What is the best treatment approach for a patient presenting with mouth ulcers, considering potential underlying causes such as autoimmune disorders, viral infections, or nutritional deficiencies?

Treatment of Mouth Ulcers

Start with topical corticosteroids as first-line therapy for all mouth ulcers, selecting the formulation based on ulcer location and extent, combined with pain control measures and oral hygiene, escalating to systemic therapy only for refractory or severe recurrent cases. 1, 2

Initial Topical Corticosteroid Therapy

The choice of topical steroid depends on whether ulcers are localized or widespread:

For localized, accessible ulcers:

• Apply clobetasol 0.05% gel or ointment directly to the dried ulcer 2-4 times daily 1, 2
• Alternatively, use triamcinolone acetonide 0.1% paste applied to dried ulcer 2-4 times daily 1, 3

For multiple or widespread ulcers:

• Use betamethasone sodium phosphate 0.5 mg dissolved in 10 mL water as a rinse-and-spit solution 4 times daily 1, 2, 3
• Dexamethasone mouth rinse (0.1 mg/mL) serves as an effective alternative 1, 2

Pain Management (Essential Concurrent Therapy)

Pain control should be initiated simultaneously with corticosteroids:

• Apply viscous lidocaine 2% topically 3-4 times daily, particularly before meals 1, 2, 3
• Use benzydamine hydrochloride rinse or spray every 3 hours, especially before eating 1, 2, 3
• For severe pain, consider amlexanox 5% oral paste (topical NSAID) 1, 2

Barrier Protection and Oral Hygiene

These measures reduce bacterial colonization and protect ulcerated mucosa:

• Apply mucoprotectant mouthwashes (Gelclair or Gengigel) 3 times daily 1, 2, 3
• Rinse with warm saline mouthwashes daily 1, 2, 3
• Use 0.2% chlorhexidine digluconate mouthwash twice daily as antiseptic rinse 1, 2, 3
• Apply white soft paraffin ointment to lips every 2 hours if affected 1

Dietary Modifications

Advise patients to avoid crunchy, spicy, acidic, or hot foods and drinks 4

Second-Line Therapy for Refractory Cases (After 1-2 Weeks)

If topical therapy fails after 1-2 weeks of treatment:

• Inject intralesional triamcinolone weekly (total dose up to 28 mg) for persistent localized ulcers 1, 2, 3
• Consider tacrolimus 0.1% ointment applied twice daily for 4 weeks for recalcitrant ulcers 2, 3

Systemic Therapy for Severe or Recurrent Cases

For recurrent aphthous stomatitis (≥4 episodes per year):

• Colchicine is the preferred first-line systemic therapy, particularly effective for patients with erythema nodosum or genital ulcers 1, 2, 3

For highly symptomatic or severe cases:

• Use prednisone/prednisolone 30-60 mg (or 1 mg/kg) for 1 week, then taper over the second week 1, 2, 3
• Critical pitfall: Do not taper corticosteroids prematurely before disease control is established 1, 3

For resistant cases unresponsive to colchicine:

• Consider azathioprine, interferon-alpha, or TNF-alpha antagonists 1, 2, 3

When to Refer or Investigate Further

Mandatory referral/biopsy indications:

• Any ulcer persisting >2 weeks despite treatment requires specialist referral 1, 2
• Biopsy is mandatory for ulcers lasting >2 weeks to rule out malignancy 1, 2

Investigate for underlying systemic conditions in recurrent cases:

• Obtain complete blood count, coagulation studies 1
• Check nutritional studies: iron, folate, vitamin B12 (28% of recurrent ulcer patients have B1, B2, or B6 deficiency) 1, 5
• Celiac serology 2
• HIV testing and syphilis serology 1
• Fasting blood glucose 1

Special Considerations for Drug-Induced Ulcers

For patients on EGFR tyrosine kinase inhibitors or immunotherapy:

Grade 1-2 (mild-moderate):

• Continue medication with supportive care including topical steroids, viscous lidocaine, and PPIs or H2 blockers 4

Grade 3 (severe):

• Discontinue medication and hospitalize for supportive care 4
• Restart at lower dose only after resolution to Grade 1 4

Grade 4 (life-threatening):

• Medication should be discontinued 4
• Refer for specialist assessment to rule out Stevens-Johnson Syndrome 4

Treatment Algorithm Summary

1. Start immediately: Topical corticosteroids (clobetasol for localized, betamethasone rinse for widespread) + pain control (lidocaine, benzydamine) + barrier agents 1, 2

2. Add concurrently: Oral hygiene measures (saline rinses, chlorhexidine) and dietary modifications 1, 2

3. If no improvement in 1-2 weeks: Add intralesional triamcinolone or tacrolimus ointment 1, 2

4. For recurrent cases (≥4/year): Start colchicine as systemic therapy 1, 2

5. For severe refractory cases: Use short course of systemic corticosteroids with proper taper 1, 2

6. Always investigate: Check for nutritional deficiencies, systemic disease, and consider biopsy if ulcers persist >2 weeks 1, 2