What are the recommended therapies for Type I vs Type II Hereditary Angioedema (HAE)?

Treatment Recommendations for Type I vs Type II Hereditary Angioedema

Both Type I and Type II HAE should be treated with the same therapeutic approaches, as they share the same pathophysiological mechanism of C1 inhibitor dysfunction, with plasma-derived C1 inhibitor concentrate being the first-line therapy for both acute attacks and prophylaxis. 1, 2

Acute Attack Management

• Plasma-derived C1 inhibitor concentrate (1000-2000 U intravenously) is the most effective first-line treatment for acute HAE attacks in both Type I and Type II HAE 1
• Early treatment is critical for both types, with on-demand treatment most effective when administered as early as possible during an attack 1
• Alternative first-line options for acute attacks include:
  • Icatibant (30 mg subcutaneously) 3
  • Ecallantide (plasma kallikrein inhibitor) - must be administered by a healthcare professional due to anaphylaxis risk 1
  • Recombinant human C1INH concentrate (rhC1INH) 1
• Standard angioedema treatments (epinephrine, corticosteroids, antihistamines) are ineffective for both Type I and Type II HAE and should not be used 1, 2

Prophylactic Treatment

Short-Term Prophylaxis

• Indicated before dental work, surgical procedures, or invasive medical procedures for both Type I and Type II HAE 2
• First-line option: Plasma-derived C1INH (1000-2000 U or 20 U/kg for children) 1, 2
• Alternative options when first-line therapy is unavailable:
  • Attenuated androgens (danazol 2.5-10 mg/kg, maximum 600 mg/day) 5 days before until 2-3 days after the procedure 3
  • Fresh frozen plasma (10-15 ml/kg) in resource-limited settings 1
  • Tranexamic acid in resource-limited settings 1

Long-Term Prophylaxis

• Indicated for patients with frequent or severe attacks in both Type I and Type II HAE 2
• First-line options:
  • Plasma-derived C1INH (has shown reduction in attack frequency from median of 3 attacks per month to less than 1 attack per 5 months) 2
  • Lanadelumab 1, 2
• Second-line options:
  • Attenuated androgens (danazol 100 mg on alternate days up to 600 mg/day) - should be titrated to lowest effective dose 2, 3
  • Antifibrinolytic agents (tranexamic acid 30-50 mg/kg/day in 2-3 divided doses, maximum 3g/day) 2, 3

Why the Same Treatments Work for Both Types

• Both Type I and Type II HAE result from mutations in the SERPING1 gene that encodes C1-INH 4
• Type I HAE (85% of cases) is characterized by decreased production of C1-INH, resulting in reduced functional activity to 5-30% of normal 5
• Type II HAE (15% of cases) involves normal or elevated quantities of C1-INH that is dysfunctional 5
• Despite different mechanisms, both types lead to the same end result: insufficient functional C1-INH activity, leading to dysregulated bradykinin production 4
• The clinical presentation and disease course are identical between Type I and Type II HAE, thus requiring the same therapeutic approach 4, 5

Special Considerations

• Pregnancy: Plasma-derived C1INH is the only recommended treatment for both acute attacks and prophylaxis in both Type I and Type II HAE 1, 2
• Children: Fresh frozen plasma and tranexamic acid are preferred for short-term prophylaxis, while tranexamic acid is preferred over androgens for long-term prophylaxis due to concerns about growth and development 2
• Laryngeal attacks: Should be observed in a medical facility capable of performing intubation or tracheostomy if necessary, with close monitoring for signs of impending airway closure 1

Common Pitfalls to Avoid

• Delaying treatment of acute attacks, especially those involving the airway, which can lead to increased morbidity and mortality 1
• Using standard angioedema treatments (antihistamines, corticosteroids, epinephrine) which are ineffective for HAE 1, 2
• Failing to adjust prophylactic dosing based on clinical response rather than laboratory values 2
• Relying on home therapy without proper training and emergency backup plans 6

Global Access Considerations

• Significant disparities exist in HAE management resources between high-income and low-income countries 7
• In resource-limited settings where first-line treatments are unavailable, fresh frozen plasma, tranexamic acid, and attenuated androgens may be used 7, 1