METHOTREXATE-INDUCED PNEUMONITIS

Abstract

TOPIC: Lung Pathology TYPE: Fellow Case Reports 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. DISCUSSION: There is a set of criteria to establish the diagnosis. Major criteria includes: 1. hypersensitivity pneumonitis by histopathology without pathogenic organisms 2. imaging with diffuse ground-glass or consolidative opacities 3. negative blood cultures (if febrile) and initial sputum cultures (if produced). Minor criteria includes: 1. dyspnea for <8 weeks 2. nonproductive cough 3. SpO2< 90% on room air at initial evaluation 4. DLCO < 70% of predicted for age and 5. WBC < 15k. Methotrexate pneumonitis is definite if major criteria 1 or 2 and major criterion 3 are present with three of the five minor criteria and probable if major criteria 2 and 3 plus two of the five minor criteria are present (1). Our patient met all major criteria and four minor criteria. CONCLUSIONS: Although rare with a prevalence of 0.3-11.6% (1,3), methotrexate pneumonitis has a mortality rate of 13-17.6% (2,4). Patients should be advised about the possibility of lung toxicity. Some data suggests patients should be screened for lung disease prior to medication initiation (5) and clinicians should be cautious using the drug in patients with underlying lung disease (6). REFERENCE #1: Salehi, Mashal et al. "Methotrexate-induced Hypersensitivity Pneumonitis appearing after 30 years of use: a case report." Journal of medical case reports vol. 11,1 174. 28 Jun. 2017, doi:10.1186/s13256-017-1333-0 DISCLOSURES: No relevant relationships by Bianca Dominguez, source=Web Response No relevant relationships by Gurjot Garcha, source=Web Response No relevant relationships by Wael Nasser, source=Web Response No relevant relationships by Olatunji Otegbeye, source=Web Response