Pulmonary fibrosis associated with rheumatoid arthritis: from pathophysiology to treatment strategies

ABSTRACT

Introduction

Rheumatoid arthritis (RA) is the most common inflammatory autoimmune disease, characterized by symmetric destructive arthritis and synovitis. Lung involvement is frequent, including in the form of interstitial lung disease (ILD). RA-ILD often presents with a radiologic and pathologic pattern of usual interstitial pneumonia, similar to idiopathic pulmonary fibrosis, highlighting the similarities between the two diseases, but other patterns and pathological associations are described.

Areas covered

This article reviews the pathogenesis of pulmonary fibrosis in the setting of rheumatoid arthritis as well as the current and future therapeutic options.

Expert opinion

Pulmonary fibrosis in the setting of RA-ILD is an example of genotype–environment interaction and involves multiple mechanisms including autoimmunity, inflammation, and fibrogenesis. Although ILD conveys most of the exceeding mortality in RA patients, there are no official guidelines for the management of RA-ILD. Attention should be paid to potential lung toxicity of RA treatment even though some of them might help stabilize the ILD. Current standard of care is often composed of glucocorticoids that may be associated with immunosuppressive therapy. Following the approval of antifibrotic therapy for ILDs with a progressive fibrosing phenotype, current works are evaluating the benefit of such treatment in RA-ILD.

KEYWORDS:

• Antifibrotics
• fibrogenesis
• pulmonary fibrosis
• rheumatoid arthritis
• rheumatoid arthritis-associated interstitial lung disease
• RA-ILD pathogenesis
• RA-ILD treatment
• usual interstitial pneumonia

Article highlights

• Rheumatoid-arthritis associated lung disease (RA-ILD) is often associated with pulmonary fibrosis and shares pathological, radiological, pathophysiological, and behavioral similarities with idiopathic pulmonary fibrosis (IPF).

• Pathogenesis includes genetics involved in tissue repair, epithelial dysfunction, antigen presentation, and telomere maintenance. The interaction between genotype and environment, and especially smoking, triggers auto-immunity and inflammation in the lung.

• Lung inflammation and autoimmunity, and especially citrullination, play a major role in the onset of both rheumatoid arthritis and RA-ILD.

• Drugs used to treat rheumatoid arthritis may be responsible for lung toxicity but some of them, including rituximab, abatacept, and possibly methotrexate, could also help stabilize the lung disease.

• Optimal management of RA-ILD is unclear and often consists of glucocorticoid therapy with or without immunosuppression. Antifibrotics are indicated for the subset of patients with progressive fibrosing phenotype. Upfront antifibrotic therapy for patients with a UIP pattern needs further evaluation.

Declaration of interest

V Cottin reports grants, personal fees and non-financial support from Boehringer Ingelheim and Roche, personal fees from Celgene/BMS, Galapagos, Galecto, Shionogi, Fibrogen, RedX, PureTech, Sanofi, and CSL Behring, outside the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.