Background/Purpose: Sarcoidosis is an inflammatory disease with unknown etiology that primarily affects the lungs and lymph glands. Sarcoidosis shares some features with rheumatoid arthritis (RA), such as joint involvement and genetic susceptibility related to HLA class II alleles. The aim of this study was to estimate the familial co-aggregation of sarcoidosis with RA.

Methods:  A case-control study using Swedish national registers was performed. Adults with sarcoidosis (cases) were identified from the National Patient Register (NPR) and required to have at least two visits listing a sarcoidosis ICD code 2001-2013. Population controls matched 10:1 on age, sex and county who were living in Sweden with no history of sarcoidosis at the time the case was diagnosed (index date) were identified from the Total Population Register. The Multigeneration Register was used to identify parents, siblings and children. Family members with at least two visits listing an ICD code for RA were identified from the NPR (2001-2013). A subset was identified who had any listing of seropositive RA (M05, M08.0). Mean number of first degree relatives (FDR) was calculated for cases and controls to assure that family structures did not differ by case status. Familial relative risks for sarcoidosis associated with having a family history of RA were estimated using odds ratios and 95% confidence intervals (OR 95%CI) from conditional logistic regression models. Models were stratified by sex of the proband. In a sensitivity analysis, cases and controls with comorbid RA were excluded.

Results: 11,669 sarcoidosis cases and 115,581 controls were identified. The average age at diagnosis was 50 and 55% were male. Cases and controls had a similar mean number of FDRs (4.8 and 4.7, respectively). A higher proportion of cases had a family history of RA compared to controls (4.4% vs. 3.3%). The OR for sarcoidosis comparing any family history of RA to no family history was 1.4 (95%CI 1.2, 1.5). The OR associated with a family history of seropositive RA was similar (OR 1.3; 95%CI 1.1, 1.6). The OR was higher for male probands (OR 1.5; 95%CI 1.3, 1.7) compared to females (OR 1.2; 95%CI 1.0, 1.4). When excluding cases and controls with comorbid RA (2% and 1%, respectively), the OR was 1.3 (95%CI 1.2, 1.5).

Conclusion:  There exists a 40% increased risk for sarcoidosis associated with a family history of RA. This indicates that, to some extent, the two diseases share a common etiology and an overlap in genetic risk.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/familial-aggregation-of-rheumatoid-arthritis-in-sarcoidosis-a-register-based-case-control-study-in-sweden/