Abstract:

Methotrexate-induced epidermal necrosis (MEN) is a cutaneous reaction that mimics Stevens–Johnsons syndrome and toxic epidermal necrolysis (SJS/TEN). MEN is rare, but life threatening, and requires prompt clinicopathologic correlation to make the correct diagnosis and manage these patients appropriately. Early signs of MEN include painful skin erosions, mucocutaneous ulcerations, thrombocytopenia, and leukopenia.(1-4) Biopsies from patients with MEN display epidermal atrophy, keratinocyte vacuolar change with dyskeratotic cells or full epidermal necrosis, reactive epidermal nuclei or epidermal atypia, along with ulcer formation with few lymphocytic infiltrates. While some of these histopathologic features of MEN overlap those seen in SJS/TEN, SJS/TEN typically lacks epidermal atrophy and tends to demonstrate subepidermal vesiculation. The underlying mechanism of MEN is direct MTX toxicity to keratinocytes without increased inflammatory cytokines, while SJS/TEN has drug-specific cytotoxic T lymphocytes with increased inflammatory cytokines and cytotoxic proteins.(1,2) These pathophysiologic differences between MEN and SJS/TEN could account for the variability in both clinical and histopathologic presentations. Physicians prescribing MTX should understand these common clinical and histopathologic presentations of MEN to ensure early identification of this process, prompt cessation of MTX, and initiation of leucovorin rescue.(1-4) The case herein presents a rare report of MEN mimicking TEN in a 52-year-old female with a history of rheumatoid arthritis, which resolved after discontinuing methotrexate and initiating leucovorin.

Financial Disclosure: No current or relevant financial relationships exist.

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Caitlin Noble, MD