2 learning resources available for this topic
Hereditary angioedema (HAE) is a rare autosomal dominant disorder characterized by recurrent episodes of non-pitting, asymmetric swelling affecting the skin, mucous membranes, and internal organs. The condition primarily results from deficiency or dysfunction of C1 esterase inhibitor, leading to uncontrolled activation of the complement and contact systems. Episodes can be life-threatening when involving the upper airway, making prompt recognition and treatment essential.
HAE occurs due to mutations in the SERPING1 gene (Type I and II) or F12 gene (Type III), leading to deficient or dysfunctional C1 esterase inhibitor protein. This deficiency results in uncontrolled activation of the complement cascade and kallikrein-kinin system, causing excessive production of bradykinin and other vasoactive mediators. The increased vascular permeability from these mediators leads to the characteristic non-inflammatory angioedema affecting deeper skin layers and mucous membranes.
Diagnosis requires high clinical suspicion in patients with recurrent angioedema episodes, especially when involving the face, lips, tongue, or genitals without urticaria. Laboratory confirmation includes measuring C4 levels (typically low during and between attacks), C1 esterase inhibitor levels, and functional C1 esterase inhibitor activity. Treatment focuses on acute management with C1 esterase inhibitor concentrate, bradykinin receptor antagonists, or kallikrein inhibitors, along with prophylactic therapy for frequent or severe episodes.