Screening for rheumatoid arthritis-associated interstitial lung disease: Current evidence and next steps needed for routine clinical use

Interstitial lung disease (ILD), characterized by pulmonary fibrosis and/or inflammation, is a common and severe extra-articular manifestation of rheumatoid arthritis (RA). RA-ILD is associated with reduced quality of life and increased mortality. Among people with RA, up to15% develop clinically significant ILD, and even more have subclinical disease (radiologic abnormalities without symptoms). The most common RA-ILD patterns on chest high-resolution computed tomography (HRCT) imaging are usual interstitial pneumonia (UIP, the prototypic fibrotic subtype) and non-specific interstitial pneumonia (the subtype characterized by inflammation). In this narrative review, we detail the current state of evidence for RA-ILD screening, and the next steps needed to justify screening in some subgroups. Some current or former smokers with RA may currently qualify for lung cancer screening with low-dose CT imaging, which may also detect ILD. The 2023 American College of Rheumatology/American College of Chest Physicians guideline for screening and monitoring of ILD conditionally recommended screening people with RA with an ILD risk factor (male sex, older age, smoking, RA-related autoantibody elevation, obesity, and high RA disease activity). Several genetic and blood biomarkers are associated with RA-ILD. The MUC5B promoter variant is the strongest genetic risk factor for RA-ILD, specifically the UIP subtype. Proposed screening strategies show promise for accurately detecting RA-ILD. However, there has been less research on other consequences of screening for RA-ILD, including cost, anxiety, radiation exposure, incidental findings, and downstream clinical follow-up. Trials are needed to identify an intervention that alters the natural history for those found to have subclinical RA-ILD on screening.