Familial complex regional pain syndrome in pediatric siblings: a diagnostic challenge and therapeutic success—a case report

BACKGROUND: Complex Regional Pain Syndrome (CRPS) is exceptionally rare in pediatric populations (Weissmann and Uziel in Pediatr Rheumatol Online J 14(1):29, 2016), with familial clustering being previously unreported in children. The diagnostic challenge is compounded by the extensive differential diagnosis of severe extremity pain in this age group (Harden et al. in Pain Med 23(Suppl 1):S1-S53, 2022; Marinus et al. in Lancet Neurol 10(7):637-648, 2011). CASE PRESENTATION: We report two pediatric siblings of Arab ethnicity who developed sequential severe extremity pain: A 3-year-old girl of Arab ethnicity with a 2-month history of progressive pain starting in the lower extremities and extending to the upper extremities, followed by her 5-year-old brother with a similar presentation 20 days later. Both children presented with severe functional impairment, autonomic dysfunction, and met the Budapest Criteria for CRPS Type 1 (Harden et al. in Pain 150(2):268-274, 2010). Comprehensive investigations systematically excluded infectious, inflammatory, neoplastic, genetic, and metabolic causes through a structured diagnostic approach. The tight temporal clustering (within a 20-day interval) suggests shared environmental triggers in genetically susceptible individuals, rather than purely hereditary factors. Both patients demonstrated remarkable improvement with Gabapentin and intravenous immunoglobulin (IVIG) therapy (Mangnus et al. in Drugs 82(5):511531, 2022; Goebel et al. in Ann Intern Med 152(3):152-158, 2010). CONCLUSIONS: This represents the first reported case of familial CRPS in pediatric siblings, demonstrating the complex interplay between environmental triggers and genetic susceptibility in CRPS pathogenesis. The case highlights the importance of systematic differential diagnosis in pediatric extremity pain and demonstrates the efficacy of early aggressive treatment with Gabapentin and IVIG in pediatric CRPS (Mangnus et al. in Drugs 82(5):511531, 2022; Goebel et al. in Ann Intern Med 152(3):152-158, 2010).