Immune-Related Comorbidities in Pediatric Familial Mediterranean Fever: A Hidden Burden Beyond Autoinflammation

Abstract

Introduction: The aim of the study was to assess the frequency and clinical-immunologic characteristics of immune-related comorbidities in children with genetically confirmed familial Mediterranean fever. Methods: This cohort study included 132 pediatric patients with a genetically confirmed diagnosis of FMF, followed at a tertiary care center. Patients were stratified into two groups based on the presence or absence of immune-related comorbidities. Clinical manifestations, laboratory parameters, MEFV mutation profiles, and treatment modalities were comparatively analyzed. Statistical significance was set at p < 0.05. Results: Immune-related comorbidities were identified in 37.8% of patients, including 12 with defined inborn errors of immunities. These patients more frequently presented with atypical symptoms such as diarrhea, rash, aphthous stomatitis, and appetite loss, while classical symptoms like fever and abdominal pain were less common. Tonsillitis was significantly more frequent in the non-comorbidity group (p = 0.046). Strong antinuclear antibody positivity and immunoglobulin deficiencies were significantly associated with the comorbidity group. Although MEFV mutation patterns did not differ between groups, intravenous immunoglobulin therapy was administered exclusively in patients with immune-related comorbidities (p < 0.001). Conclusion: A notable subset of pediatric familial Mediterranean fever patients demonstrates immune dysregulation extending beyond innate autoinflammation. These findings underscore the importance of immunologic assessment in patients with atypical features or inadequate response to colchicine. Early identification and appropriate immunomodulatory interventions may improve clinical outcomes in this distinct subgroup.