Rheumatoid Arthritis-Associated Interstitial Lung Disease

Georgiana Dinache^(1,2), Claudiu Popescu^(1,2,*), Corina Mogosan^(1,2), Luminita Enache^(1,2), Catalin Codreanu^(1,2)

1)“Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
2)“Dr. Ion Stoia” Clinical Centre for Rheumatic Diseases, Bucharest, Romania

Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting 1% of the population, characterized primarily by joint involvement but also by extra-musculoskeletal manifestations, among which interstitial lung disease (ILD) is the most clinically significant. RA-associated ILD (RA-ILD) may precede articular symptoms or remain subclinical for years, and is a leading cause of morbidity and mortality in RA, with median survival of 3-7 years after diagnosis. Risk factors include male sex, older age, smoking, high disease activity, autoantibody positivity, and genetic variants such as MUC5B rs35705950. Pathogenesis involves autoantibody formation, citrullination of lung proteins, and environmental triggers, with smoking acting as a major driver. Diagnosis relies on high-resolution computed tomography (HR-CT), pulmonary function tests (FVC, DLco), and multidisciplinary evaluation. Common HR-CT patterns include usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP), with UIP conferring a worse prognosis. Screening strategies and risk scores are under development to facilitate early detection in high-risk patients. Management of RA-ILD remains challenging. Immunomodulatory therapies such as methotrexate and mycophenolate may slow progression, while antifibrotic therapy with nintedanib has demonstrated efficacy, significantly reducing annual FVC decline. Ongoing clinical trials are evaluating novel agents, including pirfenidone, JAK inhibitors (e.g., tofacitinib in the PULMORA and RAILDTo studies), PDE4B inhibitors (FIBRONEER-ILD), and anti-IL6 biologics. Retrospective studies suggest that tocilizumab may stabilize or improve lung function in a subset of patients. Optimal management requires early identification, regular monitoring, and close collaboration between rheumatologists and pulmonologists. Future research should clarify prognostic markers, refine screening strategies, and expand therapeutic options to improve outcomes in RA-ILD.

Keywords: rheumatoid arthritis; interstitial lung disease; autoimmune disease; pulmonary involvement; connective tissue disease

Corresponding author(s): Claudiu Popescu, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania; email: claudiu.popescu@reumatologiedrstoia.ro