Hereditary angioedema
Hereditary angioedema is an autosomal dominant deficiency of C1 inhibitor that lets kallikrein generate excess bradykinin, causing recurrent bradykinin-mediated angioedema without urticaria. Attacks do not respond to epinephrine, antihistamines, or steroids, and a low C4 is the screening clue; treatment is airway protection with bradykinin-targeted on-demand therapy and long-term prophylaxis.
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What this article covers
- Overview
Definition: hereditary angioedema (HAE) is an autosomal dominant disorder of C1-inhibitor deficiency in which unregulated kallikrein activity generates excess bradykinin, causing recurrent episodes of bradykinin-mediated angioedema.
- Epidemiology
Rare and inherited: autosomal dominant, affecting roughly 1 in 50,000, with many patients having an affected first-degree relative.
- Risk factors
Family history / inherited C1-inhibitor mutation: the defining risk factor.
- Pathophysiology
C1-inhibitor deficiency: C1 inhibitor normally restrains the contact (kallikrein-kinin) system; its deficiency removes this brake.
- Clinical features
Recurrent non-pitting angioedema without urticaria: the hallmark, distinguishing HAE from allergic angioedema.
- Differential diagnosis
Allergic (histaminergic) angioedema: accompanied by urticaria and pruritus and responsive to epinephrine and antihistamines, unlike the bradykinin-mediated swelling of HAE (Angioedema).
- Diagnosis
Establish with complement studies showing C1-inhibitor deficiency: the diagnostic basis is a low C4 (present both between and during attacks) together with a low C1-inhibitor level (type 1) or low…
- Management
First, protect the airway: treat any laryngeal attack as an emergency, intubating early or obtaining a surgical airway before swelling makes it impossible.
- Complications
Death by asphyxiation: from an untreated laryngeal attack, the most feared complication.
- Prognosis
Good with modern therapy: on-demand bradykinin-targeted treatment and effective prophylaxis have sharply reduced attack frequency and airway deaths.
- Prevention
Avoid ACE inhibitors and estrogen-containing therapy, which raise bradykinin and provoke attacks.
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Related articles
- Angioedema
Angioedema is self-limited, non-pitting swelling of the deep dermis and submucosa that follows one of two mechanisms: mast cell (histamine) mediated, which occurs with urticaria and responds to epinephrine and antihistamines, or bradykinin mediated, which occurs without urticaria and does not. Distinguishing the two determines whether treatment is allergic therapy or bradykinin-targeted therapy, and airway involvement is the central danger.
- Anaphylaxis
Anaphylaxis is an acute, potentially fatal systemic hypersensitivity reaction from massive mast cell and basophil mediator release, presenting within minutes as skin, respiratory, cardiovascular, and gastrointestinal involvement after allergen exposure. It is a clinical, treat-first diagnosis, and intramuscular epinephrine is the immediate life-saving therapy.
- Urticaria
Urticaria is transient, pruritic, edematous wheals from mast cell histamine release, classified by duration into acute (under 6 weeks) and chronic (6 weeks or longer, usually spontaneous/idiopathic). Diagnosis is clinical with minimal testing, and treatment is stepwise second-generation H1 antihistamines up-titrated as needed, adding omalizumab for refractory chronic disease.