BI39 When pruritus signals toxicity: bullous eruption from high-dose methotrexate

Abstract

Cutaneous drug reactions in oncology patients are diagnostically challenging, particularly when clinical morphology is atypical and multiple potential causative agents coexist. High-dose methotrexate (MTX) is well recognized to cause systemic toxicity and mucosal ulceration; however, unusual blistering cutaneous presentations are rarely reported. We report the case of a 71-year-old male farmer with a recent diagnosis of primary central nervous system non-Hodgkin lymphoma, undergoing his second cycle of R-MPV chemotherapy (rituximab, high-dose MTX at 6 g, procarbazine and vincristine). He was referred to the on-call dermatology service with a 3-day history of acute-onset, intense generalized pruritus associated with widespread excoriations, developing shortly after initiation of the second chemotherapy cycle. Clinical examination demonstrated extensive linear excoriations over the chest, shoulders, arms and lower abdomen, with sparing of the palms, soles and genitalia. There was no mucosal involvement. Careful inspection revealed subtle small blisters containing yellowish fluid distributed along excoriated lines on the chest and arms. The patient was actively scratching during examination. In view of the fluid-filled blisters, the differential diagnosis included cutaneous infection, autoimmune blistering disease and drug-­induced reaction. Blood investigations revealed a markedly elevated MTX level (1.8 µmol L−1; normal < 0.10), rising liver enzymes, eosinophilia, thrombocytopenia and worsening anaemia. An urgent skin biopsy was performed for histological examination and direct immunofluorescence, and swabs were taken to exclude infection. Over the subsequent 48 h, the eruption progressed to confluent erythematous patches corresponding to previously pruritic areas. The patient was treated with intravenous fluids and high-dose folinic acid rescue, leading to gradual MTX clearance over 6 days, accompanied by spontaneous improvement of the cutaneous findings. Histopathology was consistent with a bullous drug-induced reaction, in keeping with MTX toxicity. This case reinforces pruritus as a manifestation of cutaneous high-dose MTX toxicity and highlights a distinctive blistering eruption as a potential, under-recognized adverse effect.