value from the manufacturer.
5. X-ray tube current: The actual value should not depart
5% by the manufacturer specification.
6. Timer: It should be
a. An automated electronic timer
b. An automated or manual preset loader with zero
or OFF position starter set
c. Automated termination after each exposure
d. The maximum pre-settable irradiation time should
be within 5 seconds, or the time required to deliver
50 milliampere-seconds, whichever is shorter.
706

7. Filtration: Radiation absorbing filters, aluminum, the


degree of attenuation should not be less than the halfvalue layer of the X-ray beam.
8. X-ray tube mechanical stability: Within the tube housing, the X-ray tube should be aligned and precisely
fixed by mechanical means without vibration, drift or
movement.
9. X-ray tube protection: By enclosing within shielded
housing. The housing should be leakage proof and
should not exceed 0.87 mGy (100 mR) in 1 hour. The
tube leakage is measured at a distance of 1 m in any
direction from focal spot.
10. Position indicating device (PID): It must be open
ended. Pointed cone or close ended applicators should
not be used. It limits the minimum focal spot to skin
distance above 18 cm.
11. Beam limiting devices: These are collimators at the end
of applicators, round or rectangular size with the size
of 7 cm or 38.5 cm2 for round and rectangular collimators, respectively.
Panoramic X-ray equipment
1.
2.

3.

4.

Position-indicating device: should not be less than


15 cm.
Collimators: should be of scanning slit dimension or
2% of the focal spot to image receptor distance,
whichever is less.
Cassette carrier: should be irradiation proof and interlocked. Irradiation is possible only with film cassette
in the cassette carrier.
Timer: The maximum presettable irradiation time must
be within 25 seconds, or the time required to deliver
250 milliampere-seconds, whichever is shorter.

Cephalometric X-ray equipment


Collimator The central beam of X-rays should be fully
blocked by the film cassette at the focal spot to film distance. The round collimator should provide the central
X-ray beam size within 30 cm in diameter or with the
rectangular collimator, 800 cm2 area, at a distance of 1.5 m
or maximum focal spot to film distance, whichever is
less.
Film receptors
The film speed standard was pioneered by the American
National Standards Institute and the International
Organization for Standardization. A, B, C, D, E and F film
speeds are available in dental radiography with A-speed
being slowest and F-speed being the fastest (Figure 2). The
exposure to the patient will be reduced by 50% without
forfeiting the diagnostic quality by the faster films. So the
films lesser than E-speed are not desirable to be used in
dental radiography.

Chapter 26 Radiation Biology

Figure 2

Typical doses from dental radiographic examinations


Acceptable X-ray exposure ranges speed
groups D, E and F film

600

Examination

Effective
dose (mSv)

Equivalent period of
natural background
radiation

2 X bitewings, 70 kV, 200 mm


FSD2, rectangular collimation,
E-speed film

0.0023

8.8 hours

2 X bitewings, 70 kV, 200 mm


FSD2, round collimation,
E-speed film

0.0043

17.5 hours

2 X bitewings, 5060 kV,


100 mm FSD2, round
collimation, E-speed film

0.0083.7

1.5 days

2 X bitewings, 5060 kV,


100 mm FSD2, round
collimation, D-speed film

0.0163.5

3 days

Dental panoramic, rare earth


intensifying screens

0.0074

1.3 days

Dental panoramic, calcium


tungstate intensifying screens

0.0144

2.6 days

550
500
450

mA of 103 Gy

400
D

350
300

250
200
F
150
100
50
0
50

60

70
80
Kilovoltage

90

100

Relationship between surface exposures delivered to


a patient by exposure of group D, E, F intraoral films and
diagnostic density at various kilovoltages

Intensifying screens used in extraoral lms reduce the


patient exposure to radiation. This accounts to 55% reduction with rare earth intensifying screen compared to its
contemporary calcium tungstate intensifying screens. The
phosphor crystals in the intensifying screen uoresce when
exposed to radiation and in turn that light exposes the
lm aiding in reduced exposure.
Film storage
For film storage, dry and cool area is preferable. The limitation for radiation perception before use should not exceed
1.75 Gy (0.2 mR). Shielding of film storage is time dependent and 1.5 mm of lead shielding is sufficient for all kinds
of workload facility.

Digital Radiography
Numerical formatting with networked computer system in
obtaining high quality image constitutes digital radiography.
This adopted software technology in imageology has the
additional advantage of reduced exposure to both patient
and operator, speedy recovery of the image, digital storage
of the image with its electronic transmission, discontinuation of chemical processing and its associated hazardous
wastage, elimination of lead foil, saving darkroom equipment and adjustable diagnostic quality of the image.

Intensifying Screen
The rare earth phosphors in modern intensifying screens
emit green light on interaction with X-rays. The rare earth
intensifying screens decrease patient exposure up to 55%
in panoramic and cephalometric radiography.
A further reduction in patient exposure during extraoral radiography may be achieved with the use of T-grain
lm. Introduced as T-Mat by the Eastman Kodak Company
in 1983, this lm contains silver halide grains that are
tabular or at in shape. With its at surface and greater
cross-section oriented toward the X-ray source, it can
gather more light from intensifying screens.
T-grain lm used with rare earth screens is twice as fast
as calcium tungstate screen-lm combinations and thrice
as fast as conventional rare earth screen-lm combinations
with retained image quality. The T-grain technology was
incorporated into intraoral lm by Kodak to achieve the
faster speeds of E and F lms.
Extraoral lms exposed by intensifying screens achieve
a level of image resolution that is about half of the direct
exposure intraoral lm. One reason for image degradation
in extraoral imaging systems is crossover; which refers to
the loss of image sharpness and resolution resulting from
light emitted by one screen passing through the X-ray lm
to expose the emulsion on the opposite side of the double
emulsion lm. The Ultra-Vision (DuPont) and Ektavision
(Kodak) screen lm systems were designed to minimize
crossover by using phosphors that emit ultraviolet light,
which is less able to pass through the lm base to expose
the opposite emulsion.
707

Section IX Basics of Radiology

Results have shown that images produced by these systems have higher resolution than corresponding rare earth
screen-lm systems. This allows for the use of a screen
one speed class higher and a 50% reduction in patient
exposure.
Unlike digital intraoral imaging, there is no signicant
dose reduction to be gained by replacing extraoral screenlm systems with digital imaging. Image resolution with
digital systems appears to approach that obtained with rare
earth regular-speed screens matches with T-Mat lm.

Source to skin distance


Distance is one of the important parameter in reducing the
exposure to an individual. Source to skin distance is one
of the parameters in reducing the exposure to an individual. The inverse square law, I/d2 is pertinent, which states
that exposure and distance are inversely proportional. If
the distance is doubled, the exposure is reduced by fourfold. I stands for intensity of radiation and d stands for
distance.
Source to image receptor distance (SID)

Grids
Grids are the devices used in extraoral radiography to
improve the image quality by reducing the scattered radiation. Though the grids require slightly higher exposure, the
advantage of obtaining high quality radiographs, transcend
the minor risk of increased radiation dose to the patient.
This in turn reduces the repeated chance of exposure.

Figure 3
16" distance

The appropriate SID is another distance related parameter


in reducing the patient exposure and also repeated exposure. Concentration of photons in patients has direct relation with SID. Longer the SID, lesser is the exposure due
to less divergent beam (Figure 3). Shorter the SID, greater
is the exposure secondary to concentration of photons.
Variation in SID results in compromised film density. So,
it is advisable to stick to recommended standardization.
The primary beam should be within 2% of the SID.
Collimation

8" distance

Source to image distance

Image
Film

Collimator reduces the radiation exposure by limiting the


primary and scattered beam of radiation which sequentially
helps in recuperating the image quality. The central X-ray
beam should be within the minimum coverage area. The
Federal Regulation (US) has recommended the restricted
diameter of collimator beam to 2.75 inches at the patients
face. To reduce the radiographic exposure in intraoral
radiographs, an inbuilt rectangular collimator in radiographic machine can be a complimentary (Figure 4). This
will reduce the radiation dose up to five-fold in comparison
with the circular ones.

Figure 4

Round and rectangular collimators

708

Chapter 26 Radiation Biology

Figure 5

Skin entrance exposure


Patient examination view

Skin entrance exposure

Dental bitewing (3 inch diameter


area)

300 mremfilm
90 mremdigital radiography
140 mremcomputed
radiography

Chest X-ray (14 17 inch area)

20 mrem

Abdominal film (14 17 inch area)

300 mrem

Lumbar spine (14 17 inch area)

350 mrem

Extremity X-ray (8 10 inch area)

30 mrem

Skull X-ray (8 10 inch area)

100 mrem

Breast (mammogram) (glandular


tissue dose)

175 mrad

Long position indicating device

lter and for above 70 kVp, 2.5 mm aluminum lter are the
recommendations.

Figure 6

Lead aprons and collars


Tube head

Cylinder tip

Cylinder

Lead
diaphragm
Aluminum filter

Aluminum filter

Position Indicating Device


A long position indicating device (PID) with open ended
and metallic lining reduces the radiation exposure by
restricting the primary beam and reducing the tissue volume exposed to radiation (Figure 5).
Filtration
The aim of filtration is to reduce the patient exposure by
absorbing low energy photons from beam of X-rays which
do not have any role in the diagnostic image (Figure 6).
Absorption of low energy photons increases the mean
energy of the primary beam in addition to its penetrating
power.
There is 20% reduction in exposure with an inbuilt
X-ray machine of 3 mm of aluminum lters. So half-value
layer is designated for specic amount of ltration in dental
X-ray machines operating at a choice of kilovoltages. For
X-ray machines operating at 5070 kVp, 1.5 mm aluminum

Lead aprons and thyroid collars are the patient protecting


equipments used against scattered radiation. The recommended lead shielding outfit for radiation workers is of
0.5 mm thickness. These protecting equipments are strongly
recommended for children and pregnant women as they are
susceptible to radiation effects but not to all adult patients
if recommended guidelines are followed stringently. As
part of maintenance and long shelf life, the leaded shields
should always be hung and not folded to prevent crack
formation.
Film and sensor holders
The clear-cut alignment of the collimated beam with the
teeth or jaws can be achieved through the film holder or the
digital sensor holders. In addition, PID also helps in proper
alignment and prevention of cone cut images. This will prevent the repeated unnecessary unacceptable images. Among
intraoral periapical radiographic techniques, paralleling
technique will reduce the exposure to more than half the
bisecting angle technique which is mainly based on the
alignment of the film holder with the PID. For safety infection control, disposable holders or sterilizable ones are
recommended.
To reduce the radiation exposure to the clinician, he/she
should not hold the holders during exposure. Under extraordinary situation, the patient attender should be under
moderation to hold the lm after being prepared with
appropriate shielding.
Kilovoltage
Kilovoltage is the energizing exposure factor that controls the
X-ray beam. This operating potential affects the radiation
709

Section IX Basics of Radiology

dose and the backscatter radiation. Though the operating


potential of dental X-ray machine ranges between 50 and
100 kVp, the operating potential between 60 and 80 kVp is
the most useful for diagnostic purposes. For less than
60 kVp machine, an internal installation of aluminum filter makes the mean beam energy to 60 kVp.
As the kVp increases, there will be an increase in the
effective energy of the X-ray beam and image contrast
will decrease. This helps in visualization of smaller difference in density within the object, better resolution and
reduction in the effective dose, for example, in periodontal
diseases.
As the kVp decreases, there will be decrease in the
effective energy of the X-ray beam and image contrast
will increase and there will be higher entrance skin dose,
for example, in visualization of caries and soft tissue
calcication.
The introduction of constant-potential (fully rectied),
high-frequency or direct current (DC) dental X-ray units
have made possible the production of diagnostic quality
radiographs with lower kilovoltage and at reduced levels
of radiation.

always beneficial to humans. Therefore, we should respect


radiation rather being afraid of it.
In spite of less radiation exposure to dental professionals compared to other fraternity, it is indispensable to
minimize occupational exposure to ionizing radiation. For
a health care worker, the maximum permissible annual
dose limit is 50 mSv and maximum permissible lifetime
dose is 10 mSv multiplied by persons the age in years. For
operating personnel, it is recommended to use protection
barrier.
For this reason, the operator protection measures including education, the implementation of a radiation protection
program, annual and lifetime limits of exposure to ionizing radiation, recommendations for personnel dosimeters
and the use of barrier shielding should be incorporated.

X-ray Equipment Installation and Related Factors


1.

Milliampere-seconds
Exposure time is the most vital factor in influencing
diagnostic quality. Both overexposed and underexposed
radiographs result in repeated exposures, thereby leading
to needless additional patient exposure. Milliampere-second
(mAs) is the combination of milli amperage and exposure
time affecting the quantity of X-rays produced and sequentially the image density.
Patient exposure is directly related to mAs. Typically a
radiograph of correct density will demonstrate very faint
soft tissue outlines. Enamel and dentin will have an optical
density of about 1.0. Optimal image density can be obtained
by using values listed, after considering the age and physical stature of the patient. For example, 3.5 mAs is suggested
for an average adult when F-speed lm and an operating
kilovoltage of 70 are used. This value may be arrived at
by using milliamperage of 10 and an exposure time of
0.35 second. If the kilovoltage is increased to reduce image
contrast, the mAs must be decreased or the radiograph will
be overexposed.
Phototiming technique uses a phototimer to measure
the quantity of radiation reaching the lm and automatically terminates the exposure when enough radiation has
reached the lm to provide the required density. A form of
this technology is currently available with some panoramic
machine.

Protecting Personnel
Radiation and humans are inseparable. Minimal usage
in daily activities, diagnostic and therapeutic modalities is
710

2.

3.

The concluding X-ray equipment installation plan,


either a new or amendment of the existing one has to
be reviewed by an appropriate government agency.
The plan and supplementary papers should clearly
state the following: (i) the design and dimension of
the X-ray equipment operating room; (ii) the materials used for construction, barrier, shielding should be
mentioned; (iii) the position of doors, windows and
louvers; (iv) status of adjacent or surrounding area,
above and below the room facility; (v) concise narration of the X-ray unit, manufacturer details and
working parameter; (vi) information on location and
orientation of dental chair, ray equipment, patient
and film supporting devices.
The X-ray equipment installation should be in a safe
environment, providing safety for both patient and
operator by directing the primary radiation always
toward the shielded barrier or an unoccupied area.
The setting of switching off the X-ray equipment
should always be located outside the room, behind an
adequate barrier with sufficient distance from the primary source.

X-ray equipment room design


1.

2.

3.

4.

First of all, the X-ray equipment installed room should


be designed such that the operator is not exposed to
the primary radiation beam.
For designing the shielding of the X-ray equipment
room, including the floor, wall, ceiling and door, the
location and dimension of the room, equipment parameters including workload, tube voltage, etc., should all
be taken into consideration.
Lead is the choice of material for room shielding. This
should be uninterrupted and with supportive barrier
to prevent drooping.
The CT room dimension should be above 25 m2.

Chapter 26 Radiation Biology

Figure 7

Figure 8

Protection of the operator

Lead gloves

Protection of the operator


1.

2.

The operator should stand at least 3 meters or 6 feet or


at an angle of 90135 degrees from the X-ray tube or
the central X-ray beam.
To view the radiographic procedures by the operator
without protective barrier, leaded glass window or
shielded barrier view is an alternative option (Figure 7).

Figure 9

Radiation protection inspection


1.

2.

It should be on a customary basis to have an updated


and validated standard of working condition according to parliamentary requirements.
Implementation and maintenance of Quality Assurance
Program.

Shielding
Radiation shielding is a mass of radiation absorbing material placed around the radiation source to reduce the radiation to a safe level for humans.
Different types of shielding in diagnostic radiology are:
1.
2.
3.
4.
5.

Operating personnel shielding


Patient shielding
X-ray equipment room shielding
X-ray tube shielding
Patient waiting room shielding.

Lead apron and thyroid collar

minimum 0.5 mm of lead equivalence protection device is


necessary.

Personnel shielding
Appropriate personnel shielding can be achieved by having
(i) a lead protective barrier of 1.5 mm between operator and
X-ray tube; (ii) lead apron and gloves of 0.25 mm thickness (Figures 8 and 9); (iii) lead gonadal shield of 0.5 mm
thickness. For any specialized radiological investigation,

Patient shielding
The susceptible organs, namely, thyroid, breasts and gonads
should be shielded in children and young adults with
0.25 mm of lead thickness for lead apron, collar and gloves
and gonadal shield of 0.5 mm of lead thickness.
711

Section IX Basics of Radiology

X-ray equipment room shielding

Patient waiting area

A few of the mandatory decisive factors about X-ray equipment room are:

1.

1.

2.
3.
4.

5.

The equipped room location should always be away


from maternity and pediatric wards and with the minimum dimension of 18 m2.
The wall opposing the central beam must be of minimum 35 cm thick brick.
The wall opposing the scattered beam must be of minimum 23 cm thick brick.
For protection of adjacent area, the door and windows
of the X-ray equipped room should be at least 23 cm
thick brick or 1.7 mm of lead equivalent.
For ventilation or natural lightening, an unshielded
opening of 2 m above height from the finished level
outside the X-ray equipped room is permissible.

Shielding of X-ray control room


It is a secondary protective measure from ionizing radiation. Based on the operating potential, the control room
can be situated either within the X-ray equipped room or
outside.
If the operating potential is up to 125 kVp, the controlling panel can be situated within X-ray equipped room with
a minimum distance of 3 m between xed X-ray equipment
and the control panel.
If the operating potential is above 125 kVp, then the control panel should be installed outside the X-ray equipped
room with appropriate shielding for the room along with
accommodation of direct vision and oral communication.
The location of the control booth should be in such a
way that the primary beam should scatter twice before
entering the room.
In addition to this, the control booth wall and window
shielding should be of 1.5 mm lead thickness.

2.

3.

The patients waiting area should be outside the X-ray


room.
A suitable alert signal in the form of red light should
be placed at a noticeable place outside the X-ray room
and should be kept in ON position during working to
warn the people.
A warning placard should be attached at the eyecatching place.

RADIATION DETECTION AND


MEASUREMENT
The principle behind detecting the radiation is the physical
and chemical effects produced by the radiation.
The following are the principal methods used to detect
radiation:
1.
2.
3.
4.

Ionization
Photographic effect
Luminescence
Scintillation.

Ionization
The process of converting an atom or molecule into an ion
by adding or removing charged particles such as electrons
or ions is termed as ionization.
Principle

Ionization in air by radiation.

Radiation detection device The ionization chamber


(Figure 10).
Functioning mode It consists of an electrode positioned
in the middle of a cylinder that contains gas. When X-rays
enter the chamber, they ionize the gas to form negative

X-ray tube shielding (source shielding)


The rationale of X-ray tube shielding is to protect the
patient and operating personnel from leakage radiation.
This can be achieved by placing thin sheets of lead lining
over tube housing, which helps in reducing the scattered
radiation.
The limitation of radiation leakage exposure rate is
0.1 R h1 at 1 m. The recommended maximum allowable
leakage radiation from tube housing should be less than
1 mGy h1/100 cm2.

Radiation in the CT Suite


In the CT suit, in order to reduce the scattered radiation
from 0.3 Gy/day to 1 mGy/year, an additional lead thickness
of 2.5 mm or 162 mm of concrete to shield the front and
rear reference point is recommended.
712

Figure 10

Radiation
source

+
A

Ionization
chamber

Ionization chamber

Chapter 26 Radiation Biology

ions (electrons) and positive ions (positrons). The electrons


are collected by the positively charged rod, while the positive ions are attracted to the negatively charged wall of
the cylinder. The resulting small current from the chamber
is subsequently amplified and measured. The strength of
the current is proportional to the radiation intensity.

Figure 11

Photographic effect
Principle The ability of radiation to blacken the photographic film.
Application

Detection of radiation exposure in films.

Luminescence
Principle The property of certain materials that emit
light when stimulated by a physiological process, a chemical or electrical action, or by heat.
Functioning mode When radiation strikes luminescence
materials, the electrons are raised to higher orbital levels.
When they fall back to their original orbital level, light is
emitted. The amount of light emitted is proportional to the
radiation intensity.
Example: Lithium fluoride will emit light when stimulated
by heat.
Radiation measuring device on luminescence property
is thermoluminescence dosimetry (TLD), a method used to
measure exposure to patients and personnel.
Scintillation

Personnel dosimeter

Radiation measurement By time-integrated dose, i.e.


the dose summed over a period of time, usually about
3 months. The dose is consequently stated as an estimate
of the effective dose equivalent to the whole body in mSv
for the reporting period. Dosimeters used for personnel
monitoring have dose measurement limit of 0.10.2 mSv
(1020 mrem).
Pocket dosimeter
It is a personnel radiation monitoring device.

Principle and working mode The property of certain


crystals such as sodium iodide and cesium iodide to absorb
radiation and convert it to light. The direction of this light
to a photomultiplier tube, converts the light into an electrical pulse. The size of the pulse is proportional to the light
intensity, which is in turn is proportional to the energy of
the radiation.

Working mode It consists of an ionization chamber with


an eyepiece and a transparent scale, as well as a hollow
charging rod and a fixed and a movable fiber. When the
X-rays enter the dosimeter, ionization causes the fibers to
lose their charges and, as a result, the movable fiber moves
closer to the fixed fiber. The movable fiber provides an
estimate of gamma or X-ray dose rate. The pocket dosimeter can measure radiation up to 50 C/kg (200 mR).

Personnel Dosimetry

Film badge monitoring

Radiation dosimeter is the instrument used to measure


radiation.

The film badge consists of small X-ray films sandwiched


between several filters, which help to detect radiation. Film
badges are inexpensive, simple mode of functioning. They are
useful for detecting radiation at or above 0.1 mSv (10 mrem).
Drawbacks of lm badge are:

Personnel dosimeter It is used for the monitoring of


individuals who are exposed to radiation during the course
of their work (Figure 11).
Personnel dosimetry policies are must for all occupationally exposed individuals. It is mandatory to wear personnel dosimeter if the annual dose is greater than 1 mSv.
The values obtained from the dosimeter are honorable
only when the dosimeters are properly worn and irradiated
only during occupational exposure and are returned on time.
Appreciation of a few personnel dosimeters are the
pocket dosimeter, the lm badge or the thermoluminescent
dosimeter.

1.
2.

3.

4.

They are insensitive to radiation below 0.1 mSv.


They cannot be worn longer than 4 weeks duration at
a stretch due to fogging as an outcome of high temperature and light.
The colossal task of chemically processing a large
number of small films and subsequently comparing
each to some standard test films.
The film badge cannot measure exposures less than
2.6 C/kg (10 mR).
713

Section IX Basics of Radiology

These two positions will indicate:

Figure 12

1.
2.

Estimation of the whole body exposure at the trunk


level badge.
Estimation of exposures to internal organs like thyroid at the collar level badge.

During fluoroscopy

Thermoluminescent dosimetry (TLD)

The protective apron should always be worn during fluoroscopy. Preferably two dosimeters should be worn by
radiation personnel.
One at the collar level outside the lead apron indicates
an accurate estimate of the radiation dose to the unprotected regions of head and neck; and the other at the trunk
level underneath the lead apron illustrates an accurate
estimate of the radiation to the protected organs. If only
one dosimeter is worn it must be worn at the collar outside
the lead apron, because, the neck receives 1020 times
more radiation than the trunk which is protected by lead.

Principle of thermoluminescence It is the property of


certain materials to emit light when they are stimulated by
heat (Figure 12).

FILM EXPOSURE AND PROCESSING

TLD badge

In India, film badges have been recently replaced by TLD


badges.

Reserves of TLD Lithium fluoride (LiF), lithium borate


(Li2B4O7), calcium fluoride (CaF2), and calcium sulfate
(CaSO4).
Working mode When an LiF crystal is exposed to radiation, a few electrons become trapped in higher energy levels. For these electrons to return to their normal energy
levels, the LiF crystal must be heated. As the electrons
return to their stable state, light is emitted because of the
energy difference between two orbital levels. The amount
of light emitted is measured (by a photomultiplier tube)
and it is proportional to the radiation dose.
Advantages of TLD are:
1.
2.
3.
4.

It can measure exposures to individuals as low as


1.3 C/kg (5 mR).
It can withstand a certain degree of heat, humidity,
and pressure.
Its crystals are reusable.
Instantaneous readings are possible if the department
has a TLD analyzer.
Disadvantage of a TLD: It is not cost effective.

Wearing the Dosimeter


During radiography
Site of personnel wearing dosimeter during radiography
are at two regions:
1.
2.

714

On the trunk of the body at the level of the waist, on


the anterior side of the individual.
On the upper chest region at the level of the collar
area on the anterior surface of the individual.

Exposure parameters and film processing events can affect


the quality of the radiographic image. The milliamperesecond is an important parameter set by the operator for
optimal quality of radiograph. Acquainting the skill of
film processing is another important dexterous parameter
as the overexposed and underdeveloping of a film, lead to
excessive patient exposure and can produce images of
poor diagnostic quality.
The methods to reduce radiation exposure, result in
radiation protection. These are stated as follows:
1.
2.

Stick on to proper exposure factors.


Maintain proper record of films.

The processing recommendations include:


1.
2.
3.
4.

Adequate ventilation for darkrooms.


Proper handling of the processing solutions.
Judicious use of safe light.
Following waste disposal regulations in relation to
processing solution and lead foil.

Darkroom
For manual processing of films, well-equipped darkroom
under recommended guidelines is obligatory to get good
quality radiographs. This will indirectly reduce the exposure to the patient.
1.
2.
3.

The darkroom must be light-taut.


The darkroom should integrate a lockable, double
doors with blackened warren entrance.
A warning light should be located outside the darkroom at the entrance and it should be in ON position
indicating work in progress.

Chapter 26 Radiation Biology

Recordings in operational check log book


Frequency

Operational check

Daily

Check the quality of a film with reference radiograph

Monthly

Check and analyze problems with the film, developing process, the X-ray unit or the user

Six monthly

Check the light leaks in processing box


Check the condition of personnel protective equipment
Check the X-ray film storage and its shelf life
Check that the oldest X-ray film is used first
Check the expiry date of the film specified by the manufacturer
Check that exposure factors for specific examinations are readily available
Check the RSO details are displayed in a prominent location adjacent to the X-ray equipment and are correct
Check the processor maintenance procedures are displayed in a prominent location contiguous to the film processor
Check the instructions for mixing chemicals and processing films are available
Check time and temperature with timer and thermometer, respectively for manual processing
Check the warning signs of X-ray equipment being displayed and control panel are in good condition

4.
5.

6.

Safelight bulbs of 15 W intensity must be placed 4 feet


above the work area within the darkroom.
Safelight filters: Red GBX-2 filters should be placed
at proper distances and must be checked regularly as
they may deteriorate with time or may crack.
The darkroom must be equipped with proper stainless
steel processing tanks with water bath and lids,
including an accurate thermometer and timing device.

The processing chemistry should be evaluated daily, and


each type of lm should be evaluated monthly or when a
new box or batch of lms is opened.
Lead aprons and thyroid collars should be inspected
visually for damage on a monthly basis and should be
examined uoroscopically on an annual basis. Lead aprons
and collars in poor condition should be disposed off using
a recycler licensed to handle lead wastes.

Quality assurance

Continuing education

Quality assurance etiquette is essential for all the user


needs. This includes X-ray machine, imaging receptor,
film processing, darkroom, and lead aprons and thyroid
collars which can be implemented in each dental health
care setting. All quality assurance procedures including
date, procedure, results and corrective action, should be
logged for documentation purposes.
A thorough survey during installation period and
re-survey in every 4 years should be done by a qualied
expert of state agencies. The lm processor should be
evaluated every month in addition to initial installation.

Radiation protection is a fundamental component of the


working infrastructure of any radiology department. Every
update about the radiation safety issues, recent models
and upgradations of equipment, materials and techniques
should be adopted by every practitioners to improve the
quality of the radiographic practices.
Before undertaking any radiological examination, it is
important that the physician, radiologist and technologist
all understand the potential risks of radiation and also its
advantages or benets to the patients in dentistry, medicine and everyday life.

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SECTION

Radiographic
Methodology

27 Radiographic Films and Accessories


28 Radiographic Techniques

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CHAPTER

Radiographic Films and


Accessories

27

Ravikiran Ongole, Praveen BN

Intraoral Films

Constituents of an Intraoral Film Packet


Composition of Intraoral Film
Dimensions of Intraoral Films

Radiographic films and accessories such as cassettes, film


holders and grids are essential in every day dental practice. Use of appropriate accessories will help in improving
diagnostic quality of the films, enhance patient care and
aid in improving work efficiency.
This chapter will describe the constituents of an intraoral lm, cassettes and intensifying screens, grids and lm
holders.

INTRAORAL FILMS
These films are used for periapical, bitewing and occlusal
radiography. These are also referred to as direct action films
(primary sensitive to X-rays) and non-screen films (not used
in combination with intensifying screens).

Constituents of an Intraoral Film Packet

Extraoral Films
Cassettes
Intensifying Screens
Grids

The outer jacket (on the tube side/white surface) is incorporated with a raised dot, which relates with a similar area on
the dental lm inside the packet. This dot aids in orientation
of the lm during the exposure (always places such that the
dot lies closer to the incisal or occlusal aspect of the teeth).
Once the lm is processed the orientation of the raised dot
is used to identify the left and right sides of the patient.
Lead foil Once the outer jacket is opened a thin sheet of
lead foil is seen. This lead foil has parallel indentations or
markings along the surface in one corner of the foil. If the
film is exposed placing the wrong side toward the tube
head, these markings are seen on the resultant radiograph.
If the wrong side of the film is exposed, though the radiograph will reveal an image, the image will appear light.
The markings on the film will help to identify the cause for

Figure 1

An intraoral film packet consists of an outer protective


jacket, lead foil, black-colored paper wrapper and the film
(Figure 1).
Film

Outer protective jacket The outer protective jacket is


essentially made of light proof and moisture proof soft
vinyl. A recent development is the use of phthalate free
film packets which are otherwise considered potentially
harmful to health.
The outer jacket is dual colored. The tube side of the
lm packet is white colored and the opposite side is twin
colored. The cover is sealed to prevent contamination of
the lm from moisture, exposure to light and ingress of
oral uids when placed in the mouth. The packet on the
non-tube side has a ap which is pulled open in the darkroom to remove the exposed lm for processing.

Black-colored
paper wrapper
Lead foil

Outer protective
plastic jacket

Contents of the intraoral film packet

719

Section X Radiographic Methodology

the underexposed or light radiograph. These markings


(diamond markings) are seen on the resultant radiograph.
Lead foil is incorporated into the lm packet to:

silver halide grains and trace amount of sulfur compounds


and gold so as to enhance the sensitivity of the silver
halide grains to X-rays.

1.

Minimize the amount of X-rays from passing through


the film and interact with the tissues beyond the film
and reflect back leading to multiple exposures, thereby
minimizing the quality of the final image.
Minimize exposure of the patients tissues, which are in
line with the X-ray beam but beyond the imaging area.

Black paper wrapper Once the lead foil is folded back,


the black paper wrapper is seen in which the film is placed.
The paper wrapper protects the film from extraneous visible light and protects the emulsion of the dental film during handling and storage. It also helps in absorbing any
moisture created within the film packet as a result of humid
storing conditions.
The lm has a raised dot on one side and the other side
has a small concave depressed area. The lm holder used
for processing is clipped onto the lm conforming to the
depressed shallow concave area. This allows a one-point
contact between the clip and the lm. The advantage of this
one-point contact is that processing solutions freely ow
into the shallow depression on the lm, thereby exposing
every single area of the lm. Holding the lm in any other
area will obscure the diagnostic details on the lm.

Composition of Intraoral Film


Intraoral films are made up of two principal components,
namely, emulsion and the base (Figure 2).
Emulsion
The emulsion is sensitive to X-rays and visible light. The
emulsion is composed of a vehicle matrix which holds the

2.

Silver halide grains: Silver bromide makes up most of


the silver halide grains that are incorporated in the
emulsion. However, silver iodide is added in small quantities as they have crystals of larger diameter which
help in increasing the sensitivity of the film.
Vehicle matrix: The vehicle matrix helps in the
even distribution and dispersion of the silver halide
grains. It is made up of gelatinous or non-gelatinous
substances.

Base
The base of the intraoral film is made up of polyester polyethylene terephthalate and is about 0.22 mm in thickness.
It is believed that a blue tinted base will improve the viewing characteristics of the radiograph.
Requirement of an ideal base:
1.
2.
3.
4.

It should support the emulsion.


It should have enough flexibility to enable easy handling of the film.
It should be uniformly translucent and should not
hamper the diagnostic quality of the film.
It should be able to withstand the effects of the chemicals in the processing solutions.

An adhesive is usually applied in between the emulsion


and base to improve the adhesion between the two.
An additional layer of the gelatinous substance is added
to the film emulsion, which is referred to as an overcoat.
It protects the film from scratching or contamination of
the film during handling or contact with the processing
tanks and it also protects the film from the pressure of
rollers of an automatic processor.

Figure 2
Overcoat

B
A
S
E

Emulsion consisting of
silver halide grains

Composition of the intraoral film. Courtesy: Dr Jaideep Shekhar

720

Chapter 27 Radiographic Films and Accessories

Dimensions of Intraoral Films


Intraoral periapical radiographs (IOPAR)
Intraoral periapical radiographs are available in three sizes
(Figure 3).
Size 0(22 35 mm) used for child patients
Size 1(24 40 mm) these narrow films are used for imaging adult anterior teeth
Size 2(31 41 mm) standard films that are used for imaging adult posterior teeth.
However, when size 1 films are not available, the size 2
adult films can be placed vertically and used for imaging
adult anterior teeth.
Bitewing radiographs
Routinely adult size 2 IOPAR is used for taking bitewing
radiographs. However, size 0 can be used in very small
Figure 3

children and size 1 can be used in children. In some instances


a longer film (size 3) is used in adults, which measures
53 26 mm.
Occlusal radiographs
The occlusal film measures 57 76 cm in dimension. It is
three times larger than a size 2 IOPAR film.

EXTRAORAL FILMS
These films are called screen films or indirect films as the
radiographic film is placed between two intensifying screens
within a cassette. Screen films are employed in extraoral
radiography such as orthopantomograph, lateral cephalograph, skull views, TMJ views, and lateral oblique views of
the mandible. Extraoral films are usually available in three
sizes: (i) 6 12 inches (orthopantomography), (ii) 8 10
inches (all other skull radiographs: PNS, PA view, lateral
cephalogram, etc.) and (iii) 6 8 inches (TMJ views, lateral
oblique).

Cassettes

Occlusal film

IOPAR film
size 2

IOPAR
pedodontic
film size 0

Various film sizes, namely, the occlusal, size 2 adult film and
size 0 child or pedo film

Cassettes are light tight containers, which help in maintaining a uniform and intimate contact between the film and
the intensifying screens. Cassettes are available in various
sizes and shapes conforming to the various sizes of radiographic film (6 8 inches, 8 10 inches and 6 12 inches).
These are usually made of plastic or thin metal. Basically
extraoral lm cassettes are available in two specications,
namely, rigid and exible cassettes.
1. Rigid cassettes These are made of thin metal framework.
The surface on the exposure side is made up of plastic and
the non-exposure surface has metal clamps, which help in

Figure 4
A

(A) Intensifying screens within an extraoral cassette. (B) Extraoral film cassette of the size 8 10 inches.
(C) Film cassette for orthopantomography of the size 6 12 inches

721

Section X Radiographic Methodology

Figure 5

Figure 6
X-ray beam
Phosphor layer
Film

Reflecting layer
Base

Composition of intensifying screen.


Courtesy: Dr Jaideep Shekhar

locking the cassette so as to ensure an intimate contact


between the film and the intensifying screens (Figure 4AC).
Rigid cassettes are easy to handle and protect the screen,
however they are expensive and may break on impact.
2. Flexible cassettes These are made up of flexible plastic and used for orthopantomography. These are delicate
and may tear with regular use. These are also difficult to
load and unload in the darkroom setting. However, these
are comparatively cheaper than rigid cassettes and require
less room for storage.

Intensifying Screens
Intensifying screens are used in pairs and are positioned
on either side of a double emulsion film.
Composition of intensifying screen Intensifying screens
are made of four principal components: the base, reflecting layer, phosphor layer and the coat (Figure 5).
Base
The base of the intensifying screen is made up of the same
material that is used in an intraoral film, i.e. polyethylene
terephthalate. The base is usually 0.25 mm in thickness.
The base acts as a supportive material.
Reflecting layer
It is made up of titanium dioxide. It is placed between the
base and the phosphor layer. It helps in reflecting back
on to the phosphor layer any light that is emitted by it.
However, the reflecting layer may add to the unsharpness
of the resultant image.

Grid

are some of the salts that are used. The presence of these
salts has led to the naming of intensifying screens as salt
screens.
However, rare earth materials are used these days such
as terbium activated gadolinium oxysulde and thulium
activated lanthanum oxybromide.
Coat
The coat is made up of plastic and has a thickness of 8 m.
It provides protection to the underlying phosphor layer.
As the coat is made up of plastic it can be easily cleaned.
It should be ensured that the coat is free from scratches
and dirt.

Grids (Figure 6)
During a radiographic exposure, almost 30% of the scattered photons (formed as a result of Compton scattering)
leave the site imaged and exit the body. These scattered
photons will result in the formation of dark areas on the
radiograph, which interfere with the diagnostic quality of
the radiographic image. However, the use of grids increases
the patient exposure by two-fold.
Therefore, grids should be used only when contrast on
a radiograph is really necessary. As the grid contains radiopaque absorbing materials, the exposure time has to be
doubled when using a grid. If the exposure time is not
changed, the resultant radiograph might show multiple
thin white lines, which minimize the density of the radiograph. These lines that are seen on the radiographic image
are called grid lines.

Phosphor layer
Radiosensitive phosphor salts are incorporated into this
layer of the intensifying screen. Inorganic salts such as
calcium tungstate, zinc sulfide, and zinc cadmium sulfate
722

Composition
A grid is made up of alternating strips of lead (radiopaque
material) and plastic (radiolucent material) spacers (Figure 7).

Chapter 27 Radiographic Films and Accessories

The effectiveness of the grid is calculated by its grid


ratio. Higher the grid ratio, greater is the efciency of the
grid in removing the scattered radiation.

Figure 7

Grid ratio It is the ratio of the thickness of the grid (t) to


the width of the radiolucent spacer material (d). A grid ratio
of 8 or 10 is most preferred.
Grid ratio = t/d

Patient

Types of grid
t

Grid
Receptor

Gridline diagram

Grids are made with varying number of pairs of spacer


and absorber material for every square inch. Grids with 80
or more line pairs per inch do not show radiolucent grid
lines on the resultant image.

1.
2.
3.
4.
5.

Linear grid
Focused grid
Pseudo focused grid
Crossed grid
Moving grid or PotterBucky diaphragm.

Functions
Grids are placed between the object to be imaged and the
image receptor system (film) to preferentially minimize the
amount of scattered radiation reaching the film. Grids
reduce film fog from scattered radiation, thereby increasing the contrast of the resultant image.

723

CHAPTER

28

Radiographic Techniques
Gail F Williamson, Kvan Kamburoglu*,
Suman Jai Sanghar, Jai Sanghar N,
Rinky Nacchyon, Apeksha Mainali,
Ravikiran Ongole, Praveen BN

CONVENTIONAL IMAGING

Intraoral X-ray Machine


X-ray Beam Angulation and Alignment
Radiographic Infection Control
Radiation Safety and Protection
Preliminary Procedures
Intraoral Radiographic Techniques
Intraoral Radiographic Procedures
Common Intraoral Technique Errors

Extraoral Radiography

TMJ Radiography

Transcranial View

Transpharyngeal View
(Parma Projection, Macqueen-Dell Technique)

Transorbital View

Lesser Known/Forgotten Extraoral


Radiographic Techniques

Technique
Landmarks for Positioning in Skull
Radiography

Townes Method or AP Axial Projection


May Method
Axiolateral Oblique Projection
Modified Parietoacanthial Projection
Acanthioparietal Projection Reverse Waters
Method

Posteroanterior Projection
Occipitofrontal Projection
PA Mandible
PA Cephalometric
Rotated PA View

Standard Occipitomental view

30 Occipitomental

Parietoacanthial View (Waters View)

Parietoacanthial View
(Open Mouth Waters View)

Modified Parietoacanthial Projection


(Modified Waters View)

Acanthoparietal Projection
(Reverse Waters Method)

Submentovertex View (Base or Full Axial


Projection, Schuller Method)

Lateral View

Lateral Cephalometry

AP Axial Projection (Townes Method)

Reverse Townes View

Lateral Oblique View


Lateral Oblique of the Body of the Mandible
and Maxilla
Lateral Oblique of the Ramus of the Mandible
Bimolar Projection

Intraoral Radiography

Panoramic Radiology
Origin of Panoramic Radiology
Concepts of Panoramic Imaging
Characteristics of Ghost Images
Indications of Panoramic Radiograph
Disadvantages and Limitations

SPECIALIZED IMAGING
Computed Tomography (CT)
Working Principle
Computed Tomographic Scanner Assembly
Advantages of CT
Disadvantages of CT
Uses of CT in Dentistry

Dentomaxillofacial Cone-Beam Computed


Tomography (CBCT)
Historical Background

*Dr Kvan Kamburog lu is grateful to Tomoloji Dentomaxillofacial Radiology Center and Gulhane Military Medical Academy, Dentomaxillofacial Radiology Center, Ankara for their support.
724

Chapter 28 Radiographic Techniques

Fundamentals of CBCT
Advantages and Disadvantages/Limitations of
CBCT
CBCT Clinical Applications

Magnetic Resonance Imaging


Historical Perspective
Principles of Magnetic Resonance Imaging
MR-contrast Agents
Methods for Obtaining Spatial (Tomographic)
Resolution of MR Signals
Uses for MRI
Advantages
Disadvantages
Common Artifacts in MRI

Nuclear Medicine
Radiopharmaceuticals
Bone Scanning
Salivary Gland Scans

Main Indications for Ultrasound in the


Head and Neck
Advantages Over Conventional X-ray Imaging
Disadvantages
Artifacts

Sialography
Indications of Sialography
Procedure
Injection of the Contrast Medium
Phases of Sialography
Contraindications of Sialography

Arthrography
Uses of Arthrography
Types of Arthrography
Procedure
Limitations
Complications

Thermography (Thermal Imaging or Infrared


Imaging)

Ultrasonography
Principle
Different Types of Scans
Different Types of Scanners Used
Instrumentation
Doppler Ultrasound

CONVENTIONAL IMAGING
INTRAORAL RADIOGRAPHY
Gail F Williamson
Intraoral radiography is an important tool for proper diagnosis and treatment. Intraoral radiographs allow the clinician to view the teeth and supporting structures revealing
conditions that may not be apparent clinically. Intraoral
radiography is accomplished by placement of a small
image receptor (IR) inside the mouth behind the teeth and
structures of interest with the X-ray beam aligned externally
over the corresponding area. Available intraoral receptors
include radiographic film, rigid digital sensors and photostimulable phosphor plates. Intraoral radiography involves
the acquisition of periapical and bitewing images that can
be combined to form surveys. Periapical radiographs record
the entire tooth or several teeth and the surrounding structures including the apical regions, the trabecular bone, the
periodontal ligament space and the lamina dura. By contrast, bitewings record the crowns, proximal contacts of the
teeth and the alveolar bone crests. Typically, a complete

Liquid Crystal Thermography


Electronic Infrared Telethermography
Patient Preparation
Procedural Requirements
Indications

or full-mouth survey consists of 1416 periapicals and


24 posterior bitewings (Figure 1A, B). In addition to periapicals and bitewings, occlusal radiographs can be taken to
record a broad region of either the maxilla or mandible. In
most instances, occlusal images are supplemental views
taken to record a larger area or to localize an object.
Intraoral radiographs can be combined with or augmented by extraoral radiographs. In extraoral radiography, both the receptor and X-ray source are housed outside
the oral cavity. Extraoral radiography requires specialized
equipment and can be accomplished with intensifying
screen-lm combinations or with digital imaging systems.
The panoramic image is the most common extraoral projection which provides a more complete view of the maxilla
and mandible, the maxillary sinuses and the temporomandibular joints (TMJ) (Figure 2). Cephalometric radiography
is more task-specic and includes a variety of skull projections. The most common application of cephalometric
radiography is the lateral skull projection used in orthodontics. The lateral skull view is used to evaluate structures,
monitor growth and development and track treatment
progress. Cone-beam computed tomography (CBCT) is the
most recent addition to extraoral dental imaging. CBCT is
725

Section X Radiographic Methodology

indicated when three-dimensional (3D) imaging is necessary to evaluate and plan treatment in situations such as
implant placement, failed endodontic treatment, pathological conditions, difcult surgical procedures and evaluation
of craniofacial anomalies.

Intraoral X-ray Machine


The typical intraoral dental X-ray machine used to expose
intraoral receptors operates at 60 or 70 kilovolts (kV),
48 milliamperes (mA) with variable exposure time

Figure 1
A

settings (Figure 3A, B). Kilovoltage controls the penetrating power of the X-ray beam and image contrast or differences in darkness. Milliamperage and time control the
number of X-rays and image density or the overall darkness of a radiographic image. Most intraoral X-ray
machines have fixed kilovoltage and milliamperage settings which permit adjustment of the exposure time only.
The length of the exposure time is dependent on a number
of factors including the kilovoltage and milliamperage
settings, collimation of the X-ray beam, patient size, area
of interest and the type of receptor.
Collimation restricts the size of the X-ray beam, reduces
patient exposure and improves image quality by reduction
of scatter radiation and minimizing penumbra production.
Collimation is accomplished with open-ended position indicating devices (PIDs) that are either circular or rectangular
in shape and vary in length from 20 to 40 cm (Figure 4).
Long rectangular collimation restricts the X-ray beam and

Figure 2
B

A typical full-mouth survey consists of 1416 periapicals


and 24 bitewings. (A) Full-mouth survey taken with
size 2 film receptors. (B) Full-mouth survey taken with
size 1 and 2 film receptors

Panoramic image demonstrating the maxilla,


mandible, dentition and TMJ

Figure 3
A

(A) Intraoral dental X-ray machine control panel. (B) X-ray head and PID;
HeliodentPlus Sirona Dental Systems, Inc., Long Island City, New York

726

Chapter 28 Radiographic Techniques

reduces the volume of tissue exposed on the skin surface


the most and, therefore, is recommended for periapical
radiography and bitewing radiography when practicable.
When selecting the exposure time, consideration should
be given to the overall size of the patient as well as the
area of interest. Recommended exposure time settings are
designed for the average adult patient. For adult patients
smaller than average, the exposure time for each area can
be reduced by one step and for larger than average,
increased by one step. Exposure time settings for children
are considerably less than for adults and frequently can
be accessed by selecting a child icon on the control panel

Figure 4

(Figure 3A). Exposure time increases as the survey progresses from the anterior to the posterior regions of the
mouth. Digital receptor exposures follow these same general principles but the time settings are lower for each area
when compared to lm. The speed of the receptor has an
inuence on the exposure time as well. Speed indicates the
sensitivity of a receptor to X-rays; the faster the receptor,
the less the radiation required to produce a diagnostic
image. Currently, F-speed is the fastest lm available for
intraoral radiography, providing signicant dose reduction
and comparable performance compared to D-speed lm.
Digital receptors, both rigid sensors and phosphor plates,
provide equal or greater dose savings than F-speed lm
with equivalent diagnostic utility. Intraoral X-ray machines
manufactured today are compatible with lm, rigid sensors
and phosphor plates.

X-ray Beam Angulation and Alignment

Collimation restricts the size of the X-ray beam and the


area of patient skin exposure. It can be accomplished with
a variety of devices including PIDs, metal devices that clip
into ringed instruments or that slide onto a PID.
Rectangular collimation is optimal

The vertical angulation of the X-ray beam varies and is


dependent on the tooth, dental arch, oral anatomy and
intraoral technique used. Vertical angulation is adjusted by
moving the X-ray head and PID up or down. Positive vertical
angulations are used for maxillary periapicals and bitewings
and negative vertical angulations are used for mandibular
periapicals. Positive vertical angulations position the X-ray
head above horizon with the PID directed downward while
negative vertical angulations position the X-ray head below
horizon with the PID directed upward (Figure 5A, B). Most
dental X-ray machines have an angle meter on the X-ray
head to indicate the degree of the vertical angulation with
horizon designated as 0. Vertical angulation controls the
length dimension of the recorded image. Errors in vertical
angulation produce images that either shorten or lengthen
the actual vertical dimension of the structures.

Figure 5
A

Vertical angulation. (A) Positive vertical angulation is used for maxillary periapicals as demonstrated by this premolar placement.
(B) Negative vertical angulation is used for mandibular periapicals as demonstrated by this incisor periapical placement

727

Section X Radiographic Methodology

Figure 6

Figure 7

Outer canthus
Pupil of eye
Ala of nose
Tip of nose

Infection control barriers for intraoral image receptors


Mentum

The horizontal angulation is adjusted by moving the


X-ray head and PID anteriorly or posteriorly (forward or
backward) along the horizontal plane. The horizontal
angulation is directed proximally for all intraoral views
and follows the curvature of the dental arches. This places
the X-ray beam perpendicular to the horizontal plane of
the teeth of interest. Errors in horizontal angulation result
in overlapping of the proximal surfaces of the teeth and
width distortion such that the teeth contacts and alveolar
bone crests cannot be properly visualized.
In order to expose the entire receptor, the center of the
X-ray beam, known as the central ray (CR), is directed
toward the middle of the receptor which is represented
externally by facial anatomic points as illustrated in
Figure 6. Failure to properly center the X-ray beam over
the receptor produces a partial image. The unexposed portion is called a cone cut, a term that dates back to the
time when closed cones were used rather than open-ended
PID collimators to direct the X-ray beam. Closed cones are
no longer used as they produce excessive scatter radiation
that signicantly increases the radiation dose delivered to
the patient.

patients and the dental professional. For the clinician, this


involves the use of personal protective equipment (PPE)
including clinical attire, eyewear, a mask and gloves to
avoid contact with patients oral fluids. For radiographic
equipment, this involves pre-cleaning, disinfection and
preferably, coverage with plastic barriers before seating the
patient and initiating radiographic procedures. An environmental protection agency (EPA)-registered hospital disinfectant with intermediate-level activity should be used to
prepare radiographic equipment and environmental surfaces. Barriers must be changed between patients but when
barriers are not used, the equipment and environmental
surfaces must be pre-cleaned and disinfected between
patients.
Disposable or radiographic instruments that can be
heat-sterilized should be used for intraoral radiography.
Intraoral digital receptors that cannot be heat-sterilized must
be covered with a FDA (Food and Drug Administration)cleared barrier (Figure 7) and cleaned and disinfected with
an EPA-registered hospital disinfectant with intermediatelevel activity between patients. Protective plastic barrier
envelopes are used to cover radiographic lm and phosphor
plates during placement in the mouth (Figure 7). After
exposure, contaminated external barrier must be disinfected
before dropping the lm or plate out of the barrier in preparation for processing. It is best to consult manufacturer
instructions for guidance on digital receptor handling and
disinfection practices.

Radiographic Infection Control

Radiation Safety and Protection

Standard infection control procedures must be utilized


when taking intraoral radiographs. During radiographic
procedures, the clinician can be exposed to a variety of
pathogens through direct contact with the patients oral
fluids or by contact with contaminated radiographic
equipment and work surfaces. The primary goals of infection control are to prevent cross-contamination and the
transmission of disease between patients and between

ALARA (As Low As Reasonably Achievable) is the guiding


principle in radiation safety and protection. It is the ethical
and professional obligation of dental professionals to keep
the radiation dose delivered to the patient to a minimum.
Although the risk of intraoral radiography is thought to be
very small, it is not risk-free and the effects of radiation
are cumulative. The measures most effective in dose reduction include the use of selection criteria, fast film or digital

Central ray entry points are facial anatomic landmarks


designed to help the clinician align the central ray to the
center of the image receptor inside the mouth

728

Chapter 28 Radiographic Techniques

Table 1

Selection criteria guidelines

Patient type

Child primary dentition

Child mixed dentition

Adolescent dentition

Adult dentate/artially

Adult edentulous

New patient

Bitewings if contacts closed


occlusals

Bitewings/panoramic

Bitewings/panoramic
FMS when indicated

Bitewings/panoramic
FMS when indicated

Individualized
Based on exam

Recall high caries


risk

Bitewings at 612 month


intervals

Bitewings at 612
month intervals

Bitewings at 612
month intervals

Bitewings at 618
month intervals

Not applicable

Recall low caries risk

Bitewings at 1224 month


intervals

Bitewings at 1224
month intervals

Bitewings at 1836
month intervals

Bitewings at 2436
month intervals

Not applicable

Recall for periodontal


patient

Selected
PAS/BWS as needed

Selected
PAS/BWS as needed

Selected
PAS/BWS as needed

Selected
PAS/BWS as needed

Not applicable

Growth and
development

Only when indicated

Only when indicated

Panoramic or PAS for


3rd molars

Not applicable

Not applicable

Other

Only in a special situation or circumstance

PAS: Periapicals; FMS: Full mouth survey; BWS: Bitewings.

receptors for intraoral radiography, rare earth screen-film


combinations or digital receptors for extraoral radiography, rectangular collimation of the X-ray beam and patient
shielding.
The clinician should practice radiation safety measures
to avoid occupational exposure and to comply with the
maximum permissible dose (MPD) limit. The annual dose
limit is 50 millisieverts (mSv) and the lifetime dose limit
is 10 mSv multiplied by the clinicians age in years. However,
the clinician should strive to completely avoid any occupational exposure. Compliance is easily achieved by not standing in or near the X-ray beam or in its path; not holding
the X-ray head or PID in place; not holding the receptor in
the patients mouth or holding the patient in position.
If assistance is needed to stabilize a patient, the parent or
guardian should be asked to assist, provided with a radiation shield and given instructions on how to restrain the
dental patient. During exposure, the clinician should stand
behind a wall barrier or 2 meters away and slightly greater
than a right angle to the X-ray beam. Personal radiation
dosimeters are commercially available to track occupational
exposure and are recommended for pregnant clinicians who
expose dental radiographs.

Preliminary Procedures
Before radiographs are prescribed, a complete medical
and dental history must be taken, reviewed and the chief
complaint identified. The dentist should examine the dentition to determine if radiographs are indicated. If radiographs
are necessary, the type and number of projections should
be identified. The American Dental Association (ADA) and
the FDA have established guidelines for the selection of
dental radiographic examinations in the United States.
Dental radiographs should be prescribed according to

these guidelines and taken for diagnostic and treatment


purposes only. Selection criteria guidelines are based on
the evidence of disease patterns and information obtained
from the patients medical and dental history, clinical signs
and symptoms of disease, risk factors, age and dentition,
and new or recall patient status. Only bitewing radiographs
are recommended on time-based regimens as determined
by patient risk factors for caries. See Table 1 for a summary
of these guidelines. Typically, radiographic procedures are
delegated to qualified dental staff (dental assistant and/or
dental hygienists) for completion.
Once the appropriate survey has been determined, the
patient should be prepared for the procedure. Facial jewelry, intraoral prostheses and eyeglasses should be removed
and safely stored. The patient should be protected with a
lead apron and thyroid collar, provided with an explanation of the purpose of the examination and given instructions to elicit cooperation (Figure 8). Preferably, the patient
is seated in an upright position with the midline centered
and the occlusal plane parallel to the oor for maxillary
periapicals and bitewings and the chin raised so that the
mandibular arch is parallel to the oor for mandibular
periapicals. The exposure time should be set for the area
before placement of the receptor inside the mouth. When
ready for exposure, the clinician should practice radiation
safety measures to avoid occupational radiation exposure.
Once the survey is acquired, proper processing techniques
should be followed as dictated by the selected image receptor. The clinician must ensure that the processed radiographic images are properly arranged in the lm mount or
computer image template according to the ADA standard.
This standard involves labial mounting and viewing of
radiographic images according to the patients right and
left sides of the dentition. Attention to correct tooth order,
proper location of surrounding anatomical structures and

729

Section X Radiographic Methodology

Figure 8

Figure 9

Paralleling technique requires placement of the receptor


parallel to the teeth with the central ray directed at
a right angle to both the teeth and receptor
Dental patients should be shielded with a
lead apron and thyroid collar during intraoral
radiographic procedures

Figure 10
observation of restorative treatments and/or missing that
match from periapical to periapical and/or periapical to
bitewing will ensure accuracy of arrangement.

Intraoral Radiographic Techniques


There are two techniques that can be utilized for taking
periapicals radiographs: the paralleling technique and the
bisecting angle technique. The paralleling technique is
preferred because it produces the most accurate and representative images of the teeth and surrounding structures.
The bisecting angle technique is considered a secondary
or alternate technique when paralleling technique cannot be accomplished due to intraoral anatomy or other
patient factors. Bisecting angle technique produces images
with inherent distortion because the buccal and lingual
aspects of the teeth and alveolar bone are not projected
evenly. This distortion must be taken into consideration
when interpreting the radiographs for caries and alveolar
bone loss.

A variety of ringed paralleling technique instruments are


commercially available. The instruments depicted here have
bite blocks designed to hold rigid digital receptors. XCP DS,
Dentsply Rinn, Elgin, Illinois

horizontal and vertical angulation and centering of the X-ray


beam (Figure 10). There are a variety of ringed instruments
commercially available with designs for all three types of
intraoral receptors. Proper assembly and parallel receptor
placement to the area of interest are necessary for optimal
results. A standard bite-block can be used for the paralleling technique as long as the clinician has the skill to align
the PID accurately.

Paralleling technique
The paralleling technique requires placement of the receptor parallel to the tooth or teeth of interest both in the
vertical and horizontal planes. The X-ray beam is directed
so that it strikes both the tooth and the receptor at a right
angle (Figure 9). Typically, the paralleling technique is
accomplished with ringed instruments that aid the clinician
in establishing the correct object to receptor relationship,

730

Bisecting angle technique


The bisecting angle technique is based on Cieszynskis rule
of isometry or the geometry of equilateral triangles. This
rule states that two triangles are equal if they share a common side and two equal angles. Applied to periapical radiography, a tooth and its projected image will be equal in
length if the X-ray beam is directed at a right angle to the

Chapter 28 Radiographic Techniques

Figure 11

Figure 12

Many types of bisecting angle instruments are commercially


available for film, rigid sensors and phosphor plate receptors.
Snap-A-Ray Xtra, Stabe Biteblock and Eezee-Grip
Digital sensor holders are shown from left to right.
Dentsply Rinn, Elgin, Illinois

Bisecting angle technique directs the central ray at


a right angle to the plane that divides the angle
formed by the teeth and receptor

Table 2

Figure 13

Bisecting angle technique

Periapical view

Maxillary

Mandibular

Incisor

40 to 50

5 to 15

Lateral-canine

40 to 50

5 to 15

Premolar
Molar

25 to 35
20 to 30

10 to 15
5 to 5

Approximate vertical angulations

common side or bisecting plane that divides the triangle


into two equal halves or equilateral triangles (Figure 11).
Care must be taken to accurately determine the bisecting
plane to avoid errors in vertical angulation. Approximate
vertical angulations used for each periapical are listed in
Table 2. The horizontal angulation and centering of the
X-ray beam remain the same as with the paralleling technique. There are instruments commercially available for
the bisecting angle technique for both film and digital
receptors (Figure 12). Bisecting angle technique requires
more technical skill and as such, more retakes tend to
occur than with the paralleling technique.
Image receptors As previously mentioned, intraoral
radiographs can be taken with three different types of
intraoral receptors: radiographic film, rigid digital sensors
or photostimulable phosphor plates. All three receptors are
considered approximately equivalent in their ability to
record dental disease states; caries, periodontal disease
and periapical pathoses. Intraoral image receptors range
in sizes from 0 to 4, however, the range of sizes depends

Radiographic film ranges from size 0 to 4. Depicted in


the front row are the size 2 bitewing, size 3 bitewing and
size 1 periapical films. In the back row are the size 4 occlusal,
size 0 periapical and size 2 periapical films. Carestream
Dental LLC, Atlanta, Georgia

on the type and manufacturer of the receptor. Periapical


receptor sizes include 0, 1 and 2 and bitewing receptor
sizes include 0, 1, 2 and 3. Size 0 is most commonly used
in pediatric imaging and the size 4 receptor is for adult
occlusal radiography.
Radiographic film Radiographic film is the traditional
medium for recording intraoral images (Figure 13). It consists of a blue-tinted plastic base material coated with a
double emulsion of gelatin and silver halide crystals, predominantly silver bromide. The film has a dot convexity
that indicates the exposure side and aids in proper arrangement and mounting of the processed radiographs. The film
is wrapped with an internal black paper with a lead foil on
the rear or non-exposure side and covered externally with
either a plastic or paper material to protect the emulsion
from light and moisture. The exposure side of the film
packet is white and the non-exposure side is two-toned

731

Section X Radiographic Methodology

Figure 14
A

Rigid wire dental sensors. (A) Size 2 and 1 rigid digital sensors. Schick CDR Elite,
Schick Technologies, Inc., Long Island City, New York. (B) Digital molar periapical image

with colors used to indicate speed and single or double


film packet. Once exposed to radiation, the emulsion captures and stores the latent image until the image is made
visible by chemical processing. Those silver halide crystals
exposed to radiation are reduced to metallic silver by the
developer solution reducing agents and form the radiolucent components of the image. The non-exposed, undeveloped silver halide crystals are removed by the fixer solution
clearing agent and become the radiopaque components of
the image. Typically film-based images are processed by
automatic processing systems that develop, fix and dry
radiographic film in approximately 5.5 minutes. The processed radiographs are ready for arrangement and mounting after exiting the processor. Care must be taken to
properly maintain the processor utilizing regular solution
replenishment, cleaning and solution change regimens.
Processing errors are a common cause of retakes in filmbased imaging.
Direct digital receptors Direct digital receptors are rigid,
wired receptors in the form of the charge-coupled device
(CCD) or complimentary metal oxide semi-conductor (CMOS)
detector (Figure 14A, B). The primary difference between
the two devices is the manner in which the latent image is
transferred to the read-out amplifier for display. The active
image area is smaller compared to film or phosphor plates
so the area of coverage is slightly diminished. These rigid
devices are area arrays composed of a matrix of pixels
with each pixel functioning as an electron well. When the
sensor is exposed to radiation, the energy that penetrates
through the structures is deposited in the electron well in
that location. The intensity of the energy or signal determines the brightness or density of the image in each area.
The digital data is processed by the computer and the
732

visible image can be viewed on the monitor almost


instantly. Rigid digital sensors are reusable receptors that
cannot be sterilized. As indicated previously, they must be
properly disinfected and covered with a barrier to avoid
direct contact with oral fluids. When positioning the
receptor in the mouth, the wire should be oriented toward
the occlusal plane for vertically placed anterior periapicals
and directed anteriorly for horizontally placed posterior
periapicals.
Direct digital receptors require less radiation exposure
than lm. The amount of exposure reduction is related
to the speed of the comparison lm. Typical exposures for
the average patient range from 0.04 to 0.06 second in the
anterior sextants to 0.080.12 second in the posterior sextants. Refer to the X-ray machine user manual for recommended exposure times.
Errors associated with rigid digital receptors are welldocumented in the dental literature. Common errors include
vertical angulation errors with foreshortened images and
crown cut-offs, placement errors, horizontal overlap, cone
cuts and problems related to patient discomfort. The rigid
nature of the receptor requires strict attention to the details
of placement, intraoral technique and accurate alignment
of the X-ray beam. A cotton roll can be placed on the
bite-block to avoid crown cut-off and reduce patient biting
pressure. To reduce patient discomfort, place rigid receptors
closer to the midline where the mouth has greater depth.
Commercially available foam tissue cushions and topical
anesthetic agents are useful in reducing discomfort and
minimizing the gag reex.
The primary advantages of direct digital receptors are
rapid image acquisition and immediate image display while
the disadvantages are the rigid, wired construction and
related placement and discomfort difculties.

Chapter 28 Radiographic Techniques

Figure 15
A

Phosphor plate receptors. (A) Size 0, 1, 2 and 4 phosphor plates. The opposite side or emulsion side is
directed toward the X-ray source. ScanX Phosphor Storage Plates, Air Techniques, Inc., Melville, New York.
(B) Phosphor plate premolar periapical

Photostimulable phosphor plates Photostimulable phosphor plates (PSPs) or storage phosphor plates (SPPs) are
wireless digital receptors that handle similar to film (Figure
15A, B). A separate plate is needed for each exposure and
a processing step is required before the images can be
viewed on the computer monitor. Phosphor plate receptors
have a single emulsion coated on the exposure side of the
plate composed of europium-activated barium fluorohalide.
Rather than an identification dot, plate receptors have a
letter or number to identify the exposure side of the receptor. Care must be taken to prevent abrasion, crimping or
creasing of the emulsion to avoid permanent image artifacts and frequent plate replacement. Once the plate is
exposed, the latent image is stored in the emulsion until
the plate is scanned by a helium laser beam (Figure 16).
When the phosphor plate is scanned, it emits light in proportion to the exposure received. The light detected by the
photomultiplier is converted from analog-to-digital data
and the visible image is displayed on the monitor for viewing. The scanning takes several seconds causing a slight
delay between image capture and display. Before reuse, the
plate must be erased by white light to remove any remnant
image. Typically, the plate is erased prior to exit from the
scanning unit. The primary advantages of the phosphor
plate are its thin, wireless construction while the disadvantages are susceptibility to emulsion scratches producing
artifacts and delayed image viewing.

Intraoral Radiographic Procedures


Periapical radiography
Periapical images provide information about tooth morphology, apical proximity to anatomic structures, abnormalities

Figure 16

Exposed phosphor plate receptors must be scanned


by a helium laser beam to digitize and display the visible
image. ScanX Intraoral Scanner, Air Techniques, Inc.,
Melville, New York

of the teeth and supporting structures such as carious


lesions, periodontal bone loss and periapical and bony
pathoses. Periapical radiographs can be taken in any area
of the mouth. There are classic placements for the incisor,
canine, premolar and molar teeth as outlined in Table 3.
When taking a full-mouth survey, it is best to take the anterior periapicals first. This allows the patient time to adjust
to the procedure before taking the posterior periapicals
733

Section X Radiographic Methodology

Table 3

Periapical and bitewing techniques

Head position: midsagittal plane perpendicular and occlusal plane parallel to floor
Projection

Teeth recorded

Horizontal angle

Vertical angle

Central ray

Maxillary incisor
periapical

Central incisor teeth


centered

Proximal between
central incisors

Parallel to teeth long


axes

Tip of nose

Maxillary lateral-canine
periapical

Lateral and canine teeth


centered

Proximal between
lateral & canine

Parallel to teeth long


axes

Ala of nose

Maxillary premolar
periapical

Distal of canine, 1st &


2nd premolar, 1st molar

Proximal between
premolar teeth

Parallel to teeth long


axes

Pupil of the eye to


mid-cheek

Maxillary molar
periapical

1st, 2nd & 3rd molar;


2nd molar centered

Proximal 1st & 2nd


molar teeth

Parallel to teeth long


axes

Outer canthus to
mid-cheek

Premolar bitewing

Canine distal, 1st & 2nd


premolar, 1st molar

Proximals between
premolar teeth

5

Pupil of eye to
occlusal plane

Molar bitewing

1st, 2nd & 3rd molars;


2nd molar centered

Proximals between
1st & 2nd molar
teeth

5

Outer canthus to
occlusal plane

Head position: midsagittal plane perpendicular and mandibular arch parallel to floor

734

Mandibular incisor
periapical

Central incisor teeth


centered

Proximal between
central incisors

Parallel to teeth long


axes

Center of chin

Mandibular lateralcanine periapical

Lateral and canine teeth


centered

Proximal between
lateral & canine

Parallel to teeth long


axes

Center of chin corner

Mandibular premolar
periapical

Canine distal, 1st & 2nd


premolar, 1st molar

Proximal between
premolar teeth

Parallel to teeth long


axes

Pupil of the eye to


mid-mandible

Mandibular molar
periapical

1st, 2nd & 3rd molar;


2nd molar centered

Proximal 1st & 2nd


molar teeth

Parallel to teeth long


axes

Outer canthus to
mid-mandible

Diagram

Chapter 28 Radiographic Techniques

which tend to be more difficult for some patients. Anterior


periapicals are placed in the vertical dimension with the
receptor identification dot or marker located in the coronal aspect of the image. For adult patients, the size 1 or 2
receptor can be used. The size 1 receptor is preferred for
narrow or crowded dental arches. Anterior periapicals are
used to record the central incisor, lateral incisor and canine
teeth (Figure 17). Posterior periapicals are oriented in the
horizontal dimension and are used to record the distal
aspect of the canine, premolar and molar teeth (Figure 18).
For adult patients, the size 2 receptor is the standard for
posterior projections.

Figure 17

Bitewing radiography
Bitewing radiographs are most frequently taken in the
posterior regions of the mouth of the premolar and molar
teeth for the detection of proximal caries and alveolar
bone loss (Figure 19A, B). For adult patients, the size 2
receptor is preferred. Bitewings can be oriented in either
the horizontal or vertical plane with the receptor positioned
parallel to the teeth crowns. Horizontal bitewings are the
most common but vertical bitewings are taken particularly
when moderate or greater alveolar bone loss is present.
Anterior bitewings can be taken to view bone levels in the
anterior segments of the mouth as well (Figure 20). A size 1
receptor is used to capture incisor and lateral-canine bitewing views. The clinician can select traditional tabs or
instrument holders to accomplish the bitewing survey.

Figure 18

Anterior mandibular periapicals of the incisor and


canine teeth

Posterior maxillary periapicals of the premolar and


molar teeth

Figure 19
A

Bitewings can be taken with a ringed instrument or with a tab. (A) Bitewing taken with the tab bitewing technique.
(B) Tab bitewing survey

735

Section X Radiographic Methodology

Figure 20

Vertical anterior and posterior bitewing survey

Table 4 Topographical occlusal technique


Projection

Head position

Placement

Maxillary anterior

Occlusal plane parallel & midsagittal perpendicular to


the floor

Horizontal or vertical in
anterior region

60

0.5 cm above tip of


nose

Maxillary posterior

Occlusal plane parallel & midsagittal perpendicular to


the floor

Vertical toward side of


interest

55

2 cm below pupil of
the eye

Mandibular anterior

Occlusal plane at 45 angle; midsagittal perpendicular


to the floor

Horizontal or vertical in
anterior region

15

Center of the mentum

The vertical angulation used for tab bitewings ranges from


5 to 10. The most common error associated with bitewing radiography is horizontal overlap which can render
the image non-diagnostic.
Occlusal radiography
There are two basic types of occlusal projections that can
be taken: topographical and cross-sectional. Topographical
occlusals provide a broad view of a segment of the maxilla
or mandible. Cross-sectional occlusals are used to localize
objects or to view the buccolingual dimensions of the dental
arches. The most common occlusal projections are topographical taken in the anterior segments of the dental
arches. Adult occlusal radiographs are taken with a size 4
intraoral receptor. The only film and phosphor plate receptors available are size 4. The receptor can be positioned
horizontally or vertically as needed to accommodate the
mouth size and arch width.
Topographical occlusals Topographical occlusals are based
on the bisecting angle technique. Topographical occlusals
have the appearance of a large periapical view of the teeth
and surrounding structures. Typical applications include
recording bilateral impactions of the permanent canine
teeth, mesiodens or large periapical or bony lesions. Topographical occlusal projections can be applied to pediatric
736

Angulation

Central ray

imaging by using a size 2 receptor and reduction of the


exposure time. In addition, anterior periapical views can
be taken using topographical occlusal technique when
mouth opening is limited or the arch is extremely narrow
or crowded. In these instances, a size 2 receptor is oriented
vertically. Table 4 summarizes the basic technical aspects
of topographical occlusal projections.
Topographical maxillary anterior occlusal The patients
head is aligned with the occlusal plane parallel to the floor
and the midsagittal plane perpendicular to the floor. The
receptor can be positioned horizontally or vertically dependent on the mouth size and arch width. With the mouth
opened slightly, the receptor is placed against the maxillary
occlusal surfaces with the dot convexity toward the palate
and positioned labially. The patient bites together lightly
to secure the receptor. The approximate bisecting angle for
this projection is 60 with the horizontal angle directed
through the proximal contacts of the maxillary central
incisors. The central ray of the X-ray beam enters through
a point located just above the tip of the nose. Generally,
the exposure time is the same time as the maxillary incisor
periapical for the selected receptor (Figure 21A, B).
Topographical maxillary posterior occlusal As with
the anterior occlusal, the patients head is positioned with
the occlusal plane parallel to the floor and midsagittal

Chapter 28 Radiographic Techniques

Figure 21
A

Topographical maxillary anterior occlusal. (A) Clinical photograph. (B) Occlusal image

Figure 22
A

Topographical maxillary posterior occlusal. (A) Clinical photograph. (B) Occlusal image

plane perpendicular to the floor. The receptor is oriented


vertically toward the side of interest and placed against
the occlusal surfaces of the maxillary teeth with the dot
placed anteriorly. The receptor should extend approximately 1 cm beyond the buccal surfaces of the posterior
teeth and inserted posteriorly until it contacts the anterior
ramus. The receptor is maintained in position by light
patient biting pressure. A 60 vertical angulation is used
with the horizontal angle directed through the premolar
teeth contacts and the central ray entering about 2 cm
below the pupil of the eye. This projection will record
one quadrant of the maxillary teeth and alveolar ridge
(Figure 22A, B).
Topographical mandibular anterior occlusal For the mandibular projection, the patients head is tilted back until the

occlusal plane is at a 45 angle above horizon. The clinician can align the X-ray head at a 45 angle to use as a
comparison to check for proper head position. The occlusal plane should be parallel to the open end of the PID. The
midsagittal plane is positioned perpendicular to the floor.
The receptor can be positioned horizontally or vertically as
needed. With the mouth opened slightly, place the receptor
against the occlusal surfaces of the mandibular teeth with
the dot convexity toward the tongue and positioned labially. The patient bites together lightly to secure the receptor. The approximate bisecting angle for this projection is
15. The horizontal angle is directed through the proximal contacts of the mandibular incisor teeth and the central ray is directed through the center of the mentum. The
exposure time is the same time as the mandibular incisor
periapical for selected receptor (Figure 23A, B).
737

Section X Radiographic Methodology

Figure 23
A

Topographical mandibular anterior occlusal. (A) Clinical photograph. (B) Occlusal image

Table 5

Cross-sectional occlusal technique

Projection

Head position

Placement

Angulation

Central ray

Maxillary

Occlusal plane parallel & midsagittal


perpendicular to the floor

Horizontal or vertical
in anterior sectant

Long axes plane of the anterior


teeth

1 cm posterior to bregma

Mandibular
anterior

Occlusal & midsagittal plane perpendicular


to the floor

Vertical toward side of


interest

Long axes of posterior mandibular 3 cm posterior to mentum &


teeth; 90 to receptor
3 cm lateral to midline

Mandibular
posterior

Occlusal & midsagittal plane perpendicular


to the floor

Horizontal or vertical
in anterior sextant

Long axes of anterior mandibular


teeth; 90 to receptor

Cross-sectional occlusals Cross-sectional occlusals are


most commonly taken for the purposes of object localization
or to view the buccolingual aspect of the dental arches.
Cross-sectional occlusal technique directs the central ray at
a right angle to the receptor. The maxillary cross-sectional
occlusal requires an X-ray machine capable of 90 kV to
enable penetration of the calvaria. Table 5 summarizes
the essential technical aspects of cross-sectional occlusal
projections.
Cross-sectional maxillary occlusal The patients head
and receptor are positioned in the same manner as the
other maxillary occlusal projections. The vertical angulation is determined by directing the X-ray beam through
the long axes of the anterior teeth. The horizontal angulation is centered with the midsagittal plane and the central
ray enters the skull 1 cm posterior to bregma, the junction
of the sagittal and coronal sutures. This projection produces an unusual horseshoe-shaped image, for it depicts
all of the maxillary teeth through the long axes dimension
end-on-end. To produce a maxillary cross-sectional image,
the exposure factors should be set at 90 kVp, maximum mA,
and a 1-second exposure. The exposure is dependent on
the selected receptor (Figure 24A, B).
738

Midline of the floor of the


mouth

Cross-sectional mandibular anterior occlusal The patients


head is positioned such that the occlusal plane is nearly
perpendicular to the floor or as far back as possible with
the midsagittal plane perpendicular to the floor. The exposure surface of the receptor should be placed against the
occlusal surfaces of the mandibular teeth. Approximately
1 cm of receptor extends beyond the labial surfaces of the
anterior teeth with the patient biting gently to secure its
position. The central ray is directed perpendicular to the
receptor and through the midline of the floor of the mouth.
The cross-sectional anterior occlusal is useful for evaluating
expansion of the anterior mandible or localizing a salivary
stone in the sublingual gland (Figure 25A, B). The exposure time is the same time as the mandibular incisor periapical for selected receptor.
Cross-sectional mandibular posterior occlusal For this
projection, the patients head is tilted back so that occlusal
plane is nearly perpendicular to the floor with the midsagittal plane perpendicular to the floor. The receptor is
positioned vertically toward the side of interest and as
posterior as possible. The exposure surface of the receptor
is placed against the occlusal surfaces of the mandibular
teeth. Approximately 1 cm of the receptor extends beyond

Chapter 28 Radiographic Techniques

Figure 24
A

Cross-sectional maxillary occlusal. (A) Clinical photograph. (B) Occlusal image

Figure 25
A

Cross-sectional mandibular anterior occlusal. (A) Clinical photograph. (B) Occlusal image

the buccal surfaces of the posterior teeth with the patient


gently biting to maintain its position. The central ray should
be directed perpendicular to the receptor and centered
3 cm posterior to the mentum and 3 cm lateral to the midline. This projection records one quadrant of the mandibular
teeth through the long axes dimension. The cross-sectional
posterior occlusal is useful for evaluating mediolateral
expansion of the posterior mandible or localizing a salivary
stone in the submandibular gland (Figure 26A, B). The
exposure time is the same time as the mandibular molar
periapical for selected receptor.

Common Intraoral Technique Errors


The clinician must have the ability to evaluate intraoral
images for diagnostic quality and be able to identify, understand and correct errors to keep retakes to a minimum and

eventually learn how to avoid them altogether. A diagnostic periapical depicts the area of interest including the
entire length of the teeth from the crown to the root apices
with at least 34 mm of bone surrounding the apices
and open proximal contacts. The image should have adequate contrast and density and be free of technical errors.
A diagnostic bitewing displays the area of interest, the
proximal surfaces of the maxillary and mandibular teeth
crowns and the alveolar bone crests. Like periapicals, adequate contrast and density and absence of technical errors
are necessary components of a quality image. When evaluating a full-mouth survey, every apex and every proximal
surface should be visible somewhere within the composite
of images.
A number of technical errors can be produced when the
parameters of intraoral technique are not properly followed.
Common errors encountered in intraoral radiography include
739

Section X Radiographic Methodology

Figure 26
A

Cross-sectional mandibular posterior occlusal. (A) Clinical photograph. (B) Occlusal image

Table 6

Common technical errors

Error

Description

Correction

Foreshortening

Structures shorter than normal; vertical angle too steep

Decrease the vertical angle of the PID

Elongation

Structures longer than normal; vertical angle not steep enough

Increase the vertical angle of the PID

Horizontal overlap

Proximal surfaces of the teeth are superimposed onto each


other with width distortion

Direct the horizontal angle through the proximal contacts


of the teeth for each view

Cone cut

Central ray of the X-ray beam is not aligned with the middle of
receptor producing a partial image or cut

Direct the central ray toward the center of the receptor


using facial landmarks or ringed instruments

Improper placement

The teeth or area of interest are cut-off because the receptor is


not placed in the right location

Follow the placement guidelines to include all structures


required on a particular view

Underexposure

Image is too light or faint because patient size was


underestimated, exposure time set too low or the exposure
incomplete

Evaluate the patient size, set the correct time for each view
and hold down the exposure button until the exposure is
complete

Overexposure

Image is too dark or dense because patient size was


overestimated or exposure time set too high

Evaluate the patient size, set the correct time for each view

placement, vertical angulation errors, horizontal overlap,


cone cuts and exposure errors. A discussion of these common errors follows. Table 6 summarizes common errors and
their corrections.

are dot reversal and a light image from lead foil absorption of the X-rays. Backward plate placement results in
reversal of the letter or number identifier.
Vertical angulation

Receptor placement
The most common technical error regardless of the type of
receptor is placement. Each periapical and bitewing placement requires inclusion of specific structures on each view.
When the expected structures are not recorded, retakes may
be necessary to gain the missing information. In addition
to incorrect location, portions of the teeth such as the
crowns or apices can be cut-off and necessitate a retake
(Figure 27). Backward placement of film and plate receptors
is possible as well. Hallmarks of backward film placement
740

Vertical angulation errors result in either foreshortening or


elongation of the teeth and surrounding structures. When
the vertical angulation is too steep, the structures are
diminished in length or foreshortened (Figure 28). This
error is corrected by decreasing the vertical angulation.
Elongation produces the opposite result with lengthened
structures as a result of inadequate or not enough vertical
angulation (Figure 29). Correction of elongation requires
an increase in vertical angulation to return the structures
to normal length.

Chapter 28 Radiographic Techniques

Figure 27

Mandibular premolar periapical receptor placement error in


which the apical portions were cut-off the image

Figure 28

Maxillary incisor periapical with image foreshortening caused


by over-angulation in the vertical plane

Horizontal overlap
Proximal overlap is the primary error that occurs when the
horizontal angulation is misdirected (Figure 30). Diagonal
rather than perpendicular entry of the X-ray beam to the
horizontal planes of the teeth causes superimposition of
the proximal surfaces from one tooth onto the next. The
proximal surfaces of the teeth and alveolar bone margins
are obscured from view and the structures are distorted in
width as well. This error is especially egregious on bitewings as it limits or prevents assessment of the teeth for
proximal caries and alveolar bone loss. The open end of
the PID should be horizontally parallel to the buccal plane
of the teeth of interest to direct the X-rays through the
teeth contacts (Figure 31).

Figure 29

Mandibular incisor periapical demonstrating elongation


caused by under-angulation in the vertical plane

Figure 30

Premolar bitewing with proximal overlap due to improper


horizontal angulation

Cone cuts
A cone or PID cut is the direct result of misalignment of the
central ray (Figure 32). When the central ray is not directed
to the middle of the receptor, a portion of the receptor is
not exposed and no image is produced in that region. Cone
cuts can occur on any aspect of a radiographic image. The
use of the classic receptor placement for each view and
central ray alignment with external entry points will help
eliminate cone cuts. Ringed instruments with beam guides
eliminate this error when properly assembled.
Exposure
A variety of exposure errors can occur that diminish
the diagnostic quality of a radiographic image. Improper
741

Section X Radiographic Methodology

Figure 31

The horizontal angulation should be aligned so that the


X-rays are directed through the proximal contacts of the
teeth on both periapicals and bitewings

Figure 33

A faint image of a maxillary molar periapical due to


underexposure of the receptor

Figure 34
Figure 32

Cone cut error on a mandibular premolar periapical.


The central ray was positioned too high relative to the
center of the receptor and central entry point

selection of the exposure time for the subject or area of


interest can produce an underexposed low density image
with a faint appearance (Figure 33) or an overexposed highdensity image with a dark appearance. Neither is desirable
and both could result in retakes. With digital imaging systems, dark images can be corrected with the imaging software as long as the image is not completely black. However,
very light images cannot be corrected by the software
because not enough exposure was received by the receptor
to form the image. Film and plate receptors can be doubleexposed producing an overly dark superimposed image
which requires two retakes (Figure 34).
742

A double exposure occurs when a film or plate receptor is


exposed twice. It produces a dark image with superimposed
structures which require two retakes

Intraoral radiography is indispensable for proper diagnosis and treatment of dental patients. A variety of intraoral projections can be taken to visualize the teeth and
surrounding structures including periapicals, bitewings and
occlusals. Intraoral radiographs should be prescribed by the
dentist according to selection criteria guidelines to ensure
that the benet of the examination outweighs the risk. The
clinician must have the requisite knowledge and skill to
effectively manage the patient and competently conduct all
aspects of the imaging procedure. Adherence to the tenants of radiographic technique will maximize the diagnostic result while at the same time minimize patient radiation
exposure through retake prevention.

Chapter 28 Radiographic Techniques

EXTRAORAL RADIOGRAPHY

As the term extraoral suggests, it is a technique in which


the image receptor is placed outside the mouth during the
X-ray exposure.

examined. Such an amount of scatter radiation induces


a deterioration of the image quality, reducing the contrast,
and it would eventually reduce the diagnostic quality.
Though grids minimize scatter radiation and improve the
quality of the resultant radiograph, they will also remove
some of the primary radiation and thus require the radiation exposure to be increased.

Technique

Landmarks for Positioning in Skull Radiography

Extraoral radiography, in contrast to the intraoral radiography, is made with indirect exposure films, where the film
is placed inside a tight cassette between intensifying screen
on either side and then the exposure is made after proper
positioning of the patient with reference to the long axis
of the cassette.

The basic localization points and planes of the skull (all of


which can be either seen or palpated) are used in radiographic positioning (Figure 35). Accurate positioning of the
skull requires a full understanding of these landmarks. The
planes, points, lines, and abbreviations most frequently used
in skull positioning are as follows:

Suman Jai Sanghar, Jai Sanghar N

Image receptors
Image receptors used here are otherwise known as screen
films or indirect exposure films, as they are used along
with intensifying screens. These screens emit visible light
on exposure to X-rays. The emitted visible light will in
turn expose the films. Due to the variation in the properties of intensifying screens, proper screen-film combination must be used as recommended by the screen and film
manufacturer so that the emission characteristics of the
screen match the absorption characteristics of the film.
Dimensions of the lms used in skull radiography are
8  10 inches and for lateral oblique views, it is 5  7 inches.
Intensifying screens
Due to density of the skull, intensifying screens must be
used to minimize the amount of radiation to the patient,
which also helps in reducing the scattered radiation. Intensifying screens permit a good radiograph to be produced
with the patient receiving a much lower dose of radiation.

Midsagittal plane (MSP)


Interpupillary line
Acanthion
Outer canthus
Infraorbital margin
External acoustic meatus (EAM)
Infraorbitomeatal line (IOML)
Orbitomeatal line (OML)
Acanthiomeatal line (AML)
Mentomeatal line (MML).

MSP The midsagittal or median plane divides the body


into right and left halves. This plane is important in accurate positioning of the cranium since, for every frontal or
lateral position, the MSP is either perpendicular to, or
parallel to, the plane of the film.
Interpupillary or interorbital line It is the line connecting either the pupils or the outer canthi of the patients
Figure 35
Glabelloalveolar
line

Speeds of intensifying screens


1. Fast screens Thick layer of relatively large crystals
used, maximum speed is attained but with some sacrifice
in image detail.
2. Slow screens or high definition screens A thin layer of
relatively small crystals are used; detail is the best, but speed
is slow necessitating a higher dose of ionizing radiation.
3. Medium screens Medium thick layer of medium sized
crystals in order to provide comprise between speed and
definition.
Grids
The grid is usually used to reduce scatter radiation, which
causes a decrease of the image contrast. The amount of
scatter radiation reaching the film would be several times
the primary radiation, depending on the part of the body

ine
al l
eat
l line
lom
eata
m
o
Orbit
Infraorbitomeatal line
Acan
thiom
eatal
M
en
line
to
me
at
al
lin
e

Nasion

el
lab

External
acoustic meatus
Angle of mandible
(gonion)

Acanthion

Mental point

Illustration depicting various radiographic planes for


positioning of the skull

743

Section X Radiographic Methodology

eyes. When the head is placed in a true lateral position, the


interpupillary line must be exactly perpendicular to the
plane of the film.
Acanthion It is the midline point at the junction of the
upper lip and the nasal septum.
IOML It is the line formed by connecting the middle of
the infraorbital margin to EAM. It is otherwise known as
anthropological baseline or Frankfurt line.
OML It is a line located between the outer canthus and
the EAM. This is also known as radiographic baseline or
canthomeatal line. This line is angled approximately 10 to
the anthropological baseline.
AML It is a line formed by connecting the acanthion to
the EAM.
MML It is the line formed by connecting mental point
(midpoint of the triangular area of the chin) and EAM.
Positioning terminology
To describe a skull projection, it is necessary to state the
relative positions of the skull planes to the image receptor
and the central ray relative to skull planes/image receptor.

Radiation protection
Routine radiation protection measures should be applied.
The most effective method of dose reduction is a careful
technique to avoid the need for repeat radiograph.
Radiographic techniques
1.

Fronto-occipital projections The central ray enters the


skull through the frontal bone and exits through the
occipital bone.
2.

Positioning errors

1.
2.

Rotationoccurs when the MSP is not parallel to the film.


Tiltoccurs when the interpupillary line is not perpendicular to the film.

3.

Submentovertex (base or full axial projection, Schuller


method)

4.

Lateral view
Modifications
Lateral cephalometric

Patient preparation

Before starting any examination, the identity of the


patient must be checked by the radiographer.

Figure 36

Illustrations showing the position of the mid-saggital plane

744

Standard occipitomental
Modifications
30 occipitomental
Parietoacanthial projection (Waters view, PNS view)
Open mouth Waters view
Modified parietoacanthial projection (modified
Waters)

Oblique projections The central ray is projected at some


angle to the median plane and the coronal plane.

Rotation and tilt are two of the most common positioning


errors (Figure 36):

Posteroanterior (PA) projection (0)


Modifications
Caldwell projection (15)
20 PA projection
PA mandible
PA skull
PA cephalometric
Rotated PA view

Occipitofrontal projections The central ray enters the skull


through the occipital bone and exits through the frontal bone.

Lateral projections The central ray passes along a coronal


plane at right angles to the MSP.

Ensure that all metal objects are removed from the


patient, for example, hair clips and hairpins, jewelleries, spectacles, hearing aids.
Bunches of hair often produce artifacts and thus
should be untied.
If the area of interest includes the mouth, then denture
(if removable) should be removed.
The patient should be provided with a clear explanation of any movements and film positions associated
with the normal operation of the skull unit.
If needed, foam pads, Velcro straps can be used as
accessories for stabilizing the patient. Forty-five degree
triangular pads are very useful for immobilizing children.
Individual side markers are essential for skull radiography.

5.

Acanthoparietal projection (reverse Waters view)

6.

AP axial projection (Townes method)

7.

Reverse Townes method

8.

Lateral oblique
Ramus of the mandible
Body of the mandible

9.

TMJ projections
Transcranial
Transpharyngeal
Transorbital.

Chapter 28 Radiographic Techniques

POSTEROANTERIOR PROJECTION

Figure 37

Occipitofrontal Projection
Occipitofrontal projections can be taken with different
degrees of beam angulation. The choice of the angulation
depends on the anatomy, which needs to be demonstrated.
10

CR

Indications

Fractures of the body, angle or ramus of the mandible,


displacement of fractures especially in a mediolateral
direction.
Le Forte I fracture of the middle third of the face.
Gross displacement of the zygomatic buttress.
Displacement of the teeth in alveolar fractures.
Cysts or tumors in the rami, showing expansion of the
bone in the mediolateral direction.
Deformity of the mandible or the maxillofacial area.

Skull position for PA view showing the central ray directed


perpendicularly through the occiput to exit the nasion

Figure 38
CR
15

Film placement
Cassette with the film is placed perpendicular to the floor,
with long axis vertically in a cassette holding device.
Patient positioning

The nose and the forehead of the patient should touch


the cassette, a position which places the OML (radiographic baseline) perpendicular to the cassette.
Mid part of the frontal bone is positioned in the center
of the cassette.
MSP is positioned perpendicular to the cassette, which
is accomplished by adjusting lateral margin of orbit or
EAM equidistant from the edges of the cassette.
Central ray
For PA projections, when frontal bone is of primary interest, the central ray is directed perpendicularly, through the
occiput to exit the nasion (Figure 37).
Variations of PA projections
15 PA

Caldwell method.

Indication For depiction of the ethmoid and frontal


sinuses that include both orbits.
Patient positioning is same as that for PA projection
except for the central ray projection, which is directed at a
caudal angle of 15 to the canthomeatal line (Figure 38).
The resultant radiograph will demonstrate the superior
border of the petrous ridge projected onto the lower third
of the orbit.
20 PA Similar to the above technique the caudal angulation alone can be changed to 2025 which helps in better visualization of the orbit, as the petrous ridges will be
projected inferiorly as the angulation is increased.

Skull position for 15 PA Caldwell view showing the central ray
directed at a caudal angle of 15 to the canthomeatal line

PA Mandible
Indication
The indication of this technique is to demonstrate the
transverse or oblique fracture of the body and rami of the
mandible, not evident in other projections.
Cassette and patient positioning is the same as that for
PA projection except that the central ray is directed perpendicular to the cassette and centered in the midline through
the cervical spine at the level of the angles of the mandible.
Limitation of this technique is that the central body of
the rami is not well shown because of the superimposed
spine.

PA Cephalometric
Cephalometric radiography ensures standardization and
reproducibility of the images.
Indications

To assess the position of unerupted canines.


To evaluate the asymmetry of facial bones.
For pre- and post-operative assessment of jaws for
both orthodontic and orthognathic procedures.
745

Section X Radiographic Methodology

Film positioning

Patient positioning

Cassette with the film is placed perpendicular to the floor,


with long axis vertically in a cassette holding device.

Patient positioning

MSP should be placed vertical and perpendicular to


the film.
Only nose should touch the film, so that the OML is
parallel with the floor which makes the radiographic
baseline to be at 10 with the film.
Head is immobilized using ear pieces inserted into the
EAM.
Film adjusted with lips centered on the film.

Patients nose and chin are placed in contact with the


midline of the cassette.
The head is then adjusted to bring the orbitomeatal
baseline to 45 angle to the cassette.
MSP is perpendicular to the cassette.
Central ray
Central ray is directed perpendicular to the film through the
occiput making its exit through the anterior nasal spine.
The nal image should be such that the petrous ridge
must appear below the oor of the maxillary sinus.

Central ray

30 OCCIPITOMENTAL

It is directed perpendicular to the film through MSP at the


level of the bridge of the nose.

Indications

Rotated PA View
Indications

To demonstrate calculi in the parotid gland.


To evaluate cysts and tumors involving the ramus of
the mandible which may have mediolateral expansion.

Technique

The film is positioned same as that of the PA view.


The head is rotated 10 toward the side of interest.
This positioning rotates the bones of the back of the
skull away from the side of the face under investigation.
The central ray is directed perpendicularly along the
side of the face.

To demonstrate fractures of the middle third of the face,


orbital floor.
Blow-out fracture of the orbit.
Fractures of the zygomatic arches.

This projection demonstrates the lower orbital margins


and the orbital floor. The zygomatic bones and arches
are opened out compared with the occipitomental projections as this technique uses a different angulation thereby
enabling detection of certain bony displacements.
Film placement
Cassette with the film is placed perpendicular to the floor,
with long axis vertically in a cassette holding device.
Patient positioning

Indications

Patients nose and chin are placed in contact with the


midline of the cassette.
The head is then adjusted to bring the orbitomeatal
baseline to 45 angle to the cassette.
MSP is perpendicular to the cassette.

Central ray

STANDARD OCCIPITOMENTAL VIEW

Diagnosis of pathologic conditions affecting air sinuses,


especially the maxillary antra. Examples: tumors, cysts,
fluid levels.
Fractures of the middle third of the facial skeleton.
This position shows the floor of the orbits in profile, the
nasal region, the maxillae, the inferior parts of the frontal
bone, the zygomatic bone and zygomatic arches, with
their entire length superimposed over a small part of the
image.
Film placement
Cassette with the film is placed perpendicular to the floor,
with long axis vertically in a cassette holding device.
746

The tube head is angled 30 caudally and centered along


the midline, such that the central ray exits at the level
of the lower orbital margins.
In a severely injured patient, a modified 30 reverse
occipitomental view can be taken. Here the cassette is
positioned vertically against the vertex of the skull supported with foam pads so that MSP is perpendicular to
the film and to the table, also to OML.
The tube is angled 20 to the horizontal (toward
the oor) and centered to the symphysis menti in the
midline.

Chapter 28 Radiographic Techniques

PARIETOACANTHIAL VIEW (Waters View)

PARIETOACANTHIAL VIEW
(Open Mouth Waters View)

Indications
This technique is useful for the evaluation of maxillary
sinuses and it also demonstrates frontal sinuses, ethmoidal
sinuses, orbit, zygomaticofrontal suture and nasal cavity.
In Waters technique the neck is hyperextended enough
to place the dense petrosae immediately below the maxillary sinus oor.
Film placement
Cassette with the film is placed perpendicular to the floor,
with long axis vertically in a cassette holding device.
Patient positioning
The patients neck is hyperextended and centered over the
cassette perpendicular to the acanthion.
The patients chin is placed resting over the cassette
and adjusted so that MSP is perpendicular to the plane of
the cassette.
The head is adjusted so that the OML forms an angle of
37 from the plane of cassette (Figure 39).
Central ray
Perpendicular to the cassette exiting at the acanthion.

Too much of angulation results in foreshortening of


maxillary sinus and the antral floors are not demonstrated.
When the neck is not fully extended, the petrosae are
projected over the inferior portion of the maxillary
sinus and obscure the underlying pathologic process,
if present.

Figure 39

This method provides an excellent demonstration of the


sphenoidal sinuses. The beam is projected through the open
mouth and is done for patients who cannot be placed in
position for submentovertex view.
Film placement
Cassette with the film is placed perpendicular to the floor,
with long axis vertically in a cassette holding device.
Patient positioning
It is similar to the positioning in Waters view, except that
the patient is asked to slowly open the mouth widely. MML
will not be perpendicular as in Waters.

MODIFIED PARIETOACANTHIAL
PROJECTION (Modified Waters View)
Indication
The modified Waters method is a good projection to demonstrate blow-out fractures.
Although the parietoacanthial (Waters) projection is
widely used, this technique is modied by making the patient
to extend his/her neck to a lesser degree. This method is
referred to as shallow Waters .
In this method, OML is adjusted to form an approximately
55 angle with the plane of the cassette (Figure 40A, B).
The resulting radiograph demonstrates the facial bone
with less axial angulation than with the Waters method.

ACANTHOPARIETAL PROJECTION
(Reverse Waters Method)
Indication
Reverse Waters method is used to demonstrate the facial bones
when the patient cannot be placed in a prone position.

37

Patient positioning

CR

Skull position such that OML forms an angle of 37


from the plane of cassette

MSP is placed perpendicular to the plane and also in


the midline of the cassette.
Neck is extended so that the OML forms a 37 angle with
the plane of the cassette (Figure 41) by raising the chin up.
If necessary, a support is placed under the patients
shoulders to help extend the neck.
MML is approximated perpendicular to the plane of
cassette.
Central ray
It enters the acanthion which is parallel with MML.
747

Section X Radiographic Methodology

Figure 40
A

55

CR
CR
35

Illustrations showing the skull position and entry of central ray for the modified Waters view

Patient positioning

Figure 41

The patients shoulders are raised and the neck is


hyperextended to bring the vertex of the skull in contact with the cassette.
The head is adjusted to bring the EAM equidistant
from the edges of the cassette (Figure 42).
The MSP should be at right angles to the cassette.
The OML should be as near as possibly parallel to the
cassette.
Central ray

37

Illustration showing the skull position such that the


OML forms a 37 angle with the plane of the cassette

Structures seen
Reverse Waters demonstrates superior facial bone. The
image is similar to that obtained with Waters method, but
facial structures are considerably magnified.

SUBMENTOVERTEX VIEW
(Base or Full Axial Projection, Schuller Method)
Indications

748

To demonstrate fractures of the zygomatic arches.


For visualization of the base of the skull.
To evaluate the angle of inclination of the head of the
codyle.

The central ray is directed at right angles to the OML and


centered midway between the EAM.
This projection is contraindicated in patients with suspected neck injuries, especially suspected fractures of
odontoid region.
Though this technique is described in supine position,
seated upright position is more comfortable because the
upright position allows a greater freedom in positioning
patients body to place the IOML parallel with the cassette.
Jug handle view It is a modification of submentovertex view (SMV) projection, wherein the whole length of
the zygomatic arch is demonstrated in profile against
the side of the skull and facial bones from which this
view derives its name.
The modication done here is a decrease in the
exposure factors.

LATERAL VIEW

Film placement

Indications

Cassette with the film is placed perpendicular to the floor,


with long axis vertically in a cassette holding device.

Backward displacement of fractures of the middle


third of the facial bones.

Chapter 28 Radiographic Techniques

Figure 42

Figure 43

CR

Skull position showing entry of central ray

Foreign body in the airway.


To evaluate the posterior walls of the antrum, for its
integrity.

CR

Illustration depicting entry of central ray for lateral skull view

To assess the skeletal pattern.


For tracing and scanning points necessary for orthodontic procedures.

Film placement

Film placement

Cassette with the film is placed perpendicular to the floor,


with long axis vertically in a cassette holding device.

Cassette with the film is placed perpendicular to the floor,


with long axis vertically in a cassette holding device.

Patient positioning

Patient positioning

The cassette is supported vertically against the side


under examination, so that the center of the cassette is
2.5 cm inferior to the outer canthus of the eye.
MSP is parallel to the cassette by ensuring that the
interorbital line is at right angle to the cassette and the
nasion and external occipital protruberance are equidistant from the margins of the cassette.

Central ray
It is directed horizontally to a point 2.5 cm inferior to the
outer canthus of the eye (Figure 43).

This technique is often reserved for gross trauma as the


facial structures are superimposed.
If lateral view is taken for a suspected foreign body
in the eye, then additional collimation and alteration in
the centering point will be required.

Sagittal plane is vertical and parallel to the cassette.


Frankfort plane should be horizontal.
The head is immobilized by guiding the ear pieces
carefully into the EAM. Metal circular markers within
the ear pieces allow the operator to rapidly recognize the
centering of the cephalostat.
The nose support is positioned over the nasion.
A wedge-shaped filter is positioned so that it will be
superimposed on the face with the thick edge placed
anteriorly for demonstration of the soft tissues.
The patient is instructed to close his/her mouth and to
bite together on his/her back teeth (centric occlusion).
Lips should be relaxed.

Central ray
Horizontal beam is centered on the EAM.

AP AXIAL PROJECTION (Townes Method)


LATERAL CEPHALOMETRY
This is a standardized true lateral projection of the skull.
Indications

To visualize the relationship of the soft and hard tissues of the face.
To assess the position of the teeth in relation to each
other and to the hard tissues and adjacent structures.

Indications

To visualize the occipital area of the skull.


Demonstrate the ascending rami of the mandible and
condyles of both sides.

Film placement
Cassette with the film is placed perpendicular to the floor,
with long axis vertically in a cassette holding device.
749

Section X Radiographic Methodology

Figure 44
CR
30

CR

The patient is then asked to keep his/her mouth wide


open. By doing so, the condylar heads move out of the
glemoid fossae.

37

Central ray
The central ray is aimed upward from below the occiput
so that the central ray forms an angle of 30 to the horizontal, and is centered through the condyles.

LATERAL OBLIQUE VIEW


Illustrations depicting patient head position and
entry of central ray for Townes method

Patient positioning

Patient is positioned such that the posterior aspect of


the skull rests on the cassette.
Patients head is adjusted so that the MSP is perpendicular to the midline of the cassette.
Flex the patients neck enough to place the OML perpendicular to the midline of the cassette.
When the neck cannot be flexed, the neck is adjusted
so that the IOML is perpendicular and has the central
ray angulation to be increased by 7 (Figure 44).
The cassette is positioned so that its upper margin is at
the level of the highest point of cranial vault. This will
place the center at or near the level of foramen magnum.

Central ray
Directed through the foramen magnum at a caudal angle of
30 to the OML or 37 to IOML. Central ray enters approximately 2 inches above the glabella and through the
level of EAM.

REVERSE TOWNES VIEW

The lateral oblique radiograph is an extraoral projection that


reveals a larger area of the jaws than intraoral radiography.
Indications

When intraoral views are unobtainable in patients


having trismus or severe gagging.
To detect unerupted teeth or impacted molars.
Fractures of the angle or the body of the mandible.
Pathologic conditions affecting the jaws.
General imaging principles

The head is rotated to ensure that the area under


examination is parallel to the film.
The film and the median plane are not parallel.
The central ray is perpendicular to the film but oblique
to the median plane.

Lateral Oblique of the Body of the Mandible


and Maxilla
This projection shows the dentition in the premolar/molar
region of the maxilla and mandible, the inferior cortex of
the mandible, and the angle and ascending ramus of the
mandible.
Position of patient and cassette

This projection shows the condylar heads and necks.

Indications

Fractures involving the condylar necks.


Developmental anamolies involving the condyle, such
as condylar hypoplasia or hyperplasia.

Film placement
Cassette with the film is placed perpendicular to the floor,
with long axis vertically in a cassette holding device.

Patient positioning

Patient positioning is similar to that in PA projection


(foreheadnose position).
OML should be at right angles to the film.
750

The patient is made to sit with the head supported. The


median plane is vertical.
A 5  7-inch cassette is used. Film markers should be
used to indicate the side.
The cassette is positioned against the patients cheek
overlying the region of the mandible under investigation, with the lower border parallel to the inferior border of the mandible but lying at least 2 cm below it.
The cassette in this position is stabilized by the patient.
The patients head is rotated to the side of interest. This
positions the contralateral ascending ramus forward and
increases the area between the neck and the shoulder
to provide space for the X-ray tube.
The chin is raised slightly to increase the space between
the posterior aspect of the mandible and the cervical spine.
The patient is asked to protrude the mandible.

Chapter 28 Radiographic Techniques

Central ray

Indications

Central ray is directed at a point 2 cm below and behind


the angle of the contralateral side of the mandible.
The central ray is perpendicular to the plane of the
film.
If the superimposition of the hyoid bone onto the body
of the mandible is to be avoided, then a downward
beam angulation of 10 can be chosen.

To demonstrate the destruction of the condyles due to


degenerative changes.
To assess the degree of movement of the joint.
Film placement
A 5  7-inch cassette is used. Film markers should be
used to indicate the side.
The cassette with the film is placed on the side of
interest, with the TMJ being centered over the cassette.
The cassette in this position is stabilized by the patient.

Lateral Oblique of the Ramus of the Mandible

Patient positioning

This projection gives an image of the ramus from the angle


of the mandible to the condyle.

MSP is parallel to the plane of the film.

Central ray
Position of patient and cassette

The patient is made to sit with the head supported. The


median plane is vertical.
A 5  7-inch cassette is used. Film markers should be
used to indicate the side.
The cassette is positioned against the patients cheek
overlying the ascending ramus and the posterior aspect
of the condyle of the mandible under investigation.
The cassette is positioned such that its lower border is
parallel with the inferior border of the mandible but
lies at least 2 cm below it.
The patient is instructed to support the cassette in this
position.
The mandible is extended as far as possible.

Central ray

The central ray is directed posteriorly with upward


angulation of 10 toward the center of the ramus of
the mandible on the side of interest.
The X-ray tube is positioned on the contralateral side of
the mandible at a point 2 cm below the inferior border
in the region of first or second molar.

Bimolar Projection
This technique is used in orthodontic practice. It shows
both left and right oblique lateral views on one film. The
technique incorporates a hinged lead shield to prevent
exposure of the other side of the film.

The central ray is directed at an angle of 25 (positive


angulation) from the opposite side, through the cranium
and above the petrous ridge of the temporal bone.
The horizontal angulation can be individually corrected
for the condylar long axis, or an average 20 anterior
angle may be used.
Transcranial, transpharyngeal and transorbital views
should be taken in both close and open mouth positions,
to assess the range of condylar movements.

TRANSPHARYNGEAL VIEW
(Parma Projection, Macqueen-Dell Technique)
This technique provides a sagittal view of the medial pole
of the condyle.
Indications

To visualize the head and neck of the condyles.


Developmental anamolies of the condyle neck.
To detect grossly displaced fracture of the condyle.

Film placement
A 5  7-inch cassette is used. Film markers should be
used to indicate the side.
The cassette with the film is placed on the side of
interest, with the TMJ being centered over the cassette.
The cassette in this position is stabilized by the patient.

Patient positioning

TMJ RADIOGRAPHY

TRANSCRANIAL VIEW

Central ray

It is a view that aids in visualizing the sagittal view of the


lateral aspects of the condyle and temporal component.

MSP is parallel to the plane of the film.

The beam is directed superiorly at an angle of 5 through


the sigmoid notch of the opposite side, and 78 from the
front, centered over the TMJ of the opposite side.
751

Section X Radiographic Methodology

TRANSORBITAL VIEW
It provides an anterior view of the TMJ, perpendicular to
the transcranial and transpharyngeal projections.
Indications

To visualize condylar neck fractures.


To detect degenerative changes or anamolies affecting
the condyle.

Dorsal sellae and posterior clinoid processes


Occipital bone
Posterior portion of the parietal bone.

Positioning of the patient


The patient is asked to stand in an upright position. Arms are
placed in comfortable position. Shoulders are made to lie in
the same horizontal plane. The midsagittal plane of the body
is centered to the center of the image receptor (Figure 45A).

Film placement

Positioning of the part

A 5  7-inch cassette is used. Film markers should be


used to indicate the side.
The cassette with the film is placed behind the skull on
the side of interest.

Patients head is adjusted such that midsagittal plane is


perpendicular to the midline of the IR. Patients neck is
flexed such that the OML is 30 to the central ray. IR
is positioned such that its upper margin is at the level of
the highest point of cranial vertex (Figure 45B).

Patient positioning
The patients head is tilted downward 10, so that the canthomeatal line is horizontal.
Central ray
Central ray is oriented downward approximately by 10
and laterally approximately 30 through the ipsilateral
orbit, centered over the TMJ of interest.
If the condylar motion is limited, then only the neck is
visible due to superimposition of the temporal component
on the condylar head.
This view is rarely being used now, due to unwanted
radiation exposure to the eyes.
In addition to the above-mentioned techniques for
viewing the TMJ, reverse Townes view and submentovertex projections can be used to assess the TMJ.

LESSER KNOWN/FORGOTTEN EXTRAORAL


RADIOGRAPHIC TECHNIQUES
There are many lesser known techniques in maxillofacial
imaging which can be used as powerful tools for demonstrating a large variety of craniofacial structures. Although
new paradigms for X-ray imaging techniques have emerged,
they may not be economic and readily feasible to be used
in many health centers. In such cases, some of these techniques can still be used as a standard procedure for demonstrating various craniofacial structures.

Townes Method or AP Axial Projection


This method demonstrates:

752

The petrous pyramids


Posterior portion of the foramen magnum

Central ray
The central ray is directed through the foramen magnum
at a caudal angle of 30 to OML. It enters approximately
2 inches (6.3 cm) above the glabella and passes through
the level of EAM (Figure 45C).
Structures shown are:

Symmetric image of the petrous pyramids


Posterior portion of the foramen magnum
Dorsal sellae and posterior clinoid processes projected
within the foramen magnum
Occipital bone
Posterior portion of the parietal bones.

May Method
When a patient with suspected fracture of zygomatic
arch comes to the department, radiographs that are usually advised for these patients are submentovertex view,
Schullers method and sometimes Waters view as well.
But there are always chances of superimpositions of other
structures on the zygomatic arch when these methods are
used. Thus, when a radiographic view of zygomatic arch is
required, the alternative method would be May method,
also known as tangential projection.
This method demonstrates:

Zygomatic arch
Temporal process of zygomatic arch
Temporal bone
Useful in patients who have depressed fractures or flat
cheek bones.

Positioning of patient
The patient is asked to stand in an upright position. Arms
are placed in comfortable position, shoulders are made to lie
in the same horizontal plane. The midsagittal plane of the
body is centered to center of the image receptor (Figure 46A).

Chapter 28 Radiographic Techniques

Figure 45
A

30

CR

(A) Position of patient in Townes method. (B) Upright radiograph. (C) Upright radiograph with central ray
directed 30 degrees to OML

Figure 46
B

15 top of head tilt

15

CR

(A) Position of the patient in May method. (B) Upright radiograph. (C) Central ray in May method

Positioning of the part


Neck is extended such that the IOML is as parallel with
the plane of the IR as possible. Chin is rested on the IR.
The midsagittal plane is rotated approximately 15. Top
of the head tilted away from the side being examined 15.
It is ensured that the central ray is tangent to the
lateral surface of the skull. The central ray skims across
the lateral portion of the parietal bone and the mandibular angle to project the zygomatic arch onto the IR
(Figure 46B).
Central ray
The central ray is directed perpendicular to the IOML and
passes through the zygomatic arch at a point approximately
1 inches posterior to the outer canthus. The IR is centered
to the central ray (Figure 46C).

Structures shown are:

Zygomatic arch free of superimposition


Temporal process of zygomatic arch
Temporal bone.

Axiolateral Oblique Projection


Another lesser known technique is the axiolateral oblique
projection, also known as original law method. This method
can otherwise be called double tube angulation.
This method demonstrates:

Mandibular condyle
Mastoid cells
Lateral portion of the petrous pyramid
Superimposed internal and external acoustic meatuses
Mastoid emissary veins.
753

Section X Radiographic Methodology

Figure 47
B

15

CR

(A) Position of the patient and direction of central ray in axiolateral oblique projection/
original law method. (B) Upright radiograph

Positioning of the patient


Patient is positioned with the head in a true lateral position, the flexion of the patients head is adjusted such that
the interpupillary line is perpendicular to the plane of the
image receptor; and the IOML and midsagittal plane are
parallel with the IR plane (Figure 47A).

Also useful for good projection demonstration of blowout fracture.

Position of the patient


The patient is placed in prone position. The midsagittal
plane of the patients body is centered to the midline of the
image receptor (Figure 48A).

Central ray

Position of the part

Central ray is directed 15 caudal and 15 anteriorly. It


enters approximately 2 inches posterior to and 2 inches
above the uppermost EAM and exits the downside mastoid
process. The IR is centered to the central ray.
The structures shown are (Figure 47B):

Mandibular condyle
Lateral portion of the petrous pyramid
Superimposed internal acoustic meatus
Mastoid emissary veins when present
Mastoid cells.

Modified Parietoacanthial Projection


This method demonstrates:

754

Facial bones with less axial angulation than with the


Waters method
Petrous ridges projected immediately below the inferior border of the orbits at a level midway through the
maxillary sinus
Maxillary sinus
Zygomatic bone
Inferior orbital margin
Nasal septum
Mandible

The patients head is rested on the tip of the extended


chin. The neck is extended to a lesser amount than done
in Waters method. OML is adjusted to form approximately 55 angle with the plane of the IR, with the
average patients nose about 3/4 inch away from the
IR. The head is adjusted so that the midsagittal plane
is perpendicular to the plane of the IR. The IR is centered at the level of the acanthion (Figure 48B).

Central ray
The central ray is directed perpendicular to exit the acanthion
(Figure 48C).
The structures shown are:

Petrous ridges
Zygomatic bone
Inferior orbital margin
Nasal septum
Mandible.

Acanthioparietal Projection Reverse Waters


Method
This method is used to demonstrate:

Superior facial bones

Chapter 28 Radiographic Techniques

Figure 48
B

55

CR
35

(A) Position of patient in parietoacanthial projection. (B) Upright radiograph. (C) Central ray

Figure 49
B

CR

37

(A) Patient positioning in acanthioparietal positioning. (B) Upright radiograph. (C) Central ray

Orbit
Zygomatic bone
Maxillary sinus
Petrous ridge.

Position of the patient


The patient is seated in upright position. The midsagittal
plane of the body is centered to the midline of the cassette
(Figure 49A).
Position of the part
The patients chin up is brought up. The extension of
the neck is adjusted so that the OML forms 37 with the
plane of the IR. The OML is made perpendicular to the
plane of the IR. The patients head is adjusted such that

the midsagittal plane is perpendicular to the plane of the


IR (Figure 49B).
Central ray
The central is directed perpendicular to enter the acanthion and centered to the IR (Figure 49C).
The structures shown are:

Superior facial bones


Orbit
Zygomatic bone
Maxillary sinus
Petrous ridge.

Thus, the forgotten techniques overcome the limitations


of newer techniques in terms of economics and feasibility,
and venture should be undertaken to refresh the forgotten
755

Section X Radiographic Methodology

techniques and bring them into use today as well. These


techniques can still be used as a standard procedure for
demonstrating various craniofacial structures.

Figure 50

PANORAMIC RADIOLOGY
Panoramic radiology is considered a curvilinear variant of
conventional tomography, in which a single tomographic
image of facial structures includes both maxillary and
mandibular dental arches and their supporting structures.
Panoramic radiography is derived from the word panorama which refers to an unobstructed or complete view
of a region in every direction. The term orthopantomography was coined by Paatero and Sairenji which is derived
from orthostraight or correct, pan (abbreviation for panorama), tomotomography is the imaging of depth of tissue layers without the interference of tissue above and
below that plane of tissue.

Origin of Panoramic Radiology


In the early days of the development of panoramic radiology, various experiments were carried out on the placement
of the X-ray source (intraoral/extraoral and stationary/
moving source), placement of the film (adapted intraorally,
lingual to teeth, or placed extraorally by adapting the film
to the jaws) and patients position (stationary/rotating
chair).
Dr H Numata, a Japanese, in 1933, devised a technique
to image the jaws by placing an intraoral lm and an
extraoral source of X-rays with a slit collimator which
rotated about the patients head to image the jaws. In his
technique the patient was stationary.
In 1943, Horst Beger devised a prototype of the panoramic machine where the lm was adapted extraorally
on the jaws and the source of X-rays was placed intraorally.
In 1946, Dr YV Paatero, experimented with a stationary
X-ray source and the patient seated in a revolving chair.
He called this technique parabolography.
In the present day panoramic imaging techniques, the
patient is stationary and the X-ray source and the cassette
carrying the lm are rotated about the patients head.
The X-ray source and cassette drive/carriage assembly are
incorporated into a C-arm. These machines have an optional
cephalostat attachment that can be used for imaging the
skull such as lateral cephalograms, Waters views, anteroposterior view, submentovertex view, etc. (Figure 50).
Many of the panoramic machines have the option of using
digital receptors such as charged-couple device (CCD) and
photostimulable phosphor (PSP) system instead of lmbased technology.

756

Panaromic machine with the cephalostat attachment

Concepts of Panoramic Imaging


Technique and imaging principles
1.

2.
3.

4.
5.

Patient is advised to remove all metallic objects in the


head and neck region such as hair clips, nose rings,
ear rings, chains, spectacles, removable dental appliances, etc.
Patient is instructed to wear a lead apron (Figure 51).
An extraoral panoramic film (5  12 inches) is loaded
into a designated panoramic rigid plastic backed cassette of the same size (Figure 52). The loaded cassette
is placed into the cassette carriage assembly.
Patient may either be seated or standing facing the
radiographer (Figure 53).
Patient is positioned such that his/her jaws are within
the imaginary focal trough.
This can be achieved by asking the patient to stand
erect with the neck extended and the chin supported
by the chin rest (this helps in establishing the vertical
height). The anteroposterior position can be achieved
by asking the patient to bite in the groove in the biteblock. The bite will also help in relieving the teeth
from occlusion thereby preventing any cuspal overlaps. Apart from these measures, the machines have
inbuilt light-beam guides that can be used for orientating the head of the patient to coincide with the
midline in the sagittal plane, ala tragal line and a line

Chapter 28 Radiographic Techniques

Figure 51

Figure 53

Patient standing upright facing the radiographer


Individual wearing a lead apron devoid of metallic
objects in the head and neck region

Figure 54

Figure 52

Panoramic cassette 5  12 inches

6.

7.

8.

of reference running along the corner of the mouth


(canine) and ala of the nose (Figures 54 and 55).
Exposure parameters are set. Most panoramic machines
are equipped to operate between 5485 kVp, 116 mA
and 16 seconds exposure for adults and 14 seconds in
the child mode.
Patient is instructed to place his/her tongue against the
roof of the mouth and remain still during the entire
exposure cycle.
The operator stands behind the lead screen and initiates the exposure by pressing the exposure timer switch
which is also referred to as the dead mans switch as
the timer needs to be pressed for the entire duration of
the 14- or 16-second cycle.

Patients chin positioned on the chin rest and


anterior teeth biting in the groove on the bite rod

Working principle
In rotational panoramic radiography, the patient is stationary and the X-ray source (tube head) and the cassette
carriage assembly (connected to each other via a C-arm),
rotate around the patients head (Figure 56).
As the C-arm rotates, the X-ray tube head and the cassette carriage assembly (Figure 57) rotate in the same direction, whereas the lm along with the cassette moves in a
direction opposite to movement of the tube head. The rate
of the lm movement is adjusted such that it matches with
the speed of the slit shaped beam imaging the patient.
A narrow beam of X-rays (facilitated by a slit collimator
within the X-ray tube head) sweeps across in a horizontal

757

Section X Radiographic Methodology

Figure 55

Figure 57

Cassette carriage
assembly

Cassette with film

Cassette carriage assembly


Light beams showing the midsagittal plane and
ala tragal line

Figure 58
Figure 56
Center of
rotation
C-arm

Cassette
carriage
assembly

X-ray
source
X-ray tube
head

Film within
film-cassette
carriage

Illustration showing moving centers of rotation

X-ray tube head and cassette carriage assembly


connected via the C-arm

plane around an intraorally placed invisible pivot (apparent


intraoral source) referred to as the center of rotation.
In the vertical plane, the X-ray beam sweeps beneath
the occipital area with a negative angulation of 4 to
7.
Unlike older panoramic machines where there was a
xed center of rotation, machines these days make use of
continuously moving center of rotation thereby allowing
the image layer to conform to the elliptical shape of the
dental arches.
The moving centers of rotation if plotted can be
traced into a shape of two arcs meeting at the midline

758

approximating the lingual aspect of the mandibular symphysis (Figure 58).


With the above understanding, in the initial few seconds of exposure, when the X-ray beam is imaging the
TMJ on the left side the center of rotation lies near the
lingual surface of the body of the mandible of the right
side. Futhermore, as different areas of the mandible are
imaged, the center of rotation correspondingly relocates
conforming to an arc shape.
Objects located between the center of rotation and lm
are imaged well (real images) and those between the X-ray
source and center of rotation are blurred (ghost images).
All objects that are in the midline such as the cervical
spine appear as double images (pair of real images).
The panoramic machine is calibrated in such a way
that the horizontal and vertical magnication is evenly

Chapter 28 Radiographic Techniques

Effect of patient positioning in the focal trough on


the resultant image

Figure 59

Dotted line enclosing


imaginary image layer
or focal trough

Illustration showing focal trough

Patient position in the focal


trough

Image characteristics

Patient overbites on the bite


block. The incisal edges of
teeth placed way ahead of
the groove on the bite

The mandibular anterior teeth


appear narrow and fuzzy and the
mandibular ramus and condyles will
be superimposed by the image of
the cervical spine
However, this technique may be
employed if the area of interest is the
maxillary sinus and the nasal cavity

Patients anterior teeth way


too short of the bite

Anterior teeth appear horizontally


magnified and blurred

Patient is positioned with the


chin tipped down too steeply

The area in the mandibular anterior


region may appear blurred. Anterior
teeth in the maxilla appear elongated
and those of the mandible will appear
stunted
Moreover, the hyoid bone may appear
superimposing on the roots of the
mandibular premolars and molars and
the TMJ region may not be imaged

matched so as to produce a nal proportionate image. This


is achieved by adjusting the speed of the X-ray tube head
with regards to the movement of the lm.
Concept of focal trough
The focal trough is also referred to as the image layer
which is roughly elliptical in shape to conform to the morphology of the dental arches. The image layer is narrower
toward the anterior teeth. Some authors describe the focal
trough as the plane of acceptable detail.
It is a three-dimensional imaginary curvilinear zone,
in which objects when positioned, will be imaged well. All
objects beyond this image layer may not be imaged or seen
as distorted and blurred images (Figure 59).
When the object of interest is positioned well within this
image layer, the vertical and horizontal dimensions will
match, resulting in a sharply dened image.

Characteristics of Ghost Images


All objects that lie between the source of X-ray beam
and center of rotation are projected as ghost images.
These are seen as blurred images on the opposite side of
the radiograph away from the real image, similar structure as the real image, positioned at the higher level on
the radiograph when compared to its real counterpart
and they are relatively more vertically blurred than
horizontally. Common ghost images seen on the orthopantomograph (OPG) are those of metallic objects such
as ear rings, hair clips and anatomic structures such as
the cervical spine, hyoid bone, angle of the mandible
including the lower border, etc.

A smile-line is created
Patient is positioned with the
chin lifted up

The occlusal plane in the resultant


image either appears flat or as a
reverse curve. This has been referred
to as a sad line or a frown
However, this technique of patient
positioning may be used to improve
imaging of mandibular anterior teeth

Improper midline orientation


of the patient within the focal
trough

Posterior teeth out of the focal trough


will appear broad and exhibit proximal
overlap, whereas on the contralateral
side the teeth will appear slender

Patients neck is slumped and


not straight and extended

A vertical opaque shadow is seen


obscuring the midline structures

Patient instructed to swallow


and hold the tongue against
the hard palate

This technique will prevent


superimposition of the pharyngeal air
space over the roots of the maxillary
anterior teeth

Indications of Panoramic Radiograph


1.

2.
3.
4.
5.

Used a screening radiograph to evaluate the gross


pathologies or developmental disorders affecting the
jaws and teeth.
Patients with limited mouth opening or in individuals
who cannot tolerate the intraoral film (severe gag reflex).
Evaluation of multiple impacted or supernumerary teeth.
Evaluation of the eruption status of teeth.
Evaluation of the size and extent of bony pathologies
such as cysts, tumors, fibro-osseous lesions, etc.

759

Section X Radiographic Methodology

6.

Assessment of the fractures of the jaws, especially the


mandible (however maxillary and mandibular midline
fractures may not be appreciated).
7. Evaluation of the TMJ (condylar pathologies such as
fractures, hyperplasia, degeneration and changes in the
morphology of articular eminence).
8. Although OPG is not the ideal imaging technique for
visualization of the maxillary sinus, the floor, medial
and posterior walls can be appreciated.
9. Gross evaluation of the interdental bone height and
pattern in periodontal disease.
10. Evaluation of styloid process.

Disadvantages and Limitations


1.

2.
3.

4.

5.

Midline structures and the pathologies in the region


may not be appreciated because of the superimposition
of the cervical spine.
Pathologies in the premolar region may be obscured
because of the proximal surface overlap in that region.
Finer details such as incipient carious lesions, minimal
interdental bone loss, trabecular pattern may not be
appreciated as the radiograph has poorer resolution
compared to an intraoral radiograph.
Panoramic radiograph cannot be taken in individuals
with cervical spine injuries and gross maxillofacial injuries that may limit ideal position into the focal trough.
Young children, mentally challenged and unconscious
patients may not be ideal candidates for this imaging
technique.

SPECIALIZED IMAGING
COMPUTED TOMOGRAPHY (CT)
It is also referred to as computed axial tomography, computed tomographic scanning, axial tomography and computerized transaxial tomography.
Godfrey Hounseld and Allan Cormack were instrumental in the development of CT and were awarded the
Nobel Prize in Medicine in 1979 for their efforts. This
radiographic technique blends the principles of thin layer
radiography (tomography) with the use of a computer to
synthesize the image (computed).

760

The intensity of the X-ray beam exiting the body is


determined by:
a.
b.
c.

The energy of the X-ray source


The distance between the source of X-rays and the
detector
The attenuation of the beam by materials in the object
being scanned.

Although a single source and a single-detector array can


produce a single scan, the efficiency of the scanning system can be increased multiple folds by using multiple X-ray
beams and equivalent number of detectors. Each scan produces a penetration or absorption profile. However, construction of the image requires profiles obtained at different
angles through the patient under study. The X-ray source
and detector assembly are rotated around the patient
(3,600) to produce multiple profiles of the particular site of
interest.
The X-ray beam attenuation is collected in a grid like
pattern called matrix. Each square in the matrix is made
up of a pixel (picture element), which represents the X-ray
attenuation of a small nite volume of tissue called voxel
(volume element). The typical image matrix for most CT
scanners is 512  512 pixels.
Each pixel represents a calculation of the actual attenuation of the X-ray beam by constituents within the body.
A number (CT number or Hounseld unit [HU]) is designated for each pixel corresponding to the degree of beam
attenuation (Table 7). The CT numbers generally range
from 1000 to 1000. By convention, water is designated
the number 0. However, some scanners may differentiate
between CT numbers that range from 2000 to 6000,
but most monitors may display only 256 gray-scales and
the human eye can perceive only 64 shades of gray.
Since the CT numbers represent attenuation or density,
the computer constructs an image by printing the numbers

Table 7

CT numbers for commonly imaged tissues

Tissue

CT number

Air

1000

Lung

200

Fat

100

Water

CSF

15

Working Principle

Blood

20

The computed tomographic image is initiated by a process


called scanning. Beams from one or several small X-ray
sources are passed through the body and intercepted by
one or more radiation detectors. These radiation detectors
produce electrical impulses that are proportional to the
intensity of the X-ray beam emerging from the body.

Gray matter

40

White matter

45

Muscle

50

Medullary bone

300

Cortical bone

1000

Chapter 28 Radiographic Techniques

or by assigning different shades of gray to each number


thereby transforming a string of numbers into an image.

contacts the detector array, thus improving CT image


quality.

Computed Tomographic Scanner Assembly

Patient support couch

Though CT scanners are available in different system configurations, they all have the same basic components:

The patient support couch helps in stabilizing the position


of a patient during a CT scan. The couch must be made of
a low-molecular-weight material such as carbon filter to
ensure that the path of the X-ray beam is not altered before
or after it traverses the patient. The couch is motorized so
that the movement of the patient for slice acquisition is
smooth controlled and reproducible. The angle of the patient
couch can be altered to capture images in different planes.
The angulation of the patient is reported as tilt on the
printout of the image.

1.
2.
3.
4.

Gantry
Patient support couch
Computer
Control console.

Gantry
The gantry is made up of the detector array, patient support couch, and the X-ray tube or source. The gantry can
be tilted up to 300. The facility to tilt helps in excluding
structures from the scan that may degrade the final image
(e.g., metallic dental restorations).
Detector array The detector is made up of multiple discrete cells or detectors. Each of these detectors acquires
specific information for each slice of the scan and transmits it to the computer. The present fourth generation CT
scanners have up to 2,400 detectors.
The detectors contain either a crystal scintillation
detector or a gas-lled detector. Commonly used scintillation detectors are manufactured with cesium iodide (CsI),
bismuth germanate or cadmium tungstate (CdWO4). These
solid-state detectors are coupled optically to a photodiode.
Solid-state detectors exhibit detection efciency that
approaches 100% but cannot be packed closely together.
Gas-lled detectors contain either xenon or a xenon
krypton mixture. These gases have a high atomic number,
are inert, and display minimal afterglow. The gas is contained under high pressure in the detector array. The individual gas-lled detectors can be placed closely together;
the gas, however, in the detector only produces approximately 50% detector efciency. Regardless of the material
used to capture information, the spacing of each discrete
detector coupled with their detection efciency determines
the efciency of the scanner and the ultimate spatial
resolution.
X-ray source The X-ray source for the currently available scanners consists of an X-ray generator and an X-ray
tube. The X-ray generator is designed to produce a high
milliampere (up to 400 mA) beam at a nearly continuous
rate. The large amount of heat generated through continuous
beam production necessitates the use of a large rotating
anode and fairly large focal spot.
The X-ray beam is collimated before it traverses through
the patient (pre-patient collimation) and at the detector
array (post-patient collimation). The pre-patient collimation
decreases the radiation dose to the patient. The post-patient
collimation reduces the amount of scattered radiation that

Computer
The rapidity of capturing the image, acquiring data, and
larger matrix size (512  512) necessitates the use of highspeed computers.
Modern CT scans require computers that can solve up
to 30,000 equations simultaneously. The time it takes the
computer to generate a visible image after data acquisition
is termed reconstruction time. Reconstruction time for a
single slice is usually about 1 second. These computers can
constitute up to one-third the cost of a CT scanner.
Control console
The control console allows the operator to select the parameters of the CT scan, view the image as they are being
generated. Many consoles have two monitors so that the
technician and the radiologist can manipulate the image
as the data is acquired. Image data is stored into the computer so that it can be formatted later into a number of
ways. Data is stored either on magnetic tapes or disks. Most
CT images are viewed on a film. The electronic data from
each view is transferred onto a film using laser cameras.
The most common film format is 14  17 inches and may
contain 415 images.

Advantages of CT

Multiplanar imagingimage acquisition in crosssectional or in other planes.


Greater geometric precisionCT solves the problem of
superimposition by allowing the clinician to view a
series of thin sections (1.510 mm) thick depending on
the anatomic site.
Manipulation of the acquired imagethe radiographic
contrast and brightness can be adjusted based on the
requirement.
Soft tissue imaginghelps in separating subtle tissue
contrast differences (as low as 0.5%).
761

Section X Radiographic Methodology

Helps in distinguishing objects of subtle differences


in density such as between blood and fat, blood
and CSF.

Disadvantages of CT

Expensive.
Patients exposure to radiationCT is considered a high
radiation dose technique (depends upon region imaged,
number of slices, thickness of slice and kVp). For a
head scan the effective dose has been calculated as
24 mSv and 515 mSv for a body scan.
A mid skull dose for a PA view (PA skull) or Townes
view is about 35 mGy, whereas a mid skull dose of
about 3455 mGy is seen with a CT.
Production of artifacts, especially when metallic restorations are located in the plane of tissue being scanned.
These streak type artifacts may obscure radiographic
findings in the CT scan and render it useless for
diagnosis.

Uses of CT in Dentistry

Evaluation of the presence and extent of clinically suspected pathology in the head and neck region including cysts, tumors and infections.
Detection of the extension of disease process into the
paranasal sinuses, base of skull and orbit.
Determination of the location, extent and displacement
of maxillofacial skeletal fractures, including detection
of subdural and epidural hematomas.
Salivary gland imaging.
Evaluation of potential implant sites using 3D image
reconstruction.
Evaluation of the components of the TMJ.
CT-guided fine needle aspiration biopsies.
Virtual surgeries.

DENTOMAXILLOFACIAL CONE-BEAM
COMPUTED TOMOGRAPHY (CBCT)
Radiology has always been a tremendous asset in clinical
dentistry. Intraoral imaging, whether digital or film, continues to provide the best spatial resolution of any imaging
method currently available. However, because spatial information is lost when it is collapsed into a two-dimensional
(2D) image, in many cases, two or three intraoral radiographs
taken from different angles are recommended. The clinical
diagnostic capacity of intraoral radiography is influenced
by a number of variables, including beam angulation,
exposure time, receptor sensitivity, processing, viewing conditions, superimposition of anatomic structures and lesion

762

location. Panoramic radiography, in which images of both


jaws are obtained through the synchronous rotation of
an X-ray source and image receptor around a stationary
patient can provide broad coverage of both jaws and teeth,
but without the anatomical detail available with intraoral
radiography. Moreover, due to the distance between the
radiation source, object and image receptor, there is a
magnifying factor associated with image formation, and
projection geometry results in image distortion and a
marked overlapping of tooth crowns. In order to reduce
the level of image distortion and ensure that image quality
is not affected by ghost images, accurate preparation and
positioning of patients is needed. In contrast to both intraoral and panoramic techniques, which by their nature are
incapable of capturing information about the third dimension of teeth and adjacent structures, and can thus provide
only limited information about lesion origin, size and
location, medical CT devices are able to provide 3D images
of the dentomaxillofacial region. However, high patient
doses, high cost and lack of availability precludes the routine use of medical CT in dentistry. In response to the high
demand for a technique that could provide 3D data at a
lower cost and with lower radiation doses than the conventional CT used in medical radiology, CBCT was developed and introduced specifically for dentomaxillofacial
imaging.

Historical Background
Computed tomography (tomography is derived from the
Greek words tomos, meaning slice or section, and graphia,
meaning describing) was introduced in 1972 by the engineer Godfrey Hounsfield and the physicist Allan Cormack.
In 1979, Cormack and Hounsfield, who had worked independently to develop CT, were jointly awarded the Nobel
Prize in Physiology or Medicine for their work on the
tomographic principles used in computing the spatial distribution of a physical quantity of an object examined
from different directions and transferring this data into
easily readable images. CT represented the first practical
medical application of the tomographic principle in the
field of medicine, providing high-contrast images without
superimposition of adjacent anatomic structures. The first
clinical CT scanners, installed between 1974 and 1976,
were dedicated to head-imaging only, and whole body
systems became available in 1976. Several hours were
needed just to acquire the raw data necessary to produce a
single image slice, and several days were required to
reconstruct an image from this raw data. Great improvements have since been achieved in speed, patient comfort
and resolution. Today, more anatomy can be scanned in
less time, which helps to eliminate artifacts from patient
motion and provides excellent diagnostic image quality at
the lowest possible effective doses.

Chapter 28 Radiographic Techniques

Figure 60
A

X-ray source

X-ray source

Translation

Translation
Rotation

Rotation
Object

Object

Detector
Detector

X-ray source

X-ray source

E
Object

Helical X-ray beam path


Detector

Detector

(A) First generation. (B) Second generation. (C) Third generation. (D) Fourth generation. (E) Helical CT.
Evolution of CT scanners from the original design

CT scanners have developed over four generations from


the original design in which both X-ray source and detector
revolved around the patient to one in which a xed circular array detects the remnant beam originating from a
revolving X-ray tube. First generation scanners used parallel pencil beams of X-rays for data acquisition and
required both translation and rotation of the beam source
and a single-detector apparatus (Figure 60A). Second generation scanners also operated in a translation-rotation mode,
but employed multiple detectors that captured a small, fanshaped beam in an attempt to reduce scan time (Figure 60B).
With third generation scanners, scan time was further
reduced through the use of a single-detector arc in conjunction with fan-beam X-ray geometry (Figure 60C), and
with the fourth generation design, stationary detectors were
distributed along a full circle to form a detector ring, with
only the X-ray source in orbit (Figure 60D).
From 1974 to 1987, CT scanners employed high-voltage
cables wrapped around an elaborate set of rotating drums
and pulleys to transfer power to the X-ray tube. A rotating
frame or gantry, would spin 360 in one direction to produce an image or slice, and then spin 360 in reverse to
produce a second slice. Between each slice, the gantry would
come to a complete stop, and the patient table would be
moved forward by an increment equal to the slice thickness. In the mid-1980s, the elaborate X-ray cable-and-drum

system was replaced by an innovation called the power


slip ring, which transferred electric power from a stationary
source onto the continuously rotating gantry. The innovation of the power slip ring led to the introduction in 1989
of a helical CT, in which the patient moves continuously
through the gantry while the X-ray source moves simultaneously down and around the patient in the same direction (Figure 60E) to acquire a continuous helix of data. By
combining data acquisition with continuous movement of
the patient through the gantry during scanning, multiple
image slices can be captured quickly, reducing exposure
time and artifact motion. The most recent technological
advancement in CT acquisition occurred in 1998, when the
single row of detectors was replaced with multiple rows
arranged along the long axis of the human body. This
increased the width of the volume acquired in each rotation, resulting in a more efcient use of the X-ray beam.
Contemporary CT multidetector scanners possess detector
arrays with between 4 and 512 rows of detectors. In current
practice, most systems use a combination of helical and multidetector technology; however, despite the reduced scan
times of multidetector helical CT (MDCT), radiation doses
are still relatively high, as are the costs.
Over time, concerns over detector costs, radiation and
acquisition time led to the development of CT scanners in
which the fan-beam is replaced by cone-beam geometry.

763

Section X Radiographic Methodology

First adapted for potential clinical use in 1982 at the Mayo


Clinic Biodynamics Research Laboratory, the initial interest
in CBCT was focused primarily on applications in angiography, radiotherapy and mammography. A practical conebeam algorithm for tomographic reconstruction of 2D
projection data was rst illustrated by Feldkamp et al who
instead of a fan-beam reconstruction formula, used a convolution back-projection formula to directly reconstruct
a 3D density function from a set of 2D projections. The
formula provided convenient computation with useful properties and relatively small errors in many practical applications, and today, a modied Feldkamp algorithm is the
reconstruction algorithm most frequently used in dentomaxillofacial CBCT. Despite the fact that the original Feldkamp
back-projection algorithm was published in 1984, CBCT
units dedicated to dentomaxillofacial radiology could not
be marketed for another 15 years because economic X-ray
tubes, high-quality detector systems and sufciently powerful personal computers were unavailable. Eventually, in
1999, the rst dentomaxillofacial CBCT (DMCT) unit, the
NewTom DVT 9000, designed by Attilio Tacconi and Piero
Mozzo and produced by QR, Inc. of Verona, Italy, was
introduced in Europe and was followed in 2001 by the introduction in Japan of the 3D Accuitomo-XYZ Slice View
tomography system (J Morita Mfg Corp., Kyoto, Japan).
A spate of revolutionary CBCT applications reached the
dental market in the 2000s, marking the beginning of a
new era in the eld of dentomaxillofacial radiology. New
technological specications and settings include multiple
eld of views (FOVs) and voxels that can better address a
variety of specic tasks and imaging which can be conducted with the patient in supine, seated, or standing positions. There are also several hybrid machines offering CBCT
imaging along with panoramic and cephalometric radiography. Table 8 provides specications of some contemporary CBCT systems, including product, manufacturer and
software name; detector type; patient positioning options;
FOV and voxel size options; effective doses according to FOV
(for adults); and additional features. Figure 61A, B show,
respectively, a large FOV CBCT unit (iCAT Next Generation,
Imaging Sciences, Hateld, PA, USA) with a seated patient
and a small FOV CBCT unit (Kodak 9000, Carestream,
Rochester, NY, USA) with a standing patient. All units are
similar in size and shape to a panoramic machine.

Fundamentals of CBCT
Whereas conventional CT scanners emit a fan-shaped X-ray
beam and require a stack of multiple slices to obtain a complete image, CBCT systems operate by focusing a coneshaped beam on a 2D detector that performs one pass or
less around the patients head to produce a series of 2D
images. A cone-beam algorithm is then applied to this image
dataset, allowing the operator to extract planar and curved
reconstructions of varying thicknesses in any orientation
and to generate accurate 3D images of bone and soft tissue
764

surfaces that can be read on a computer monitor. The use


of special algorithms allows not only conventional axial
plane reconstructions, but multiplanar, reformatted 2D, 3D
and panoramic reconstructions as well. Whereas fan-beam
geometry uses primary reconstruction of data to produce
axial slices from which orthogonal planar images are generated using secondary reconstruction, cone-beam geometry uses multiple-basis data projections to secondarily
reconstruct orthogonal images. Raw primary data consists
of a series of single-projection imagesindividually referred
to as basis, frame or raw imagesthat resemble cephalometric radiographic images, only each image in the series
is slightly offset from the next. An image volume is usually
calculated and constructed from several hundred 2D basis
images, the complete series of which is referred to as the
projection data. The number of individual images comprising the projection data is determined by the frame rate
(number of images acquired per second), the completeness
of the scan arc (generally 180360) and the speed of rotation. Figure 62 shows schematic diagram of cone-beam
and fan-beam imaging geometries and secondary reconstruction processes.
When the X-ray beam passes through different layers of
tissues, the transmitted intensity will be equal to the sum
of the attenuation values of the various voxels that lie in
the specic straight path of the X-ray beam. An average
attenuation coefcient value for each voxel in the section
is derived from the different rays surrounding the area of
interest. By calculating the attenuation value of each voxel,
it is possible to differentiate between various tissues in
a slice based on their computed attenuation values. Most
visualization software offer a default presentation consisting of a series of contiguous, interrelated 2D images in three
orthogonal planes (axial, sagittal and coronal). Figure 63
shows schematic diagram of axial, coronal and sagittal
planes and corresponding CBCT images. In contrast to
medical CT, in which data is usually transferred from an
acquisition workstation to a separate console for formatting, with CBCT, both image acquisition and visualization
are generally performed on the same computer.
X-ray generation
Medical CT systems utilize high-power X-ray generators
to acquire large volumes of data at high speeds, which
requires high X-ray energy. Typically, CT systems operate
in a range of 80140 kVp, with a maximum power of
20100 kW; however, these systems can only be operated
at maximum power for a limited time, usually from 3060
seconds. CBCT systems operate at 80120 kVp, with most
units functioning at the lower end of this range, which
does not differ substantially from the operating parameters of panoramic radiographic equipment. Although CBCT
and CT have similar focal spot sizes (0.50.8 mm), unlike
CT, many CBCT systems possess a stationary anode, with a
tube current generally within the range of 120 mA, which

Table 8

Specications of some contemporary CBCT systems, including product, manufacturer and software name; detector type; patient positioning options; FOV and voxel
size options; effective doses according to FOV (for adults); and additional features

Company

Model

CBCT image
detector

Patient
positioning

Field of view
diameter/height

Voxel size
options

Estimated effective
doses for adult (ICRP
2007)

Software

Extra features

Quantitative
Radiology,
Verona, Italy

NewTomVGi
CBCT

Amorphous
silicon flat
panel

Standing
Seated
Wheelchair

Five FOVs from


6  6 cm to
15  15 cm

From 0.075 to
0.30 mm

15  15 FOV (194 Sv)


(Pauwels et al, 2012)

NNT viewer

Safe beam*
Pulse system**
FS: 0.3 mm

Quantitative
Radiology,
Verona, Italy

NewTom 5G
CBCT

Amorphous
silicon flat
panel, 20 
25 cm

Supine

Five FOVs from


6  6 cm to
18  16 cm

Ultra high:
0.075 mm;
High: 0.15 mm;
Low: 0.30 mm

Studies are running

NNT viewer

Safe beam*
Pulse system**
FS: 0.3 mm in standard
mode
FS: 0.15 mm in zoom
mode
Ergonomic, two stage
patient chair

J. Morita,
Kyoto, Japan

Veraviewepocs
3D and
Veraviewepocs
3De

CMOS flat
panel detector

Standing

Veraviewepocs 3D
4  4 cm;
4  8 cm;
8  8 cm
Veraviewepocs 3De
4  4 cm;
4  8 cm

0.125 mm

73 Sv (with 8  8 cm
FOV)
(Pauwels et al, 2012)

i-Dixel 2.0/One
data viewer/
One volume
viewer

Specifically designed for


endo, perio and general
dentistry.
Dose reduction feature

CBCT  Pano/
Ceph options
(Hybrid model)
3D Accuitomo
170
CBCT

CMOS flat
panel detector

Seated

Nine FOVs ranging


between 4  4 cm
and 17  12 cm

From 0.08 to
0.250 mm

43 Sv (with the


smallest FOV); 50 Sv
(with 10  5 cm FOV)
(Pauwels et al, 2012)

i-Dixel 2.0/One
data viewer/
One volume
viewer

High-quality images with


low dose

Imaging
Sciences,
Hatfield,
PA, USA

I-CAT Classic
CBCT

Amorphous
silicon flat
panel, 20 
25 cm

Seated

16  1322 cm

Between 0.2 and


0.4 mm

Standard scan 69 Sv


(Ludlow and Ivanovic,
2008)

Xoran Cat
iCATvision
3DVR

Quick launch
InVivoDental and
Dolphin software

Imaging
Sciences,
Hatfield,
PA, USA

I-CAT Next
Generation
CBCT

Amorphous
silicon flat
panel, 20 
25 cm

Seated

Standard: 16 
6, 8, 10, 13 cm
Extended:
17  23 cm

From 0.125 to
0.4 mm

87 Sv (with 16  13 cm)


(Ludlow and Ivanovic,
2008)

iCATvision
InVivoDental
3DVR

720 rotation possible with


extended FOV

Vatech,
E-WOO
Technology,
South Korea

PaX-Duo 3D
Pano  CBCT

Amorphous
flat panel

Standing
Wheelchair
accessible

From 5  5 to
15  13.5 cm

0.080.3 mm

FOV (5  5 cm)
42.52 Sv
FOV (12  8.5 cm)
120.69 Sv
Provided from company.
Unpublished

EasyDent/Ez3D

Auto-switching system
between sensors
Pulsed scan**

(Contd...)

Chapter 28 Radiographic Techniques

J. Morita,
Kyoto, Japan

765

766

Table 8

Continued
Model

CBCT image
detector

Patient
positioning

Field of view
diameter/height

Voxel size
options

Estimated effective
doses for adult (ICRP
2007)

Software

Extra features

Vatech,
E-WOO
Technology,
South Korea

PaX-Reve 3D
CBCT/Pano/
Ceph

Amorphous
flat panel

Standing
Wheelchair
accessible

From 5  5 cm to
15  19 cm

From 0.08 to
0.25 mm

FOV 5  5 cm 12.16 Sv


FOV (15  15 cm)
71.47 Sv
Provided from company.
Unpublished

EasyDent/Ez3D

Metal artifact removal


Pulsed scan**

Kodak Dental
Systems,
Carestream,
Rochester,
NY, USA

Kodak 9000
3D & 9000c 3D
CBCT/Pano/
Ceph

CMOS sensor
with optical
fiber

Seated
Standing
Wheelchair

5  3.8 cm single
9  7  3.75 cm
stitched

0.0760.2 mm

5  3.8 cm
1940 Sv
(Pauwels et al, 2012)

Kodak Imaging
Software

Focused small FOV


Stitching#

Kodak Dental
Systems,
Carestream,
Rochester,
NY, USA

Kodak 9500
FOV CBCT

Amorphous
silicon flat
panel

Seated
Standing
Wheelchair

Medium:
15  9 cm
Large:
18.4  20.6 cm

0.20.3 mm

Medium FOV: 92 Sv;


large FOV: 136 Sv
(Pauwels et al, 2012)

Kodak Imaging
Software

Planmeca
Oy, Helsinki,
Finland

Promax 3D
CBCT/Pano/
Ceph/

Flat panel
sensor

Seated
Standing
Wheelchair

8  8 cm, 8  5 cm,
4  8 cm, 4  5 cm

0.1, 0.2, 0.4 mm

30306 Sv
(Qu et al, 2010)

Romexis

Improved artifact removal


Extraoral bitewing
Stitching#

Planmeca
Oy, Helsinki,
Finland

Promax 3D
Max CBCT

Flat panel
sensor

Seated
Standing
Wheelchair

5.5  5 cm to
23  16 cm;
full skull: 26  23 cm

0.1, 0.2, 0.4,


0.6 mm

Studies are running

Romexis

Artifact removal
Full skull scan

Soredex,
Tuusulu,
Finland

Scanora 3D
CBCT  Pano

CMOS flat
panel

Seated

From 6  6 cm to
14.5  13 cm

0.130.35 mm

Largest FOV: 68 Sv


(Pauwels et al, 2012)

On Demand

Specific ear, nose, throat


imaging possible

Soredex,
Tuusulu,
Finland

Scanora 3Dx
CBCT Pano

CMOS flat
panel

Seated

From 5  5 cm to
24  17 cm

0.10.5 mm

Not available

On Demand

MyRay,
Cefla Dental
Group, Imola,
Italy

Skyview CBCT

Image
Intensifier
CCD sensor

Supine

FOV diameter:
11, 15, 17 cm

0.17, 0.23, 0.33

Largest FOV: 87 Sv


(Pauwels et al, 2012)

Myray skyVIEW

Pulsed emission**

Sirona Dental
Systems,
Bensheim,
Germany

Galileos
Comfort CBCT
Cephalometric

Proprietary
Siemens
Technology

Standing
Seated

15  15  15 cm

0.150.3 mm

84 Sv
(Pauwels et al, 2012)

Galaxis, Sidexis,
Galelios Implant

Galelios surgical guides

*Safe Beam technology reduces radiation level according to patient size. **Pulse system that activates the X-ray source only when needed. Generally CBCT systems have stationary focal spot (FS) size of
0.50.8 mm. NewTom 5G allows the patient to be seated initially and then moved comfortably into a supine position. #Separate scans can be combined to obtain the whole arc.
Data is collected from different company sites and articles. Most features are optional and effective dose measurements vary between devices according to settings used.

Section X Radiographic Methodology

Company

Chapter 28 Radiographic Techniques

Figure 61
A

(A) Large FOV CBCT unit (iCAT Next Generation, Imaging Sciences, Hatfield, PA, USA) with a seated patient.
(B) Small FOV CBCT unit (Kodak 9000, Carestream, Rochester, NY, USA) with a standing patient

Figure 62
Cone-beam

Fan-beam
X-ray source

X-ray source
Detector
Secondary
reconstructions

Detector
Basis projections

Primary
reconstruction

Schematic diagram of cone-beam and fan-beam imaging geometries and secondary reconstruction processes

is much lower than CT and which reduces not only generator power, but also heat production. Finally, most CBCT
systems generate a pulsed X-ray beam that coincides with
detector activation, which markedly reduces total scan time
as well as heat production, which translates into lower
radiation doses to patients.
Detectors
All CBCT systems utilize an area detector to capture and
record images. Initially, CBCT detectors were configured

from an image intensifier combined with a charge-coupleddevice (II/CCD) detector, making them large and bulky,
and they tended to produce circular basis image areas
(spherical volumes) rather than rectangular ones (cylindrical
volumes). Nowadays, most CBCT units use flat panel detectors (FPD) comprising a large-area pixel array of hydrogenated amorphous silicon thin-film transistors or in some
more recent cases, large, complementary metal oxide semiconductor technology (CMOS) arrays. X-rays are detected
indirectly by a scintillator such as thallium-doped cesium
iodide or terbium-activated gadolinium oxysulfide, which
767

Section X Radiographic Methodology

Figure 63

Sagittal

Axial

Coronal
Axial

Coronal
Sagittal

Schematic diagram showing axial, coronal and sagittal planes and corresponding CBCT images

Figure 64

Anisotropic
x=yz

Isotropic
x=y=z

spatial-resolving potential than their X-ray intensifier/


charge-coupled device (CCD) predecessors. For each basis
image, the detector records incident X-ray photons, collects
a charge, and sends a signal to the computer. The speed
with which a detector performs this acquisition is called the
frame rate as mentioned earlier in the section Fundamentals of CBCT. For most CBCT units, a full rotation usually
requires between 5 and 20 seconds (similar to or faster than
panoramic radiography), so that each basis image is acquired
and sent within milliseconds, and hundreds of basis images
are acquired within a single exposure rotation. FPDs have
limitations in their performance, including linearity of
response to the radiation spectrum, lack of uniformity of
response throughout the area of the detector, and bad-pixels.
The effects of these on image quality are most noticeable
at lower and higher exposures. In order to ensure that these
inherent limitations of FPD do not affect image quality,
periodic recalibration of detectors is required.
Voxels

A comparison of volume datasets obtained anisotropically


(left) and isotropically (right)

covers the FPD silicon matrix. This scintillator converts


the X-rays to visible light, which is registered by an array of
photo-diodes that produce an electrical charge proportional
to the incident X-ray energy. FPD arrays afford greater

768

A voxel describes the smallest distinguishable box-shaped


part of a 3D image. In CBCT imaging, voxels are isotropic
(equal in all dimensions) and range from 0.4 mm to as small
as 0.076  0.076  0.076 mm. Because voxels are isotropic,
images can be constructed in any plane with high fidelity.
In theory, CBCT can improve the spatial resolution of
high-contrast structures in any chosen viewing plane. This
superior spatial resolution, i.e. the ability to discriminate

Chapter 28 Radiographic Techniques

Figure 65
B

4 4 cm

6 6 cm

10 10 cm

8 8 cm

14 10 cm

17 12 cm

CBCT images of a dry skull obtained using different FOVs of Accuitomo 170 (J Morita, Kyoto, Japan).
(A) 4  4 cm; (B) 6  6 cm; (C) 8  8 cm; (D) 10  10 cm; (E) 14  10 cm; (F) 17  12 cm

objects of different attenuation separated by very small


distances, is one of the most attractive qualities of CBCT
imaging and is largely the result of FPD technology and
isotropic data acquisition. CBCT also reduces the negative
effects of partial-volume averaging, a characteristic of
both conventional fan-beam CT and CBCT imaging that
occurs when the voxel resolution of the scan is greater
than the spatial resolution of the object to be imaged. In
such cases, the pixel is not representative of either the tissue or the boundary, but is given a weighted average of
the different CT values. Figure 64 shows a comparison of
volume datasets obtained anisotropically (left) and isotropically (right).
Field of view
Field of view (FOV) is the term used to refer to the scan
volume of a particular CBCT unit. FOV is determined by

detector size and shape, beam projection geometry and


beam collimation, which limit radiation exposure to a particular region of interest. The availability of different FOVs makes
it possible to select the most appropriate FOV for a specific
application. CBCT units are classified based on FOV size as
small-, medium-, or large-volume units. Because the amount
of X-ray scatter, or noise, decreases with decrease in FOV,
small-volume units tend to offer the highest image resolution. Small-volume units are used to scan either a sextant,
quadrant or single jaw, medium-volume units are used to
scan both jaws, and large-volume units are used to scan the
entire head. Because larger FOVs result in higher effective
radiation doses, as a rule, smaller FOVs are recommended
for dental imaging, with the use of larger FOVs restricted to
cases where a wider view is required, such as orthodontic
and orthognathic surgery treatment planning. Figure 65AF
shows CBCT images of a dry skull obtained using different
FOVs of Accuitomo 170 (J Morita, Kyoto, Japan).

769

Section X Radiographic Methodology

Table 9

Advantages and disadvantages/limitations of CBCT in routine clinical practice

Advantages
Lower radiation doses than conventional CT and beam collimation

Higher radiation doses than 2D imaging

Lower time, space and cost requirements than conventional CT

Less soft tissue discrimination than medical CT

Greater hard tissue definition than medical CT

Limited bone density measurements

Interactive display modes applicable to maxillofacial imaging

Scatter and artifacts created by metal subjects

Interactive treatment planning and computer-aided surgery

Liability

Advantages and Disadvantages/


Limitations of CBCT

basis images acquired, resolution and reconstruction


algorithm.

In clinical practice, CBCT possesses a number of advantages over medical CT, such as lower effective radiation
doses, lower costs, fewer space requirements, easier image
acquisition, higher image accuracy and interactive display
modes such as mutiplanar reconstruction that are applicable to maxillofacial imaging. However, the disadvantages
of CBCT include higher doses than 2D imaging; the inability to accurately represent the internal structure of soft
tissues and soft tissue lesions; a limited correlation with
HUs for standardized quantification of bone density; and
the presence of various types of image artifacts, mainly those
produced by metal restorations, that can interfere with the
diagnostic process by masking underlying structures. In
addition, liability issues related to CBCT remain unresolved.
Table 9 shows advantages and disadvantages/limitations
of CBCT in routine clinical practice.

Greater hard tissue definition than medical CT One of


the most attractive qualities of CBCT imaging systems is
their high spatial resolution, i.e. their ability to discriminate between objects of different attenuations separated by
only small distances. CBCT images possess sub-millimeter
isotropic voxel resolution ranging from 0.4 mm to as low
as 0.076 mm. This superior spatial resolutiona requirement for the accurate depiction of highly detailed small
tooth and osseous structuresis made possible by the isotropic acquisition of the CBCT image detector.

Advantages
Lower radiation doses than conventional CT CBCT
scanners provide adequate image quality for dentomaxillofacial examinations while delivering considerably smaller
effective doses than medical CT. Although not available
on all CBCT systems, beam collimation, which limits radiation to the area of interest, is a highly desirable function
that reduces doses by adjusting the irradiated field according to the FOV. In general, doses range from 13 to 82 Sv for
small and medium FOV CBCT, compared to 4741160 Sv
for medical CT. To ensure that optimal doses are achieved,
diagnostic and image quality requirements should be evaluated on a case-by-case basis and appropriate exposure
parameters and FOVs selected accordingly.
Lower time, space and cost requirements than conventional CT Dental CBCTs are compact (4 m2), easy to
operate, reasonably affordable and require relatively low
maintenance, making them a suitable choice not only for
hospitals and medical centers, but also for many dentists
in private practice. Scan time is comparable to that of
panoramic radiography, varying anywhere from approximately 120 minutes, depending upon FOV, number of
770

Limitations/disadvantages

Interactive display modes CBCT data reconstruction


capabilities make it possible to reorient images generated
in axial, sagittal and coronal planes to realign the anatomical features of the patient. CBCT software also offer
various digital enhancement tools, including zoom/magnification, window/level, ability to add annotation and
real-time measurement free from distortion and magnification. Three distinct categories of display modes are
availablemultiplanar reformatted (MPR), ray-sum and
volumetric images. MPR modes usually include oblique,
curved planar, i.e. distortion-free simulated panoramic
and serial transplanar, i.e. cross-sectionalimage reformation. Ray-sum mode uses images of increasing sectional
thickness to create an image slab representing a specific
volume of the patient. Ray-sum images can be used to
generate simulated projections, such as lateral cephalometric images, that lack the magnification and distortion
of conventional X-rays. However, the technique requires
the use of the entire volumetric dataset, and interpretation
suffers from anatomic noise, i.e. the superimposition of
multiple sections. Volumetric rendering includes two different techniques by which 3D data can be visualized by
integrating and selectively displaying large volumes of
adjacent voxels. Whereas indirect volume rendering (IVR)
involves a complex process that requires the selection and
graphic representation of a range of gray-scale intensities at
the voxel level, direct volume rendering (DVR) is a somewhat simpler process in which an arbitrary threshold of
voxel intensities is selected and all gray values below or
above this threshold are eliminated. The most common

Chapter 28 Radiographic Techniques

Figure 66
A

CBCT image taken with (iCAT Next Generation, Imaging Sciences, Hatfield, PA, USA): (A) Axial view; (B) Simulated panoramic;
(C) Volumetric 3D representation of hard tissue; (D) Serial cross-sectional images; (E) Right generated cephalometric (MIP);
(F) Left generated cephalometric (MIP)

DVR technique is maximum intensity projection (MIP),


which produces visualizations by evaluating the value of
each voxel along an imaginary ray projected from a particular volume of interest toward the eye of the observer,
selecting the highest value as the display value and eliminating voxel intensities that are below an arbitrary threshold. Figure 66 shows simulated panoramic and serial
cross-sectional images along with volume rendering
images. Figure 67 shows the comparison of CBCT ray-sum
generated simulated lateral cephalometric image and lateral view of volumetric rendering with superimposition of
airway space of the same patient (images created using
Invivo software [Anatomage, San Jose, CA]).

Interactive treatment planning and computer-aided


surgery CBCT datasets can be exported in standardized
2D or 3D file formats for visualization and further processing with third-party software. This software, as well as
software produced by CBCT manufacturers themselves,
have increased the clinical applicability of CBCT by, for
example, simulating implant placement, bone grafts and
orthognathic surgical procedures in a true and accurate
virtual environment. The fusion of CBCT images with optical
datasets obtained with 3D optical cameras is a relatively
new concept that provides a digital cast with an accurate
surface to be used or transferred to therapeutic applications
via CAD/CAM (computer added design/computer added
771

Section X Radiographic Methodology

Figure 67
A

Comparison of CBCT ray-sum generated simulated lateral cephalometric image (A) and lateral view of volumetric rendering with
superimposition of airway space of the same patient (B). Images created using Invivo software (Anatomage, San Jose, CA)

Figure 68

Implant placement procedure by combining optical digital impression CEREC and Galileos CBCT images
(Sirona Dental Systems, Bernsheim, Germany)

manufacturing). Eventually, greater simplification and automation can be expected to lead to more precise dental
restorations that can be custom-fit to an individual patient.
Figure 68 shows an implant placement procedure by combining optical digital impression CEREC and Galileos CBCT
images (Sirona Dental Systems, Bernsheim, Germany).
Several CBCT units are also now capable of integrated facial
scanning, whereby CBCT acquisition is accompanied by a
concomitant 3D laser scan of facial soft tissue that is then
overlaid on the bony skull image; the availability of fully
integrated, accurate 3D information of both face and bone
772

allows for more effective planning and prediction of treatment outcomes.


Disadvantages/limitations
Higher radiation doses than 2D imaging CBCT doses,
while lower than those from conventional CT, are still significantly higher than those from conventional dental
radiography. Differences in CBCT device, FOV, exposure
parameters (kVp, mA) and other technical factors result in
substantial differences in radiation doses. Dose is strongly
related to FOV, which varies according to indication.

Chapter 28 Radiographic Techniques

Figure 69
A

(A) Axial CBCT and (B) MDCT images. Arrows show definitely higher soft tissue contrast in
MDCT image compared to CBCT

According to International Commission on Radiological


Protection (ICRP) 2007, effective doses range from 19 to
368 Sv, which is higher than the effective doses from
full-mouth radiographs (FMX) taken with photostimulable
phosphor (PSP) storage and F-speed film with rectangular
collimation (34.9 Sv), FMX taken with PSP and F-speed
film taken with round collimation (170.7 Sv) and panoramic (CCD) (14.224.3 Sv), posterioanterior cephalometric (PSP) (5.1 Sv) and lateral cephalometric (PSP)
(5.6 Sv) radiographs. The largest contributors to effective
dose from CBCT are remainder tissues (37%), salivary gland
(24%) and thyroid gland (21%) tissues.
Recent technological improvements have begun to lower
doses from CBCT. Most scanners now employ a pulse system, in which the X-ray source is activated only when
needed, which is very useful in terms of radiation protection. The use of newer, smart-beam and smart-sensor
technologies, in which the radiation level is set according
to the patient size, should also be encouraged as a method
of radiation protection. Taking into account the higher
radiosensitivity of children, it is imperative that the use of
CBCT in children is fully justied over conventional X-ray
imaging. Needless to say, conducting routine or screening
imaging before obtaining a medical history and performing a clinical examination is an unacceptable practice.
Less soft tissue discrimination than medical CT Dynamic
range refers to the range of incident signal intensities that
can be successfully detected and transmitted as image
data. In general, the greater the dynamic range, the better
the contrast resolution, i.e. the ability of an imaging system to discriminate differences in tissue attenuation, which
varies according to the composition and nature of the tissue imaged. A low power configuration is often associated
with increased noise and a smaller dynamic range, resulting in lower contrast resolution. Currently available CBCT

systems in the market are typically described as having soft


tissue contrast discrimination of approximately 10 HU, the
numeric information contained in each pixel of a CT image
which represents tissue density, whereas modern medical
CT scanners have contrast resolution of 13 HU. This limited
contrast resolution remains a barrier to the extension of
CBCT technologies into diagnostic imaging, which requires
the ability to detect the internal structure of soft tissue.
Figure 69 shows the difference between axial CBCT and
MDCT images in soft tissue differentiation.
Limited bone density measurements Radiodensity, measured in HU is inaccurate in CBCT scans. CBCT gray-scale
values cannot provide reliable information on site-specific
bone density for purposes such as implant placement
because the X-ray attenuation of CBCT acquisition systems
currently produces different HU values for similar bony and
soft tissue structures in different areas of a scanned volume (e.g. the image value of dense bone at the level of the
menton differs significantly from the image value of the
same bone at the level of the cranial base). In the absence
of such standardization, it is difficult to interpret the gray
levels and impossible to compare the values resulting from
different machines. A method for establishing attenuation
coefficients from which actual HU values can be derived
from CBCT has been proposed; however, further research
is essential before this can be accepted. Despite its limitations in terms of bone quantity information, evaluation of
bone quality from CBCT images has a high correlation with
structural analysis of dental implants.
Scatter The amount of scatter generated and recorded by
cone-beam image acquisition is substantially higher than
that of conventional medical CT. In medical CT, collimation
at the X-ray source restricts the z-axis coverage of the fanbeam, allowing scatter (sinusoidal lines) from only a thin
773

Section X Radiographic Methodology

axial volume of tissue to reach the detector elements during


section acquisition. In contrast, CBCT expands the z-axis
coverage of the beam, allowing X-ray scatter generated
from the entire volume of coverage to reach the detector
elements as the image is acquired. This scatter contribution, expressed as scatter-to-primary ratio (SPR), can be as
high as 3 in large-volume CBCT systems, compared to 0.2
in conventional medical CT systems. Higher amounts of
scatter can reduce diagnostic capabilities by reducing image
contrast and increasing both patient dose and image noise,
the inhomogeneity of gray levels that occurs as a result of
statistical fluctuations in the distribution of X-ray photons
registered by the detector.
Artifacts A significant limitation to CBCT imaging is the
presence of metallic artifacts, i.e. image flaws that are
unrelated to the scanned object, which are caused by metal
and amalgam restorations and, to a lesser extent, rootcanal filling material and implants. Such artifacts include
streaks around materials as well as dark zones that affect
the overall quality of the image. Streak artifacts appear as
linear hyperdensities that radiate from a metallic object
and may extend to the width of the field, affecting visualization of areas even on the opposite side of an image.
Beam-hardening artifacts, which appear as dark bands
adjacent to high-density structures, may mimic disease.
Artifacts originating from root-canal filling material, for
example, may mimic root fractures, whereas dark bands
around dental implants may mimic loss of osseointegration.
Artifacts may also occur as a result of beam-hardening,
i.e. the preferential gradual absorption of lower energy X-ray
photons as they traverse through layers of tissue, resulting
in a gradual increase in the mean energy of the residual
beam. Beam-hardening may be more pronounced in CBCT

than in medical CT, mainly because of the lower kVp and


thus lower mean energy of the X-ray beam in CBCT systems. Figure 70 shows streak and beam-hardening artifacts
in CBCT images.
Patient motion is another source of image artifacts.
Motion artifacts appear as double-margins around a structure and may increase with increases in scan time, which
can be as long as 2030 seconds. In order to reduce the
likelihood of motion artifacts, CBCT units, unlike medical
CT, provide specic devices to stabilize the head during
examination.
Nowadays, CBCT companies are actively developing
artifact-reducing algorithms to be used during image
reconstruction. These processes, although contributory,
are rather slow and may add to the total reconstruction
time. More modern approaches attempt to avoid reconstruction errors either by supplementing missing or incorrect information in projection images or by integrating
some sort of meta-information into an iterative reconstruction process. All of these methods, however, require massive computational power, which has so far prevented them
from being used in daily routine work performed by commercial scanners. Luckily, increasing computational speed
and advances in graphics processing units can be expected
to overcome this problem.
Liability CBCT machines are increasingly being marketed specifically to orthodontists and implantologists or
dentists who place implants in private practices. Unlike
other advanced medical imaging systems, CBCT scanners
are generally owned and operated by non-radiologists
who lack the training necessary to interpret CBCT images
beyond the confines of their specialty or daily spheres of
practice. However, clinicians who order CBCT scans are

Figure 70
A

(A and B) Axial and (C) coronal CBCT images. Streak artifacts appear as linear hyperdensities that radiate from a metallic
object are shown with black arrows. Beam-hardening artifacts, which appear as dark bands adjacent to high-density
structures are shown with blue arrows

774

Chapter 28 Radiographic Techniques

responsible for interpreting the entire image volume, given


the possibility that incidental findingsthe likelihood of
which increase when a larger head volume is included in
the scanmay have significant health consequences for
the patient. With the exception of individuals who have
completed a formal program in oral and maxillofacial
radiology, most orthodontists and other dental practitioners do not have the necessary expertise to interpret CBCT
scans, nor do they feel comfortable in doing so, yet there
is no informed consent process or signature waiver that
would allow the clinician to interpret only a specific area
of an image volume. As a result, the clinician may be considered liable for a missed diagnosis, even one that falls
outside the area of his/her expertise. In case of any questions regarding image data interpretation, referral to a
specialist in oral and maxillofacial or medical radiology is
recommended.

CBCT: Clinical Applications


Whereas early CBCT devices were dedicated to implantology and dental imaging, today, applications extend to the
face and skull base as a whole. In fact, CBCT has largely
replaced conventional tomography for most dental diagnostic tasks and is now commonly used for a variety of
purposes in oral implantology, dentomaxillofacial surgery,
image-guided surgical procedures, endodontics, periodontics and orthodontics.

Oral implantology
The International Congress of Oral Implantologists,
Consensus Report cites four different areas in which CBCT
can be of use in oral implantology:
1. Diagnostics CBCT can be used in the identification
and evaluation of pathology, foreign bodies and defects.
2. Implant planning CBCT images not only have been
proven successful when used for linear measurement, but
also have been shown to provide reliable 3D information
for the assessment of relative bone quality and quantity, 3D
evaluation of ridge topography and pre-implantation
identification of vital anatomical structures such as the inferior alveolar nerve, mental foramen, incisive canal, maxillary sinus, ostium and nasal cavity floor. This information
can be used in the treatment planning process to identify
suitable implant sites and to determine whether or not
there is a need for surgical procedures, such as sinus lifting
and bone augmentation. CBCT is also recommended in
sinus grafting operations as a mean of better predicting
complications, thereby achieving better surgical outcomes.
Figure 71 shows curved and cross-sectional views used to
assess implant sites and nerve canal in the mandible. CBCT
bone images can also be fused with soft tissue images
acquired with digital impression techniques to enhance
planning efficiency (Figure 68).
3. Surgical guidance CBCT images have yielded promising results when used for surgical guidance. Commercially

Figure 71

Curved and cross-sectional views used to assess implant sites and nerve canal in the mandible

775

Section X Radiographic Methodology

Figure 72

Stereolithographic guidance systems constructed for implant placement using implant software StentCad
(Ay Tasarim Ltd., Ankara, Turkey)

available implant simulation software can be used to


process CBCT data to provide pre-operative views of anatomical structures in the jaw bone, and the use of a stereolithographic guide can ensure that pre-operatively planned
implant positions are accurately transferred to the surgical
field. Figure 72 shows stereolithographic guidance systems
constructed for implant placement using implant software.
4. Post-implant and/or post-grafting evaluation CBCT can
be used to localize implants after placement; to assess boneimplant interfaces; to evaluate demineralized bone and bone
transplants; and to identify peri-implant defects. However,
it should be noted that metal artifacts caused by implants
may complicate assessment and measurement; moreover,
keeping in mind concerns over dose, CBCT should only be
used if 2D techniques have been unsuccessful. Figure 73
shows cross-sectional CBCT images taken from patients
complaining of pain and discomfort in the implant region.
Dentomaxillofacial surgery
Dentomaxillofacial surgery is important area in which 3D
views may become necessary, such as the following:
776

1. Eruption problems CBCT images may help in identifying and localizing impacted or displaced permanent,
supernumerary or supplementary teeth, such as third
molars and canine supernumeraries. In particular, CBCT
images can be used in the pre-surgical assessment of the
relationship between third molar apices and the mandibular canal. Figure 74 shows CBCT images taken from a
patient prior to surgical extraction of impacted third molar
tooth.
2. Oral and maxillofacial pathologies CBCT enables the
surgeon to visualize oral and maxillofacial pathologic
entities such as benign jaw bone tumors and cysts in three
dimensions, thereby assisting in diagnosis as well as in
planning appropriate treatment. Figure 75 shows CBCT
images of well-defined cystic pathologic lesions.
3. TMJ-related problems CBCT provides information
essential to the diagnosis of a variety of TMJ disorders,
including osteoarthritis, inflammatory arthritis, trauma
and developmental disorders. The ability to provide highresolution multiplanar images with a lower dose than CT
is rapidly making CBCT the imaging modality of choice

Chapter 28 Radiographic Techniques

Figure 73
A

Cross-sectional CBCT images of patients with pain and discomfort in the implant region that reveal
implants mistakenly placed in the maxillary sinus (A), mandibular canal (B) and out of cortical plate (C).
Please see arrows (Courtesy: Dr Ilker Cebeci, Tomoloji Dentomaxillofacial Radiology Center, Ankara, Turkey)

Figure 74
A

CBCT images taken from a patient before surgical extraction of impacted right third molar tooth. Conventional panoramic
radiograph showing a possible relation between right mandibular molar tooth and mandibular canal (A). CBCT generated
panoramic (B) and cross-sectional views show a relationship with third molar apex and mandibular canal (C)

for the evaluation of the osseous components of the TMJ.


It is imperative that the clinician evaluate not just the
structures of the TMJ, but the entire CBCT volume, as TMJ
dysfunction may be accompanied by pathological changes

in adjacent structures, including the mastoid and the


external and middle ear, and because pathological conditions such as impacted teeth, dental disease and paranasal
sinusitis may mimic TMJ pain and result in misdiagnosis.
777

Section X Radiographic Methodology

Figure 75

Patient 1

Patient 2
CBCT images of well-defined cystic pathologic lesions of two different patients

778

Figure 76 shows CBCT images of a patient with bone


changes in TMJ.

fracture, dental root fracture and anterior maxillary tooth


displacement.

4. Craniofacial fractures CBCT has been used to document craniofacial fractures, including mandibular head

5. Tooth autotransplantation CBCT has recently been used


to assist in tooth transplantation.

Chapter 28 Radiographic Techniques

Figure 76

CBCT images of a patient with bone changes in TMJ. Images were reformatted in TMJ mode

Endodontics
The use of CBCT in endodontics is increasing rapidly. Units
with small FOVs offering high-resolution images of teeth
and related structures have been specifically recommended
in cases where 2D systems have failed to provide sufficient
information regarding the following:
1. Root-canal morphology CBCT images can be used to
precisely determine root curvature and to definitively
identify accessory canals and other anomalies when conventional imaging has suggested the presence of complex
tooth morphology.
2. Periapical pathosis CBCT can assist in the diagnosis of
dental periapical pathosis in patients who present contradictory or non-specific clinical signs and symptoms; who have
poorly localized symptoms associated with an untreated or
previously endodontically treated tooth, with no evidence of
pathosis identified by conventional imaging; and in cases
where anatomic superimposition of roots or areas of the
maxillofacial skeleton are required to perform task-specific
procedures. CBCT can also support a diagnosis of pathosis
that is non-endodontic in origin, determines the extent of the
lesion and identifies its effect on surrounding structures.

3. Pre-, intra- and post-operative assessment CBCT can


support pre-surgical case planning by determining the exact
location of root apices in relation to adjacent anatomical
structures. CBCT can also help in identifying endodontic
treatment complications, such as overextended obturation
material, separated endodontic instruments, calcified canals
and perforations.
4. Dentoalveolar trauma CBCT images can be used in the
diagnosis and management of dentoalveolar trauma, especially root fracture, tooth luxation and/or displacement,
and alveolar fracture.
5. Root resorption CBCT can be used to localize and differentiate between external and internal root resorption
and invasive cervical resorption and other conditions to
identify appropriate treatment as well as prognosis.
Figure 77 shows CBCT images taken for endodontic
purposes.
Periodontics
CBCT can be used as a supplementary imaging technique
in situations where traditional 2D techniques have been
779

Section X Radiographic Methodology

Figure 77
A

(A) CBCT axial image showing a root fracture line and (B) CBCT sagittal image showing a periapical lesion with
bony reaction and maxillary sinusitis. Please see arrows

Figure 78

CBCT image of a cleft palate patient with eruption problems

unable to provide sufficient reliable information for periodontal assessment and treatment. CBCT may play a role
in the assessment of marginal bone contours and 3D defects,
especially furcations and infrabony defects, in which defect
780

morphology directly influences treatment planning and


prognosis. Specifically, CBCT is able to assess buccal and
lingual/palatal surface defects better, which are difficult to
visualize in 2D imaging.

Chapter 28 Radiographic Techniques

Orthodontics
The use of CBCT in orthodontics has been gaining substantial popularity, although it is primarily recommended in
cases where conventional radiography cannot supply satisfactory diagnostic information. This can include assessments
of cleft-palate patients, unerupted and supernumerary tooth
localization, identification of root resorption caused by
unerupted teeth, evaluation of boundary conditions and
orthognathic surgery planning. CBCT imaging may also be
performed in other cases where it is likely to provide valuable diagnostic information. Figure 78 shows CBCT images
of a cleft palate patient with eruption problems.
Head and neck
Depending on the FOV used, CBCT images may show part
or all of the nasal cavity, paranasal sinuses, airway, cervical
vertebrae and temporal bone. In fact, specific ear, nose and
throat imaging programs have been increasingly included
in CBCT systems, suggesting that CBCT may at some point
entirely replace medical CT imaging in certain otolaryngology-related applications. For example, an innovative
C-arm CBCT system has been used in image-guided surgery of the frontal recess; the technology is portable and
provides near-real-time imaging to confirm and guide surgical treatment, thereby reducing the risk of disorientation
and iatrogenic injury. CBCT has also been found to provide reliable and accurate 3D analysis of the upper airway
that can be of help in assessing the presence and severity
of obstructive sleep apnea (Figure 67). Imaging of the temporal bone represents another promising area for CBCT,
whose high-resolution and nearly artifact-free multi-planar
reconstruction images make it possible to precisely assess
the intra-cochlear position of the electrode, including
visualization of each individual contact. It is this capacity
for precision that makes CBCT a perfect candidate for the
post-operative assessment and follow-up of cochlear implantation electrodes.

MAGNETIC RESONANCE IMAGING


Magnetic resonance imaging (MRI) is a non-invasive method
for mapping the internal structure within the body which
uses non-ionizing electromagnetic radiation and employs
radiofrequency radiation in the presence of carefully controlled magnetic fields to produce high-quality cross-sectional
images of the body in any plane.

Historical Perspective
The phenomenon of nuclear induction later to be termed
as nuclear magnetic resonance (NMR) was described independently but almost simultaneously by Bloch and Purcell

and their colleagues in 1946 and for this they were jointly
awarded Nobel Prize in 1952. Much later, the term nuclear
was dropped, it is now commonly referred to as magnetic
resonance (MR).
In 1971, Damadian noted that in vitro animal tumors had
elevated MR relaxation times when compared to normal
control tissue and he formed an apparatus and method for
detecting cancer in tissue.
In 1973, Lauterbur published a paper and showed how
MR could be applied to imaging by applying a linearly
varying magnetic eld across a liquid. Paul C Lauterbur is
known as the Father of MRI.
In 1977, human Invivo images were demonstrated by
Manseld and Maudsley.
In 1980, multiplanar imaging ability were rst demonstrated by Hawkes.
In 1992, functional MRI (fMRI) of the brain was introduced by Ogawa.

Principles of Magnetic Resonance Imaging


1.
2.
3.
4.
5.
6.

Nuclear magnetic dipole moment


MR scanner
Proton magnetization
Resonance
Relaxation
Spin-echo phenomenon.

Nuclear magnetic dipole moment


The individual protons and neutrons in the nuclei of all
atoms possess a spin or angular momentum. In nuclei with
equal number of protons and neutrons with an electrical
charge, a magnetic field is generated in nuclei with an
electrical charge, a magnetic field is generated in nuclei of
unpaired nucleons, causing these nuclei to act as magnets
with north and south poles (magnetic dipoles) and having
magnetic momentum. The most common of these atoms,
the magnetic resonance active nuclei, are hydrogen, carbon, nitrogen, oxygen, fluorine, sodium and phosphorous.
Hydrogen atom is the most ubiquitous of these atoms in
the body. A hydrogen nucleus consists of a single unpaired
proton and therefore acts as a magnetic dipole. MRI is based
on magnetic dipole moment.
MR scanner
The MR scanner consists of a magnet (Figure 79). Inside
the bore of the main magnet, there are three sets of coils
installed to produce magnetic field gradient, one in the direction of the main field (the z-axis) and two perpendicular to
this (the x and y axes). The gradient field strengths over the
entire patient are less than 1% of the main field strength
and can be rapidly varied in time. Inside the gradient coil
assembly, radiofrequency (RF) transmitter/receiver coil is
mounted. Surface coil is placed directly on the surface of
781

Section X Radiographic Methodology

Figure 79
Gradient coils

Main magnet

RF coil

Couch

z
x

RF receiver/
transmitter
switch

Main magnet
power supply

X-gradient
power supply

RF pulse
generator

Y-gradient
power supply

Z-gradient
power supply

RF pulse
amplifier

Image
processor

Central pulse
sequence controller

MR scanner

the body that improves the signal-to-noise ratio and the


resolution in the final image, but limits the volume that
can be examined. Patient is installed on a couch centrally
in the bore. Central pulse sequence controller operates the
gradient coil power supplies and transmitter-receiver switch
of the RF coil through the complex sequences used for the
various MR-imaging modes. Received radiofrequency signals are analyzed by Fourier transformation which are
spatially decoded in the image processor to be displayed as
an image, which is a map of the amplitude of radiofrequency signals emitted from small-volume elements, voxels,
in an imaginary slice of the patient.

Figure 80
B0
Axis of precession

Axis of spin
proton

Proton magnetization
Proton exposed to a steady external magnetic field creates
a force that will act on its magnetic dipole moment and
orient it parallel with the external field, but due to the
spin, it does not swing in as a compass needle would do.
Instead, it performs a maintained circular movement called
precession which has its own axis of spin and rotates at an
angle around another axis that is parallel with the external field like toy spinning top in the gravitational field
(Figure 80). Magnetic dipole moment of the precessing proton have magnitude and a direction expressed by a vector
which is resolved in one component aligned with the axis
of precession known as the longitudinal component.
The second component which is oriented perpendicular
to the external eld and rotating with the frequency of
precession is called the transverse component. Within a
magnetic eld, all protons precess at the same frequency
782

w
External field

Proton spin and precession

which is determined by the strength of the magnetic eld


and a constant. Relation between these two is expressed
by the Larmor equation:
F  yB0
F  precessional frequency,
B0  strength of the external magnetic eld and
y  gyromagnetic ratio unit of magnetic eld strengthtesla (T).
The precessional frequency of protons is 42.58 MHz/T.

Chapter 28 Radiographic Techniques

Figure 81

Figure 82
Low energy state

z
Longitudinal net
magnetization vector

B0

External field

xy transversal vectors
cancel because out of
phase

High energy state

Illustration showing net magnetization vector of protons

Illustration showing proton spin levels

Larmor frequency is not exactly the same for all protons,


but may differ by a few ppm (parts per million) depending
on the chemical bonds they have established. Larmor frequency of protons in water and in aliphatic fatty acid chains
vary. Such differences are designated chemical shifts.
Proton spin levels When exposed to the external field,
the spin of the proton may be at one of two discrete energy
levels. At low spin-energy level, longitudinal component
of the magnetic vector points in the same direction as the
external field. At the high energy level it points in the
opposite direction (Figure 81). The fractional distribution
of protons between these two states depends upon temperature and strength of external magnetic field.
The difference manifests itself as a net magnetization of
the population of protons in the material/tissue within the
eld. Net magnetization vector is the statistical equilibrium
of a huge population of protons, constantly inuenced by
thermal motion, and shifting between the two spin-energy
levels (Figure 82).
Resonance
When a body part or tissue is installed in a strong, steady
and uniform magnetic field of the MR scanner, the equilibrium state is represented by the net magnetization vector which is established within seconds. When disturbed
and shifted by a pulse of electromagnetic waves at the
Larmor frequency of the protons (42.58 MHz in an IT field)
entering perpendicular to the main field, only RF waves
(photons) of precisely this frequency will transfer energy
by resonance to the precessing protons. This transfer of
energy by resonance has two effects on the precessing
protons:
i.

Protons at the low spin-energy level, having absorbed


the energy of a RF photon, shift to the high energy

ii.

level accompanied by a shift in the orientation of


their magnetic dipole moments. The magnitude of the
longitudinal net magnetization vector as more protons
shift to the high energy level. At a certain RF energy
input, the longitudinal vector disappears. By further
input of RF energy, a surplus of proton is lifted to the
high spin-energy level, the longitudinal vector reappears, but in the opposite direction.
It forces the protons into coherent precession with the
appearance of transverse net magnetization vector which
rotates with the Larmor frequency. The net magnetization vector is the resultant of longitudinal and transverse magnetization vectors. Increase in RF energy input
increases the longitudinal vector and decreases the
transverse vector. The angle between the direction of the
main field and net magnetization vector is flip angle.

90 pulse: RF pulse delivering energy just sufficient to tilt


the net magnetization vector into the transverse orientation.
180 pulse: RF pulse of twice 90 magnitude causes reappearance of a longitudinal vector, but in the opposite direction, and will also cause the transverse vector to rotate in
the opposite direction relative to the main field. The duration of such excitatory RF pulses is in the order of a few
milliseconds.
Relaxation
When RF pulse is turned off, the excited protons return
over a period of time to the initial equilibrium state, this is
called as relaxation. Recovery of longitudinal magnetization and the decay of transversal magnetization follow different and independent time courses according to simple
exponential functions but with different time conducted:
i.
ii.

T1Recovery of longitudinal magnetization


T2Decay of transversal magnetization.
783

Section X Radiographic Methodology

Table 10

Comparative features of T1 and T2

Table 12

T1

T2

Repetition time (TR)

Echo time (TE)

This is the time at


which the longitudinal
magnetization has
recovered 63% of its
equilibrium magnitude

This is the time at which the induced


transversal magnetization has decayed
63% of its maximum strength

Duration between repeat RF


pulses

Time after application of RF pulse


when the MR signal is read
Controls the amount of T2
relaxation that has occurred when
the signal is collected

Loss of energy whereby


those protons that
were lifted to the high
spin-energy level during
magnetization give up
this energy and fall back

Loss of phase coherence between the


precessing protons has its origin in mutual
magnetic interactions between the protons,
and between the protons and local field in
homogeneities

Time between pulse repetition


determines the amount of T1
relaxation that has occurred at
the time the signal is collected

Thermal nature with


a molecular basis in
random collisions with
surrounding molecules,
collectively called the
lattice-thermal relaxation
time or the spin-lattice
relaxation time

Interactions between nuclei with different


spinsthe spin-spin relaxation time

T1 longer than T2

Table 11

Pure liquids
Solids
Mobile molecules Molecules fixed
Intrinsic and local Local intrinsic field
field variations are
inhomogeneities
rapidly fluctuating
more permanent
and tend to
causing protons to
average out
systematically
dephase
Longer (seconds) Short (milliseconds)

Fat
Bone marrow

T1 time (ms)

T2 time (ms)

240250

6080

550

50

White matter of cerebrum

780

90

Gray matter of cerebrum

920

100

Muscle
CSF (water)

Table 13

Difference between T1 weighted image and T2


weighted image

T1 weighted image

T2 weighted image

Emphasizes T1 value of
tissues

Emphasizes differences in T2 values


of tissues

Accomplished by use of short


TR (300700 ms) and TE
time (20 ms)

Accomplished by use of long TR


(2,000 ms) and TE time (60 ms)

Fast T1 time, e.g. Fat-bright


Long T1 time, e.g. Water-dark

Short T2 time, e.g. Fat-dark


Long T2 time, e.g. CSF/water-bright

To demonstrate anatomy

To identify inflammatory/pathological
changes
Other techniques allow the signal
from fat or water to be enhanced/
supressed
Fat saturationnulls the signal
from fat

T1 and T2 relaxation times in a main eld of 1.5 T

Tissue type

860900

50

2,2002,400

5001,400

The two relaxation processes reflect two types of interactions


between the precessing protons and their surroundings
(Table 10).
The chemical shift (3 ppm) between protons of water and
fatty acids causes rapid decay of transverse magnetization
in tissues where fat and watery tissue are intimately mixed,
e.g. in bone marrow. The mineralized bone tissue has few
mobile protons which yield detectable T1 signals in diagnostic imaging. The concentration of protons detectable
by MR-imaging in a tissue is spin density/proton density.
MR-imaging is directed at detection and visualization of differences in parameters such as T1, T2 or the spin density
between different tissues and uids within the body (Table 11).
During the period of relaxation of the magnetized tissues,
an electromotive force can be induced in receiver coil as
an RF signal in synchrony with the precessing protons.
784

Pulse sequence: basic features

The RF signal is analyzed and encoded to be displayed


as an image. Only protons that precess in phase give rise
to detectable radiosignals. Thus, to detect differences in
T1 between tissues, and to fully exploit differences in T2,
complex excitatory pulse sequences are applied.
Radiofrequency pulses sequences The components are
set by the operator and determine the appearance of the
resultant image. Most basic features of a pulse sequence
are depicted in Table 12.
Tissue contrast Tissue contrast is governed by intrinsic
features of the tissues including proton density T1 and T2
times of the issues being imaged and how the TR and TE
times are adjusted to emphasize these features, e.g. tissue
has high proton density, strong transverse magnetization
vector at TE, strong magnetic resonance signal, appear
bright on MR image. Conversely, low proton density low
transverse magnetization vector at TE weak signal dark on
MR-image (Table 13).
Spin-echo phenomenon
Loss of phase coherence is called as dephasing characterized by loss of RF signal due to the spin-spin relaxation
(T2) which is an inherent property of the material/tissue.

Chapter 28 Radiographic Techniques

Figure 83

Figure 84
z

B0
z

90 RF pulse
y

MZ

Mxymax
w

A strong radiosignal emitting at the


Larmor frequency

Illustration showing proton magnetization vectors out of


phase in the equilibrium state

Figure 85
z

180 RF pulse

Mxymax
y

Mz
x

x
Mz

Illustrations showing fanning out of the transverse component after the end of a 90 pulse and the application of
a 180 pulse reversing the longitudinal vector

The rate of decay of phase coherence (T2) is always faster


because of inhomogeneities in the magnetic field. The other
reason is due to external disturbance of the measurement
can be cancelled by the spin-echo manoeuvre (action) and
gradient-echos (reversal of the magnetic gradients).
In equilibrium state, all the transverse (Mxy) components of the proton magnetization vectors are out of phase
(Figure 83). Sum of the longitudinal components (Mz) are
aligned with the main eld.
A 90 RF pulse ips the longitudinal vector into the
transverse plane and forces the transverse components of
the proton magnetization vectors to precess in phase. The
single resultant Mxy vector is large and emits a strong
radiosignal at the Larmor frequency (Figure 84).
After termination of the 90 pulse, the transverse
component begins to fan out due to small differences in
precessional frequency of the individual protons, i.e. T2
relaxation. At the same time the longitudinal vector begins
to grow up due to T1 relaxation (Figure 85). A 180 RF
pulse reverses the longitudinal vector and the direction of

Figure 86
z

y
Mxy

Mz
x

Illustration showing closing of the fan of vectors

precession faster precessing protons catch up with the


slower, i.e. the fan of vectors closes again (Figure 86).
At time, TE, the transverse components of the proton
magnetization vectors regather and emit again a strong
radiosignal.
785

Section X Radiographic Methodology

MR-contrast Agents
The relaxation times (expressed by T1 and T2) is shortened
when paramagnetic substance is targeted to tissue, disturbing admixture of strong magnetic dipoles due to the unpaired
electrons in their atoms.
Gadolinium (Gd) chelated to DTPAit is a rare earth
element which does not cross the normal bloodbrain barrier. This is used to detect defects in this barrier excreted in
the urine. It is utilized in urological MR-imaging. Using
additional ligands, Gd-chelates may be directed to biliary
excretion. Agents based on manganese (Mn) having paramagnetic properties similar to gadolinium have been
developed.
Gd and Mn based compounds are positive contrast agents
because of their inuence on the relaxation constants, notably T1, is utilized to produce images (T1 weighted) where
the MR signal strength is proportional to the concentration
of the agent.
Iron oxide particles effectively produce local eld in
homogeneities. These are negative contrast agents which
produce signal voids by strongly shortening T2. After IV
administration, it shortens the relaxation time in liver, spleen
and bone marrow, but not in tumors lodged in these tissues. This is used for gastrointestinal imaging.

Methods for Obtaining Spatial (Tomographic)


Resolution of MR Signals
The final MR-image is a square matrix of pixels containing small-volume element called as voxel in an imaginary
slice of the patient. Each pixel is given a gray tone value
proportional to the amplitude of the radio signal emitted
from the corresponding voxel in a defined period of time
following a sequence of RF excitations.
Scanner gradient
These are used to generate image that produce discrete slice
of tissue. It is accomplished by using two gradient coils
which are required to modify the magnetic field surrounding the patient. X gradient refers to left to right, Y gradiant refers to anterior to posterior, Z gradient refers to head
to toe (Figure 87). When one coil is turned on, it creates a
gradient in the intensity of magnetic field. Thus, in a 1.5 T
scanner, when the Z gradient is turned on, the strength of
the magnetic field at the head might be 1.4 T and that of
toe is 1.6 T.
When this gradient eld is applied, the precessional frequency of hydrogen nuclei will vary linearly along the magnetic variant. Accordingly, when the RF pulse is applied,
only those nuclei precessing at the same frequency as the
applied signal will resonate. This allows selecting the desired
slice of tissue along the Z gradient slope of the gradient
applied and the bandwidth of the RF pulse determine the
786

Figure 87
y
z

Illustration depicting the scanner gradient

thickness of the slice location of the signal within the X


and Y planes of the selected longitudinal plane derived by
switching off the Z gradient coil followed by rapidly turning on the X and Y gradient coils. This sequence alters the
phase and precessional frequencies of the nuclei in the
selected slice. The resulting magnetic resonance signals
from the patient is read out while the frequency encoding
gradient is applied. The signal from the patient contains
many frequencies that is decomposed by the fast Fourier
transformer into amplitude and frequency.
This information, which reects the number of hydrogen nuclei and their T1 and T2 properties at each X and Y
location in the selected longitudinal plane is reconstructed
into MR images. The phase encoding gradient applied perpendicular to sIice selecting gradient is switched on for
short period of time (35 ms) after the excitatory RF pulse
has been switched off, produces a continuous change in
precessional phase across the slice, so that a particular
phase derives from particular rows of voxels (horizontal
row). The frequency encoding gradient is applied at right
angles to both the slice-selecting gradient and the phase
encoding gradient-switched on after the phase encoding
gradient has been switched off, and is maintained during
the period where the RF signals are sampled establishes a
continuous increase in precessional (Larmor) frequencies
from one edge of the section to the opposite edge, so that
a particular frequency derives from a particular row of
voxels across the slice (vertical row). The commonly used
image matrix is 256  256 pixels. To achieve the same
resolution in the X- and Y-directions, the image must be
constructed from 256 data samples, recorded with 256 different settings of the phase encoding gradient which is the
main reason for the long data aquisition time in MRI compared to CT imaging (Table 14). The amplitude is assigned
a gray tone that is proportional to its magnitude and is

Chapter 28 Radiographic Techniques

Table 14

2.

Differences between CT and MRI

CT

MRI

Ionizing radiation

Radiofrequency

Less expensive

Expensive

Short time

Long time

CI in pregnancy and children

Can be used

Suppression of image not


possible

Suppression of certain image


possible

5.

Measured in terms of density

Measured in terms of intensity

6.

Two planesaxial and coronal

Multiplanaroblique view possible

Indicated for trauma patients


with acute bleeding

Not for trauma patients

Applicable for fractures

Not for fractures

Contrast used: Iodine, barium

Contrast used: Gd, Mn

For chronic stages

For strokes, edema, initial stage of


inflammation, cranial nerves, vessels

Between bones and soft tissues

Between soft tissues

3.
4.

7.

Advantages
Best resolution of tissues with low inherent contrast.
Uses non-ionizing radiationnon-hazardous.
Accurate and rapid localization of intracranial pathologies.
No streaking artifacts.
High-contrast images achievable.

Disadvantages

Image interpretation

Tissue

T1 image

T2 image

Water

Dark

Very bright

Tumors

Intermediate

Bright

Old blood

Bright

Bright

Fibrous tissue

Dark

Dark

Air

Dark

Dark

Bone calcium

Dark

Dark

Fresh blood

Dark

Dark

Organs

Intermediate

Dark

Fat

Very bright

Bright

displayed as the corresponding pixel in the image. High


signal amplitudes appear white while low amplitudes
appear black on the gray tone scale. As in CT imaging,
window width and the window level can be varied.

Uses for MRI (Table 15)


1.

1.
2.
3.
4.
5.

CI: Contraindicated

Table 15

Congenital disorders: T1 weighted sequences with coronal and axial images demonstrate abnormalities like
cleft lip and palate.
Infections: AIDS-generalized cervical lymphadenopathy with cystic lesions in the parotid.
Sinusitis: When complicated by serious condition like
a tumor, venous sinus thrombosis or an intracranial
extension of the infection.
Benign tumors: Hemangiomas, lymphangiomas, neurofibromas and schwannomas.
Malignant tumors: Diagnosis, staging and monitoring
of malignant tumors affecting the head and neck region.
TMJ: Articular disk perforations and disk displacements.

For head and neck lesions: T1 weighted images


defining anatomy of the lesion. T2 weighted images
assessing the invasion of the lesion into surrounding
structures.
Contrast enhanced MRIextension of the lesion into
muscles, brain or blood vessels can be studied. Coronal
scan-assessment of lesions involving the base of the
skull and the perineural extensions of tumors.

1.
2.
3.
4.
5.
6.

Some patients may complain of mild pain or tingling


sensation.
Noise produced may cause discomfort to the patient.
Contraindicated in patients with cardiac pacemakers.
Not used in patients with ferromagnetic substances
implanted in the body.
Expensive, not easily available.
Room used should be free of ferromagnetic materials.

Common Artifacts in MRI


Flow effect and movement artifacts in MRI
Artifacts occur due to flow in blood vessels and CSF.
Depending on the RF pulse sequences applied, the presence
of flow may give rise to weaker or stronger signals than
expected. Fast flow perpendicular to the section carry away
those protons that should have given a signal during the RF
signal sampling period. Blood vessel becomes signal void
and is displayed in black on the image. Protons with strong
signals may be carried into the section by flow which disturb the spatial XY encoding/decoding leading to artifacts.
Wherever flowing blood is imaged the artifacts may be
present as streaks through a vessel, extending across the
image in the direction of the phase encoding gradient.
Artifacts in magnetic resonance image due to
motion and use of denture
See Table 14.
787

Section X Radiographic Methodology

NUCLEAR MEDICINE
Nuclear medicine is a diagnostic radiation science utilizing radioactive compounds or tracers having affinities for
particular tissues or organs in the body (iodine to the thyroid gland); these are termed as target tissues.
The radioactive agents are administered to the patient
either orally, intravenous or intrathecally. These agents
concentrate in target tissues and emit radiation. These are
detected and imaged by a variety of external detectors and
imaging systems. This helps in studying the target tissue
under static and dynamic conditions. Such studies are called
scintigraphic scans, scintiscans or radionuclide scans.
When these are utilized for studying bone they referred
to as bone scans and when performed for salivary gland they
are termed as salivary gland scans. Other scans include
heart scans (to identify normal or abnormal blood ow to
the heart muscle, measure heart function or determine the
existence or extent of damage to the heart tissues after a
heart attack); thyroid iodine scans (to analyze the thyroid
function and show the structure of the gland. Larger doses
of radioactive iodine are used to destroy thyroid nodules
in the case of Graves syndrome); gallbladder or hepatobiliary scans (to evaluate both liver as well as gallbladder
function such as presence of gallstones); lung scans (to
evaluate the ow of blood and movements into and out of
the lungs, as well as the determination of the presence of
blood clots); Gallium scans (to evaluate infection and tumor),
brain scans and gastrointestinal scans.
Nuclear medicine tests are extremely sensitive to abnormalities in body organs structure and function. Tests using
nuclear medicine techniques are more sensitive and specic
for disease detection than most tests because they identify
abnormalities very early in the progression of a disease,
long before the medical problem would be apparent with
other diagnostic tests.
In 1958, Hal Angler used scintillation camera for imaging the entire system. In 1971, Subramanian and McFee used
99m-Tc (Technetium) labeled MDP (methylene diphosphonate) in bone scanning.

Radiopharmaceuticals
These are radioactive agents used in nuclear medicine procedures for imaging. They are produced using nuclear reactors and cyclotrons. Radiopharmaceuticals circulate and
concentrate to varying degrees in different organs throughout the body. The localized tracer uptake is dependent on
changes in regional blood flow and areas of altered bone
physiology and pathology which show an invariable alteration in the osteoblastic and osteoclastic activity.
The organs that receive the greatest exposure are referred
to as critical organs. For example, in bone scanning the bladder, skeleton and bone marrow receive the highest exposure.
788

Types of radiopharmaceuticals
1.
2.

Radioactive elements/compounds (Technetium-99m,


Fluorine-18, Iodine-131)
Non-radioactive carrier compound with a radioisotope (Gallium-67 labeled citrate, Iodine-125 labeled
polyphosphate and Technetium labeled human serum
albumin).

Labeling various phosphate compounds with 99Tc results in


the agents concentration in the skeleton hence used in bone
scans. Labeling sulfur colloid with 99Tc gives an agent
that is taken up by the reticuloendothelial cells of the liver
and spleen, hence used in scans of the liver and spleen.
Technetium-99m methylene diphosphonate (Tc-99m
MDP) is the most widely used radiopharmaceutical. It has
a short half-life (6.5 h), hence there is minimal radiation
exposure and has superior physical and biological properties.
MDP is localized in bone by chemiabsorption onto immature
hydroxy apatite crystal within newly formed inorganic
matrix and cannot be metabolized by the enzyme system.

Bone Scanning
Procedure
Ten to fifteen millicuries of 99m-Tc labeled compound is
injected IV. A waiting period of 23 hours permits the compound to accumulate in the skeleton and to be removed
from vascular and soft tissues via the urinary system. The
patient is then positioned under the gamma camera and
the desired bones are imaged. Whole body radiation dose
in bone scan is approximately 0.10.5 rad.
Working principle
Following administration of the radioisotope, they reach the
desired organs and emit gamma radiation, which is picked
up by the detectors placed outside the body within the
gamma cameras.
Gamma cameras are devices used to image the radioisotope distribution in the body, within the eld of view.
It consists of a sodium iodide detector of about 40 cm in
diameter. The detector assembly has a collimator which is
similar to a grid in radiography. The gamma radiation emitted by the patient passes through the holes in the collimator and reaches the detector, where they are converted into
light scintillation.
The photomultiplier tubes convert the light into electric
pulse which is then passed onto the computer. The computer constructs the distribution of the radioisotopes and
displays it on the monitor.
Interpretation of bone scans
Abnormalities in bone are manifested in a scan mostly as
areas of increased tracer concentration or as areas of very

Chapter 28 Radiographic Techniques

limited uptake. Areas of increased tracer uptake seen


as hot spots and cold spots are areas of decreased tracer
uptake. In rare instances the entire skeleton will be diffusely hot which is termed as super scans.
In a normal scan the tracer will show bilateral, uniform and symmetrical distribution. The normal activity and
uptake of the tracer depends on bone mass/density and
bone stress in weight bearing areas. Soft tissue and the
urinary tract may show some background activity.
Clinical applications of bone scans
1. Trauma: Absence of tracer uptake even 2448 hours
after an injury excludes a fracture. Bone scans can help
determine the age of a fracture.

Salivary Gland Scans


Procedure
Patient is advised to lie supine. Intravenously 40150 megabecquerel (MBq) 99m-Tc pertechnetate is injected. For the
next 25 minutes, sequential images are taken at 1 minute
intervals. A large field of view gamma camera equipped
with a low-energy, high-resolution, parallel-hole collimator is used. Roughly, 15 minutes following the procedure,
secretogogue like lemon juice may be given to enhance
salivary secretion. The effective equivalent radiation dose
to the patient is 0.41.6 mSv.
Clinical applications for salivary scans

2. Viability of bone grafts: An unsuccessful graft (nonvascularized) appears as a cold spot. On the other hand,
osteoblastic activity associated with a vascularized bone
graft is seen as a hot spot.

Salivary scintigraphy may be used to assess obstructions


in the salivary ducts with or without parenchymal damage,
Sjogrens syndrome, parenchymal impairment after radioiodine treatment in patients suffering from thyroid cancer.

3. TMJ changes: Early articular surface changes of the


TMJ can be determined.

ULTRASONOGRAPHY

4. Osteomyelitis: Early detection (12 days of symptom


onset) of osteomyelitis is represented by the radionuclide
hyperactivity.
5. Metabolic bone disorders: Bone disorders such as
osteomalacia, hyperparathyroidism and renal osteodystrophy can be assessed.
6. Detection of skeletal metastasis: Carcinoma of the
breast, lung and kidney which have a tendency for skeletal
metastasis appear as multiple hot spots on a bone scan.
7. Extraosseous localization: 99m-Tc MDP apart from localizing in the skeleton also localizes in several soft tissues
lesions such as muscle injuries, myocardial infarct, primary
breast lump and lung metastasis from osteosarcoma.
Advantages of bone scanning over conventional
radiography
A bone scan helps in detection of a lesion at the early
stage (less than 5% demineralization of bone is adequate),
compared to conventional radiographs which require at
least 3050% demineralization of bone. Bone scans can
depict the functional state of an organ or tissue whereas
conventional radiographic procedures detect the anatomical
structure.
Limitations
In interpreting bone scans of the skull and face, care
should be taken to avoid misinterpretation of activity in the
mandible and maxillary alveolar ridges which are common
sites of uptake due to the frequent dental infections and
extraction sites.

The production of sound is the result of periodic changes


in the pressure of air against the ear-drum. The periodicity
of these changes lie between 1500 and 20,000 cycles per
second (Hertz). Human hearing is usually in the range of
20 Hz20 kHz. Diagnostic ultrasonography uses vibratory
frequencies in the range of 120 MHz. Sonography comes
from a Latin word sonus meaning sound and a Greek word
graphein to write. Sonography precisely means imaging
with ultrasound. An ultrasound produces a visible image
of invisible organs inside the human body (Table 16).

Principle
Images with ultrasound are accomplished with pulse-echo
technique with the help of transducer. Ultrasound transducers convert electrical energy into ultrasound energy
and vice versa. In ultrasonography, sound waves (pulse)
generated by the transducer emitted inside the patient will
be reflected back (echo) at organ boundaries and within
tissues depending on the composition of the matter. These
echoes then return to the transducer, where they are converted into electrical energy and then presented on the
display of sonographic instruments. The ultrasound instruments processes the echoes and present them as visible
dots. The location of each dot corresponds to the anatomic
location of the echo-generating structure. Gray-scale
image is achieved by different echo-strength and the echo
arrival time is used to determine the depth of the structure
that produced the echo. The ultrasound instruments processes the echoes and present them as visible dots, which
form the anatomic image on the display. Not all the ultrasound pulses are reflected back from any interface. Rather
789

Section X Radiographic Methodology

Table 16

Terms associated with ultrasonography

Acoustic
impedance

Product of density of the medium propagating the


sound and the velocity of propagation

Reflection

The way ultrasound is reflected when it strikes an


acoustic interface is determined by the size and
surface feature of the interface

Refraction

If the direction of sound changes as it crosses a


boundary, then the transmission angle is different
than the incidence angle

Attenuation

Reduction in amplitude and intensity of sound as it


propagates. It is the result of the combined effects
of absorption, scattering and reflection

Anechoic

Without internal echoes; structure is fluid filled and


transmits sound easily
Example: amniotic cavity, gall bladder

Hyperechoic

Echo producing structure, reflects sound with a


brighter intensity
Example: gall stones, fat, bone

Hypoechoic

Low level echoes within a structure


Example: enlarged lymph nodes

Isoechoic

Very close to the normal parenchyma echogenicity


pattern
Example: muscles

most of the original pulse continues to be reflected back


from deeper interfaces. If process is repeated, but with different starting points for each subsequent pulse, a crosssectional image of the anatomy is built up.
Velocity of sound depends on the medium. Sound is
attenuated through most bony structures thus velocity is
faster in solids whereas it is slow in gas-lled structures
such as bowel because it impedes the sound transmission.
Contrast agent can also be injected into the circulation
to increase echogenicity. Contrast agent contain micro
bubbles of gas and they produce strong echoes because
impedence of gas is different from that of suspended liquid
that enhance echogencity from perfused tissues in grayscale sonography and Doppler ultrasound.
For many years, ultrasonography was limited to 2D
cross-sectional scan, now it has been extended into 3D
scanning and imaging. This requires scanning the ultrasound through many adjacent tissue cross-sections to build
up 3D volume of echo-information.

Different Types of Scans


1.

790

B-scan (gray-scale scan) images are produced by


scanning the ultrasound through the imaged crosssection (i.e. sending pulses through all regions of the
cross-section). B-scan converts the echo-strength into
the brightness of each represented echo on the display. (Hence B-scan or brightness scan.)

2.

3.

A-scan images appear as spikes extending upward


from the baseline (point of contact of skin and the
transducer is representative of the baseline). A-scans,
showing the relationship between amplitude and
depth are used for measuring the distance between
boundaries of tissues with different acoustic properties. These are used to distinguish between solid and
cystic lesions.
M-scan used to show the motion of cardiac structures.
It is a display form that presents depth versus time.
Display of changes in echo is useful in evaluation of
rapidly moving structure like cardiac valve.

Different Types of Scanners Used


1. Linear scan These cross-sectional images have been
produced with vertical parallel scan lines that are so close
together that they cannot be identified individually.
2. Sector scan Each pulse originates from the same starting point, but subsequent pulses go out in slightly different directions from the previous ones. This results in a
scan which is shaped like a slice of pie.
There is a combination of both too, where pulses originate from different starting points but each pulse travels
in a slightly different direction than the previous one.

Instrumentation
1.
2.

3.

Transmitter provides high amplitude voltage and controls the rate of pulses emitted by the transducer.
Transducers operate according to the principle of piezoelectricity. This principle states that some materials
(ceramics, quartz) produce a voltage when deformed
by an applied pressure. Piezoelectric crystal used in
ultrasonography is lead zirconate titanate. When the
transducer receives the electric impulses, the dipoles
inside the crystals are realigned to the electric field
causing the changes in the thickness of the crystal.
This leads to the formation of sound which is transmitted inside the patient. The echo reflected back to
the transducers which change in the shape of crystal
that results in the production of small oscillating voltages that can be measured or recorded.
Receiver and displayafter amplification the echo
voltages are digitalized, i.e. they pass through analogto-digital converters (ADC). Electric information from
image processor drives the display, which produces a
visual image.

Coupling agents
Even a very thin layer of air between the transducer and
the skin surface reflects all the sound, preventing any penetration into the tissue, thus an aqueous gel is applied over

Chapter 28 Radiographic Techniques

the skin before application of the transducer which eliminates the air layer and facilitates sound passage in and out
of the tissue. Coupling agent consists of:
1.
2.
3.
4.
5.

Carbomer10 g
EDTA0.25 g
Propylene glycol75 g
Trolamine12.5 g
Distilled water up to 500 g.

Doppler Ultrasound
Echoes produced by moving objects have different frequencies than the pulses sent into the body. This is called
the Doppler effect, which is put to use in detecting and
measuring tissue motion and blood flow. Color depends
on the flow of blood toward or away from the transducer.
Colors are always opposite for artery and vein, so if artery
is red, vein will be blue or vice versa. This is used to see
tissue motion, obstruction and thrombosis. In addition, it can
also detect direction, speed and character of blood flow.
Color Doppler ultrasonography minimizes the need for
biopsy or ne needle aspiration cytology (FNAC). The
presence of blood ow signals in the center of node (this
indirectly denotes the existence of the converging sinuses)
suggests that the node is benign. The presence of peripheral ow suggests a malignant nature (tumors larger than
a few millimeters in diameter stimulate the growth of new
vessels).
It has also been applied to automatic door openers and
to burglar alarms.

Main Indications for Ultrasound in the


Head and Neck
Ultrasound is a very valuable tool in the diagnosis of the
head and neck. Optimal ultrasound examination of the
superficial structures of the head and neck requires appropriate equipment with high-resolution small part transducers that make use of high frequency ultrasound.
Ultrasound sequence between 5 and 20 MHz is used. Either
the transducer is used directly on the skin or a silicon
stand-off pad is placed between the transducer and the
skin to get the ideal contact with the surface, especially in
the angle of the jaw and neck. A systematic examination
protocol is mandatory for the evaluation of the head and
neck. It begins with the examination of the thyroid gland
where the instrument is adjusted. The examination is continued along the vascular sheath to the floor of the mouth,
tongue, salivary glands and tonsils. Next step is the examination of status of lymph nodes.
1. Cervical lymph nodes
The majority of the normal lymph nodes in the head and
neck show an axial diameter of 25 mm with the exception

of the jugulodigastric and the juguloomohyoid lymph nodes,


which are larger and show axial diameter of 810 mm and
longitudinal diameter of 1520 mm, normal nodes are difficult to detect because of their high echogenecity, which
is similar to that of the surrounding fatty tissues.
Reactive lymph nodes Enlarged reactive lymphnodes
are most frequently encountered in head and neck, most
commonly the submandibular and lateral cervical nodes.
The typical sonographic appearance shows a longitudinaloval shape with rounded poles and smooth border. The
echogenecity is low and homogenous with hyperechoic
periphery. The axial diameter is usually less than 8 mm,
whereas the longitudinal diameter can range from 15 to
20 mm.
Inflammatory lymph nodes Shape of inflammatory
lymph node is longitudinal or ovoid with rounded poles.
In addition, they may be round to spherical with smooth
borders and display a hypoechoic appearance. The ratio
between longitudinal and transverse diameter of lymphnode
is termed roundness index (RI). If RI 2 (longitudinal),
it indicates inflammatory disease, whereas RI  1.5 (spherical) favors metastatic involvement.
In subatue inammation, the lymph nodes tend to become
smaller. In chronic inammation, they are small, soft,
movable, slightly hypoechoic with smooth borders, and
have longitudinal shape.
Specific lymphadenitis (tuberculosis) They range from
large, round, non-echoic to cystic necrotic nodes with blurred
borders. Fistulas appear as hypoechoic or non-echoic linear
stripes.
Primary lymph node disease
i. Sarcoidosis (benign)
ii. Hodgkins and non-Hodgkins (malignant)
Individual lymph nodes are round to oval and occasionally appear as very large, non-echoic, simulating a cyst.
Lymph node metastasis Lymph nodes appear round to
spherical, are hypoechoic but occasionally inhomogenously
echogenic with loss of hilar definition visible. In case of
extranodular involvement, borders are poorly defined.
2. Salivary glands
Glands are typically homogenous echogenic structures.
Intraglandular and extraglandular ducts can only be visualized using high frequency, high-resolution transducers.
Sialadenitis It reveals inhomogenous hypoechogenicity
which is more dominant in acute than in chronic inflammation.
Sjogrens syndrome It reveals inhomogenous and hypoechogenicity. In severe cases, multiple cystic lesions appear
due to destruction of parenchyma.
791

Section X Radiographic Methodology

Sarcoidosis of the parotid glands It reveals multiple


small hypoechogenic granulomatous nodules, which are
diffusely distributed throughout the gland.

Sialolithiasis It reveals echogenic complex with sound


shadowing. Sialoliths which are smaller than 2 mm may
not show shadow in sonography. Accuracy of sonography
for diagnosis of sialolith is 8094%.

Sialadenosis It reveals homogenous, echogenic parenchyma extending enlargement of the glands secondary to
tumor.
Pleomorphic adenoma It reveals homogenous ultrasonic
pattern with decreased echogenicity and smooth borders.
But occasionally, tumor is hyperechoic with cystic areas of
calcification.
Cystadenolymphoma It reveals hypoechogenic with
smooth border. Hypoechogenicity is homogenous/inhomogenous with cystic areas with multiple septae.

Evaluation of swelling of the neck, particularly those


involving the thyroid, cervical lymph nodes or the
major salivary glands. Ultrasound is now regarded as
the investigation of choice for detecting solid and cystic soft tissue masses.
Detection of salivary gland and duct calculi.
3. Primary soft tissue tumors
Hemangiomas and lymphangiomas Echogenicity is
variable and depends on the size of cystic compound. They
can be hyoechoic or isoechoic but usually are hyperechoic
compared to surrounding cervical soft tissues.

Advantages Over Conventional X-ray Imaging

Sound waves are not ionizing radiation.


There are no known harmful effects on any tissues at
the energies and doses currently used in diagnostic
ultrasound.
Images show good differentiation between different
soft tissues and are very sensitive for detecting focal
disease in the salivary glands.
Technique is widely available and inexpensive.

Cystic hygroma They appear non-echoic.

Disadvantages

Lipoma Fat containing lipomas are relatively hypoechoic.


Fibrolipoma reveals high echogenicity with striated feathery appearance.

Carcinoma Most frequent tumor is carcinoma of the


tongue. It appears hypoechoic, inhomogenous, space occupying lesion with blurred borders. Sonograpy can evaluate
extension across midline and infiltration of the floor of
mouth, and relation of tumor to the mandible.

Infections of tongue, floor of mouth. Abscess appears


as circumscribed hypoechogenic or non-echogenic,
space occupying lesion with irregular border. Central
area of abscess contains fluid like pus, thus anechoic
and soft tissue remnants, blood vessels or foreign bodies appear echogenic. Aerobic bacteria may produce
small bubbles of air, bright reflexes.
Therapeutically in conjunction with the newly developed sialolithotripter, to break up salivary calculi into
approximately 2 mm fragments which can then pass
out of the ductal system so avoiding major surgery.
792

Ultrasound-guided fine needle aspiration biopsy. Mainly


used for detection of subclinical ipsilateral nodes. This
helps in accurate analysis of the size of nodes. 18-gauge
needle is used for FNAC.
Determination of the relationship of vascular structures and vascularity of masses with the addition of
color flow Doppler imaging.
Detection of foreign bodies in soft tissues.
Caries detection: The ultrasonic caries detector consists of a PC-controlled ultrasonic pulse receiver and a
probe (diameter 4.5 mm) attached to a handle. The display showed a correct waveform with a recognizable
echo, and a thickness value appeared on the monitor.
Measurements of the soft tissue thickness using an
ultrasonic gingival-thickness meter could help practitioners select the proper orthodontic miniscrew. The
meters monitor displays the soft tissue thickness.
Assessment of blood flow in the carotids and carotid
body tumor.
Assessment of the ventricular system in babies by
imaging through open frontenelles.

Ultrasound had limited use in the head and neck


region because soundwaves are absorbed by bone. Its
use is therefore restricted to the superficial structures.
Technique is operator dependent.
Images can be difficult to interpret for inexperienced
operators because image resolution is often poor.
Real-time imaging means that the radiologist must be
present during the investigation.
Ultrasonic waves of high intensity ultrasound generate cavitation in liquids.

Artifacts
1.

2.

Section thickness: It results from beam width perpendicular to the scan plane. Echoes are received that
originate not only from the center of beam but also
from off center. Third dimension volume is visible.
Reverberation (multiple reflection): It can occur between
the transducer and a strong reflector. Multiple echoes
may be sufficiently strong to be detected and cause

Chapter 28 Radiographic Techniques

3.

4.

5.

6.

7.

confusion on display. The hyperechoic areas are separated at equal interval.


Comet tail artifact: When the reflecting surfaces are
closely spaced they appear in a form of comet tail.
Irregularities of the surface of the lung may cause
transient comet tail artifacts.
Refraction: Refraction can cause a reflector to be
positioned laterally (e.g. abdominal midline) producing two images of single object. The reflector is at 1
but system places it at 2. One real structure is imaged
as two artifactual objects.
Ghost artifact: In transverse scan, sound rays are
refracted at the muscle or fat interfaces in such a way
that smaller structures in the abdomen or pelvis may
be completely duplicated. Artifact disappears if transducer is angled.
Mirror image artifact: Air-filled lung, covered by visceral pleura, causes a highly reflective beam into the
chest. Thus, a sonography will produce pattern of bright
echoes (mirror image).
Gliding sign: Longitudinal image with transducer directly
on the ribs appear as curving bright interfaces that cast
dense acoustic shadows. The lung surface moves with
respiration, thus appear as gliding sign in sonography.

SIALOGRAPHY
Sialography is the retrograde injection of contrast agent
(usually iodine based) into the ductal system of a salivary
gland. In 1925, Barsony introduced the technique of injecting a radiopaque medium (20% potassium iodide) into the
ductal system of salivary glands.

Indications of Sialography
1.
2.
3.
4.
5.
6.
7.

To assess the ductal architecture of the salivary glands


to assess developmental disturbances.
Detection or confirmation of small parotid or submandibular gland sialoliths or foreign bodies.
Evaluation of the extent of irreversible ductal damage
present as a result of chronic infection.
Differentiating between diseases such as chronic sialadenitis, Sjogrens syndrome and sialosis.
Evaluation of fistulas, strictures, diverticula, communicating cysts and ductal trauma.
Rarely, as a dilating procedure for mild ductal stenosis.
Evaluation of masses within the submandibular or
parotid salivary gland in conjunction with a CT scan.

Procedure
Armamentarium
1.

Sialographic cannulas (Rabinov cannulas, cannulas


designed by Lowman and Bezella)

2.
3.
4.
5.
6.
7.

A set of lacrimal dilators (0000 through 0 caliber)


Iodinated contrast agent (oil or water based)
5 ml or 10 ml syringe, guaze pads
Secretogogue to stimulate salivary flow such as fresh
lemon or 2% citric acid
Adequately focused lighting (a headlight unit)
High powered magnifying glass.

Preimaging assessment
Patient should be asked about the following:
1.
2.
3.
4.

5.

History of allergy to iodine/contrast agents.


Medical history about medications.
Previous salivary diagnostic tests and the results of
the same.
Ask the patient whether any thyroid function tests are
scheduled in the near future (absorption of iodine across
glandular mucosa may interfere with thyroid function
tests, in such a case it is recommended that the sialography be deferred after the thyroid tests have been
performed).
Examine the ductal orifice, if purulent discharge is
evident then the procedure should be deferred until
the condition has resolved.

Preimaging instructions to the patient


1.
2.
3.

4.

Explain the procedure to the patient.


Patient is told to expect a sense of fullness or pressure
within the gland during the procedure.
The patient should be instructed to indicate to the
examiner by means of a predetermined signal, when the
injection of the contrast agent is becoming uncomfortable (this is the accepted end point for injecting
the contrast agent).
Patient should be informed to expect a mild amount
of discomfort and swelling of the gland in question,
which usually subsides in 2448 hours.

Technique
1.
2.

3.
4.
5.

Patient is made to lie down in the supine position.


Scout radiographs, comprising PA view, PA puffed
cheek view and lateral views are taken for the parotid
gland and for the submandibular gland; AP view,
lateral oblique view and a submentovertex view are
taken.
The scout radiographs are taken for two reasons:
(i) to evaluate for any large calcifications within the
salivary glands and they are used as base radiographs
against which the sialograph can be compared.
The salivary duct orifice is located.
Lacrimal dilators are used to dilate the salivary duct
orifice.
Cannulas are gently maneuvered into the orifice to
locate the salivary duct. At this stage, asking the patient
793

Section X Radiographic Methodology

6.

to suck on freshly cut lemon will produce saliva aiding in locating the duct orifice.
Contrast medium is injected into the salivary duct.

Injection of the Contrast Medium


Contrast medium can be injected by three techniques:
1.
2.
3.

Hydrostatic injection technique


Distention injection technique
Hand injection technique.

Hydrostatic injection technique


In this technique, a reservoir is used which contains the
contrast media. This reservoir is placed about 70 cm above
the patients head. This arrangement permits the constant
perfusion of the ductal system with a water-soluble contrast agent. This system provides for a uniform pressure
during injection without the examiner being physically
present in the room. This technique is useful in CT-guided
sialography.
Distention injection technique
Distention sialography involves the hand injection of the
contrast media until the gland physically bulges. This usually requires 2.53 ml of the contrast media (in normal cases
where routine hand injections are used 0.50.75 ml is used).
This technique was popular in the pre-CT era to evaluate
and visualize small peripheral masses within the duct or
the gland. This technique is not preferred any more.
Hand injection technique
This is the most preferred technique for injecting the contrast media into the gland. The contrast media is injected
gently using a steady constant pressure. The injection is
performed under fluoroscopic observation and stopped
immediately when the patient indicates that the injection
is becoming uncomfortable. Normally the parotid can
accommodate 0.50.75 ml of the contrast media and the
submandibular gland can accommodate about 0.5 ml of
the agent.
The lling of the salivary duct and the gland can either be
examined under uoroscopy in real time or routine radiographs can be taken after the contrast media is injected.

Phases of Sialography
1.
2.
3.

Ductal phase
Acinar phase
Evacuation phase

Ductal phase
The ductal phase begins with the injection of the contrast
medium and terminates once the parenchyma becomes
794

hazy (reflects the onset of acinar opacification). The ductal


phase of the normal parotid sialogram should demonstrate
the main duct to be of uniform caliber extending from the
ductal orifice to the hilus of the gland. The intraglandular
portion of the parotid ductal system should demonstrate
a progressive arborization of the secondary and tertiary
ducts. This configuration is often described as a leafless tree
appearance on a sialogram.
The ductal phase of the submandibular sialogram can
be divided into two substages.
The rst substage involves the lling of the deep portion
of the main duct; the second substage involves the lling of
the supercial segment perpendicular to the mylohyoid muscle as well as the remainder of the ductal system. In contrast to the orderly arborization seen in the parotid duct, the
submandibular ducts are often noted to terminate abruptly
with poor or incomplete lling of the tertiary elements.
Acinar phase
The acinar phase begins with the completion of ductal
opacification and ends when there is a generalized increase
in density of the gland. This phase was of special importance in the pre-CT era, when sialography was intended to
demonstrate the presence of intraglandular and extraglandular masses.
Evacuation phase
The evacuation phase of a sialogram provides an estimate
of the secretory function of the salivary gland as well as
demonstrating or accentuating ductal pathology that might
not have been evident on other views.
The evacuation phase is divided into two subphases:
a.
b.

Nonstimulated evacuation of the gland and ductal


system
Stimulated evacuation of the gland and ductal system.

The evacuation phase evaluated under intermittent fluoroscopy for about one minute, while checking for spontaneous clearing of the contrast agent from the gland. A
normally functioning, unobstructed gland should be able
to clear nearly the entire contrast agent.
The second subphase is an evaluation of the glandular
response to stimulation using a sialogogue or 2% citric
acid drops placed on the tongue and intermittently monitoring the clearing of the contrast from the gland. The second subphase is performed if a signicant amount of
contrast is still present in the ductal system after the rst
subphase. The nonclearing or partial clearing of the gland
may be due to a stricture, a sialolith or both or an underlying physiologic abnormality.
Post-stimulation views of the gland may demonstrate
adequate clearing of the ductal system and intraparenchymal collections of contrast. Small 13 mm uniformly distributed collections of contrast agent may be seen as a

Chapter 28 Radiographic Techniques

result of pseudo sialectases whereas irregularly distributed


or larger collections can result from abscess formation or
tumor necrosis.

Contraindications of Sialography

Acute salivary gland infections or patients recovering


fom acute infections.
Malignant lesions involving the salivary gland.
Patient is allergic to contrast agent.
Patients who have to undergo thyroid function tests
during the period of sialography.
Pregnancy (high doses of radiation is used especially
for fluoroscopy).

One of the more commonly used approaches involves injection of contrast material into the lower joint spaces, referred
to as lower joint space or single contrast arthrography.
Perforations of the disk or posterior attachment are
demonstrated by contrast material simultaneously owing
into the upper joint space as the lower space is injected.
Another variation of the technique involves injecting contrast material into both the spaces and viewing the more
central portions of the joint with tomography. Because
contrast material is in both joint spaces, the outline of the
disk is proled, showing its conguration and position.
The outline of the disk can often be enhanced by using double contrast arthrography. This technique involves injecting a small amount of air along with a small amount of
contrast material into both joint spaces, producing a thin
coat around the periphery of both joint spaces that highlights the disk and the joint spaces.

ARTHROGRAPHY
Arthrography involves injection of a radiopaque contrast
material into the joint spaces. The space occupied by the
disk can then be visualized lying between the layers of
contrast material.
Dr Fleming Norgaard, in 1947 was the rst to successfully use contrast arthrography. But it was in the 1970s that
Wilkes and others introduced and popularaized the technique in the United States.

Procedure
1.

2.

Uses of Arthrography

Arthrography provides information regarding the soft


tissue components, specifically the shape and position
of the articular disk. It has been demonstrated that
with the addition of tomography, the diagnosis of
abnormalities in the position and shape of the disk is
accurate.
Fluoroscopic observation of the injection may reveal
the presence of adhesions, perforations and discontinuities in the capsule and provides a dynamic study of
disk movements, also any abnormal accumulation of
joint fluid may be evident.
Synovial fluid sampling (arthrocentesis) and lavage
of the joint can accompany the procedure of arthrography.
Arthrography assures a correct pre-operative diagnosis
of loose bodies (joint mice).
An arthrogram can clearly distinguish the synovial
changes of an inflammatory arthritis from an internal
derangement resulting from meniscal dysfunction.

3.

4.

5.

6.

7.

Types of Arthrography
1.
2.

Single contrast arthrography


Double contrast arthrography

8.

The patient is placed on the fluoroscopic table in a


lateral recumbent position with the head tilted on the
tabletop. This allows the joint to project over the skull
above the facial bones in a manner similar to a transcranial radiograph.
Under fluoroscopic guidance the posterosuperior aspect
of the mandibular condyle is identified with a metal
marker. This area is marked with an indelible pen.
Local anesthetic lidocaine is infiltrated into the superficial skin.
A 0.75- or 1-inch scalp vein needle and the attached
tubing is filled with contrast material and care is taken
to eliminate air bubbles. Air bubbles may simulate bodies within the joint space.
In a direction perpendicular to the skin and X-ray beam,
the 23-gauge needle is introduced in a predetermined
region of the condyle with the jaw in the closed position. Advancement of the needle is done under fluoroscopic observation to ensure proper positioning.
When the condyle is encountered, the patient is instructed
to open the jaw very slightly, and the needle is guided
by the feel of the posterior slope of the bony condylar
margin. On fluoroscopic observation, the needle will
appear contiguous with the posterior condylar outline.
Approximately 0.40.5 ml of contrast material is injected
into the lower joint compartment under fluoroscopic
guidance. If the contrast is successfully placed into
the lower joint space, the opaque material will be seen
flowing freely anterior to the condyle in the anterior
recess of the lower joint compartment.
The needle is then withdrawn and fluoroscopic videotape images are recorded during opening and closing
maneuvers of the jaws.
Spot radiographs are obtained during the fluoroscopic
procedure.
795

Section X Radiographic Methodology

Limitations
1.
2.

periosteum of the condyle and as the joint is distended


with contrast material. This discomfort is transient in a
majority of cases. If persistent joint pain occurs following the procedure, aspirin or acetaminophen and cold
compress application to the affected side is recommended.

Direct medial or lateral displacements are difficult to


interpret with arthrography.
Cannot be used when the disk is severely deformed.

Complications
1.

2.

3.

4.

5.
6.

7.

8.

THERMOGRAPHY

The rare serious complications associated with arthrography include joint sepsis, allergic reaction to the
iodinated contrast medium and hemarthrosis.
Pain during and after the procedure, extravasation of the
contrast medium, disk perforation and transient facial
paralysis are less serious complications of arthrography.
The radiation exposure to the patient can be significant, depending on the duration of fluoroscopy and
the number of tomographic exposures made.
The most frequent complication of the technique is the
extravasation of contrast medium into the capsule and
soft tissues around the joint, causing pain. Nonionic
contrast media will be the agents of choice to minimize
this discomfort.
Parotitis has been reported following arthrography with
large needles and cannulas.
Some patients experience a vagal reaction, as a result
of increased anxiety during the procedure, this can be
managed by administering 0.6 mg of atropine intravenously.
Intravasation of contrast material infrequently occurs.
Epinephrine in a dose of 0.03 ml (1:1000) per 3 ml of
contrast material is recommended because there is a
risk of an acute hypotensive episode with intravasation of higher doses.
Transient facial paralysis may result from a rapid infiltration of lidocaine. Some patients experience a moderate degree of pain as the needle is placed on the

It is also called thermal imaging or infrared imaging.


Thermography is a non-invasive diagnostic imaging procedure that detects, records, and produces an image (thermogram) of a patients skin surface temperatures and/or
thermal patterns (Figures 88 and 89). The procedure uses
equipment that can provide both qualitative and quantitative information on the normal and abnormal functioning
of the sensory and sympathetic nervous systems, vascular
system, musculoskeletal system, and local inammatory
processes.
There are presently two recognized techniques of thermal
imaging, namely, electronic infrared telethermography and
liquid crystal thermography.

Liquid Crystal Thermography


Liquid crystal thermography (LCT) utilizes a range of interchangeable screens impregnated with cholesteric methylester derivatives that change color as a function of their
temperature. The screens are placed on the anatomic surface for development. A 35 mm or polaroid picture of the
image is taken for later analysis and archiving.

Electronic Infrared Telethermography


Infrared telethermography (IRT) equipment incorporates
single or multiple infrared detectors that survey the region

Figure 88
37.0
36.2
35.4
34.6
33.8
33.0
32.2
31.4
30.6
29.8
29.0
C

Two examples of infrared images of the lateral aspect of the face. Courtesy: Prof Francis Ring, Head of Group,
Thermography, University of Glamorgan, UK

796

Chapter 28 Radiographic Techniques

Figure 89

38.5 C
38
36
34
32
30
28
26
25.5 C

Infrared and visual image of a subject with an elevated body temperature. The color alarm clearly shows
the parts of the head with a temperature higher than 38C

to be studied in two directions simultaneously. The process


does not involve any contact with the surface of the skin.

Patient Preparation

The patient should be instructed not to use lotions,


creams, powders, makeup, deodorants or antiperspirants on the body area to be imaged on the day of the
examination.
The body areas included in the image should not be
shaved within 4 hours of the examination.
No physical therapy, ultrasound treatment, acupuncture or hot/cold pack should be used 24 hours before
the examination.
No exercise should be done 4 hours before the examination.
Patient should not bathe for an hour before the examination.
The area to be imaged should remain completely uncovered of clothing or jewelry.

Procedural Requirements
The room should be of adequate size to maintain a uniform temperature. A room approximately 8  10 feet size
is adequate to meet these requirements. During the examination, the patient should be positioned relatively equidistant and adequately spaced from each wall. The room
should be carpeted. Curtains may be used to prevent outside infrared radiation from entering the room. The room

must be free from drafts. Windows and doors should be


adequately sealed to prevent airflow in the area where the
patient is positioned. Incandescent lighting should not be
used during the examination due to the amount of infrared radiation produced. Standard fluorescent lighting is
adequate. The temperature range in the room should be
maintained between 18 and 23C. Room temperature transitions during the course of an examination must be gradual so that steady state physiology is maintained and all
parts of the body can adjust uniformly.
The temperature of the room should not vary more than
1C during the course of a study. The humidity of the room
must also be controlled such that there is no air moisture
build up on the skin, perspiration, or vapor levels that can
interact with radiant infrared energy.

Indications
Merla et al (2004) assessed the use of functional infrared
imaging in the diagnosis of the myofascial pain. They
concluded that functional infrared imaging seemed to distinguish healthy subjects from the patients suffering myofascial pain.
Gratt and Anbar (1998) summarized the following clinical applications for thermography in dentistry:
1.
2.
3.
4.

Evaluation of atypical odontalgia


Diagnosis of chronic orofacial pain
Assessment of TMJ disorders (internal derangement of
TMJ)
Assessment of inferior alveolar nerve deficit.

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SECTION

XI

Processing of
Radiographs and
Radiographic
Interpretation
29 Latent Image Formation
30 Processing of Radiographic Films
31 Radiographic Faults

801
803
812

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CHAPTER

29

Latent Image Formation


Ravikiran Ongole, Praveen BN

Formation of a visible radiographic image is a three-stage


process:

2.

1.

3.

Interaction of X-ray beams with the object of interest.

Interaction of the information carrying X-ray beam


with the photosensitive silver halide crystals in the
film (latent image formation).
Chemical action of developing solutions which convert
the latent into visible image.

Figure 1
Silver ion

Bromide ion

Sensitivity site
X-ray photon

Silver bromide

ee-

X-ray film
Interstitial
silver ions

e- e- e e-

e-

eee- e
e-

Latent image formation. Courtesy: Dr Jaideep Shekhar

801

Section XI Processing of Radiographs and Radiographic Interpretation

FORMATION OF LATENT IMAGE


To understand the formation of latent image, one needs to
know the composition of an intraoral film. A dental film
comprises of an emulsion suspended in gelatinous vehicle
that is coated onto a plastic supporting base.
The emulsion is composed mainly of photosensitive silver bromide crystals and to a lesser extent silver iodide
crystals and very small amounts of free silver ions interspersed in the crystal lattice (interstitial silver ions), iodide
ions (produce the physical irregularity in the array of silver
and bromide ions) and traces of sulfur compounds, which
bind to the surface of the crystals. These sulfur compounds
along with the physical irregularities on the surface of the
silver halide crystal form the latent image sites.

Steps in Latent Image Formation (Figure 1)


1.
2.

802

X-ray photons pass through the object of interest and


carry information to the film.
X-ray photons strike the film and interact with the
bromide ions primarily (bromide ions are about oneand-a-half times larger in diameter when compared to
silver ions).

3.

4.

5.
6.

7.

As a result of Compton and photoelectric effects, electrons are displaced from the bromide ions producing
high-speed electrons (recoil electron) and scattered
X-ray photons.
These recoil electrons travel within the silver halide
crystal creating additional bromine atoms, scattered
photons and secondary recoil electrons until their
energy is dissipated.
These recoil electrons get trapped in the latent image
site and impart a negative charge to these sites.
The free interstitial silver ions which are positively
charged are drawn toward the negatively charged
latent image sites.
Within these sites the silver ion is neutralized resulting in an atom of sliver that gets deposited.

This process repeats multiple times at every single latent


site leading to the further deposition of silver atoms which
ultimately gives rise to the latent image.
Once these radiographs are placed in the developer
solution, the silver atoms in the latent image sites are converted to black metallic silver grains and the unexposed
silver halide crystals are removed by the clearing agent in
the xing solution resulting in the formation of a visible
image.

CHAPTER

Processing of Radiographic
Films
Ravikiran Ongole

Daylight Processor
Self-developing Film

Techniques of Film Processing

Manual Processing of Films


Darkroom
Visual Method
TimeTemperature Controlled Method

Following exposure to radiation, the latent image formed


on the film is converted to a visible image by a technique
referred to as film processing. Radiographic films have
been traditionally processed in a darkroom. However, over
the years, techniques such as daylight processing, automatic processing and self-developing films have eliminated
the need to use a darkroom for processing films.

30

Automatic Processing
Working Mechanism
Composition of Processing Solutions

Ideal requirements
1.

2.

Darkroom should be spacious enough to permit at least


one person to work comfortably and should measure
at least 4 5 feet in dimension (Figure 1).
An ideal darkroom should have a doorless maze pattern (Figure 2A) or a conch shell design (Figure 2B) to
prevent entry of light into working area.

Techniques of Film Processing


1.

2.

Manual processing
Timetemperature method (darkroom technique)
Visual method (darkroom technique)
Daylight processing (darkroom not required)
Self-developing films (darkroom not required)
Automatic processing.

Figure 1

MANUAL PROCESSING OF FILMS


Traditionally radiographic films are processed in a darkroom. Before one learns the art of radiographic film processing, it is essential to be familiar with the designing of
the darkroom and its contents.

Darkroom
Radiographic films are sensitive to X-rays and visible
light. In order to prevent exposure of the films to visible
light it is necessary to process the exposed radiograph in a
room specially designed to keep away visible light.

Photograph of a compact darkroom of adequate size

803

Section XI Processing of Radiographs and Radiographic Interpretation

Figure 2
A

Conch shell
design

Working
area

Doorless maze pattern


Working area

(A) Illustration showing the doorless maze pattern of a darkroom. (B) Conch shell design for the darkroom.
Courtesy: Dr Jaideep Shekhar

Figure 3

Figure 4

Photograph showing the contents of the darkroom


such as the processing tanks, wash basin, drying racks,
film holders and safe light

Darkroom infrastructure (Figure 4)


An ideal darkroom should contain the following:

Light tight door with a locking mechanism for the


darkroom

3.

804

In the event of having a door it should be light tight and


should have provisions for locking to prevent accidental opening of the door, which might unnecessarily
expose the image receptors to visible light (Figure 3).

1. Processing tanks (master tank with developer and


fixer tanks)
2. Safe light
3. Visible light source (tube lights)
4. Working area (to load extraoral film cassettes and
unwrap films)
5. Dryer
6. Thermometer and stop clock
7. Storage facility (to store unexposed films)

Chapter 30 Processing of Radiographic Films

Figure 5
A

(A) Master tank with water and containing the developer and fixer solution tanks.
(B) Master tank covered with a lid when not in use

8. Exhaust and appropriate ventilation


9. Drying racks
10. Processing solution stirrer and film retrievers.
Processing tank
The film processing tank is commercially available and
made of inert plastic (RinnTM) or can be made custommade out of stainless steel or bricks and mortar (to prevent
reaction with the chemicals of the processing solutions).
The processing tank should be placed at a convenient
height and away from the working area where films are
unwrapped or loaded into cassettes.
Commercially available tanks comprise of a large master tank and two smaller removable inserts (for the developer and xer solution) which are placed within the master
tank that contains water (Figure 5A). Many of the commercially available master tanks measure 8 10 inches
and the smaller tanks hold about 9 liters of the xer and
developer solution.
The master tank holds either running water or water
stored at room temperature. The temperature of the water
in the master tank will help regulate the temperature of
the developer and xer. The water contained in the master
tank is also used for rinsing the lm during processing. A
lid should always be placed over the tank to minimize the
oxidation of the processing solutions by atmospheric oxygen and evaporation (Figure 5B).

the films. However, the visible lights may be switched on


once the films are placed in the fixer tank.
The safe light should ideally be 15 W bulb in the orangered-yellow spectrum of light (Figure 5B) as these colors
have the longest wavelength and low penetrating power
(X-rays are highly sensitive to blue and green colors).
A red GBX-2 lter may be placed over the safe light.
One or two safe lights may be used based on the size of
the darkroom. One safe light over the processing tanks (ideally on the right hand side or the xer solution side of the
tank) and one over the working area (place where the lms
are loaded). The safe lights should ideally be placed 4 feet
above the working area and processing tanks (Figure 6B).
Floating thermometer and stop clock
A floating thermometer (Figure 7A) and stop clock are
used for the timetemperature method of processing films.
The thermometer helps to assess the temperature of the
processing solutions so that the duration for which the
film should be developed is known. The thermometer is
left floating in the water in the master tank prior to the
processing (Figure 7B). Alcohol containing thermometer is
preferred as mercury containing thermometers may contaminate the processing solutions in the event of a breakage. The stop clock helps to set the exact time for the
developing procedure.
Drying racks and film hangers

Safe light and visible light illumination


Visible light illumination can be in the form of ceiling or
wall mounted light source (Figure 6A). However, care should
be taken to ensure that these tube lights are switched off
during loading the films into cassettes or while processing

Drying racks should strategically be located above the


washing area in the darkroom. Once the films are removed
from film hangers after drying, the empty hangers should
be thoroughly rinsed and left to hang dry over the drying
racks (Figure 8).
805

Section XI Processing of Radiographs and Radiographic Interpretation

Figure 6
A

(A) Photograph showing the visible light mounted on the ceiling. (B) 15 W safe light in the orange-red spectrum of light

Figure 7
A

(A) Floating thermometer. (B) Photograph showing the floating thermometer in the master tank containing water

Presence of any remnant xer solution remaining on


the hangers may result in faulty radiographs in the form
of light spots. Water droplets on the hangers may produce
watermarks on the lms, which might obscure diagnostic
details in the radiographic image.

Figure 8

Dryer cabinet
Wet films following the processing can be dried effectively
using cabinet driers, which help in circulating warm air
(produced by heaters) around the films thereby hastening
the drying process (Figure 9).
However, lms should not be placed close to the heat
source in the cabinet drier as they can get distorted. Alternatively, wall mounted fans over the drying racks can be
used. Cabinet driers may also be placed outside the darkroom.
Processing technique
Film hangers shown drying after use

806

Timetemperature method of processing films is the most


ideal method of processing films manually. However,

Chapter 30 Processing of Radiographic Films

Table 1

Figure 9

Cabinet film dryer

when the facility of temperature controlled processing is


not available, the visual method can be employed.

Visual Method
In this method, there is no predetermined time for which
the film is placed in the developer solution. The exposed
film is placed in the developer solution and taken out at
regular intervals and examined under safe light for the most
calcified/radiopaque structures to be evident. Appearance
of radiopaque structures (like the enamel cap, restorations,
artificial crowns) indicates the end point of developing
time. At this juncture, films are taken out of the developer
solution, rinsed in water and placed in the fixer solution.
Disadvantage Quality of images is not reproducible as
the technique is very subjective.

TimeTemperature Controlled Method


The timetemperature method for processing films ensures
optimal film quality.
Steps in processing the film
1. Ensure that the levels in the developer and fixer tank
are adequate (the entire film should submerge into the
solutions).
2. Make sure that the solutions are not too old. Depleted
developer solution appears brownish black. On an average developer and fixing solutions are changed every
15 days (taking into account that approximately 30
intraoral and 5 extraoral films are processed per day).

Timetemperature reference chart

Temperature of the processing


solutions (Fahrenheit)

Development time
(minute)

68

70

4.5

72

76

80

2.5

3. Use a separate stirrer for the developer and fixing


solutions and stir the solutions each day in the morning. Stirring will help even distribution of the contents of the solutions and may help in maintaining a
constant temperature throughout the solutions.
4. Generally the metal insert containing the developer
solution is placed toward the left hand side of the
master tank and the fixing solution is placed on the
right hand side of the master tank (with the personnel
facing the master tank). However, as the inserts are
generally not labeled it is wise to check the solutions
before processing the films. This can be done by dipping a finger into one of the tanks and gently rubbing
the fingertips. The developer solution will feel soapy
as it is alkaline in nature.
5. Once the solutions are stirred evenly, the temperature
of the solutions is assessed by placing the floating
thermometer in the water bath. For intraoral films the
manufacturer specified duration of developing can be
used. The following timetemperature reference chart
may be used (Table 1).
6. Film hanger is selected and ensured that it is dry and
does not contain any trace of water or processing
solutions. The film packet is opened in the darkroom
and the film is clipped onto the hanger. The film thus
clipped is drawn out of the film packet thereby ensuring that the film does not come in contact with the
fingers of the operator, which might obscure diagnostic details on the resultant radiographic image.
7. Once the film is placed in the developing solution, the
stop clock is started. Initially the hanger is gently agitated for a few seconds to eliminate any air bubbles
on the film. Later the hanger is placed in the developer tank for the predetermined time based on the
temperature of the processing solutions. After the preset time, the hanger holding the film is removed gently and all excess developer solution clinging onto the
film is let to drain away into the master tank by holding the hanger over the master tank containing water
for a couple of seconds.
8. The film is then placed into the master tank containing
water for about 30 seconds. The hanger holding the
film should be agitated gently so that all the excess
807

Section XI Processing of Radiographs and Radiographic Interpretation

9.

10.

11.
12.

developer solution is removed from the film (this halts


the developing process) and the fixer solution is not
contaminated by the developer solution (contamination of the fixer solution causes the acidic fixer solution
to be neutralized by the alkaline developer solution).
Once the films are rinsed, they are placed in the fixer
solution for about 4 minutes. The hanger holding the
film is agitated at regular intervals to bring the fixer
solution to evenly contact the film.
After the films are taken out of the fixer solution they
are held under running water for about 5 minutes
ensuring that all the surfaces of the film come under
the running water and remnants of the processing
solutions are totally washed away. The film is gently
shaken to remove water drops clinging onto the surface of the film.
The hanger holding films are then dried using a fan or
a cabinet dryer.
Dried films are placed in a film mount before interpreting the films using an illuminated viewer box.

Daylight Processor
It is essentially a plastic housing with a 15 W bulb. The
housing is just large enough to cover three plastic bowls
that contain developer, water and fixer solutions. It is like
a make-shift arrangement for a darkroom especially for
dental clinics and mobile dental clinics.
The operator can slide his/her hands via two sleeves provided at the sides of the plastic housing and then unwrap
the lm. A plastic, tinted see-through lid at the top of the
housing enables the operator to see within the plastic case
without causing unnecessary light exposure (Figure 10A, B).
Under safe light conditions, provided by the 15 W
orange-red bulb, the lm can be unwrapped, helped with

a single lm holder and processed traditionally by dipping


the lm rst into the developer, water and nally the xing solution. Once processed, the lm can be washed outside the housing under running water and subsequently
dried.

Self-developing Film
These have also been referred to as rapid autodeveloping
films. It is essentially a one-piece soft plastic (polyvinyl
chloride) pouch designed such that the film is located at
one end and a monobath of developer and fixer is located
at the other end. Both the ends are connected via a narrow
corridor that helps in carrying the processing solutions to
the film (Figure 11).
During the exposure, the lm end is positioned in the
mouth with the other end hanging outside the mouth. Once
the exposure is made, the pouch is rst washed to remove
the patients saliva. Then the lm is developed by holding the
monobath end of the pouch upright and rolling it down
until the processing chamber ruptures and empties into the
corridor. Continuing to roll the pouch ensures that all of
the monobath solution travels toward the lm end.
The user continues to hold the pouch upright and massages the monobath around in the lm end of the pouch
Figure 11

Self-developing film

Figure 10
A

(A) Daylight processing unit. (B) Small cups filled with processing solutions within the daylight processor

808

Chapter 30 Processing of Radiographic Films

for 50 seconds. When development is complete, the pouch


is turned upside down and the monobath is massaged back
to its original location at the opposite end. The lm end of
the pouch is then opened by pulling apart the tabs and the
lm is removed. The lm is rinsed under water to remove
the remaining monobath solution.

Circulation-filtration system (Figure 15)


The roller-transport system squeezes the chemicals into
and out of film emulsion, providing an agitating action,
which promotes even processing and increases the speed

Figure 13

AUTOMATIC PROCESSING
Automatic film processing refers to the processing of
radiographs using machines specifically designed for that
purpose. Most automatic processors are not universal
(there are separate machines to process extraoral and
intraoral films). These processors have inherent limitations
with regard to the need for regular maintenance and cost
(Figure 12).

Working Mechanism
The automatic processor is made up of five basic systems
the transport system, the circulation and filtration system, the
replenishment system, the tempering system, and the dryer
system.

Roller mechanism within the automatic processor

Figure 14

Roller-transport system (Figure 13)


The roller-transport system is composed of a feed tray, a
main drive, and a number of rollers called crossovers and
racks.
As the lm is placed in the feed tray, two feed rollers
draw the lm into the machine (Figure 14). The lm moves
circularly through a crossover and vertically down in the
developer by means of a series of rollers. It moves the
same way through the rest of the chemicals.

Film placement slots within the automatic processor

Figure 12

Figure 15

Intraoral film automatic processor

Processing solutions and the roller mechanism


within the automatic processor

809

Section XI Processing of Radiographs and Radiographic Interpretation

of reactions. A circulation-filtration system is used to


boost this action. The circulation pump recirculates the
solutions through filters, keeping the chemicals properly
mixed and clean as well as in a state of agitation.

helps in converting the silver ions into metallic silver at


the latent image sites. However, in this process phenidone
gets oxidized and becomes inactive. Hydroquinone in the
developer solution reduces the oxidized phenidone thereby
helping in its reactivation.

Replenishment system
As each film passes through the automatic processor, the
chemicals are changed slightly. To offset the resulting
deficiencies, new developer and fixer in measured amounts
are pumped into the solutions via the replenishment tanks
attached to the processor. These tanks should be checked
weekly and refilled periodically.
Tempering system
To maintain the desired temperature of the developer and
fixer, a heating device and automatic thermostat are used.
Water is passed through a mixing valve, so that it is 4F or
5F below the desired temperature, and then heated to the
desired temperature by the heating element in the machine.
The wash water temperature is controlled by a mixing
valve, which mixes the hot and cold water. A thermometer
gauge is located between the mixing valve and the wash
tank near the mixing valve.
Air-dryer system
To dry the film, there is a heater to heat the air and a
blower to direct the air. An efficient exhaust system ensures
that the warm, moist air is removed and only hot, dry air
is directed over the films as they move through the rollertransport system.

Composition of Processing Solutions


Processing solutions are composed of a developer and
fixer solution.
Developer solution
Function To reduce the silver ions in the exposed crystals
of silver halide (latent image) to specks of black metallic
silver (diagnostic, visible image).
Composition Developer solution contains four constituents, which are dissolved in water. They are:

Developer
Activator
Preservative
Restrainer.

Developer
Function It converts the exposed silver halide grains to
black metallic silver. It is made up of phenidone and
hydroquinone. Phenidone acts as an electron donor and
810

Activator
Function Activators help in maintaining the alkaline pH
of the developer solution and cause the gelatin of the film
to swell thereby helping the diffusion of the developing
agents into the emulsion and reach the silver halide crystals. Developer solutions are active at an alkaline pH
(approximately 10).
This alkaline pH is achieved and maintained by the
addition of alkaline agents such as sodium or potassium
hydrozide and buffers like sodium carbonate, sodium
hydroxide and sodium metaborate or tetraborate.
Preservative
Function It prevents the oxidation of the developer solution by atmospheric oxygen. It also combines with the
oxidized developer solution (appears brown) and forms a
colorless soluble compound. The preservative is an antioxidant and is usually sodium sulfite.
Restrainer
Function It acts as an antifog agent. It minimizes/
restrains the development of unexposed silver halide grains.
Potassium bromide or sodium bromide is used as the
restrainer in the developer solution.
Fixing solution
Functions Fixing solution helps in removal of the
undeveloped silver halide grains from the emulsion. If the
unexposed silver halide grains remain on the film the radiographic image will appear black and will result in a nondiagnostic image.
Composition The fixer solution contains four constituents, which are dissolved in water. They are:

Clearing agent
Acidifier
Preservative
Hardener.

Clearing agent
Function Dissolves and removes the unexposed silver
halide crystals from the emulsion of the film. The removal
of the unexposed crystals takes place at a controlled slow
pace, however fixing for a prolonged time can lead to a
gradual loss of film density (silver grains dissolve in acetic
acid of the fixing solution).

Chapter 30 Processing of Radiographic Films

Aqueous solution of ammonium thiosulfate is used as


the clearing agent.
Acidifier
Function The acidifier has two important functions. It
helps in the diffusion of ammonium thiosulfate into the
emulsion and the exit of silver thiosulfate complex from
the emulsion. It inactivates remnants of developer solution
that is present over the film thereby halting the developing
process of any unexposed silver halide crystals during the
process of fixing. The acidifier used is acetic acid buffer
system (pH of 44.5).
Preservative
Function It prevents the oxidation of the clearing agent.
It also combines with the oxidized developer solution,
which is carried over to the fixing solution and thereby
preventing staining of the film. The preservative used is
sodium sulfite or ammonium sulfite.
Hardener
Function The hardening agents combine with the gelatin
and prevent damage to the gelatin during handling of the
film. It also reduces the swelling of the emulsion thereby

limiting water absorption, which helps in drying the film


faster. Aluminum salts are used as hardeners.
Comparison between manual and automatic processing
Manual processing

Automatic processing

Darkroom is required

Use of darkroom eliminated

Technique sensitive

Non-technique sensitive as the


films are processed automatically

Direct exposure to hazardous


processing chemicals

No direct exposure to hazardous


chemicals

Films need to be manually dried

Films are dried automatically

Processing solutions need to be


manually prepared

Processing solutions are available


readymade

Longer time for processing

Short processing time

Negligible maintenanceneed to
clean the tanks and replace fresh
solutions every 23 weeks

Regular maintenanceneed to
clean rollers and servicing gear
mechanism

Relatively inexpensive (not


considering the construction
of a darkroom)

Expensive

Universal for intraoral and


extraoral radiographs (provided
the tanks are large enough)

Separate processors are required


for extraoral and intraoral
radiographs

Penny Test
Penny test or coin test is used to assess the safe light condition in the darkroom. It is a known fact that radiographic
film is sensitive to visible light and X-rays. Excessive exposure to safe light or an improper safe light condition can
lead to exposure of the film resulting in film fog.
Procedure
1.
2.
3.

In the darkroom, an exposed film is removed from the film packet and placed on the working bench in an area
where films are usually unwrapped.
A coin is placed on the film and left in place for a few minutes (usually the time it takes for a film to be unwrapped
and clipped onto a film holder for processing.
Process the film as usual. If the image of the coin is seen on the processed film then the darkroom does not have
optimum safe lighting.

Test to Determine the Quality of the Processing Solutions


Over a period of time the processing solutions deteriorate and need to be changed. On an average the processing solutions need to be changed every 2 weeks (depending on the number of films processed per day).
A practical method of evaluating the solutions can be done by exposing a dental radiograph and using freshly
prepared solution to process this lm. The lm can then be used as a reference lm. All successive lms processed
can be compared with this lm for contrast and density. Loss of image contrast and density is an indicator for solution
change.

811

CHAPTER

31

Radiographic Faults
Ravikiran Ongole, Praveen BN

Errors in Film Storage and Handling

Film Fog
Emulsion Peel and Scratched Film
Dark Spots or Lines
Static Electricity Artifact
Nail Marks or Kink Marks

Artifacts

A radiograph is considered ideal when it is dimensionally


accurate, covers the area of interest completely and has
optimum density and contrast. When the above criteria are
not met the radiograph is termed faulty. A faulty radiograph
is non-diagnostic and necessitates retaking the radiograph
which leads to unnecessary patient exposure.

ERRORS IN FILM STORAGE AND HANDLING

Causes of faulty radiograph

Film Fog

Radiographic faults can occur at any stage in the radiographic process, right from handling and storing of films
to the processing. The causes for radiographic faults can
be categorized as:

The overall appearance of the radiograph is dark. The


radiographic image will show decreased image contrast and
detail and as some authors believe they appear as though
the radiographs are being viewed through a fog thereby
obscuring the image (Figure 1).

812

Blank Radiograph
Dark Radiograph
Light Radiographs
Film Fog
Insufficient Contrast
Yellow or Brown Stains
Partial Image
Blisters on the Film
White Spots
Dark Spots on the Radiograph
Light Spots on the Radiograph
Emulsion Wash Away
Reticulation of Emulsion
Hyporetention
Dyschroic Fog
No Image/Blank Radiograph

Errors in Film Placement and Projection


Technique
Herring Bone Effect, Tyre Mark Pattern, Raised
Diamond Markings/Knurled Effect
Cone Cut
Slanting of the Occlusal Plane
Apical Ends of the Teeth Not Imaged (Partial
Image)
Crown Portion of Teeth Not Imaged (Partial
Image)
Overlapped Image
Fore-shortened Image
Elongated Image (Total)
Elongated Image (Partial)
Blurred Image

Errors in Exposure Parameters and Processing


Technique

Errors in film storage and handling


Errors in film placement and projection technique
Errors in exposure parameters and processing technique
Artifacts.

These can occur prior to the radiographic exposure and


after the processing especially before the film is completely dry.

Causes

Films stored at high temperatures and humidity

Chapter 31 Radiographic Faults

Outdated films
Films exposed to extraneous radiation.

Ideal film storage temperature is between 50F and 70F


(1020C) and between 30% and 50% relative humidity.
Any increase is known to cause increased sensitization of
the film emulsion. The expiry date of the film packets have
to be checked and it is also recommended that the radiology unit stocks only sufficient number of film packets that
can be used within 2 months time.
Extraoral lms should be stored in a vertical orientation
to prevent pressure artifacts.

Emulsion Peel and Scratched Film


Emulsion is coated onto the plastic supportive base of the
film and it adheres to the base via a coat of adhesive agent.

However, during the developing process, the emulsion is


rendered soft to aid in the rapid diffusion of the developing
agents into the emulsion and reacts with the silver halide
grains. However, the hardeners in the fixing solution shrink
and harden the gelatin to prevent its damage. White lines
appear when the soft film emulsion is removed from the
film base by sharp objects.
Causes

Wet film in contact with finger nails or other sharp


objects such as film clips (Figure 2A, B).
Placing wet films on unclean surfaces.
After processing, films must not come into contact
with each other until completely dry as the wet emulsions can stick together and peel off the emulsions
when they are separated.
Care must be taken when placing the film holder in the
processing solutions and drier. Avoid contact with other
film hangers and with the tank walls.

Figure 1

Dark Spots or Lines


Cause
Finger print contamination.

Dark finger marks: from improper handling of the film


(holding the film with greasy fingers on the surface of
the film, especially when the fingers are contaminated
with developer solution).
Clear finger marks or white fingerprint marks can be
caused by fixer solution or oily substances on the fingers that prevent the emulsion from developing.
Fogged radiograph

Films should be held by the edges only.

Figure 2
A

(A) Emulsion peel. (B) Scratched film

813

Section XI Processing of Radiographs and Radiographic Interpretation

Figure 3

Figure 4

Static electricity artifact on a panoramic film


Crescent shaped nail mark

Static Electricity Artifact


Causes
Static electricity artifacts are formed due to the build-up
of electrons in the emulsion. They are frequently caused
by low humidity/dry weather or static producing objects
such as synthetic materials used in uniforms. Moreover,
when films are removed from the film packet or the cassette too rapidly in a dry atmosphere, a small charge of
electricity can be released producing these artifacts.
Static artifacts have two common appearances: tree like
and smudges. Tree like artifacts (Figure 3) are produced
when lms are unwrapped rapidly and appear as black
lines running across the lm and smudge static electricity
is produced by polyester clothing and appear as black
smudges on the lm.

Nail Marks or Kink Marks

Figure 5
A

Appear as a crescent shaped radiolucent finger nail marks


(Figure 4).
Cause
Excessive bending of the film.

ERRORS IN FILM PLACEMENT AND


PROJECTION TECHNIQUE
Herring Bone Effect, Tyre Mark Pattern,
Raised Diamond Markings/Knurled Effect
A lead foil is placed within every intraoral radiographic
film packet to prevent unnecessary exposure to surrounding structures from the residual X-ray beam and also protects the film from back scatter or secondary radiation that
may result in film fog.
814

(A) Radiograph showing the tyre mark or raised diamond


pattern. (B) Knurled pattern on a nut

Though the term herring bone pattern is widely used,


many of the new lm packets do not display this pattern
on the lead foil, rather the tyre mark (Figure 5A) or knurled
pattern (Figure 5B) are common.

Chapter 31 Radiographic Faults

Cause

Slanting of the Occlusal Plane

Wrong side (opposite side) of the film exposed to radiation.

A part of the radiographic image appears blank on the


radiograph (Figure 6), which confirms to the circular shape
of the position indicating device (PID).

The radiographic film should ideally be held in the mouth


using an appropriate film holder which stabilizes the
film during exposure. Slanting of the occlusal plane is
usually seen when the patient attempts to stabilize the film
with a finger. Ideally when the film is placed in the mouth
the edge of the film should be parallel to the occlusal
plane.

Causes

Cause

Improper placement of the film.

Cone Cut

Improper placement of film


Improper placement of the PID (film partially outside
the area covered by the PID).

Apical Ends of the Teeth Not Imaged


(Partial Image)
Ideally the tooth to be imaged should be positioned in the
center of the film. Also care should taken during film
placement that at least 2 mm all around the tooth of interest should be visible in the resultant radiograph.

Figure 6

Causes

Insufficient vertical angulation


Film not placed sufficiently deep into the palatal vault
(Figure 7A) or lingual vestibule
Patient opens mouth just short of the exposure
(Figure 7B).

Crown Portion of Teeth Not Imaged


(Partial Image)
Cone cut

When the film is placed against the tooth in bisecting


angle technique, it should be ensured that the edge of the

Figure 7
A

(A) Partial image due to improper film placement resulting in the apices of premolars cut-off. (B) Partial image caused due to
opening of the patients mouth during exposure

815

Section XI Processing of Radiographs and Radiographic Interpretation

Figure 8

Film placed too apically resulting in crowns not imaged

film should be placed about 2 mm beyond the cuspal tips


or incisal edges of teeth.

Figure 9

Overlapped proximal aspects of teeth due to improper


horizontal angulation

Figure 10

Cause
Improper placement of film (Figure 8).

Overlapped Image
For all practical purposes, the central beam of X-rays should
be directed perpendicular to the film and tooth (in paralleling technique) and to the imaginary bisector bisecting
the long axis of tooth and long axis of film (in bisecting
angle technique) thereby passing through the interproximal
contacts between teeth.
Causes

Improper horizontal angulation (Figure 9)


Double exposure.

If an already exposed film is re-used by mistake, then the


resultant radiograph will show two overlapped images
(Figure 10).

Overlapped images due to double exposure

Figure 11

Fore-shortened Image
The radiograph exhibits unusually short images (Figure 11).
Causes

Increased vertical angulation (bisecting angle technique)


Film not placed parallel to the long axis of the tooth
(paralleling technique).

Elongated Image (Total)


Unusually long radiographic images are seen (Figure 12).
816

Fore-shortened images

Chapter 31 Radiographic Faults

Causes

Decreased vertical angulation (bisecting angle technique)


Film not placed parallel to the long axis of the tooth
(paralleling technique).

Elongated Image (Partial)


Only part of the image appears elongated.
Cause
Excessive bending of the film (Figure 13).

placed in the mouth due to the curvature of the palate or


lingual arch such as canines, third molars or mandibular
anteriors. Receptors can be flexed but should never be
bent as that causes creasing of the emulsion, which in turn
compromises the quality of the image.
Total blurring occurs either due to the movement of
the patient or the X-ray tube head (Figure 14A). It is wise
to wait for a few seconds after adjusting the X-ray tube
head before making an exposure. Also, patients should
be instructed to remain still during the exposure.
Causes

Blurred Image
Blurred images can either be total or partial. Partial blurring occurs when the film gets bent excessively when

Movement of the film or patient during the exposure


(image totally blurred)
Excessive bending of the film (image partially blurred,
Figure 14B).

Figure 13
Figure 12

Partial elongation due to bending of film


during film placement

Elongated images

Figure 14
A

(A) Total blurring of image. (B) Partial blurring of image

817

Section XI Processing of Radiographs and Radiographic Interpretation

Figure 15

Figure 17

Partially blank radiograph

Light radiograph

Figure 16
b.

Processing errors
Developer temperature too high
Film developed for a longer time
Concentration of the developer too high
Accidental exposure to light
Improper safe lighting.

Light Radiographs (Figure 17)


Causes
a.

Exposure errors
Insufficient mA, insufficient kVp, insufficient
exposure time
Film packet placed with the wrong side facing the
X-ray source
Increased film source distance
Processing errors
Placed in the developer solution for a short duration of time
Temperature of the developer solution too low
Depleted developer solution
Diluted or contaminated developer solution
Prolonged fixation.

Dark radiograph

ERRORS IN EXPOSURE PARAMETERS AND


PROCESSING TECHNIQUE

b.

Blank Radiograph
Causes

Unexposed film (Figure 15)


Exposed film dipped into the fixer solution before it
was placed into the developer solution.

Dark Radiograph (Figure 16)


Causes
a.

Exposure errors
Excessive milliampere (mA), excessive kilovolt peak
(kVp), excessive exposure time
Insufficient filmX-ray source distance

818

Film Fog
Causes

Improper wattage of the safe light


Prolonged exposure of the film to safe light
Safe light not at a proper distance from the working
place
Light leaks from cracked safe light filters/light from
doors and ventilators.

Chapter 31 Radiographic Faults

Figure 18

Figure 19

Yellow/brown stains

Insufficient Contrast
Causes

Blisters on the film

Figure 20

Underexposed to radiation
Insufficient developing time.

Yellow or Brown Stains (Figure 18)


Causes

Film inadequately fixed


Depleted developer solution
Depleted fixer solution
Film inadequately washed in water
Contaminated processing solutions.

Partial Image

White spots

Cause
Part of the film not immersed into the developer solution.

These can be avoided by gently agitating the film


holders in the processing solutions.

Dark Spots on the Radiograph

Blisters on the Film

Causes

Causes

Air bubbles on the film while developing


Temperature difference between the developer and fixer
solutions (Figure 19)
Increased acidity of the developer solution.

White Spots (Figure 20)


Causes

Air trapped on film surface after the film is placed


in the processing solutions, air bubbles prevent the
chemicals from affecting the emulsion in that area.

Excessive bending of film, fingerprints


Film contaminated with the developer solution before
the actual processing
Film in contact with another film or tank walls during
the fixing procedure.

Light Spots on the Radiograph (Figure 21)

Film contaminated with the fixer solution before the


actual processing (remnants of fixing solution present
on the hangers for processing will cause this artifact).
Film in contact with the tank wall or another film during the developing process.
819

Section XI Processing of Radiographs and Radiographic Interpretation

Figure 21

Figure 23

Light spots on the radiograph

Yellow stain in the film due to


hyporetention

Figure 22
Causes

Inadequate washing
Remaining thiosulfate from fixer solution.

Dyschroic Fog
Fogging of the radiograph, characterized by the appearance of a pink surface when the film is viewed by transmitted light and a green surface when the film is seen by
reflected light.
Cause
Reticulation of the emulsion

Emulsion Wash Away


Radiograph with part of the emulsion lost due to a prolonged washing.

Reticulation of Emulsion
Cause
Reticulation of emulsion results when a film is subjected
to a sudden temperature change between the developer
solution and the water bath (Figure 22).

Hyporetention
It appears as a yellowish stain on the radiograph that is
processed (Figure 23).
820

Exhaustion of the acid content of the fixing solution


(incomplete fixation).

No Image/Blank Radiograph
Since none of the X-rays reach the film to form the latent
image, all the unexposed silver halide grains are removed
by the clearing agent resulting in a blank radiograph
(Figure 24).
Causes

Mechanical problems such as electrical failure, failure


to turn on the machine
Improper alignment of the PID or the film.

ARTIFACTS
An artifact is a structure or radiographic appearance that
is normally not present in the radiograph and is produced

Chapter 31 Radiographic Faults

Figure 24

Blank radiograph

by artificial means. It might be considered as foreign body


image on the radiograph.
The common artifacts are metallic objects in the path
of the X-ray beam such as jewelry (Figure 25A, B), dental
appliances (Figure 25C, D), etc. or placement of the nger
between the X-ray tube and the lm (such as using the
nger to stabilize the lm in the mouth) resulting in a
phalangioma (Figure 25E).
Prior to taking a radiograph, patients should be instructed
to remove all removable metallic objects such as jewelry,
prosthodontics appliances (removable partial and complete
dentures), spectacles, hair clips, etc. that are in the area to
be imaged. These foreign objects may superimpose over
image and obscure the ndings. Thyroid collars or lead
aprons may also be imaged on radiographs.

Figure 25
B

(A) Nose stud artifact. (B) Hair clip, nose stud and earrings artifacts. (C) Intraoral appliance.
(D) Cast partial denture. (E) Phalangioma

821

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SECTION

XII

Radiographic
Landmarks

32 Intraoral Radiographic Anatomical Landmarks


33 Extraoral Radiographic Landmarks
34 Site Selection, Evaluation and Imaging for
Dental Implants

825
837
842

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CHAPTER

Intraoral Radiographic
Anatomical Landmarks

32

Ravikiran Ongole

Landmarks Common to Both the Maxillary and

Landmarks Unique to the Maxillary Intraoral


Periapical Radiograph

Landmarks Unique to the Mandibular Intraoral


Periapical Radiograph

Mandibular Radiographs
Teeth
Periodontal Ligament Space
Alveolar Bone

During the process of interpreting a radiograph the radiologist is expected to identify normal radiographic anatomy, thereby distinguishing normal features from
pathology. These normal radiographical anatomical landmarks are unique to each area of the maxilla or mandible
and appear either radiopaque or radiolucent. They may be
used to identify a specific area of the jaw. For example, the
intermaxillary suture is unique to the radiographs of the
maxillary central incisors, mental foramen is typically
associated with the radiographs of the mandibular premolars etc. On occasions, these landmarks may exhibit some
minor variations (such as a bifid mandibular canal) or may
not be very evident on a faulty radiograph.
The landmarks discussed here are those that are seen in
intraoral periapical radiographs.

Teeth
Enamel cap, dentin, cementum, pulp.
Enamel appears almost snow white and is seen extending from the neck of the tooth, i.e. the cementoenamel
junction from one side to the other covering the tooth like
a cap (enamel cap). It is the most mineralized structure on
the radiograph (90% mineralized) and appears more radiopaque than other structures (Figure 1).
Dentin is seen as homogenous radiopacity (less radiopaque than enamel as it is 75% mineralized) and radiographically has the density of bone.

Figure 1

Intraoral radiographic landmarks


1.
2.
3.

Landmarks common to both the maxillary and mandibular radiographs


Landmarks unique to the maxillary radiograph
Landmarks unique to the mandibular radiograph.

LANDMARKS COMMON TO BOTH


THE MAXILLARY AND MANDIBULAR
RADIOGRAPHS

Teethenamel cap, dentin, cementum, pulp


Periodontal ligament space
Alveolar bonelamina dura, alveolar crestal bone,
marrow spaces and trabecular bone.

Radiograph showing enamel, dentin and pulp. Enamel is the


most radiopaque and pulp is radiolucent

825

Section XII Radiographic Landmarks

Figure 2

Dental papilla enclosed by the radiopaque bony crypt in


a root yet to be completely formed

Cementum is not appreciated radiographically because


the contrast between it and dentin is minimal. Cementum
is 50% mineralized.
Pulp appears radiolucent. The coronal pulp (pulp chamber) extends inferiorly into the roots, which is referred to
as radicular portion of pulp.
In a developing tooth, the pulp canal diverges and the
walls of the root taper to a knife edge. A small round area
of radiolucency is seen at the root tip which is surrounded
by a thin layer of hyperostotic bone which is the dental
papilla enclosed by the bony crypt (Figure 2).

Figure 3

Radiololucent periodontal ligament space confined between


the radiopaque surface of the root and the lamina dura

Figure 4

Periodontal Ligament Space


The periodontal ligament space is seen as a radiolucent
area between the root surface and the lamina dura. It is
seen all around the root extending from the alveolar crest
on one side to the other (Figure 3). The width of the periodontal ligament space varies from 0.15 to 0.36 mm; it is
generally thinner in the middle third of the root and wider
near the alveolar crest and the apical region of the root.
However due to projection errors, the periodontal ligament
space may not be discernible on some radiographs.

Alveolar Bone
Lamina dura, alveolar crestal bone, cancellous trabecular
bone.
Lamina dura
Lamina dura is a radiographic term used to describe alveolar bone proper (cortical bone), which forms the sockets of
teeth. It is also considered to be a specialized continuation of the cortical plate. Radiographically, lamina dura is
826

Radiograph showing the radiopaque lamina dura


surrounding the roots of the teeth

seen as a well-defined radiopaque line that surrounds the


roots of teeth in health (Figure 4). The appearance of lamina dura on a radiograph is because of the attenuation of
the X-ray beam as it passes through the thin layer of bone
tangentially.
Usually lamina dura is well-dened. However, on occasions, even in a healthy tooth lamina dura may appear
indistinct and diffuse because of an obliquely directed
X-ray beam. Lamina dura is generally more radiodense
and thick around the roots of teeth under heavy occlusal
forces. A double lamina dura is seen when the surfaces of
the mesial and distal root are in the path of the central
beam of the X-ray. Loss of lamina dura either partially or
generalized may indicate the presence of a local periapical
pathology or an underlying systemic disturbance.

Chapter 32 Intraoral Radiographic Anatomical Landmarks

Figure 5

Figure 6

Pointed radiopaque crest of the interdental alveolar bone in


the anterior teeth

Flat topped radiopaque interdental bone in the posterior


teeth that runs parallel to the cementoenamel junction

Figure 7
A

(A) Trabeculae are fine and dense in the maxillary anterior region. (B) Trabeculae are oriented irregularly and
bone marrow spaces are relatively

Alveolar crest
Crest of the alveolar bone is a radiopaque structure. It is
seen as a continuation of the lamina dura (cortical bone).
The junction between the alveolar crest and lamina dura is
seen as a sharp well-defined angle. Generally the crest of
the alveolar ridge is 1.5 mm apical to the cementoenamel
junction. In the anterior teeth, the alveolar crest terminates as a pointed projection and in the posterior teeth it
appears flat and parallel to the cementoenamel junction
(Figures 5 and 6).
Cancellous bone
It is present between the buccal and lingual cortical plates
in the maxilla and the mandible and accounts for most of
the bulk of the alveolar bone. The cancellous bone is made

up of a network of radiopaque trabeculae that enclose radiolucent bone marrow spaces.


In the maxillary anterior region, the trabeculae are
ne and dense and in the posterior region the bone marrow spaces are relatively larger and oriented irregularly
(Figure 7A). In the anterior region of the mandible, the
trabeculae are fewer in number and oriented horizontally.
In the posterior region of the mandible the bone marrow
spaces are larger (Figure 7B).

LANDMARKS UNIQUE TO THE MAXILLARY


INTRAORAL PERIAPICAL RADIOGRAPH

Intermaxillary suture
Anterior nasal spine
827

Section XII Radiographic Landmarks

Figure 8
A

(A) Radiograph of the mandibular anterior region showing less number of trabeculae that are oriented horizontally.
(B) Radiograph of the mandibular posterior region showing large bone marrow spaces

Nasal fossae and floor of the nasal fossae


Nasal septum
Incisive foramen
Tip of the nose shadow
Lateral fossa
Canine fossa
Nasopalatine canal
Superior foramina of the nasopalatine canal
Nasolacrimal canal
Nasolabial fold
Inverted Y line of Innes
Maxillary sinus
Zygomatic process and zygomatic bone
Maxillary tuberosity
Pterygoid plates
Hamular process
Coronoid process of the mandible.

Intermaxillary suture/median suture


Anatomical location/projection The intermaxillary suture
runs from the alveolar crest between the maxillary central
incisors to the posterior aspect of the hard palate. It is seen
when an intraoral periapical radiograph (IOPAR) is taken
for the upper central incisors.
Radiographic appearance (Figure 8A) It is seen as a linear radiolucency bounded by radiopaque lines extending
from the crest of the alveolar bone between the maxillary
central incisors to the anterior nasal spine on an IOPAR.
Occasionally it is seen as a V-shaped enlargement at the
alveolar crest.

828

Figure 9

Radiograph showing the intermaxillary suture as a linear


radiolucent line extending from the crest of the alveolar bone
between the maxillary central incisors to the anterior nasal spine

fossa. When an IOPAR is taken for the upper central incisors it is located between and roughly 2 cm beyond the
periapices of the central incisors.
Radiographic appearance (Figure 8B) It is a V-shaped
radiopaque structure.
Nasal fossae and floor of the nasal fossa

Anterior nasal spine

Anatomical location/projection The inferior portion and


floor of the nasal fossae are seen on an IOPAR beyond the
periapical regions of the maxillary anterior teeth, when an
IOPAR is taken for the upper central and lateral incisors.

Anatomical location/projection Seen on an IOPAR at


the junction of the nasal septum and the floor of the nasal

Radiographic appearance (Figure 9) The floor of the


nasal fossae appear as well-defined radiopaque lines that

Chapter 32 Intraoral Radiographic Anatomical Landmarks

Figure 10

Anterior nasal spine seen as a V-shaped radiopaque


structure at the junction of the nasal septum and
the floor of the nasal fossa

extend bilaterally on either side of the anterior nasal spine.


The radiolucent region above the floor of the nasal fossae
is the inferior portion of the nasal fossa.

Figure 11

Radiograph showing floors of the nasal fossae as well-defined


radiopaque lines extending bilaterally on either side of the
anterior nasal spine and the inferior portion of the nasal
fossae are seen as radiolucent areas above the nasal floor

Figure 12

Nasal septum
Anatomical location/projection It is seen on periapical
radiographs taken in relation to maxillary central incisors.
It is a midline structure and seen extending superiorly
from the anterior nasal spine.
Radiographic appearance (Figure 10) The nasal septum
is a sharply defined linear radiopacity, which may generally appear to be deviated from the midline. However, on
occasions the image of septal cartilage and the vomer bone
may be superimposed over the nasal septum.
Incisive foramen
Anatomical location/projection Incisive foramen is
seen in relation to the middle and apical one-third of the
roots of the maxillary central incisors. It is seen on periapical radiographs taken in relation to maxillary central
incisors.
Radiographic appearance (Figure 11) It is radiolucent and
may have various appearances ranging from a smoothly
symmetric outline to irregular or ill-defined border and usually smaller than 1 cm in diameter.
Tip of the nose
Anatomical location/projection The image of the tip
of the nose is superimposed over the apical one-third of
the roots of the maxillary central and lateral incisors. It is
usually seen in individuals with a prominent and bulbous

Radiograph depicting the nasal septum as a sharply defined


linear radiopacity extending superiorly from the anterior nasal
spine and dividing the nasal fossae

nose tip. The shadow of the tip of the nose is seen when a
radiograph is taken for the maxillary central incisors.
Radiographic appearance (Figure 12) It appears as a
homogenous cup-shaped radiopacity with a definite outline.
Lateral fossa/incisive fossa
Anatomical location/projection It is seen in relation to
the apical region of the maxillary lateral incisor. Radiographs
of the lateral incisors will reveal this anatomic landmark.
Radiographic appearance (Figure 13) It appears as a
diffuse radiolucency.
829

Section XII Radiographic Landmarks

Figure 13

Incisive foramen seen as a well-defined radiolucent


area in relation to the middle and apical one-third of the
roots of the maxillary central incisors

Figure 14

Figure 15

Lateral fossa seen as diffuse radioluceny in relation to the


apical region of the maxillary lateral incisor

of maxillary central incisors, when taken with an increased


vertical angulation.
Radiographic appearance (Figure 15) They appear as
well-defined oval radiolucencies on either side of the nasal
septum (superimposed close to the floor of the nasal fossa).
Nasolacrimal canal
Anatomical location/projection Rarely visualized on a
periapical radiograph. When an increased vertical angulation is used, the nasolacrimal canal may be seen in the
periapical region of the canine. In maxillary occlusal
radiographs, they are seen in relation to the apices of the
molars.

The tip of nose shadow is seen as a homogenous cup shaped


radiopacity superimposed over the apical one-third of the
roots of the maxillary central and lateral incisors

Nasopalatine canal
Anatomical location/projection The nasopalatine canal
is rarely seen on periapical radiographs. However, they may
be evident on radiographs taken in relation to the maxillary central incisors.
Radiographic appearance (Figure 14) The lateral walls
of the nasopalatine canal appear radiopaque and extend
from the incisive foramen to the floor of the nasal fossa.

Radiographic appearance (Figure 16) Well-defined ovoid/


round radiolucencies.
Nasolabial fold
Anatomical location/projection The nasolabial fold is seen
extending across the middle and apical one-third of the
roots of the canine and first premolar. It is seen on IOPAR
taken on the maxillary canine.
Radiographic appearance (Figure 17) The nasolabial
fold appears as a linear radiopaque shadow. Occasionally,
a zone of increased radiopacity is seen above this shadow
which is caused by the superimposition of the buccal
mucosa and alveolus.
Inverted Y line of Innes

Superior foramina of the nasopalatine canal


Anatomical location/projection Generally seen on maxillary occlusal radiographs or on a periapical radiograph
830

Anatomical location/projection The inverted Y line or Y


line of Innes is seen when radiographs are taken in the
maxillary canine region.

Chapter 32 Intraoral Radiographic Anatomical Landmarks

Figure 16

Radiograph showing the nasaopalatine canal at the


periapical region of the maxillary lateral incisor

Figure 17

Radiograph reveals superior foramina of the nasopalatine


canal as well-defined oval radiolucencies, superimposed
close to the floor of the nasal fossa

Figure 18

Maxillary occlusal radiograph showing nasolacrimal


canals as well-defined ovoid radiolucencies in relation to
the apices of the molars

Figure 19

IOPAR of the maxillary premolar region showing the


nasolabial fold as a linear radiopaque shadow extending
across the middle and apical one third of the roots of the
canine and first premolar

Maxillary sinus
Radiographic appearance In relation to the periapex of
the canine, the floor of the maxillary sinus and the floor of
the nasal fossa cross one another forming an inverted Y,
which is referred to as Y line of Innes (Figure 18).
Canine fossa
Anatomical location/projection Seen at the periapical
regions of the maxillary canine (Figure 19).
Radiographic appearance Seen as a diffuse radiolucency.

Anatomical location/projection The floor and a minimal


portion of the inferior aspect of the maxillary sinus are seen
on periapical radiographs taken in relation to the maxillary
premolar and molar teeth.
Radiographic appearance The maxillary sinus appears as
a uniformly radiolucent structure bounded by well-defined
thin radiopaque line.
The roots of the maxillary molars appear to project
into the maxillary antrum as a result of the angulation of
the X-ray beam (Figure 20).
831

Section XII Radiographic Landmarks

Figure 20

Radiograph showing the inverted Y line of Innes in relation to


the maxillary canine-first premolar region

Figure 22

Radiograph of the maxillary first molar reveals the scalloped


well-defined radiopaque floor of the maxillary sinus and the
radiolucent maxillary sinus

Figure 21
the maxillary sinus in relation to the apices of the molar
teeth. It is seen as a U-shaped or V-shaped radiopaque line.
The zygomatic bone is seen as a homogenous radiopacity
over the apices of the second and third molars, generally
obscuring the periapical region.
Pterygoid plates and hamular process
Anatomical location/projection The pterygoid plates and
hamular process are seen distal to the maxillary tuberosity.
They are generally seen on intraoral periapical radiographs
taken in relation to the third molars. However, in most
cases they may not be evident.

IOPAR showing the canine fossa as a diffuse radiolucency at


the periapical region of the maxillary canine

In edentulous spaces, the oor of the sinus dips down


and lies close to the alveolar ridge (pneumatization of
the sinus). Occasionally thin radiolucent lines are seen to
traverse the sinus walls. These radiolucent tracks represent
the neural and vascular supply of the sinus.
Zygomatic process and zygomatic bone
Anatomical location/projection The zygomatic bone and
the zygomatic process of the maxilla are seen in the periapical regions of the second and third molars. Zygomatic
bone is usually seen when an excessive vertical angulation
is used.
Radiographic appearance (Figure 21) Zygomatic process of the maxilla is seen above the level of the floor of
832

Radiographic appearance (Figure 22) The pterygoid


plates are seen as a radiopaque shadow distal to the maxillary tuberosity and the hamular process is evident as a
single radiopaque linear structure extending from the
inferior aspect of the medial pterygoid plate.
Coronoid process
Anatomical location/projection The coronoid process
of the mandible is usually seen superimposed over the
periapical regions of the second and third maxillary molars
and sometimes over the maxillary tuberosity region. The
position of the image of the coronoid process on the radiograph depends on the extent to which the mouth was
opened during the radiographic projection. It is seen
when an IOPAR is taken for the upper second and third
molars.
Radiographic appearance (Figure 23) The coronoid
process appears as a homogenous triangular shaped radiopacity with the tip facing the occlusal aspects of the
teeth.

Chapter 32 Intraoral Radiographic Anatomical Landmarks

Figure 23

IOPAR of the maxillary molars reveals a V-shaped radiopaque


structure seen above the level of the floor of the maxillary
sinus projecting downward toward the apices of molar teeth

Figure 25

IOPAR of the maxillary third molar showing the mandibular


coronoid process as a homogenous triangular shaped
radiopacity with the tip facing the occlusal aspects of
the upper teeth

Figure 24
Symphysis
Anatomical location/projection Seen only in the first year
of life. It is seen in the region corresponding to the midline
of the mandible. It is seen on the radiographs of the deciduous mandibular central incisors.
Radiographic appearance Symphysis appears as a linear
radiolucency between the deciduous mandibular central
incisors and extending inferiorly to involve the lower border of the mandible (Figure 24).
Genial tubercles (mental spine) and lingual
foramen
Radiograph showing the pterygoid plates as a radiopaque
shadow distal to the maxillary tuberosity and the hamular
process as a radiopaque linear structure extending from the
inferior aspect of the medial pterygoid plate

LANDMARKS UNIQUE TO THE MANDIBULAR


INTRAORAL PERIAPICAL RADIOGRAPH

Symphysis
Genial tubercles
Mental ridge
Mental fossa
Mental foramen
Mandibular canal
Mylohyoid ridge
Submandibular gland fossa
External oblique ridge
Inferior border of mandible.

Anatomical location/projection They are generally evident on the periapical radiographs of mandibular central
incisors and mandibular occlusal radiographs.
Radiographic appearance Genial tubercles are seen on
mandibular occlusal radiographs as discrete radiopaque
structures measuring about 4 mm in diameter. They are
present beneath the apices of the mandibular central incisors in the midline.
In periapical radiographs, they are seen as a well-dened
radiopaque mass enclosing a circular radiolucent area which
is referred to as the lingual foramen (incisal branches of
mental nerve exit out of the lingual foramen to innervate
the incisor teeth) (Figure 25).
Mental ridge
Anatomical location/projection Mental ridge is seen
superimposed over the apical one-third of the roots of the
mandibular central and lateral incisors. It appears to extend
833

Section XII Radiographic Landmarks

Figure 26

IOPAR showing well-defined radiopaque mass


(genial tubercles) enclosing a circular radiolucent
lingual foramen

from the premolar region up to the central incisors. These


are seen in IOPAR taken for the mandibular incisors.

Figure 27

Radiograph of the mandibular incisor region showing two


well-defined radiopaque lines extending bilaterally from the
premolar region toward the midline

Figure 28

Radiographic appearance Seen as two well-defined radiopaque lines extending bilaterally from the premolar region
toward the midline.
Mental fossa
Anatomical location/projection The mental fossa is an
anatomical depression present on the labial aspect of the
mandible extending bilaterally from the midline to the lateral incisor and occasionally up to the canine.
Radiographic appearance It is seen as a diffuse radiolucent area, which is superimposed over the roots of the
mandibular anterior teeth. The mental fossa is bounded
superiorly by the alveolar ridge and inferiorly by the mental ridge (Figure 26).

Mental fossa seen as a diffuse radiolucency superimposed


over the roots of the mandibular anterior teeth

Mental foramen
Anatomical location/projection The mental foramen is
usually seen at the periapical regions of mandibular premolars. It is usually present equidistant from the both the
lower border of the mandible and the alveolar ridge.
Radiographic appearance It appears radiolucent and has a
round, ovoid or an elongated shape. It may or may not have
a well-defined radiopaque corticated border (Figure 27).
Mandibular canal
Anatomical location/projection The mandibular canal is
usually seen on periapical projection of mandibular molars.
The apices of the molar teeth may some times lie close to
the canal.
834

Radiographic appearance (Figure 28) It is seen as linear


radiolucent canal running along the apices of the molar
teeth. The course of the canal is generally lined by thin
radiopaque lamellae of bone.
Mylohyoid ridge or internal oblique ridge
Anatomical location/projection The mylohyoid ridge is
seen extending from the third molar region to the premolars usually along the apices of these teeth. Usually seen
when radiographs are taken for the mandibular molars.
Radiographic appearance (Figure 29) It is generally seen
as a well-demarcated radiopaque line below the level of

Chapter 32 Intraoral Radiographic Anatomical Landmarks

Figure 29

IOPAR of the mandibular premolar region showing a


well-defined radiolucent area at the periapical region of the
2nd premolar

Figure 31

Radiograph showing the mylohyoid ridge as a


well-demarcated radiopaque line running along the
apical thirds of the mandibular molar teeth

Figure 30
Figure 32

Radiograph of the mandibular molar region showing the


mandibular canal as a linear radiolucent canal running along
the apices of the molar teeth

the external oblique ridge that runs along the apical thirds
of these teeth.
External oblique ridge
Anatomical location/projection It is seen on IOPARs of
mandibular posterior teeth. The external oblique ridge is
seen above and parallel to the mylohyoid ridge.
Radiographic appearance (Figure 30) The external
oblique ridge appears as a linear radiopacity which merges
with the alveolar bone as it traverses toward the premolar
region and superiorly it continues as the ascending ramus
of the mandible.

IOPAR showing the external oblique ridge as a linear


radiopacity which continues as the ascending ramus
superiorly

Submandibular gland fossa


Anatomical location/projection The submandibular gland
fossa is an anatomical depression that houses the submandibular gland. It is seen in the periapical region of
molar teeth, below the level of the mylohyoid ridge. It is
extends up to the premolar region anteriorly and to the
ascending ramus posteriorly. It is seen when a radiograph
is taken for the lower molar teeth especially second and
third molars.
Radiographic appearance (Figure 32) It appears as a
diffuse radiolucency.
835

Section XII Radiographic Landmarks

Figure 33

Inferior border of the mandible


Anatomical location/projection May be seen in any of
the projections of the mandibular teeth. It is usually seen
when the film is placed deep within the lingual sulcus and
the vertical angulation is increased.
Radiographic appearance (Figure 33) The inferior border of the mandible is rarely seen on intraoral periapical
radiographs. It is evident as a radiopaque strip of uniform
thickness (cortical portion) of bone along the inferior edge
of the mandible.
Radiopaque anatomical landmarks

IOPAR of the mandibular third molar region showing the


submandibular gland fossa as a diffuse radiolucency beneath
the level of the mylohyoid ridge and mandibular canal

Figure 34

Maxilla

Mandible

Anterior nasal spine


Floor of nasal fossa
Tip of nose, nasolabial fold
Floor of maxillary sinus
Zygomatic process of maxilla
Zygomatic bone
Maxillary tuberosity
Pterygoid plates
Hamular process
Coronoid process

Genial tubercles
Mental ridge
Mylohyoid ridge
External oblique ridge
Inferior border of the mandible

Radiolucent anatomical landmarks

IOPAR showing the inferior border of the mandible as a


well-defined linear radiopaque strip of uniform thickness of
bone along the inferior edge of the mandible

836

Maxilla

Mandible

Intermaxillary suture
Nasal fossa
Incisive foramen
Superior foramina of nasopalatine
canal
Lateral fossa/incisive fossa
Canine fossa
Nasolacrimal canal
Maxillary sinus

Symphysis
Lingual foramen
Mental foramen
Mandibular canal
Submandibular gland fossa

CHAPTER

Extraoral Radiographic
Landmarks

33

Praveen BN

Figure 1

23

20
22

12

21

10

24

16
8

17
1
19

11
13
18

15

6
7
4

14

1. External auditory meatus


2. Hyoid bone
3. Dorsum of tongue
4. Hard palate
5. Anterior nasal spine
6. Soft palate
7. Floor of orbit
8. Frontal process of zygoma
9. Nasal bone
10. Nasion
11. Inferior rim of orbit
12. Ethmoid air cells
13. Posterior wall of maxillary sinus
14. Posterior arch of atlas
15. Occipital condyle
16. Mastoid air cells
17. Condyle
18. Articular eminence
19. Base of skull
20. Sella turcica
21. Sphenoid sinus
22. Posterior clinoid process
23. Roof of orbit
24. Clivus

3
2

Lateral cephalogram

837

Section XII Radiographic Landmarks

Figure 2
1
2
8
9

4
10
5
6

11
7
12
13

14
1. Supraorbital canal
2. Nasal septum
3. Infraorbital margin
4. Ala of nose
5. Zygomatic bone
6. Maxillary sinus
7. Lateral wall of maxillary sinus

8. Frontal sinus
9. Zygomaticofrontal suture
10. Innominate line
11. Inferior orbital fissure
12. Sphenoid sinus
13. Foramen rotundum
14. Mid-palatal suture

Paranasal sinus radiograph

Figure 3
1

2
3
4
3
5
7

14

15
8
16

9
10

13

1. Nasal septum
2. Mid-palatal suture
3. Sphenoid sinuses
4. Coronoid process of mandible
5. Ramus
6. Condyle of mandible
7. Clivus
8. Posterior pharyngeal
9. Anterior arch of atlas
10. Dens
11. Occipital condyle
12. Ossicles
13. External auditory meatus
14. Foramen spinosum
15. Foramen ovale
16. Hyoid bone

11
12

Submentovertex (base of skull) view

838

Chapter 33 Extraoral Radiographic Landmarks

Figure 4
2
2

1. Lateral pole of condyle


2. Superior surface of condyle
3. Medial pole of condyle
4. Coronoid process

Open mouth

Closed mouth

Temporomandibular joint (posteroanterior) viewclosed and open mouth position

Figure 5

19
18

17

2
3

16

5
15

6
8

9
14
11
13

1. Superior rim of orbit


2. Lesser wing of sphenoid
3. Innominate line
4. Mastoid process
5. Foramen rotundum
6. Pterygoid process
7. Base of skull
8. Maxillary antrum
9. Zygomatic process of maxilla
10. Inferior turbinate
11. Intermaxillary suture
12. Nasal septum
13. Articulation between atlas and axis
14. Coronoid process
15. Infraorbital canal
16. Superior border of petrous
17. Superior orbital fissure
18. Ethmoid air cells
19. Frontal sinus

10

12
7

Posteroanterior view of the skull

839

Section XII Radiographic Landmarks

Figure 6

1
1. Condyle head
2. Articular fossa
3. Articular eminence

2
3

Open mouth

Closed mouth

Temporomandibular joint (lateral) viewclosed and open mouth position

Figure 7

13

2
3

12
4

5
11

10

7
6

9
8

Reverse Townes view

840

1. Foramen magnum
2. Posterior arch of atlas
3. Dorsum sellae
4. Frontal process of zygoma
5. Posterior wall of maxillary sinus
6. Inferior orbital fissure
7. Zygoma
8. Inferior rim of orbit
9. Nasal septum
10. Coronoid process of mandible
11. Condyle of mandible
12. Internal auditory meatus
13. Articular eminence

Chapter 33 Extraoral Radiographic Landmarks

Figure 8
15

16
13

10

18
12

14

5
3

11

17

7
4

19

8
20

1. Mandibular canal
2. Inferior border of zygomatic arch
3. Posterior wall of maxillary sinus
4. Floor of maxillary sinus
5. Anterior wall of maxillary sinus
6. Inferior orbital canal
7. Nasal septum

8. Mental foramen
9. Soft tissue of inferior turbinate
10. Pterygomaxillary fissure
11. Coronoid process
12. Condyle
13. Inferior orbital rim
14. External auditory meatus

15. Condylar fossa


16. Articular eminence
17. Real image of hard palate
18. Common meatus of nose
19. Ghost image of inferior edge
of contralateral ramus
20. Body of hyoid

Orthopantomogram

Figure 9
27
28
22
25
21

22

21
21

21

21

21
24
26

29

23
30

21. Outline of base and dorsum of tongue


22. Air-space above the tongue
23. Hypoglossal air space
24. Oropharyngeal air space

25. Nasopharyngeal air space


26. External oblique ridge
27. Ghost image of left palate
28. Sigmoid notch

29. Angle of mandible


30. Inferior border of mandible

Orthopantomogram

841

CHAPTER

34

Site Selection, Evaluation


and Imaging for Dental
Implants
Muralidhar Mupparapu

Historical Perspectives
Indications for Dental Implants
Patient Management with Dental Implants

Dental implants are prosthetic devices implanted into the


oral tissues either beneath the mucoperiosteal layer or in
the bone to provide retention and support for the fixed
or removable prosthesis. Although fabrication of dental
implants dates back to many decades, the advent of dental
root form implants (DRFIs) have paved way for universal
acceptance of implants as replacement for lost teeth. The
dental implant restorations not only enhance the esthetics
for the patients, but also improve the oral function for
speech and mastication. Hence, the dental root form implants
(Figure 1) gained immense popularity among the dental
practitioners as well as the patients in the dental profession. Nothing is more important in the dental implantology
than the precise evaluation and placement of the implant
structures in the maxilla and mandible. In order to do this
effectively, one needs to precisely understand the surgical
Figure 1

Upper lip

Implant
fixture
Crown
prosthesis

Diagrammatic representation of the typical implant fixture and


the crown properly placed within the maxillary alveolus

842

Identification of the Implant Site


Selection of the Implant Site
Imaging of the Implant Site

anatomy of the maxillofacial region and the anatomical


variations that might be encountered. Secondly, they need
to grasp the biomechanics of the dental implant material.
Fortunately, now, the science behind the dental implantology is strong, backed with research and evidence-based
trials. The fruits of the decades of clinical trials using various dental implant materials along with numerous loading
protocols have refined the predictability of dental implants
for the maxillofacial region.

Historical Perspectives
The treatment options that are available for replacement
of single or multiple teeth in the oral cavity are removable
partial denture (RPD), fixed partial denture (FPD) and
implant prosthesis (IP). The RPDs which were not helpful
in the maintenance of existing bone, compromise the
esthetic result, need more bulk for cross-arch stabilization,
easily trap food debris and plaque, and interfere with the
speech and function. Similarly, the FPDs especially promote caries of the abutment teeth but if not well fabricated, lead to plaque retention in the pontic increasing
periodontal risk, involve damage to adjacent teeth, fracturing of the porcelain, and have esthetic concerns for the
anterior regions. The FPDs are contraindicated when there
is poor abutment support, inadequate hard and soft tissues
in the esthetic regions and in young patients with large
pulp horns. The dental implants would be an ideal alternative for replacement of teeth.
Historically, there were three distinct forms of dental
implants, namely, the subperiosteal (epiosteal), the transosseous (staple bone or transmandibular) and the endosteal
(blade or plate, ramusframe and root form) types. Dental
practitioners should be familiar with the radiographic
appearances of older dental implant systems although many

Chapter 34 Site Selection, Evaluation and Imaging for Dental Implants

CAD/CAM fabrication of the framework, eliminating the


need for impressions via surgery. Subperiosteal implants
are no longer preferred after the success of endosteal
implants although one can occasionally see them in clinical practice with varying degrees of presentation (Beddis
et al, 2012).

Figure 2
Posts will remain
outside the gingiva
as anchors for the
new prosthesis

Transosseous implants

Subperiosteal metal
framework

The transosseous implants, also known as staple bone


implants or transmandibular implants are restricted to the
anterior region of the mandible. They penetrate both cortical plates and pass through the entire thickness of the bone.

Mandible
Gingiva covering the
implant framework

Diagrammatic representation of subperiosteal implant


framework and the posts in the edentulous mandible

of them are rarely used after the advent of the dental root
form implants.
Subperiosteal implants
Subperiosteal implants are metallic meshes that are custombuilt to fit over the alveolar processes and are located
underneath the periosteum (Mupparapu and Beideman,
2000). Direct bone impressions via surgery would lead
to the fabrication of mesh in a laboratory that fits under
the mucoperiosteum (Figure 2). The framework normally
rests on the mandible with no penetration into the bone.
Two surgeries were involved in the fabrication of these
implants. First surgery is for the impression and the second surgery is for the placement of the mesh. The first
subperiosteal dental implant in the world was placed by
George Dahl in Sweden. The first American subperiosteal
implants were developed in 1947. Gershkoff and Goldberg
placed the first subperiosteal complete denture implant
manufactured with Vitallium (Moore and Hansen, 2004).
Dr Leonard Linkow of New York made significant changes
to the original design by incorporating fenestrations into
the buccal peripheral struts which made it possible for the
mucoperiosteum to reattach the bone in between these
fenestrations. He also holds 35 patents on various designs
of subperiosteal and oral implants. Multiple metallic posts
extend from the mesh into the oral cavity crossing the
mucoperiosteal barrier to support the prosthesis. Mandibular subperiosteal implants have been shown to be successful in many clinical studies and some of the implants
reviewed were present in the mouth for more than 10 years.
The success rate for these implants varied in many studies
with higher success rate for 10-year periods and lower
success rates for longer periods (Moore and Hansen, 2004).
Computed tomography (CT) scans were also used to allow

Endosteal implants
There are three forms of endosteal implants: the root form,
the ramus frame and the plate or blade form implants.
Blade implants are rectangular in shape similar to a razor
blade. These are used over horizontal column of bone. One
or more posts usually extend into the oral cavity to permit
fixation of the prosthesis. The only blade implants that are
seen clinically at present are the previously placed implants
that either failed or fractured and the patient reported for
treatment. One such example where the blade implant failure led to the osteomyelitis in the mandible is shown in
Figure 3. The root form implants can be either cylindertype, screw root type or a combination of both. These
implants use the vertical column of bone unlike the blade
implants.
Types of dental implants available
(according to the material used)
The following are the commonly used implants according
to the type of material used for fabrication:
1. Metallic implants
a. Titanium
b. Cobaltchromiummolybdenum alloy with titanium,
aluminum, vanadium
c. Cobaltchromiummolybdenum
d. Stainless steel
e. Zirconium
f. Tantalum
g. Gold
h. Platinum
2. Non-metallic implants
a. Ceramics
b. Carbon.
The most commonly used implants are:
1. Commercially pure (CP) titanium This is light weight,
biocompatible and corrosion resistant. The material is many
times stronger than compact bone and the modulus of
elasticity is five times greater than that of compact bone.
This equals the mechanical stress transfer of compact bone.
843

Section XII Radiographic Landmarks

Figure 3

Failing blade implants in the mandibular molar region as seen from the panoramic reformatted image from a
Denta-Scan CT study. On the right is a picture of a premolar blade implant manufactured by Oraltronics, Russia

Figure 4

Facial profile changes after loss of teeth including the collapse of the perioral soft tissues and loss of vertical dimension

2. Titaniumaluminumvanadium alloy (Ti6Al4V)


This is stronger and used for small diameter implants.

Indications for Dental Implants


Implants are indicated in many situations in patients with
partial or full edentulism. They are indicated in patients
with a history of difficulty in wearing a removable partial
denture or have a long span fixed partial denture. They are
also indicated in patients with severe bony changes secondary to prolonged use of complete or partial dentures.
The implants are ideal for patients with poor oral muscular
coordination and in those with parafunctional habits compromising the stability of the prosthesis. Patients with
hyperactive gag reflex, unfavorable number and location
of abutments, single tooth loss and those who refuse to
844

wear dentures for psychological reasons are all candidates


for dental implants. In patients wearing complete dentures, bite force is decreased from about 200 to 50 psi
with decreased masticatory efficiency. Food selection is
limited and healthy food intake is decreased among these
patients. Hence the dental implants will greatly help them
in getting back the normal occlusal function added with
the enhanced esthetics. Finally, in patients with tooth
agenesis (congenitally missing teeth), the implants are
ideally suited.
Patients who lost the entire dentition will show signicant changes to the facial prole after loss of teeth chiey
due to the alveolar resorption and the loss of vertical dimension (Figure 4). Restoration of function and esthetics would
then become the goal for any prosthesis without compromising on the masticatory efciency.

Chapter 34 Site Selection, Evaluation and Imaging for Dental Implants

Patient Management with Dental Implants


There are three aspects of patient management that the
practitioner should remember when planning treatment
for dental implants:
1. Identification of the appropriate site for implant placement via preimplant assessment This requires patient
assessment via thorough medical and dental history, laboratory findings and radiographic evaluation of the existing teeth and edentulous ridges.
2. Selection of appropriate dental implant system (DIS) and
fabrication of necessary guides for surgery This involves
selection of appropriate implant material and imaging software to display the cone beam computed tomographic volumes and a good communication with the laboratory.
3. Planning and designing appropriate abutment This
could be easily accomplished via virtual implant selection
and placement. The identification of appropriate length and
width of the implant fixture would be determined at this
stage taking into consideration, the proximity of the nerve
canal and/or sinus cavity.

Identification of the Implant Site


Selection of the patient
Patient selection is a key factor in going forward with the
identification of future implant site(s). This essentially boils
down to the assessment of the medical and dental status of
the patient. If the patients medical and dental history precludes a dental implant placement and a good prognosis,
then that should be communicated to the patient ahead of
time. Systemic health of the patient plays a vital role in the
overall selection of the patient. Any medical condition that
delays or alters wound healing should be identified first.
A good example for this is diabetes mellitus. Uncontrolled
type 1/type 2 diabetes or untreated diabetes usually results
in delayed wound healing. Diabetes (type 1 and type 2
combined) affects approximately 25.8 million people in the
Unites States alone. There are at least 79 million people
who are considered prediabetics (National Diabetes Fact
Sheet, 2011, Centers for Disease Control and Prevention
[http://www.cdc.gov/diabetes]). Worldwide, as per 2011
World Health Organization estimates, around 346 million
people have diabetes (http://www.who.int/mediacentre/
factsheets/fs312/en/index.html).
Wound healing occurs as a cellular response to injury
and involves activation of keratinocytes, broblasts, endothelial cells, macrophages and platelets. Many growth factors and cytokines released by these cell types are essential
for coordination and maintenance of healing process
(Brem and Tomic-Canic, 2007). Deciency of any of the
above factors would lead to improper and sometimes nonhealing of the extraction site as well as the implanted site.

Since the success of implant therapy is tied to the osseointegration, this is a crucial step in the overall implant therapy. Several medical conditions that would jeopardize the
success of an implant should be considered during the
screening process. The list (Hwang and Wang, 2006) includes
the following absolute contraindications and relative contraindications:
Absolute contraindications
1. Recent myocardial infarction or cerebrovascular accident
Due to the increased risk of complications following a
myocardial infarction (MI) or a cerebrovascular accident
(CVA), the dental practitioner must wait until preliminary
stabilization. It is recommended that elective dental care is
deferred for at least 6 months status post MI or CVA and
the patient is medically stable.
2. Valvular prosthesis placement It is essential that the
dental practitioner defers placement of implants in these
patients for 6 months to 1 year after the cardiac surgery.
Anticoagulants would be used depending on whether the
valve is bioprosthetic or mechanical in which case, caution
should be exercised.
3. Prior history of bleeding Since uncontrolled bleeding
stems from a multitude of systemic conditions, patients who
are on oral anticoagulant therapy should be carefully evaluated and the bleeding time, international normalized ratio
(INR) must be assessed. An INR of 2.2 or lower is recommended for surgical procedures by Fazio and Fang (2003).
4. Immunosuppression If the WBC count falls below
1,5003,000 cells/mm3 the patient is not considered a good
candidate to receive implants as the ability to combat infections, repair or regeneration would be compromised. With
a near normal WBC count and a grossly abnormal neutrophil
count (less than 2,000 cells/mm3), the normal range being
3,5007,000 cells/mm3, a medical consultation is necessary
before planning dental implants. It is generally considered
that when the patients CD4 T-cell count measures below
500 cells/mm3, he/she is considered immunosuppressed and
appropriate care should be exercised.
5. Active radiation and/or chemotherapy Both ionizing
radiation and chemotherapy disrupt hematopoiesis, and
implantation should be deferred in such situations as wound
healing is delayed. In addition, if the salivary glands are
involved in the line of fire, there would be substantial
xerostomia which in turn, would contribute to poor oral
hygiene and increase in dental caries secondary to xerostomia. Studies have shown that in about 335% of patients,
spontaneous or traumatic osteoradionecrosis would be a
complication (Marx and Johnson, 1987). When the patient
is on cytotoxic anticancer drugs, granulocytopenia followed by thrombocytopenia are expected which might
lead to infection, hemorrhage, mucositis and pain. Implant
845

Section XII Radiographic Landmarks

therapy should be deferred until after the patient is completely off the cytotoxic medication.
6. Psychiatric disorders If a patient is unable to comprehend and anticipate dental treatment logically, then it is
advised not to place implants. Several conditions including psychotic disorders like schizophrenia, severe character
associated conditions like hysteria, borderline personality
disorders, dysmorphophobia, cerebral lesions, presenile
dementia as well as alcohol and drug abuse. Although
there are no biological reasons for patients with most of
the above disorders to lose implants, there are reported
cases of removal of osseointegrated fixtures based on psychiatric factors (Hwang and Wang, 2006).
7. Intravenous bisphosphonate treatment There is enough
evidence to date linking bisphosphonate use to either spontaneous or traumatic induction of osteonecrosis of the jaw.
Bisphosphonates inhibit bone resorption and hence are
used for treatment of osteoporosis, hypercalcemia of malignancy and Pagets disease. Bisphosphonates may inhibit
osteoclast precursors and cholesterol synthesis as well as
promote osteoclast apoptosis and osteoblast proliferation.
In a large study, among all the different forms of bisphosphonates that were used in cancer patients, pamidronate
(Aredia, Novartis, Basel, Switzerland) and zoledronic acid
(Zometa, Novartis, Basel, Switzerland) stood out as the
agents that were associated with most cases of osteonecrosis, majority of them being mandibular necrosis with recent
dentoalveolar procedures performed on them (Ruggiero et al,
2004). So far, there are no published studies on the risk
stratification of osteonecrosis of the jaws after drug discontinuation. Hence, the risk is omnipresent once the bisphosphonates have been used and even if they are discontinued.
Professional organizations like the American Dental Association, the American Association of Oral and Maxillofacial
Surgeons and the American Academy of Oral Medicine have
issued guidelines regarding the identification and management of bisphosphonate-related osteonecrosis of the jaw.
8. Acute infection The presence of acute infection is an
absolute contraindication for oral implant therapy. The
soft tissues and bone should be completely devoid of any
infection before the implant therapy can be instituted.
9. Morphology of the edentulous bone crest and vestibule
Intraoral inspection and palpation may reveal information
about the type of ridge, a suspected thin ridge or a flabby
ridge, shape of the ridge, muscle insertions, mandibular tori
and the floor of the mouth. A radiographic evaluation of
the crestal bone is mandatory before treatment planning.
A knife-edged ridge often needs correction before inserting implants. A bony plateau must be created that is wide
enough to insert implants with an adequate width. This
could mean reducing the existing crest by a few millimeters.
The depth of vestibule is an important factor to consider.
Bone resorption often leads to shallow vestibule. If that is
846

the case, an implant-supported overdenture is more likely


to provide greater lip support in such cases, giving more
acceptable esthetic result (Wismeijer et al, 2010).
Relative contraindications
There are situations where the condition lends to a milder,
often local complications or loss of implants in a patient
(Hwang and Wang, 2007). The following list, although
comprehensive may not include every single situation and
or condition that might predispose local loss of bone and
eventual failure of the implant:
1. Age of the patient Bone growth in the maxilla and
mandible is dynamic in growing children and adolescents.
The implants simulate an ankylosed tooth in the growing
alveolus and might not be able to catch up with the vertical growth of the alveolar process that happens naturally
with the other permanent teeth. This might lead to infraocclusion or displacement with time with respect to the
natural dentition. It is considered prudent to wait until the
completion of skeletal maturation before placement of
implants in the younger patients to avoid imperfect fixture
positioning and/or stunt osseous expansion. The elderly
tend to have greater prevalence of local conditions like the
ridge resorption, nerve proximity, xerostomia as well as
systemic conditions like osteoporosis, hypertension and diabetes. Although old age does not seem to be a major contributing factor in the long-term survival of the implants,
the associated factors might lead to certain complications
(Hwang and Wang, 2007).
2. Osteoporosis Osteoporosis is a condition that is prevalent in the fourth or fifth decade in both men and women
in which, there is universal reduction in bone mass with no
other abnormality. The resorption overtakes deposition of
bone. Although it is generally thought to be a risk factor for
failure of osseointegration, the clinical studies that were
done revealed little effect of this condition on implant success, at least in the lower jaw (Minsk and Polson, 1998).
3. Smoking Studies have shown that persistent tobacco
use following implantation lessened the ability of bone or
other periodontal tissues to adapt over time and contributing to the failure of treatment after fixture uncovering
(Lambert et al, 2000). The authors suggested smoking cessation for all future implant receiving patients. More recent
studies that have examined the effect of smoking in patients
with treated periodontal disease show mixed results and it
is suggested that since smoking appears to reduce implant
success especially in the maxilla, smoking cessation before
implant rehabilitation might lead to better results (Hwang
and Wang, 2007).
4. Diabetes Patients with both type 1 (previously called the
insulin-dependent diabetes mellitus or the juvenile onset
diabetes) and the type 2 (previously called the non-insulin
dependent diabetes mellitus) diabetes mellitus are at risk

Chapter 34 Site Selection, Evaluation and Imaging for Dental Implants

for implant failure due to the pathologic changes that are


brought about by the disease in the cardiovascular, renal
and circulatory systems which in turn lead to changes at
local level. The American Diabetic Association recommends
a hemoglobin A1C (HbA1C) level less than 7.0% in patients
with type 2 diabetes. With appropriate glycemic control,
diabetes does not compromise implant success (Hwang
et al, 2007).
5. Cardiovascular disease All forms of cardiovascular
diseases including the hypertension, coronary artery disease, vascular stenosis, atherosclerosis, congestive heart
failure may impair the healing process after implant placement. Although cardiovascular disease leads to physiological alterations, generally, it does not seem to affect the
clinical implant success (Hwang et al, 2007).
6. HIV disease Acquired immunodeficiency syndrome
remains one of the leading causes of death in the world
even though the mortality rate from HIV infection has
substantially declined in the past decade due to advent of
highly active antiretroviral therapies (HAART). This has
become a chronic, manageable disease. In patients with
CD4 count of more than 200 cells/mm3, successful osseointegration and function after 4 years was noticed and in
patients with CD4 count less than 200 cells/mm3, a regimen
of the antibiotic amoxicillin was suggested post-operatively
for a successful outcome (Hwang et al, 2007).
7. Hypothyroidism Thyroid disorders generally affect
the bone metabolism. Both T4 and T3 regulate several
homeostatic processes. Wound healing in both soft tissue
and bone is controlled by these hormones. Hypothyroidism
decreases bone cell recruitment, maturation and activity,
possibly by reducing the circulatory levels of insulin-like
growth factor-1; this ultimately suppresses the bone formation as well as resorption. Implant sites healing and osseointegration would be potentially delayed. Even though in
theory, the hypothyroid state might lead to potential failure in implant osseointegration, the studies that were done
in this area did not present data that corroborate the theory. Hence, it can be concluded that in a well-controlled
patient, hypothyroidism has no effect on the survival of
the dental implants.
8. Past history of periodontal disease The risks related to
implant loss in patients who lost their teeth to periodontal
disease are much higher than the patients who lost their
teeth to caries or trauma. The patients who lost their teeth
as a result of periodontal disease run a higher risk of
developing peri-implant infection even if they are completely edentulous (Heitz-Mayfield, 2008).

Selection of the Implant Site


Imaging plays a key role in the selection of the site for mandible or maxilla, whether the implant is for a single site or

Figure 5

Diagrammatic representation of the Misch classification using


mandibular bone. The short arrow with long arrow head
points to the dense cortical bone in D1. The long arrow with
short arrow head in D4 points to the generalized fine
trabecular bone with absence of cortical bone

for multiple sites. Historically, the most frequently used and


available intraoral and extraoral radiographs were used to
evaluate the sites receiving the dental implant. Misch classified the bone density to four different groups based on
the observed density of the bone (Misch, 1990).

D1 bone (1,250 Hounsfield unit [HU]) bone is composed of almost all cortical bone mass located primarily in the anterior mandible.
D2 bone (8501,250 HU) bone is composed of a thick
crestal layer of cortical bone and coarse trabecular bone
underneath the cortical bone. This type of bone can
mostly be found in the anterior maxilla and mandible
and in the posterior mandible.
D3 bone (350850 HU) is composed of a porous crestal
layer of cortical bone and fine trabecular bone underneath the cortical bone. This type of bone can mostly
be found in the anterior and posterior maxilla but also
in the posterior mandible. It is also seen after osteoplasty of D2 bone.
D4 bone (150350 HU) bone is composed of primarily
fine trabecular bone and often the absence of cortical
bone. This type of bone can mostly be found in the
posterior maxilla and poses the greatest challenge in
implant placement (Figure 5). Implants usually placed
in D1 or D2 bone stand a very good chance of undergoing osseointegration, while the implants placed in
D3 or D4 bone either undergo fibrointegration or fail
to integrate at all. There are many factors that affect
the long-term success or failure of an implant.

Misch classification is a subjective grading of bone density


and the site in question might not always fall under a certain category as the bony anatomy is more complex than
what appears visually. The visual radiographic analysis has
to be augmented with other parameters of bone quality
analysis. This might include factors such as the total
847

Section XII Radiographic Landmarks

overall availability of bone and the health of the alveolar


bone and number of implants to be placed in the area.
They include correct initial placement of the fixture, successful osseointegration of the fixture, and the ability of
the surrounding bone to withstand the occlusal and masticatory forces. A properly placed implant fixture can also
fail if the occlusal forces are excessive, leading to a breakdown of the bone around the fixture. Hence, it is important
to identify the correct occlusal scheme for the patient even
before restoring the implant. Three-dimensional and crosssectional reformatted images of the patients jaw through
the areas of interest demonstrate the spatial relationships
of the opposing arches. The cross-sectional images are
very helpful in assessing the direction of various force
vectors acting on an implant placed and gives the clinician clues for preimplantation bone augmentation surgery
(Delbalso et al, 1994).
The widely available panoramic radiography and the
linear tomography have a very limited value in the assessment of bone quality. Preoperative assessment of bone
density is now performed primarily by radiographic means
that includes the cross-sectional data. More recently dental
CT has become more acceptable standard procedure.

Imaging of the Implant Site


Diagnostic imaging is an essential and integral component of the implant treatment planning. Until the late
1980s, conventional radiographic techniques, namely, intraoral, panoramic, cephalometric radiographs have been the
accepted standard (Harris et al, 2002). Developments in
the cross-sectional imaging techniques such as complex
motion tomography, reformatted CT have become available and were found to be useful compared with the previously accepted imaging techniques. Additionally, available
proprietary and third party software paved way for the
visualization of the third dimension and virtual positioning of the implant in the radiographic volumes before the
implant surgery. The European Association for Osseointegration (EAO) recommended that even for single implant
site, cross-sectional imaging may be beneficial and allows
for more precise treatment planning. For all posterior
maxillary and mandibular sites that are partially or fully
edentulous, a cross-sectional imaging will provide sufficient
information regarding the bone volume and the proximity
to the inferior alveolar nerve canal and/or the maxillary
sinus. Cross-sectional images will also help in the predictability of prosthetic results and transferring this information to guide the clinician or the implantologist in implant
positioning. Special techniques such as zygomatic implants
may also dictate the need for additional imaging. Postoperative monitoring cross-sectional imaging is not a part
of the routine protocol unless there is a need for such an
imaging due to an infection or suspected endangerment of
the neighboring vital structures.
848

Figure 6

Edentulous maxillary areas showing alveolar extensions of


the maxillary sinus and one of the periapical images of
right maxillary molar region showing the presence of a
compound odontoma in the right maxillary sinus

Standard periapical radiographs


Although standard periapical radiographs have value in
the evaluation of single implant sites for the availability
of bone in the superior-inferior direction (Figure 6), the
evaluation of bucco-lingual width of the bone is not possible with this two-dimensional (2D) imaging technique.
The periapical radiographs can be used to identify the areas
for possible implant placement and select the appropriate
advanced imaging procedure. However, the periapical radiographs can be used for post-placement evaluation of the
implants for angulations and evaluation of suspected periimplantitis (Figure 7).
Panoramic radiography
Panoramic radiographs were used in the past for identification of the implant sites via radiographic markers but lacked
the third dimension (Figure 8). The uneven and unreliable
magnification of the image as well as the projection artifacts made it impossible to be accurate especially when an
implant is being placed close to the mental foramen, mandibular canal or the maxillary sinus floor. This technique
became largely outdated after the advent of the crosssectional imaging. The technique still has value for postoperative assessment of the implant fixture similar to the
periapical radiographs.
Conventional tomography
(linear or complex motion cross-sectional tomography)
Quint Sectograph was one of the first linear tomographic
machines that were available in the United States market

Chapter 34 Site Selection, Evaluation and Imaging for Dental Implants

Figure 7

Periapical radiograph of maxillary left first molar region


showing the grafted bone in the maxillary sinus and the
root form implant in place. The implant appears to be
stable with no evidence of peri-implantitis.
Courtesy: Dale Rosenbach, DMD

Figure 9

Tomax ultrascan complex motion tomographic


machine

Figure 8
Dental computed tomography

Cropped panoramic radiograph showing the edentulous


maxilla and partially edentulous mandible. The two linear
opacities above the crestal level in the region of the
left mandibular molars are the radiopaque markers
(gutta percha) that were used with imaging

when linear tomography became available as a modality


in the early 1930s. They were eventually used worldwide.
The complex motion tomographic machines were introduced to dental imaging market in the 1990s. The machines
like Tomax (Figure 9) and Commcat were used successfully for TMJ imaging as well as implant related crosssectional imaging. A digital acquisition charge coupled
device camera was available with the Tomax ultrascan but
the technology was soon outdated by the introduction of
dental CT and eventually by the CBCT.

Multidetector computed tomography (MDCT) is an imaging technique that uses reconstruction mathematics to
create images based on a series of radiographs. The initial
CT concepts were developed by Alan Cormack and later
brought to fruition by a British engineer Godfrey Hounsfield
in 1972. The technique was first used to produce crosssectional images of the brain. The radiographic densities
of the imaged structures were compared along a scale with
the standard densities of water, air and the bone. The units
came to be known as Hounsfield units (HU) or CT numbers. The HU has been used for measurement of radiodensity of structures being examined. The numerical scale
ranges from air (1,000) to water (0) and to bone (1,000)
and upward of 1,000 for even denser structures. The application of HU measurement can decrease the observer bias
inherent in the interpretation of plain films. Overall, the
HUs are important in an objective determination of bone
density. Dental CT and the concepts of curved plane
tomography were first published by Schwarz and coworkers
in 1987 (Schwarz et al, 1987), which were utilized in the
dental CT studies for reformatting the multiplanar and
cross-sectional views. In addition, the dental CT programs
like the DentaScan were able to produce the panoramic
reformation from the conventional CT datasets (Figure 10).
This gained acceptance by the dental practitioners. Even
though the CT radiation dose was higher compared to all
the previous radiographic modalities, the benefit of accurate placement of implants outweighed any potential
risks.
849

Section XII Radiographic Landmarks

Figure 10

DentaScan software generated CT images. Courtesy: General Electric Company, USA

Cone beam computed tomography (CBCT)


Introduced in the mid 90s, this dental specific CT scanning
technology became a well-liked imaging technology, mostly
due to the smaller footprint of the machines that can be
purchased and installed in dental offices. Secondly, the
radiation doses were much lower compared to the MDCT
scanners, which were located mostly in the hospitals. CBCT
is a relatively new technique, which shares some of the
basic principles with MDCT. CBCT uses a cone beam instead
of a fan shaped beam and all the basis images are acquired
in one single pass instead of multiple passes as in MDCT.
The acquisition speed and relatively low dose in CBCT lead
to increased noise and lower image resolution when compared to MDCT. Hence, utilization of HUs derived from
CBCT imaging has come under criticism due to the differences in acquisition of CBCT volumes as compared to the
MDCT. The CBCT volumes are acquired via a 360-degree
rotation of the X-ray source using a flat panel detector.
The raw data as shown in the Figure 11 will be transmitted
first back to the workstation. When the technologist confirms the field of view (FOV), the actual acquisition will be
completed, and the entire study is stored as digital imaging
850

and communications in medicine (DICOM) format. These


DICOM sets (with a file extension of .dcm) are used for
reconstruction and display using appropriate software.
The acquisition of CBCT volumes and the resultant
anatomy is dictated by what is known as the FOV. The
scanners FOV determines how much of the patients anatomy one can visualize. Scanners using at panel detectors
describe the dimensions of their cylindrical FOVs as height
by width (H  W). Scanners that use image intensiers and
charge-coupled devices (CCDs) as their detectors identify
their spherical FOVs as cm3. Figure 12 shows the grouping
of the FOVs based on their largest unstitched FOVs. A scanner with large FOV (at least 16  18 cm) will demonstrate
at least the roof of the orbits superiorly and the hyoid
bone inferiorly. The large FOV scans are used for orthodontic, maxillofacial prosthodontic or oral surgical purposes commonly but can also be used in other situations
where there is a need for such a volume (Figure 13). The
voxel sizes vary from scanner to scanner and the range is
from 0.075 to 0.4 mm. Medium FOV (at least 8  14 cm)
scanner capture typically from the infraorbital area superiorly down to lower border of the mandible inferiorly and
from condyle to condyle horizontally. These views are

Chapter 34 Site Selection, Evaluation and Imaging for Dental Implants

Figure 11

Figure 13

Appearance of a raw CBCT scan volume

Showing the CBCT machine, Kodak 9500 that has multiple


FOV settings. Both medium and large FOV settings are
available in this machine

Figure 12

Large volume
Height: >16 cm
Width: >18 cm

Small volume (Limited)


Height: >4 cm
Width: >4 cm
Medium volume
Height: >8 cm
Width: >14 cm

Diagrammatic representation of large, medium and


small volume CBCT field of view (FOV)

used commonly for preimplant assessment in maxilla and


mandible and the assessment of maxillary sinuses and the
TMJs bilaterally. The range of minimum voxel sizes vary
from 0.080 to 0.13 mm and the maximum could be as
large as 0.4 mm. Small FOV (at least 4  4 cm) scanners are
used for capturing a small area within the mandible or
maxilla, usually for preimplant assessment or periodontal
or endodontic needs. The minimum voxel sizes here vary
from 0.076 to 0.15 mm. Generally, smaller voxel sizes are
used in small FOV scanners and larger voxel sizes are used
in medium and large FOV scanners. The data volume of
the CBCT study depends on the voxel size and to keep the

volumes practical for storage and transmission, optimal


voxel sizes are employed.
In a recent consensus of the International Congress of
Oral Iimplantologists, the use of CBCT implant placement
was discussed and the proceedings were recently published
(Benavides et al, 2012). It is recommended that the CBCT
along with all other radiographic examinations must be
justied on an individual need basis for implant planning.
The benets of these examinations must clearly outweigh
the potential radiation related risks. CBCT should be used
as an imaging alternative in cases where the projected
implant receptor site or the bone augmentation sites are
suspects for adequacy of bone. When used, the smallest
possible volume should be imaged and the entire volume
should be interpreted.
Implant manufacturers have developed specic designs
for their implant xtures taking into consideration the
anatomy, retentive capacity and osseointegration ability
of each implant. The implant interface that will face the
bone is designed to promote osseointegration with the bone
after implants are placed. Hence, the biocompatibility of
implant material is very important for the success and
long-term prognosis of the implant xture.
Radiographic appearance of screw-type and
cylinder-type implants
As shown in Figure 14, the implant fixtures are unique to
each manufacturer and the type of implant can perhaps be
recognized by the radiographic appearance of the fixture.
The figure shows various Nobel Biocares root form implants.
In Figure 15, the cylinder-type implants are noted (IMZ
dental implants). The radiographic appearances will be
useful in post-operative radiographic identification of the
type of implants.
851

Section XII Radiographic Landmarks

Figure 14

Nobel Biocare
Replace Select
Straight RP
[4.3 11.5 mm]

Nobel Biocare
Nobel Speedy
Groovy RP
[4.0 13 mm]

Nobel Biocare
Nobel Speedy
Shorty WP
[6.0 7 mm]

Nobel Biocare
Nobel Perfect
(View A)
[4.3 10 mm]

Nobel Biocare
Nobel Perfect
(View B)
[4.3 10 mm]

Nobel Biocare
Immediate
Provisional Implant

Nobel Biocare
(Branemark)
Self-tapping
[3.75 mm]

Nobel Biocare
(Branemark)
Conical Self-tapping
[3.75 10 mm]

Nobel Biocare
(Branemark)
Branemark MK I
[3.75 10 mm]

Nobel Biocare
(Branemark)
Branemark MK I
[3.75 13 mm]

Radiographic appearance of screw-type dental implants manufactured by Nobel Biocare.


Courtesy: www.whatimplantisthat.com

Figure 15

IMZ (Attachments Int.)


High Cyclinder
[4.25 11 mm]

IMZ (Attachments Int.)


High Cyclinder
[4.25 11 mm]

IMZ (Attachments Int.)


High Cyclinder
[3.3 10 mm]

IMZ (Attachments Int.)


Hex Head
[4.0 mm]

Cylinder-type IMZs dental implants. Courtesy: www.whatimplantisthat.com

Placement of implants, software manipulation and


assessment of osseointegration
The anatomy of the site should be thoroughly checked
before attempting to measure the area. Typically, the height
852

and the width of the remaining bone are measured. This


knowledge will help the clinician choose the implant with
appropriate dimensions. In order to make sure that the
implant size and placement angulation are predictable, the

Chapter 34 Site Selection, Evaluation and Imaging for Dental Implants

clinician uses software that are either provided by the


manufacturer or by utilizing the third party software separately via importing the data volume to the software. The
implant is virtually placed within the volume. Before
placing the implant, the mandibular canal is mapped out

Figure 16

The existing complete denture can be used for


fabrication of a radiographic guide and a surgical guide.
Courtesy: Hani Braidy, DMD

via a process called paint the canal using pre-identified


coordinates. If a radiographic template/guide (Figure 16)
was used before the radiographic examination, then that
template can be converted to a surgical template by the
laboratory using the information gained from the CT scans.

Figure 17

Lab prepared surgical guide in the patients mouth before


implant placement. Courtesy: Hani Braidy, DMD

Figure 18

CBCT showing the anterior extension of the mental foramen (arrows) in the edentulous mandible. The CBCT-based
cross-sections near the midline demonstrate the lingual foramen which would be a blind sac that derives the
neurovascular bundle from the lingual nerve and artery

853

Section XII Radiographic Landmarks

The surgical template so formed will have the prefabricated implant guides. A typical surgical guide that has
been fabricated using an existing denture is shown in the
Figure 17.

The surgeon or the implantologist places the implant


xture using a surgical guide and based on whether the
system is one-stage or two-stage, healing abutments would
be placed before closure of the wound. Single-stage implants

Figure 19

CBCT cross-sectional views (parasagittal views) of the left mandible showing the dumbbell-shaped anatomy and
the clear delineation of the mandibular canal and the mental foramen (arrow)

Figure 20

Another instance of preimplant CBCT scan showing the reformatted panoramic view and cross-sectional views of the
left molar area. Note the measurements that are directly digitally obtained from the sections

854

Chapter 34 Site Selection, Evaluation and Imaging for Dental Implants

Figure 21

CBCT reformatted panoramic view and maxillary anterior cross-sections showing knife-edge shaped ridge

Figure 22

CBCT reformatted panoramic view and maxillary posterior cross-sections showing severely resorbed ridges bilaterally

855

Section XII Radiographic Landmarks

Figure 23

Bone grafting completed in the maxilla bilaterally via sinus lift procedure as shown in the
panoramic reconstruction of CBCT and left cross-sectional views of the maxilla

can be loaded immediately and the clinician can make that


determination based on the type of implant, anatomy of
the implant site and other pertinent factors.
The inferior alveolar nerve canal is typically very distinct bilaterally up to the mental foramen. From mental
foramen onward medially toward the midline, there are
instances where the smaller branches of the mandibular
canal continue even after the mental foramen, Figure 18
demonstrates one such example. Trauma to this foramen
leads to excessive bleeding from the lingual vessels. A nerve
injury in this area might lead to numbness of the sublingual area close to the genial tubercles. Hence, care should
be exercised while planning implants in the anterior mandible between the two canines. In the posterior areas of
the mandible, the location of the mental foramen and the
mandibular canal are important landmarks for identication and measurement of the residual alveolar bone. The
bone height and width are carefully measured and the
bony anatomy of the ridge and the basal bone is observed
for anatomical variations. One such variation could be a
dumbbell-shaped mandible as shown in Figure 19. If the
bone width and alveolar bone direction is misjudged in
such situations, it leads to selection of the wrong type of
implant and possibly an unsuccessful outcome.
During preimplant assessment of the site, the measurements
are digitally obtained using the measuring tool provided
856

by the display and enhancement software (Figure 20).


The measurements are usually considered 1:1 without any
signicant magnication or distortion. Hence, the measurements can be translated directly to the selection of appropriate implant sizes. Ridge resorption is noted commonly
in the anterior maxilla as shown in Figure 21. Once a knifeedge like ridge is noted, then bone grafting becomes necessary to be able to place root form implants in that region.
Posteriorly, if the ridge is severely resorbed (Figure 22)
bone grafting can be done via sinus-lift procedure and
the appropriate implants can be placed using the newly
gained bone volume (Figure 23). This has become increasingly common and complications are relatively rare with
the improvements in both the technique and the materials
used for grafting. If appropriate imaging is not performed
before the implant placement, the implant xtures could
be disastrously placed sometimes leading to immediate loss
of implants (Figure 24). Adequacy of bone and the quality
of the bone is paramount to the success of the root form
implant. The effective radiation doses are an important
consideration before selecting any radiographic procedure.
CBCT examinations should be prescribed only after a thorough patient examination preceded by collection of an
equally thorough medical and dental history as was discussed in the beginning of this chapter. The effective radiation doses for CBCT-based procedures are in the range

Chapter 34 Site Selection, Evaluation and Imaging for Dental Implants

Figure 24

A SimPlant study of a patient showing the disastrous outcome of the implant fixtures. Poor planning and
lack of preimplant imaging usually leads to such results. Note the displacement of an implant
into the left maxillary sinus. Courtesy: Barry E Zweig, DDS

of 30400 Sv as compared to a panoramic radiograph


(2.723 Sv) and maxilla-mandibular CT (1802,100 Sv).
These measurements are based on effective radiation dose
compilation from various studies. The dose comparisons
can be found online at the European CBCT guidelines site
for dental and maxillofacial radiology (www.sedentext.eu).
Post-operative evaluation of implants and
future directions
Imaging modalities used in the post-operative evaluation
of the dental implant patient include intraoral periapical
radiography and panoramic radiography for assessment of

bone healing around the fixture. Three-dimensional imaging is recommended only when complications arise from
the placement. A good example would be to evaluate the
nerve canal proximity if the patient is symptomatic for
nerve injury. In such situations, a limited volume CBCT
would be ideal to evaluate the area. Dental implantology
and implant imaging are rapidly expanding areas of dentistry. The information presented in this chapter should
provide some basic concepts regarding implant selection,
imaging and placement strategies for both doctoral and
graduate level dental students. However, the reader is
encouraged to follow the literature on the subject for a
more up-to-date knowledge.

857

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SECTION

Appendices

XIII

Appendix 1
Appendix 2
Appendix 3
Appendix 4
Appendix 5

Terminologies
Summary of Radiographic Pathology
Characteristics of Ideal Radiograph
Indications for Intraoral Radiography
Patient Position for Extraoral Radiography

861
867
871
872
873

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APPENDIX

Terminologies
Ravikiran Ongole

Abrasion Pathologic wearing away of tooth substance


due to an abnormal mechanical process, e.g. faulty toothbrushing technique.

Anomaly An irregularity or deviation from normal; an


abnormal structure.

Abscess

Antibody An immunoglobulin molecule that reacts with


a specific antigen that induced its synthesis. Synthesized
by B lymphocytes that have been activated by the binding
of an antigen to a cell surface receptor.

Localized collection of pus.

Absorbed dose It is a measure of the total energy


absorbed by any type of ionizing radiation per unit mass
of any type of matter. It is given by D d/dm, where d
is the mean energy imparted to matter of mass (dm) by
ionizing radiation. The SI unit for absorbed dose is gray
(Gy). 1 Gy 1 joule per kilogram (J/kg). The traditional unit
of absorbed dose is rad (radiation absorbed dose).
Acantholysis Dissolution of the intercellular bridges of
the prickle cell layer of the epithelium.
Acanthosis Hypertrophy or thickening of the prickle cell
layer of the skin.
Acute

Sudden onset of signs and a short course.

Agenesis
organ.
Ageusia

Absence or failure of formation of any part or


A total lack of taste perception.

Agnosia Inability to classify or contrast odors, although


able to detect odors.
ALARA As Low As Reasonably Achievable, means that
exposure to ionizing radiation should be kept as low as
reasonably achievable, economic and social factors being
taken into consideration.

Anosmia

Inability to detect odors.

Antigen Any substance, almost always a protein, not


normally present in the body which when introduced to
the body stimulates a specific immune response and the
production of antibodies.
Apoptosis (Greekfalling off) It is defined as programed
cell death. The cell gets fragmented into membrane-bound
particles that are subsequently eliminated by phagocytosis.
Atopy A clinical hypersensitivity state which is subject
to hereditary influences, e.g. asthma, eczema.
Atresia Absence or closure of a normal body orifice or
passage.
Atrophy A decrease in the size of a normally developed
organ or tissue.
Attrition It is the physiological wearing away of tooth
substance as a result of tooth-to-tooth contact, e.g. agerelated wearing away of the occlusal/incisal surfaces.
Bacteremia

Presence of bacteria in blood.

Analgesia A drug that dulls the sense of pain. It relieves


pain without loss of consciousness.

Becquerel (Bq) It is the international unit of radioactivity.


It is defined as the number of radioactive decays (disintegrations)/unit of time. 1 Bq 60 disintegrations/minute or
1 Bq 1 disintegration/second.

Anaphylaxis The immediate immunologic (allergic)


reaction initiated by the combination of antigen (allergen)
with mast cell cytophilic antibody (chiefly IgE).

Blanching (Frenchwhite) It refers to change in color


of a tissue to a paler and lighter shade when pressure is
applied.

Anaplasia A condition in tumor cells in which there is


loss of normal differentiation, organization and specific
function. (Adult cells that have changed irreversibly
toward more primitive cell types. These changes are often
malignant.)

Bulla Elevated blister containing clear fluid and greater


than 1 cm in diameter, e.g. pemphigus, pemphigoid.
Cachexia This refers to a state of decreased tissue or organ
mass resulting from a state of malnutrition or underlying
severe debilitating disease.
861

Section XIII Appendices

Carcinoma in situ The most severe stage of epithelial


dysplasia, involving the entire thickness of the epithelium,
with the epithelial basement membrane remaining intact.
Cellulitis Acute inflammation which spreads rapidly
through tissue spaces and along tissue planes. It is usually
suppurative in nature.
Chancre Painless ulceration formed during the primary
stage of syphilis. This infectious lesion forms approximately
21 days after the initial exposure to Treponema pallidum.
Cheilitis

Inflammation of the lips.

Cheilosis Condition characterized by fissuring and dry


scaling of the vermilion border of lips (usually seen as a
feature in riboflavin deficiency).
Chloroma Malignant green color tumor occurring anywhere on the body and originating from myeloid tissue.
These are associated with myelogenous leukemia.
Choristoma Microscopically normal cells that are present
in abnormal location.
Chronic Slow onset, mild but continuous manifestations
and long-lasting, often progressive effects.
Congenital Conditions that are present at birth, regardless of their causation.
Contusion A bruise; an injury of a part without a break in
the skin, characterized by swelling, discoloration, and pain.
Consanguinity In genetics, the term is generally used to
describe mating or marriages among close relatives.
Controlled area It is a limited access area in which the occupational exposure of personnel to radiation is under the supervision of an individual incharge of radiation protection. The
reduced exposure in that area is to be 26 mC/kg/week.
Curie (Ci) The number of radioactive decays (disintegrations)/unit of time.
1 Ci 2.2 1012 disintegrations/minute
1 Ci 3.7 1010 disintegrations/second.
Cyst It is a pathological cavity filled with a fluid, semifluid or gaseous material but not by pus, which may frequently but not always lined by epithelium.
Decay Radioactive decay or the disintegration of the
nucleus of an unstable atom by spontaneous emission of
energy in the form of high speed particles or electromagnetic waves.

862

Diagnosis, final It is the diagnosis that is arrived at after


all the necessary data history, clinical examination and
investigations have been collected, analyzed and subjected
to a logical thought process.
Disintegration

A spontaneous nuclear transformation.

Disorder, congenital It is the disorder which occurs during the development process (intrauterine life). The manifestation of which is seen either at birth or later in life.
Disorder, developmental It is the abnormality that occurs
during the formative stage of an organ or tissue.
Disorder, genetic It is a disorder caused by abnormality
in the gene or an abnormality in mutation.
Disorder, inherited It is the disorder, which is transmitted
through genes to the offspring of the next generation or to
subsequent generations.
Dose It is the amount of energy absorbed per unit of mass
at a site of interest. Expressed in units of rad or gray.
Dose equivalent (DE) Absorbed dose multiplied by certain modifying factors. The principle factor is the quality
factor (QF), which corrects absorbed dose for relative biological damage for quality factors for:
Beta, gamma and X-rays 1
Alpha 20
1 rad 1 rem for beta, gamma and X-ray.
Various types of radiation, expressed in units of rem or
sievert.
a.

b.
c.

Deep dose equivalentapplies to the external whole


body exposure in terms of dose equivalent at a tissue
depth of 1 cm (1,000 mg/cm2).
Shallow dose equivalentapplies to the skin at a max.
Tissue depth of 0.007 cm (7 mg/cm2).
Effective dose equivalentis the sum of the product of
the dose equivalents each weighted by a factor for the
tissue organ in question.

Dose, loading A larger than normal dose administered as


the first in a series of doses, the others of which are smaller
than loading dose but equal to each other. The loading
dose is administered in order to achieve a therapeutic
amount in the body more rapidly than would occur only
by accumulation of the repeated smaller doses.
Dose, maintenance The smaller doses which are given
after the loading dose are called maintenance doses.

Diagnosis, clinical/provisional/tentative It is the diagnosis


that is made after thorough case history taking and clinical
examination but before any investigations are performed.

Drug, bioavailability The percentage of dose entering


the systemic circulation after administration of a given
dosage form.

Diagnosis, differential Identification of a particular disease by differentiating it from all other disease processes
that may have similar symptoms and signs.

Drug, first pass effect All drugs that are absorbed from
the intestine enter the hepatic portal vein and pass through
the liver before they are distributed systemically.

Appendix 1 Terminologies

Drug, half-life The period of time required for the concentration or amount of drug in the body to be reduced to
exactly one-half of a given concentration or amount.
Dysgeusia

An altered taste sensation.

Dysosmia

Distorted identification of smell.

Dysphagia
lowing.

Painful swallowing or difficulty in swal-

Dysplasia An abnormality of development characterized


by the loss of normal cellular architecture.
Ecchymosis Larger purpuric lesions.
Edema Accumulation of excess fluid in the intercellular
or interstitial tissue spaces or body cavities.
Effective dose (E) It is a radiation quantity used to estimate the risk in humans.
It is the tissue-weighted sum of the equivalent doses in
all specied tissues and organs of the body, given by the
expression:
E T WT RWRDT, R

or

E WT X HT

where HT or WR DT, R is the equivalent dose in a tissue or


organ T, and WT is the tissue weighting factor. The unit for
the effective dose is the same as for absorbed dose, J kg1,
and its special name is sievert (Sv).
Epiphora

Tearing from the eye.

Epistaxis

Bleeding from the nose.

Equivalent dose (HT) It is a radiation quantity used to


compare the biological effects of different types of radiation on a tissue or organ.
The dose in a tissue or organ T is given by:
HT WRDT, R
where DT, R is the mean absorbed dose from radiation R in
a tissue or organ T and WR is the radiation weighting factor. Since WR is dimensionless, the unit for the equivalent
dose is sievert (Sv). 1 Sv 1 Gy. Traditional unit of equivalent dose is the rem (Roentgen equivalent man).
Erosion A shallow defect in the oral mucosa representing
a loss of covering epithelium down to, but not involving
the stratum germinatum, e.g. erosive lichen planus.
Erosion (wasting disease) It is the loss of tooth substance by a chemical process that does not involve known
bacteria, e.g. excessive consumption of citrus fruits.
Exposure A special radiation quantity of ionization in air
from X-rays or gamma rays. It is measured as the amount
of charge per mass of air, which is coulombs/kg. Units are
expressed in roentgen (R). 1 R 2.58 104 C/kg.
External exposure Radiation exposure from a source
outside the body.

Exudate Fluid with a high concentration of protein and


cellular debris which has escaped from blood vessels and
has been deposited in tissues, or on tissue surfaces, usually
as a result of inflammation. (Specific gravity can be 1.020
or higher and high protein content can be 16 g/dl.)
Fascial spaces Potential tissue spaces through which
infection spreads easily, e.g. submandibular space, buccal
space, pterygomandibular space.
Final diagnosis It is the diagnosis arrived at after all the
data has been collected, analyzed and subjected to logical
thought.
Fistula It is an abnormal communicating tract between
two epithelial surfaces or organs. A fistulous tract is generally lined with granulation tissue but over a period of
time may become epithelialized.
Pain in the tongue.

Glossodynia
Glossopyrosis

Burning sensation in the tongue.

Granuloma Tumor-like mass of inflammatory tissue consisting of a central collection of macrophages, often with
multinucleated giant cells, surrounded by lymphocytes.
Granulomatous Pertaining to a well-defined area that
has developed as a reaction to the presence of living
organisms or a foreign body. The tissue consists primarily
of histiocytes.
Gray (Gy) The international unit of absorbed dose.
1 Gy 100 rad; 1 Gy 1 joule/kilogram (J/kg).
Hamartoma Abnormal proliferation of tissues of structures native to the part.
Hematoma Tumor-like mass produced by coagulation of
extravasated blood into tissues from ruptured blood vessels.
Hemiparesis
Hemiplegia

Weakness on one side of the body.


Paralysis of one side of the body.

Hereditary A condition that may be genetically transmitted from parent to offspring.


High radiation area It is defined as an area, accessible to
individuals, in which radiation levels from radiation
sources, external to the body could result in an individual
receiving a dose equivalent in excess of 0.1 rem (100 mrem)
in 1 hour at 30 cm from the radiation source or from any
surface that the radiation penetrates.
Hyperemia Presence of an increased amount of blood in
a part or an organ.
Hyperplasia Enlargement caused by an increase in the
number of normal cells.
Hypertelorism Abnormal increased distance between two
organs or parts. Ocular hypertelorism refers to increased
interorbital distance.
863

Section XIII Appendices

Hypertrophy Increase in the size or volume of a tissue or


organ as a result of enlargement of the cell.
Hypogeusia

Substantial loss of all taste sensation.

Hypoplasia Incomplete development of a tissue or organ;


a tissue reduced in size because of a decreased number of
constituent cells.
Hyposmia

Decreased ability to detect odors.

Iatrogenic Adverse condition in a patient resulting from


treatment by a physician or surgeon.
Id reaction Hypersensitivity reaction to candidal antigen,
manifests as vesicular and papular rash on skin of patients
with chronic candidiasis.
Idiopathic Occurring without known cause.
Induration Abnormally hard portion of a tissue with
respect to the surrounding similar tissue; often used to
describe the feel of locally invasive malignant tissue on
palpation.
Ischemia A local deficiency of blood due in part to functional constriction or actual mechanical obstruction of a
blood vessel.
Kerma (K) It is the quotient of the sum of the kinetic energies, dEtr, of all charged particles liberated by uncharged
particles in a mass, dm, of material.
K dEtr/dm

Nevus A small flat elevated pigmented or non-pigmented


lesion of congenital origin involving the skin or mucous
membrane.
Nodule Solid, elevated lesion varying in size from 5 mm
to 2 cm, e.g. fibroma.
Oral diagnosis It is the art of using scientific knowledge
to identify oral disease process and to distinguish one disease process from the others.
Oral medicine It is the specialty of dentistry that is concerned with the oral healthcare of medically compromised
patients and with the diagnosis and non-surgical management of medically related disorders or conditions affecting
the oral and maxillofacial region. Oral medicine specialists
are concerned with the non-surgical medical aspects of dentistry. These specialists are involved in the primary diagnosis and treatment of oral diseases that do not respond to
conventional dental or maxillofacial surgical procedures.
The practice of oral medicine will provide optimal health to
all people through the diagnosis and management of oral
diseases.
Papule Small circumscribed solid elevated lesion varying
in size from a pinhead to 5 mm, e.g. Fordyces granules.
Paraparesis

Weakness affecting the lower extremities.

Kerma is a non-stochastic quantity and dEtr is the expectation value of the sum of the kinetic energies. The unit for
kerma is joule per kilogram (J/kg) and its special name is
gray (Gy).

Paraplegia

Lesion A morphological alteration of the tissue with


objective signs of disease.

Paresthesia It is an altered sensation or abnormal sensation (tingling sensation).

Linear energy transfer (L or LET) It is the average linear


rate of energy loss of charged particle radiation in a medium,
i.e. the radiation energy lost per unit length of path through
a material. That is, the quotient of dE by dl where dE is the
mean energy lost by a charged particle owing to collisions
with electrons in traversing a distance dl in matter.

Parosmia Altered perception of smell in the presence of


an odor, usually unpleasant.

L dE/dl

Paresis

Paralysis of the lower limbs.

Slight or partial paralysis.

Paroxysmal

Recurring sudden attacks of symptoms.

Parulis A sessile nodule on the gingiva at the site where


a draining sinus tract reaches the surface.
Petechiae Pinpoint purpuric spots, 12 mm in diameter.

The unit of L is Jm1, often given in keV m1.

Phantosmia Perception of smell without an odor present.

Macule It is a circumscribed non-raised area of altered


coloration varying in size from a pinhead to several centimeters in diameter, e.g. petechiae, melanin pigmentation
in Addisons disease.

Plaque A circumscribed solid elevated lesion greater than


5 mm in diameter, e.g. leukoplakia.

Metastasis The transport of neoplastic cells to parts of


the body remote from the primary tumor and the establishment of new tumors in those sites.
Necrosis
864

Neoplasm Abnormal mass of tissue, the growth of which


exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after cessation of the stimuli which evoked the change.

Death of a cell as a result of disease or injury.

Precancerous condition Generalized state associated with


a significantly increased risk of cancer, e.g. Plummer
Vinson syndrome, oral submucous fibrosis.
Precancerous lesion A morphologically altered tissue in
which cancer is more likely to occur than its normal counterpart, e.g. erythroplakia, leukoplakia.

Appendix 1 Terminologies

Prognosis It is the prediction of the course, duration and


termination of a disease and the likelihood of its response
to treatment.
Ptosis

Drooping of the upper eyelid.

Purpura Reddish to purple flat lesions caused by blood


leaking into the subcutaneous tissue. They do not blanch
on pressure. Depending on their size they are termed as
purpura or petechiae. Larger petechiae are purpura.

It accounts for the different degrees of damage produced by equal doses of different radiations.
Example: Radiation weighing factor (Wr): for X-rays,
gamma rays, beta particles 1
Neutrons (range) 220; alpha particles 20.
Sarcoma It is a malignant tumor arising from connective
tissue.
Septicemia

Presence of bacterial toxins in blood.

Pustule It is a vesicular type of lesion containing pus,


e.g. pyostomatitis.

Sessile The term describes the base of the lesion which is


flat or broad.

Quadriplegic

Sievert (Sv) The special name for the SI unit of equivalent dose, effective dose, and operational dose quantities.
The unit is joule per kilogram (J kg1).
1 Sv 100 rem; 1 Sv 1 Gy Wr.

Paralyzed in all four limbs.

Quality factor (QF) A linear energy transfer dependent


factor by which absorbed dose is multiplied to obtain a
dose quantity, dose equivalent, to indicate the biological
effectiveness of absorbed dose.
Radiation The emission and propagation of energy
through space.
Radiation absorbed dose (rad) The energy absorbed per
gram of material. It represents the amount of energy that
is absorbed by the material of interest, e.g. person, organ,
tissue, cells. 1 rad 100 erg/g.
Radiation area It is an area, accessible to individuals, in
which radiation levels could result in an individual receiving a dose equivalent in excess of 0.005 rem (5 mrem) in
1 hour at 30 cm from the radiation source or from any
surface where the radiation penetrates.
Radiation weighting factor (WR) A dimensionless factor
by which the organ or tissue absorbed dose is multiplied to
reflect the higher biological effectiveness of high-LET
radiations compared with low-LET radiations. It is used to
derive the equivalent dose from the absorbed dose averaged over a tissue or organ.
Red lesion A non-specific term used to describe any area
on the oral mucosa that on clinical examination appears
more red than the surrounding tissues and is usually velvety or granular or smooth in texture.
Restricted area An area, access to which is limited by the
licensee for the purpose of protecting individuals against
undue risks from exposure to radiation and radioactive
materials.
Roentgen (R) It is a unit of radiation exposure in air.
It is defined as the amount of X-ray or gamma radiation
that will generate 2.58 104 coulombs (a measure of electrical charge) per kilogram of air at standard temperature
and pressure. This can also be defined as the amount of
energy absorbed in air. This unit is applied for only X-rays
and gamma rays.
Roentgen equivalent man (rem) The product of the
amount of energy absorbed (rad) times the coefficient of
radiation in producing damage. rem rad (Wr)

Sign Any change in the body or its function, which is perceptible to a trained observer and may indicate a disease.
Sinus It is a blind tract that connects a cavity lined by
granulation tissue to the epithelial surface. This lining
may subsequently become epithelialized.
Stochastic effect It is the sub-lethal changes in the DNA
of an individual cell and the heritable effects for which the
probability of an effect occurs, but not its severity. It is
regarded as a function of dose without threshold.
Swelling It is a non-specific term used to describe any
enlargement or protuberance in the body.
Symptom Any change in the body or its function, which
is perceptible to the patient and may indicate a disease.
Teratoma A true neoplasm made up of a number of different types of tissues, none of which is native to the area
in which it occurs.
Therapy, curative Treatment directed toward eradication
of one or more of the agencies etiologic to the patients
condition, e.g. use of antibiotics such as penicillin.
Therapy, palliative or symptomatic Treatment directed
only toward relief of the patients symptoms. The natural
course of the disease is unaffected.
Therapy, restorative Therapy directed at rapid restoration
of health, usually regardless of the nature of the original
disease; restorative therapy is most frequently given during
convalescence, e.g. vitamin supplements.
Therapy, substitutive or replacement Treatment directed
toward supplying a material normally present in the body,
but absent in a specific patient because of disease, injury,
congenital deficiencies, etc., e.g. use of hormones.
Therapy, supportive Treatment directed toward maintaining the patients physiological or functional integrity
until more definitive treatment can be carried out, or until
the patients recuperative powers function to obviate the
need for further treatment.
865

Section XIII Appendices

Tissue weighting factor (WT) The factor by which the


equivalent dose in a tissue or organ T is weighted to represent the relative contribution of that tissue or organ to
the total health detriment resulting from uniform irradiation of the body. It is weighted such that:
WT 1.
Tumor Any enlargement, especially one due to a pathological overgrowth of tissue.
Ulcer Breach in the continuity of the surface epithelium
of the skin or mucous membrane to involve the underlying connective tissue as a result of micromolecular cell
death of the surface epithelium or its traumatic removal.

866

Uncontrolled area It is an area where access is neither controlled nor restricted. In an uncontrolled area the shielding
should reduce the exposure rate to 2.6 mC/kg/week.
Vesicle Elevated blisters containing clear fluid and less
than 1 cm in diameter, e.g. herpes simplex infection,
herpangina, herpes zoster.
Viremia Presence of viruses in blood.
White lesion Non-specific term used to describe any
area of the oral mucosa that on clinical examination
appears whiter than the surrounding tissues and is usually
raised, roughened or otherwise of a different texture than
the adjacent normal tissue.

APPENDIX

Summary of Radiographic
Pathology

Medha Babshet

Table 1

Radiolucent lesions affecting the jaws


Unilocular

Associated with teeth


Pericoronal

Periapical

Others

Inflammatory paradental cyst


Dentigerous cyst
Mural ameloblastoma
Keratocystic odontogenic tumor (OKC)
Adenomatoid odontogenic tumor
(early stage)
Ameloblastic fibroma

Periapical granuloma
Periapical cyst
Dentoalveolar abscess
Periapical scar
Periapical cemento-osseous
dysplasia (lytic stage)

Not associated with


teeth

Traumatic bone cysts


Globulomaxillary cyst
Incisive canal cyst
Lateral periodontal cyst
Gingival cyst of adult
Cemento-ossifying fibroma (early stage)
Residual cysts
Squamous odontogenic tumor

Primordial cyst
Stafnes bone cyst
Neurilemmoma
Traumatic neuroma
Post-surgical maxillary
cyst

Multilocular
Associated with teeth

Not associated with teeth

Ameloblastoma
Keratocystic odontogenic tumor (OKC)
Botryoid odontogenic cyst
Odontogenic myxoma
Glandular odontogenic cyst
Central odontogenic fibroma

Central giant cell granuloma


Brown tumor of hyperparathyroidism
Cherubism
Aneurysmal bone cyst
Central hemangioma
Arteriovenous malformation
Desmoplastic fibroma
Metastatic tumors of jaw
Focal osteoporotic bone marrow defects

867

Section XIII Appendices

Table 2

Radiopaque lesions affecting the jaws


Focal

Generalized

Associated with teeth

Not associated with teeth

Condensing osteitis
Idiopathic osteosclerosis
Garreys osteomyelitis
Hypercementosis
Periapical cemento-osseous dysplasia
Focal cemento-osseous dysplasia
Cemento-ossifying fibroma
Cementoblastoma
Complex odontoma

Table 3

Tori
Exostosis
Osteomas
Foreign bodies
Mucosal cysts of maxillary sinus
Ectopic calcification
Sialolith
Rhinolith
Calcified lymph node
Phlebolith
Arterial calcification

Florid cemento-osseous dysplasia


Pagets disease
Osteopetrosis
Albrights syndrome
Gardners syndrome
Caffes disease (infantile cortical hyperostosis)
Familial gigantiform cementoma

Mixed radiolucent-radiopaque lesions of the jaws


Associated with teeth

868

Not associated with teeth

Periapical

Pericoronal

Rarefying and condensing osteitis


Periapical cemento-osseous dysplasia (intermediate stage)
Cemento-ossifying fibroma

Odontoma (intermediate stage)


Adenomatoid odontogenic tumor
Calcifying epithelial odontogenic cyst
Calcifying epithelial odontogenic tumor
Ameloblastic fibro-odontoma
Ameloblastic odontoma
Ameloblastic fibrodentinoma
Dentinoma

Chronic osteomyelitis
Osteoradionecrosis
Focal cemento-osseous dysplasia
Florid cemento-osseous dysplasia
Fibrous dysplasia
Pagets disease (intermediate stage)
Cemento-ossifying fibroma
Osteogenic sarcoma
Desmoplastic ameloblastoma
Osteoblatic metastatic carcinoma
Chondroma
Chondrosarcoma

Appendix 2 Summary of Radiographic Pathology

Table 4

Characteristic radiographic ndings of jaw pathologies

Characteristic radiographic finding

Jaw lesions

Cotton wool

Ground glass

Hyperparathyroidism
Fibrous dysplasia

Orange peel

Fibrous dysplasia

Soap bubble appearance

Honeycomb appearance

Ameloblastoma
Central hemangioma of bone

Tennis racket appearance

Odontogenic myxoma

Moth eaten

Driven snow

Pindborgs tumor (CEOT)

Codmans triangle
Cumulus cloud formation

Osteosarcoma

Onion peel appearance

Garres osteomyelitis
Calcifying subperiosteal hematoma
Ewings sarcoma
Osteogenic sarcoma
Leukemia
Syphilis
Hypervitaminoses A
Caffeys disease
Metastatic neuroblastoma
Fracture callus

Sunray (sun burst) appearance

Osteosarcoma
Ewings sarcoma
Hemangioma (central)
Chondrosarcoma
Odontoma (rarely)
Burkitts lymphoma

Hair-on-end

Sickle cell anemia


Thalassemia
Chronic iron deficiency anemia

Stepladder appearance

Thalassemia
Sickle cell anemia

Chicken wire appearance of enlarged marrow spaces

Thalassemia

Pagets disease
Diffuse sclerosing osteomyelitis
Florid osseous dysplasia
Sclerotic cemental masses

Hemangioma
Aneurysmal bone cyst
Cherubism
Ameloblastoma
Giant cell lesion of hyperparathyroidism
Central giant cell granuloma
Odontogenic cysts like odontogenic keratocyst, follicular and residual
Arteriovenous malformation

Burkitts lymphoma
Chronic suppurative osteomyelitis
Lytic variety of osteosarcoma
Osteoradionecrosis
Osteosarcoma (lytic type)

(Contd.)

869

Section XIII Appendices

Table 4

Continued

Characteristic radiographic finding

Jaw lesions

Beaten silver

Punched out

Multiple myeloma
Histiocytosis X
Eosinophilic granuloma

Salt and pepper

Metastatic lesions
Hyperparathyroidism
Fibrous dysplasia

Floating teeth appearance

Ballooning expansion

Follicular cyst
Aneurysmal bone cyst

Candle stick appearance

Progressive systemic sclerosis


Pyknodysostosis

Chalk like appearance

Osteopetrosis
Hyperparathyroidism
Pyknodysostosis

Egg shell appearance

Multilocular cyst
Ameloblastoma

Heart-shaped radiolucency

Nasopalatine cyst

Pear-shaped radiolucency

Globulomaxillary cyst

Craniofacial synostosis & dysostosis


Calcifying subperiosteal hematoma
Leukemia
Caffeys disease
Metastatic neuroblastoma
Hypervitaminoses A
Syphilis

Histiocytosis X
Squamous cell carcinoma of gingiva
PapillonLefevre syndrome
Advanced periodontitis
Cherubism

Other characteristic radiographic findings

870

Bulls eye appearance

Dilaceration of roots

Moth eaten appearance of crowns of teeth

Amelogenesis imperfecta especially the hypocalcified type

Shell teeth

Dentinogenesis imperfecta

Thistle tube-shaped pulp chambers in anteriors


Flame-shaped pulp chambers in molars

Type II/coronal dentin dysplasia

Ghost-like teeth

Regional odontodysplasia

Trap door sign

Blow-out fracture involving the orbit

Hanging drop/tear drop sign

Herniation of orbital contents into the maxillary sinus

Joint mice

Small calcifications (Loose bodies) within the temporomandibular joint space

APPENDIX

Characteristics of
Ideal Radiograph

Ravikiran Ongole, Praveen BN

CHARACTERISTICS OF IDEAL RADIOGRAPH


Ideal radiograph is one with optimum density and contrast
showing all the details which are well defined with minimum or negligible distortion.
An ideal radiograph should have optimum visual characteristics (density and contrast), geometric characteristics
(sharpness, minimal or no magnication and distortion),
record anatomical accuracy of radiographic images and
exhibit adequate coverage of anatomic region of interest.
A radiograph should record the complete area of interest. For an intraoral periapical radiograph (IOPAR) the full
length of root and at least 2 mm of periapical bone should
be visible.

a short gray scale. A low contrast radiograph displays many


shades of gray and thus exhibits a long gray scale. For all
practical purposes, an ideal radiograph is a compromise
between high and low contrast.

Sharpness
Sharpness is also referred to as detail, resolution or definition. It refers to the capability of X-rays to reproduce distinct outlines of an object or to reproduce the smallest
details of an object.
Intraoral periapical radiographs have better resolution
than panoramic radiograph and computed tomographic
scans. Resolution is described as line pairs per mm.

Density

Magnification

Density is the degree of overall blackness or darkness of a


dental radiograph.
The primary factors that affect density are kilovoltage
peak (kVp), milliamperage (mA), exposure time and the
source to lm distance. Some of the secondary factors the
affect density are development characteristics (dark and
light radiographs), subject thickness, speed of lm, lm
latitude, use of screens and grids and extent of ltration.

Radiographic image that appears larger than the object it


represents, because of the divergent path of X-rays.

Contrast
Contrast is difference in the degree of blackness (densities)
between adjacent areas on a dental radiograph.
A high contrast radiograph is one with very dark and
very light areas. Such a radiograph is considered to exhibit

Distortion
Distortion is the variation in the true size and shape of the
object being recorded. It results from unequal magnification
of different parts of the object.

Characteristic Curve
Characteristic curve is a graphic plot of relationship
between film density and exposure. It is also called H
and D curve after Hunter and Driffield.

871

APPENDIX

Ravikiran Ongole, Praveen BN

Indications for Intraoral Periapical Radiography

Indications of Bitewing Radiography

872

Indications for
Intraoral Radiography

Assessment of developmental disturbances affecting


the root morphology for diagnosis, exodontia and
endodontic treatment
Assessment of dental caries and periapical pathology
(including status of periodontal ligament space, integrity of lamina dura and bone changes at the periapical
region of teeth)
Assessment of the periodontal ligament space and
interdental bone in periodontal diseases
Detection of dento-alveolar fractures
Assessment of the quality of the bone prior to placement of dental implants
Detection of small cysts and tumors affecting the jaw
bones
Detection of the presence and position of the impacted
teeth (supernumerary, odontomes, etc.)
Detection of secondary caries beneath restorations
and crowns
Detection of foreign material embedded within the
soft tissue such as the lip, buccal mucosa
Detection of the status of eruption of primary/permanent teeth
Assessment of endodontic treatment
Assessment of alveolar bone grafts

Proximal regions of three maxillary and three


mandibular teeth can be assessed in a single radiograph
Detection of incipient proximal caries (however, if the
carious lesions is deep, IOPAR should be taken to
assess any periapical change)
Detection of alveolar crestal bone loss
Assessment of ill-fitting/overcontoured crowns
Assessment of overhanging restorations
Detection of secondary caries

Indications of Occlusal Radiography

Provides a birds eye view of the dental arches


Detection of cortical plate changes caused by bony
pathology (cysts, tumors) in a buccolingual direction
(such as expansion, resorption, pathological fractures,
laminar bone formation etc.)
Location of impacted teeth (buccal/lingual position)
Detection of sialoliths (calculi in the ducts of the submandibular salivary gland and sublingual gland)
Detection of symphyseal, parasymphyseal mandibular
fractures

APPENDIX

Patient Position for


Extraoral Radiography

Suman Jai Sanghar, Jai Sanghar N

Figure 1

Figure 2

Posteroanterior view

Posteroanterior Calwell view

OML: orbitomeatal line, CR: central ray.


873

Section XIII Appendices

Figure 3

Figure 5

Posteroanterior mandible

Figure 4

Figure 6

Standard occipitomental view

874

30 occipitomental view

Waters view

Appendix 5 Patient Position for Extraoral Radiography

Figure 7

Figure 9

Open mouth Waters view

Figure 8

Patients head positioning for reverse Waters view

Patients head position for submentovertex view

Figure 10

Patients head position for lateral view projection

875

Section XIII Appendices

Figure 11

Figure 13

Patients head position for Townes view

Figure 12

Patients head position for reverse Townes view

876

Patients head position for lateral oblique view of


the ramus

Figure 14

Patients head position for transcranial view

Appendix 5 Patient Position for Extraoral Radiography

Figure 15

Figure 16

Patients head position for transorbital view

Patients head position for transpharyngeal view

877

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References

CHAPTER 1
Burket LW. Oral Medicine: Diagnosis and Treatment. Lippincott: New York,
1946.
Cooke BE. History of oral medicine. Br Dent J 1981;151(1):1113.
Gies WJ. Dental education in the United States and Canada: a report to
the Carnegie Foundation for the Advancement of Teaching. Carnegie
Foundation: New York, Bulletin 19. 1926.
Grossman RI, Youssem DM. NeuroradiologyThe Requisites. Mosby:
St. Louis, MO, 1994.
Hashimoto K, Kawashima S, Araki M, et al. Comparison of image performance between cone-beam computed tomography for dental use and
four-row multidetector helical CT. J Oral Sci 2006;48(1):2734.
http://www.aaom.com
http://www.dciindia.org/
Larheim TA. Role of magnetic resonance imaging in the clinical diagnosis of
the temporomandibular joint. Cells Tissues Organs 2005;180(1):621.
Morimoto Y, Ono K, Tanaka T, et al. The functional evaluation of salivary
glands using dynamic MR sialography following citric acid stimulation:
a preliminary study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod
2005;100(3):35764.
Venkatraman BK. Guest editorial in JIAOMR. 2003;15(3).

CHAPTER 2
Al Quran FA, Al-Dwairi ZN. Torus palatinus and torus mandibularis in
edentulous patients. J Contemp Dent Pract 2006;7(2):1129.
Amir E, Gorsky M, Buchner A, et al. Physiologic pigmentation of the oral
mucosa in Israeli children. Oral Surg Oral Med Oral Pathol 1991;71(3):
3968.
Asbjrnsen H, Kuwelker M, Sfteland E. A case of unexpected difficult airway due to lingual tonsil hypertrophy. Acta Anaesthesiol Scand 2008;
52(2):3102.
Ballard JL, Auer CE, Khoury JC. Ankyloglossia: assessment, incidence, and
effect of frenuloplasty on the breastfeeding dyad. Pediatrics 2002;110:e63.
Banoczy J, Szabo L, Csiba A. Migratory glossitis: a clinical-histologic review
of seventy cases. Oral Surg Oral Med Oral Pathol 1975;39:11321.
Bean WB. The caviar lesion under the tongue. Trans Am Clin Climatol Assoc
1952;64:409;discussion, 4951.
Berardesca E, Maibach H. Racial differences in skin pathophysiology. J Am
Acad Dermatol 1996;34(4):66772.
Berman FR, Fay JT. The retrocuspid papilla. A clinical survey. Oral Surg Oral
Med Oral Pathol 1976;42(1):805.

Brannon RB, Pousson RR. The retrocuspid papillae: a clinical evaluation of


51 cases. J Dent Hyg 2003;77(3):1804.
Buchner A, Merrell PW, Hansen LS, et al. The retrocuspid papilla of the
mandibular lingual gingiva. J Periodontol 1990;61(9):5859.
Borrie F, Musthyala R, Macintyre D. Ectopic geographic tonguea case
report. Dent Update 2007;34(2):1212.
Canaan TJ, Meehan SC. Variations of structure and appearance of the oral
mucosa. Dent Clin North Am 2005;49(1):114.
Castellanos JL, Daz-Guzmn L. Lesions of the oral mucosa: an epidemiological study of 23785 Mexican patients. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 2008;105(1):7985.
Chohayeb AA, Volpe AR. Occurrence of torus palatinus and mandibularis
among women of different ethnic groups. Am J Dent 2001;14(5):27880.
Eidelman E, Chosack A, Cohen T. Scrotal tongue and geographic tongue:
polygenic and associated traits. Oral Surg Oral Med Oral Pathol 1976;
42:5916.
Ettinger RL, Manderson. Clinical study of sublingual varices. Oral Surg 1974;
38:5405.
Gasparini G, Saltarel A, Carboni A. Surgical management of macroglossia:
discussion of 7 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod
2002;94(5):56671.
Gerressen M, Ghassemi A, Stockbrink G, et al. Melkersson-Rosenthal syndrome: case report of a 30-year misdiagnosis. J Oral Maxillofac Surg
2005;63(7):10359.
Gibson J, et al. Geographic tongue: the clinical response to zinc supplementation. J Trace Elem Experim Med 1990;3:2038.
Gonzaga HF, Torres EA, Alchorne MM, et al. Both psoriasis and benign
migratory glossitis are associated with HLA-Cw6. Br J Dermatol 1996;
135(3):36870.

CHAPTER 3
Amir E, Gorsky M, Buchner A, et. al. Physiologic pigmentation of the oral
mucosa in Israeli children. Oral Surg Oral Med Oral Pathol 1991;71(3):3968.
Ashri N, Gazi M. More unusual pigmentations of the gingiva. Oral Surg Oral
Med Oral Pathol 1990;70(4):4459.
Brown FH, Housten GD. Smokers melanosis. A case report. J Periodontol
1991;62(8):5247.
Buchner A, Hansen LS. Amalgam pigmentation (amalgam tattoo) of the
oral mucosa. A clinicopathologic study of 268 cases. Oral Surg Oral Med
Oral Pathol 1980;9(2):13947.
Buchner A, Hansen LS. Melanotic macule of the oral mucosa. A clinicopathologic study of 105 cases. Oral Surg Oral Med Oral Pathol 1979;48(3):
2449.

879

References

Cale AE, Freedman PD, Lumermant H. Pigmentation of the jawbones and teeth
secondary to minocycline hydrochloride therapy. J Periodontol 1988;59(2):
1124.
Ciek Y, Ertas U. The normal and pathological pigmentation of oral mucous
membrane: a review. J Contemp Dent Pract 2003;4(3):7686.
Dummet CO, Barens G. Oromucosal pigmentation: an updated literary review.
J Periodontol 1971;42(11):72636.
Dummett CO. Oral tissue color changes (I). Quintessence Int 1979;10(11):
3945.
Dummett CO, Barens G. Pigmentation of the oral tissues: a rewiew of the
literature. J Periodontol 1967;38:36078.

CHAPTER 4
Akar N. Noma. Lancet 2006;368(9540):989.
Alavandar G. Botryomycosis of mandible. J Indian Dent Assoc 1979;51(6):
1814.
Atespare A, Keskin G, Erin C, et al. Actinomycosis of the tongue: a diagnostic dilemma. J Laryngol Otol 2006;120(8):6813.
Bunch TJ, Thalji MK, Pellikka PA, et al. Respiratory failure in tetanus: case
report and review of a 25-year experience. Chest 2002;122(4):148892.
Caetano M, Amorin I. Erysipelas. Acta Med Port 2005;18(5):38593.
Celestin R, Brown J, Kihiczak G, et al. Erysipelas: a common potentially dangerous infection. Acta Dermatovenerol Alp Panonica Adriat 2007;16(3):
1237.
Cheng AC, Currie BJ. Melioidosis: epidemiology, pathophysiology, and
management. Clin Microbiol Rev 2005;18(2):383416.
Chidzonga MM, Mahomva L. Recurrent noma (cancrum oris) in human
immnuodeficiency virus infection and acquired immunodeficiency syndrome
(HIV and AIDS): report of a case. J Oral Maxillofac Surg 2008;66(8):172630.
Dittrich KC, Keilany B. Tetanus: lest we forget. CJEM 2001;3(1):4750.
Edwards J, Green P, Haase D. A blistering disease: bullous erysipelas. CMAJ
2006;175(3):244.

CHAPTER 5
Aaron LA, Burke MM, Buchwald D. Overlapping conditions among patients
with chronic fatigue syndrome, fibromyalgia and temporomandibular
disorder. Arch Intern Med 2000;160:2217.
Adreani CM, Hill JM, Kaufman MP. Responses of group III and IV muscle
afferents to dynamic exercise. J Appl Physiol 1997;82(6):181117.
Bagheri SC, Farhidvash F, Perciaccante VJ. Diagnosis and treatment of patients
with trigeminal neuralgia. JADA 2004;135:17137.
Bell WE. Orofacial Pains: Classification, Diagnosis, Management, 4th edn.
Chicago: Year Book, 1989;23984.
Bennetto L, Patel NK, Fuller G. Trigeminal neuralgia and its management.
BMJ 2007;334:2015.
Bergdhal M, Bergdhal J. Burning mouth syndrome: prevalence and associated
factors. J Oral Pathol Med 1999;28:3504.
Boggia R. The ups and downs of barodontalgia. Br Dent J 1998;184(5):
209.
Calder IM, Ramsey JD. Odontecrexis the effects of rapid decompression on
restored teeth. J Dent 1983;84(11):31823.
Carlson CR, Bertrand PM, Ehrlich AD, et al. Physical self-regulation training
for the management of temporomandibular disorders. J Orofac Pain 2001;
15(1):4755.

880

Curran SL, Sherman JJ, Cunningham LL, et al. Physical and sexual abuse
among orofacial pain patients: linkages with pain and psychological distress.
J Orofac Pain 1995;9(4):3406.

CHAPTER 6
Albrecht M, Banoczy J, Dinya E, et al. Occurrence of oral leukoplakia and
lichen planus in diabetes mellitus and oral disease. Acta Diabetol 1992;
38(2):5762.
Axell T, Holmstrup P, Kramer IRH, et al. International seminar on oral leukoplakia and associated lesions related to tobacco habits. Community Dent
Oral Epidemiol 1984;12:14554.
Axell TA. A prevalence study of oral mucosal lesions in an adult Swedish
population. Odontol Rev 1976;27(Suppl 36).
Axell T, Pindborg JJ, Smith CJ, et al and an international collaborative group
on oral white lesions with special reference to precancerous and tobaccorelated lesions; conclusions of an international symposium held in Uppsala.
Sweden, May 1821, 1994. J Oral Pathol Med 1996;25:4954.
Bancoczy J, Sugar L. Longitudinal studies on oral leukoplakia. Oral Pathol
1972;1:2659.
Banoczy J, Rigo O. Prevalence study of precancerous Lesions within a complex
screening system in Hungary. Community Dent Oral Epidemiol 1991;19:
265267.
Batsakis JG, Suarez P, El-Naggar AK. Proliferative verrucousleukoplakia and
its related lesions. Oral Oncol 1999;35:3549.
Bouquot JE, Gorlin RJ. Leukoplakia, lichen planus, and other oral keratosis in
23,616 white Americans over the age of 35 years. Oral Surg Oral Med Oral
Pathol 1986;61:37381.

CHAPTER 7
Arduino PG, Porter SR. Herpes simplex virus type 1 infection: overview on
relevant clinico-pathological features. J Oral Pathol Med 2008;37(2):10721.
Arduino PG, Porter SR. Oral and perioral herpes simplex virus type 1 (HSV-1)
infection: review of its management. Oral Dis 2006;12(3):25470.
Chang LY, King CC, Hsu KH. Risk factors of enterovirus 71 infection and
associated hand, foot, and mouth disease/herpangina in children during
an epidemic in Taiwan. Pediatrics 2002;109(6):e88.
Deshpande JM, Nadkarni SS, Francis PP. Enterovirus 71 isolated from a case of
acute flaccid paralysis in India represents a new genotype. Current Science
2003;84;13503.
Dietrich W, et al. Antibodies to tissue transglutaminase as serologic markers
in patients with dermatitis herpetiformis. J Invest Dermatol 1999;113:133.
Eisen D. The clinical characteristics of intraoral herpes simplex virus infection
in 52 immunocompetent patients. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 1998;86:4327.
Farthing P, Bagan JV, Scully C. Mucosal disease series. Number IV. Erythema
multiforme. Oral Dis 2005;11(5):2617.
Klotz RW. Herpetic whitlow: an occupational hazard. AANA J 1990;58(1):
813.
Miller CS, Danaher RJ, Jacob RJ. Molecular aspects of herpes simplex virus I
latency, reactivation and recurrence. Crit Rev Oral Biol Med 1998;9:
54162.
Langenberg AG, Corey L, Ashley RL, et al. A prospective study of new infections with herpes simplex virus type 1 and type 2. N Engl J Med 1999;341:
14328.

References

CHAPTER 8
Abenavoli L, Proietti I, Leggio L, et al. Cutaneous manifestations in celiac
disease. World J Gastroenterol 2006;12(6):84352.
Adams SP. Dermacase. Hand-foot-and-mouth disease. Can Fam Physician
1998;44:98593.
Ajar AH, Chauvin PJ. Acute Herpetic Gingivostomatitis in adults: a review of
13 cases, including diagnosis and management. J Can Dent Assoc 2002;
68(4):247051.
Alam F, Argiriadou AS, Hodgson TA, et al. Primary syphilis remains a cause of
oral ulceration. Br Dent J 2000;189:3524.
Ann M. Arvin. Varicella-Zoster Virus. Clin Microbiol Rev 1996;9(3):36181.
Ban M, Ohtani M, Seishima M, et al. A case of secondary syphilis with mucous
patches on the hard palate. J Dermatol 1995;22:524.
Baroni A, Capristo C, Rossiello L, et al. Lingual traumatic ulceration (RigaFede disease). Int J Dermatol 2006;45(9):10967.
Bastuji-Garin S, Rzany B, Stern RS, et al. Clinical classification of cases of toxic
epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme.
Arch Dermatol 1993;129:926.
Berlucchi M, Meini A, Plebani A, et al. Update on treatment of PFAPAsyndrome: report of five cases with review of the literature. Ann Otol
Rhinol Laryngol 2003;112:3659.
Bouquot JE. Common oral lesions found during a mass screening examination.
J Am Dent Assoc 1986;112(1):507.

Assael LA. Temporomandibular disorders in surgical practice: does science


support treatment decisions? J Oral Maxillofac Surg 2009;67(5):9356.
Barr T, Carmichael NM, Sndor GK. Juvenile idiopathic arthritis: a chronic
pediatric musculoskeletal condition with significant orofacial manifestations.
J Can Dent Assoc 2008;74(9):81321.
Bradley P, James D, Norman B. Injuries of the condylar and coronoid process.
In: Williams JL, ed. Maxillofacial Injuries, Churchill Livingstone 1994;1(2):
40574.
Brooks SL, Brand JW, Gibbs SJ, et al. Imaging of the temporomandibular
joint: a position paper of the American Academy of Oral and Maxillofacial
Radiology. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;83(5):
60918.
Bush FM. Temporomandibular Terminology. J Am Dent Assoc 2008;139(6):
6646.
Caminiti MF, Weinberg S. Chronic mandibular dislocation: the role of nonsurgical and surgical treatment. J Can Dent Assoc 1998;64(7):48491.
Cascos-Romero J, Vzquez-Delgado E, Vzquez-Rodrguez E, et al. The use
of tricyclic antidepressants in the treatment of temporomandibular joint
disorders: systematic review of the literature of the last 20 years. Med Oral
Patol Oral Cir Bucal 2009;14(1):E37.
Cholitgul W, Petersson A, Rohlin M, et al. Clinical and radiological findings in
temporomandibular joints with disc perforation. Int J Oral Maxillofac Surg
1990;19(4):2205.
Da Silva K, Mandel L. Bilateral temporalis muscle hypertrophy: a case report.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;102(1):e13.

CHAPTER 9

CHAPTER 11

Abel MD, Carrasco LR. Ehlers-Danlos syndrome: classifications, oral manifestations, and dental considerations. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 2006;102:58290.
Aho K, Ahnoven P, Lansus A, et al. HLA-B27 and reactive arthritis. Lancet
1973;11:157.
Akovbyan VA, Talanin NY, Arifov SS, et al. Successful treatment of acanthosis
nigricans with etretinate. J Am Acad Dermatol 1994;31:11820.
Alan BS. Continuing medical education: Lichen Planus. Am Acad Dermatol
1991;25:593619.
Alfredo R. Lichen planus and the liver. Int J Dermatol 1992;31(6):3925.
Aria S, Vogelsang GB. Management of graft versus host disease. Blood Rev
2000;14:190204.
Bardin T, Enel C, Cornelis F, et al. Antibiotic treatment of venereal disease
and Reiters syndrome in a Greenland population. Arthritis Rheum 1992;
35:1904.
Barrett AP, Bilous AM. Oral patterns of acute and chronic graft versus host
disease. Arch Dermatol 1984;120:14615.
Bowden PE, Haley JL, Kansky A, et al. Mutation of a type II keratin gene (K6a)
in Pachyonychia Congenita. Nat Genet 1995;10(3):3635.
Breathnach SM. Current understanding of the aetiology and clinical implications of cutaneous graft versus host disease. Br J Dermatol 1986;114:
13943.

Almadori G, Ottaviani F, Del Nimmo M, et al. Monolateral aplasia of the


parotid gland. Ann Otol Rhinol Laryngol 1997;106:5225.
Amin MA, Bailey BM. Congenital atresia of the orifice of the submandibular
duct: a report of 2 cases and review. Br J Oral Maxillofac Surg 2001;
39(6):4802.
Barrett AW, Speight PM. Adenomatoid hyperplasia of oral minor salivary glands.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995;79(4):4827.
Bryant C, Manisali M, Barrett AW. Adenomatoid hyperplasia of palatal minor
salivary glands. J Laryngol Otol 1996;110(2):1679.
Buchner A, Merrell PW, Carpenter WM, et al. Adenomatoid hyperplasia of
minor salivary glands. Oral Surg Oral Med Oral Pathol 1991;71(5):5837.
Daniel SJ, Blaser S, Forte V. Unilateral agenesis of the parotid gland: an unusual
entity. Int J Pediatr Otorhinolaryngol 2003;67:3957.
Ferguson MM, Ponnambalam Y. Aplasia of the parotid gland in Down
syndrome. Br J Oral Maxillofac Surg 2005;43(2):1137.
Gelbier MJ, Winter GB. Absence of salivary glands in children with rampant
dental caries: report of seven cases. Int J Paediatr Dent 1995;5:2537.
Gomez RS, Aguiar MJ, Ferreira AP, et al. Congenital absence of parotid glands
and lacrimal puncta. J Clin Pediatr Dent 1998;22:2478.
Gruber W. Congenitaler mangel beider glandulae submaxillarie bei einem
wohlgebildeten, erwachsenen subjecte. Arch Pathol Anat Physiol 1885;
109:931.

CHAPTER 10
Abe S, Takasaki I, Ichikawa K, et al. Investigations of the run and the attachment of the lateral pterygoid muscle in Japanese. Bull Tokyo Dent Coll
1993;34(3):1359.

CHAPTER 12
Harris M, Toller P. The pathogenesis of dental cysts. Br Med Bull 1975;31:
15963.
Harris M, Goldhaber P. The Production of a Bone Resorbing Factor by Dental
Cysts In Vitro. Br J Oral Surg 1973;10:3348.

881

References

Harris M, Jenkins MV, Bennett A, et al. Prostaglandin Production and Bone


Resorption by Dental Cysts. Nature 1973;245:21315.
Kramer IR. Changing views on oral disease. Proc R Soc Med 1974;67(4):2716.
Kubota Y, Ninomiya T, Oka S, et al. Interleukin-1alpha-dependent regulation of
matrix metalloproteinase-9(MMP-9) secretion and activation in the epithelial
cells of odontogenic jaw cysts. J Dent Res 2000;79(6):142330.
Kubota Y, Yamashiro T, Oka S, et al. Relation between size of odontogenic
jaw cysts and the pressure of fluid within. Br J Oral Maxillofac Surg 2004;
42(5):3915.
Oka S, Kubota Y, Yamashiro T, et al. Effects of positive pressure in odontogenic
keratocysts. J Dent Res 2005;84(10):9138.
Pindborg JJ, Kramer IR, Torloni H. Histological typing of odontogenic tumours,
jaw cysts and allied lesions. International Histological Classification of
tumours. No 5. Geneva: World Health Organization; 1971.
Regezi JA. Odontogenic cysts, odontogenic tumors, fibroosseous, and giant
cell lesions of the jaws. Mod Pathol 2002;15(3):33141.
Shafer WG, Hine MK, Levy BM. A text book of oral pathology. 4th edn.
Philadelphia: WB Saunders: 1983:789.

Dandona P, Thusu K, Cook S, et al. Oxidative damage to DNA in diabetes


mellitus. Lancet 1996;347(8999):4445.
Dickenson AJ, Currie WJ, Avery BS. Screening for syphilis in patients with
carcinoma of the tongue. Br J Oral Maxillofac Surg 1995;33:31920.
DSouza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med 2007;356:194456.
Elmore JG, Horwitz RI. Oral cancer and mouthwash use: evaluation of the
epidemiologic evidence. Otolaryngol Head Neck Surg 1995;113:25361.
Epstein J, Silverman S Jr. HIV-associated malignancies. Oral Surg Oral Med
Oral Pathol 1992;73:193200.
Franceschi S, Barra S, La Vecchia C, et al. Risk factors for cancer of the tongue
and the mouth: a case-control study from Northern Italy. Cancer 1992;
70:222733.
Franceschi S, Talamini R, Barra S, et al. Smoking and drinking in relation to
cancers of the oral cavity, pharynx, larynx, and esophagus in Northern Italy.
Cancer Res 1990;50:65027.

CHAPTER 15
CHAPTER 13
Auluck A, Shetty S, Desai R, et al. Recurrent ameloblastoma of the infratemporal
fossa: diagnostic implications and a review of the literature. Dentomaxillofac
Radiol 2007;36(7):4169.
Barnes L, Eveson JW, Reichart PA, et al. (eds) World Health Organization classification of tumours. Pathology and genetics of head and neck tumours.
IARC Press: Lyon 2005:284.
Chen Y, Wang JM, Li TJ. Ameloblastic fibroma: a review of published studies
with special reference to its nature and biological behavior. Oral Oncol
2007;43(10):9609.
Daley TD, Multari J, Darling MR. A case report of a solid keratocystic odontogenic tumor: is it the missing link? Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 2007;103(4):5125.
Gonzlez-Alva P, Tanaka A, Oku Y, et al. Keratocystic odontogenic tumor:
a retrospective study of 183 cases. J Oral Sci 2008;50(2):20512.
Habibi A, Saghravanian N, Habibi M, et al. Keratocystic odontogenic tumor:
a 10-year retrospective study of 83 cases in an Iranian population. J Oral
Sci 2007;49(3):22935.
Hans Peter Philipsen et al. Classification of odontogenic tumours. A historical
review. Journal of Oral Pathology & Medicine 35(9):5259.
Pindborg JJ. The Calcifying Epithelial Odontogenic Tumor. Review of Literature
and Report of An Extra-Osseous Case. Acta Odontologica Scandinavica
1966;24(4):41930.
Kitsoulis P, Charchanti A, Paraskevas G, et al. Adamantinoma. Acta Orthop
Belg 2007;73(4):42531.
Madras J, Lapointe H. Keratocystic odontogenic tumour: reclassification of
the odontogenic keratocyst from cyst to tumour. J Can Dent Assoc 2008;
74(2):16565.

CHAPTER 14
Ankathil R, Mathew A, Joseph F, et al. Is oral cancer susceptibility inherited?
Report of five oral cancer families. Oral Oncology 1996;32B:637.
Block G. Vitamin C and cancer prevention: the epidemiologic evidence. Am J
Clin Nutr 1991;53(Suppl 1):270S82S.
Cogliano V, Straif K, Baab R, et al. Smokeless tobacco and tobacco-related
nitrosamines. Lancet Oncology 2004;5:708.

882

Acton RT, et al. Association of MHC genes with levels of caries-inducing


organisms and caries severity in African-American women. Human Immunol
1999;60:9849.
Aherne CA, OMullane D, Barrett BE. Indices of root surface caries. J Dent Res
1990;69(5):12226.
Alvarez JO, Navia JM. Nutritional status, tooth eruption, and dental caries:
a review. Am J Clin Nutr 1989;49(3):41726.
Angmar-Mnsson B, ten Bosch JJ. Advances in methods for diagnosing coronal
cariesa review. Adv Dent Res 1993;7(2):709.
Anusavice KJ. Present and future approaches for the control of caries. J Dent
Educ 2005;69(5):53854.
Arends J, Christoffersen J. The nature of early caries lesions in enamel. J Dent
Res 1986;65(1):211.
Bader JD, Shugars DA. A systematic review of the performance of a laser
fluorescence device for detecting caries. J Am Dent Assoc 2004;135(10):
141326.
Bachrach FH, Young M. A comparison of the degree of resemblance in dental
characters shown in pairs of twins of identical and fraternal types. Br Dent
J 1927;48:1293304.
Baehni PC, Guggenheim B. Potential of diagnostic microbiology for treatment and prognosis of dental caries and periodontal diseases. Crit Rev Oral
Biol Med 1996;7(3):25977.
Banting DW. Diagnosis and prediction of root caries. Adv Dent Res 1993;
7(2):806.

CHAPTER 16
Barr PN, Brown NC, Hammer JE. Hyperphosphatasia: report of 2 cases with
dental findings. Periodontics 1964;2:20915.
Carranza FA Jr, Cabrini RL, Lofrez Otero. Histometric analysis of interadicular
bone in protein deficient animals J Periodontal Res 1969;4:292.
Cawson RA 1962. The Oral changes in Gargoylism Proceeding of the Royal
Society of Medicine 1962;55:106677.
Charon J, Margenhagen S, Gallin J. Ginvitis and oral ulceration in patients
with neutrophil destruction. J Oral Pathol 1985;14:1595.
Corman KS, Crane A, Wang HY, et al. The interleukin I Genotype as a severity
factor in adult periodontal disease. J Clin periodontal 1997;24:727.

References

Glickman I: Acute vitamin C deficiency and periodontal disease. The periodontal tissue of guinea pig in acute vitamin C deficiency. J Dent Res 1948;27:9.
Frandsen AM, Periodontal tissue changes in deficient young rats. Acta
Odontol Scand 1963;21:19.
Lindhe J, Attstrom R. Gingival exudation during menstrual cycle. J Periodontal
Res 1967;2:1948.
Mann AW, Spices TD, springs M. Oral manifestation of vitamin B complex
deficiencies, J Dent Res 1941;20:269.
Marazita M, Lu H, Cooper M, et al. Genetic segregation analysis of IgG2
levels. Am J Hum Gent 1996;58:10429.

CHAPTER 17
Al-Dlaigan YH, Shaw L, Smith A. Dental erosion in a group of British 14-yearold, school children. Part I: Prevalence and influence of differing socioeconomic backgrounds. BDJ 2001;190(3):1459.
Aw TC, Lepe X, Johnson GH, et al. Characteristics of noncarious cervical
lesions: a clinical investigation. J Am Dent Assoc 2002;133:72533.
Bartlett D, Ganss C, Lussi A. Basic Erosive Wear Examination (BEWE): a new
scoring system for scientific and clinical needs. Clin Oral Investig 2008;
12(Suppl 1):S658. Epub 2008 Jan 29.
Bartlett DW, Shah P. A critical review of non-carious cervical (wear) lesions and
the role of abfraction, erosion, and abrasion. J Dent Res 2006;85(4):30612.
Bell EJ, Kaidonis J, Townsend GC. Tooth wear in children with Down syndrome.
Aust Dent J 2002;47(1):305.
Bodecker CF. Local acidity: a cause of dental erosion-abrasion. Ann Dent
1945;4(1):505.
Centerwall BS, Armstrong CW, Funkhouser LS, et al. Erosion of dental
enamel among competitive swimmers at a gas-chlorinated swimming
pool. Am J Epidemiol 1986;123:6417.
Chaudhry SI, Harris JL, Challacombe SJ. Dental erosion in a wine merchant:
an occupational hazard? Br Dent J 1997;182:2268.
Chikte UM, Grobler SR, Kotze TJ. In vitro human dental enamel erosion by
three different wine samples. SADJ 2003;58:3602.
Chikte UM, Naidoo S, Kolze TJ, et al. Patterns of tooth surface loss among
winemakers. SADJ 2005;60:3704.

Jowett NI, Cabot IB. Patients with cardiac disease: considerations for the
dental practitioner. BDJ 2000;189(6):297302.
Lessard E, Glick M, Ahmed S, et al. The patient with a heart Murmur,
Evaluation, assessment and dental considerations. JADA 2005;136:34756.
Little JW, Falace DA, Miller CS, et al. Dental management of the medically
compromised patient, 6th edn. St. Louis: C.V. Mosby Co., 2002.

CHAPTER 19
Abdelsayed RA, Eversole LR, Singh BS, et al. Gigantiform cementoma: clinicopathologic presentation of 3 cases. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 2001;91(4):43844.
Adekeye EO, Edwards MB, Goubran GF. Fibro-osseous lesions of the skull,
face and jaws in Kaduna. Nigeria Br J Oral Surg 1980;18:5772.
Agazzi C, Belloni L. Gli odontomi duri dei mascellari: contributo clinicorontgenologico e anatomo-microscopico con particolare riguardo alle
forme ad ampia estensione e alla comparsa familiare. Arch Ital Otol 1953;
64(Suppl 16):3102.
Albright F. Polyostotic fibrous dysplasia: a defense of the entity. J Clin
Endocrinol 1947;7:30724.
Albright F, Butler AM, Hampton AO, et al. Syndrome characterized by osteitis
fibrosa disseminata, areas of pigmentation and endocrine dysfunction,
with precocious puberty in females: report of five cases. N Engl J Med
1937;216:72746.
Benjamins CE. Das osteoid-fibroma mit atypischer Verkalkung im sinus frontalis Acta Otolaryngol 1938;26:2643.
Bradley ES Jr, Leake D. Ossifying fibroma involving the maxilla and the
mandible; report of a case. Oral Surg Oral Med Oral Pathol 1968;26:
60514.
Cannon JS, Keller EE, Dahlin DC. Gigantiform cementoma: report of two
cases (mother and son). J Oral Surg 1980;38:6570.
Daffner RH, Kirks DR, Gehweiler JA Jr, et al. Computed tomography of
fibrous dysplasia, AJR Am J Roentgenol 1982;139:9438.
Edwards PA, Corio RL. Benign fibro-osseous lesions of the jaws. Ear Nose
Throat J 1984;63:38392.

CHAPTER 18

CHAPTER 20

Brand HS, Abraham-Inpijn L. Cardiovascular responses induced by dental


treatment. Eur J Oral Sc 1996;104:24552.
Carmona IT, Scully C. An update on the controversies in bacterial endocarditis
of oral origin. Oral surg Oral Med Oral Pathol Oral Radiol Endod 2002;
93:66070.
Dajani AS, Taubert KA, Wilson W, et al. Prevention of bacterial endocarditis:
Recommendations by the American Heart Association. JAMA 1997;277:
1794801.
Demmer RT, Desvarieux M. Periodontal infections and cardiovascular disease:
the heart of the matter. J Am Dent Assoc 2006;137(Suppl):14S20S.
Genco R, Offenbacher S, Beck J. Periodontal disease and cardiovascular
disease: epidemiology and possible mechanisms. J Am Dent Assoc 2002;
133(Suppl):14S22S.
Glick M. Screening for traditional risk factors for cardiovascular disease: a review
for oral health care providers. J Am Dent Assoc 2002;133(3):291300.
Imperiale TF, Horwitz RI. Does prophylaxis prevent postdental infective endocarditis? A controlled evaluation of protective efficacy. Am J Med 1990;
88:1316.

Aaron Samsula, Alan Menter M. Persistent rash on the face and lips. Proc
(Bayl Univ Med Cent) 2003;16(4):48890.
Abaza Nabil et al. The role of labial salivary gland biopsy in the diagnosis of
Sjogrens syndrome: Report of Three Cases. J Oral Maxillofac Surg 1993;
51:57480.
Anavi Y, Mintz S. Benign Lymphoepithelial lesions of the sublingual gland.
J Oral Maxillofac Surg 1992;50:111113.
Andrade RE, Hagenk A, Manivel JC. Distribution and immuno phenotype of
the inflammatory cell population in the benign lymphoepithelial lesion.
Human Pathol 1988;19:93241.
Anhalt JG. Paraneoplastic pemphigus- An autoimmune mucocutaneous disease
associated with neoplasia. N Engl J Med 1990;323:172935.
Anusaksthrin O, Dolby AE. Autoimmunity and periodontal disease. J Oral
Pathol 1991;20:1017.
Altman RD, Medsgar TA Jr, Bloch DA, et al. Predictors of survival in systemic
sclerosis. Arthritis Rheum 1991;34:40313.
Artlett CM, Smith JB, Jimenez SA: New perspectives on the etiology of systemic
sclerosis. Mol Med Today 1999;5(2):748.

883

References

Auluck A, KM Pai, C Shetty, et al. Mandibular resorption in progressive systemic


sclerosis: a report of three cases. Dentomaxillofacial Radiology (2005);34:
3846.
Barbara R et al. The pathogenic effect of Ig G 4 antibodies in endemic pemphigus foliaceous. N Engl J Med 1989;320:14639.

CHAPTER 21
Britton WJ, Lockwood DN. Leprosy. Lancet 2004;363(9416):120919.
de Abreu MA, Michalany NS, Weckx LL, et al. The oral mucosa in leprosy:
a clinical and histopathological study. Rev Bras Otorrinolaringol (Engl Ed)
2006;72(3):3126.
Lockwood D. Leprosy. Clin Evid 2006;(15):107987.
Morgado de Abreu MA, Mota de Avelar Alchorne M, Michalany NS, et al.
The oral mucosa in paucibacillary leprosy: a clinical and histopathological
study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;[Epub
ahead of print].
Ridley DS, Jopling WH. Classification of leprosy according to immunity. A fivegroup system. Int J Lepr Other Mycobact Dis 1966;34(3):25573.
Scollard DM, Skinsnes OK. Oropharyngeal leprosy in art, history, and medicine.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87(4):46370.
Srinivasan S, Nehru VI, Bapuraj JR, et al. CT findings in involvement of the
paranasal sinuses by lepromatous leprosy. Br J Radiol 1999;72(855):2713.
Tuberculosis in Canada 2005 Pre-Release a publication by the Public Health
Agency of Canada; report accessed at http://www.publichealth.gc.ca/
tuberculosis Jan 2007.
WHO facts sheet at http://www.who.int/mediacentre/factsheets/fs104/en/
index.html.
Yepes JF, Sullivan J, Pinto A. Tuberculosis: Medical Management update. Oral
Surg Oral Med Oral Pathol Oral Radiol Endod 2004;98:26773.

CHAPTER 22
Alexander WN, Nagy WW. Gonococcal arthritis of the temporomandibular
joint. Report of a case. Oral Surg Oral Med Oral Pathol 1973;36(6):80913.
Barsh LI. Molluscum contagiosum of the oral mucosa. Report of a case.
Oral Surg Oral Med Oral Pathol 1966;22(1):426.
Bonci A, Di Lernia V, Lo Scocco G, et al. A patient with primary syphilis of the
finger. Acta Derm Venereol 2001;81(5):3823.
Brown TJ, Yen-Moore A, Tyring SK. An overview of sexually transmitted
diseases. Part I. J Am Acad Dermatol 1999;41(4):51132.
Bruce AJ, Rogers RS 3rd. Oral manifestations of sexually transmitted diseases.
Clin Dermatol 2004;22(6):5207.
Buntin DM, Rosen T, Lesher JL Jr, et al. Sexually transmitted diseases: bacterial
infections. Committee on Sexually Transmitted Diseases of the American
Academy of Dermatology. J Am Acad Dermatol 1991;25(2 Pt 1):28799.
Buntin DM, Roser T, Lesher JL Jr, et al. Sexually transmitted diseases: viruses and
ectoparasites. Committee on Sexually Transmitted Diseases of the American
Academy of Dermatology. J Am Acad Dermatol 1991;25(3):52734.
Chaudhary M, Kulkarni M. Molluscum contagiosum in human immunodeficiency virus infected patients. Indian J Dent Res 2008;19(2):1559.
Chue PW. Gonococcal arthritis of the temporomandibular joint. Oral Surg
Oral Med Oral Pathol 1975;39(4):5727.
Cohen MS, Shugars DC, Fiscus SA. Limits on oral transmission of HIV-1.
Lancet 2000;356(9226):272.
Note: References for the Radiology section uploaded on the web link.

884

CHAPTER 23
Akca AE, Ucok O, Akar A, et al. The role of lipoid proteinosis in gingival
hypertrophy. Quintessence Int 2004;35(7):5846.
Alpoz AR, Coker M, Celen E. The oral manifestations of MaroteauxLamysyndrome (mucopolysaccharidosis VI): A case report. Oral Surg Oral
Med Oral Pathol Oral Radiol Endod 2006;101:6327.
American Dietetic Association. Position of The American Dietetic Association:
Oral health and nutrition. J Am Diet Assoc 1996;96(2):1849.
Ardekian L, Peled M, Rosen D, et al. Clinical and radiographic features of
eosinophilic granuloma in the jaws: Review of 41 lesions treated by surgery
and low-dose radiotherapy. Oral Surg Oral Med Oral Pathol Oral Radiol
Endod 1999;87:23842.
Asaumi J, Konouchi H, Hisatomi M, et al. Two cases of polyostotic eosinophilic granuloma. Dentomaxillofac Radiol 2000;29(6):3825.
Bamji MS. Less recognized micronutrient deficiencies in India. Nutrition
Foundation of India. April 1998.
Bamji MS, Arya S, Sarma KVR, et al. Impact of long-term low-dose B-complex
vitamin supplements on the vitamin status and psychomotor performance
of rural school boys. Nutr Res 1982;2:14753.
Banoczy J, Hadas E, Estzari I. Three year results of clinical longitudinal experiments with sorbitol. Caries Res 1981;15:201.
Bari AU. Congenital erythropoietic porphyria in three siblings. Indian J Dermatol
Venereol Leprol 2007;73(5):3402.
Bazopoulou-Kyrkanidou E, Tosios KI, Zabelis G, et al. Hyalinosis cutis et
mucosae: gingival involvement. J Oral Pathol Med 1998;27(5):2337.

CHAPTER 24
Acharya AB, Sivapathasundharam B. Forensic Odontology, In: Rajendran R,
Sivapathasundharam B, (eds). Shafers Textbook of Oral Pathology, 5th
edn, Elsevier, New Delhi, 1199227.
Acharya AB, Taylor JA. Are a minimum number of concordant matches needed
to establish identity in Forensic Odontology? J Forensic Odonto-Stomatology
2003;21(1):613.
American Board of Forensic Odontology, Inc, ABFO Guidelines and Standards,
in: Bowers CM, Bell GL. (eds). Manual of Forensic Odontology, 3rd edn,
Printing Specialists, Vermont, 1995;33441.
Arany S, Iino M, Yoshioka N. Radiographic survey of third molar development
in relation to chronological age among Japanese Juveniles. J Forensic Sci
2004;49(3):5348.
Austin-Smith D, Maples WR. The reliability of skull/photograph superimposition in individual identification. J Forensic Sci 1994;39(2):44655.
Ball J. The current status of lip prints and their use in identification. J Forensic
Odonto-Stomatology 2002;20(2):436.
Bcart A, Hdouin V, Martin-Bouyer L, et al. The Oral Health Status of Drug
Addicts: A Prison Survey in Lille, France. J Forensic Odonto-Stomatology
1997;15(2):279.
Bilge Y, Kedici PS, Alako YD, et al. The identification of a dismembered
human body: A multidisciplinary approach. Forensic Sci Int 2003;137(23):
1416.
Bockholdt B, Maxeiner H. Hemorrhages of the tongue in the postmortem
diagnostics of strangulation. Forensic Sci Int 2002;126:21420.
Borrman HIM, DiZinno JA, Wasn J, et al. On denture marking. J Forensic
Odonto-Stomatology 1999;17(1):206.

Index

A
ABCDE warning signs, 369
Abdominal ultrasonography, 397
Abfraction, 458, 464
Abrasion, 452, 460
Acanthomatous ameloblastoma, 335
Acanthosis nigricans, 227
Accessory cusps, 44
Acid-enzyme theory, 407
Acinic cell adenocarcinoma, 297
Ackermans tumor, 366
Acquired immune deficiency syndrome
(AIDS), 99
Acquired immunity, 590
Acquired melanocytic nevus, 348
Acrodermatitis enteropathica, 228
Acrodynia, 63
Acromegaly, 536
Acrosclerosis, 601
Actinomycosis, 86
Activated partial thromboplastin time, 498
Acute adrenal insufficiency, 547
Acute dental caries, 413
Acute intermittent porphyria, 642, 643
Acute leukemia, 492
Acute lymphocytic leukemia, 386, 492
Acute lymphonodular pharyngitis, 90
Acute monocytic leukemia, 492
Acute necrotizing ulcerative gingivitis
(ANUG), 204, 452
Acute pain, 115
Acute pseudomembranous candidiasis,
135, 154
Acute radiation syndrome, 699
Acute sinusitis, 105
Acute suppurative osteomyelitis, 433
Added filtration, 694
Addisons disease, 66, 546
Adenocarcinoma, 295, 297
Adenoid cystic carcinoma, 298
Adenomatoid odontogenic tumor, 338
Adherence and adhesions, 247
Adult periodontitis, 442
Aerodontalgia, 118
African Kaposis sarcoma, 377
Agammaglobulinemia, 456
Age estimation methods, 669
Agenesis, 266
Aggressive periodontitis, 442
Aglossia, 22

Agnathia, 30
Agranulocytic angina, 491
Agranulocytosis, 455
Ankyloglossia, 23
classification, 23
ALARA principle, 704, 728
AlbersSchnberg disease, 578
Alcohol, 139, 384
Alkaptonuria, 76
Allergic rhinitis, 506
Allergic salute, 507
Allergic shiners, 507
Allodynia, 111
Allowable occupational dose, 704
Amalgam tattoo, 63
Ameloblastic
carcinoma, 363
fibrodentinoma, 342
fibroma, 342
fibro-odontoma, 342
fibrosarcoma, 366
sarcoma, 366
Ameloblastoma, 33
Amelogenesis imperfecta, 53, 54, 77
Amine odor test, 632
Amino acids, 635
Amlodipine, 446
Amorphous calcium phosphate, 464
Amputation caries, 401
Amyloid, 642
Amyloidosis, 642
Anaphylaxis, 481
Anatomical variations, 842
Androgens, 445
Andy Gump facies, 255
Anemia, 456, 485
Aneurysmal bone cyst, 322
Angina pectoris, 478
Angiogenesis, 385, 401
Angiolipoma, 355
Angiosarcoma, 377
Angles classification of malocclusion, 255
Angular cheilitis (perleche), 155, 156, 487
Anhidrotic ectodermal dysplasia, 222
Ankyloglossia, 23
Ankylosis, 253
Ann Arbor classification, 495
Annual dose limits, 710
Anodontia, 45
Anorexia nervosa, 524

Anorexia, 287
Antemortem radiographs, 657
Anterior median lingual cyst, 323
Antidiuretic hormone, 538
Antihypertensive therapy, 477
Anti-mongoloid eyelids, 646
Antinuclear antibody (ANA), 599
Anti-Saccharomyces cerevisiae antibodies, 624
Antiseptic mouthrinses, 508
Antistreptolysin O titers, 480
Antoni type B cells, 356
Antral polyps, 318
Antrocystectomy, 330
AP axial projection, 752
APECED, 600
Aphthous stomatitis, 211, 591
Aphthous ulcers, 104, 210, 211, 520, 591
Apical periodontal cyst, see Periapical cyst
Aplastic anemia, 448
Apnea, 512
Apple-green birefringence, 642
Areca nut, 383, 463
Argyll Robertson pupil, 627
Argyria, 64
Aromatic hydrocarbons, 383
Arrested caries, 412
Arsenic, 63
Arteriovenous malformations, 359
Arthrography, 795796
Articular capsule, 239
Articular disk, 239, 240, 246
Articular eminence, 239
Artifacts, 820
Aryl hydrocarbon hydroxylase, 383
Aschers syndrome, 27
Aschoffs nodules, 480
Ascorbate, 639
Ascorbic acid, 499, 639
Ash leaf macules, 233
AshboeHansen sign, 212
Aspergillosis, 109, 207, 615
Aspiration biopsy, 393
Aspirin, 483, 500
Asteroid bodies, 290, 619
Asthma, 508, 510
Atherosclerosis, 478
Atrophic glossitis, 487
Atrophic lichen planus, 148, 150
Attached gingiva, 210, 312, 346
Attrition, 459, 670

885

Index

Atypical facial pain, 126


Atypical odontalgia, 125
AUPD cells, 552
Aura, 530
Auriculocondylar syndrome, 33
Auspitzs sign, 221, 234
Autoimmune hepatitis, 527
Autoimmune hypothyroidism atrophic
thyroiditis, 539
Hashimotos thyroiditis, 539
Autoimmune polyendocrinopathy-candidiasisectodermal dystrophy, 551, 600
Autoimmune theory, 407
Autoimmunity, 590
Avulsion, 673
Azotemia, 514
A fibers, 112

B
Bacille CalmetteGurin (BCG) vaccination,
610
Baclofen, 122
Bacterial pharyngitis, 508
Bacterial sialadenitis, 282
Baelzs disease, 283
Barodontalgia, 118
Barosinusitis, 119
Barrel-shaped rib cage, 577
Bartholins duct, 267
Basal cell adenoma, 293
Basal cell carcinoma, 367
Basal cell nevus syndrome, 342
Battles sign, 263
Bay cyst, 320
B-cell immunity, 590
Beam limiting devices, 706
Bean-shaped cyst, 347
Bean-shaped radiopacities, 646
Bearded infant appearance, 584
BeckwithWiedemann syndrome, 27
Beedis, 381, 382, 383
Behets disease or syndrome, 31, 216
Bejel, 626
Bells palsy, 529
Bence Jones proteins, 497
Benign chondroblastoma, 351
Benign lymphoepithelial lesion, 277, 591
Benign migratory glossitis, 24
Benign mucosal cysts, 317
Benign mucous membrane pemphigoid, 188,
212
Benign osteoblastoma, 351
Benzopyrene, 383
Benzydamine hydrochloride, 25, 401
Beriberi, 640
BernardSoulier syndrome, 500
Betel quid chewers, 463
Betel quid lichenoid lesion, 153
Bifid condyles, 33
Bifid tongue, 24
Bilaminar zone, 240
Bilirubin, 61
Biliverdin, 62
Biological indicators, 671
Bird face deformity, 255
Bismuth grip, 63

886

Bisphosphonates, 588
Bite mark procedures, 672
Black beard sign, 588
Black box, 522
Black hairy tongue, 18
Black tarry stools, 523
Blade of grass lesion, 588
Blank radiograph, 820
Blastomycosis, 107, 613
Bleeding time, 498
Bleomycin, 402
Blepharosis moniliformis, 646
BlochSulzberger syndrome, 231
Blood dyscrasias, 440
Blood pressure, 475
Blood studies, 397
Bloody crusted appearance, 191
Blue bloaters, 510
Blue colored sclera, 577
Blue dye, 394
Blue, purple or gray tinted sclera,
577
Blurred image, 817
Bone scanning, 788
Bohns nodules, 316
Bollingers granules, 88
Botryoid odontogenic cyst, 311
Botryomycosis, 88
Bouins solution, 219
Boundary lubrication, 247
Brachytherapy, 400
Bradykinesia, 531
Brazilian pemphigus, 596
Breathlessness, 475, 505
Bremsstrahlung radiation, 688, 689
BreschetGorham syndrome, 585
Brim sign, 588
Brittle bone disease, 576
Broad saddle nose, 644
Bronchodilators, 510
Bronchogenic carcinomas, 511
Bronze diabetes, 67
Brown tumors, 516, 543
Bruck syndrome, 578
Brueghels syndrome, 532
Brush biopsy, 395, 398
Bruxism, 459
Buccal space, 427, 429
Bulimia, 287
Bulimia-related sialadenosis, see Anorexia
Bulimia nervosa, 524
Bull neck appearance, 431
Bulla spreading sign, see AshboeHansen
sign
Bulldog jaw, 628
Bulls eye lesion, 190
Bullous impetigo, 84, 193
Bullous pemphigoid, 185, 212, 596
Burkitts lymphoma, 496
Burning feet, 514
Burning mouth sensation, 487
Burning mouth syndrome, 127
Burning tongue, 272
Burtonian line, 64
BusseBuschke disease, 109
Butterfly rash, 84, 598

C
Caf-au-lait macules, 536
pigmentations, 66
spots, 234, 576
Caffeys disease, 583
CaffeySilverman syndrome, 583
Calcifying epithelial odontogenic tumor, 337
Calcifying odontogenic cyst, 312, 339
Calcium, 477
channel blockers, 446
hydroxide, 463
oxide, 463
Calculus, 451
Cameron ulcers, 523
Canalicular adenoma, 293
Cancrum oris, see Noma
Candida leukoplakia, see Chronic hyperplastic
candidiasis
Candidiasis, 101, 140, 153
classification, 154
Canine space, 429
Canker sores, 591
Capillary fragility test, 498
Capillary malformations, 359
Caplans syndrome, 594
Capsulitis, 249
Carbamazepine, 122
Carbohydrates, 634
Carbon monoxide, 383, 531
Carbonic acid, 463
Carboxymethylcellulose, 401
Carcinogens, 384
Carcinoma ex ameloblastoma, 364
Carious lesions, 410, 425
Carotenoids, 637
Carotid sheaths, 393
Carpal tunnel syndrome, 537, 540
Cascading waterfall appearance, 58
Casein phosphopeptide, 464
Caseous necrosis, 608, 609
Cat-scratch disease, 89
Causalgia, 311
Caviar lesions, 16
Celiac disease, 53, 214
Cell mediated immunity, 157, 590
Cell rests of Serres, 305
Cemental tears, 452
Cementicles, 470
Cementifying fibroma, 571
Cementoblastoma, 343
Cemento-ossifying fibroma, 571
Cephalometric radiography, 725
Cervical burn out, 461
Cervical enamel extensions, 43
Cervical esophagus, 393
Cervical lymphadenopathy, 508
Cetuximab, 402
Chalky, ground glass, granular and salt and
pepper appearance of bone, 516
Chancre, 206, 612, 626
Characteristic radiation, 688, 689
Charcots joints, 627
ChediakHigashi syndrome, 453, 491
Cheilitis glandularis, 283
Cheilitis glandularis apostematosa, 283
Cheilitis granulomatosa, 289, 620

Index

Chelation, 406
Chemical burn, 135
Chemical indicator, 706
Chemo-osteonecrosis, 588
Chemotherapeutic agents, 401
Chemotherapy, 104, 401, 845
Cherubism, 580
Chest pain, 475, 505
Chicken pox, 178, 201
Chicken-wire appearance, 490
Chicken-wire pattern, 351
Chinese script writing, 575
Chlamydial infections, 631
Chloasma, 64
Chloasma gravidarum, 551
Chloromas, 493
Chloroquine, 64, 65
Cholesterol clefts, 320
Cholesterol crystals, 318, 326
Chondroma, 350
Chondrosarcomas, 261, 372
Christmas disease, 503
Christmas tree pattern, 226
ChristSiemensTouraine syndrome, see
Hypohidrolic ectodermal dysplasia
Chromogenic bacteria, 73
Chronic atrophic candidiasis, 155
Chronic bronchitis, 505, 509
Chronic dental caries, 413
Chronic diffuse sclerosing osteomyelitis, 437
Chronic fatigue syndrome, 90
Chronic focal sclerosing osteomyelitis, 436
Chronic myelocytic leukemia, 493
Chronic hyperplastic candidiasis, 154
Chronic irreversible pulpitis, 414, 418
Chronic leukemia, 493
Chronic lymphocytic leukemia, 493
Chronic lymphoid leukemia, 493
Chronic mucocutaneous candidiasis
(CMC), 156
Chronic obstructive airway disease, 509
Chronic obstructive pulmonary disease, 509
Chronic osteomyelitis with proliferative
periostitis, see Periostitis ossificans
Chronic pain, 115
Chronic periapical abscess, 415
Chronic renal failure, 513
Chronic sclerosing sialadenitis, 285
Chronic sinusitis, 105
Chronic suppurative osteomyelitis, 434
Chronological hypoplasias, 52
Chvostek sign, 544
Chylothorax, 586
Cicatricial pemphigoid, 186, 213, 596
Cigarettes, 139, 381, 383
Cigars, 381
Ciprofloxacin, 79
Circumferential caries, 401
Circumscribed morphea, 601
Circumvallate papillae, 16
Cisplatin, 402
Civatte, hyaline, cytoid bodies, 150
Classification and staging system for oral
leukoplakia, 138
Classification of ankyloglossia, 23
Classification system for Kaposis sarcoma, 377

Clay modeling, 667


Clear or gargoyle cells, 644
Cleft lip, 27
Cleft palate, 27
Cleft tongue, 24
Cleidocranial dysplasia and Maroteaux-Lamy
syndrome, 307
Clinical forms of leukoplakia, 140
Closed lock, 248
Clotting mechanism, 497
Cluttons joints, 628
Cobblestone appearance, 622
Cod fish vertebrae, 578
Codmans triangle appearance, 371
Codmans tumor, see Benign chondroblastoma
Coffee ground vomitus, 523
Cogans lid twitch, 604
Coherent scatter, 695
Cold test, 422
Collagenases, 385
Collarette, 193
Collimators, 694
functions, 694
types, 694
Colloid bodies, 694
clvatte, 694
hyaline, 694
cytoid, 694
Color changes in burned teeth, 661
Colpitis macularis, 631
Comb sign, 522
Commissural lip pits, 26
Complex odontome, 341
Composite odontome, 341
Compound hemangiomas, 358
Compound nevus, 348
Compton effect, 696
Compton scatter, 695
Computed tomography (CT), 760762
Concept of referred pain, 114
Concrescence, 36
Condensing osteitis, 414
Condylar aplasia, 33
Condylar hyperplasia, 33
Condylar neck fractures, 262
Condyloma acuminatum, 347, 630
Cone-beam computed tomography (CBCT), 762
Cone cuts, 741
Congenital heart disease, 479
hemoglobinopathies, 490
lip pits, 26
rubella syndrome, 91
syphilis, 628
teeth, 46
Congenital aplasia, see Agenesis
Congenital epulis of newborn, 355
Congo red staining, 642
Conns syndrome, 549
Contact stomatitis, 209
Cooper type scissors, 659
Coronary artery disease, 847
Coronary heart disease, 478
Coronoid hyperplasia, 34
Corrosion, see Erosion
Cotton-wool appearance, 438, 588
Cough, 504

Coxa vara, 577


Cowdry type A, 240
CPP-ACP, 464
Cracked tooth syndrome, 466
Cracker sign, 268
Cranial arteritis, 591
Cranial suture pattern, 664
Craniotabes, 638
Crazing, 660
C-reactive protein, 253, 624
Crescent-shaped lesions, 464
CREST syndrome, 603
Cretinism, 539
Cricoid cartilage, 393
Crohns disease, 520, 521, 622
Croup, 505
Cryptococcosis, 109, 207
Cullens sign, 90
Cushings syndrome, 545
Cusp of Carabelli, 44
Cyanosis, 68, 475
Cyclic neutropenia, 455, 492
Cyclosporine, 446
Cylindertype implants, 851
radiographic appearance, 851
Cystic fibrosis, 511
Cystic hygroma, 326, 792
Cystic PIOC, 364
Cysticercosis, 327

D
Dane particle, 526
Dapsone, 611
Dark-field microscopic examination, 613
Darkroom infrastructure, 804
Dark spots, 819
Daylight processor, 808
De Mussets sign, 627
De novo ameloblastic carcinoma, 364
Dead tracts, 468
Debulking, 399
Decortication, 436
Deep cervical nodes, 12
Deep fascia, 426
Deep fungal infections, 613
Deep hemangiomas, 207
Degenerative joint diseases 358
Demirjians method, 250
DennieMorgan lines, 670
Dens evaginatus, 41
Dens in dente, 40
Dens invaginatus, 40, 41
Dental attrition, 670
Dental caries, 405
classification, 410
Dental computed tomography, 849
Dental floss, 417, 460
Dental fluorosis, 55, 79
Dental identification, 654
procedure, 655
Dental implants, 842845
forms, 842
historical perspectives, 842
indications, 844
patient management, 845
post-operative evaluation, 857

887

Index

Dental implants (Contd.)


treatment options, 842
types, 843
Dental plaque, 406, 440, 442
Dental records, 657
Dental transposition, 47
Dentifrices, 460
Dentigerous cyst, 306
Dentin dysplasia, 58, 78
Dentinal caries, 414
Dentinal hypersensitivity, 464
Dentinogenesis imperfecta, 55, 56, 77
Denture marking systems, 663
Dermatitis herpetiformis, 180
Dermoid cysts, 327
Desmoglein-I, 181
Desmoplastic fibroma, 344
Developmental cysts, 304
Diabetes, 384, 454, 846
insipidus, 538
mellitus, 288
mellitus-associated gingivitis, 440
mellitus type I insulin dependent
(IDDM), 600
Diabetic ketoacidoses, 108
Diascopy test, 68
Digastric muscle, 244
Digital radiography, 707
Dilaceration, 38
Dimple wart, see Molluscum contagiosum
Diphtheria, 83
Diphtheritic membrane, 83
Diplopia, 390
Direct digital receptors, 732
Direct target theory, 399
Discal ligaments, 241
Discoid lupus erythematosus, 170
Disinfection, 104
Disk displacement, 248
with reduction, 248
without reduction, 248
Disk thinning and prerforation, 246
Dislocation, 248
types, 249
Displacement of diskcondyle complex, 248
hypermobility, 248
Disseminated form of histoplasmosis, 107
Disseminated intravascular coagulation
(DIC), 498
Distodens, 46
Distomolar, 46
Doppler ultrasound, 791
Dose limits, 704
Double lip, 26
Down syndrome, 22, 35, 43, 326
Driven snow patterns, 337
Drug influenced enlargements, 440
Drug influenced gingival diseases, 440
Drug-induced pigmentation, 64
Dry beriberi, 640
Dry mouth, 223, 269, 272
Duchenne muscular dystrophy, 532
Dwarfism, 535
Dyschroic fog, 820
Dysesthesia, 387
Dysgeusia, 518

888

Dyskeratosis congenita, 166, 225


Dysostosis multiplex, 645
Dyspnea, see Breathlessness
Dystonia, 532
Dystrophic calcification, 16
Dystrophic epidermolysis bullosa, 194

E
Eagles syndrome, 122
Eating disorders, 524
Echelon lymph nodes, 393
Ectodermal dysplasia, 222
Edrophonium test, 604
EDTA, 463
EhlersDanlos syndrome, 223, 453, 499
EkmanLobstein syndrome, 576
Electrical insulating oil, 693
Electric pulp tester, 423
Electromagnetic spectrum, 687, 688
ELISA test, 102
Elongated image, 816
Ely cyst, 251
Emphysema, 509
Enamel caries, 414
Enamel hypoplasia, 511, 516
Enamel pearls, 42
Enameloma, 42
Enchondromas, 350
Endarteritis obliterans, 612
Endemic Kaposis sarcoma, see African
Kaposis sarcoma
Endobone, 579
Endocrine glands, 532
Endocrinopathic pigmentation, 546
Energy requirement, 633
Enostosis, 584
Entropion, 195
Enucleation, 330
Environmental enamel hypoplasia, 51
Enzymatic theory, 407
Eosinophilic granuloma, 647
Epidermal growth factor receptor, 402
Epidermoid cysts, 327
Epidermolysis bullosa (EB), 193
types, 193
Epidermolysis bullosa acquisita, 596
Epilepsy, 530
Epiloia, see Tuberous sclerosis complex
Epiphora, 390
Epistaxis, 499
Epithelial dysplasias, 143
Epithelial rests of Malassez, 318
Epithelioid macrophages, 605
Epithelioma contagiosum, see
Molluscum contagiosum
Epithelioma cuniculatum, 367
Epsilon-aminocaproic acid (EACA), 502
Epstein pearls, 316
EpsteinBarr virus (EBV), 385, 450
Epulis fissurata, 354
Erbs palsy, 584
Erosion, 461
Erosive lichen planus, 147
Eruption sequestrum, 47
Erysipelas, 84
Erythema multiforme, 177, 189

Erythema nodosum, 619


Erythematous candidiasis, see Chronic atropic
candidiasis
Erythrodontia, 76, 643
Erythroleukoplakia, 141, 142
Erythroplakia, 168
Esophageal reflux disease, 213, 519
Esophageal webs, 487
Estrogens, 445
Ethyl alcohol, 384
Eumelanin, 18
Eustachian tube, 390
Evaginatus odontomas, 41
Ewings sarcoma, 376
Examination of temporomandibular joint, 243
Exanthematous diseases/infections, 52
Exertional dyspnea, 475
Exfoliative cytology, 397, 395
Exocrine glands, 532
Exophytic growth, 390
Exostoses, 19, 35
Exposure parameters and processing
technique, 818
errors, 818
blank radiograph, 818
dark radiograph, 818
film fog, 818
light radiographs, 818
External resorption, 466
Extraoral films, 721
Extraoral radiographic techniques, 752
axiolateral oblique projection, 753
lesser known/forgotten, 752
acanthioparietal projection reverse
Waters method, 754
May method, 752
modified parietoacanthial
projection, 754
Townes method, 752
Extraoral radiography, 743
grids, 743
image receptors, 743
intensifying screens, 743
Extraskeletal chondroma, 350
Extrinsic asthma, 508
Extrinsic cysts, 316, 318
Extrinsic discoloration, 71
Extrinsic stains, 72
Eye to heaven appearance, 581
Eyelid beading, 646
Eyelid twitch response, 604

F
Faces pain scale, 116, 117
Facet, 459
Facial approximation, 667
Facial hirsutism, 643
Facial neuropathies, 628
Facies leprosa, 611
Factitial injury, 452
Falling snowflakes, 328
Familial fibrous dysplasia, see Cherubism
Fanconis anemia, 488
Fascia, 428, 429
Fascial spaces, 426
Fat soluble vitamin, 636

Index

Fatty acids, 635


Fatty degeneration, 401
Fellatio syndrome, 625
Fergusson, 659
Fever, 598
Fibroma, 345
Fibromatoses, 361
Fibromatosis gingivae, 29
Fibromyalgia, 259
Fibro-osseous lesions, 568
Fibro-osseous metaplasia, 675
Fibrosarcoma, 370
Fibrous dysplasia, 573
Fibrous hyperplasia, 354
Filiform papillae, 19, 24
Film badge monitoring, 713
Film badges, 713
Film placement and projection technique, 814
errors, 814
Film processing, 803
techniques, 803
automatic, 809
manual, 803
steps in processing, 807
visual method, 807
Film receptors, 706
Film storage, 707
Film storage and handling, 812
errors, 812
dark spots or lines, 812
emulsion peel, 812
film fog, 812
nail marks or kink marks, 814
scratched film, 812
static electricity artifact, 814
Films and processing of films, 687
Filters, 694
Finger clubbing, 475, 519
Fish scale appearance, 577
Fishy scale odor, 515
Fissured tongue, 13, 24
Fite method, 611
FitzHughCurtis syndrome, 630
Flapping tremors, 525
Floating in air apperance teeth, 647
Floating in space, 395
Floating thermometer, 805
Floating tooth syndrome, 582
Florid cemento-osseous dysplasia, 569
Florid osseous dysplasia, 570
Fluid deprivation test, 538
Fluid level appearance, 105, 106
Fluid-fluid levels, 323
Fluorescent treponemal antibody-absorbed
(FTA-ABS) test, 613
Fluorosis, 52
FNAC, 396
Foamy macrophages, 648
Focal cemento-osseous dysplasia, 611
Focal epithelial hyperplasia, 165, 347
Focal reversible pulpitis, 439
Focal sclerosing osteomyelitis, 414
Focal sialadenitis, 271
Focal trough, 759
concept, 759
effect of patient positioning, 759

Fogo selvagem, see Brazilian pemphigus


Folate, 385
Foliate papillitis, 168
Folic acid deficiency, 487
Follicular cyst, see Dentigerous cyst
Forchheimer spots, 91
Fordyce granules, 11, 29
Foreign body granulomas, 616
Forensic dentistry, 654678
Fore-shortened image, 816
Fothergills disease, 120
Fourniers molars, 52
Fractionated irradiation, 400
Framed vertebrae, 588
Free radicals, 384
Free-floating desmosomes, 646
Frictional traumatic keratosis, 135
Frontal bossae of parrot, 628
Frontal sinus configuration, 664
Full axial projection, 748
Fulminant hepatitis, 528
Functional capacity, 475
Fusion, 28, 36

G
GABHS, 507, 508
Gag reflex, 844
Galacturonic acid, 463
Galvanizing, 464
Gamma rays, 687
Gangrenous, see Noma
GAPO, 48
Gardners syndrome, 341, 349
Gargoylism, 644
Garrs osteomyelitis, 437
Gastroesophageal reflux disease (GERD), 519
Gastrointestinal syndrome, 700
Gate control theory, 114
Gaucher cells, 648
Gaucher disease, 648
Gemination, 36
Generalized seizures, 530
Geniculate neuralgia, 124
Genital wart, see Condyloma acuminatum
Geographic tongue, 24
German measles, 91
Gestant odontome, 40
Ghost cells, 365
Ghost images, 759
Ghost-like appearance, 60
Giant cell arteritis, 591
Giant cell fibroma, 360
Giant cell granuloma, 352
Giant cell reparative granuloma, 352
Giant cell tumors, 542
Giant osteoid osteoma, 352
Gigantiform cementoma, 570
Gigantism, 656
Gilchrist disease, 107, 207
Gingival cyst of infants, 305
Gingival diseases modified by
medications, 440
Gingival hyperplasia, 483, 644
Gingival recession, 425
Ginglymodiarthroidal joints, 239
Glanders like disease, 85

Glands of Blandin and Nuhn, 267


Glands of von Ebner, 267
Glanzmanns thrombasthenia, 500
Glenoid fossa, 239
Glomeruloid appearance, 365
Glomerulonephritis, 617
Glossitis, 628, 487
Glossocele, 323
Glossopharyngeal neuralgia, 122
Glucocerebroside, 648
Glucose-6-phosphate dehydrogenase
deficiency, 488
Goldenhaars syndrome, 33
Golgi tendon organs, 241
GoltzGorlin syndrome, 228
Gomori methenamine silver stain, 108
Gonococcal arthritis of TMJ, 631
Gonorrhea, 630
Gorhams disease, 585
Gorhams osteolysis, 585
GorhamStout syndrome, 585
Gorlins sign, 224
Gout, 253
Graft versus host disease, 234
Graham-Little syndrome, 149
Grand mal seizures, 530
Granulocytes, 490
Granuloma, 504, 605
Granuloma pyogenicum, 353
Granulomatous diseases, 511, 605
Graves disease, 541
Grids, 708, 722
composition, 722
functions, 723
types, 723
Grinspan syndrome, 149
Grocott methenamine silver stain, 621
Grocott-Gomori methenamine silver, 208
Ground glass appearance, 517, 574
Growth hormone, 535
in children, 535
GuillainBarre syndrome, 599
Gumma, 207, 613
Gunthers disease, 643
Gutkha, 381

H
HaileyHailey disease, 229
Hair-on-end radiographic appearance,
489, 490
Hairy leukoplakia, 102, 516
Hairy tongue, 18
Half value layer, 694
Halitosis, 561
Hallopeau type pemphigus vegetans, 596
Halo-shadow, 438
Hand, foot and mouth (HFM) disease,
179, 204
HandSchullerChristian disease, 647
Hangar-Rose skin test, 89
Hanging teeth, 390
Hansens disease, 610
Heart failure, 482
Heartburn, 519
Heat test, 423
Hebra nose, 88

889

Index

Hecks disease, see Focal epithelial


hyperplasia
Heerfordt syndrome, 619
Heinz bodies, 488
Heister mouth gags, 659
Helicobacter pylori, 519
Hemangiomas, 68, 357
Hemarthrosis, 501
Hematological diseases, 489
Hematomas, 69
Hematopoietic syndrome, 699
Hemifacial atrophy, 32
Hemifacial hyperplasia, 31
Hemifacial hypertrophy, 31
Hemihyperplasia, 35
Hemochromatosis, 67
Hemodialysis, 481, 517
Hemoglobinopathies, 489, 490
Hemophilia A, B and C, 502, 503
Hemoptysis, 505
Hemorrhage, 662
Hemosiderin, 62
Heparin therapy, 484
Hepatitis, 526
A, 526
B, 526
B surface antigen, 528
C, 527
D, 527
G virus, 527
Hereditary benign intraepithelial
dyskeratosis, 165
Hereditary corpoporphyria, 643
Hereditary gingival fibromatosis, 449
Hereditary fibrous dysplasia,
see Cherubism
Hereditary opalescent dentin, 57
Hermanns syndrome, 341
Herpangina, 180, 203
Herpes labialis, 201
Herpes simplex viruses (HSV), 175, 385
type 1, 175
type 2, 175
Herpes viruses, 175
Herpes zoster, 178, 203
Herpetic gingivostomatitis, 449
Herpetiform ulcers, 211
Herring bone pattern, 814
Hiatal hernia, 522
High performance laser spectroscopy-laser
induced fluorescence (HPLC-LIF), 395
High voltage transformer, 693
Highly differentiated squamous
cellcarcinoma, 398
Higoumenakis sign, 235
Hilar lymphadenopathy, 607
Histiocytosis X, 647
Histoplasmosis, 106, 207, 614
Hodgkins disease, 495
Homogeneous leukoplakia, 141
Honeycomb like appearance, 243, 374
Honeycomb pattern, 351
Honiton lace, 219
Horizontal overlap, 741
Hormone resistance, 535
Hormones, 533

890

Host modulation, 444


Hot potato voice, 508
Howships lacunae, 579
HoyeraalHreidarsson syndrome, 225
HPA axis, 535
Human herpes virus-8, 175, 376
Human immunodeficiency virus (HIV),
92, 285, 385,
oral manifestations, 101
structure of HIV-1 virion, 92
transmission, 97
Human papilloma viruses, 385
Humoral immunity, 590
Hunter syndrome, 644
Hurler syndrome, 644
Hutchinson teeth, 613
Hutchinsons incisor, 52
Hutchinsons triad, 628
Hyalinosis cutis et mucosae, 646
Hydatid disease, 328
Hydrostatic enlargement of cysts, 305
Hydroxyl radicals, 384
Hyperacusis, 529
Hyperalgesia, 111
Hyperbaric oxygen (HBO), 436
Hypercalcemia, 497, 542
Hypercarotenemia, 637
Hypercementosis, 470
Hyperdontia, 45
Hyperglycemia, 600
Hypermobility, 224, 248
Hyperostosis, 584
Hyperparathyroidism, 542
Hyperpigmentation, 400
Hyperplasia of minor salivary glands, 266
Hypersensitivity, 459
Hypertension, 476, 549
Hyperthyroidism, 540
Hyperuricemia, 253
Hyperventilation, 544
Hypodontia, 45
Hypoesthesia, 111
Hypoglycemia, 540
Hypohidrotic ectodermal dysplasia, see
Anhidrotic ectodermal dysplasia
Hypomineralized enamel, 50
Hypoparathyroidism, 544
Hypopharynx, 392
Hypophosphatasia, 453
Hypoplastic enamel, 50
Hypoplastic teeth, 640
Hypopnea, 512
Hyposalivation, 267, 268
Hypovolemia, 523

I
Ice pack test, 604
Icterus, see Jaundice
Idiopathic hypertension, see Hypertension
Idiopathic osteolysis, 586
Idiopathic osteosclerosis, 584
Idiopathic thrombocytopenic
purpura, 500
IgA, 195, 409
IgG, 409
Image guided radiotherapy (IGRT), 400

Immune granulomas, 605


Immune-mediated granulomatous
inflammation, 605
Immunity, 157
Immunomodulators, 184
Impacted teeth, 49
Impetigo, 84
Implant site identification, 845
absolute contraindications, 845
conventional tomography, 848
imaging, 848
panoramic radiography, 848
relative contraindications, 846
selection of the implant site, 847
selection of the patient, 845
standard periapical radiographs, 848
Incinerated teeth, 660
Incineration, 659
Incipient caries, 411
Incontinentia pigmenti, 231
Indirect target theory, 399
Indwelling catheters and stents, 481
Infantile cortical hyperostosis, 583
Infantile osteomyelitis, 436
Infectious arthritis, 252
Infectious mononucleosis, 90
Inflammatory bowel disease, 519
Inflammatory cysts, 304
Infrabony defects, 456
Infrared telethermography (IRT), 796
Infratemporal fossa space, 429
Inherent filtration, 694
Inherited coagulation disorders, 502
Intensifying screens, 707, 722
Intensity modulated radiation therapy
(IMRT), 400
Internal replacement, 467
Internal resorption, 466, 467
International normalized ratio (INR), 484
Interstitial glossitis, 613
Intradermal injections, 611
Intramuscular injections, 502
Intraoral films, 719, 720
composition, 720
dimensions, 721
uses, 719
Intraoral herpes, 201
Intraoral radiography, 725
common technical errors, 740
preliminary procedures, 729
procedures, 733
bitewing radiography, 735
occlusal radiography, 736
periapical radiography, 733
selection criteria guidelines, 729
techniques, 730
bisecting angle, 730
common technique errors, 739
paralleling, 730
Intraoral X-ray machine, 691, 693, 726
components, 691
dissipation of heat from, 693
working mechanism of, 693
Intraoral X-ray units, 690
mobile intraoral radiographic
units, 690

Index

Intraosseous mucoepidermoid carcinoma,


296, 365
Intravenous bisphosphonate treatment, 846
Intrinsic cysts, 316
Intrinsic discoloration, 81
Inverted pear-shaped radiolucency, 315
Inverted Y line of Innes, 830
Ionization chambers, 712
Ionizing radiation, 384
Iris lesion, 190
Iron deficiency anemia, 210, 486
Iron, 210
Ischemic heart disease, 478
Isotope tracer probe, 394
Ivory-white papules, 645
Ivy bleeding time, 498

J
JadassohnLewandowsky syndrome, 225
JaffeLichtenstein syndrome, 574
Jaundice, 68, 525
Jaw resection, 659
Jewels sign, 195
Jigsaw puzzle pattern, 588
JodBasedow phenomenon, 540
Joint mice, 251
Jugulo-digastric lymph nodes, 393
Junctional epidermolysis bullosa, 194
Junctional nevus, 348
Juvenile idiopathic arthritis, 251
Juvenile ossifying fibroma, 348, 572
Juxta articular chondromas, 350

K
Kaposis sarcoma, 69, 376
classification system, 377
Kassowitzs law, 628
Kawasaki disease, 232
Keratin pearls, 399
Keratoacanthoma, 347
Keratoconjunctivitis sicca, 270
Keratocystic odontogenic tumor, 304,
307, 339
Khaini, 381
Kidney shaped cyst, 316
Kilovoltage, 709
Kissing disease, see Infectious mononucleosis
Klestadts cyst, 315
Klinefelter syndrome, 326
KlippelTrenaunay syndrome, 358
Knurled effect, 814
Koebners phenomenon, 147
Koenens tumors, 233
Kohlschutter-Tonz syndrome, 56
Koiloncychia, 486
Kopliks spots, 91
Kuttner tumor, see Chronic sclerosing sialadenitis
Kvaals radiographic method, 672
Kveim test, 620
Kwashiorkor, 635

L
Labial salivary gland biopsy, 275
Lacrimal sac, 390
Lacrimo-auriculo-dento-digital (LADD)
syndrome, 266

Lagophthalmos, 610
Lamina dura, 825
Langhans type giant cells, 605
Latent bone cyst, 323
Latent image formation, 802
steps, 802
Latent syphilis, 627
Lateral oblique view, 750
Lateral periodontal cyst, 311
Lateral pharyngeal space, 430
Lateral pterygoid muscle, 242
Lateral radicular cyst, 319
Lazy leukocyte syndrome, 453, 456
Lead aprons, 709, 711, 715
Left shift, 492
Legionnaires disease (legionellosis), 504
Leiomyoma, 357
Leiomyosarcoma, 377
Lemierres syndrome, 90
Leongs premolar, see Dens evaginatus
Leontiasis ossea, 31
Lepra cells, 611
Lepromatous leprosy, 610, 611
Lepromin test, 611
Leprosy, 610
LettererSiwe disease, 648
Leucovorin, 402
Leukemia, 447, 455
Leukemia associated gingivitis, 440, 447
Leukemoid reaction, 492
Leukocyte disorders, 455
Leukocytosis, 492
Leukoedema, 13
Leukopenia, 491
Leukoplakia, 137, 225
classification and staging system, 138
clinical features, 140
medical management, 144
Leutic glossitis, 628
Levines ionic see-saw theory, 407
Levines sign, 478
LevyHollister syndrome, 266
Lichen planopilaris, 147
Lichen planus, 172, 189, 218
Lichenoid drug reaction, 152
Lichenoid mucosal reactions, 521
Lichenoid stomatitis, 483
Light spots, 819
Lincolns highway, 430
Lincolns sign, 588
Linea alba buccalis, 134
Linear en coup de sabre, 601
Linear accelerators, 400
Linear enamel caries, 411
Linear gingival erythema (LGE), 448
Linear IgA bullous dermatosis, 195
Linear IgA disease, 195
Lines of Zahn, 16
Lingual frenum, 626
Lingual pits 26
Lingual thyroid, 25
Lingual tonsils, 12
Lingual varices, 15, 69
Lip print, 678
Lipids, 635
Lipoid proteinosis, 646

Lipoma, 355
Liposarcoma, 373
Lipschtz bodies, 240
Lipstick sign, 268
Liquid crystal thermography (LCT), 796
Liver disease, 68, 503, 525
functions, 525
Liver metastasis, 397
Localized microdontia, 35
Lockjaw, 85
Lfgren syndrome, 619
Log wheel rigidity, 531
Loose bodies, see Joint mice
Loss of taste, 401
Lowenstein tumor, 367
Lower respiratory tract infections, 504, 508
LT ratio, 396
Ludwigs angina, 428
Lues, 626
Lues maligna, 207, 627
Luminescence, 713
Lumpy jaw, 86
Lupus erythematosus (LE), 170, 600
Luxation, 779
Lyells syndrome, 189
Lymph nodes, 495
Lymphatic malformations, 359
Lymphatics, 392
Lymphoid nodules, 595
Lymphomas, 495
Lymphoproliferative syndrome, 491
Lyonization effect/Lyon hypothesis, 54
Lysosomal storage diseases, 641
Lysosomes, 641

M
Macqueen-dell technique, 751
Macrodontia, 35
Macroglossia, 22
Macrognathia, 30
Macrophages, 605
Maculopapular lesions, 627
Maculopapular rash, 612
MAGIC syndrome, 215
Magnetic resonance imaging (MRI), 781
advantages, 787
common artifacts, 787
due to motion and use of
denture, 787
flow effect and movement
artifacts, 787
contrast agents, 786
disadvantages, 787
historical perspective, 781
image interpretation, 787
methods for obtaining spatial
resolution, 786
principles, 781
MR scanner, 781
nuclear magnetic dipole moment, 781
proton magnetization, 782
relaxation, 783
resonance, 783
spin-echo phenomenon, 784
uses, 787
Maillard pigments, 79

891

Index

Main d accoucheur sign, 544


Major aphthous ulcers, 211
Malignant ameloblastoma, 363
Malignant epithelial odontogenic
ghost cell tumor, 365
Malignant hypertension, 477
Malignant melanoma, 368
Malignant schwannoma, 378
Malignant tumors, 261, 380
Mandibular advancement devices, 512
Mandibular buccal bifurcation cyst, 321
Mandibular condyle, 239
Mandibular infected buccal cyst, 321
Man-made radiation, 702
Manual and automatic processing, 811
comparisons, 811
Marasmus, 635
Marble bone disease, 579
Marfan syndrome, 249
Marijuana, 383
MaroteauxLamy syndrome, 645
Marsupialization, 349
Mask-like appearance of face, 602
Masseter, 244
Masseter muscle, 241, 258
Massive osteolysis, 586
Masson-Fontana silver stain, 110
Masticatory abrasion, 460
Masticatory space, 429
Matrix metalloproteinases, 444
Maxillary tuberosity, 831
Maximum permissable dose, 703
MayHegglin anomaly, 500
Mayer mucicarmine stain, 110
McGill pain questionnaire, 116
McGregor line, 578
Measles, 91
Measles-mumps-rubella (MMR) vaccine, 91
Meckels diverticulum, 523
Medial pterygoid muscle, 242, 258
Median mandibular cysts, 316
Median rhomboid glossitis, 155, 168
Mediastinal group lymph nodes, 393
Melanin, 62, 18
Melanin incontinence, 29
Melanoacanthosis, see Oral melanoacanthoma
Melanocarcinoma, see Malignant melanoma
Melanocytic nevi, 62
Melanomas, 369
Melanotic macule 69
Melioidosis, 84
MelkerssonRosenthal syndrome, 13,
289, 521, 620
Menaquinones, 638
Menstrual cycle-associated gingivitis, 445
Mercury, 661
Mercury poisoning, 63
Merkel cell carcinoma, 552
Mesh-like pattern, 577
Mesiodens, 46
Metabolic disorders, 52, 641
Metachromatic dye, 397
Metastases, 392
Methenamine silver stains, 108
Methotrexate, 402
Michels solution, 219

892

Microbial plaque, 442


Microdontia, 35
Microfracture, 464
Microglossia, 22
Micrognathia, 30
Midline cysts, 324
Migratory glossitis, 168
Mikulicz cells, 89
Mikuliczs disease, 277, 591
Mikulicz ulcer, 211
Milia, 194
Miliary tuberculosis, 607
Mineralocorticoids, 549
Minocycline, 64, 78, 79
Minor aphthous ulcers, 211
Mishri, 381
Mobility, 497
Moderately differentiated squamous cell
carcinoma, 398
Modified Waters view, see Skull
radiography
Molar-incisor hypomineralization, 77
Molluscum contagiosum, 629
Monocytes, 490
Monoglandular fever, see Infectious
mononucleosis
Monomorphic adenoma, 293
Mononucleosis, 450
Monounsaturated fatty acids, 635
Moon face, 546, 635
Moons molars, 52
Moorrees method, 670
Morquio syndrome, 33
Morsicatio buccarum, 134
Morsicatio labiorum, 135
Morsicatio linguarum, 135
Mosaic pattern, 588
Moth-eaten appearance, 395, 435
Mottled enamel, 52
Mouse-like facies, 602
Mouth mirror test, 268
Mucic acid, 463
Mucocele(s), 278
Mucocutaneous lymph node syndrome, 232
Mucoepidermoid carcinoma, 295
Mucopolysaccharidoses, 454, 644
Mucormycosis, 108, 207, 615
Mucosa-associated lymphoid tissue (MALT)
lymphoma, 277
Mucositis, 700
Mucous membrane pemphigoid, 186
Mucous patches, 206, 627
Mucous retention cyst, 316
Mulberry molars, 52, 613
Multidrug-resistant tuberculosis, 609
Multifocal eosinophilic granuloma, 647
Multinucleated giant cells, 582
Multiple endocrine neoplasia (MEN), 552
MEN I, 552
MEN II, 552
MEN III, 552
Multiple mucosal neuroma syndrome, 552
Multiple myeloma, 496
Multiple sclerosis, 531
Munros abscesses, 222
Mural growth theory, 304

Muscle splinting, 256


Muscles of mastication, 244
Muscular dystrophy, 532
Muscular hypertrophy, 258
Musculoskeletal disorders, 115
Mushroom fracture, 254
Mushroom-shaped skull, 577
Myasthenia gravis, 532, 603
Mycobacterium tuberculosis, 606
Myocardial infarction, 479
Myofascial pain, 119, 257
Myofibroblastoma, 362
Myositis, 256
Myospasm, 257
Myotomy, 659

N
Nanocomplex, 464
Nasal obstruction, 390
Nasopalatine duct cyst, 314
Nasopharyngeal cysts, 323
Natal and neonatal teeth, 46
Natal teeth, 46
Neck dissection, 399
Necrotic pulp, 466
Necrotizing fasciitis, 428
Necrotizing sialometaplasia, 215, 284
Necrotizing stomatitis, see Noma
Neisseria gonorrhoeae, 254
Neonatal line, 52
Neonatal lupus erythematosus, 598
Neonatal teeth, 46
Neonatal tetanus, 86
Neospinothalamic tract, 113
Nervus intermedius neuralgia, 124
Neuralgia, 120
Neurofibroma, 356
Neurofibrosarcoma, 378, 379
Neurogenic sarcoma, see Neurofibrosarcoma
Neurohypophysis, 538
Neuromelanin, 18
Neurosyphilis, 628
Neurovascular syndrome, 700
Neutropenia, 455, 491
Nevoid basal cell carcinoma syndrome
(NBCCS), 304
Nevus cells, 348
Niacin deficiency, 455
Nicotinamide adenine dinucleotide phosphate
(NADPH) oxidase, 384
Nicotine, 382
Nicotine stomatitis, 136
NiemannPick disease, 649
Nifedipine, 447, 483
Nikolskys sign, 182, 235
Nitrosamine, see Nicotine
Nitrosodiethanolamine, 382
Nitrosoproline, 382
Nociception, 111
Nociceptors, 11, 112
Noma, 87
Noma neonatorum, 87
Noma pudendi, 87
Non-Hodgkins lymphoma (NHL), 495
Non-homogeneous leukoplakia, 141
Non-lipid reticuloendothelioses, 647

Index

Non-odontogenic cysts, 314


Non-specific sialadenitis, 281
Non-starch polysaccharides, 634
Non-suppurative osteomyelitis, 433
Noonan syndrome, 326
North American blastomycosis, 207
Nuclear medicine, 788
types, 788
NUG, 449
NUP, 449
Nursing bottle caries, 412
Nutrients, 633
Nutriology, 633

O
Obstructive sleep apnea syndrome, 512
Occipital neuralgia, 125
Occlusal enamel pearl, see Dens evaginatus
Occlusal radiographs, 395, 721
Occupational exposure, 703
Occupational hazards, 390
Odontecrexis, 119
Odontoameloblastoma, 336
Odontogenic carcinomas, 363
Odontogenic carcinosarcoma, 366
Odontogenic fibroma, 344
Odontogenic keratocyst, 307
Odontogenic myxomas, 344
Odontogenic sarcomas, 365
Odontogenic tumors, 332, 344
Olfactory reference syndrome, 561
Oligodontia, 45
Olympian row, 628
Omohyoid muscle, 399
Oncocytoma, 295
Oncogenes, 386
Opalescent brittle teeth, 577
Open apices method, 671
Open lock, see Dislocation
Open mouth Waters view, see Skull
radiography
OPG, 306, 320
Oral contraceptive, 447
Oral hairy leukoplakia, 100, 516
Oral melanoacanthoma, 347
Oral submucous fibrosis, 159
Oral warts, 346
Orofacial digital syndrome, 24
Orofacial granulomatosis, 289, 620
Orofacial pain, 115
Oromandibular dystonia, 532
Oromandibular limb hypogenesis syndrome, 22
Oropharyngeal candidiasis, 509
Oropharyngeal trichomonal infection, 631
Orthokeratinized odontogenic cyst, 307
Orthopnea, 475
Orthostatic hypotension, 563
OSMF, 159, 160, 161
Ossifying fibroma, 348, 571
Osteitis fibrosa generalisata, 543
Osteoarthritis, 251
Osteoarthrosis, 250
Osteoclast, 543, 578
Osteodentin, 640
Osteodystrophia deformans, 587
Osteogenesis imperfecta, 576

Osteogenic sarcoma, 573


Osteoma, 349
Osteomalacia, 455, 638
Osteomyelitis, 431
microorganisms responsible, 432
Osteopetrosis, 578
congenita, 579
tarda, 579
Osteoporosis, 846
Osteoporosis circumscripta, 588
Osteoradionecrosis, 401, 701
Osteosarcoma, 373, 374
Otalgia, 387
Overlapped image, 816
Oxyphilic adenoma, 295
Oxytocin, 538

P
Paan, 381, 382
Pacemakers, 484
Pachyonychia congenita, 225
Pagets disease, 586
Palatal cancer, 590
Palatal rugae, 15, 663
Palatal torus, 19, 20
Paleospinothalamic tract, 113
Pancreatin, 511
Pancytopenia, 226, 488
Panhypopituitarism, 536
Pannus, 252
Panoramic radiograph, 759
disadvantages and limitations, 760
indications, 759
Panoramic radiology, 756
concepts, 756
technique and imaging principles, 756
working principle, 757
origin, 756
Pansinusitis, 105
Papillary cystadenoma lymphomatosum, 294
PapillonLefevre syndrome, 453
Paracoccidioidomycosis, 208
Parade ground fracture, 262
Paradental cyst, 320
Paramedian lip pits, 26
Paramolar, 46, 47
Paraneoplastic pemphigus, 184, 185, 596
Parapharyngeal space, 427
Parasitic cysts, 327
Parathyroid glands, 542
Paratracheal lymphadenopathy, 607
Parinaud oculoglandular syndrome, 89
Parkinsons disease, 278, 531
Parma projection, 751
Parotid enlargement, 290
Parotid papillae, 17
Paroxysmal nocturnal dyspnea, 475
Partial seizures, 530
Pastias lines, 82, 508
Patch test, 153
PatersonKelly syndrome, 487
Pathological fracture, 395, 396
Pathological wear, 464
Patient shielding, 711
Paul-Bunnell test, 90
Pediatric medicines, 462

Peg lateral, 35
PelEbstein fever, 495
Pellagra, see Niacin deficiency
Pelvic inflammatory disease, 630
Pemphigoid, 212, 596, 597
Pemphigus, 212, 596
Pemphigus erythematosus, 596
Pemphigus foliaceous, 181, 596
Pemphigus vegetans, 181, 596
Pemphigus vulgaris, 181, 596
Penny test, 811
Peptic ulcer disease, 523
Percussion test, 466
Perforations, 795
Periadenitis mucosa necrotica recurrents,
see Major aphthous ulcers
Periapical cemento-osseous dysplasia, 569
Periapical cyst, 318, 416
Periapical granuloma, 416, 419
Periapical pocket cyst, 320
Periodontal disease, 101, 440, 450, 592
Periodontal pain, 118
Periostitis ossificans, 437
Peripheral edema, 475
Peripheral giant cell granuloma, 352
Peripheral ossifying fibroma, 348
Pernicious anemia, 488
Personal protective equipment (PPE), 728
Personnel dosimeter, 713
Personnel shielding, 711
Petechiae, 69
Petit mal seizures, 530
Peutz-Jeghers syndrome, 66
PFAPA syndrome, 215
Phantom bone disease, 585
Pharyngitis, 507
Pharyngotonsillitis, 508
Phenytoin-induced gingival enlargement, 446
Pheochromocytoma, 549
Pheomelanin, 18
Phleboliths, 16
Phoenix abscess, 415
Phosphate, 488
Phosphopeptide, 464
Photoelectric effect, 696
Photographic effect, 713
Photopheresis, 184
Photostimulable phosphor plates, 733
Phycomycosis, 615
Pilocarpine, 288
Pink disease, 63
Pink form, 655
Pink panters, 510
Pink puffers, 510
Pink tooth, 466, 467
Pink tooth of Mummery, 80
Pinta, 626
Pintos ligament, 241
Pit and fissure caries, 410
Pituitary dwarfs, 536
Pityriasis rosea, 226
Plancks constant, 687
Plasmapheresis, 600
Platelet count, 500
Platelet disorders, 499
Platelets, 497

893

Index

Platyspondyly, 578
Pleomorphic adenoma, 291, 792
Pleomorphism, 398
Plumbism, 64
PlummerVinson syndrome, 487
Pocket dosimeter, 713
Podophyllin, 103, 630
Polonium, 382
Polyarthritides, 252
Polycyclic aromatic hydrocarbon (tars), 382
Polycythemia, 485
Polycythemia rubra vera, 485
Polyunsaturated fatty acids, 635
Pontiac fever, 512
Poorly differentiated squamous cell
carcinoma, 399
Popcorn calcifications, 578
Porphyria, 642
Porphyria cutanea tarda, 643
Portable handheld X-ray unit, 691
Position indicating device (PID), 694, 706, 709
Positive identification, 657, 678
Positron emission tomography, 294
Possible identification, 657, 678
Posterior auricular nodes, 91
Posterior cervical muscles, 245
Postmortem dental examination, 655
Postmortem identification, 655
Postmortem pink teeth, 661
Postmortem radiographs, 657
Postnasal drip, 105
Pregnancy, 445, 462, 550
Pregnancy gingivitis, 551
Pregnancy tumor, 445
Pregnancy-associated gingivitis, 445
Prenatal diagnosis of clefts, 28
Prevotella intermedia, 454
Prickle cells, 398, 399
Primary herpetic gingivostomatitis, 176, 200
Primary HPT, 542
Primary intraosseous squamous cell
carcinoma, 364
Primary hypertension, see Hypertension
Prinzmetals angina, 478
Probable identification, 657
Probe, 394, 395
Processing solutions, 810, 811
composition, 810
developer solution, 810
fixing solution, 810
test to determine the quality, 811
Progesterone, 550
Proliferative verrucous leukoplakia, 142
Proptosis, 390
Prostaglandins, 112
Protective co-contraction, 256
Protein energy malnutrition (PEM), 635
Proteins, 635
Proteolysis-chelation theory, 406
Proteolytic theory, 406
Prothrombin time, 498
Proton pump inhibitors, 269, 523
Protostylid, 44, 45
Protruded tongue, 662
Proximal surface caries, 417
Psammomatoid ossicles, 573

894

Pseudo macroglossia, 22
Pseudomicrodontia, 35
Psoriasis, 165, 221
Psychosomatic factors, 455
Pterygomandibular space, 427, 430
Ptyalism, 63, 278
Puberty-associated gingivitis, 445
Pulmonary tuberculosis, 608
Pulp calcifications, 468
Pulp canals, 42, 459
Pulp hyperemia, see Focal reversible pulpitis
Pulpal pain, 116
Pulse oximetry, 424
Pulse rate, 476
Pulse rhythm, 476
Punch biopsy, 398
Punched-out radiolucencies, 497
Purified protein derivative, 609
Pyoderma gangrenosum, 520
Pyogenic granuloma, 353
Pyostomatitis vegetans, 623

Q
Qualitative disorders, 491
Qualitative neutrophil defects, 488
Quantitative defects, 485

R
Rabbit fever, 83
Racial pigmentation, 17
Radiation, 701
sources, 701
cosmic sources, 702
natural radiation, 702
terrestrial sources, 702
Radiation biology, 690, 697
deterministic effects, 699
of total body radiation, 699
on tissues and organs, 699
effects on living systems, 697
bystander effect, 699
cell cycle effects, 698
direct effect, 697
effects in the developing embryo
and fetus, 700
on oral tissues, 700
film exposure and processing, 714
stochastic effects, 699
Radiation caries, 401, 412, 426, 701
types, 701
Radiation dose, 399
Radiation hazards, 685
Radiation-induced cancer, 700
Radiation-induced heritable diseases, 700
Radiation monitoring devices, 713
Radiation physics, 687
fundamentals, 687
electromagnetic radiation, 687
ionizing and non-ionizing
radiation, 688
particulate radiation, 687
production of X-rays, 688
radiation, 687
Radiation protection survey, 711
Radiation safety and protection, 701, 728
historical events in, 701

Radioallergosorbent test, 507


Radicular cyst, see Periapical cyst
Radiculomegaly, 35
Radiographic evaluation of carious lesions, 425
Radiographic faults, 812
causes, 812
Radiographic film, 731
Radiographic image formation, 801
Radiographic infection control, 728
Radiographic landmarks, 83, 825
common to both the maxillary and
mandibular radiographs, 825
extraoral, 837
radiolucent anatomical, 836
radiopaque anatomical, 836
unique to the mandibular radiograph,
825, 833
unique to the maxillary radiograph, 825, 827
Radiographic techniques, 724797
conventional imaging, 724, 725
extraoral radiography, 724
intraoral radiography, 724
specialized imaging, 724, 760
arthrography, 725
computed tomography (CT), 724
dentomaxillofacial cone-beam
computed tomography (CBCT), 724
magnetic resonance imaging, 725
nuclear medicine, 725
sialography, 725
thermography (thermal imaging or
infrared imaging), 725
ultrasonography, 725
Radiography, 703
dose limits, 703
patient exposure, 703
reducing dental exposure, 703
Radioisotope scan, 394
Radionuclide imaging, 294, 541, 588
Radiotherapy, 363, 364, 399
Radiotracer, 395, 584
Raman spectroscopy, 395
Rampant caries, 411, 426
Ramsay Hunt syndrome, 124, 125, 179, 529
Ranula, 279
Rapid plasma reagin (RPR), 613
Ras protein, 386
Raspberry like papillomas, 228
Rathkes pouch, 324
Raw-ham colored lesions, 627
Ray phenomenon, 87
RBC disorders, 210
Reactive leukocytosis, 492
Receptor placement, 740
Recommended dietary allowance (RDA), 633
Recurrent caries, 412, 425
Recurrent erythema multiforme, 190
Red lesion, 134
Red strawberry tongue, 83
Referral pattern for myofascial pain, 258
Regional odontodysplasia, 59
Reiters syndrome, 215
Renal failure, 513
Renal osteodystrophy, 516, 542
Renal rickets, 516
Rendu-Osler-Weber syndrome, 69

Index

Reparative dentin, 468


Residual cyst, 320
Respiratory infections, 504
Respiratory tract diseases, 506
Resting and reversal lines, 588
Rests of Malassez, 318, 320, 337, 363
Reticular atrophy of pulp, 468
Reticular forms, 148
Retrocuspid papilla, 14
Retrodiscitis, 249
Retrograde parotitis, 515
Retropharyngeal space, 427, 430
Retrozygomatic space, see Infratemporal
fossa space
Reverse smoking, 383, 390
Reverse Townes view, 750
Reverse Waters method, see Skull
radiography
Rhabdomyoma, 357
RHD, 480
Rheumatic fever, 480
Rheumatoid arthritis, 252, 592, 595
Rheumatoid factor, 253, 600
Rheumatoid synovial fluid, 594
Rhinocerebral zygomycosis, 616
Rhinoscleroma, 88
Rhinoviruses, 506
Rhizomegaly, 35
Rhizomicry, 35
Rhodopsin, 636
Riboflavin deficiency (riboflavinosis), 455
Rickets, 52, 638
Rickety rosary, 638
RigaFede disease, 47, 197
Rigor mortis, 659
Risus sardonicus, 85
Rodent ulcer, 367
Root caries, 425
Root dwarfism, 35
Root end cyst, see Periapical cyst
Root surface caries, 410, 417, 461
Rootless teeth, 58
Rose bengal staining, 272
Row of tombstones, 183
Rubella, 91
Rubeola, 91
Rugger-jersey sign, 579
Rushtons hyaline bodies, 319
Russel bodies, 89

S
Sabourauds agar, 108, 109, 157
Saddle nose, 617, 628
Safe light, 805
Saliva, 267
Saliva swab, 676
Salivary calculi, 280
Salivary dysfunction, 75, 400
Salivary flow rate, 408
Salivary gland scans, 789
clinical applications, 789
procedure, 789
Sandpaper rash, 82
Sandpaper-like exanthema, 508
Sanfilippo syndrome, 645
Sarcoidosis, 289, 618

Saucerization, 436
Scarlet fever, 82
Schaumann bodies, 290, 619
Scheie syndrome, 644
Schirmers test, 271, 272
Schuller method, 748
Schwannoma, 356
Scintigraphy, 271, 496, 543
Scintillation, 713
Sclerotic cemental masses, 570
SCOFF questionnaire, 525
Scooped dentin, 464
Scratch test, 81
Screw-driver appearance, 52
Screwdriver edge-shaped central incisors, 628
Screwdriver-shaped incisors, 613
Screw-type implants, 851
radiographic appearance, 851
Scrofula, 608
Scrotal tongue, 13
Scurvy, 499
Secondary aldosteronism, 549
Secondary dentin, 468
Secondary hypertension, 476
Secondary pulmonary tuberculosis, 607, 608
Selenium, 144, 385
Self-developing film, 808
Self-healing carcinoma, 347
SenearUsher syndrome, 596
Sentinel node, 394
Septic arthritis, 252
Sequelae of pulpitis, 413, 416
Sequestrated bone, 401
Sequestrectomy, 436
Serous non-secretory cyst, 317
Serum alkaline phosphatase levels, 575, 584
Serum bilirubin, 525, 526, 528
Sex hormones, 454
Sexually transmitted diseases, 625
Shagreen patch, 233
Shell teeth, 57
Shepherds crook deformity, 575
Shingles, 178, 201
Shovel-shaped incisors, 41
Sialadenitis, 281
Sialadenosis, 287
Sialography, 793, 795
contraindications, 795
indications, 793
injection of the contrast medium, 794
phases, 794
procedure, 793
armamentarium, 793
preimaging assessment, 793
preimaging instructions to the
patient, 793
technique, 793
Sialolithiasis, 280
Sialometry, 274, 290
Sialorrhea, 278
Sialosis, 287
Sicca complex, 277
Sicca syndrome, 271
Sickle cell anemia, 489
Sickle cell trait, 489
Siga, 409, 462

Silent thyroiditis, 539, 540


Simian gait, 587
Simmonds disease, 536
Sinusitis, 104
Sistrunk procedure, 325
Situs inversus, 22
Sjgrens syndrome, 791
Skin prick test, 507
Skull-photograph superimposition, 666
Skull radiography, 743
landmarks for positioning, 743
patient preparation, 744
planes for positioning of the skull, 743
positioning errors, 744
positioning terminology, 744
radiation protection, 744
techniques, 744
acanthoparietal projection, 747
AP axial projection, 749
bimolar projection, 751
lateral cephalometry, 749
lateral oblique of the ramus of the
mandible, 751
lateral view, 748
modified parietoacanthial
projection, 747
30 occipitomental, 746
PA cephalometric, 745
PA mandible, 745
parietoacanthial view, 747
posteroanterior projection, 745
rotated PA view, 746
standard occipitomental view, 746
submentovertex view, 748
Slaked lime, 139, 381
Slow virus, 587
SLUDGE syndrome, 604
Sly syndrome, 645
Smokers melanosis, 65
Smokers palate, 136
Smoking, 452
Smooth surface caries, 410
Snail track ulcers, 207, 613, 627
Snarling face, 603
Snuff, 139, 382
Snuff dippers cancer, 366
Soap bubble appearance, 322, 334, 362
Social profiling, 662
Sodium valproate, 446, 566
Solid PIOC, 364
Somatostatin analog, 537
Source to image receptor distance (SID), 708
South American blastomycosis,
see Paracoccidiodomycosis
Spatula test, 86
Speckled leukoplakia, 219
Sphenomandibular ligament, 241
Spindle-shaped fibroblasts, 582
Splendore-Hoeppli phenomenon, 88
Splenus capitis, 245
Split papules, 206, 627
Spoon-shaped nails, see Koilonychia
Squamous cell carcinoma, 364, 398, 399
Squamous odontogenic tumor, 337
Squamous papilloma, 345
St. Anthonys fire, 84

895

Index

Stable angina, 478


Stafnes bone cyst, 323
Static bone cyst, 323
Stellate-shaped fibroblasts, 570
Stensens duct, 17, 267, 285
Step down transformer, 693
Sterilization, 104
Sternocleidomastoid, 245
Steroids, 186, 509, 533, 580
StevensJohnson syndrome (SJS), 191, 216
management guidelines, 512
Stills disease, 254
Stomatitis medicamentosa, 209
Stomatitis venenata, 209
Strawberry cervix, 631
Strawberry gingivitis, 108, 617, 618
Strawberry tongue, 83, 232, 508
Stress reflux syndrome, 461
Stretch test, 14
Stridor, 428, 505
String of beads sign, 195
Stunted roots, 401, 578
SturgeWeber syndrome, 40, 45, 68
Stylomandibular ligament, 241
Subacute necrotizing sialadenitis, 283
Subchondral bone cysts, 251
Subcutaneous injections, 580
Subglottic larynx, 393
Sublingual space, 427, 429, 431
Subluxation, 248, 249
Submandibular nodes, 389
Submandibular space, 427, 429, 431
Submental nodes, 393, 394, 429
Submental space, 429
Submerged teeth, 49
Succinic acid, 463
Sucrose chelation theory, 406
Sugar substitutes, 634
Sulcus terminalis, 16
Sulfur colloid, 394, 788
Sulfur granules, 86, 87
Sunray appearance, 362, 371, 374, 375
Superficial fascia, 426
Superficial hemangiomas, 358
Superior joint space, 240, 247
Supernumerary teeth, see Hyperdontia
Supine hypotensive syndrome, 551
Supplemental teeth, 46, 47
Suppurative osteomyelitis, 433, 434
Supraclavicular nodes, 393, 608
Supraomohyoid triangle, 394
Suprasternal notch, 325, 393
Suttons ulcers, see Major aphthous ulcers
Sweet criteria, 121
Swift disease, 63
Swimmers erosion, 464
Swiss cheese pattern, 298
Symblepharon, 187, 195, 227
Synovial chondromatosis, 261, 262
Synovial chondrosarcoma, 261
Synovial fluid, 240
Synovial sarcomas, 261, 372
Synovitis, 249
Syphilis, 384, 612, 626
Syphilitic aortitis, 627
Syphilitic osteomyelitis, 628

896

Systemic lupus erythematosus


(SLE), 172, 597
Systemic sclerosis, 601

T
Tabes dorsalis, 612, 627
Talon cusp, 39, 40
Tam OShanter skull, 578
Tanakas ligament, 241
Target or double halo appearance, 522
Target lesion, 190
Tars, 382383
Taurodontism, 42, 43
T-cell immunity, 590
Technetium scan, 394
Teletherapy, 400
Telomeres, 225, 385
Temporal space, 429
Temporalis muscle, 241
Temporomandibular joint (TMJ), 239,
241, 243, 593, 840
arterial supply, 243
examination, 243
radiography, 751
sensory innervation, 243
transcranial view, 751
transorbital view, 752
transpharyngeal view, 751
venous drainage, 243
Temporomandibular joint imaging, 849
Teratoid cysts, 327
Tertiary syphilis, 627, 628
Test cavity, 422
Tetanolysin, 85
Tetanospasmin, 85, 86
Tetanus, 85
Tetracycline, 78, 444
Thalassemia, 490
Thermal burns, 135
Thermography, 796
indications, 797
patient preparation, 797
procedural requirements, 797
techniques, 796
Thermoluminescent dosimetry (TLD)
badges, 714
Thiamin deficiency, 455
Thinning of articular disk, 246
Thiocyanate, 383
Third molars in age estimation, 671
Thistle-tube-shaped pulp chamber, 59
Thorny radiation, 585
Thrombocytopenia, 488, 500
Thrombocytopenic purpura, 456, 500
Thrombotic thrombocytopenic purpura, 500
Thyroid collars, 709, 711, 715
Thyroid gland, 538, 539, 542
Thyroid storm, 541
Thyrotoxic crisis, 541
Thyrotoxicosis, 540, 591
Thyroxin, 538, 540
Tic douloureux, see Trigeminal neuralgia
Tissue biopsy, 395, 614
TNM staging, 391
Tobacco, 138, 381
Toluidine blue staining, 142, 397

Tongue hemorrhage, 662


Tonsillar pillars, 91, 110, 390
Tonsillitis, 83, 507
Topographical occlusal technique, 736
Tori, 19
Tornwaldts bursa, 324
Torus mandibularis, 19, 20
Torus palatinus, 20
Total filtration, 694
Tourniquet test, 498
Townes method, 749
Toxic epidermal necrolysis (TEN), 191
management guidelines, 512
Traditional CT, 397
Tram line calcifications, 68
Transcutaneous electric nerve stimulation
(TENS), 258, 484
Transient neonatal MG, 603
Transmigration, 48
Trapezius, 245
Traumatic arthritis, 252
Traumatic bone cyst, 321
Traumatic neuroma, 357
Traumatic ulcers, 197, 199
Treacher Collins syndrome, 27, 31, 33
Treponema pallidum, 200, 206, 612, 626
Triangular shaped face, 577
Trichiasis, 195
Trichinosis, 329
Trifid condyles, 34
Trifacial neuralgia, 120
Trigeminal neuralgia, 120123
Trigeminal neuropathy, 101, 628
Trigger point therapy, 258
Trigger points, 120, 125
Trismus, 85, 428
Trisomy, 22, 43
Trousseaus sign, 544
True cysts, 303, 304
True macroglossia, 22
TSH, 533, 535, 540
Tuberculoid leprosy, 610, 611
Tuberculosis, 101, 205, 606611
Tuberculous lymphadenitis, 608
Tuberculous meningitis, 607
Tuberculous osteomyelitis, 205, 608
Tuberous sclerosis complex, 232
Tularemia, 8384
Tumor markers, see Blood studies
Tumor suppressor genes, 143, 386
Tunneling technique, 659
Turner syndrome, 45, 326, 550
Turners hypoplasia, 51
Turners tooth, 51
Type I collagen, 543, 576, 592
Types of dislocation, 249
Tzanck cells, 176, 177
Tzanck smear, 201, 648
Tzanck test, 183

U
Ugly duckling sign, 369
Ulcerative colitis, 214, 520
Ulceronodular disease, 207, 627
Ultrasonography, 789792
Unicystic ameloblastoma, 336

Index

Unifocal eosinophilic granuloma, 647


Universal precautions, 104
Unstable angina, 478
Upper respiratory tract infections, 506
UrbachWiethe disease, 646
Uremia, 514, 515
Uremic fetor, 514
Uremic frost, 515
Uremic gastroenteritis, 514
Uremic stomatitis, 518
Uremic syndrome, 514
Uremic toxin, 514, 517
Usher syndrome, 56, 596
Uto-Aztecan premolar, 44

B1-thiamine, 640
B2-riboflavin, 640
C, 455, 639
D, 455, 637
E, 145, 455
K, 502, 638
Vitamin K deficiency, 503
Volatile sulfur compounds, 444
Von Ebners glands, 17
Von Recklinghausen disease of bone, 542
Von Willebrand factor, 497
Von Willebrands disease, 503
Vrolik syndrome, 576

W
V
Vanishing bone disease, 585
Varicella zoster infection, 178, 201
Variegate porphyria, 643
Vascular disorders, 474, 476, 498, 499
Vascular malformations, 68, 357, 358
Velscope and Vizilite plus, 395
Venereal disease research laboratory (VDRL)
tests, 613, 628
Venereal diseases, 625
Venereal wart, see Condyloma acuminatum
Verapamil, 446
Verocay bodies, 356
Verruca vulgaris, 346
Verrucous carcinoma, 366367
Verrucous hyperplasia, 346
Verrucous leukoplakia, 138, 141
Vertical angulation, 740
Vietnamese time-bomb, 85
Viral pharyngitis, 507
Visual analog scale (VAS), 116
Vital signs, 482, 550
Vital staining, 395, 397
Vitality tests, 468, 522
Vitamin(s), 636641
A (retinol), 636
B complex, 455, 640

Waddling, 587
Wallerian degeneration, 529
Wall mounted intraoral radiographic unit,
690
Warfarin, 484, 504
WarthinStarry method, 89, 613
Warthins tumor, 294, 295
Water brash, 278, 519
Water-clear cells, 310
Water lily sign, 328
Water soluble vitamins, 636, 639
Waters view, see Skull radiography
WBC disorders, 210
Weber and Fechners law, 111
Webers glands, 267
Weeping lubrication, 247
Wegeners granulomatosis, 617, 618
Well-differentiated squamous cell
carcinoma, 398
Wet beriberi, 640
Whartons duct, 267, 280
Wheezing, 505
Whiff test, 631
White blood cells, 490
White coat hypertension, 477
White lesion, 133
White sponge nevus, 166

White spots, 819


White strawberry tongue, 83
Wickhams striae, 147, 219, 236
Wilms tumor, 31
Winchester syndrome, 586
Witkops disease, see Hereditary benign
intraepithelial dyskeratosis
Wood-hard tongue, 646
Wormian bones, 540, 578

X
Xeroderma pigmentosum, 226
Xerophthalmia, 271, 636
Xerosis, 636
Xerostomia, 267270, 700
X-rays, 685, 687, 689
properties, 689
publications, 685
X-ray beam angulation and
alignment, 727
X-ray equipment, 706, 710, 712
X-ray photons, 695
X-ray tube, 692
schematic diagram, 692
Xylitol, 276, 634

Y
Yaws, 612, 626
Yellow form, 657
YunisVaron syndrome, 48

Z
Zahn lines, 16
ZiehlNeelsen stain, 606, 609
Zinc sulfate, 229, 401
ZinsserEngman-Cole syndrome, 225
ZollingerEllison syndrome, 523
Zoster ophthalmicus, 179, 235
Zoster sine herpete, 124, 179
Zygomatic bone, 832
Zygomatic process, 832
Zygomycosis, 615

897

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