Methotrexate and lung disease in rheumatoid arthritis

Rheumatoid arthritis (RA) is a common chronic inflammatory disease affecting many tissues and resulting in substantial morbidity and increased mortality. Arthritis is the most notable clinical feature, but extra-articular features can have devastating consequences. Pulmonary manifestations are common in RA, with high rates of disease related lung disease and a propensity to pulmonary infections. Respiratory illness remains a leading cause of death among RA populations. Modern medicine greatly reduces the illness burden among patients with RA, particularly through the use of disease-modifying medications. Methotrexate is recommended as the first-line treatment of RA as it effectively reduces disease activity, morbidity and mortality. However, it has long been implicated as a causative agent in lung disease. The evidence for a cause and effect relationship in modern populations is contentious, but critically important. Increasing recognition of the importance and prevalence of interstitial lung disease in RA, and recent studies on the incidence of lung disease among RA and non-RA populations have cast doubt on the role of methotrexate as a causative agent. A correct understanding of the complex pulmonary disease processes in RA is crucial if we are to improve outcomes in this patient group. In this article we will discuss the epidemiology and characteristics of lung disease in rheumatoid arthritis and its possible relationship to methotrexate use.