• Clinical science
  • Clinician



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.


Differentiation between histamine-mediated angioedema and bradykinin-mediated angioedema
Histamine-mediated angioedema [1][2] Bradykinin-mediated angioedema [1][2]
Hereditary angioedema types I–III Acquired angioedema
  • Minutes
  • Hours
  • 12–24 hours
  • 24–48 hours
Usual age
  • Any
  • < 20 years
  • Acquired C1-INH deficiency: > 40 years
  • ACE inhibitor-induced: any
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


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

Bradykinin-mediated angioedema [1][2]

Angioedema of unknown cause [1][2]

Clinical features

Common symptoms

Histamine-mediated angioedema

Bradykinin-mediated angioedema



  • Initial evaluation
    • The diagnosis is mainly based on history and clinical findings.
    • Flexible fiberoptic laryngoscopy should be performed if there is no clear obstruction but clinical suspicion of angioedema is high. [2]
  • Further evaluation: indicated for follow-up or if the etiology is unclear [2][1]
Laboratory findings in bradykinin-mediated angioedema [1]
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 diagnoses

  • Anaphylaxis is the most important differential diagnosis.

The differential diagnoses listed here are not exhaustive.



Emergency management [1][2][6]

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 [1][2]

Treatment of histamine-mediated angioedema and treatment of idiopathic angioedema

Treatment of bradykinin-mediated angioedema and treatment of hereditary angioedema

  • Administer one of the following targeted therapies:
    • Purified C1-INH concentrate (protein replacement)
      • Plasma-derived [1]
      • Recombinant
    • Kallikrein inhibitor: ecallantide
    • Bradykinin-B2 receptor antagonist: icatibant
  • Second-line or suspected ACE inhibitor-induced etiology: fresh frozen plasma (FFP)

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 checklist


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