What are the treatment options for C1 esterase deficiency, also known as Hereditary Angioedema (HAE)?

Treatment Options for C1 Esterase Deficiency (Hereditary Angioedema)

Plasma-derived C1 inhibitor (C1-INH) replacement therapy is the most effective and safe treatment for both acute attacks and long-term prophylaxis of hereditary angioedema. 1

Acute Attack Management

First-line treatments for acute HAE attacks:

• C1-INH concentrates: 20 IU/kg IV 1, 2
  • Onset of relief typically within 30 minutes (19.8 minutes for abdominal attacks, 28.2 minutes for facial attacks) 3
  • Complete resolution within approximately 11 hours 3
• Icatibant (bradykinin B2 receptor antagonist): 30 mg subcutaneously in abdominal area 4
  • May repeat at 6-hour intervals (maximum 3 injections in 24 hours)
• Ecallantide (plasma kallikrein inhibitor) 1

Important considerations for acute attacks:

• Airway involvement requires immediate attention - consider early elective intubation if signs of impending airway closure develop 4
• Conventional treatments are ineffective - epinephrine, corticosteroids, and antihistamines are not efficacious and not recommended 1
• Fresh frozen plasma can be used if specific HAE medications are unavailable, but caution is required as it may exacerbate some attacks 1
• Self-administration is appropriate for appropriately trained patients upon recognition of an HAE attack 2

Prophylactic Treatment

Long-term prophylaxis options:

1. Plasma-derived C1-INH (first-line) 1, 4

   • Available in IV and subcutaneous formulations
   • Administered twice weekly
   • Preferred option during pregnancy 1

2. Anabolic androgens (e.g., danazol 100-600 mg daily) 1, 4

   • Effective and relatively safe for many patients
   • Lower cost compared to newer agents
   • Contraindications: pregnancy, breast cancer, childhood, liver disease 1
   • Monitor for virilization, liver dysfunction, lipid abnormalities

3. Antifibrinolytic agents (e.g., tranexamic acid 30-50 mg/kg/day) 1, 4

   • Less effective than androgens but safer profile
   • Option when C1-INH and androgens are contraindicated
   • Particularly useful in acquired C1-INH deficiency 1

4. Lanadelumab - newer option for long-term prophylaxis 4, 5

Short-term prophylaxis (before procedures):

• Plasma-derived C1-INH (preferred) 1
• Fresh frozen plasma (if C1-INH unavailable) 1
• Short-term high-dose anabolic androgens 1

Special Populations

Pregnancy:

• Attacks may increase in frequency and severity 1
• Anabolic androgens are contraindicated 1
• Plasma-derived C1-INH is the preferred treatment 1
• Consider prophylaxis before delivery, especially with forceps/vacuum extraction or cesarean section 1
• Regional anesthesia preferred over endotracheal intubation 1

Women of reproductive age:

• Avoid estrogen-containing contraceptives 1, 4
• Safe options include barrier methods, intrauterine devices, and progestins 1

Acquired C1-INH deficiency:

• Treatment approach similar to HAE but with key differences 1:
  • Increased efficacy of antifibrinolytics
  • Decreased efficacy of C1-INH replacement
  • Need to treat underlying conditions (e.g., lymphoma)

Adjunctive Strategies

• Avoid ACE inhibitors - can trigger or worsen angioedema 1, 4
• Avoid estrogen therapy when possible 1
• Stress reduction techniques 1
• Patient education on early recognition of attacks 4
• Emergency action plans and medical alert identification 4

Treatment Decision Algorithm

1. Assess attack severity and location:

   • Laryngeal involvement: Immediate treatment and medical attention
   • Facial/abdominal/peripheral: Prompt treatment

2. For acute attacks:

   • Administer C1-INH concentrate 20 IU/kg IV
   • Alternative: icatibant 30 mg SC or ecallantide

3. For prophylaxis decision:

   • Consider frequency and severity of attacks
   • Impact on quality of life
   • Access to acute care
   • Comorbid conditions

4. Prophylaxis selection:

   • First choice: Plasma-derived C1-INH
   • If unavailable/contraindicated: Consider anabolic androgens (if not pregnant/no contraindications)
   • If both unavailable: Antifibrinolytic agents

Human C1-INH replacement provides the most physiologic approach to treatment by directly addressing the underlying deficiency, making it the cornerstone of both acute and prophylactic management of hereditary angioedema.