Recent Advances in Basic and Clinical Aspects of Rheumatoid Arthritis-associated Interstitial Lung Diseases

Abstract

Rheumatoid arthritis (RA) is a common autoimmune disease that mainly affects the joints and systemic organs, such as the skin, eyes, heart, gastrointestinal tract, and lungs. In particular, among various pulmonary involvements, interstitial lung disease (ILD) is closely related to the selection of anti-rheumatic drugs and the long-term prognosis of patients with RA. Although the exact pathogenesis of RA-ILD is not well defined, several mechanistic pathways, similar to those of idiopathic pulmonary fibrosis, have been elucidated recently. Conversely, RA-related autoantibodies, including anti-cyclic citrullinated peptide antibody, are detectable in circulation and in the lungs, even in the absence of articular symptoms. RA-ILD can also predate years before the occurrence of joint symptoms. This evidence supports the fact that local dysregulated mucosal immunity in the lung causes systemic autoimmunity, resulting in clinically evident polyarthritis of RA. Because the early diagnosis of RA-ILD is important, imaging tests, such as computed tomography and pulmonary function tests, are being used for early diagnosis, but there is no dear guideline for the early diagnosis of RA-ILD and selection of optimal disease-modifying anti-rheumatic drugs for the treatment of patients with RA with ILD. In addition, the efficacy of nintedanib, a new anti-fibrotic agent, for RA-ILD treatment, has been investigated recently. This review collectively discusses the basic and clinical aspects, such as pathogenesis, animal models, diagnosis, and treatment, of RA-ILD.