Ulcerative Lesions of the Oral Cavity
Oral Pathology · Core Clinical Science
TL;DR
Oral ulcers are among the most common complaints in dental practice. The vast majority are benign and self-limiting, but a subset represents serious conditions including malignancy, systemic autoimmune disease, and infectious illness. The key clinical rule is that any oral ulcer persisting beyond 2–3 weeks without a clear benign cause requires biopsy.
- Recurrent aphthous stomatitis (RAS) is the most common oral mucosal disease — affecting up to 25% of the population — with three clinical forms: minor, major, and herpetiform.
- Herpes simplex virus (HSV) produces primary herpetic gingivostomatitis (a severe first infection) and recurrent herpes labialis (“cold sores”); intraoral recurrences occur on keratinised mucosa (hard palate, gingiva).
- Oral squamous cell carcinoma (SCC) most commonly presents as a painless, indurated, non-healing ulcer — typically on the lateral tongue or floor of mouth; late diagnosis dramatically worsens prognosis.
- Pemphigus vulgaris and mucous membrane pemphigoid are autoimmune blistering diseases that produce chronic, painful oral ulcers and require systemic immunosuppressive management.
- Multiple or severe oral ulcers may be the oral manifestation of systemic conditions: Behçet disease, inflammatory bowel disease, coeliac disease, haematological malignancy, or HIV.
Key Facts
What Are They?
An ulcer is defined as a breach in an epithelial surface exposing the underlying connective tissue. In the oral cavity, ulcers appear as painful, depressed areas with a fibrinous, yellow-grey pseudomembrane (slough) overlying the base, surrounded by an erythematous halo of inflamed mucosa. Unlike erosions (which are superficial), true ulcers extend through the full thickness of the epithelium.
The causes of oral ulceration are numerous and span multiple aetiological categories: traumatic, infective (viral, bacterial, fungal), immune-mediated (aphthous, autoimmune blistering diseases, drug reactions), neoplastic, and systemic. A systematic clinical approach — considering the history (duration, frequency, number, triggers), site (keratinised vs. non-keratinised mucosa), appearance (single vs. multiple, regular vs. irregular borders, indurated vs. soft base), and any associated systemic symptoms — is the cornerstone of accurate diagnosis.
The most important clinical decision in managing any oral ulcer is whether to biopsy. The threshold for biopsy should be low. Any ulcer that does not have a clearly attributable benign cause and has been present for more than two to three weeks must be biopsied without delay.
Why It Matters (Clinical + Exam Context)
Oral ulcers are among the most common reasons patients seek dental or medical advice. Their importance is disproportionate to their prevalence because mismanagement — particularly missing an oral carcinoma masquerading as a “recurrent” or “traumatic” ulcer — can have fatal consequences.
Clinical Relevance
- Oral cancer and the two-week rule: National guidelines in multiple countries specify that any unexplained oral ulcer present for more than two weeks must be urgently referred for specialist assessment (the “two-week wait” pathway in the UK/NHS). The 5-year survival for oral SCC is approximately 50% overall, rising to over 80% when diagnosed at stage I. Early detection is transformational.
- Intraoral HSV recurrences occur on keratinised mucosa: Understanding this prevents misdiagnosis. Recurrent intraoral herpes presents as clusters of small ulcers on the hard palate or gingiva — not the buccal mucosa or floor of mouth. Aphthous ulcers occur on non-keratinised (unattached, moveable) mucosa. This anatomical distinction is diagnostically valuable.
- Drug-induced ulceration: Many medications cause oral ulceration — methotrexate, NSAIDs, nicorandil, alendronate (bisphosphonate-related osteonecrosis is a related entity), and numerous others. A thorough drug history is mandatory in any patient with recurrent or treatment-resistant oral ulcers.
- Haematological causes: Recurrent, severe, or atypical oral ulcers may be the presenting feature of agranulocytosis, neutropenia, leukaemia, or iron/vitamin B12/folate deficiency. Haematological workup (FBC, ferritin, B12, folate) is indicated in patients with recurrent aphthae or worsening ulceration without a clear cause.
Recurrent Oral Ulcers
Recurrent Aphthous Stomatitis (RAS)
RAS is the most common oral mucosal disease, affecting approximately 15–25% of the population. It is characterised by recurrent, painful, well-defined round or oval ulcers with a yellow-grey fibrinous base and an erythematous halo, occurring on non-keratinised mucosa (buccal and labial mucosa, floor of mouth, ventral tongue, soft palate). Three clinical subtypes are recognised:
- Minor aphthous ulcers (MiRAS): The most common form (~80% of RAS). Ulcers are ≤10 mm, round or oval, occurring singly or in small crops; they heal without scarring in 7–14 days. Trauma, stress, and certain foods (citrus fruits, chocolate, nuts) are recognised triggers.
- Major aphthous ulcers (MaRAS / Sutton’s disease): Ulcers are >10 mm (often 1–3 cm), deeply penetrating, irregularly shaped, and may persist for weeks to months. They heal with scarring and may produce significant functional impairment. They are more common in HIV-positive patients and immunosuppressed individuals.
- Herpetiform ulcers: Multiple (10–100) tiny (1–3 mm) ulcers that coalesce to form irregular larger ulcers. Despite the name, they are NOT caused by HSV. They occur on any oral mucosal surface and may be continuous without clear healing periods.
The aetiology of RAS is multifactorial — immune dysregulation, genetic predisposition, hormonal factors, haematological deficiencies (iron, B12, folate), and stress all play a role. Management is symptomatic: topical corticosteroids (triamcinolone acetonide paste, betamethasone mouthwash), topical analgesics, chlorhexidine mouthwash. Severe or refractory cases may require systemic agents (colchicine, dapsone, thalidomide — the latter reserved for specialist use).
Traumatic Ulcers
Traumatic ulcers are the most common type of acute single oral ulcer. They result from mechanical injury (sharp food, cheek biting, dental appliance, accidental biting during dental procedures), thermal injury (hot food or drink), or chemical injury (aspirin burn, sodium hypochlorite spill). Traumatic ulcers are typically irregular in shape, corresponding to the shape of the causative agent; they have a soft, non-indurated base; they occur at the site of injury; and they heal within 7–10 days once the cause is removed. Any ulcer at a site of trauma that does not heal within 2 weeks after the trauma source is eliminated must be biopsied, as SCC can arise at traumatised sites and trauma cannot be assumed to be the cause of a malignant ulcer.
Infective Ulcers
Herpes Simplex Virus (HSV) Infections
HSV-1 is the most common oral viral pathogen. It produces two distinct clinical presentations:
- Primary herpetic gingivostomatitis: The first infection with HSV-1, most common in children under 5 years old and in young adults. It presents acutely with high fever, malaise, cervical lymphadenopathy, and widespread oral ulceration involving the gingivae (which become swollen, erythematous, and bleed easily) and all mucosal surfaces — keratinised and non-keratinised alike. The ulcers begin as vesicles that rapidly rupture. The condition is self-limiting, resolving in 10–14 days, but antiviral therapy (aciclovir, started within 72 hours of onset) reduces severity and duration. Secondary bacterial infection may complicate severe cases.
- Recurrent herpes labialis (“cold sores”): Following primary infection, HSV-1 establishes latency in the trigeminal ganglion. Reactivation is triggered by sunlight, stress, fever, immunosuppression, or local trauma, producing the classic “cold sore” on the vermilion border of the lip — a cluster of vesicles progressing to a crusted ulcer, resolving in 7–10 days. Intraoral recurrences occur exclusively on keratinised mucosa (hard palate, attached gingiva), presenting as clusters of pinpoint ulcers.
Herpes Zoster (Shingles)
Reactivation of varicella-zoster virus (VZV) along the distribution of the trigeminal nerve can produce severe, unilateral, dermatomal pain and vesicular eruptions in the oral cavity and on the face. The oral ulcers are characteristically unilateral and do not cross the midline, following the distribution of a single division of the trigeminal nerve (most commonly V2 or V3). Post-herpetic neuralgia — persistent pain in the affected dermatome for months or years after resolution of the skin lesions — is a significant complication, particularly in older or immunocompromised patients. Antiviral therapy (aciclovir, valaciclovir) within 72 hours significantly reduces both severity and post-herpetic neuralgia risk.
Acute Necrotising Ulcerative Gingivitis (ANUG)
ANUG (also called Vincent’s disease or trench mouth) is a specific, rapidly destructive bacterial infection of the gingivae caused by a synergistic interaction of anaerobic bacteria — predominantly Fusobacterium nucleatum, Treponema spp., and Prevotella intermedia. The clinical presentation is dramatic and distinctive: punched-out, cratered ulcers at the tips of the interdental papillae; a grey pseudomembranous slough; intense gingival pain; fetid halitosis (characteristic “gangrenous” odour); fever; and malaise. ANUG is strongly associated with stress, poor oral hygiene, smoking, malnutrition, and immunosuppression. Treatment is mechanical debridement plus systemic metronidazole (400 mg three times daily for 3 days), with careful follow-up to address underlying periodontal disease and risk factors.
Autoimmune & Immune-Mediated Ulcers
Pemphigus Vulgaris
Pemphigus vulgaris (PV) is a potentially life-threatening autoimmune blistering disease caused by IgG autoantibodies against desmoglein-3 (and sometimes desmoglein-1), the desmosomal cadherins that anchor epithelial cells to each other within the spinous layer. Loss of intercellular adhesion (acantholysis) causes suprabasal cleft formation and intraepithelial bullae. The oral mucosa is involved in virtually all patients with PV, and oral lesions are the first manifestation in over 50% of cases — often preceding skin lesions by months. Oral PV presents as fragile, superficial, irregularly shaped ulcers that arise from bullae that rupture almost immediately. The Nikolsky sign (lateral pressure on apparently normal mucosa adjacent to an ulcer causes the epithelium to slide/peel) is classically positive but is not pathognomonic. Diagnosis requires biopsy with histopathology (suprabasal acantholysis, “row of tombstones” basal cells) and direct immunofluorescence (intercellular IgG and C3 deposition in a “fishnet” pattern). Treatment requires systemic immunosuppression — oral prednisolone (often high-dose) with a steroid-sparing agent (azathioprine, mycophenolate mofetil, rituximab).
Mucous Membrane Pemphigoid (MMP)
MMP (also called cicatricial pemphigoid) is an autoimmune subepithelial blistering disease targeting various components of the epithelial basement membrane zone (BP180, BP230, laminin-332, and others). Unlike PV, the bullae in MMP are subepithelial and therefore more intact and persistent. The gingiva is the most commonly affected site, presenting as desquamative gingivitis — diffuse, fiery red, painful, fragile gingiva that peels off in sheets (positive Nikolsky sign on gingiva). Direct immunofluorescence shows linear IgG, IgA, and/or C3 deposition along the basement membrane zone. MMP may also affect the conjunctiva (causing symblepharon and blindness if untreated), pharynx, oesophagus, skin, and genitalia. Treatment is topical corticosteroids for mild oral disease; systemic immunosuppression and ophthalmological involvement require specialist multidisciplinary management.
Erosive Lichen Planus
Lichen planus (LP) is a common chronic inflammatory condition affecting skin and mucous membranes, mediated by T-lymphocyte-driven destruction of basal keratinocytes. The classic oral form is reticular lichen planus — bilateral, symmetrical white lacy striae (Wickham’s striae) on the buccal mucosa, which is asymptomatic and requires no treatment. However, the erosive and atrophic forms produce chronic, painful ulceration and erythema, particularly affecting the gingiva (desquamative gingivitis), buccal mucosa, and tongue. Oral LP carries an approximately 0.5–3% malignant transformation rate, requiring regular monitoring. Management of symptomatic erosive LP includes topical corticosteroids, tacrolimus 0.1% ointment, and for severe cases, systemic agents.
Behçet Disease
Behçet disease is a rare multisystem vasculitis characterised by the triad of recurrent oral ulcers, genital ulcers, and uveitis. Oral ulcers in Behçet disease are clinically indistinguishable from major aphthous ulcers — they are the most common manifestation and are required for diagnosis by most classification criteria. The pathergy test (skin hyperreactivity to needle prick) may be positive in patients from high-prevalence regions (Turkey, Middle East, East Asia). Behçet disease can also affect the CNS, cardiovascular system, GI tract, and joints. Treatment is systemic and requires rheumatological expertise; colchicine, azathioprine, and biologics (anti-TNF agents) are used depending on disease severity.
Malignant Ulceration
Oral Squamous Cell Carcinoma (SCC)
Oral SCC accounts for approximately 90% of all oral malignancies. The lateral border and ventral surface of the tongue, floor of the mouth, and retromolar area are the highest-risk sites — partly due to pooling of carcinogens in these areas. Major risk factors are tobacco use (smoking and smokeless), heavy alcohol consumption (synergistic effect with tobacco), HPV infection (particularly HPV 16, associated with oropharyngeal SCC), and chronic trauma.
Early oral SCC may present as a subtle mucosal change — a persistent red patch (erythroplakia), a mixed red-white lesion, a thickened white plaque (leukoplakia), or a small ulcer. The classic presentation of established SCC is a painless (this is the danger — lack of pain leads to delay), indurated, irregular-bordered ulcer with a raised, everted edge and a hard, non-healing base, sometimes with surface necrosis. The floor of mouth is a site where early lesions are easily missed under the tongue — every oral examination must include lifting the tongue to inspect the floor of mouth.
| Feature | Benign Ulcer (e.g., aphthae) | Malignant Ulcer (SCC) |
|---|---|---|
| Duration | <2–3 weeks; self-limiting | >3 weeks; progressive |
| Pain | Usually painful | Often painless in early stages |
| Border | Regular, well-defined | Irregular, raised, rolled, everted |
| Base | Soft, fibrinous | Indurated, hard, necrotic |
| Surrounding tissue | Erythematous halo, no induration | Fixed, indurated, satellite lesions possible |
| Number | Often multiple, recurrent | Usually solitary, progressive |
| Lymph nodes | Reactive (tender, mobile) | Hard, fixed, non-tender (metastatic) |
Clinical Considerations
- The two-week rule: Any oral ulcer present for more than two weeks without a clear, attributable benign cause must be biopsied and/or urgently referred for specialist assessment. This applies even if the patient describes it as “just a recurring ulcer” — major aphthae and SCC can both recur at similar sites.
- Incisional biopsy technique: For any suspected malignant ulcer, incisional biopsy should include tissue from the edge of the ulcer (including both abnormal and apparently normal mucosa at the transition) and the base, avoiding the central necrotic slough which provides poor histological material. Biopsy instruments should not be allowed to contaminate the specimen with adjacent normal tissue.
- Haematological screen for RAS: In any patient with recurrent aphthous ulcers, request a full blood count, ferritin, serum B12, and red cell folate. Deficiency of iron, B12, or folate is found in approximately 20% of patients with RAS and correction of the deficiency alone may resolve the aphthae.
- Systemic causes to exclude: Multiple, severe, or recalcitrant oral ulcers should prompt consideration of: coeliac disease (IgA anti-tissue transglutaminase antibodies; gluten-free diet may resolve oral ulcers), inflammatory bowel disease (Crohn’s disease produces cobblestone buccal mucosa, aphthae, and lip swelling; ulcerative colitis causes aphthae), HIV (major aphthae, HSV, and CMV ulcers are common), Behçet disease, and haematological malignancy.
- Desquamative gingivitis workup: Desquamative gingivitis (diffuse, painful gingival erythema and fragility) has a narrow differential: erosive LP, MMP, and pemphigus vulgaris are the three most important causes. Biopsy (including perilesional tissue for direct immunofluorescence) is mandatory to differentiate these — their management differs significantly.
Common Mistakes & Misconceptions
-
Misconception: “A patient who says their ulcer keeps coming back must have RAS.”
Correction: SCC can also recur or persist in the same site, and patients may report “it comes and goes” because the ulcer partially heals and then re-ulcerates. The history of recurrence does not exclude malignancy. Persistent or recurrent ulceration at the same site requires biopsy. -
Misconception: “Herpes simplex ulcers can occur anywhere in the mouth.”
Correction: Recurrent intraoral HSV ulcers occur only on keratinised (attached) mucosa — the hard palate and attached gingiva. Primary herpetic gingivostomatitis affects all oral mucosal surfaces but is a distinct entity. Ulcers on non-keratinised mucosa that resemble herpes are far more likely to be aphthous ulcers. -
Misconception: “Aphthous ulcers can be confirmed without investigations.”
Correction: RAS is a diagnosis of exclusion. Haematological screen (FBC, ferritin, B12, folate), and occasionally coeliac antibodies, are required to exclude treatable deficiencies and systemic causes before a confident diagnosis of idiopathic RAS can be made. -
Misconception: “Pemphigus vulgaris and mucous membrane pemphigoid are the same disease.”
Correction: They are distinct diseases with different autoantibody targets, histological cleavage planes, immunofluorescence patterns, and clinical outcomes. PV is intraepithelial (suprabasal cleft); MMP is subepithelial (below the basement membrane). Direct immunofluorescence is required to differentiate them reliably.
Related Topics
References & Sources
- Neville BW, Damm DD, Allen CM, Chi AC. (2016). Oral and Maxillofacial Pathology, 4th ed. Elsevier.
- Regezi JA, Sciubba JJ, Jordan RCK. (2017). Oral Pathology: Clinical Pathologic Correlations, 7th ed. Elsevier.
- Odell EW (Ed.). (2017). Cawson’s Essentials of Oral Pathology and Oral Medicine, 9th ed. Elsevier.
- Scully C, Gorsky M, Lozada-Nur F. (2003). The diagnosis and management of recurrent aphthous stomatitis. Journal of the American Dental Association, 134(2), 200–207.
- Warnakulasuriya S. (2009). Global epidemiology of oral and oropharyngeal cancer. Oral Oncology, 45(4–5), 309–316.
Summary
Oral ulcerative lesions represent one of the most diagnostically important areas in oral medicine. From the ubiquitous minor aphthous ulcer to the life-threatening oral squamous cell carcinoma, a systematic and methodical approach — characterising each ulcer by its duration, site, borders, base, and associated features — allows the clinician to differentiate the vast majority of benign ulcers from those requiring urgent investigation. The two-week rule is the single most important clinical principle: any unexplained oral ulcer lasting more than two weeks must be biopsied.
Key Takeaways
- RAS is the most common oral ulcer: Occurs on non-keratinised mucosa; well-defined, round, painful, self-limiting; screen for haematological deficiencies (iron, B12, folate) before diagnosing idiopathic RAS.
- Intraoral HSV recurrences only occur on keratinised mucosa: Hard palate and attached gingiva — not buccal mucosa or floor of mouth. This distinction separates recurrent HSV from aphthous ulcers.
- Oral SCC is often painless: A firm, indurated, non-healing ulcer with irregular, everted borders on the lateral tongue or floor of mouth must be biopsied urgently — pain is an unreliable warning sign.
- Desquamative gingivitis = biopsy with immunofluorescence: Erosive LP, MMP, and pemphigus vulgaris all cause gingival ulceration and fragility; direct immunofluorescence on perilesional tissue is required to differentiate them.
- Any ulcer lasting >2–3 weeks needs biopsy: This is the single most important rule in oral ulcer management — no exceptions for “probably aphthae” or “I think it’s traumatic.”
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