Novelties in the Diagnosis and Treatment of Angioedema

J Investig Allergol Clin Immunol. 2016;26(4):212-21; quiz two pages after page 221. doi: 10.18176/jiaci.0087.


Angioedema is defined as local, noninflammatory, self-limiting edema that is circumscribed owing to increased leakage of plasma from the capillaries located in the deep layers of the skin and the mucosae. Two mediators, histamine and bradykinin, account for most cases of angioedema. Angioedema can occur with wheals as a manifestation of urticaria, and this form is frequently allergic. In the present review, we discuss nonallergic angioedema without wheals, which can be divided into 3 acquired and 4 hereditary forms. Histamine is the mediator in acquired angioedema of unknown etiology (idiopathic histaminergic acquired angioedema), whereas in other forms the main mediator is bradykinin. Angioedema can be caused by C1-inhibitor deficiency (C1-INH-hereditary angioedema and C1-INH-acquired angioedema), mutations in coagulation factor XII (FXII-hereditary angioedema), and treatment with angiotensin-converting enzyme inhibitors (ACEI-acquired angioedema). Etiology remains unclear in acquired angioedema (idiopathic nonhistaminergic acquired angioedema) and in 1 type of hereditary angioedema (hereditary angioedema of unknown origin). Several treatments are licensed for hereditary C1-INH deficiency. Plasma-derived and recombinant C1-INHs, the bradykinin receptor blocker icatibant, and the plasma kallikrein inhibitor ecallantide have been approved for on-demand treatment to reverse angioedema symptoms. Attenuated androgen and plasma-derived C1-INH are approved for prophylaxis.

Keywords: Angioedema; Angiotensin-converting enzyme inhibitors; Bradykinin; C1 inhibitor; Coagulation factor XII; Histamine; Urticaria.

Publication types

  • Review

MeSH terms

  • Angioedema / diagnosis*
  • Angioedema / drug therapy*
  • Angioedema / etiology
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Bradykinin / analogs & derivatives
  • Bradykinin / therapeutic use
  • Complement C1 Inhibitor Protein / therapeutic use
  • Humans


  • Angiotensin-Converting Enzyme Inhibitors
  • Complement C1 Inhibitor Protein
  • icatibant
  • Bradykinin