Recurrent Aphthous Stomatitis

Recurrent aphthous stomatitis (recurrent aphthous ulcers) is a common disorder of repeated, painful, round or oval ulcers of the non-keratinised oral mucosa, with a yellow grey base and erythematous halo, in otherwise well people, with ulcer free intervals between episodes.

• Prevalence is about 5 to 25 percent; onset is usually in childhood or adolescence, and many have a family history.
• Minor aphthae (about 80 percent): under 10 mm, 1 to 5 ulcers on the lips, cheeks, floor of mouth and tongue, heal in 7 to 14 days without scarring.
• Major aphthae: over 10 mm, deep, last 2 to 6 weeks or longer, heal with scarring, and affect the soft palate and pharynx as well.
• Herpetiform aphthae: crops of 10 to 100 pinpoint ulcers (1 to 3 mm) that coalesce, lasting 1 to 2 weeks; unrelated to herpes simplex virus.
• Triggers and associations: local trauma, stress, haematinic deficiency (iron, vitamin B12, folate), coeliac disease, inflammatory bowel disease, food hypersensitivity (chocolate, nuts, citrus, cinnamon, cheese), sodium lauryl sulfate in toothpaste, stopping smoking, menstruation, drugs (NSAIDs, nicorandil, methotrexate, beta blockers), HIV, and cyclic neutropenia.
• Systemic syndromes with aphthae: Behçet disease (genital ulcers, uveitis, skin lesions), PFAPA syndrome in children (periodic fever, pharyngitis, adenitis), MAGIC syndrome, and Sweet syndrome.

• Prodrome of tingling or burning for 24 hours, then a round or oval shallow ulcer with a well defined margin, grey yellow floor and red halo; painful, especially when eating, drinking and speaking.
• Sites: labial and buccal mucosa, sulci, floor of mouth, ventral tongue and soft palate; hard palate, gingiva and dorsum of tongue are usually spared in minor aphthae.
• Minor aphthae occur 1 to 3 times a year in many people and monthly or more often in some.
• Major aphthae can impair eating, cause weight loss and distress.
• Red flags: ulcers lasting more than 3 weeks, hard or raised margins, ulcers in the keratinised mucosa, associated white or red patch, painless ulcer, neck node, systemic symptoms (weight loss, diarrhoea, genital ulcers, eye pain, joint pain, fever).

• Clinical, from the history of recurrent self-limiting ulcers and the typical appearance.
• Investigations in frequent, severe or atypical disease: FBC, ferritin, vitamin B12, red cell folate, coeliac serology (tissue transglutaminase IgA with total IgA), HbA1c, ESR or CRP, HIV (if risk), zinc, and a medication review.
• Biopsy (with immunofluorescence) for ulcers persisting beyond 3 weeks, atypical appearance, or suspicion of cancer, lichen planus, pemphigus, pemphigoid or granulomatous disease.
• Swab or PCR for herpes simplex virus if the lesions involve the keratinised mucosa or follow a vesicular prodrome.
• Differentials: herpes simplex (vesicles on keratinised mucosa), traumatic ulcer, hand-foot-and-mouth disease, herpangina, erythema multiforme, lichen planus, pemphigus vulgaris, mucous membrane pemphigoid, Behçet disease, Crohn disease, HIV-related ulcers, syphilis, and squamous cell carcinoma.

Education and self-care

• Explain that ulcers are not infectious and are self-limiting; identify and avoid triggers; use a soft toothbrush and sodium lauryl sulfate free toothpaste; avoid hot, spicy, acidic and abrasive foods; keep good oral hygiene.

Correct deficiencies and treat associated disease

• Iron deficiency: ferrous sulfate 200 mg orally once daily or on alternate days; vitamin B12 deficiency: hydroxocobalamin 1 mg intramuscularly (alternate days for 2 weeks, then every 3 months) or oral cyanocobalamin 1000 micrograms daily if there is no neurological disease; folate deficiency: folic acid 5 mg daily for 4 months. Replacement reduces recurrences in deficient patients.
• Coeliac disease: gluten free diet; inflammatory bowel disease: gastroenterology care.

Topical therapy (first line; start at the first sign of an ulcer)

• Analgesic and anti-inflammatory: benzydamine hydrochloride 0.15 percent mouthwash or spray 15 mL (or 4 to 8 sprays) every 1.5 to 3 hours as needed, for up to 7 days (not in children under 12 years for the mouthwash; dilute with water if it stings).
• Antiseptic: chlorhexidine gluconate 0.2 percent mouthwash 10 mL twice daily for 1 minute, to reduce secondary infection and ulcer duration.
• Topical corticosteroids:
  • Hydrocortisone mucoadhesive buccal tablets 2.5 mg, dissolved against the ulcer four times daily (after meals and at night) until healed.
  • Triamcinolone acetonide 0.1 percent in carboxymethylcellulose paste (oral paste) applied thinly to a dried ulcer 2 to 3 times daily after food.
  • Betamethasone sodium phosphate 0.5 mg soluble tablet dissolved in 20 mL water and used as a mouthwash for 2 to 3 minutes up to four times daily and spat out (for multiple ulcers).
  • Clobetasol propionate 0.05 percent gel in an adhesive base twice daily for major aphthae (for up to 2 weeks).
• Local anaesthetic: lidocaine 2 percent gel or viscous solution 5 mL, limited to 4 times daily and not before meals in children (risk of aspiration and choking).
• Tetracycline mouthwash: doxycycline 100 mg dissolved in 10 mL of water, rinsed for 2 minutes, four times daily for 3 days (not in children under 12 years, pregnancy or breastfeeding).

Systemic therapy for frequent or major disease (specialist)

• Prednisolone 30 to 60 mg orally daily for 5 to 7 days (reducing quickly) for severe major ulcers.
• Colchicine 0.5 mg orally twice daily, increasing to three times daily, in recurrent disease and Behçet disease (diarrhoea; reduce in renal impairment; avoid in pregnancy).
• Others: dapsone 50 to 100 mg daily (check G6PD), azathioprine, pentoxifylline 400 mg three times daily, apremilast 30 mg twice daily (Behçet), thalidomide 50 to 100 mg at night (strictly specialist, teratogenic and neuropathy).

Follow up

• Review at 4 weeks; reassess investigations if recurrences continue; refer to oral medicine, gastroenterology or rheumatology for refractory disease, suspected Behçet disease, or any ulcer persisting over 3 weeks.

Special groups

• Children: avoid tetracycline, colchicine, thalidomide and benzydamine mouthwash in young children; use triamcinolone paste or hydrocortisone buccal tablets, chlorhexidine gel, and look for PFAPA syndrome, coeliac disease and iron deficiency.
• Pregnancy: avoid tetracyclines, colchicine, thalidomide and dapsone; use topical hydrocortisone, benzydamine and chlorhexidine.