What is the recommended treatment for chronic recurrent angioedema, specifically hereditary angioedema?

Treatment of Hereditary Angioedema (HAE)

For hereditary angioedema, the recommended treatment approach includes both on-demand therapy for acute attacks and prophylactic therapy to prevent attacks, with C1 inhibitor concentrates being the preferred first-line treatment for both acute management and long-term prophylaxis. 1

Diagnostic Approach

Before initiating treatment, proper diagnosis is essential:

1. Confirm recurrent angioedema without hives

   • Document episodes with photos or imaging
   • For abdominal attacks, obtain imaging during attacks to confirm bowel wall edema
   • Collect detailed family and medication history

2. Laboratory testing

   • Measure C4, C1INH antigen, and C1INH function
   • Normal C1INH levels with recurrent angioedema suggest HAE with normal C1INH (HAE-nC1INH)
   • Consider genetic testing for known HAE pathogenic variants

Treatment Strategy

Acute Attack Management

• First-line: C1 inhibitor concentrates - Rapidly halt attack progression, reducing symptom severity and duration 1
• Alternative options:
  • Bradykinin B2 receptor antagonist (icatibant)
  • Plasma kallikrein inhibitor (ecallantide)
  • Fresh frozen plasma (if specific HAE medications unavailable, though may occasionally worsen attacks) 1

Long-term Prophylaxis

Treatment selection should be based on attack frequency, severity, and impact on quality of life:

1. First-line: Plasma-derived C1 inhibitor

   • Most effective and safe option 1
   • Preferred during pregnancy (androgens contraindicated) 1

2. Second-line: Attenuated androgens (Danazol)

   • Starting dose: 200 mg 2-3 times daily
   • After favorable response, decrease by 50% or less at 1-3 month intervals
   • If attack occurs, may increase daily dose by up to 200 mg 2
   • Effective by increasing levels of deficient C1 esterase inhibitor 2, 3
   • Limitations: contraindicated in pregnancy, potential androgenic side effects

3. Third-line: Antifibrinolytic agents (tranexamic acid)

   • Less effective than androgens but relatively safe 1
   • May be particularly effective in certain genetic variants 1

Special Considerations

Pregnancy

• Avoid androgens - contraindicated due to risk of fetal harm
• Use plasma-derived C1INH - preferred option during pregnancy 1
• Have C1INH available in delivery suite for potential attacks 1

Adjunctive Strategies

• Avoid triggers:
  • ACE inhibitors (can worsen angioedema)
  • Estrogen-containing medications (birth control, HRT)
  • Physical trauma and stress
  • Implement stress reduction techniques 1

HAE with Normal C1INH

• Consider targeted gene sequencing if accessible
• May respond to same treatments as HAE with C1INH deficiency
• Some variants (especially in women) may be estrogen-dependent 1

Monitoring and Follow-up

• Regularly assess attack frequency and severity
• Monitor for treatment side effects, especially with androgens
• Consider screening family members for HAE 1
• Adjust prophylactic therapy based on clinical response rather than laboratory parameters 1

Pitfalls to Avoid

• Do not rely on antihistamines, corticosteroids, or epinephrine - ineffective for HAE 1
• Do not delay treatment of acute attacks - especially those involving the airway
• Avoid assuming all angioedema is histamine-mediated - HAE is bradykinin-mediated
• Do not continue ineffective treatments - if a prophylactic regimen isn't working, switch to another option
• Avoid using androgens in women planning pregnancy - switch to C1INH well before conception

By following this structured approach to diagnosis and treatment, patients with HAE can experience significant reductions in attack frequency and severity, leading to improved quality of life and reduced mortality risk.