INTRODUCTION:Methotrexate is an analogue of folic acid that inhibits cellular proliferation by inducing an intracellular deficiency of folate coenzymes. Lung toxicity, while rare, often occurs after weeks to months of low dose oral methotrexate therapy.CASE PRESENTATION: A 46 year old male with a history of T cell lymphoma status post chemotherapy on POMP maintenance therapy and pleurX catheter for malignant pleural effusion presented to the ED with fever for 4 days. Associated symptoms were dry cough, chills, and fatigue. He denied drug allergies.BP 153/84, HR 135, SpO2 98% on room air, and temperature 101.5F. WBC was 3.2 and COVID PCR was negative. Broad spectrum antibiotics were initiated. CT thorax showed upper lobe predominant ground-glass opacities suggestive of a multifocal pneumonia or drug reaction. He became hypoxic requiring 3L of oxygen and underwent bronchoscopy. Transbronchial biopsy revealed lung parenchyma with isolated giant cells and loosely formed granulomas consistent with hypersensitivity pneumonia. Left upper lobe broncho-alveolar lavage had lymphocytic predominance and elevated CD4:CD8 ratio (4.7), all supporting the diagnosis of methotrexate pneumonitis. Empiric treatment for PJP and Prednisone were started. Viral, bacterial, fungal studies and PJP stain were negative. Antibiotics were stopped and steroids were continued for 2 weeks. His symptoms improved and fevers subsided. As an outpatient, repeat CT thorax and PFTs were ordered and he continues to improve clinically.

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