POS0184 GENETICALLY DEFINED SYSTEMIC AUTOINFLAMMATORY DISEASES IN PEDIATRIC PATIENTS WITH BEHÇET’S DISEASE – A SINGLE CENTER EXPERIENCE
Authors: S. Zheng, X. Huang, X. Chen, J. Chen, P. Y. Lee, Q. Zhou, T. Li
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Behçet's disease (BD) is a form of systemic vasculitis that is rare in children. Early development of BD may be a manifestation of genetically defined systemic autoinflammatory diseases (SAID). <h3>Objectives:</h3> The aim of this study is to characterize genetically defined SAID in a cohort of children with BD. <h3>Methods:</h3> We studied 28 cases of pediatric BD treated in our center from 2019 to 2023. All cases fulfilled the 2015 classification criteria for paediatric BD [1]. Whole exome sequencing was performed to identify potential genetic causes of disease. Clinical characteristics of cases with or without genetically defined SAID were compared. <h3>Results:</h3> We performed whole exome sequencing on 28 patients with pediatric BD and identified 6 cases with genetic findings associated with SAID (SAID+ group). Five patients possessed pathogenic or likely pathogenic germline variants in RELA, TNFAIP3 (encoding A20), and GATA2, compatible with the diagnoses of RELA haploinsufficiency (2 cases), haploinsufficiency of A20 (HA20; 2 cases), and GATA2 deficiency (1 case), respectively. One patient was found to have trisomy 8. Three of the 6 cases exhibited parentally inherited variants (2 case with RELA haploinsufficiency and 1 case with HA20) while the remainder possessed de novo variants. Compared to pediatric BD patients without genetically determined SAID (SAID- group; n = 22), the SAID+ group exhibited earlier disease onset (3.31±3.58 vs. 7.24±4.38, P=0.046) and greater prevalence of recurrent fever episodes, intestinal involvement, and hematologic abnormalities (Table 1). Oral ulceration affected all patients and was the initial symptom in the majority of cases in both groups. Laboratory studies revealed higher levels of C-reactive protein (31.37±34.69 vs. 6.38±7.07, P=0.035), erythrocyte sedimentation rate (60.83±19.11 vs. 25.97±18.73, P=0.003), and multiple cytokines including IL-6, TNF-α, IL-1β, IL-10, and IL-2 (Figure 1). Corticosteroid treatment was commonly utilized in both groups while the use of biologic DMARDs was more common in the SAID+ group (100% vs. 40.9% in the SAID- group; Table 1). SAID+ patients were treated with adalimumab (3 cases), etanercept (2 cases), tocilizumab (1 case), and Infliximab (1 case). <h3>Conclusion:</h3> Genetic evaluation of pediatric-onset BD is important as genetically defined SAID account for a substantial proportion of cases. Pediatric BD patients with SAID display greater levels of systemic inflammation and require more aggressive immunosuppressive therapy. <h3>REFERENCES:</h3> [1] Koné-Paut I, Fahrad Shahram, Martha Darce-Bello, et al. Consensus classification criteria for paediatric Behçet's disease from a prospective observational cohort: PEDBD. Ann Rheum Dis 2015;0:1–7. <h3>Acknowledgements:</h3> Medical Scientific Research Foundation of Guangdong Province (B2022162, A2023045. <h3>Disclosure of Interests:</h3> <b>None declared.</b>