Low-dose methotrexate toxicity leading to pancytopenia: leucovorin as a rescue treatment

Low-dose methotrexate has several known side effects associated with mild toxicity including nausea, oral ulcers, and anemia. However, it is rare for patients taking low-dose methotrexate to present with symptoms of severe toxicity including pancytopenia, macular punctate rash, and severe stomatitis. Here we present an 83-year-old patient with a history of rheumatoid arthritis on low-dose methotrexate for 1 year presenting with 5 days of worsening facial swelling, oral lesions, and a macular rash to the extremities. Initial workup revealed severe leukopenia, thrombocytopenia, and previously undiagnosed chronic kidney injury. Computed tomography showed edema surrounding a left maxillary dental implant suggestive of infection. The patient was admitted for suspected methotrexate toxicity complicated by possible dental infection. Methotrexate was withheld. The patient's stomatitis and facial swelling improved with administration of folate, leucovorin, and piperacillin/tazobactam. The patient's severe neutropenia gradually resolved following administration of granulocyte colony-stimulating factor. Infectious workup was negative throughout admission. This case report details factors that precipitate severe methotrexate toxicity at low doses.