+1 Recommend
1 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Refractory Sarcoidosis: A Review

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Sarcoidosis is a multi-system disease of unknown etiology characterized by granuloma formation in various organs (especially lung and mediastinohilar lymph nodes). In more than half of patients, the disease resolves spontaneously. When indicated, it usually responds to corticosteroids, the first-line treatment, but some patients may not respond or tolerate them. An absence of treatment response is rare and urges for verifying the absence of a diagnosis error, the good adherence of the treatment, the presence of active lesions susceptible to respond since fibrotic lesions are irreversible. That is when second-line treatments, immunosuppressants (methotrexate, leflunomide, azathioprine, mycophenolate mofetil, hydroxychloroquine), should be considered. Methotrexate is the only first-line immunosuppressant validated by a randomized controlled trial. Refractory sarcoidosis is not yet a well-defined condition, but it remains a real challenge for the physicians. Herein, we considered refractory sarcoidosis as a disease in which second-line treatments are not sufficient to achieve satisfying disease control or satisfying corticosteroids tapering. Tumor necrosis alpha inhibitors, third-line treatments, have been validated through randomized controlled trials. There are currently no guidelines or recommendations regarding refractory sarcoidosis. Moreover, criteria defining non-response to treatment need to be clearly specified. The delay to achieve response to organ involvement and drugs also should be defined. In the past ten years, the efficacy of several immunosuppressants beforehand used in other autoimmune or inflammatory diseases was reported in refractory cases series. Among them, anti-CD20 antibodies (rituximab), repository corticotrophin injection, and anti-JAK therapy anti-interleukin-6 receptor monoclonal antibody (tocilizumab) were the main reported. Unfortunately, no clinical trial is available to validate their use in the case of sarcoidosis. Currently, other immunosuppressants such as JAK inhibitors are on trial to assess their efficacy in sarcoidosis. In this review, we propose to summarize the state of the art regarding the use of immunosuppressants and their management in the case of refractory or multidrug-resistant sarcoidosis.

          Related collections

          Most cited references 161

          • Record: found
          • Abstract: found
          • Article: not found


          Sarcoidosis is a systemic disease of unknown cause that is characterised by the formation of immune granulomas in various organs, mainly the lungs and the lymphatic system. Studies show that sarcoidosis might be the result of an exaggerated granulomatous reaction after exposure to unidentified antigens in individuals who are genetically susceptible. Several new insights have been made, particularly with regards to the diagnosis and care of some important manifestations of sarcoidosis. The indications for endobronchial ultrasound in diagnosis and for PET in the assessment of inflammatory activity are now better specified. Recognition of unexplained persistent disabling symptoms, fatigue, small-fibre neurological impairment, cognitive failure, and changes to health state and quality of life, has improved. Mortality in patients with sarcoidosis is higher than that of the general population, mainly due to pulmonary fibrosis. Predicted advances for the future are finding the cause of sarcoidosis, and the elucidation of relevant biomarkers, reliable endpoints, and new efficient treatments, particularly in patients with refractory sarcoidosis, lung fibrosis, and those with persistent disabling symptoms. Copyright © 2014 Elsevier Ltd. All rights reserved.
            • Record: found
            • Abstract: found
            • Article: not found

            Nintedanib in Progressive Fibrosing Interstitial Lung Diseases

            Preclinical data have suggested that nintedanib, an intracellular inhibitor of tyrosine kinases, inhibits processes involved in the progression of lung fibrosis. Although the efficacy of nintedanib has been shown in idiopathic pulmonary fibrosis, its efficacy across a broad range of fibrosing lung diseases is unknown.
              • Record: found
              • Abstract: found
              • Article: not found

              Nintedanib for Systemic Sclerosis–Associated Interstitial Lung Disease

              Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis and a leading cause of systemic sclerosis-related death. Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and antiinflammatory effects in preclinical models of systemic sclerosis and ILD.

                Author and article information

                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                17 April 2020
                : 16
                : 323-345
                [1 ]Department of Internal Medicine, Lyon University Hospital , Lyon, France
                [2 ]Department of Pneumology, Assistance Publique - Hôpitaux de Paris, Hôpital Avicenne et Université Paris 13, Sorbonne Paris Cité , Bobigny, France
                [3 ]Hospices Civils de Lyon, Pôle IMER, Lyon, F-69003, France, University Claude Bernard Lyon 1, HESPER EA 7425 , Lyon F-69008, France
                Author notes
                Correspondence: Pascal Sève Service de Médecine Interne, Groupement Hospitalier Nord , 103 Grande rue de la Croix-Rousse, LyonF-69004, FranceTel +33 426 732 636Fax +33 426 732 637 Email pascal.seve@chu-lyon.fr
                © 2020 El Jammal et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Tables: 5, References: 172, Pages: 23


                refractory sarcoidosis, jak inhibitors, anti-tnf


                Comment on this article