Sarcoidosis

Abstract

Sarcoidosis is an inflammatory disorder of unknown cause that is characterized by granuloma formation in affected organs, most often in the lungs. Patients frequently suffer from cough, shortness of breath, chest pain and pronounced fatigue and are at risk of developing lung fibrosis or irreversible damage to other organs. The disease develops in genetically predisposed individuals with exposure to an as-yet unknown antigen. Genetic factors affect not only the risk of developing sarcoidosis but also the disease course, which is highly variable and difficult to predict. The typical T cell accumulation, local T cell immune response and granuloma formation in the lungs indicate that the inflammatory response in sarcoidosis is induced by specific antigens, possibly including self-antigens, which is consistent with an autoimmune involvement. Diagnosis can be challenging for clinicians because of the potential for almost any organ to be affected. As the aetiology of sarcoidosis is unknown, no specific treatment and no pathognomic markers exist. Thus, improved biomarkers to determine disease activity and to identify patients at risk of developing fibrosis are needed. Corticosteroids still constitute the first-line treatment, but new treatment strategies, including those targeting quality-of-life issues, are being evaluated and should yield appropriate, personalized and more effective treatments.

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Fig. 1: Incidence of sarcoidosis.
Fig. 2: Survival in sarcoidosis.
Fig. 3: Immunological features of granuloma formation in sarcoidosis.
Fig. 4: Histology of lymph node and granuloma in sarcoidosis.
Fig. 5: Granuloma resolution or progression in sarcoidosis.
Fig. 6: Whole body 18F-FDG-PET scan of a patient with sarcoidosis.
Fig. 7: Extrapulmonary manifestations of sarcoidosis.
Fig. 8: Proposed algorithm for diagnosing sarcoidosis.
Fig. 9: High-resolution CT imaging of pulmonary sarcoidosis.
Fig. 10: Proposed algorithm for choice of therapy or disease monitoring in sarcoidosis.

Change history

  • 16 July 2019

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Acknowledgements

The authors thank A. Eklund and Y. Kaiser for their help with this article as well as research nurses G. de Forest, M. Dahl and H. Blomqvist and biomedical analyst B. Dahlberg (all at Respiratory Medicine Unit, Karolinska University Hospital, Solna, Sweden) for skilful assistance in bronchoscopy and lavage and in sample preparation and processing. The authors thank C. A. Seldenrijk (Department of Pathology), R. G. M. Keijsers (Department of Nuclear Medicine) and H. W. van Es (Department of Radiology), all at St Antonius Hospital, Nieuwegein, Netherlands, for providing the histopathology, PET and CT images, respectively. J.G. is supported by the Swedish Heart Lung Foundation (HLF 20160354 and 20160300), the Swedish Research Council (2016–01209) and the US NIH (R01HL136137) through the regional agreement on medical training and clinical research (ALF) between the Stockholm County Council and the Karolinska Institutet, The King Gustaf V and Queen Victoria’s Freemasons’ Foundation and the Karolinska Institutet.

Author information

Introduction (J.G.); Epidemiology (E.V.A.); Mechanisms/pathophysiology (J.G. and D.R.M.); Diagnosis, screening and prevention (J.C.G.); Management (J.M.-Q.); Quality of life (L.A.S.); Outlook (J.G., J.C.G., E.V.A., L.A.S., D.R.M. and J.M.-Q.); Overview of the Primer (J.G.)

Correspondence to Johan Grunewald.

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Competing interests

D.R.M. is the Chairman and Chief Technology Officer of Sarcoidosis Diagnostic Testing, LLC. J.M.-Q. is supported by the German Research Foundation (Mu692/12) and Bristol-Myers-Squibb for investigator-initiated trials in sarcoidosis. All other authors declare no competing interests.

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