Comparison Between Systemic Lupus Erythematosus Patients with and Without Family History of Systemic Lupus Erythematosus—A Single-Center Retrospective Study

Background: A positive family history of systemic lupus erythematosus (SLE) reflects the substantial genetic contribution to disease susceptibility; however, it remains unclear whether patients with a family history of SLE represent a distinct clinical phenotype. Methods: A retrospective single-center study was conducted in adult patients fulfilling the 2019 EULAR/ACR classification criteria for SLE who were treated at the University Hospital in Kraków, Poland, between 2012 and 2022. Demographic, clinical, laboratory, comorbidity, and treatment data, as well as mortality data, were extracted from medical records. Patients with and without a documented/reported family history of SLE were compared, and those with positive family history of SLE were further stratified according to the degree of kinship of the affected relative. Patients with SLE for whom data on a family history of SLE were unavailable were not included in the analysis. Benjamini–Hochberg false discovery rate correction was applied across the primary comparisons, while the kinship analysis was corrected separately. Results: Among 723 patients with SLE, 47 (6.5%) reported a family history of SLE. Patients with a family history of SLE had a similar overall demographic and clinical profile to those without a family history. Arthralgia was nominally more frequent in patients with a family history of SLE (97.8% vs. 88.5%, p = 0.049), but this association did not remain significant after correction for multiple comparisons (q = 1.000). Similarly, myocardial infarction was more frequent in patients with a family history of SLE (7/47 [14.9%] vs. 37/676 [5.5%], p = 0.019), but the association was not significant after FDR correction (q = 0.912). No significant differences were observed in the serological profile, antiphospholipid antibody prevalence, treatment exposure, or mortality after correction for multiple comparisons. In the kinship analysis, several nominal differences in clinical manifestations were observed between patients with affected first-degree and more distant relatives, including arthritis, malar rash, oral/nasal ulcers, and thrombocytopenia; however, none remained statistically significant after correction for multiple comparisons. Conclusions: A positive family history of SLE was reported by a small proportion of patients in this European cohort and was not associated with a distinct overall clinical, serological, or treatment profile after correction for multiple comparisons. Nominal associations with selected clinical manifestations and myocardial infarction, as well as differences observed according to the degree of kinship, should be interpreted cautiously given the small familial subgroup and multiple comparisons. These findings are hypothesis-generating and require confirmation in larger prospective multicenter cohorts.