Widespread skin necrosis due to methotrexate overdose in a patient with CKD

Abstract

A 55-year-old man with psoriasis vulgaris presented with a progressive painful skin eruption over the body for 10 days. He also had fever, dysphagia, leg edema, and reduced urine output for 3 days. Physical examination showed diffuse ulceration of the oral mucosa, and widespread, coalescing ulcerative plaques with background erythema and sloughing epidermis in association with edema over the trunk and extremities (Figure 1, Supplementary Figures S1–S3 online). The eruption appeared to involve both psoriatic lesions and non-psoriatic skin. Laboratory data revealed serum creatinine of 11 mg/dl, impaired liver function, hyperbilirubinemia, and pancytopenia. Abdominal echo revealed parenchymal renal disease with decreased bilateral renal sizes. With a recent history of methotrexate treatment for psoriasis (2.5 mg per day for more than 6 days), methotrexate overdose was suspected. The diagnosis was further supported by a skin biopsy showing vacuolar interface dermatitis with parakeratosis with neutrophilic infiltrate in the horny layer and edema with necrosis of keratinocytes in the epidermis, and minimal inflammation without evidence of vasculitis in the dermis (Figure 2, Supplementary Figures S4–S6 online), and an elevated serum methotrexate (0.01 μmol/l, sampled after two sessions of hemodialysis). On tracing his history, his serum creatinine was about 2.0–2.2 mg/dl, and chronic kidney disease (CKD) was diagnosed by a local doctor about 2 years ago; however, he did not receive any follow-up renal function test during the past 2 years. His blood counts returned to normal and skin lesions resolved within 3 weeks after hemodialysis and supportive care. His serum creatinine levels returned to about 4 mg/dl. Methotrexate is mainly excreted in unchanged form by the kidney. Impaired kidney function delays methotrexate clearance and may lead to serious toxicity; thus, before the prescription of methotrexate, physicians should be cautious about patient’s history of renal diseases, and a renal function test is suggested for patients with risk(s) for CKD.