Rheumatoid arthritis-associated interstitial lung disease: A review

Melanie David; Philippe Dieude; Pierre-Antoine Juge; Marie Pierre Debray; Pierre LE Guen; Bruno Crestani; Raphael Borie

doi:10.1016/j.resmer.2026.101260

Rheumatoid arthritis-associated interstitial lung disease: A review

Respir Med Res. 2026 Mar 6:89:101260. doi: 10.1016/j.resmer.2026.101260. Online ahead of print.

Authors

Melanie David¹, Philippe Dieude², Pierre-Antoine Juge², Marie Pierre Debray³, Pierre LE Guen⁴, Bruno Crestani⁴, Raphael Borie⁴

Affiliations

¹ Department of Pulmonology, Foch Hospital, Suresnes, France. Electronic address: mlaniedavid94@gmail.com.
² Rhumatology Department, Hospital Bichat, APHP, Paris, France and University of Paris Cité, Inserm, PHERE, F-75018 Paris, France.
³ Radiology Department, Hospital Bichat, APHP, Paris, France.
⁴ Department of Pulmonology, Allergy and Transplantation, Constituent Center of the Reference Center for Rare Pulmonary Diseases, FHU INFIRE, Bichat Hospital, AP-HP and Paris Cité University, Inserm UMR 1149, CRI, Paris, France.

PMID: 41903441
DOI: 10.1016/j.resmer.2026.101260

Abstract

Background: 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.

Objective: 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).

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Antifibrotic agents; Immunosuppressive therapy; Interstitial lung diseases; Methotrexate; Rheumatoid arthritis; Usual interstitial pneumonia.