Genetically defined systemic autoinflammatory diseases in pediatric patients with Behçet’s disease

Objectives The aim of this study was to characterize the genetic basis of Behçet’s disease (BD) and mimics in a pediatric cohort. Methods We retrospectively studied 34 patients of pediatric BD and mimics who underwent whole-exome sequencing (WES) in our center from 2020 to 2025. Clinical characteristics and laboratory parameters of the patients with or without genetically defined systemic autoinflammatory diseases (SAIDs) were compared. Results WES identified 10 probands with genetically defined SAID (the SAID+ group). Nine probands possessed pathogenic or likely pathogenic germline variants in RELA , TNFAIP3 (encoding A20), or GATA2 . One proband was found to have trisomy 8. Five of the SAID+ probands exhibited parentally inherited variants, while the remaining four probands possessed de novo variants. Compared to pediatric BD patients without genetically determined SAID (the ped-BD group, n = 24), the SAID+ group exhibited earlier disease onset and greater prevalence of recurrent fever episodes, intestinal involvement, and hematologic abnormalities. Laboratory studies revealed higher levels of inflammatory markers and serum cytokines including IL-1β, IL-2, IL-10, and TNFα in the SAID+ group. Corticosteroid treatment was commonly utilized in all patients, while the use of biologic DMARDs was more common in the SAID+ group. Conclusion Pediatric patients with autoinflammatory diseases mimicking BD have heightened systemic inflammation and more severe organ involvement that necessitate intensified immunosuppressive regimens. Genetic evaluation should be considered for BD cases with early disease onset, recurrent fever, enteritis, intestinal ulcers, or hematologic abnormalities.