Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a severe and frequent extra-articular manifestation of rheumatoid arthritis (RA), significantly impacting morbidity and mortality. Despite growing recognition, evidence-based recommendations for its screening and management remain limited.

This review aims to provide a comprehensive overview of current knowledge on RA-ILD, including its epidemiology, risk factors, pathophysiology, diagnostic challenges, and therapeutic strategies, with a focus on the controversial role of methotrexate (MTX).

We synthesized data from observational studies, randomized controlled trials (RCTs), and international guidelines to summarize the key clinical aspects of RA-ILD, including its natural history, imaging features, management approaches, and therapeutic options.

RA-ILD presents heterogeneous clinical and radiological profiles, with usual interstitial pneumonia (UIP) as the predominant high-resolution computed tomography (HRCT) pattern. MTX, historically suspected of causing or worsening ILD, does not appear to increase the risk of RA-ILD, and may even be associated with lower incidence, though a protective effect remains unproven. Several immunosuppressive agents (e.g., mycophenolate mofetil, rituximab, abatacept) and antifibrotic therapies (e.g., nintedanib, pirfenidone) show promise, although evidence remains limited. A multidisciplinary approach is essential for diagnosis and treatment decisions.

RA-ILD is a complex, multifaceted condition requiring individualized care. Optimal control of RA remains the cornerstone of RA-ILD management and recent data challenge the historical contraindication of MTX. Robust prospective studies and collaboration between rheumatologists and pulmonologists are crucial for improving patient outcomes.