Interstitial Lung Disease (ILD) is a well-known complication of rheumatoid arthritis
(RA) which often results in significant morbidity and mortality. It is often diagnosed late in the disease
process via descriptive criteria. Multiple subtypes of RA-ILD exist as defined by chest CT and
histopathology. In the absence of formal natural history studies and definitive diagnostics, a conventional
dogma has emerged that there are two major subtypes of RA-ILD (nonspecific interstitial
pneumonia (NSIP) and Usual Interstitial Pneumonia (UIP)). These subtypes are based on clinical
experience and correlation studies. However, recent animal model data are incongruous with established
paradigms of RA-ILD and beg reassessment of the clinical evidence in order to better understand
etiology, pathogenesis, prognosis, and response to therapy. To this end, here we: 1) review
the literature on epidemiology, radiology, histopathology and clinical outcomes of the various RAILD
subtypes, existing animal models, and current theories on RA-ILD pathogenesis; 2) highlight
the major gaps in our knowledge; and 3) propose future research to test an emerging theory of RAILD
that posits initial rheumatic lung inflammation in the form of NSIP-like pathology transforms
mesenchymal cells to derive chimeric disease, and subsequently develops into frank UIP-like fibrosis
in some RA patients. Elucidation of the pathogenesis of RA-ILD is critical for the development
of effective interventions for RA-ILD.
Keywords: Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD), Nonspecific Interstitial Pneumonia (NSIP),
Usual Interstitial Pneumonia (UIP), Computed Tomography (CT), Histology, inflammation, fibrosis, animal models.
Conway R, et al. Methotrexate and interstitial lung disease in rheumatoid arthritis-a systematic literature review and meta-analysis. Ir J Med Sci 2013; 182: S94-4.
Rights & PermissionsPrintExport