Methotrexate-induced epidermal necrosis: A case series of 24 patients

Publication date: Available online 10 May 2017
Source:Journal of the American Academy of Dermatology
Author(s): Ting-Jui Chen, Wen-Hung Chung, Chun-Bing Chen, Rosaline Chung-Yee Hui, Yu-Huei Huang, Yueh-Tsung Lu, Chang-Wei Wang, Kuo-Hsien Wang, Li-Cheng Yang, Shuen-Iu Hung
BackgroundMethotrexate-induced epidermal necrosis (MEN) is a rare but life-threatening cutaneous reaction that mimics Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).ObjectivesTo investigate the clinicopathology, risk factors, and prognostic factors of MEN.MethodsWe enrolled 24 patients with MEN and 150 controls and analyzed the demographics, pathology, and plasma concentrations of methotrexate (MTX).ResultsPatients with MEN showed extensive skin necrosis (mean, 33.2% total body surface area) but no target lesions. The histopathology displayed keratinocyte dystrophy. Early signs of MEN included painful skin erosions, oral ulcers, and leukopenia/thrombocytopenia. Although 79.2% patients received leucovorin treatment, there was 16.7% mortality. Risk factors for MEN included older age (>60 years), chronic kidney disease, and high initial dosage of MTX without folic acid supplementation. Renal insufficiency delayed MTX clearance. Severe renal disease and leukopenia predicted poor prognosis in MEN, but none of the SCORe of Toxic Epidermal Necrosis criteria were associated with mortality of MEN.LimitationsThe study was limited by the small sample size.ConclusionMEN exhibited distinct clinicopathologic features from SJS/TEN. Recognition of the early signs and prognostic factors is important, because the rapid institution of leucovorin may be helpful. To reduce the risk of MEN, physicians should avoid prescribing MTX to high-risk patients and titrate the dosage slowly upward with folic acid supplementation.



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