Subclinical Interstitial Lung Disease in Rheumatoid Arthritis: Implications for Early Detection and Management

Abstract

Topic importance: Subclinical interstitial lung disease (ILD) is common in patients with rheumatoid arthritis (RA). Some patients with subclinical RA-ILD will progress to clinical ILD, which is associated with increased morbidity and mortality. Recently, the American College of Rheumatology (ACR) and American College of Chest Physicians (ACCP) have published guidelines addressing screening for ILD in patients with RA, though much is unknown about risk of progression or optimal treatment strategies after recognition of subclinical RA-ILD.

Findings: Prospective studies have reported subclinical ILD in around 25% of patients with RA. Demographic risk factors associated with subclinical disease include older age, male sex, and smoking. RA specific risk factors for subclinical ILD include higher C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) at RA diagnosis, severity of RA disease activity as measured by Disease Activity Score 28 (DAS28), as well as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody positivity. Biomarkers associated with subclinical disease include the MUC5B promoter variant and serum levels of matrix metalloproteinase 7 (MMP-7), pulmonary and activation-regulated chemokine (PARC), and surfactant protein D (SPD). The optimal treatment approach for subclinical disease is currently unknown.

Summary: Future research should focus on defining high-risk populations that will benefit from screening. Further, understanding disease progression in subclinical RA-ILD and the potential for early intervention to impact the development of clinically significant disease will be critical.