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Updated: Sep 11, 2025

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Published on: March 14, 2025
Methotrexate-induced epidermal necrosis
Christopher Kennedy1,2, John A Thompson1,2
1Oregon Health and Science University, Portland, OR, USA.
Introduction:
Methotrexate-induced epidermal necrosis is a rare, potentially fatal mucocutaneous reaction that clinically mimics Stevens-Johnson syndrome/toxic epidermal necrolysis. Early clinical manifestations include leukopenia, thrombocytopenia, mucositis and skin erosions. Risk factors for methotrexate-induced epidermal necrosis include age greater than 60 years, chronic kidney disease, and high initial dose of methotrexate (>10 mg/weekly) without folic acid supplementation.
Case Summary:
A 63-year-old female with a history of psoriasis started taking oral methotrexate 10 mg weekly without folic acid supplementation and developed a desquamating rash covering more than 70% of her body. Her rash developed within two weeks of starting methotrexate. She received treatment with calcium folinate and made a full recovery.
Images:
Clinical images obtained on hospital day two show diffuse skin erosions and necrosis.
Conclusion:
Methotrexate-induced epidermal necrosis is an uncommon, potentially fatal, adverse reaction to methotrexate. Early diagnosis of methotrexate-induced epidermal necrosis can prompt early intervention with calcium folinate and hopefully mitigate potentially fatal outcomes associated with methotrexate toxicity.
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