What is the treatment for angioedema?

Treatment of Angioedema

The treatment of angioedema depends on its type, with first-line therapies for hereditary angioedema (HAE) including plasma-derived C1 inhibitor, icatibant, or ecallantide, while histamine-mediated angioedema responds to antihistamines, corticosteroids, and epinephrine. 1

Types of Angioedema 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 without hives through clinical history, photos, and imaging evidence to differentiate true angioedema from factitious angioedema 2
• Detailed family history and medication history are essential, with special attention to ACE inhibitors which can precipitate attacks by decreasing bradykinin catabolism 2

Treatment Algorithm Based on Angioedema Type

Histamine-Mediated Angioedema

• First-line treatment includes high-dose second-generation H1 antihistamines (fourfold the standard dose), with addition of montelukast if antihistamines alone fail 2
• If unresponsive to antihistamines plus montelukast, a course of omalizumab (4-6 months) is recommended, as most cases of mast cell-mediated angioedema respond well to this treatment 2

Bradykinin-Mediated Angioedema (HAE)

• For acute HAE attacks, first-line treatments include:
  • Plasma-derived C1 inhibitor (20 International Units per kg body weight) administered intravenously 3
  • Icatibant (30 mg subcutaneously) 1
  • Ecallantide (administered by healthcare provider within 8 hours of attack onset) 2
• Early treatment is critical, with on-demand treatment most effective when administered as early as possible in an attack 1, 4
• For ACE inhibitor-induced angioedema, immediate discontinuation of the ACE inhibitor is essential, with consideration of bradykinin pathway-targeted therapies such as icatibant 1, 5

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, 6
• Laryngeal attacks are potentially life-threatening with historical mortality rates of approximately 30% or higher, requiring immediate medical attention following self-administration of medication 2
• Abdominal attacks can cause severe pain, intractable nausea, vomiting, and third-space fluid sequestration leading to hypotension, often resulting in unnecessary surgical interventions if misdiagnosed 2

Prophylaxis for HAE Patients

• Short-term prophylaxis before dental or surgical procedures includes plasma-derived C1 inhibitor (1000-2000 U intravenously) and androgens (danazol) 1
• Long-term prophylaxis is recommended for patients with frequent attacks, with options including:
  • Androgens (danazol 100 mg on alternate days) 1
  • Antifibrinolytic agents (tranexamic acid 30-50 mg/kg/day) 1, 7
• Patients with HAE should have an established plan for responding to severe angioedema attacks, including self-administration of medication when appropriate 2, 1

Diagnostic Workup for Recurrent Angioedema

• Measure C4, C1INH antigen, and C1INH function to exclude C1INH deficiency 2
• If acquired C1INH deficiency is suspected based on age of symptom onset, C1q level and anti-C1INH antibodies should be measured 2
• For patients with suspected HAE with normal C1 inhibitor, targeted genetic screening may be necessary to identify pathogenic variants 2