Hereditary Angioedema

Abstract

Hereditary angioedema (HAE) is an autosomal dominant disease that afflicts 1 in 10,000 to 1 in 150,000 persons; HAE has been reported in all races, and no sex predominance has been found. It manifests as recurrent attacks of intense, massive, localized edema without concomitant pruritus, often resulting from one of several known triggers. However, attacks can occur in the absence of any identifiable initiating event. Historically, 2 types of HAE have been described. However, a variant, possibly X-linked, inherited angioedema has recently been described, and tentatively it has been named "type 3" HAE. Signs and symptoms are identical in all types of HAE. Skin and visceral organs may be involved by the typically massive local edema. The most commonly involved viscera are the respiratory and gastrointestinal systems. Involvement of the upper airways can result in severe life-threatening symptoms, including the risk of asphyxiation, unless appropriate interventions are taken. Quantitative and functional analyses of C1 esterase inhibitor and complement components C4 and C1q should be performed when HAE is suspected. Acute exacerbations of the disease should be treated with intravenous purified C1 esterase inhibitor concentrate, where available. Intravenous administration of fresh frozen plasma is also useful in acute HAE; however, it occasionally exacerbates symptoms. Corticosteroids, antihistamines, and epinephrine can be useful adjuncts but typically are not efficacious in aborting acute attacks. Prophylactic management involves long-term use of attenuated androgens or antifibrinolytic agents. Clinicians should keep this disorder in their differential diagnosis of unexplained, episodic cutaneous angioedema or abdominal pain.

Hereditary Angioedema Caused By C1-Esterase Inhibitor Deficiency: A Literature-Based Analysis and Clinical Commentary on Prophylaxis Treatment Strategies

“…HAE is not generally diagnosed at initial presentation, and the time of diagnosis has been shown to range from 8 to 22 years from the first attack[6,21,22]. Attacks often occur without a trigger; however, precipitating factors that have been shown to contribute to the frequency of attacks include stress, trauma, infection, menstruation, and pregnancy[3,4,9,21,23]. Various medications, such as estrogen-containing agents and angiotensin-converting enzyme inhibitors, may also induce HAE attacks[3,4,9,21,23].…”

“…Attacks often occur without a trigger; however, precipitating factors that have been shown to contribute to the frequency of attacks include stress, trauma, infection, menstruation, and pregnancy[3,4,9,21,23]. Various medications, such as estrogen-containing agents and angiotensin-converting enzyme inhibitors, may also induce HAE attacks[3,4,9,21,23]. Before attacks, many patients experience prodromal symptoms that can include tingling sensations or erythema marginatum, a nonpruritic and not raised rash (Figure 1)[4,21,24].…”

“…Ecallantide is a human plasma kallikrein inhibitor that treats HAE symptoms by directly inhibiting plasma kallikrein and decreasing the conversion of high-molecular-weight kininogen to bradykinin[41]. Fresh frozen plasma has been used, but its utility is limited because it contains additional kinins and complement factors, posing a potential threat of worsening HAE symptoms[3,34]. Nevertheless, successful use of fresh frozen plasma has been reported for both acute treatment and prophylaxis[50-52].…”

“…Although HAE is an inherited disorder, 25% of cases arise from spontaneous mutations[3]. HAE is characterized by recurrent attacks of intense, massive, localized subcutaneous edema, without pruritus, involving the extremities, genitalia, face, or trunk, or submucosal edema of the upper airway or bowels[2,4].…”

“…Estimates indicate that approximately 1 in 50,000 people in the general population has HAE[8]. No sex or race predominance has been described[3]. …”