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      Risk of first and recurrent serious infection in sarcoidosis: a Swedish register-based cohort study

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          Abstract

          Serious infections impair quality of life and increase costs. Our aim was to determine if sarcoidosis is associated with a higher rate of serious infection and whether this varies by age, sex, time since diagnosis or treatment status around diagnosis.

          We compared individuals with sarcoidosis (at least two International Classification of Diseases codes in the Swedish National Patient Register 2003–2013; n=8737) and general population comparators matched 10:1 on age, sex and residential location (n=86 376). Patients diagnosed in 2006–2013 who were dispensed at least one immunosuppressant ±3 months from diagnosis (Swedish Prescribed Drug Register) were identified. Cases and comparators were followed in the National Patient Register for hospitalisations for infection. Using Cox and flexible parametric models, we estimated adjusted hazard ratios (aHR) and 95% confidence intervals for first and recurrent serious infections (new serious infection >30 days after previous).

          We identified 895 first serious infections in sarcoidosis patients and 3881 in comparators. The rate of serious infection was increased 1.8-fold in sarcoidosis compared to the general population (aHR 1.81, 95% CI 1.65–1.98). The aHR was higher in females than males and during the first 2 years of follow-up. Sarcoidosis cases treated with immunosuppressants around diagnosis had a three-fold increased risk, whereas nontreated patients had a 50% increased risk. The rate of serious infection recurrence was 2.8-fold higher in cases than in comparators.

          Serious infections are more common in sarcoidosis than in the general population, particularly during the first few years after diagnosis. Patients who need immunosuppressant treatment around diagnosis are twice as likely to develop a serious infection than those who do not.

          Abstract

          Sarcoidosis is associated with an increased risk of serious infections, especially during the first 2 years after diagnosis. Patients in need of immunosuppressants around diagnosis are twice as likely to develop serious infections than those who do not. https://bit.ly/2VFOvSo

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          Most cited references16

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          Sarcoidosis

          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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            The immune paradox of sarcoidosis and regulatory T cells

            Sarcoidosis is characterized by extensive local inflammation (granuloma, cytokine secretion) associated with anergy (poor response to antigens in vitro and in vivo). We postulated that this paradoxical situation would correspond to a disequilibrium between effector and regulatory T lymphocytes (T reg cells). We show that CD4+CD25brightFoxP3+ cells accumulate at the periphery of sarcoid granulomas, in bronchoalveolar lavage fluid, and in peripheral blood of patients with active disease. These cells exhibited powerful antiproliferative activity, yet did not completely inhibit TNF-α production. Sarcoidosis is therefore associated with a global T reg cell subset amplification whose activity would be insufficient to control local inflammation. At the same time, peripheral T reg cells exert powerful antiproliferative activity that may account for the state of anergy. Altogether, these findings advance our conceptual understanding of immune regulation in a way that resolves the immune paradox of sarcoidosis and permit us to envisage a profound clinical impact of T reg cell manipulation on immunity.
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              Serious infections among adult Medicaid beneficiaries with systemic lupus erythematosus and lupus nephritis.

              To examine the epidemiology of serious infections, a significant cause of morbidity and mortality in systemic lupus erythematosus (SLE), in a nationwide cohort of SLE and lupus nephritis (LN) patients.
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                Author and article information

                Journal
                Eur Respir J
                Eur. Respir. J
                ERJ
                erj
                The European Respiratory Journal
                European Respiratory Society
                0903-1936
                1399-3003
                September 2020
                03 September 2020
                : 56
                : 3
                : 2000767
                Affiliations
                [1 ]Clinical Epidemiology Division, Dept of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
                [2 ]Respiratory Medicine Division, Dept of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
                [3 ]Respiratory Medicine, Theme Inflammation and Infection, Karolinska University Hospital, Stockholm, Sweden
                [4 ]Rheumatology, Theme Inflammation and Infection, Karolinska University Hospital, Stockholm, Sweden
                Author notes
                Marios Rossides, Karolinska Institutet, Dept of Medicine Solna, Clinical Epidemiology Division, Karolinska University Hospital T2, 171 76 Stockholm, Sweden. E-mail: marios.rossides@ 123456ki.se
                Author information
                https://orcid.org/0000-0002-9769-324X
                https://orcid.org/0000-0002-3677-9736
                Article
                ERJ-00767-2020
                10.1183/13993003.00767-2020
                7469972
                32366492
                e3d5b2fa-0557-4017-a016-d2d72cdfe90b
                Copyright ©ERS 2020

                This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.

                History
                : 19 March 2020
                : 22 April 2020
                Funding
                Funded by: Svenska Läkaresällskapet, open-funder-registry 10.13039/501100007687;
                Funded by: Hjärt-Lungfonden, open-funder-registry 10.13039/501100003793;
                Award ID: 20170412
                Award ID: 20190478
                Categories
                Original Articles
                Sarcoidosis

                Respiratory medicine
                Respiratory medicine

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