Abstract:

Methotrexate (MTX) is an inhibitor of folate biosynthesis; preventing DNA synthesis of T lymphocytes and epidermal keratinocytes that may be used for the treatment of moderate to severe psoriasis. As a result of inhibiting DNA synthesis in rapidly proliferating cells acute methotrexate-induced toxicity may ensue manifesting as mucocutaneous ulceration, bone marrow depression, and renal injury. We report an 83-year-old male with multiple comorbidities including psoriasis and dermatitis herpetiformis, who developed worsening skin ulcers with surrounding erythema on the abdomen, buttocks, and bilateral lower extremities on the background of violaceous macules as well as painful mucosal ulcers after starting MTX for a recent psoriasis flare. Serologies revealed profound pancytopenia. The clinical differential diagnosis included atypical presentation of dermatitis herpetiformis, drug hypersensitivity, disseminated HSV/VZV infection, and in the setting of fever of unknown origin and painful mucosal ulcers, Bechet disease. Two skin punch biopsies were performed and sections revealed vacuolar interface changes with dyskeratotic keratinocytes, squamous dysmaturation, and superficial to deep perivascular lymphocytic infiltrate with eosinophils and erythrocyte extravasation. Vasculitis was not seen. HSV/VZV immunostains were negative. Clinicopathologic correlation was consistent with acute MTX induced skin toxicity with mucositis. MTX withdrawal and appropriate wound care led to clinical improvement of the skin and mucosal lesions with recovery of blood counts within two weeks of the initial presentation. This case raises awareness of an unusual adverse reaction to MTX with mucosal ulcers clinically mimicking Behcet disease.

Financial Disclosure:
No current or relevant financial relationships exist.

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Sara Moradi, MD