Diagnostic methods of rheumatoid arthritis-associated interstitial lung disease: a systematic review

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a potentially life-threatening extra-articular complication affecting 10-60% of patients with rheumatoid arthritis. Despite its clinical significance, the optimal diagnostic strategy remains uncertain. This systematic review assessed the diagnostic value of currently available methods for detecting RA-ILD. The review followed PRISMA guidelines. Databases were searched for studies evaluating imaging modalities (chest X-ray, high-resolution computed tomography [HRCT], lung ultrasound), pulmonary function tests (forced vital capacity [FVC], total lung capacity [TLC], diffusing capacity for carbon monoxide [DLCO]), clinical features, and serum biomarkers. The risk of bias was assessed using QUADAS-2 tool.Thirty-six studies were included. Risk of bias was low in 20, high in 1, and unclear in 15 studies. Applicability concerns were low in 18, unclear in 17 and high in 1 study. Lung ultrasound was most frequently evaluated, showing sensitivity of 70-100% and specificity of 56-97%. Only one HRCT study was identified; it demonstrated high specificity but moderate sensitivity for detecting a UIP pattern. No studies assessing lung volumes (FVC, TLC) were found. DLCO showed sensitivity for RA-ILD detection but limited specificity and uncertain optimal cut-off values. Among biomarkers, KL-6 was most studied (sensitivity 61-100%, specificity 78-91%), while other biomarkers demonstrated inconsistent results and lacked validation. Lung ultrasound appears diagnostically useful in RA-ILD. Evidence supporting pulmonary function tests is limited. Although KL-6 shows promise, biomarkers cannot currently serve as standalone diagnostic tools. Further well-designed prospective studies are required.  https://www.crd.york.ac.uk/PROSPERO/view/CRD420251035610 .