Sarcoidosis--scientific progress and clinical challenges

Abstract

Sarcoidosis is an uncommon systemic inflammatory disorder characterized by noncaseating granulomatous inflammation that most commonly affects the lungs, intrathoracic lymph nodes, eyes and skin. One-third or more of patients with sarcoidosis have chronic, unremitting inflammation with progressive organ impairment. Findings of family and genetic studies indicate a genetic susceptibility to sarcoidosis, with genes in the MHC region having a dominant role. Immunologic hallmarks of the disease include highly polarized expression of cytokines produced by type 1 T helper cells and tumor necrosis factor (TNF) at sites of inflammation. Increasing evidence obtained within the past decade suggests the etiology of sarcoidosis predominantly involves microbial triggers, with the most convincing data implicating mycobacterial or propionibacterial organisms. Innate immune mechanisms, possibly involving misfolding and aggregation of serum amyloid A, might have a critical role in the pathobiology of sarcoidosis. Despite these advances, there are no clinically useful biomarkers that can assist the clinician in diagnosis, prognosis or assessment of treatment effects. Corticosteroids remain the cornerstone of therapy when organ function is threatened or progressively impaired. The role of immunosuppressive drugs and anti-TNF agents in the treatment of sarcoidosis remains uncertain, and there are no FDA-approved therapies. Meaningful progress in developing clinically useful tools and new therapies will depend on further advances in understanding the pathogenesis of sarcoidosis and its disease-specific pathways.