What is the primary treatment for hereditary angioedema?

Primary Treatment for Hereditary Angioedema

For acute HAE attacks, plasma-derived C1 inhibitor concentrate (1000-2000 U intravenously) is the first-line treatment, with icatibant (30 mg subcutaneously) and ecallantide as equally effective alternatives. 1, 2, 3

Acute Attack Management

First-Line On-Demand Treatments

All patients with HAE require access to effective on-demand therapy, as attacks occur even in those on prophylaxis. 4, 3 The following are approved first-line options:

• Plasma-derived C1 inhibitor (pdC1INH): Administer 1000-2000 U (or 20 U/kg in children) intravenously at the earliest sign of an attack. 1, 2, 3 This is FDA-approved for patients aged ≥2 years. 4

• Icatibant: Administer 30 mg subcutaneously for adults ≥18 years. 1, 5 This bradykinin B2 receptor antagonist provides rapid symptom relief. 1

• Ecallantide: Administer as a plasma kallikrein inhibitor for patients ≥12 years, though it requires healthcare professional administration due to anaphylaxis risk. 4, 1, 3

• Recombinant human C1INH (rhC1INH): An alternative C1INH replacement therapy for acute attacks. 4, 2

Critical Timing Principle

Early treatment is paramount—administering therapy at the first sign of symptoms results in milder attacks, more rapid resolution, and shorter duration compared to delayed treatment. 3, 6 The median time to symptom relief with pdC1INH 20 U/kg is 0.5 hours versus 1.5 hours with placebo, with even greater benefit in severe attacks (0.5 vs 13.5 hours). 7

Airway Management Priority

Before any pharmacologic intervention, immediately assess for airway compromise—this is the most critical first step. 1 Patients with oropharyngeal or laryngeal involvement require monitoring in a facility capable of intubation or tracheostomy. 1, 3 Consider elective intubation if the patient exhibits voice changes, inability to swallow, or breathing difficulty. 1

What NOT to Use

Standard angioedema treatments—epinephrine, corticosteroids, and antihistamines—are completely ineffective for HAE attacks and should never be used as first-line therapy. 1, 2, 3 This is a critical pitfall, as HAE is bradykinin-mediated, not histamine-mediated. 1

Prophylactic Treatment Strategies

Short-Term Prophylaxis

Before dental work, surgical procedures, or invasive medical interventions, administer pdC1INH (1000-2000 U or 20 U/kg for children) as first-line prevention. 1, 2, 3 Alternative options when first-line therapy is unavailable include attenuated androgens (danazol 2.5-10 mg/kg), tranexamic acid, or fresh frozen plasma. 1, 2

Long-Term Prophylaxis

For patients with frequent or severe attacks, long-term prophylaxis options include:

• First-line: Plasma-derived C1INH or lanadelumab. 2, 3

• Second-line: Attenuated androgens (danazol 100 mg on alternate days, titrated to lowest effective dose) or tranexamic acid (30-50 mg/kg/day). 1, 2, 3

Patients on androgens require regular monitoring with blood tests and periodic hepatic ultrasounds due to side effect burden. 1

Special Population Considerations

Pregnancy

Plasma-derived C1INH is the only recommended treatment for both acute attacks and prophylaxis during pregnancy. 1, 2, 3 Androgens must be discontinued at least 2 months before attempting conception due to teratogenic risk. 3

Children

Tranexamic acid is preferred for long-term prophylaxis in children where first-line agents are unavailable, as androgens carry high side effect burden including effects on growth and development. 1, 2 Fresh frozen plasma may be considered for acute treatment when specific therapies are unavailable. 1, 2

Resource-Limited Settings

When first-line therapies are unavailable, fresh frozen plasma (10-15 mL/kg) may be used for acute attacks, while tranexamic acid and attenuated androgens serve as alternative prophylactic options. 1, 2, 3 Significant global disparities exist in HAE management resources between high-income and low-income countries. 2, 3

Common Clinical Pitfalls

• Delaying treatment of acute attacks, especially airway-involved attacks, increases morbidity and mortality. 3 Laryngeal attacks historically carried approximately 30% mortality. 1, 3

• Using ineffective therapies (antihistamines, corticosteroids, epinephrine) delays appropriate treatment and worsens outcomes. 1, 2, 3

• Premature discharge of patients with oropharyngeal or laryngeal involvement without adequate observation. 1

• Failing to provide home therapy access: Self-administration of pdC1INH or icatibant significantly improves quality of life and enables immediate treatment. 3, 8, 9