Treatment of Hereditary Angioedema

Introduction to Hereditary Angioedema

• Hereditary angioedema (HAE) typically presents with episodic attacks of swelling rather than continuous daily swelling, and abdominal attacks can cause severe pain, nausea, vomiting, and fluid sequestration, while laryngeal attacks can be life-threatening, with a historical mortality rate of 30% 1
• HAE can cause sudden pharyngeal swelling that can be life-threatening and potentially lead to asphyxiation, characterized by sudden onset swelling of the pharynx, larynx, or both, with progressive worsening over 24 hours before gradually resolving over the following 48-72 hours 1

Classification and Diagnosis of Angioedema

• Angioedema can be classified into two main categories: histamine-mediated and bradykinin-mediated, which determine the effectiveness of treatment, with the latter including hereditary angioedema (HAE), acquired C1 inhibitor deficiency, and angioedema associated with ACE inhibitors, and histamine-mediated angioedema usually presents with urticaria (hives) and is often associated with allergen exposure, while bradykinin-mediated angioedema does not present with urticaria 1, 2, 3

Medication Efficacy for Hereditary Angioedema

• Fresh frozen plasma can be used as a treatment option if specific treatments are unavailable, however it may occasionally worsen attacks, according to the American Academy of Allergy, Asthma, and Immunology 1
• Epinephrine, corticosteroids, and antihistamines are not effective for hereditary angioedema (HAE) and other bradykinin-mediated angioedema, and using these standard treatments may lead to poor outcomes, as recommended by the American Academy of Allergy, Asthma, and Immunology 1
• The following treatment options are available for HAE:

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• Icatibant 30 mg subcutaneously in abdominal area (may repeat at 6-hour intervals, not exceeding 3 injections in 24 hours) is recommended for HAE treatment, as recommended by the American Heart Association 1, 5
• Plasma-derived C1 esterase inhibitor (20 IU/kg) is recommended for HAE treatment, as recommended by the American Heart Association 1, 5

Medication Efficacy for Histamine-Mediated Angioedema

• For histamine-mediated angioedema, H1 antihistamines are the first-line treatment, with non-sedating second-generation antihistamines (cetirizine, fexofenadine) often used at 2-4 times the FDA-approved doses for better efficacy, according to the American Academy of Allergy, Asthma, and Immunology 6
• The American Academy of Allergy, Asthma, and Immunology recommends that for post-anaphylaxis management, H1 antihistamine (diphenhydramine every 6 hours for 2-3 days) plus H2 antihistamine (ranitidine twice daily for 2-3 days) should be used 2

Antihistamine Considerations

• First-generation antihistamines can cause significant sedation and cognitive impairment, particularly in elderly patients, according to the American Academy of Allergy, Asthma, and Immunology 6
• Antihistamines should not delay epinephrine administration in anaphylaxis, as this may place patients at increased risk for progression to life-threatening reactions, as stated by the American Academy of Allergy, Asthma, and Immunology 2
• Antihistamines work better as prophylactic treatment than for acute management of established symptoms, as once histamine has bound to receptors, blocking additional binding has limited effect, according to the American Academy of Allergy, Asthma, and Immunology 6

Allergy Testing and Contraception Considerations

• When performing oral food challenges or other allergy testing, antihistamines should be discontinued for the following periods: cetirizine (5-7 days), diphenhydramine (3 days), fexofenadine (3 days), hydroxyzine (7-10 days), and loratadine (7 days), as recommended by the American Academy of Allergy, Asthma, and Immunology 7
• ACE inhibitors can trigger or worsen angioedema and should be avoided 1
• Estrogen-containing contraceptives should be avoided 1, 8
• Safe options for contraception include barrier methods, intrauterine devices, and progestins 8

Pregnancy and Lactation Considerations

• In pregnancy, pdC1INH is the preferred treatment, but FFP can be used if pdC1INH is unavailable, as recommended by the American Academy of Allergy, Asthma, and Immunology 8
• Plasma-derived C1-INH is available in IV and subcutaneous formulations, administered twice weekly, and is the preferred option during pregnancy 1, 8

Patient Education and Emergency Planning

• Patient education on early recognition of attacks, emergency action plans, home access to appropriate medications, and medical alert identification are crucial for managing HAE, as recommended by Clinical Reviews in Allergy and Immunology 4
• The American Academy of Allergy, Asthma, and Immunology recommends that all patients with HAE should have an established emergency plan for responding to laryngeal attacks, and have immediate access to on-demand HAE-specific medications 1
• Early treatment is crucial for pharyngeal attacks to prevent progression to complete airway obstruction 1
• Long-term prophylaxis must be individualized based on attack frequency and severity, location of attacks, access to acute care, comorbid conditions, and patient preference 1
• The American Academy of Allergy, Asthma, and Immunology recommends Cinryze (pdC1INH) for prophylactic therapy, starting with a dose of 1000 U every 3-4 days, adjusted based on response 1
• Cinryze (pdC1INH) significantly reduces attack frequency, making attacks milder and shorter in duration, with a reported reduction of 6.26 attacks per 12 weeks compared to 12.73 with placebo 1