Recurrent pediatric mast cell-mediated angioedema a retrospective case series and reflection on classification

Abstract

Background: Mast cell-mediated angioedema (MC-AE) is an increasingly recognized entity in pediatric allergy, distinct from bradykinin-mediated and allergic angioedema. Despite its clinical relevance, pediatric data remain limited, and classification remains challenging in the absence of validated biomarkers.
Objective: To describe the clinical presentation, diagnostic workup, and therapeutic outcomes of a pediatric case series with recurrent MC-AE without wheals.
Methods: A retrospective review was conducted comprising pediatric patients with recurrent angioedema without urticaria, evaluated at a tertiary pediatric allergy unit in Barcelona between January 2021 and November 2024. Inclusion required ≥2 episodes, no wheals, and follow-up ≥12 months. Data collected included demographics, clinical features, laboratory evaluation, treatment response, and outcomes.
Results: Seven children (six females, median age at onset 6 years) met inclusion criteria. All had superficial, well-demarcated, self-limiting angioedema, most commonly periorbital. C1-inhibitor studies were normal, excluding hereditary angioedema. All responded to high-dose second-generation antihistamines; corticosteroids were used transiently in moderate/ severe episodes. No patients required biologics or hospital admission. Basophil activation was positive in 1/6 tested patients. Episode frequency decreased during follow-up.
Conclusion: Pediatric MC-AE appears to represent a clinically identifiable phenotype characterized by recurrent superficial swelling, normal complement testing, and consistent antihistamine responsiveness. These findings support mechanism-oriented classification frameworks and highlight the importance of timely recognition to optimize management.