Description

Hereditary angioedema (HAE) is an autosomal dominant condition characterized by recurrent, unpredictable, and potentially life-threatening swelling. The swelling results from excess production of bradykinin which is a potent vasodilator. Most commonly, this production results from a deficiency or dysfunction of C1 esterase inhibitor (C1-INH) which leads to unregulated activation of complement and plasma kinin–forming pathways and angioedema. There are three main classifications of HAE and one additional category of acquired angioedema:

• Type I HAE: deficiency of C1-INH (~85% of patients)
• Type II HAE: dysfunction of C1-INH (~15%)
• HAE with normal C1-INH (previously called type III HAE): unclear mechanism (very rare)
• Acquired angioedema, ACE inhibitor–induced angioedema, and idiopathic angioedema (These are not HAE and will be minimally discussed here)

Epidemiology

• HAE type I or II
  • Prevalence between 1 in 10,000 and 1 in 150,000
  • All genders and races affected equally
  • Onset before puberty in ~50% of patients
  • Symptoms tend to worsen during puberty and persist into adulthood.
• HAE with normal C1-INH
  • Only a few families described, mostly women of childbearing age

Risk Factors

Pathophysiology

• Deficiency/dysfunction of C1-INH leads to unopposed activation of the classical complement pathway and conversion of prekallikrein to kallikrein.
• Kallikrein increases formation of bradykinin, which produces angioedema.
• Histamine and other mast cell mediators are NOT involved.

Commonly Associated Conditions

Mildly increased risk of autoimmunity