Is Methotrexate effective for treating eczema?

Methotrexate for Eczema Treatment

Yes, methotrexate is effective for treating moderate-to-severe eczema (atopic dermatitis) that has failed conventional topical therapies, with evidence showing approximately 40-75% of patients achieve significant improvement. 1

Evidence Quality and Regulatory Status

• Methotrexate is not FDA-approved for eczema in the United States or UK—it is only licensed for psoriasis among dermatologic conditions 1
• However, the British Association of Dermatologists 2016 guidelines explicitly recognize methotrexate as an established off-label treatment for atopic eczema with Strength of Recommendation D and Level of Evidence 3 1
• The American Academy of Dermatology 2014 guidelines recommend methotrexate as a systemic agent for refractory atopic dermatitis 1

Clinical Efficacy Data

The highest quality evidence comes from a 2011 randomized controlled trial comparing methotrexate to azathioprine in 42 adults with severe atopic eczema 2:

• Methotrexate achieved 42% mean reduction in disease severity at 12 weeks (using SCORAD scoring) 2
• This was equivalent to azathioprine (39% reduction, P=0.52) 2
• Both treatments were deemed safe with no serious adverse events 2
• Doses used: 10-22.5 mg weekly for methotrexate 2

Supporting prospective studies demonstrate consistent efficacy 3:

• A 2007 open-label trial of 12 adults showed 52% average improvement in disease activity (SASSAD score) at 24 weeks 3
• Importantly, 34% improvement persisted 12 weeks after stopping methotrexate, suggesting disease-modifying effects 3
• Maximum benefit typically occurs by week 10-12, with minimal additional improvement after 12-16 weeks 1, 3

Pediatric data supports use in children 4, 5:

• A case series of 25 children with discoid eczema showed 64% complete clearance after average 10.5 months of treatment 4
• A retrospective review of 31 pediatric patients found methotrexate effective or very effective in 75% 5

Dosing Protocol for Your Patient

The prescribed dose of 7.5 mg weekly is appropriate as a starting dose 1:

• Start at 7.5-10 mg weekly after a 5 mg test dose 1, 3
• Titrate upward by 2.5 mg increments every 2-4 weeks based on response and tolerability 1
• Target dose range: 10-25 mg weekly for adults 1
• Average effective dose in clinical trials: 15-20 mg weekly 1, 3, 2

Critical dosing considerations:

• If no response by week 12 at 15 mg weekly, further dose escalation is unlikely to help 3
• Single weekly dosing is standard, though divided dosing (every 12 hours for 3 doses) is an alternative 1
• Folic acid supplementation (5 mg daily or weekly) should be given to reduce side effects 1

Monitoring Requirements

Baseline assessment required 1:

• Complete blood count, liver function tests, serum creatinine 1
• History and physical examination focusing on hepatic disease, anemia, leucopenia, thrombocytopenia 1

Ongoing monitoring schedule 1:

• Weekly monitoring initially: CBC, liver enzymes, creatinine 1
• Once stable, extend to every 1-2 months 1
• Long-term risk of hepatic fibrosis relates to cumulative lifetime dose 1

Contraindications and Precautions

Absolute contraindications 1:

• Pregnancy and breastfeeding 1
• Wish to father children (causes spermal abnormalities) 1
• Significant hepatic damage, severe anemia, leucopenia, thrombocytopenia 1

Mandatory contraception in both men and women during treatment and for at least one menstrual cycle after stopping in women 1

Common Pitfalls to Avoid

• Do not use NSAIDs concurrently—they reduce methotrexate renal elimination and can precipitate severe toxicity 6
• Do not underdose—the 7.5 mg starting dose should be escalated to 15-20 mg weekly for optimal effect 1, 3
• Do not continue indefinitely without response—if no improvement by 12 weeks at adequate dosing, consider alternative agents 3
• Do not omit folic acid supplementation—this significantly reduces gastrointestinal side effects and liver enzyme elevations 1

Expected Timeline and Side Effects

Response timeline 1:

• Initial improvement: 4-8 weeks 1, 3, 7
• Maximum effect: 10-12 weeks 1, 3
• Response time listed in guidelines: 2 weeks (though clinical trials show longer) 1

Common manageable side effects 1, 3, 7:

• Nausea, anorexia, fatigue occurring on dosing day 1
• Minimize by taking with food, at bedtime, or switching to subcutaneous injection 1
• Minor liver enzyme elevations (monitor closely) 3, 7, 2

Serious toxicities requiring vigilance 1:

• Bone marrow suppression (can occur after even a single dose) 6
• Hepatic fibrosis with cumulative dosing 1
• Pulmonary fibrosis (rare but serious) 1