Recognition, Evaluation, and Management of Pediatric Hereditary Angioedema

Abstract

Hereditary angioedema (HAE) is a rare, often underrecognized genetic disorder caused by either a C1 esterase inhibitor deficiency (type 1) or mutation (type 2). This leads to overproduction of bradykinin resulting in vasodilation, vascular leakage, and transient nonpitting angioedema occurring most frequently in the face, neck, upper airway, abdomen, and/or extremities. Involvement of the tongue and laryngopharynx has been associated with asphyxiation and death. Hereditary angioedema is an autosomal-dominant condition; therefore, there is a 50% chance an offspring will inherit this disorder. Any patient presenting with isolated angioedema should be screened with a C4 measurement, as 25% of cases have no family history of HAE. All patients with HAE will have a functional deficiency of C1 esterase inhibitor. Contributors that delay the diagnosis of HAE include recognition delay by clinicians who confuse this condition with histaminergic angioedema, the disease's varied presentations, and limitations to timely testing. Pediatric emergency clinicians should be knowledgeable about how to distinguish between bradykinin- and histamine-mediated angioedema, as there are significant differences in the diagnostic testing, treatment, and clinical response between these 2 different conditions. Evidence indicates that early diagnosis and treatment of HAE reduces morbidity and mortality. Clinician recognition of the mechanistically different problems will ensure patients are appropriately referred to an expert for outpatient management.

The international WAO/EAACI guideline for the management of hereditary angioedema—The 2021 revision and update

“…HAE‐1/2 patients are encouraged to find a health care provider with HAE‐specific knowledge, interest, expertise, and experience. All patients with HAE should be treated by a specialist with specific expertise in HAE (Recommendation 25) 4,176,244,297,346,347,355 …”

“…All patients with HAE should be treated by a specialist with specific expertise in HAE (Recommendation 25). 4,176,244,297,346,347,355 There are several barriers for HAE patients to obtain optimal care. They include long delays in obtaining the correct diagnosis, physicians with little HAE knowledge and experience, not enough time allocated for their visits and communication with their physician, disconnects between patients' beliefs, expectations, and priorities and those of their physicians, administrative and payer-related requirements for obtaining appropriate treatment, and the lack of therapies in their country.…”

“…Good dental care can reduce extractions, need for aggressive dental procedures and prevent acute or chronic intraoral inflammation, which may reduce the threshold for attacks. 164,167,312,315,378,379 The severe acute respiratory syndrome coronavirus type 2 4,176,297,355,[385][386][387] Delayed diagnosis leads to morbidity and decreased quality of life due to delayed introduction of appropriate therapy. There is a risk that the first HAE attack may affect the airway or the abdomen and could cause asphyxia or unnecessary surgery.…”

The international WAO/EAACI guideline for the management of hereditary angioedema – The 2021 revision and update

“…All patients with HAE should be treated by a specialist with specific expertise in HAE (Recommendation 25). 4 , 176 , 244 , 297 , 346 , 347 , 355 …”

“…Family members including grandparents, parents, siblings, children, and grandchildren of HAE-1/2 patients should be screened for C1–INH function, C1–INH protein, and C4 plasma levels (Recommendation 28). 4 , 176 , 297 , 355 , 385 , 386 , 387 Delayed diagnosis leads to morbidity and decreased quality of life due to delayed introduction of appropriate therapy. There is a risk that the first HAE attack may affect the airway or the abdomen and could cause asphyxia or unnecessary surgery.…”