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 - Volume 18, Issue 3 (August
2000) - Copyright © 2000 W. B. Saunders Company - About This Journal
DOI: 10.1016/S0733-8627%2805%2970144 -9

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1
University of Chicago Adult Emergency Services (RAM)
2
Section of Emergency Medicine, Department of Medicine, University of Chicago
Hospitals, Chicago, Illinois (RAM, MJC)

Address reprint requests to

Robert A. Mulliken, MD, FACEP
Department of Medicine
Section of Emergency Medicine
The University of Chicago Hospitals
5841 South Maryland Avenue
MC 5068
Chicago, IL 60637

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Lesions in the mouth are characteristic features of nutritional deficiency.

Unfortunately, few of these lesions are pathognomic for a particular deficiency and
can in fact occur when no deficiency is present.
Ö ossitis is is generalized inflammation of the surface of the tongue and is
characterized by an enlarged, erythematous, and painful tongue. Median rhomboid
g ossitis is a congenital diamond-shaped area of redness and swelling just anterior to
the circumvallate papillae and is not associated with disease. Chei osis (also known as
angu ar stomatitis), a fissuring of the angles of the lips without inflammation, is often
associated with candidal infections or overexposure to sunlight.

Angular stomatitis was once thought to be pathognomonic for riboflavin (vitamin B 2 )

deficiency but has been seen with other deficiencies. Other oral symptoms include a
burning sensation in the mouth, glossitis, bleeding gums, and atrophy of the tongue.
Oral lesions are common early in niacin deficiency (pellagra), including glossitis,
stomatitis, fissuring and atrophy of the tongue, and mouth soreness. The advanced
form of niacin deficiency is characterized by the triad of dermatitis, diarrhea, and
dementia. Vitamin C (ascorbic acid) deficiency, or scurvy, is mainly dietary in origin
and is characterized by an increased tendency to bleed. Oral manifestations include
swollen, bleeding gums (a symptom not found in edentulous patients), loss of teeth,
and xerostomia (loss of normal salivation with dryness of the mouth).

Patients with pyridoxine (vitamin B6 ), vitamin B12 , and folate deficiencies present
with glossitis and stomatitis. Iron deficiency, although usually associated with
anemia, can also cause angular stomatitis, atrophy of the lingual papillae, and
glossitis. The syndrome of cheilosis, glossitis, and dysphagia (caused by esophageal
webs) associated with iron deficiency anemia is termed the P ummer-Vinson
syndrome.



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Several extraoral gastrointestinal diseases can cause oral symptoms. Amongst the
most prominent of these diseases is the Peutz-Jeghers syndrome, an autosomal
dominant syndrome characterized by multiple hamartomatous polyps throughout the
gastrointestinal tract. Oral signs include dark-brown melanotic spots on the lips and
buccal mucosa. Malignant transformation of the polyps is rare. Another polyposis
syndrome, Cowden's syndrome, is characterized by multiple hamartomas throughout
the body. Oral papillomas are common, as are tricho emmomas (flesh-colored adnexal
tumors found on the tongue and gingiva). Cowden's syndrome carries a high risk of
skin and thyroid malignancy.

The inflammatory bowel diseases, ulcerative colitis and Crohn's disease, are
commonly associated with oral pathology. These diseases are idiopathic chronic
inflammatory processes involving the bowel. Ulcerative colitis is limited to the colon
and occasionally the distal small bowel and consists of superficial inflammation
causing abdominal cramping, bloody diarrhea, fever, and weight loss. Five percent to
10% of patients develop aphthous u cers (i.e., small, painful, round ulcers found
anywhere in the oral cavity; Fig. 1) and angular stomatitis, both of which arise during
the active phase of the disease and then disappear as the colitis resolves.

"-! Aphthous ulcers on the base of the tongue.

Crohn's disease is characterized by focal, transmural inflammation of the bowel wall
and can involve any portion of the gastrointestinal tract. Symptoms include abdominal
cramping, nonbloody diarrhea, fever, and weight loss. The mouth can be a site of
active disease, presenting as aphthoid u cers, minute painful ulcerations clinically
indistinguishable from aphthous ulcers, which also can occur with active disease.

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The collagen vascular diseases are characterized by diffuse, multiple-system

manifestations, and the mouth is often involved. mystemic upus erythematosis is a
syndrome of autoimmune origin consisting of inflammation occurring in different
organ systems. Diagnosis of lupus is clinical, based on the presence of various
criteria, including multiple, painless ulcers on the hard and soft palate. These ulcers
are seen in as many as 40% of patients with lupus and are usually benign, although
rarely they are the cause of airway compromise. Although not one of the criteria for
diagnosis, vasculitis lesions the lips, such as purpura or subcutaneous nodules are
sometimes found in these patients.

m o gren syndrome is characterized by lymphocytic infiltration of salivary and

lacrimal glands, with a resulting decrease in production of tears and saliva known as
the sicca syndrome. Sjogren syndrome can be primary or can arise secondary to other
autoimmune diseases, such as rheumatoid arthritis or SLE. The decrease in saliva
production causes dryness of the mouth (xerostomia), causing difficulty swallowing
dry foods, an inability to speak continuously, and a burning sensation in the mouth.
The presence of dental caries becomes more common. Physical examination
demonstrates dryness of the mouth as well as atrophy of the filiform papillae on the
dorsum of the tongue, giving the tongue a smooth, glossy appearance. Two thirds of
patients with primary Sjogren syndrome also have parotid gland enlargement owing
to lymphocytic infiltration.

The sicca syndrome is not limited to Sjogren syndrome. Xerostomia can be caused by
viral infections, diabetes, trauma, irradiation, and medications (particularly
psychotherapeutic, antihypertensive, and parasymptholytic). Bilateral parotid gland
enlargement can be caused by viral infections (particularly mumps and HIV),
sarcoidosis, amyloidosis, diabetes, acromegaly, and bulimia. Treatment of xerostomia
includes increased fluid intake and methylcellulose, and strict attention to dental
hygiene must be stressed. Parotid gland enlargement resolves with systemic
corticosteroids, but treatment usually is reserved for episodes of painful swelling.

Bec het disease is a vasculitic syndrome of unknown etiology; 97% of patients with
this disease present with recurrent, painful ulcers. These ulcers are 2 to 10 mm in
diameter, can be shallow or deep, and have a yellow, necrotic base. They appear
anywhere in the oral cavity, last 1 to 2 weeks, and resolve without scarring. Other
aspects of the disease include recurrent genital ulcers, uveitis, cutaneous vasculitis,
arthritis, or meningoencephalitis. Treatment of oral ulcers is with topical
corticosteroids, and azathioprine has been shown to be useful in reducing recurrences.
Patients taking acyclovir have shown no improvement in the course of their disease.

‘eiter syndrome is a common cause of inflammatory oligoarthropathy in young male

patients. The arthritis is accompanied by conjunctivitis and urethritis. An association
with HLA-B27 and chlamydia urethritis or shige a dysentery has been demonstrated.
A common symptom of Reiter syndrome is superficial ulceration of the buccal
mucosa, which is usually transient and asymptomatic.

mystemic sc erosis, or sc eroderma is a syndrome characterized by increased fibrosis

of connective tissue of the skin and internal organs. Dermatologic symptoms include
thickened skin that is smooth and has limited range of motion. Patients with
scleroderma involving the face will demonstrate a decrease in the intercommisural
distance of the lips, a decrease in the interincisal distance on maximal mouth opening,
and a decreased oral aperture. The presence of oral mucosal telangiectasia is common,
as is a sicca syndrome similar to that of Sjogren syndrome.

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Acromega y is a syndrome of soft tissue swelling and bony hypertrophy caused by

excessive growth hormone secretion during adult life, usually the result of a pituitary
tumor. Symptoms are usually insidious and are best determined by comparing the
patient with photographs taken a decade earlier. Oral signs include an enlarged
tongue, which has characteristic indentations of the lateral edges resulting from the
tongue being compressed against the teeth. A similar finding is present in
hypothyroidism and is the result of myxedematous deposition in the tongue.
Prognathism (jutting of the jaw), malocclusion of the teeth, and wide spacing between
the teeth can also be seen in the acromegalic patient, and is the result of hypertrophy
of the mandible.

Addison disease is adrenal insufficiency caused by destruction of the adrenal cortex.

The resulting loss of glucocorticoids results in uninhibited adrenocorticotrophic
hormone (ACTH) release. ACTH is derived from the polypeptide pro-
opiomelanocortin, which also contains melanocyte-stimulating hormone (MSH). The
increased MSH results in generalized hyperpigmentation. In the mouth, bluish-black
patches are seen in up to 82% of patients. This hyperpigmentation is not seen in
secondary adrenal insufficiency, in which the release of ACTH (and, therefore, pro-
opiomelanocortin) is inhibited by exogenous steroids.

Diabetes mellitus does not produce specific oral lesions but does predispose to oral
infections, particularly Candida.

 

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Pemphigus vu garis is an acquired autoimmune phenomenon causing acantholysis

(i.e., loss of adhesion between layers of the epidermis), resulting in superficial bullae.
These bullae form in areas of stress or pressure, and the oral mucosa is involved in
90% of cases (bullae in the mouth are the presenting symptom in one half of the
patients seen). Untreated pemphigus can progress to generalized sloughing of the
epidermis, leading to fluid loss, sepsis, and death. Treatment is with high-dose
steroids, methotrexate, or intramuscular gold. Bu ous pemphigoid is an autoimmune
disorder of elderly patients, resulting in large, tense blisters that do not spread and are
not life threatening. Oral lesions are present in one third of patients. Pemphigus is
distinguished from bullous pemphigoid by the presence of the Niko sky sign (i.e.,
extension of cleavage by lateral pressure on bullae).

Erythema mu tiforme is a dermatitis caused by circulating immune complexes as a

response to an antigenic stimulus. As the name suggests, the dermatitis takes on a
variety of forms, including erythematous plaques, blisters, and target lesions (i.e., a
central, purple region surrounded by a pale zone that is itself surrounded by an
erythematous ring). Involvement of the mucous membranes (including the oral
mucosa) is termed the mtevens-Johnson syndrome. The inciting antigen can be a
medication (e.g., penicillin, sulfa, phenytoin), or infection (i.e., herpes simplex virus
[HSV], mtreptococcus, Mycop asma), but one half of all cases are idiopathic.
Intravenous fluids and airway protection can be necessary if oral involvement is
extensive.

Lichen p anus is a papulosquamous disorder affecting mucus membranes,

characterized by a pruritic, flat-topped, violaceous lesion topped with a network of
greyish lines, termed Wickham striae. Oral involvement is rare, but, when present, is a
bilateral, netlike eruption on the buccal mucosa. Treatment is with topical
corticosteroids. The etiology is often unknown but can be a reaction to certain
medications (e.g., thiazides, antimalarials, phenothiazines, or gold).


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There are a multitude of infectious diseases that can invade the oral mucosa directly.
This section describes those systemic infections that are associated with oral lesions,
and those oral infections that are associated with disease states.

mcar et fever, a manifestation of group A streptococcus infection, has characteristic

findings that include sore throat, fever, and a confluent, papular rash with a
sandpaper-like texture found on the neck and chest. Oral lesions include circumoral
pallor, punctate redness of the palate (Fig. 2) , and the classic "strawberry tongue"
(i.e., a white-coated tongue through which inflamed papillae project; Fig. 3) . The
strawberry tongue is also associated with toxic shock syndrome, (TSS) caused by
mtaphy ococcus aureus infection. TSS, often associated with tampon use or prolonged
nasal packing, also produces a generalized, erythematous, macular eruption that
blanches under pressure. The strawberry tongue occasionally is denuded of its
epithelium, leaving behind a smooth, red surface dotted with papillae, termed the
"raspberry tongue."

"0! Punctate erythematous lesions on the palate, seen in patients with scarlet fever.
 "1! mtrawberry tongue. Note the enlarged papillae projecting above the surface of the
tongue, which is smooth and red.

myphi is, caused by the spirochete Treponema pa idum, frequently demonstrates oral
manifestations characteristic of the stage of disease. Primary syphilis is characterized
by the chancre, a single, painless papule that becomes eroded and indurated, taking
several weeks to heal. Although genital chancre is more common, oral chancre can be
the presenting lesion of primary syphilis, especially in homosexual men.

Secondary syphilis is characterized by lesions arriving 1 to 2 months after the initial

chancre. Superficial mucosal erosions occur in the mouths of 10% to 15% of patients
with secondary syphilis accompanied by generalized lymphadenopathy. Both these
lesions and the primary chancre are highly contagious. Finally, the gumma is a late
manifestation of syphilis, occurring 1 to 10 years after primary infection, and is now
uncommon because of the use of penicillin. Lesions begin as painless nodules that
ulcerate and spread, with undulating borders, and can occur in the mouth. All of the
above syphilitic lesions respond rapidly to penicillin.

Congenita syphi is occurs when the spirochete passes through the placenta; this can
occur at any time during maternal infection (although the greatest risk is early in the
course of the disease). This disorder produces characteristic dental abnormalities
including Hutchinson's teeth, widely spaced upper central incisors which are centrally
notched. The molars are also malformed, with multiple, poorly defined cusps (giving
rise to the name mu berry mo ar). Extraoral manifestations include vasculitic rash,
deformity of the nasal bones and the tibia, and late-onset arthritis of the knees.

Routine immunizations against many of the viruses causing systemic disease with oral
lesions has greatly decreased exposure to these diseases, making diagnosis more
difficult in case of sporadic outbreaks. Patients with meas es (rubeola) present with a
prodrome of fever, coryza, cough, and conjunctivitis, followed by the outbreak of
rash. Kop ik spots are commonly described lesions on the buccal mucosa, consisting
of tiny white spots mounted on a bluish-red areola. Koplik spots usually precede the
generalized wash by 1 day.

Öerman meas es (rubella) has a prodrome of malaise, headaches, fever, and

conjunctivitis, although children can develop a rash without the prodrome.
Forscheimer spots are small, red lesions on the soft palate that also precede the
generalized rash. Finally, patients with mumps present with a low-grade fever,
malaise, headache, and anorexia, followed by parotitis (i.e., edema of bilateral parotid
glands caused by edema of Stensen's duct.)

Several viruses cause intraoral ulcerations. HSV causes a gingivostomatitis during

primary infection, presenting as vesicular lesions of the gums and lips that ulcerate
and are painful. Recurrent attacks of HSV tend to occur on the vermilion border of the
lip, and intraoral recurrences are rare. Varice a zoster virus (VZV) causes chicken
pox, with a generalized vesicular rash over the entire body. Intraoral vesicles are
common, especially when the infection occurs in adults. Coxsackie A virus is the
suspected causal agent for herpangina, characterized by painful vesicles on the tongue
and oropharynx, which then ulcerate. Also associated with coxsackie A is hand-foot-
mouth disease, in which oral ulcers are accompanied by painful lesions on the feet
and the fingers.

Fungal infections of the mouth are common, with Candida a bicans representing most
symptomatic infections. Candida is part of the normal flora of the mouth and tends to
produce symptoms only when the normal host defenses or the normal flora are
altered. Common disruptions include systemic antibiotics, xerostomia, diabetes
mellitus, anemia, and immunocompromise.

Candida infections produce one of three syndromes: pseudomembranous,

erythematous, and hyperplastic. Pseudomembranous candida, also known as thrush,
appears as a thick, white plaque that can be rubbed off to reveal red, occasionally
bleeding, tissue underneath. Hyperp astic candida is the result of fungal hyphae
invading the epithelial layers and presents as raised, whitish plaques that do not rub
off; common locations are the anterior buccal mucosa and the tongue. Erythematous
candida produces a diffuse mucosal erythema without plaque formation and is found
most commonly in patients with xerostomia. Common associated symptoms are
atrophy of the filiform papillae and a burning sensation in the mouth. Candida is also
a common cause of angular chelitis, and overgrowth can occur in angular chelitis
from other causes.

Infection with the human immunodeficiency virus (HIV) is associated with an

increased risk of fungal and viral infections in the mouth, as well as several lesions
unique to this condition. Oral thrush is exceedingly common, occurring in 80% to
90% of all cases of AIDs. Other mycoses are also common, including aspergillosis,
histoplasmosis, zygomycosis (mucormycosis), and cryptococcosis. Patients with these
mycoses can present with fungal overgrowths, chronic ulcerations, or bizarre lesions.
Diagnosis is made by visualization of fungal hyphae under microscopy.

Chronic aphthous ulcers are more common in patients with AIDs than in normal
hosts, and the cause is often unknown, although cytomegalovirus and HSV are often
suspected. Outbreaks of HSV are more common in patients with AIDs and tend to be
more severe. Infection with human papillomavirus can cause oral warts, especially in
homosexual men. Mollusca contagiosum is an uncommon oral infestation in these
patients.

Kaposi sarcoma (KS) is a multifocal, vascular malignant tumor that appears as

erythematous, purplish, raised lesions. They can appear anywhere on the skin, mucous
membranes, and internal organs. In the mouth, the palate is a common site for KS
lesions. An association with HSV 8 has been proposed. Treatment is excision and
localized irradiation. Lymphomas also can occur in the mouth.

Ora hairy eukop akia consists of white, fibrillar projections on the sides of the
tongue and is a lesion unique to HIV disease. An association with Epstein-Barr virus
is suspected, and treatment is with acyclovir.
Öingivitis and periodontitis are more common in patients with AIDs than in the
normal population. Treatment is with antibiotics to cover oral flora, including
anaerobic organisms. The gingivitis occasionally can become necrotizing, in which
case anaerobic coverage should be added.

 
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Heavy metal poisoning can leave evidence in the oral mucosa. Lead ingestion, which
is normally accidental, produces a blue-gray gingival line just underneath the teeth.
This line, which represents deposition of lead in the mucous membranes, is found in
up to 20% of adults with lead poisoning but is uncommon in children. Inhalation of
elemental mercury vapor can also cause a gingival line and is often complicated by
loosening of teeth, gingivitis, and stomatitis.

Amy oidosis is a disease of unknown etiology, in which a protein, amyloid, is

deposited in the extracellular spaces of any tissue. In the mouth, such deposition can
be seen as raised, waxy papules and plaques on the surface of the tongue.

Kawasaki syndrome is a disease of unknown etiology occurring primarily in children.

In addition to a scarletiniform rash of the trunk and extremities, patients present with
magenta discoloration of the palms and soles, which eventually desquamate. The oral
manifestations include red, cracked lips, erythema of the mucous membranes, and
strawberry tongue. This syndrome carries a high risk of coronary artery aneurysm,
with an associated death rate of up to 30% in untreated patients.

One of the more prominent side effects of phenytoin (Dilantin) use is gingival
hyperplasia caused by fibrin deposition in the subcutaneous tissues. Similar
deposition has been reported with nifedipine and cyclosporin use.

Pregnancy-associated gingivitis produces hyperemia and swelling of the gums

associated with pyogenic granuloma formation. An epu is is a localized, highly
vascular welling of the gums that occurs during the pregnancy and resolves after
delivery.

The triad of teeth erosion, rampant dental caries, and parotid gland swelling are often
found in patients with bulimia. A typical high-carbohydrate diet contributes to the
formation of caries, whereas repeated forced vomiting causes acid erosion of the teeth
and reactive edema of the salivary glands.

,


Many systemic diseases have associated oral symptoms. Occasionally, patients with
these diseases present with lesions that occur primarily in the mouth. Although few
systemic diseases have strictly pathognomonic lesions of the oral mucosa, a careful
examination of the oral cavity can often lend important clues to making a diagnosis.

2c3 


The authors would like to thank Steve Lilyveld, MD, of the Department of Pediatrics,
University of Chicago Hospitals, Chicago, IL, for his aid in collecting photographs.



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