Hereditary Angioedema

Disease / Phenomenon

Hereditary angioedema (HAE) is a rare genetic disorder causing recurrent, unpredictable attacks of deep tissue swelling. Episodes typically affect the extremities, face, genitals, gastrointestinal tract, and — most dangerously — the larynx, where swelling can obstruct the airway. Unlike allergic angioedema, HAE attacks are not accompanied by hives or itching and do not respond to antihistamines, corticosteroids, or epinephrine, a distinction that is critical to recognize and one that historically led to delayed diagnosis. Abdominal attacks produce severe pain, vomiting, and distension that can be mistaken for a surgical emergency. Attacks are frequently precipitated by physical trauma, dental procedures, infection, emotional stress, or hormonal changes including estrogen exposure.

The disorder is usually caused by mutations in SERPING1, which encodes C1 esterase inhibitor. Type I involves reduced protein levels and type II a dysfunctional protein; a normal-C1-INH variant often involves factor XII mutations. C1 inhibitor normally restrains the contact activation system, so deficiency permits unchecked activation of factor XII and plasma kallikrein, which cleaves high-molecular-weight kininogen to release bradykinin. Bradykinin acting on B2 receptors on endothelium increases vascular permeability, producing the characteristic swelling. This page organizes HAE into its biological processes, pathways, and biomarkers.