What is the treatment for angioedema?

Treatment of Angioedema

The treatment of angioedema depends on its type, with histamine-mediated angioedema responding to antihistamines, corticosteroids, and epinephrine, while bradykinin-mediated angioedema (including hereditary angioedema) requires specific therapies such as C1 inhibitors, icatibant, or ecallantide. 1

Classification and Initial Assessment

• Angioedema can be classified as hereditary angioedema (HAE), acquired C1 inhibitor deficiency, ACE inhibitor-induced, or allergic/histamine-mediated, with immediate assessment for airway compromise being critical 1
• Diagnosis requires confirmation of recurrent angioedema through clinical history, photos, and imaging evidence to differentiate true angioedema from factitious angioedema 1
• Detailed family history and medication history are essential, with special attention to ACE inhibitors which can precipitate attacks by decreasing bradykinin catabolism 1, 2

Treatment Algorithm Based on Angioedema Type

Histamine-Mediated Angioedema

• First-line treatment includes high-dose second-generation H1 antihistamines (up to fourfold the standard dose) 1
• Add epinephrine for severe reactions, particularly with airway involvement, though caution is needed due to potential side effects including elevated arterial pressure and cardiac arrhythmias 3
• Corticosteroids may be added for more persistent symptoms 2
• Montelukast can be added if antihistamines alone fail 1

Bradykinin-Mediated Angioedema (HAE and ACE inhibitor-induced)

• First-line treatments for HAE attacks include:
  • Icatibant (30 mg subcutaneously) 1
  • Ecallantide (administered by healthcare provider within 8 hours of attack onset) 4, 1
  • Plasma-derived C1 inhibitor 1, 5
  • Recombinant human C1-inhibitor (rhC1INH) - shown to provide significantly faster symptom relief compared to placebo (66-122 minutes vs 495 minutes) 4
• For ACE inhibitor-induced angioedema, discontinuation of the medication is the most important action 2, 6

Prophylaxis for HAE Patients

• Short-term prophylaxis before dental or surgical procedures includes plasma-derived C1 inhibitor (1000-2000 U intravenously) 1
• Long-term prophylaxis is recommended for patients with frequent attacks, with options including androgens (such as danazol 100 mg on alternate days) 1, 7

Important Considerations and Pitfalls

• Standard angioedema treatments (epinephrine, corticosteroids, antihistamines) are NOT effective for HAE or ACE inhibitor-induced angioedema, which is a common treatment error in emergency settings 1, 8
• Laryngeal attacks are potentially life-threatening with historical mortality rates of approximately 30% or higher, requiring immediate medical attention 1, 5
• In the emergency department, acute airway angioedema should initially be treated with anaphylactic protocols (airway management, epinephrine, antihistamines, steroids) 8
• If standard treatment is ineffective despite proper dosing, bradykinin-induced angioedema should be considered and treated with specific therapies 8
• For moderate to severe HAE attacks that negatively affect activities of daily living, treatment should be administered as soon as possible, ideally within 8 hours of attack onset 4
• The appearance of angioedema following long-term treatment with ACE inhibitors does not lessen the probability that such an agent could be the cause 2

Diagnostic Workup for Recurrent Angioedema

• Measure C4, C1INH antigen, and C1INH function to exclude C1INH deficiency 1
• If acquired C1INH deficiency is suspected based on age of symptom onset, C1q level and anti-C1INH antibodies should be measured 1
• For patients with suspected HAE with normal C1 inhibitor, targeted genetic screening may be necessary to identify pathogenic variants 1