Pulmonary Disease Complicating Intermittent Therapy With Methotrexate

A severe but self-limited respiratory illness characterized by fever, cough, dyspnea, cyanosis, and bilateral pulmonary infiltrates developed in seven consecutive patients with acute lymphoblastic leukemia who received intermittent therapy with methotrexate, while in clinical and hematologic remission of the leukemia. No infectious agent could be identified, and a moderate blood eosinophil count accompanied the illness in five of the seven patients. Lung biopsy performed on one patient revealed an allergic type granulomatous reaction. It is suggested but not proved that the pulmonary disease represented an adverse reaction to methotrexate therapy.