Aliment Pharmacol Ther 2005; 21: 295306.

doi: 10.1111/j.1365-2036.2005.02333.x

Review article: oral ulcers and its relevance to systemic disorders

S. R. PORTER* & J. C. LEAO
*Oral Medicine, Division of Maxillofacial Diagnostic, Medical and Surgical Sciences, Eastman Dental Institute for Oral Health
Care Sciences, UCL, University of London, London, UK; Departamento de Clinica e Odontologia Preventiva, Disciplina de
Estomatologia, Universidade Federal de Pernambuco, Brazil
Accepted for publication 9 November 2004

SUMMARY

Oral ulceration is a common problem, and is sometimes

a marker of gastroenterological disease. Patients with
signs or symptoms of oral ulcers are sometimes referred
to gastroenterology clinics, however, in most instances
the ulcers does not reflect gastrointestinal disease.

INTRODUCTION

Oral ulcers is a very common disorder of the oral

mucosa. Several predisposing factors have been suggested and oral ulcers can be a feature of various systemic
disorders including inflammatory bowel disease. The
nature, site, duration and frequency of oral ulcers are
determined by the underlying systemic condition. In
addition, usually histopathological examination warrants a definitive diagnosis in the majority of conditions
described in this paper. Clearly, it is not possible to
discuss all oral conditions giving rise to oral mucosal
ulcers; hence, the present article will focus on ulcerative
disorders either of general clinical significance, or
relevant to gastroenterology.
ORAL ULCERS TRAUMATIC AETIOLOGY

Most traumatic ulcers of the mucosa are due to

physical trauma. In addition, ulcers may arise with
Correspondence to: Prof. S. R. Porter, Oral Medicine, Division of Maxillofacial Diagnostic, Medical and Surgical Sciences, Eastman Dental Institute for Oral Health Care Sciences, UCL, University of London, 256 Grays
Inn Road, London WC1X 8LD, UK.
E-mail: sporter@eastman.ucl.ac.uk
2005 Blackwell Publishing Ltd

Indeed, a spectrum of disorders other than those of

the gut can give rise to oral mucosal ulcers ranging
from minor local trauma to significant local disease
such as malignancy or systemic illness. This present
article reviews aspects of the aetiology, diagnosis and
management of common ulcerative disorders of the oral
mucosa.

local application of aspirin,1 cocaine or smoking

crack cocaine (e.g. on the palate).2 Snorting cocaine
may rarely cause necrosis, possibly associated
with ischaemia, at the floor of nose and eventual
ulcers of the hard palate and oronasal fistula formation.3
Local radiotherapy and some cytotoxic chemotherapy
regimes can cause oral mucositis. This manifests as
multiple areas of painful mucosal erythema, ulcers and
sloughing.4 The precise aetiology of the mucositis
remains unclear, although most likely reflects a loss of
basal cell proliferation5 rather than a reaction to
changes in the local oral microflora (e.g. rises in
Gram-negative bacteria, particularly Enterobacteriaceae).6 This mucositis, akin to that of the bowel, is
difficult to manage specifically. Benzydamine hydrochloride mouthrinse or spray may provide symptomatic
relief, but often effective analgesia requires opioids. The
clinical feature of oral mucositis does not significantly
improve with topical chlorhexidine gluconate, although
this is commonly used in clinical practice. Novel
regimes for the treatment of mucositis include granulocyte-macrophage colony-stimulating factor (GM-CSF)
and protegrins, although these are presently in the early
stages of clinical trial.7, 8
295

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S. R. PORTER & J. C. LEAO

Necrotizing sialometaplasia
Necrotizing sialometaplasia is an uncommon disorder
that typically gives rise to large areas of deep ulcers of
one side of the hard and/or soft palate.9 Necrotizing
sialometaplasia typically has a traumatic basis and can
be a feature of the bulimia nervosa.10 It is suggested
that the local trauma causes ischaemia with resultant
tissue necrosis. The clinical features may mimic those of
squamous cell carcinoma (SCC), and histopathologically
the profound epithelial hyperplasia, together with
salivary gland squamous metaplasia, can be confound
with neoplasia.
VIRAL DISEASES: HERPES SIMPLEX INFECTION

Herpes simplex virus 1

As detailed in Table 1, a wide range of infections can give
rise to oral ulcers. Primary herpes simplex type 1 (HSV-1)
remains the most common viral precipitant of ulcers.
Affected individuals may have widespread, small, superficial ulcers of the oral mucosa (Figure 1). The gingiva are
often swollen and ulcerated, giving rise to features akin to
acute necrotizing ulcerative gingivitis (ANUG) (see
below). While previously regarded as a disease of
childhood, often primary HSV-1 infection arises in the
second or third decade of life.11 Severe and/or recurrent
HSV-1 infection sometimes presenting atypically may be
Table 1. Infectious causes of oral mucosal ulcers
Viral

Bacterial

Fungal

Protozoal

Herpes group
Human herpes simplex 1
Human herpes simplex 2
EpsteinBarr virus
Varicella zoster virus
Cytomegalovirus
Human herpesvirus 8
(Kaposis sarcoma herpesvirus)
Coxsackie viruses (e.g. herpangina,
hand foot and mouth disease)
Human immunodeficiency viruses
Treponema pallidum (syphilis)
Acute necrotizing ulcerative gingivitis
Mycobacterium tuberculosis
Other mycobacterioses
Candida albicans (uncommon)
Aspergillosis
Paracoccidiodomycosis
Histoplasmosis
Mucormycosis
Leishmaniasis

Figure 1. Oral ulcers on the ventral surface of tongue in primary

herpes simplex infection.

suggestive of underlying immunodeficiency, in particular

lymphoproliferative disease or HIV disease.12
Therapy typically comprises symptomatic relief,
although systemic aciclovir and other anti-virals should
be considered when disease is severe, recurrent or
atypical.13 Aciclovir resistance may arise in immunosuppressed patients receiving repeated therapy, hence
the need for famciclovir, valciclovir or foscarnet.14
Interestingly, foscarnet itself may give rise to oral
ulcers,15 and while aciclovir may be effective and useful
in the treatment of erythema multiforme, it can itself
give rise to this mucosal disorder.
About 5% of patients who have primary HSV-1
infection will develop recurrent episodes of herpes
labialis (cold sores). This comprises episodes of paraesthesia, erythema, vesiculation, pustulization and ulcers
at the mucocutaneous junctions of the lips and/or nose.
Precipitants of herpes labialis include concurrent illness,
UV light and pregnancy. Effective therapy comprises 5%
aciclovir16 or 1% penciclovir.17 Herpes labialis may
itself be a precipitant of erythema multiforme.18
Herpes simplex virus 2
Although uncommon, HSV-2 can give rise to oral ulcers
akin to that of mild primary HSV-1 infection. This oral
ulcers arises as a consequence of orogenital transmission of the causative virus.
EpsteinBarr virus
Ulcers caused by EpsteinBarr virus (EBV) is rare, but
may be a feature of infectious mononucleosis. The
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REVIEW: ORAL ULCERS AND SYSTEMIC DISORDERS

297

ulcers comprises a few small superficial ulcers of the oral

mucosa. EBV is more typically associated with the ulcers
of some non-Hodgkins lymphomas19 or white patches
termed oral hairy leukoplakia (OHL) that may arise in
immunodeficiency (e.g. HIV disease, corticosteroid or
other systemic immunosuppressant therapy, etc.). Of
relevance, OHL has been observed in patients with
inflammatory bowel disease receiving immunosuppressive regimes.20
Cytomegalovirus
Cytomegalovirus (CMV) may give rise to large, chronic
ulcers of the oral mucosa or gingiva.21 These CMVrelated ulcers occur exclusively in significant immunodeficiency, notably severe HIV disease. The diagnosis of
such ulcers is difficult and is often only confirmed by
resolution of ulcers with ganciclovir therapy.22
Human herpesvirus 8 (Kaposis sarcoma herpes virus)
Human herpesvirus 8 (HHV-8) is the cause of Kaposis
sarcoma (KS), a lesion commonly arising within the
mouth of patients with severe HIV disease or a feature
of profound iatrogenic immunosuppression (e.g. in
patients with inflammatory bowel disease). Oral KS
typically affects the palate or gingiva and manifests as
red, blue or purple macules, papules, nodules or
ulcers.23 Confusingly, oral KS may occasionally be
non-pigmented, and hence may mimic SCC.24
Kaposis sarcoma of the anterior gingiva may be
unsightly, and rarely gingival lesions will cause destruction of the underlying periodontal tissues leading to loss
of teeth and sequestration of bone.
Oral KS in HIV disease may reduce or resolve with
highly active antiretroviral therapy (HAART), although
some oral lesions have been reported to resolve
(probably transiently) with local radiotherapy, local
injection of cytotoxics or sclerosants.2527
Human immunodeficiency virus
The oral consequences of HIV disease are reviewed in
detail elsewhere.28, 29 Infection with HIV gives rise to a
wide spectrum of oral ulcerative lesions (Table 1). The
majority of these are detailed in other sections of the
review. A minority of patients with severe HIV disease
can develop deep, necrotic ulcers of unknown aetiology
(Figure 2). These ulcers are painful, cause profound
2005 Blackwell Publishing Ltd, Aliment Pharmacol Ther 21, 295306

Figure 2. Deep, necrotic ulcer in HIV infection.

dysphagia and/or dysarthria and can arise on any oral

mucosal surface, although the buccal and pharyngeal
mucosae are the more commonly affected sites. The
precise aetiology of these HIV-related ulcers is
unknown.30 HHV-8 DNA has been detected within
these, although whether the virus is causative or merely
a passenger remains unclear.31 Of note, the ulcers
typically resolve with systemic thalidomide (e.g.
200 mg daily) perhaps reflecting an antitumour necrosis factor (TNF)-a effect in keeping with a viral
aetiology.32 Small number of patients with HIV disease
may have ulcers similar to that of recurrent aphthous
stomatitis (RAS), although whether the frequency of
RAS in HIV is truly increased remains unclear.33

BACTERIAL INFECTION

Acute necrotizing ulcerative gingivitis

Acute necrotizing ulcerative gingivitis (Vincents disease, trench mouth, acute ulcerative gingivitis) is a nonspecific ulcerative disorder almost always localized to
the gingivae.34 Associated contributing factors include
poorly controlled diabetes mellitus, tobacco smoking,
immunodeficiency (notably severe HIV disease) and
possibly psychological stress.
Acute necrotizing ulcerative gingivitis manifests as
painful ulcers of the gingival margins, particularly the
interdental areas (Figure 3). The ulcers may be localized
or generalized and when severe will give rise to cervical
lymphadenopathy and very rarely pyrexia and malaise.
There is often oral malodour. Long-standing or recurrent

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S. R. PORTER & J. C. LEAO

Figure 3. Inverted papillae in acute necrotizing ulcerative gingivitis.

disease may lead to destruction and loss of interdental

papillae.
An ANUG-like disease termed cancrum oris (noma) can
arise in profoundly malnourished children and adults.
Unlike the ANUG in immunocompetent individuals, the
ulcers of cancrum oris spreads to the adjacent soft tissues
leading to necrosis of the lips and/or cheeks. Cancrum oris
has most commonly been reported in children in Central
Africa, the malnourishment arising from poverty because
of political and economical unrest.35
An ANUG-like disorder which spreads to the underlying bone and adjacent soft tissues termed necrotizing
stomatitis has been reported in a small number of
patients with severe HIV disease. Occasionally, this
disorder may be the first, and/or only clinical manifestation of HIV disease.36
The ulcers of the ANUG typically resolves with the
removal of deposits of plaque and calculus and the
topical application of chlorhexidine gluconate mouthrinse (0.2%) or gel (1%). Systemic antimicrobials
(e.g. metronidazole or phenoxymethyl penicillin) may
be required when the gingival is profound and/or
there is systemic upset. Cancrum oris additionally
requires tissue debridement and correction of the
underlying malnourishment, however, the prognosis
of affected children is often poor.37 Posthealing fibrosis
and scarring is a significant complication of cancrum
oris.

number of subjects affecting with Treponema pallidum.38

Oral ulcers can arise in primary, secondary or tertiary
disease. In primary disease, a chancre can develop on
the oral mucosa as a consequence of direct contact with
an infective lesion. The ulcers of primary infection
typically arises on the upper (in females) or lower lip (in
males) (Figure 4) and manifests as a superficial to deep
isolated ulcer sometimes with a rolled edge. Occasionally, there can be isolated ulcers of the gingiva.39 The
oral chancre typically resolves with antimicrobial
therapy.40 Secondary syphilis can give rise to multiple
areas of superficial papules and ulcers, some of the latter
being serpiginous and thus termed snail-track ulcers.
Tertiary disease may produce ulcers as a consequence of
gumma formation, the ulcers manifesting as isolated
areas of chronic ulceration sometimes with the destruction of the underlying soft and/or hard tissues
(e.g. palate or tongue).
Mycobacterial infection
Primary oral infection of Mycobacterium tuberculosis is
rare;41 more commonly, tuberculosis infection of the
oral mucosa arises secondary to pulmonary disease.
Tuberculosis typically presents as solitary, necrotic
ulcers of the tongue. Infection by atypical mycobacteria
(e.g. Mycobacterium avium complex) is rare but may
affect the oral mucosa or gingiva, usually in HIVinfected individuals.42

Treponema pallidum
The frequency of oral ulcers because of infective syphilis
is likely to increase as a consequence of the rising

Figure 4. Solitary ulcer (chancre) on the lower lip of a patient

diagnosed with primary syphilis.
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REVIEW: ORAL ULCERS AND SYSTEMIC DISORDERS

FUNGAL INFECTIONS

Table 2. Systemic disease likely to give rise to oral ulcers

While Candida species, usually Candida albicans, is the

most common fungal infection of the mouth, this rarely
gives rise to oral ulcers. Although chronic mucocutaneous candidosis (CMC) may occasionally give rise to
ulcers of the dorsum of tongue. Systemic mycoses may
cause oral ulcers, typically in immunosuppressed hosts.
In HIV disease, Aspergillus fumigatum may give rise to
long-standing ulcers of the gingiva43 or oral mucosa as
may Histoplasma capsulatum.44 South America paracoccidiodomycosis (South American Blastomycosis) may
give rise to large areas of ulcers reminiscent of oral SCC,
this infection arising in both immunocompetent and
immunosuppressed individuals.45, 46 The other infective
causes of oral ulcers are outlined in Table 2.

Haematological

IDIOPATHIC ULCERS

Recurrent aphthous stomatitis

Recurrent aphthous stomatitis is the most common
non-infectious and non-traumatic oral mucosal ulcerative disorder. It is characterized clinically by recurrent
bouts of oral mucosal ulcers in an otherwise well
subject. The ulcers arises every 412 weeks and may be
classified as minor, major and herpetiform (Table 3).
The ulcers are superficial, rounded and have a yellow
coloured slough with surrounding erythema. The ulcers
of major RAS (Figure 5) may cause scarring on healing,
and it has been suggested that the ulcers of herpetiform
RAS (Figure 6) may coalesce to produce large areas of
ulcers that heal with scarring. Rarely major aphthous
stomatitis may cause tissue destruction (e.g. of the soft
palate).
Undoubtedly RAS has an immunologically mediated
pathogenesis but the precise cause of RAS remains
unclear.47 Suggested aetiologies, include idiopathic
haematinic deficiency, cessation of tobacco smoking
and psychological stress, but there is little scientific
evidence in support of any of these. While superficial
ulcers similar to RAS may arise in gluten-sensitive
enteropathy,48 the vast majority of patients with RAS
have no clinical, gastroenterological or serological
features of this small bowel disorder. To date no
common viral or bacterial infection of the mouth has
been implicated in the aetiology of RAS.47 There is no
consistent association between Helicobacter pylori infection and RAS.49
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299

Anaemias
Lymphoproliferative disease
Leukaemias (almost all)
Non-Hodgkins lymphoma
Hodgkins lymphoma (rare)
Myeloproliferative disease
(usually multiple myeloma)
Myelodysplasias
Neutropenia (any cause)
Gastroenterological Gluten-sensitive enteropathy
Crohns disease and related disorders
Dermatitis herpetiformis
Ulcerative colitis
Dermatological
Lichen planus
Pemphigus usually vulgaris,
rarely vegetans, folacous
or paraneoplastic
Pemphigoid usually mucous membrane,
occasionally bullous
Linear IgA disease
Epidermylosis bullosa
Others (many)
Immunological
Wegeners granulomatosis
Sarcoidosis
Immunodeficiency (usually defects of
neutrophil number or function)
Malignancy
Oral squamous cell carcinoma
Non-Hodgkins lymphoma
Kaposis sarcoma
Salivary gland malignancy
(e.g. mucoepidermoid tumour,
adenoid cystic carcinoma)
Metastatic deposits (uncommon)
Drug induced
Lichenoid drug reactions (e.g. b-blockers,
antimalarials, NSAIDs, interferon)
Erythema multiforme (e.g. barbiturates,
carbamazepine, sulphonamides)
Pemphigus (e.g. penicillamine,
ACE inhibitors, rifampicin)
Lupus (e.g. minocycline, statins, terbinafine)
Pemphigoid (e.g. clonidine, psoralens)
Drug-induced neutropenia/anaemia
(e.g. azathioprine, carbamazepine)
Drug-induced mucositis
(e.g. cyclophosphamide, methotrexate)
Others (e.g. nicorandil)
ACE, angiotensin-converting enzyme; NSAID, non-steroidal antiinflammatory drugs; IgA, immunoglobulin A.

The treatment of RAS remains unsatisfactory. Therapy

is directed towards reducing the duration and/or
frequency of ulcers.50 The mainstay of therapy is topical
corticosteroids, however, few of these have been found

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S. R. PORTER & J. C. LEAO

Table 3. Classification and characteristics of recurrent aphthous

stomatitis

Type

Average
duration
of ulcers

Minor

<1 cm

Major
Herpetiform

>1 cm
12 mm

Number
of ulcers
36
12
10100

Sites
Mobile
surfaces
Any
Any

Percentage of
affected
individuals
80
10
10*

* Probably an overestimate.

provides some symptomatic relief but does not hasten

ulcer healing. Although effective, systemic therapy with
prednisolone is rarely warranted, while the role of
immunosuppressants is unclear.5254 Thalidomide is
highly effective but in view of the adverse side-effects of
teratogenicity and neurotoxicity its routine application
for such a recurrent and minor disorder is contraindicated.55
Ulcers similar to RAS is one of the cardinal features of
Behcets disease. The ulcers has been rarely described in
detail but seem to have the same clinical features as
RAS (Figures 7 and 8). A detailed discussion of Behcets
disease can be found elsewhere.56 Other disorders that
can give rise to RAS-like ulcers include a variant of
Behcets disease termed MAGIC syndrome, Sweets
syndrome and HIV disease.57 A rare disorder in
childhood characterized by pyrexia, pharyngitis,

Figure 5. Major recurrent aphthous stomatitis in the oropharix.

Figure 7. Oral ulcers in Behcets disease.

Figure 6. Small ulcers in herpetiform recurrent aphthous stomatitis.

to be significantly effective in appropriate clinical

studies. Chlorhexidine gluconate mouthrinse may be
of some benefit (and has been evaluated in detail),51 but
it really has limited clinical value in the management of
RAS. Benzydamine hydrochloride spray or mouthrinse

Figure 8. Pathergy in Behcets disease.

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REVIEW: ORAL ULCERS AND SYSTEMIC DISORDERS

301

cervical lymphadenopathy and aphthous-like ulcers

sometimes termed PFAPA (periodic fever, aphthae,
pharyngitis and adenitis) has been described.58
ORAL ULCERS RELATED TO SYSTEMIC DISEASE

Gastrointestinal disease
Gluten-sensitive enteropathy. Superficial oral mucosal
ulcers similar to RAS may be a feature of 15% patients
with undiagnosed, untreated gluten-sensitive enteropathy.59 The ulceration is presumably due to the associated haematinic deficiencies.
Dermatitis herpetiformis and related disorders
Oral lesions in dermatitis herpetiformis have been rarely
described. These may comprise oral mucosal vesicles,
blood-filled blisters, irregular ulcers and desquamative
gingitivitis. Linear IgA disease may likewise give rise to
blood-filled vesicles or bullae, irregular ulcers and
desquamative gingivitis.60

Figure 10. Irregular superficial ulcers on ventral surface of

tongue in Crohns disease.

Oral ulcers arises in approximately 9% of patients

with undiagnosed Crohns disease and can be the first
and/or only clinical features of this disorder.61 Two
types of oral ulcers can arise in orofacial granulomatosis (OFG) and Crohns disease (Figures 9 and 10)
chronic deep linear ulcers, usually of the buccal
vestibules, which often have a rolled edge because of
mucosal tags, and superficial oral mucosal ulcers
presumably because of haematinic deficiency. The

diagnosis of such ulcers requires establishing the

presence of non-caseating granulomas and the exclusion of other granulomatous disease such as sarcoidosis (Figure 11).
The precise relationship between OFG and gastrointestinal Crohns disease remains unclear as there are
few studies examining the gastrointestinal tract of
children and adults with OFG. Certainly, there are
reports of OFG being an initial presentation of Crohns
disease.62, 63 Likewise, OFG-like disease may be a
feature of patients with concurrent gastrointestinal
Crohns disease.64, 65 The human leucocyte antigen
(HLA) haplotype of patients with OFG differs from that
of Crohns disease.66 The exact association between
OFG and gastrointestinal Crohns disease is thus not
known.

Figure 9. Linear ulcers in orofacial granulomatosis.

Figure 11. Gingival enlargement in sarcoidosis.

Crohns disease and related disorders

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S. R. PORTER & J. C. LEAO

Ulcerative colitis
Ulcerative colitis can give rise to either aphthous ulcers
or multiple pustules termed pyostomatitis vegetans. The
ulcers of the latter arise on the upper and lower anterior
vestibules, the soft palate and posterior hard palate
(Figure 12). Pyostomatitis vegetans tends to arise in
patients with undiagnosed or active ulcerative colitis.
Although most frequently associated with ulcerative
colitis, pyostomatitis vegetans may occasionally arise in
Crohns disease.67 Pyoderma gangrenosum, manifesting as a solitary, necrotic mucosal ulcer has rarely been
reported in the mouth.68
Others
As discussed above necrotizing sialometaplasia may
arise secondary to palatal trauma in bulimia nervosa.
Gastro-oesophageal reflux does not cause oral ulceration, although it has been associated with erosion of the
palatal aspects of the upper teeth.69

Table 4. Oral ulcers and other oral manifestations of gastrointestinal disease

Gastrointestinal disorder

Oral manifestations

Bulimia nervosa

Necrotizing sialometaplasia
Superficial oral ulcers
Dental erosion
Bilateral parotid enlargement
Chronic mucocutaneous
candidosis

Post-cricoid webbing

Gastro-oesophageal
reflux disease
Gluten-sensitive enteropathy
Dermatitis herpetiformis
(and linear IgA dermatosis)
Peutz-Jeghers syndrome
Cystic fibrosis

Congenital hepatic disease

and biliary atresia
Hepatitis C virus infection

DERMATOLOGICAL DISEASE

A spectrum of cutaneous disorders can give rise to oral

ulcers (Table 2).

Primary biliary cirrhosis

Crohns disease*

Lichen planus
Lichen planus is by far the most common dermatological disorder to give rise to oral ulcers. The clinical
features of oral lichen planus are reviewed in Table 4.
Lichen planus is an immunologically mediated disorder

Ulcerative colitis
Colonic malignancy

Dental erosion
Superficial ulcers
Enamel hypoplasia in children
Vesicles, bullae
Desquamative gingivitis
Enamel hypoplasia (in children)
Perilabial pigmented macules
Enamel hypoplasia
Tetracycline staining of teeth
Superficial oral ulcers
Pigmentation of the gingivae

Xerostomia
Salivary gland disease
Lichen planus (possibly)
Telangiectasia
Xerostomia
Labial (and facial) enlargement
Fissuring of the tongue
Linear ulcers of the buccal
and labial vestibules
Superficial oral ulcers
Gingival enlargement
Facial nerve palsy
Pyostomatitis vegetans
Pyoderma gangrenosum
Superficial oral ulcers
Acanthosis nigricans

* Sometimes disease localized to the mouth is termed orofacial granulomatosis.

Figure 12. Pyostomatitis vegetans in a patient with ulcerative

colitis.

histopathologically characterized by an intense dermal

infiltrate of T-lymphocytes. The precise trigger for this
immunological reaction is unclear. There is no evidence that the clinical features of idiopathic oral lichen
planus are any different to those of drug-associated
disease.71
Likewise, although histopathological differences
between idiopathic lichen planus and drug-related
disease have been described there is profound inconsistency between the proposed pathological hallmarks of
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REVIEW: ORAL ULCERS AND SYSTEMIC DISORDERS

these two disorders.72 Drugs that may commonly give

rise to lichen planus-like disease include sulphonyureas, non-steroidal anti-inflammatory drugs, b-blockers, antimalarials, penicillamine and gold. Associations
between hepatitis C virus and oral lichen planus
probably reflect the epidemiology of hepatitis C virus
infection and/or use of interferon-a.73 A lichen planuslike disorder can arise in chronic graft-versus-host
disease.
Lichen planus only warrants treatment in patients
who are having painful symptoms and/or there are
signs of erosion, ulcers or blister formation. Typical
treatment comprises topical corticosteroids,74 although
severe disease may warrant local (e.g. topical tacrolimus) and systemic immunosuppressant therapy75, 76
the use of the latter does not have a strong evidence
base.
Of note, it has been suggested that oral lichen planus
may be potentially malignant. The evidence for this is
generally based upon retrospective studies of large
numbers of affected patients. It is suggested that
approximately 13% of patients with long-standing
lichen planus may develop oral SCC.77 Often, however,
the descriptions have not detailed whether the tumour
has arisen within existing lichen planus and no detailed
prospective control studies of the development of oral
SCC in long-standing lichen planus has ever been
undertaken.
Other dermatological disorders likely to give rise to oral
mucosal ulcers are summarized in Table 2.
HAEMATOLOGICAL DISEASE

303

mobility and very rarely a pathological fracture of the

mandible.
Oral SCC remains one of the more common cancers
worldwide, particularly in developing countries such as
India.7880 Of note, however, there is a rising frequency
of oral SCC in the middle age adult in the developed
world. High tobacco (in any form) and alcohol
consumption are the principal aetiological factors of
oral SCC. Other suggestive aetiologies include human
papilloma virus, malnourishment (in particular deficiencies of vitamins A and C) and perhaps poor oral
hygiene.
Non-Hodgkins lymphoma
Non-Hodgkins lymphoma may manifest as a solitary
area of necrotic ulcers typically affecting the gingiva,
palate and fauces. This tumour may arise de novo but
often is associated with iatrogenic immunosuppression
in HIV disease. A detailed review of non-Hodgkins
lymphoma of the mouth can be found elsewhere.81 NK/
T-cell lymphoma tends to affect the upper anterior
gingival and palate; this is a T-cell lymphoma in
contrast to most non-Hodgkins lymphoma of the
mouth.82
Drug therapy
A wide range of drugs can give rise to ulcers of the
oral mucosa (Figure 13).83 The mechanisms by which
drugs cause oral ulcers include drug-induced neutropenia and anaemia (e.g. cytotoxics), lichenoid disease

The haematological disorders likely to give rise to oral

ulcers are summarized in Table 2. In general, ulcers
arises as a consequence of haematinic deficiency,
neutropenia and associated opportunistic viral infection.
MALIGNANCY

The common malignancies of the mouth that may

manifest as oral ulcers are summarized in Table 2. SCC
is the most common tumour of the mouth, and typically
manifests as a solitary ulcer of the dorsum of tongue or
floor of mouth. The ulceration is locally destructive and
when affecting the tongue may give rise to lingual and/
or hypoglossal nerve damage with or without dysarthria or dysphagia. Gingival SCC may give rise to tooth
2005 Blackwell Publishing Ltd, Aliment Pharmacol Ther 21, 295306

Figure 13. Drug-induced (nicorandil) oral ulcers on lateral border

of tongue.

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S. R. PORTER & J. C. LEAO

Table 5. Oral manifestations associated with the therapy of

gastrointestinal disease
Oral manifestation

Drugs

Pseudomembranous candidosis

Corticosteroids,
immunosuppressants
Corticosteroids,
immunosuppressants
Corticosteroids,
immunosuppressants
Omeprazole (rare)
Dapsone
Ciclosporin

Chronic erythematous candidosis

Oral hairy leukoplakia
Xerostomia
Lingual pigmentation (blue)
Gingival enlargement

(e.g. sulphanylureas, b-blockers, gold, penicillamine),

pemphigus (e.g. angiotensin-converting enzyme inhibitors), lupus disease and IgA dermatoses. Table 5
summarizes the adverse oral side-effects of common
drug therapies of gastrointestinal disease.
CONCLUSION

The present article has presented an overview of the

common clinical presentations of oral ulceration. Gastrointestinal disease, particularly undiagnosed glutensensitive enteropathy, Crohns disease and ulcerative
colitis, can give rise to ulcers of the mouth. However,
these and other gut diseases can give rise to a range of
other oral features (Table 2), hence, it is important to
ask patients who present with gastrointestinal disease
about their symptoms and to examine the mouth
carefully when assessing patients with possible disease
of the gastrointestinal tract.
ACKNOWLEDGEMENT

JCL is partially funded by a grant from CNPq (Ministry

of Science and Technology), Brazil.
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