The therapeutic dilemma triangle in rheumatoid arthritis-related respiratory disease

Rheumatoid arthritis (RA) is increasingly well controlled with conventional disease-modifying antirheumatic drugs (DMARDs) including methotrexate, as well as the widespread use of biologic agents and Janus kinase (JAK) inhibitors, which have improved joint outcomes and the overall prognosis. Nevertheless, respiratory complications remain a major determinant of clinical outcomes and often fundamentally shape therapeutic strategies in routine practice. Respiratory manifestations of RA are diverse and include interstitial lung disease (ILD), airway disease (e.g., bronchiectasis and bronchiolitis), pleural disease, pulmonary vascular involvement, respiratory infections, and drug-induced lung injury, with multiple entities frequently coexisting in the same patient. Importantly, airway disease and ILD are not only sources of chronic respiratory symptoms but also provide a substrate for recurrent pneumonia and chronic lower respiratory tract infection, including Pseudomonas aeruginosa and non-tuberculous mycobacteria. These infectious events may necessitate interruption or modification of antirheumatic therapy, thereby precipitating a vicious cycle of worsening arthritis and respiratory disease. In this mini-review, we focus on RA-associated respiratory disease-particularly ILD and airway disease-and summarize how major respiratory infections (P. aeruginosa, Mycobacterium tuberculosis, non-tuberculous mycobacteria, Aspergillus, Pneumocystis jirovecii, and cytomegalovirus) interact with antirheumatic drug selection in ways that directly influence clinical decision-making. We further conceptualize these bidirectional interactions as the "Therapeutic Dilemma Triangle," defined as the interplay among underlying RA-related respiratory disease, respiratory infections, and antirheumatic therapies, and propose a practical framework aimed at promoting the early diagnosis and timely treatment of infections and standardizing key pre-escalation respiratory assessment and interruption/restart decisions to preserve therapeutic options and improve outcomes.