Methotrexate and the lung: a narrative review

Methotrexate remains a core drug for most inflammatory rheumatic diseases, particularly rheumatoid arthritis. Although usually well tolerated, methotrexate can also be associated with diverse direct and indirect adverse drug reactions, each with distinct latencies and clinical phenotype. Pulmonary adverse events embrace a broad range of inflammatory, infectious and rarely neoplastic disorders, affecting lung parenchyma, upper and lower airways, or pleura. As the clinical and imaging features of suspected drug reactions can overlap substantially with respiratory complications of rheumatic diseases or opportunistic infection, correct attribution is important but frequently challenging. We review here the historical and most recent evidence describing the putative spectrum of methotrexate associated lung disease, potential underlying mechanisms and implications for management. Priorities for future research are suggested.