Methotrexate-Induced Leukocytoclastic Vasculitis: A Case Report and Literature Review

Abstract

Methotrexate (MTX) is widely utilized for the management of autoimmune diseases and neoplasms. It may cause several adverse effects, including myelosuppression, hepatitis, and mucositis, and in rare cases, can result in cutaneous vasculitis. We present a case involving a 60-year-old female patient receiving 5 milligrams (mg) of MTX weekly for the treatment of systemic lupus erythematosus (SLE). Her underlying condition was end-stage renal disease (ESRD), requiring hemodialysis (HD). Ten weeks after MTX treatment, she developed oral ulcers, pancytopenia, and hepatitis, followed by multiple non-blanchable erythematous papules, along with a few vesicles and pustules on the neck, trunk and arms. Laboratory results indicated elevated serum MTX levels, and skin biopsy demonstrated dense superficial perivascular and interstitial lymphocytic, eosinophilic, and neutrophilic infiltration, along with nuclear debris and extravasated erythrocytes, indicative of early leukocytoclastic vasculitis (LCV). Direct immunofluorescence (DIF) identified C3 deposits at the dermo-epidermal junction and superficial blood vessels, indicating possible immune complex-mediated vascular disease. The patient was diagnosed with MTX toxicity and histologically confirmed LCV secondary to MTX. MTX toxicity was effectively treated with intravenous folinic acid and cessation of MTX, alongside prescriptions of oral prednisolone and emollients for LCV management. Serum MTX levels became undetectable after a five-day treatment regimen. Skin lesion resolution occurred within one week. Additionally, a review of existing literatures on MTX-induced LCV was conducted.