31.1 Recurrent Aphthous Stomatitis
Key Takeaways
- Minor aphthae measure under 10 mm, occur on non-keratinised mucosa and heal within 10 to 14 days without scarring.
- Major aphthae exceed 10 mm, favour the posterior mouth and oropharynx, persist for weeks to months and heal with scarring.
- Herpetiform ulceration produces crops of 1 to 2 mm pinpoint ulcers that may coalesce, healing in 10 to 14 days.
- Haematinic deficiency of iron, folate or vitamin B12 is found in about 5% to 10% of patients and warrants blood screening.
- Any single ulcer persisting beyond three weeks must be treated as possible malignancy and referred urgently, not redressed.
Last updated: September 2026
Recurrent Aphthous Stomatitis (RAS)
Recurrent aphthous stomatitis (RAS), or aphthae, is the most common non-traumatic ulcerative disease of the oral mucosa, affecting approximately 20% of the global population. It is characterized by recurrent, painful, well-demarcated ovoid necrotising ulcers that develop in childhood or adolescence and recur at variable intervals.
Etiopathogenesis
The precise primary trigger remains idiopathic, but the disease represents a cell-mediated immune dysregulation (type IV hypersensitivity response). Cytotoxic CD8+ T-lymphocytes and tumour necrosis factor-alpha (TNF-α) mediate focal epithelial necrosis and basement membrane destruction, exacerbated by local microtrauma, emotional stress, hormonal fluctuations, and genetic susceptibility (HLA-B51, HLA-Cw7).
Clinical Classification
RAS is classified into three clinically distinct variants based on ulcer size, number, distribution, healing duration, and scarring potential:
Recurrent Aphthous Stomatitis (RAS)
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Minor Aphthae Major Aphthae Herpetiform Ulceration
• 80% of all cases • 10% of all cases • 5–10% of cases
• <10 mm (typically 2–5 mm) • >10 mm (often 1–3 cm) • 1–2 mm pinpoint crops
• 1–5 ulcers per crop • 1–3 ulcers per crop • 10–100 ulcers coalescing
• Non-keratinised mucosa only • Keratinised + non-keratinised • Non-keratinised + keratinised
• Heals in 10–14 days • Persists weeks to months • Heals in 10–14 days
• NO scarring • HEALS WITH SCARRING • Scarring unusual
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Minor Aphthous Ulcers (Mikulicz's Aphthae):
- Account for approximately 80% of all RAS presentations.
- Morphology: Round to ovoid, shallow ulcers with a grey-yellow necrotic pseudomembranous floor surrounded by an intense, raised erythematous halo.
- Size & Number: Measuring <10 mm in diameter (typically 2–5 mm), occurring in crops of 1 to 5 ulcers.
- Anatomical Distribution: Confined strictly to non-keratinised mobile oral mucosa (labial mucosa, buccal mucosa, ventral tongue, floor of the mouth, and unattached sulcal mucosa). They notably spare the hard palate, attached gingiva, and dorsal tongue.
- Natural History: Painful during the initial 3–4 days; heal spontaneously within 10 to 14 days without tissue scarring.
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Major Aphthous Ulcers (Sutton's Disease / Periadenitis Mucosa Necrotica Recurrens):
- Account for approximately 10% of cases.
- Morphology: Deep, punched-out, crateriform ulcerations with rolled, indurated, raised margins and severe background edema.
- Size & Number: Measuring >10 mm in diameter (frequently 10–30 mm), presenting as 1 to 3 simultaneous lesions.
- Anatomical Distribution: Involves both non-keratinised and keratinised mucosa, exhibiting a distinct predilection for the posterior oral cavity and oropharynx (soft palate, tonsillar pillars, palatopharyngeal folds, and dorsum of the tongue).
- Natural History: Highly debilitating; lesions persist for weeks to months (typically 3–6 weeks or longer). They heal with permanent fibrous scarring and mucosal architecture distortion.
- Critical Diagnostic Milestone: Because of their large size, raised indurated borders, and chronicity, major aphthae closely mimic Oral Squamous Cell Carcinoma (OSCC) or deep fungal/mycobacterial infections. Any indurated solitary ulcer persisting >3 weeks requires an urgent suspected cancer referral for incisional biopsy.
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Herpetiform Ulceration:
- Accounts for 5% to 10% of cases.
- Morphology: Crops of multiple tiny, pinpoint, shallow ulcerations measuring 1 to 2 mm across that rapidly coalesce into irregular, ragged, painful erosive maps.
- Size & Number: Characterized by extensive crops of 10 to 100 ulcers simultaneously.
- Anatomical Distribution: Can affect any mucosal surface, but exhibits a predilection for the ventral tongue, lateral borders of the tongue, and floor of the mouth.
- Natural History: Heal within 10 to 14 days; scarring is generally absent unless confluence produces deep secondary necrosis.
- Pathology Distinction: Despite the name "herpetiform", this condition has no viral aetiology (it is entirely unrelated to Herpes Simplex Virus; cultures and PCR for HSV-1 are negative, and there is no preceding vesicular stage).
| Clinical Parameter | Minor Aphthae | Major Aphthae (Sutton's) | Herpetiform Ulcers |
|---|---|---|---|
| Proportion of Cases | ~80% | ~10% | 5–10% |
| Ulcer Diameter | <10 mm (typically 2–5 mm) | >10 mm (often 10–30 mm) | 1–2 mm (pinpoint) |
| Number per Episode | 1–5 | 1–3 | 10–100 (crops) |
| Mucosal Site | Non-keratinised mucosa only | Keratinised and non-keratinised (palatopharyngeal) | Non-keratinised and keratinised (ventral tongue) |
| Duration of Episode | 10–14 days | Weeks to months | 10–14 days |
| Healing Sequelae | No scarring | Heals with scarring | Rare scarring |
| Aetiology | T-cell mediated | T-cell mediated (severe) | T-cell mediated (no HSV involvement) |
Systemic Associations & Screening Protocol
While the vast majority of RAS cases are idiopathic, secondary aphthous-like ulceration can represent the initial sign of severe underlying haematological, gastrointestinal, or rheumatological disease. In the UK, initial screening in primary dental care or secondary oral medicine clinics requires systematic laboratory investigation:
Systemic Investigation of RAS
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Haematinic Profile Coeliac Serology IBD Evaluation Behçet's
• Serum Ferritin • Anti-tTG IgA • Faecal Calprotectin• Orogenital
• Serum Folate • Total Serum IgA (exclude IgA deficiency) • Colonoscopy / MRE Ulceration
• Serum B12 • Duodenal biopsy gold standard • Orofacial Granuloma• Uveitis
• Full Blood Count • Snail-track ulcers • Pathergy
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Haematinic Deficiencies:
- Deficiencies in serum ferritin (iron stores), vitamin B12 (cobalamin), and red cell / serum folate occur in 15–20% of patients with severe recurrent aphthae. Correction of the specific nutritional deficit produces complete remission or dramatic reduction in ulcer frequency in over 70% of deficient patients.
- Complete Blood Count (CBC/FBC) assesses for microcytic hypochromic anaemia (iron deficiency) or macrocytic megaloblastic anaemia (B12/folate deficiency).
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Coeliac Disease (Gluten-Sensitive Enteropathy):
- An autoimmune enteropathy induced by dietary gluten ingestion in genetically susceptible individuals (HLA-DQ2/DQ8).
- Up to 5% of patients with intractable aphthae have silent coeliac disease. It impairs intestinal villous absorption, precipitating secondary iron, folate, and calcium deficiencies.
- Screening: Serum anti-tissue transglutaminase IgA (anti-tTG IgA) antibodies alongside total serum IgA (to rule out selective IgA deficiency, which gives false-negative anti-tTG results; if IgA deficient, IgG-based anti-DGP or anti-tTG IgG must be assayed). Definitive diagnosis: small bowel / duodenal endoscopic biopsy showing subtotal villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis.
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Inflammatory Bowel Disease (IBD):
- Crohn's Disease: Transmural granulomatous inflammation of any GI tract segment. Intraoral manifestations frequently precede intestinal symptoms: deep, linear, "snail-track" or fissured ulcers in the buccal sulci with hyperplastic folded margins, diffuse lip and cheek swelling (orofacial granulomatosis / OFG), "cobblestone" mucosal architecture from submucosal lymphoedema, and polypoid mucosal tags.
- Ulcerative Colitis: Mucosal inflammation confined to the colon and rectum; oral manifestations include aphthae and pyostomatitis vegetans (multiple tiny pustules and vegetating friable mucosal folds that rupture into "snail-track" ulcerations).
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Behçet's Syndrome (Behçet's Disease):
- A chronic, relapsing, multisystem systemic vasculitis of unknown aetiology characterized by occlusive necrotising endarteritis of small and large vessels.
- International Diagnostic Criteria: Recurrent oral aphthae (observed by clinician or reliably reported at least 3 times in a 12-month period) plus at least two of the following:
- Recurrent genital ulceration (painful, scarring scrotal or vulval ulcers).
- Ocular inflammation (anterior or posterior uveitis, hypopyon, retinal vasculitis causing visual loss).
- Cutaneous lesions (erythema nodosum, pseudofolliculitis, acneiform nodules).
- Positive Pathergy Test: An exaggerated sterile erythematous papule or pustule developing 24–48 hours following oblique skin puncture with a sterile 20-gauge needle.
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Other Rare Associations:
- Cyclic Neutropenia: Autosomal dominant ELANE mutation; regular 21-day cycles of severe peripheral neutropenia (<0.5 × 10⁹/L) presenting with recurrent severe aphthous ulceration, fever, cervical lymphadenopathy, and aggressive periodontal bone loss.
- MAGIC Syndrome: Mouth And Genital ulcers with Inflamed Cartilage (features of both Behçet's and relapsing polychondritis).
- PFAPA Syndrome: Periodic Fever, Aphthous stomatitis, Pharyngitis, and Adenitis in young children.
Clinical Management Ladder in the UK
Management aims to alleviate pain, accelerate re-epithelialisation, reduce ulcer duration, and prolong disease-free remission:
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First-Line (Topical Symptomatic & Barrier Therapy):
- Analgesic / Anti-inflammatory mouthwashes: Benzydamine hydrochloride 0.15% oral rinse or spray (Difflam) every 2–3 hours before meals to reduce pain.
- Barrier agents: Carmellose sodium paste (Orabase) applied over lesions to shield exposed nerve endings from salivary enzymes and mechanical friction.
- Antimicrobial rinses: Chlorhexidine gluconate 0.2% mouthwash (10 mL bd) or hydrogen peroxide 1.5% mouthwash to prevent secondary bacterial infection and hasten healing.
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Second-Line (Topical Corticosteroids):
- Hydrocortisone Oromucosal Pellets (2.5 mg): 1 pellet dissolved in the mouth in close proximity to the ulcer 4 times daily (qds). Best initiated during the prodromal stinging phase.
- Betamethasone Soluble Tablets (0.5 mg): 1 tablet dissolved in 10 mL of water, used as an intensive mouthwash for 2–3 minutes and then spat out, 2 to 4 times daily. (Avoid swallowing to minimise systemic absorption and hypothalamic-pituitary-adrenal [HPA] axis suppression).
- Beclometasone Dipropionate Inhaler (50–100 μg/actuation): 1–2 sprays targeted directly onto localized lesions twice daily.
- Clobetasol Propionate Ointment (0.05%) mixed 1:1 with Orabase: Applied topically tid for recalcitrant major aphthae.
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Third-Line (Secondary Care Specialist Systemic Immunomodulation):
- Reserved for debilitating major aphthae or Behçet's disease managed by Oral Medicine consultants: short courses of systemic prednisolone (30–40 mg/day tapered over 2–3 weeks), colchicine (500 μg bd–tid), dapsone, thalidomide (strictly controlled due to teratogenicity / phocomelia and peripheral neuropathy), or anti-TNF-α biologic therapies (infliximab, adalimumab).