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Prevalence has been estimated at 1/100,000.

Onset may occur at any age but is most common during childhood or adolescence. Patients present with white, circumscribed nonpruritic edemas that remain for a period of 48 to 72 hours and recur with variable frequency. Edemas may involve the digestive tract resulting in a clinical picture similar to that seen in intestinal occlusion syndrome, sometimes associated with ascites and hypovolemic shock. Laryngeal edema can be life-threatening with a risk of death of 25% in the absence of appropriate treatment. Dental procedures are a triggering factor for laryngeal edema. Edemas of the face are a risk factor for laryngeal involvement.

Three types of HAE have been described. HAE types 1 and 2 are caused by anomalies in the SERPING1 gene (11q12-q13-1) encoding the C1 inhibitor (C1-INH): type 1 is caused by deletion or by expression of a truncated transcript leading to a quantitative defect in C1-INH; type 2 is caused by point mutations leading to a qualitative defect in C1-INH. Transmission is autosomal dominant and most cases involve heterozygotes. The edemas are triggered by increased permeability of the blood vessels in response to elevated levels of bradykinin as a result of the C1-INH deficiency. HAE type 3 predominantly involves females, with the use of estrogen-containing oral contraceptives and pregnancy being precipitating factors. HAE type 3 is not caused by C1-INH deficiency but is associated with an increase in kininogenase activity leading to elevated levels of bradykinin. Some cases are associated with coagulation factor 12 (Hageman factor; F12; 5q33-qter) gain-of-function mutations but other genetic anomalies remain to be identified.

Diagnosis of HAE types 1 and 2 relies on measurement of C4 concentrations and on quantitative and functional analysis of C1-INH. Diagnosis of HAE type 3 revolves around recognition of the clinical picture; C4 and C1-INH levels are normal. Analysis for mutations in the F12 gene may be proposed but are present in only 15% of patients.

The differential diagnosis should include acquired angioedema, intestinal occlusion syndrome and histamine-induced angioedema (of allergenic or nonallergenic origin) generally associated with urticaria. Screening of family members, including asymptomatic individuals, is recommended.

Corticosteroid treatments are not effective. In Europe, acute attacks should be treated with subcutaneous icatibant (a bradykinin receptor antagonist) or intravenous administration of C1-INH concentrate. Prophylactic treatment with tranexamic acid or danazol may be proposed for patients with frequent episodes.

The vital prognosis is good for patients who have been diagnosed and have access to the proper treatment in case of an ear-nose-throat (ENT) edema. Significant morbidity may be associated with digestive involvement resulting in pain and patients becoming bedridden for at least three days following an episode.

Last update: August 2011 - Expert reviewer(s): Pr Laurence BOUILLET