Background: Behçet’s disease (BD) exhibits a diverse clinical spectrum, ranging from mucocutaneous manifestations to systemic involvements such as ocular, neurologic, gastrointestinal, or vascular complications, influenced by genetic and environmental factors. Phenotypic heterogeneity poses significant challenges in understanding and managing the disease, with studies identifying consistent clusters like the acne-arthritis-enthesitis triad and associations between genetic markers, such as HLA-B*51, and specific symptoms like mucocutaneous findings and ocular involvement. Familial aggregation of BD, reported in up to 18% of cases [1], highlights the potential hereditary nature of certain symptoms and shared phenotypic patterns within families, suggesting that genetic and environmental factors may contribute to clinical similarities.

Objectives: This study aims to compare the clinical features of familial and non-familial BD to better understand the mechanisms driving phenotypic diversity.

Methods: Patients with BD from three Turkish tertiary rheumatology outpatient clinics were evaluated. Demographic and clinical characteristics of the familial group with either first- or second-degree relative with BD and non-familial group were compared. Afterwards, patients in the familial disease group for 5 years or longer were divided into two an “index patient” and “first-degree relative patient” and the presence of BD manifestations was compared between these two groups.

Results: Of a total of 864 BD (mean age (SD): 47.9 (12) years, disease duration (SD): 83.7 (65.3) months and male/female rate: 368/496) patients, 251 (29.1%) had a family history of BD and 135 (16%) of them had first-degree relatives affected. When we compared the familial and non-familial BD groups, the disease duration was statistically significantly longer in the familial group (p<0.001) which was also significantly younger (p=0.013) at the time of diagnosis. In addition, genital ulcers (p=0.002) and papulopustular lesions (p<0.001) were detected significantly more frequently in the familial group. Immunosuppressive therapy was received by 125 patients (49.8%) in the familial group and 342 patients (55.8%) in the non-familial group. There was no statistically significant difference between the two groups (p=0.301). According to Holm-Bonferroni adjusted analysis, disease duration was significantly longer in the familial BD group (p=0.015), and the frequency of genital ulcers and papulopustular lesions was significantly higher in the familial group (p=0.03 and p=0.015, respectively). However, the difference in age at diagnosis between the two groups did not reach statistical significance (p=0.182). In the familial group, there were 51 index patients (and 51 relatives) who were followed up with their relatives in the same center. Data from 36 (72 patients in total) of these 51 index & first-degree relative pairs with a follow-up period of 5 years or more were included in the final analysis. Of the 36 patient pairs in the familial group, 29 (80.5%) were siblings and 27 (75%) were of the same gender. When we analysed the phenotypic similarity of each patient with their relative individually in the familial group, statistically significant correlations were detected between the index patient and the first-degree relative-patient in terms of gender (OR (95% CI): 6.3 (1.3-31.1), r: 0.358, p: 0.032), presence of erythema nodosum-like lesion (OR (95% CI): 5.8 (1.3-25.6), r: 0.398, p: 0.016), pathergy test positivity (OR (95% CI): 13.3 (2.2-82), r: 0.561, p: 0.002), peripheral joint involvement (OR (95% CI): 15.6 (2.7-91.6), r: 0.563, p < 0.001) and vascular involvement (OR (95% CI): 11.7 (1.2-114.6), r: 0.408, p: 0.014). No statistically significant family co-occurrence was found in genital ulcers, papulopustular lesions, uveitis, neuro-Behcet or entero-Behcet (Table 1).

Conclusion: Familial BD may difference from sporadic BD. Additionally, erythema nodosum-like lesions, pathergy test positivity, and vascular and joint involvement may tend to show familial aggregation.

REFERENCES: [1] Ahn HS, Kim HJ, Kazmi SZ, et al. Rheumatology (Oxford ). Jun 18 2021;60(6):2697-2705.

Acknowledgements: NIL.

Disclosure of Interests: Kerem Abacar: None declared, Ayşe Elif Boncukcuoğlu: None declared, Rabia Deniz: None declared, Burcu Ceren Uludoğan: None declared, Dilara Kaş: None declared, Elifnur Alkan: None declared, Gamzenur Kaya: None declared, Tugce Bozkurt: None declared, Nazife Sule Yasar Bilge: None declared, Cemal Bes: None declared, Timuçin Kaşifoğlu: None declared, Dennis McGonagle AbbVie, Janssen, Eli Lilly, Novartis, and UCB, AbbVie, Janssen, Eli Lilly, Novartis, and UCB, AbbVie, Janssen, Eli Lilly, Novartis, and UCB, AbbVie, Janssen, Eli Lilly, Novartis, and UCB, Tülin Ergun: None declared, Haner Direskeneli: None declared, Fatma Alibaz- Oner: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.