Cutaneous ulceration as a sign of methotrexate toxicity
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Updated: Oct 4, 2026

A Standardized Procedure of Dressing Management for Toxic Epidermal Necrolysis
Published on: March 14, 2025
J Del Pozo1, W Martínez, J García-Silva
1Department of Dermatology, Hospital Juan Canalejo, Xulbias de Arriba 84, 15006 La Coruña, Spain.
Abstract:
Methotrexate (MTX) inhibits DNA synthesis by competition with dihydrofolate reductase. Adverse cutaneous reactions to MTX are usually dose-related and have been mainly reported in patients receiving extremely large doses of chemotherapy. Painful erosion of psoriatic plaques has been often reported as an early sign of MTX toxicity, but cutaneous ulceration as a sign of MTX toxicity in patients without psoriasis has only been described in one case. We report a patient with rheumatoid arthritis and without psoriasis who developed cutaneous ulceration on the knuckles as a sign of MTX toxicity. Cutaneous ulceration by MTX toxicity is an exclusion diagnosis and its pathogenic mechanism may be multifactorial, including direct toxicity of the drug in addition to local factors.
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