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

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.

To describe the clinical presentation, diagnostic workup, and therapeutic outcomes of a pediatric case series with recurrent MC-AE without wheals.

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.

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.

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.