Last updated: July 26, 2023

Summarytoggle arrow icon

Angioedema is a self-limited, localized swelling of the dermis, subcutaneous tissues, and/or submucosal tissues caused by fluid leakage into the interstitial tissue. It is mediated by vasoactive substances and can be classified as histamine-mediated (often secondary to allergic reactions and NSAIDs), bradykinin-mediated (due to ACE inhibitor use or enzyme deficiencies), or unknown (idiopathic). Patients usually present with swelling of the eyelids, lips, and tongue. However, life-threatening laryngeal edema may occur, which requires immediate airway protection. Treatment generally consists of aggressive supportive care and avoidance of triggers, if applicable. In acute cases, histamine-mediated angioedema is treated with systemic glucocorticoids, antihistamines, and, if necessary, epinephrine for anaphylaxis. Bradykinin-mediated angioedema is treated with C1 inhibitor (C1-INH) concentrate, bradykinin-B2-receptor antagonists, or kallikrein inhibitors.

Overviewtoggle arrow icon

Differentiation between histamine-mediated angioedema and bradykinin-mediated angioedema [1][2]
Histamine-mediated angioedema Bradykinin-mediated angioedema
Hereditary angioedema types I–III Acquired angioedema
  • Minutes
  • Hours
  • 12–24 hours
  • 24–48 hours
Usual age
  • Any
  • < 20 years
Family history
  • Possible
  • Common
  • Uncommon
Cause/trigger [3][4]


  • No
  • Common
  • Uncommon

Associated symptoms

Laryngeal edema
  • Possible
  • Common
Extremity or truncal edema
Gastrointestinal symptoms
  • Common
  • Uncommon
Response to standard anaphylaxis treatment
  • Good
  • Poor

Classificationtoggle arrow icon

Histamine-mediated angioedema (mast cell-mediated angioedema) [1][2]

Bradykinin-mediated angioedema [2][6]

Angioedema of unknown cause [2][5]

Clinical featurestoggle arrow icon

Common symptoms

Histamine-mediated angioedema

Bradykinin-mediated angioedema


Diagnosticstoggle arrow icon

Laboratory findings in bradykinin-mediated angioedema [6]
Hereditary angioedema Acquired angioedema
Type I Type II Type III ACE-inhibitor induced C1-INH deficiency
C1-INH level Normal Normal Normal
C1-INH function Normal Normal
C4 level ↓ During acute attacks ↓ During acute attacks Normal Normal
C1q level Normal Normal Normal Normal

Differential diagnosestoggle arrow icon

The differential diagnoses listed here are not exhaustive.

Managementtoggle arrow icon


Emergency management [2][5][9][10]

If airway compromise is suspected (stridor, wheezing, diminished air movement) or the patient is in shock, administer IM epinephrine immediately, start oxygen and IV fluids, and consider intubation to protect the airway. Once acute therapy has been initiated, the type and cause of angioedema should be determined.

Intubation is very risky in patients with angioedema and should only be performed by an expert. If there is no time for help, then preparation for the procedure must also include rescue devices and surgical airway equipment.

Case-based specific treatment [2][5]

Treatment of histamine-mediated angioedema and treatment of idiopathic angioedema

Treatment of bradykinin-mediated angioedema and treatment of hereditary angioedema [8][10]

Epinephrine, glucocorticoids, and antihistamines are usually not effective in acute hereditary angioedema attacks! If these have been given empirically (e.g., for suspected anaphylaxis with airway compromise) and there is a poor response, then targeted therapy for bradykinin-mediated angioedema should be considered as the next step.

Acute management checklisttoggle arrow icon

Preventiontoggle arrow icon

General [2]

  • Trigger avoidance (e.g., allergens, offending medications, environmental factors)
  • Counseling on symptom recognition and instructions for when to return to the hospital
  • Prespecified treatment action plans


Referencestoggle arrow icon

  1. Moellman JJ, Bernstein JA, Lindsell C, et al. A Consensus Parameter for the Evaluation and Management of Angioedema in the Emergency Department. Academic Emergency Medicine. 2014; 21 (4): p.469-484.doi: 10.1111/acem.12341 . | Open in Read by QxMD
  2. Busse PJ, Christiansen SC. Hereditary Angioedema. N Engl J Med. 2020; 382 (12): p.1136-1148.doi: 10.1056/nejmra1808012 . | Open in Read by QxMD
  3. Busse PJ, Christiansen SC, Riedl MA, et al. US HAEA Medical Advisory Board 2020 Guidelines for the Management of Hereditary Angioedema. J Allergy Clin Immunol Pract. 2020; 9 (1): p.132-150.e3.doi: 10.1016/j.jaip.2020.08.046 . | Open in Read by QxMD
  4. Zuraw B, Bingham CO III. An Overview of Angioedema: Clinical Features, Diagnosis, and Management. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. Last updated: July 21, 2015. Accessed: March 10, 2017.
  5. Maurer M, Magerl M. Differences and Similarities in the Mechanisms and Clinical Expression of Bradykinin-Mediated vs. Mast Cell–Mediated Angioedema. Clin Rev Allergy Immunol. 2021; 61 (1): p.40-49.doi: 10.1007/s12016-021-08841-w . | Open in Read by QxMD
  6. Zotter Z, Csuka D, Szabó E, et al. The influence of trigger factors on hereditary angioedema due to C1-inhibitor deficiency. Orphanet J Rare Dis. 2014; 9 (1): p.44.doi: 10.1186/1750-1172-9-44 . | Open in Read by QxMD
  7. Banerji A, Riedl M. Managing the Female Patient with Hereditary Angioedema. Women's Health. 2016; 12 (3): p.351-361.doi: 10.2217/whe.16.6 . | Open in Read by QxMD
  8. Long B, Koyfman A, Gottlieb M. Evaluation and Management of Angioedema in the Emergency Department. Western Journal of Emergency Medicine. 2019; 20 (4): p.587-600.doi: 10.5811/westjem.2019.5.42650 . | Open in Read by QxMD
  9. Maurer M, Magerl M, Betschel S, et al. The international WAO/EAACI guideline for the management of hereditary angioedema – The 2021 revision and update. Allergy. 2022; 15 (3): p.100627.doi: 10.1016/j.waojou.2022.100627 . | Open in Read by QxMD
  10. Craig T, Busse P, Gower RG, et al. Long-term prophylaxis therapy in patients with hereditary angioedema with C1 inhibitor deficiency. Annals of Allergy, Asthma & Immunology. 2018; 121 (6): p.673-679.doi: 10.1016/j.anai.2018.07.025 . | Open in Read by QxMD
  11. Hahn J, Hoffmann TK, Bock B, Nordmann-Kleiner M, Trainotti S, Greve J. Angioedema - an interdisciplinary emergency. Dtsch Arztebl Int. 2017; 114 (29-30): p.489-496.doi: 10.3238/arztebl.2017.0489 . | Open in Read by QxMD
  12. Frank MM. Hereditary Angioedema. Hereditary Angioedema. New York, NY: WebMD. Updated: July 27, 2016. Accessed: February 17, 2017.
  13. Hereditary and Acquired Angioedema.,-autoimmune,-and-other-hypersensitivity-disorders/hereditary-and-acquired-angioedema. Updated: June 1, 2016. Accessed: February 17, 2017.
  14. Cicardi M. Acquired C1 Inhibitor Deficiency: Clinical Manifestations, Epidemiology, Pathogenesis, and Diagnosis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. Last updated: August 29, 2016. Accessed: March 10, 2017.
  15. Guyer AC, Banerji A. ACE Inhibitor-Induced Angioedema. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. Last updated: June 4, 2015. Accessed: March 10, 2017.
  16. Zuraw B, Bingham CO III. An Overview of Angioedema: Pathogenesis and Causes. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. Last updated: November 11, 2016. Accessed: March 10, 2017.
  17. Li HH. Angioedema. In: Kaliner MA, Angioedema. New York, NY: WebMD. Updated: July 28, 2016. Accessed: March 10, 2017.
  18. Cicardi M, Bruce Zuraw B, Saini S, Feldweg AM. Hereditary Angioedema: Treatment of Acute Attacks. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. Last updated: August 29, 2016. Accessed: May 30, 2018.

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