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A6903 - Methotrexate Toxicity: Skin in the Game
Author Block: S. Noronha, D. R. Brown; Mayo Clinic, Rochester, MN, United States.
Introduction: Methotrexate-induced Epidermal Necrolysis (MEN) is a rare complication of high-dose Methotrexate therapy. Early identification and appropriate treatment is key to the management of this condition. Description: Our patient was a 29 year old woman with a history of morbid obesity and recently diagnosed B-cell acute lymphoblastic leukemia (ALL) and had been treated with the chemotherapeutic regimen of HyperCVAD and Dasatinib, followed by Rituximab, Cytarabine and high-dose Methotrexate. Six days following this treatment, she developed painful blisters and an erythematous rash that began on her feet but spread to include her entire body, sparing her neck and face. The rash evolved into a coalescent bullous pattern with positive Nikolsky and Asboe-Hansen signs. She also developed an erosive oral mucositis. When she was initially transferred to our hospital, six days after receiving Methotrexate, her serum Methotrexate level was 0.23 micromole/liter, more than twice the upper therapeutic level. A skin biopsy confirmed the diagnosis as Methotrexate-induced epidermal necrolysis. Analgesic administration ultimately required endotracheal intubation for airway protection. Her Methotrexate levels remained elevated despite Leucovorin rescue and alkalinizing her urine. She was then administered Glucarpidase with a rapid improvement of her Methotrexate level. While her skin lesions had begun to re-epithelialize, she developed a posterior thigh skin infection with fungal Curvularia species. She additionally developed a candidemia and a bacteremia with Enterococcus faecium, in the setting of post-chemotherapeutic pancytopenia. She developed multi-organ failure and despite aggressive efforts to treat her infections, her condition did not improve and she was transitioned to comfort care. Discussion: High-dose Methotrexate is a staple of numerous chemotherapeutic regimens, and while hepatic, renal and pulmonary manifestations of Methotrexate toxicity have been widely described, Methotrexate-induced epidermal necrolysis is rare, only sporadically reported in the literature. Clinical features overlap with Toxic Epidermal Necrolysis, as in this case, and the diagnosis is settled through pathological examination. Treatment includes Leucovorin rescue, alkalinization of urine to aid Methotrexate excretion, and Glucarpidase to enzymatically break down Methotrexate.