What is the treatment for recurrent oral ulceration?

Treatment of Recurrent Oral Ulceration

Start with topical corticosteroids as first-line therapy for all recurrent oral ulcers, selecting the formulation based on ulcer location and extent, then escalate to systemic colchicine for recurrent episodes (≥4 per year), and reserve immunosuppressives for refractory cases. 1, 2

Initial Topical Therapy

For Localized Ulcers

• Apply clobetasol gel or ointment 0.05% directly to dried ulcer 2-4 times daily as the most potent topical option for accessible lesions 1, 2
• Alternatively, use triamcinolone acetonide 0.1% paste applied directly to dried ulcer 2-4 times daily for less severe localized lesions 1

For Multiple or Widespread Ulcers

• Use betamethasone sodium phosphate 0.5 mg dissolved in 10 mL water as a rinse-and-spit solution 2-4 times daily for ulcers that are difficult to reach 1, 2
• Dexamethasone mouth rinse (0.1 mg/mL) serves as an alternative for widespread involvement 1
• Fluticasone propionate nasules diluted in 10 mL water twice daily can be substituted when other topical steroids are unavailable 2, 3

Pain Management (Use Concurrently)

• Apply viscous lidocaine 2% before meals for immediate pain relief 1, 3
• Use benzydamine hydrochloride rinse or spray every 3 hours, particularly before eating, for anti-inflammatory pain control 1, 2
• Apply barrier preparations (Gelclair or Gengigel) three times daily for mucosal protection 1, 3

Oral Hygiene Measures

• Clean mouth daily with warm saline mouthwashes to reduce bacterial colonization 1, 3
• Use antiseptic oral rinses twice daily (0.2% chlorhexidine digluconate or 1.5% hydrogen peroxide) 1, 2

Second-Line Therapy for Inadequate Response to Topicals

Intralesional Steroids

• Administer intralesional triamcinolone injections weekly (total dose 28 mg) in conjunction with topical clobetasol for ulcers persisting beyond 2 weeks of topical therapy 1, 2

Short-Course Systemic Corticosteroids

• Give prednisone/prednisolone 30-60 mg (or 1 mg/kg) for 1 week, then taper over the second week for highly symptomatic or severe ulcers 1, 2, 3
• This approach is particularly useful for major aphthous ulcers or severe flares 1

Critical Pitfall: Never taper corticosteroids prematurely before disease control is established, as this leads to rebound ulceration 1

Third-Line Therapy for Recurrent Disease (≥4 Episodes Per Year)

Colchicine as First-Line Systemic Prevention

• Start colchicine for patients with recurrent aphthous stomatitis experiencing 4 or more episodes annually, especially when erythema nodosum or genital ulcers are present 4, 1, 2
• This recommendation comes from the European League Against Rheumatism guidelines for Behçet's syndrome but applies to recurrent aphthous stomatitis more broadly 4, 1

Immunosuppressives for Refractory Cases

• Consider azathioprine, interferon-alpha, or TNF-alpha inhibitors when colchicine fails to prevent recurrences 1, 2
• Apremilast represents a newer option for selected refractory cases 1
• Tacrolimus 0.1% ointment applied twice daily for 4 weeks can be effective for recalcitrant localized ulcers 2, 3

Critical Pitfall: Avoid ciclosporine A in patients with any neurological symptoms due to neurotoxicity risk 1

Special Considerations for Behçet's Syndrome

When recurrent oral ulcers occur with genital ulcers, eye inflammation, or systemic vasculitis:

• Begin with topical steroids and colchicine as outlined above 4, 1
• Escalate rapidly to immunosuppressives (azathioprine, interferon-alpha, or TNF-alpha antagonists) when chronic ulceration causes scarring to prevent oropharyngeal narrowing and deforming genital scarring 4
• Sucralfate suspension has demonstrated efficacy in randomized trials for oral and genital ulcers in Behçet's disease 1

When to Refer or Investigate Further

• Refer to specialist for ulcers lasting more than 2 weeks or not responding to 1-2 weeks of treatment 1
• Perform biopsy for ulcers persisting beyond 2 weeks to exclude malignancy and other serious conditions 1
• Check full blood count, coagulation studies, fasting glucose, HIV antibody, and syphilis serology before biopsy to exclude contraindications and provide diagnostic clues 1

Evidence Quality Note

The Cochrane systematic review found insufficient evidence to definitively support any single systemic intervention, likely reflecting poor methodological quality of trials rather than true lack of efficacy 5. However, the guideline recommendations from the European League Against Rheumatism 4 and synthesized evidence from multiple specialty societies 1, 2, 3 provide the strongest basis for the stepwise approach outlined above, prioritizing topical therapy first, then colchicine for recurrent disease, and reserving immunosuppressives for refractory cases.