D3.311 - Screening for Hereditary Angioedema in Pediatric Patients with Autoinflammatory Diseases and Chronic Abdominal Pain

Hereditary angioedema (HAE) is a rare autosomal dominant disorder, resulting from either a deficiency or impaired function of the C1 esterase inhibitor. It manifests as repeated episodes of swelling affecting the skin and mucous membranes, with the potential for severe, life- threatening swelling of the larynx. Additionally, gastrointestinal involvement may lead to persistent abdominal discomfort, resembling symptoms seen in autoinflammatory conditions like Familial Mediterranean Fever (FMF), Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS), Mevalonate Kinase Deficiency, NLRP3-Linked Autoinflammatory Disease, and PFAPA syndrome. This symptom similarity poses challenges for accurate diagnosis, especially in FMF cases unresponsive to colchicine therapy.

This prospective observational research involved pediatric patients aged 1 to 21 years, recruited from the Pediatric Rheumatology outpatient department between July 2021 and July 2022. The study group included individuals diagnosed with FMF carrying either heterozygous or homozygous MEFV gene variants and showing resistance to colchicine, as well as patients with other autoinflammatory disorders exhibiting non-disease-causing mutations, and those prescribed colchicine based on clinical presentation alone. Levels and activity of serum C4 and C1 esterase inhibitor were evaluated in all participants.

The study enrolled 51 patients, with an average age of 10.11 years (standard deviation ± 4.33 years) and 31.4% being female. Among them, 74.5% reported abdominal pain, 43.1% had episodes of fever, and 29.4% experienced joint discomfort. Nearly all participants exhibited normal serum C4 and C1 esterase inhibitor concentrations, except for one individual who demonstrated diminished C1 esterase inhibitor activity, leading to a diagnosis of HAE type 2.

These findings emphasize the value of evaluating pediatric patients with autoinflammatory conditions and persistent abdominal pain for HAE. The discovery of HAE type 2 in one case illustrates the possibility of diagnostic confusion between these disorders. Additional studies are warranted to better understand the relationship between HAE and autoinflammatory diseases in children.