Methotrexate and The Lung in Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is a common systemic rheumatic disease. While the most visible manifestation of RA is articular involvement, it is a true systemic disease with the potential to affect multiple organs. Methotrexate (MTX) is the most commonly used medication to treat RA. MTX pneumonitis (MTX-pneu) is a rare disease entity reported in MTX users. It usually develops acutely or subacutely in the first year of treatment. MTX-pneu presents with cough, dyspnoea, and often fever. Pre-existing lung disease is a major risk factor and the clinical diagnosis is based on MTX exposure, symptoms, and laboratory and imaging findings. Treatment involves MTX cessation and high-dose glucocorticoids. Interstitial lung disease (ILD) is a common manifestation of RA with clinical RA-ILD affecting up to 10% of patients. RA-ILD tends to be a more indolent process than MTX-pneu and frequently develops over years but can also be acute. Similar to MTX-pneu, RA-ILD presents with cough, dyspnoea, and often fever. Risk factors include age, male sex, disease activity, seropositivity, and smoking. Treatment is aimed at optimal control of RA disease and within this strategy there may be particular roles for rituximab, tocilizumab, and abatacept. Antifibrotics may also have a role. Given the distinct pathologies, the differentiation of these two entities is crucial. The treatment approach differs significantly and what is beneficial for one may be harmful for the other. In this paper, the authors discuss and contrast contemporary knowledge of MTX-pneu and RA-ILD.