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Summary

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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. 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.


Introduction

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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

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Most traumatic ulcers of the mucosa are due to physical trauma. In addition, ulcers may arise with 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

Necrotizing sialometaplasia

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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

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Herpes simplex virus 1

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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 suggestive of underlying immunodeficiency, in particular lymphoproliferative disease or HIV disease.12

Table 1.  Infectious causes of oral mucosal ulcers
ViralHerpes group
 Human herpes simplex 1
 Human herpes simplex 2
 Epstein–Barr virus
 Varicella zoster virus
 Cytomegalovirus
 Human herpesvirus 8 (Kaposi's sarcoma herpesvirus)
Coxsackie viruses (e.g. herpangina, hand foot and mouth disease)
Human immunodeficiency viruses
BacterialTreponema pallidum (syphilis)
Acute necrotizing ulcerative gingivitis
Mycobacterium tuberculosis
Other mycobacterioses
FungalCandida albicans (uncommon)
Aspergillosis
Paracoccidiodomycosis
Histoplasmosis
Mucormycosis
ProtozoalLeishmaniasis
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Figure 1. Oral ulcers on the ventral surface of tongue in primary herpes simplex infection.

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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

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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.

Epstein–Barr virus

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Ulcers caused by Epstein–Barr virus (EBV) is rare, but may be a feature of infectious mononucleosis. The ulcers comprises a few small superficial ulcers of the oral mucosa. EBV is more typically associated with the ulcers of some non-Hodgkin's 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

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Cytomegalovirus (CMV) may give rise to large, chronic ulcers of the oral mucosa or gingiva.21 These CMV-related 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 (Kaposi's sarcoma herpes virus)

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Human herpesvirus 8 (HHV-8) is the cause of Kaposi's 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

Kaposi's 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.25–27

Human immunodeficiency virus

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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 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)-α 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

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Figure 2. Deep, necrotic ulcer in HIV infection.

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Bacterial infection

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Acute necrotizing ulcerative gingivitis

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Acute necrotizing ulcerative gingivitis (Vincent's disease, trench mouth, acute ulcerative gingivitis) is a non-specific 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 disease may lead to destruction and loss of interdental papillae.

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Figure 3. Inverted papillae in acute necrotizing ulcerative gingivitis.

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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.

Treponema pallidum

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

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Figure 4. Solitary ulcer (chancre) on the lower lip of a patient diagnosed with primary syphilis.

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Mycobacterial infection

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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 HIV-infected individuals.42

Fungal infections

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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.

Table 2.  Systemic disease likely to give rise to oral ulcers
  1. ACE, angiotensin-converting enzyme; NSAID, non-steroidal anti-inflammatory drugs; IgA, immunoglobulin A.

HaematologicalAnaemias
Lymphoproliferative disease
 Leukaemias (almost all)
 Non-Hodgkin's lymphoma
 Hodgkin's lymphoma (rare)
Myeloproliferative disease
 (usually multiple myeloma)
Myelodysplasias
Neutropenia (any cause)
GastroenterologicalGluten-sensitive enteropathy
Crohn's disease and related disorders
Dermatitis herpetiformis
Ulcerative colitis
DermatologicalLichen planus
Pemphigus – usually vulgaris, rarely vegetans, folacous or paraneoplastic
Pemphigoid – usually mucous membrane, occasionally bullous
Linear IgA disease
Epidermylosis bullosa
Others (many)
ImmunologicalWegener's granulomatosis
Sarcoidosis
Immunodeficiency (usually defects of neutrophil number or function)
MalignancyOral squamous cell carcinoma
Non-Hodgkin's lymphoma
Kaposi's sarcoma
Salivary gland malignancy (e.g. mucoepidermoid tumour, adenoid cystic carcinoma)
Metastatic deposits (uncommon)
Drug inducedLichenoid drug reactions (e.g. β-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)

Recurrent aphthous stomatitis

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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 4–12 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).

Table 3.  Classification and characteristics of recurrent aphthous stomatitis
TypeAverage duration of ulcersNumber of ulcersSitesPercentage of affected individuals
  1. * Probably an overestimate.

Minor<1 cm3–6Mobile surfaces80
Major>1 cm1–2Any10
Herpetiform1–2 mm10–100Any10*
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Figure 5. Major recurrent aphthous stomatitis in the oropharix.

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Figure 6. Small ulcers in herpetiform recurrent aphthous stomatitis.

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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

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 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 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.52–54 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 Behcet's 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 Behcet's disease can be found elsewhere.56 Other disorders that can give rise to RAS-like ulcers include a variant of Behcet's disease termed MAGIC syndrome, Sweet's syndrome and HIV disease.57 A rare disorder in childhood characterized by pyrexia, pharyngitis, cervical lymphadenopathy and aphthous-like ulcers sometimes termed PFAPA (periodic fever, aphthae, pharyngitis and adenitis) has been described.58

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Figure 7. Oral ulcers in Behcet's disease.

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Figure 8. Pathergy in Behcet's disease.

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Oral ulcers related to systemic disease

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Gastrointestinal disease

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Gluten-sensitive enteropathy.  Superficial oral mucosal ulcers similar to RAS may be a feature of 1–5% patients with undiagnosed, untreated gluten-sensitive enteropathy.59 The ulceration is presumably due to the associated haematinic deficiencies.

Dermatitis herpetiformis and related disorders

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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

Crohn's disease and related disorders

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Oral ulcers arises in approximately 9% of patients with undiagnosed Crohn's 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 Crohn's 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).

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Figure 9. Linear ulcers in orofacial granulomatosis.

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Figure 10. Irregular superficial ulcers on ventral surface of tongue in Crohn's disease.

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Figure 11. Gingival enlargement in sarcoidosis.

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The precise relationship between OFG and gastrointestinal Crohn's 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 Crohn's disease.62, 63 Likewise, OFG-like disease may be a feature of patients with concurrent gastrointestinal Crohn's disease.64, 65 The human leucocyte antigen (HLA) haplotype of patients with OFG differs from that of Crohn's disease.66 The exact association between OFG and gastrointestinal Crohn's disease is thus not known.

Ulcerative colitis

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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 Crohn's disease.67 Pyoderma gangrenosum, manifesting as a solitary, necrotic mucosal ulcer has rarely been reported in the mouth.68

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Figure 12. Pyostomatitis vegetans in a patient with ulcerative colitis.

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Others

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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

Dermatological disease

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A spectrum of cutaneous disorders can give rise to oral ulcers (Table 2).

Lichen planus

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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 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

Table 4.  Oral ulcers and other oral manifestations of gastrointestinal disease
Gastrointestinal disorderOral manifestations
  1. * Sometimes disease localized to the mouth is termed orofacial granulomatosis.

Bulimia nervosaNecrotizing sialometaplasia Superficial oral ulcers Dental erosion Bilateral parotid enlargement
Post-cricoid webbingChronic mucocutaneous candidosis
Gastro-oesophageal reflux diseaseDental erosion
Gluten-sensitive enteropathySuperficial ulcers Enamel hypoplasia in children
Dermatitis herpetiformis (and linear IgA dermatosis)Vesicles, bullae Desquamative gingivitis Enamel hypoplasia (in children)
Peutz-Jegher's syndromePerilabial pigmented macules
Cystic fibrosisEnamel hypoplasia Tetracycline staining of teeth Superficial oral ulcers
Congenital hepatic disease and biliary atresiaPigmentation of the gingivae
Hepatitis C virus infectionXerostomia Salivary gland disease Lichen planus (possibly)
Primary biliary cirrhosisTelangiectasia Xerostomia
Crohn's disease*Labial (and facial) enlargement Fissuring of the tongue Linear ulcers of the buccal and labial vestibules Superficial oral ulcers Gingival enlargement Facial nerve palsy
Ulcerative colitisPyostomatitis vegetans Pyoderma gangrenosum
Colonic malignancySuperficial oral ulcers Acanthosis nigricans

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 these two disorders.72 Drugs that may commonly give rise to lichen planus-like disease include sulphonyureas, non-steroidal anti-inflammatory drugs, β-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-α.73 A lichen planus-like 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 1–3% 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

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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

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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 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.78–80 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-Hodgkin's lymphoma

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Non-Hodgkin's 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-Hodgkin's 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-Hodgkin's lymphoma of the mouth.82

Drug therapy

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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 (e.g. sulphanylureas, β-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.

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

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Table 5.  Oral manifestations associated with the therapy of gastrointestinal disease
Oral manifestationDrugs
Pseudomembranous candidosisCorticosteroids, immunosuppressants
Chronic erythematous candidosisCorticosteroids, immunosuppressants
Oral hairy leukoplakiaCorticosteroids, immunosuppressants
XerostomiaOmeprazole (rare)
Lingual pigmentation (blue)Dapsone
Gingival enlargementCiclosporin

Conclusion

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The present article has presented an overview of the common clinical presentations of oral ulceration. Gastrointestinal disease, particularly undiagnosed gluten-sensitive enteropathy, Crohn's 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

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JCL is partially funded by a grant from CNPq (Ministry of Science and Technology), Brazil.

References

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