• Julie Delyon, Nicolas Ortonne, Emmanuel Benayoun, Julien Moroch, Pierre Wolkenstein, Emilie Sbidian, and Olivier Chosidow.
• Département de Dermatologie, Assistance Publique-Hôpitaux de Paris (AP-HP) Hôpitaux universitaires Henri Mondor, Créteil, France.
• J. Am. Acad. Dermatol. 2015 Sep 1; 73 (3): 484-90.

BackgroundSkin toxicity during low-dose methotrexate therapy is rare, ill described, and reported to have nonspecific histologic characteristics. Thus, misdiagnosis is common in patients with mucosal ulcers and/or skin erosions related to low-dose methotrexate.ObjectiveWe sought to describe the features of skin toxicity induced by low-dose methotrexate.MethodsWe evaluated the clinical and histologic features in 5 patients who experienced skin toxicity induced by low-dose methotrexate between 2011 and 2013.ResultsAll 5 patients had acute mucosal ulcers, 4 had moderately abnormal blood cell counts, and 3 had skin erosions. In 3 patients, methotrexate dosage or dosing-schedule errors were identified. No other contributing factors (eg, renal dysfunction or interacting drugs) were identified. Mucocutaneous biopsy specimens consistently showed multiple dystrophic keratinocytes.LimitationsWe studied only 5 patients and obtained no sensitivity or specificity data on the diagnostic value of keratinocyte dystrophy.ConclusionKeratinocyte dystrophy may help to diagnose skin toxicity of low-dose methotrexate, even in the absence of known risk factors or methotrexate administration errors. Studies of the diagnostic performance of this histologic sign are needed.Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

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