What is the treatment for angioedema?

Treatment of Angioedema

First-line treatment for angioedema should be with specific targeted therapies including plasma-derived C1 inhibitor, icatibant (bradykinin B2 receptor antagonist), or ecallantide (plasma kallikrein inhibitor), as these have been shown to be safe and efficacious for acute angioedema attacks. 1

Types of Angioedema and Initial Assessment

• Angioedema can be classified as either hereditary angioedema (HAE), acquired C1 inhibitor deficiency, ACE inhibitor-induced, or allergic/histamine-mediated 1
• Assess for airway compromise immediately, as laryngeal angioedema represents a potentially life-threatening emergency requiring close monitoring in a medical facility capable of performing intubation or tracheostomy 2, 3
• Evaluate for potential triggers such as medications (especially ACE inhibitors), trauma, emotional stress, or hormonal factors 3

Treatment Algorithm Based on Angioedema Type

Hereditary Angioedema (HAE) Attacks:

1. First-line treatments (administer as early as possible in an attack):

   • Plasma-derived C1 inhibitor: 1000-2000 U intravenously 1, 3
   • Icatibant: 30 mg subcutaneously in the abdominal area 1, 3
   • Ecallantide: 30 mg subcutaneously (FDA-approved for HAE patients ≥12 years) 4

2. If first-line treatments unavailable:

   • Fresh frozen plasma (FFP): 10-15 ml/kg, though caution is required as it may occasionally worsen symptoms 1
   • Supportive care for specific symptoms 1

3. For laryngeal attacks:

   • Consider early intubation or tracheostomy if upper airway edema is present 1, 2
   • Observe in a medical facility capable of advanced airway management 2, 3

ACE Inhibitor-Induced Angioedema:

1. Immediate management:

   • Discontinue the ACE inhibitor permanently 2
   • Consider bradykinin pathway-targeted therapies such as icatibant (30 mg subcutaneously) 2
   • Fresh frozen plasma may be effective in some cases 2

2. Standard treatments have limited efficacy:

   • Antihistamines, corticosteroids, and epinephrine are generally not effective for ACE inhibitor-induced angioedema 2, 3

Histamine-Mediated/Allergic Angioedema:

1. First-line treatment:

   • Non-sedating H1 antihistamines 3
   • Epinephrine for severe cases 5
   • Systemic corticosteroids for moderate to severe cases 3

2. Supportive care:

   • Identify and avoid triggers 3

Symptomatic Management for All Types

• For abdominal attacks: analgesics, antiemetics, and aggressive hydration due to third-space sequestration of fluid 1
• For laryngeal attacks: monitor for signs of impending airway closure (change in voice, loss of ability to swallow, difficulty breathing) 1
• Self-administration of medication should be encouraged when appropriate, as it significantly reduces time to treatment and improves outcomes 1

Important Considerations and Pitfalls

• Standard angioedema treatment modalities (epinephrine, corticosteroids, antihistamines) are NOT effective for HAE or ACE inhibitor-induced angioedema 1
• Early treatment is critical - on-demand treatment is most effective when administered as early as possible in an attack 1
• Patients with HAE should have an established plan in place regarding how to respond to a severe attack 1
• The propensity to develop angioedema can continue for up to 6 weeks after discontinuation of an ACE inhibitor 2
• Avoid direct visualization of the airway unless necessary, as trauma from the procedure can worsen angioedema 2

Prophylaxis for HAE Patients

• Short-term prophylaxis before dental or surgical procedures:

  • Plasma-derived C1 inhibitor: 1000-2000 U intravenously 1, 3
  • Androgens (danazol 2.5-10 mg/kg, maximum 600 mg/day) 5 days before until 2-3 days after the procedure 3

• Long-term prophylaxis for frequent attacks:

  • Androgens (danazol 100 mg on alternate days up to 600 mg/day) 3
  • Antifibrinolytic agents (tranexamic acid 30-50 mg/kg/day in 2-3 divided doses, maximum 3 g/day) 3
  • Plasma-derived C1INH (1000 U every 3 to 4 days) 1