Abstract and Introduction
Abstract
Rheumatoid arthritis (RA) is a common chronic systemic autoimmune disease characterized by joint inflammation and, in a proportion of patients, extra-articular manifestations (EAM). Lung disease, either as an EAM of the disease, related to the drug therapy for RA, or related to comorbid conditions, is the second commonest cause of mortality. All areas of the lung including the pleura, airways, parenchyma, and vasculature may be involved, with interstitial and pleural disease and infection being the most common problems. High-resolution computed tomography of the chest forms the basis of investigation and when combined with clinical information and measures of physiology, a multidisciplinary team can frequently establish the diagnosis without the need for an invasive biopsy procedure. The most frequent patterns of interstitial lung disease (ILD) are usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP), with some evidence for the prognosis being better than for the idiopathic equivalents. Risk factors depend on the type of disease but for ILD (mainly UIP and NSIP) include smoking, male gender, human leukocyte antigen haplotype, rheumatoid factor, and anticitrullinated protein antibodies (ACPAs). Citrullination of proteins in the lung, frequently thought to be incited by smoking, and the subsequent development of ACPA appear to play an important role in the development of lung and possibly joint disease. The biologic and nonbiological disease modifying antirheumatic drugs (DMARDs) have had a substantial impact on morbidity and mortality from RA, and although there multiple reports of drug-related lung toxicity and possible exacerbation of underlying ILD, overall these reactions are rare and should only preclude the use of DMARDs in a minority of patients. Common scenarios facing pulmonologists and rheumatologists are addressed using the current best evidence; these include screening the new patient; monitoring and choosing RA treatment in the presence of subclinical disease; treating deteriorating ILD; and establishing a diagnosis in a patient with an acute respiratory presentation.
Introduction
Rheumatoid arthritis (RA), a systemic autoimmune process characterized by a chronic symmetrical erosive synovitis, is frequently progressive and results in significant disability, especially if treatment is delayed. In addition to articular disease, multiple other organ systems may be involved, with extra-articular manifestations (EAM) in the heart and vascular system, lungs, skin, and eyes, contributing to the excess morbidity and mortality of patients with RA. The lung and pleura are frequently involved and contribute to 10 to 20% of overall mortality. The type of involvement is very varied and can precede the development of joint symptoms or diagnosis of RA. With improvements in imaging of the lung, we now have a better understanding of the amount, severity, and type of lung and pleural disease that occurs in patients with RA. Recent findings provide fascinating insights into the pathogenesis of lung disease and how it may relate to the development of RA. The role of antibodies to specific citrullinated proteins in the diagnosis of early RA, as markers of RA-associated interstitial lung disease (ILD) and in the pathogenesis of both lung and joint disease is intriguing and may offer new options for detection, monitoring, and therapy. Second, despite the availability of highly sensitive tools such as the high-resolution computed tomography (HRCT), the questions of which pleuropulmonary abnormalities are important, how screening and monitoring should be performed, and whether treatment directed at the RA should be modified because of the presence of subclinical or clinically apparent lung abnormalities is not clear. Outcome from the interplay between lung disease and the new biological disease modifying antirheumatic drugs (bDMARDs) used to treat joint disease is unclear and hence the risk versus benefit of bDMARDs in an individual patient with pulmonary EAM is uncertain. Systematic reviews, however, suggest concerns about pulmonary complications with the use of DMARDs in patients with RA may be overstated. This review will outline the breadth of lung involvement in patients with RA, but focus on the commonest forms in terms of pathogenesis, treatment, and uncertainties as outlined earlier. Interstitial, pleural, airway, and vascular disease and infection are either the most common or the most difficult to manage lung problems in patients with RA. Drug-induced lung disease is of importance and may complicate the management of patients with RA. On the basis of this review, we aim to provide a guide as to how to approach patients with possible lung involvement, whether as a rheumatologist managing someone presenting with predominately joint disease, or as a pulmonologist needing to determine the type, significance, and management of lung disease.