Angioedema: etiology, pathophysiology, current and emerging therapies

J Emerg Med. 2013 Nov;45(5):789-96. doi: 10.1016/j.jemermed.2013.03.045. Epub 2013 Aug 29.


Background: Angioedema (AE) is characterized by nonpitting edema of the dermis and subcutaneous layers. The most common sites of involvement are the tongue, lips, face, and throat; however, swelling can also occur in the extremities, genitalia, and viscera. Life-threatening airway swelling can also occur. AE may be allergic or nonallergic. The overall lifetime incidence of AE is reported to be as high as 15%.

Objective: This article summarizes the etiology, pathophysiology, and current treatment of several forms of nonallergic AE (including hereditary, acquired, and idiopathic AE) and focuses on angiotensin-converting enzyme inhibitor-induced angioedema (ACEi-AE), which is responsible for 30%-40% of all AE seen in United States emergency departments.

Discussion: Although the triggers, which are primary biologic mechanisms, and treatments for ACEi-AE may differ from those of the hereditary and acquired forms of AE, the clinical effects of ACEi-AE are mediated through a shared pathway, the kallikrein-kinin system. Thus, although current therapeutic options for ACEi-AE are limited, recent advances in the treatment of hereditary AE (HAE) appear promising for improving the outcomes of patients with ACEi-AE.

Conclusions: New HAE medications that correct imbalances in the kallikrein-kinin system may prove safe and efficacious in the treatment of ACEi-AE.

Keywords: angioedema; angiotensin-converting enzyme inhibitor–induced angioedema; ecallantide; icatibant; kallikrein-kinin system.

Publication types

  • Review

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use
  • Angioedema* / classification
  • Angioedema* / epidemiology
  • Angioedema* / etiology
  • Angioedema* / therapy
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects*
  • Bradykinin / analogs & derivatives
  • Bradykinin / therapeutic use
  • Complement C1 Inhibitor Protein / therapeutic use
  • Endoscopy
  • Humans
  • Incidence
  • Intubation, Intratracheal
  • Kallikreins / antagonists & inhibitors
  • Peptides / therapeutic use
  • Risk Factors


  • Adrenergic beta-Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Complement C1 Inhibitor Protein
  • Peptides
  • ecallantide
  • icatibant
  • Kallikreins
  • Bradykinin