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Sarcoidosis—scientific progress and clinical challenges

Nature Reviews Rheumatology volume 7, pages 457–467 (2011)Cite this article

Subjects

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.

Key Points

  • Sarcoidosis is a multisystem disease characterized by noncaseating granulomatous inflammation with striking heterogeneity in its clinical manifestations

  • Results of immunologic and clinical association studies indicate that a highly polarized type 1 T helper cell immune response is a hallmark of sarcoidosis

  • Sarcoidosis is thought to result from both genetic susceptibility and specific environmental triggers

  • No useful diagnostic, prognostic or therapeutic biomarkers are currently available to assist in the clinical management of patients with sarcoidosis

  • Further clinical trials are needed to establish the role of immunosuppressive drugs, anti-tumor necrosis factor therapies and other biologic immunomodulators in the treatment of sarcoidosis

  • Improved understanding of the pathogenic mechanisms in sarcoidosis might provide new strategies to treat and potentially cure this disease

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Figure 1: Serum amyloid A misfolding hypothesis of the pathobiology of sarcoidosis.

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Acknowledgements

This work was supported in part by the Hospital for the Consumptives of Maryland (Eudowood) and the Life and Breath Foundation.

C. P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape, LLC-accredited continuing medical education activity associated with this article.

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  1. Division of Pulmonary and Critical Care Medicine, Department of Medicine, The Johns Hopkins University, 5501 Hopkins Bayview Circle, Room 4B63, Baltimore, 21224, MD, USA

    Edward S. Chen & David R. Moller

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  1. Edward S. Chen
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  2. David R. Moller
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E. S. Chen and D. R. Moller contributed equally to all aspects of preparation of this manuscript.

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Correspondence to David R. Moller.

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Competing interests

D. R. Moller declares that an appeal against a rejection for a patent for using mKatG in diagnosis of sarcoidosis is ongoing. E. S. Chen declares no competing interests.

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Chen, E., Moller, D. Sarcoidosis—scientific progress and clinical challenges. Nat Rev Rheumatol 7, 457–467 (2011). https://doi.org/10.1038/nrrheum.2011.93

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