What is the recommended treatment for hereditary angioedema?

Treatment of Hereditary Angioedema

For hereditary angioedema (HAE), the recommended first-line treatment for acute attacks is plasma-derived C1 inhibitor concentrate (pdC1INH) administered intravenously at a dose of 1000-2000 U. 1, 2

Acute Attack Management

• Plasma-derived C1 inhibitor concentrate (pdC1INH) is the most effective first-line treatment for acute HAE attacks, administered at a dose of 1000-2000 U intravenously 2
• Alternative first-line treatments include icatibant (30 mg subcutaneously), a bradykinin B2 receptor antagonist, approved for treatment of HAE attacks in adults 3, 4
• Ecallantide (plasma kallikrein inhibitor) and recombinant human C1INH concentrate (rhC1INH) are also effective for acute attacks, though ecallantide must be administered by a healthcare professional due to anaphylaxis risk 5
• Early treatment is critical - administering treatment as soon as possible during an attack significantly reduces duration and severity of symptoms 1, 2
• Standard angioedema treatments (antihistamines, corticosteroids, epinephrine) are NOT effective for HAE and should not be used as first-line treatment 1, 2

Treatment Based on Attack Location

• Laryngeal attacks require immediate treatment and observation in a medical facility capable of performing intubation or tracheostomy if necessary 2, 3
• Abdominal attacks should be treated promptly with HAE-specific therapy and may require supportive care including analgesics, antiemetics, and hydration 3
• Peripheral attacks (extremities, face) should also receive prompt treatment rather than a "wait-and-see" approach, as early intervention prevents avoidable pain and reduces disruption to the patient's life 5

Prophylactic Treatment

Short-Term Prophylaxis

• Indicated before dental work, surgical procedures, or invasive medical procedures 2
• First-line option is plasma-derived C1INH at a dose of 1000-2000 U intravenously 1, 2
• When first-line therapy is unavailable, alternatives include attenuated androgens (danazol 2.5-10 mg/kg) or tranexamic acid 1

Long-Term Prophylaxis

• Consider for patients with frequent or severe attacks 2
• First-line options include plasma-derived C1INH and lanadelumab 2
• Second-line options include attenuated androgens (danazol 100 mg on alternate days) and antifibrinolytic agents (tranexamic acid 30-50 mg/kg/day) 1, 2
• Anabolic androgens should be initiated at either high or low dose and then slowly titrated to the lowest effective dose 2

Special Populations

Children

• Tranexamic acid is the preferred drug for long-term prophylaxis in children where first-line agents are unavailable 1, 3
• Fresh frozen plasma should be considered for acute treatment where first-line agents are unavailable 1
• Attenuated androgens may exceptionally be considered but side effect burden is likely to be high 1

Pregnant Patients

• C1-INH is the only recommended acute and prophylactic treatment for pregnant patients with HAE 1, 2
• Anabolic androgens should be discontinued at least 2 months before attempting conception due to risk of fetal abnormalities 2

Self-Administration and Home Treatment

• All patients with HAE should have access to an effective on-demand HAE-specific agent and a contingency plan for management of acute attacks 2
• Self-administration of medication should be encouraged when appropriate, as this allows for earlier treatment 3
• C1INH concentrates and icatibant can be self-administered, while ecallantide requires healthcare professional administration due to anaphylaxis risk 5

Common Pitfalls to Avoid

• Delaying treatment of acute attacks, especially those involving the airway, can lead to increased morbidity and mortality 2
• Using standard angioedema treatments (antihistamines, corticosteroids, epinephrine) for HAE is ineffective and delays appropriate treatment 1, 2
• Discharging patients with oropharyngeal or laryngeal involvement without adequate observation 3
• Failing to recognize that laryngeal attacks are potentially life-threatening with historical mortality rates of approximately 30% 5

Global Access Considerations

• Significant disparities exist in HAE management resources between high-income and low-income countries 5
• In resource-limited settings where first-line treatments are unavailable, fresh frozen plasma (10-15 ml/kg) may be considered for acute attacks 1, 5
• Tranexamic acid and attenuated androgens may be used for prophylaxis in settings where first-line agents are not available 5