• Marios Rossides, Susanna Kullberg, and Elizabeth V Arkema.
• Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Respiratory Medicine and Allergy, Theme Inflammation and Ageing, Karolinska University Hospital, Stockholm, Sweden. Electronic address: marios.rossides@ki.se.
• Chest. 2024 Nov 1; 166 (5): 108210921082-1092.

BackgroundAn autoimmune component in the cause of sarcoidosis has long been debated, but population-based data on the clustering of immune-mediated diseases (IMDs) and sarcoidosis in individuals and families suggestive of shared cause are limited.Research QuestionDo patients with a history of IMDs have a higher risk of sarcoidosis and do IMDs cluster in families with sarcoidosis?Study Design And MethodsWe conducted a case-control-family study (2001-2020). Patients with sarcoidosis (N = 14,146) were identified in the Swedish National Patient Register using a previously validated definition (≥ 2 International Classification of Diseases [ICD]-coded inpatient or outpatient visits). At diagnosis, patients were matched to up to 10 control participants from the general population (N = 118,478) for birth year, sex, and residential location. Patients, control participants, and their first-degree relatives (FDRs; Multi-Generation Register) were ascertained for IMDs by means of ICD codes in the Patient Register (1968-2020). Conditional logistic regression was used to estimate ORs and 95% CIs of sarcoidosis associated with a history of IMDs in patients and control participants and in FDRs.ResultsPatients with sarcoidosis exhibited a higher prevalence of IMDs compared with control participants (7.7% vs 4.7%), especially connective tissue diseases, cytopenia, and celiac disease. Familial aggregation was observed across IMDs; the strongest association was with celiac disease (OR, 2.09; 95% CI, 1.22-3.58), followed by cytopenia (OR, 1.88; 95% CI, 0.97-3.65), thyroiditis (OR, 1.72; 95% CI, 1.14-2.60), skin psoriasis (OR, 1.70; 95% CI, 1.34-2.15), inflammatory bowel disease (OR, 1.53; 95% CI, 1.14-2.03), immune-mediated arthritis (OR, 1.49; 95% CI, 1.20-1.85), and connective tissue disease (OR, 1.39; 95% CI, 1.00-1.93).InterpretationThis study showed that IMDs confer a higher risk of sarcoidosis and they aggregate in families with sarcoidosis, signaling a shared cause between IMDs and sarcoidosis. Our findings warrant further evaluation of shared genetic mechanisms.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

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