What is the treatment for methotrexate (MTX) induced oral ulcers?

Treatment of Methotrexate-Induced Oral Ulcers

The first-line treatment for methotrexate-induced oral ulcers is immediate discontinuation or dose reduction of methotrexate combined with folic acid supplementation, followed by topical corticosteroids and pain management. 1, 2

Immediate Management Steps

Stop or Reduce Methotrexate

• Discontinue methotrexate immediately when oral ulcers develop 1, 3, 4
• The ulcers typically resolve within 2 weeks of stopping the medication 3
• If continuation is necessary, reduce the dose significantly 5

Folic Acid Supplementation

• Initiate or increase folic acid supplementation to 5 mg weekly (1-2 days after methotrexate dose) or 1 mg daily 1
• Folic acid reduces gastrointestinal and oral toxicity from methotrexate 1
• Non-compliance with folic acid is a known risk factor for developing methotrexate-induced oral ulcers 6

Topical Treatment Protocol

First-Line Topical Therapy

• Apply high-potency topical corticosteroids as the primary treatment 2, 7
• For localized ulcers: Use clobetasol gel or ointment 0.05% applied directly to dried ulcer 2-4 times daily 2, 7
• For widespread or multiple ulcers: Use betamethasone sodium phosphate 0.5 mg dissolved in 10 mL water as a rinse-and-spit solution 2-4 times daily 2, 7
• Alternative: Dexamethasone mouth rinse (0.1 mg/mL) for difficult-to-reach lesions 2

Pain Management

• Use topical anesthetic mouthwashes (viscous lidocaine 2%) before meals 2
• Apply benzydamine hydrochloride rinse or spray every 3 hours, particularly before eating 2
• If traditional pain management fails, consider morphine mouthwash solution 6
  • This is a safer alternative to systemic opioids and may promote healing through effects on cell proliferation 6
  • One case report showed improvement within 48 hours when magic mouthwash failed 6

Mucosal Protection

• Apply barrier preparations such as Gelclair or Gengigel three times daily 2, 7
• Use white soft paraffin ointment to lips every 2 hours 2

Oral Hygiene and Supportive Care

• Clean the mouth daily with warm saline mouthwashes 2
• Use antiseptic oral rinses twice daily (1.5% hydrogen peroxide or 0.2% chlorhexidine digluconate) 2
• Monitor for secondary infections, as the risk is high in immunosuppressed patients 5
• Treat concurrent candidal infections with nystatin oral suspension or miconazole oral gel 7

Second-Line Management for Refractory Cases

Intralesional Steroids

• For persistent ulcers not responding to topical therapy, inject intralesional triamcinolone weekly (total dose 28 mg) 2, 7

Systemic Corticosteroids

• For highly symptomatic or recurrent ulcers, use prednisone/prednisolone 30-60 mg or 1 mg/kg for 1 week with tapering over the second week 2, 7
• This should be reserved for severe cases that don't respond to topical measures 2

Critical Pitfalls to Avoid

• Do not continue methotrexate at the same dose when oral ulcers develop 1, 3
• The British Association of Dermatologists specifically warns patients to seek urgent medical attention for mouth ulceration as a sign of methotrexate toxicity 1
• Do not assume all oral ulcers in methotrexate patients are drug-induced 4
  • The histopathologic features can mimic lymphoproliferative disorders 4
  • Consider biopsy for ulcers lasting over 2 weeks or not responding to treatment 2
• Be aware of drug interactions that can precipitate methotrexate toxicity 4
  • Ciprofloxacin and other medications can trigger acute methotrexate-induced ulceration 4
• Recognize that methotrexate-induced ulcers can occur within psoriatic plaques, not just on normal mucosa 3

When to Refer

• Refer to a specialist for oral ulcers lasting more than 2 weeks or not responding to 1-2 weeks of treatment 2
• Consider referral if there is concern for lymphoproliferative disorder or atypical presentation 4