ISSN: 0034-8376
eISSN: 2564-8896
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Abstract

Rheumatoid Arthritis-Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis: Shared Mechanistic and Phenotypic Traits Suggest Overlapping Disease Mechanisms

VOLUME 67 - NUMBER 5 / September - October (Brief Review)

Francisco Paulin, Internal Medicine Division, Hospital Juan A. Fernández, Buenos Aires, Argentina
Tracy J. Doyle, Pulmonary and Critical Care Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
Elaine A. Fletcher, Cornell University, Ithaca, NY, USA
Dana P. Ascherman, Division of Rheumatology, University of Miami Miller School of Medicine, Miami, FL, USA
Ivan O. Rosas, Pulmonary and Critical Care Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

The prevalence of clinically evident interstitial lung disease in patients with rheumatoid arthritis is approximately 10%. An additional 33% of undiagnosed patients have interstitial lung abnormalities that can be detected with high-resolution computed tomography. Rheumatoid arthritis-interstitial lung disease patients have three times the risk of death compared to those with rheumatoid arthritis occurring in the absence of interstitial lung disease, and the mortality related to interstitial lung disease is rising. Rheumatoid arthritis-interstitial lung disease is most commonly classified as the usual interstitial pneumonia pattern, overlapping mechanistically and phenotypically with idiopathic pulmonary fibrosis, but can occur in a non-usual interstitial pneumonia pattern, mainly nonspecific interstitial pneumonia. Based on this, we propose two possible pathways to explain the coexistence of rheumatoid arthritis and interstitial lung disease: (i) Rheumatoid arthritis-interstitial lung disease with a non-usual interstitial pneumonia pattern may come about when an immune response against citrullinated peptides taking place in another site (e.g. the joints) subsequently affects the lungs; (ii) Rheumatoid arthritis-interstitial lung disease with a usual interstitial pneumonia pattern may represent a disease process in which idiopathic pulmonary fibrosis-like pathology triggers an immune response against citrullinated proteins that promotes articular disease indicative of rheumatoid arthritis. More studies focused on elucidating the basic mechanisms leading to different sub-phenotypes of rheumatoid arthritis-interstitial lung disease and the overlap with idiopathic pulmonary fibrosis are necessary to improve our understanding of the disease process and to define new therapeutic targets.

Keywords: Interstitial lung disease. Rheumatoid arthritis. Idiopathic pulmonary fibrosis. Citrullination.

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