Objective: Hereditary angioedema (HAE) is a rare autosomal dominant disorder characterized by recurrent episodes of skin and mucosal swelling, potentially leading to life-threatening laryngeal edema. Its gastrointestinal manifestations may mimic those of autoinflammatory diseases such as Familial Mediterranean Fever (FMF), complicating the diagnostic process, particularly in patients resistant to colchicine therapy.

Materials and Methods: This prospective observational study included pediatric patients aged 1-21 years attending the Pediatric Rheumatology clinic between July 2021 and July 2022. Eligible participants either had a diagnosis of FMF confirmed by heterozygous or homozygous MEFV mutations and were resistant to colchicine therapy or displayed autoinflammatory features with non-pathogenic mutations while receiving empirical colchicine treatment. Serum C4 and C1 esterase inhibitor (C1-INH) levels and activity were measured in all patients.

Results: A total of 51 patients (mean age 10.1 ± 4.3 years; 31.4% female) were enrolled. The most frequently reported symptom was abdominal pain (74.5%), followed by fever (43.1%), and joint pain (29.4%). All patients exhibited normal C4 and C1-INH levels, except for one case in which decreased C1-INH activity led to the diagnosis of type II HAE.

Conclusion: This study emphasizes the importance of considering HAE in pediatric patients presenting with persistent abdominal symptoms and suspected autoinflammatory disease, particularly in cases unresponsive to colchicine therapy. The identification of type II HAE in this context highlights the potential for diagnostic overlap and underscores the need for increased clinical vigilance. These findings support the inclusion of HAE in the differential diagnosis of abdominal pain in pediatric patients with autoinflammatory features.