What medications are used to treat reoccurring angioedema?

Medications for Treating Recurrent Angioedema

The treatment of recurrent angioedema should follow a stepwise approach based on the underlying cause, with antihistamines as first-line for histaminergic forms and bradykinin pathway-targeted treatments for non-histaminergic forms. 1

Determining Angioedema Type

Before selecting treatment, it's crucial to identify the type of angioedema:

1. Histaminergic (Mast Cell-Mediated) Angioedema

   • Often accompanied by urticaria (hives)
   • May respond to antihistamines
   • Common causes: allergies, idiopathic

2. Bradykinin-Mediated Angioedema

   • No urticaria
   • Poor response to antihistamines/steroids
   • Types:
     • Hereditary Angioedema (HAE)
     • Acquired C1-Inhibitor Deficiency
     • ACE Inhibitor-Induced Angioedema

Treatment Algorithm for Histaminergic Angioedema

1. First-line: H1 Antihistamines

   • Second-generation non-sedating antihistamines (cetirizine, desloratadine, fexofenadine, loratadine)
   • Up to 4× standard dose for adequate trial period 1
   • Note: High incidence (36%) of antihistamine-refractory cases has been observed 2

2. Second-line: Add Leukotriene Receptor Antagonist

   • Montelukast if antihistamines alone fail 1

3. Third-line: Omalizumab

   • 4-6 month course if unresponsive to high-dose antihistamines plus montelukast
   • Most cases of mast cell-mediated angioedema respond well to omalizumab 3, 1

Treatment for Bradykinin-Mediated Angioedema

Hereditary Angioedema (HAE)

1. Acute Attack Treatment:

   • Icatibant (bradykinin B2 receptor antagonist): 30 mg subcutaneously, can repeat after 6 hours if needed (maximum 3 doses/24 hours) 4
   • C1 Inhibitor Concentrate: For emergency treatment of serious attacks or prophylaxis before surgery 3
   • Fresh frozen plasma: May be used as substitute in emergency if C1 inhibitor not available 3

2. Maintenance/Prophylactic Therapy:

   • Anabolic steroids (e.g., danazol): First choice for most adults but avoid in children 3
   • Tranexamic acid: Alternative maintenance therapy, especially for idiopathic angioedema without weals 3
   • Regular monitoring required for both options (liver function, eye exams) 3

ACE Inhibitor-Induced Angioedema

• Immediate discontinuation of the ACE inhibitor is the cornerstone of therapy 3
• Note that angioedema may persist for weeks after discontinuation 3
• Antihistamines, corticosteroids, and epinephrine have not shown efficacy 3, 5
• Icatibant may be effective but lacks controlled studies 3

Special Considerations

1. Antihistamine-Refractory Cases

   • 40% of patients on antihistamine prophylaxis still suffer from ≥1 attack per month 2
   • Consider bradykinin pathway involvement even without family history

2. Laryngeal Angioedema

   • Life-threatening risk (25-40% mortality if untreated) 6
   • Requires immediate treatment with appropriate medication based on type
   • Airway management may be necessary

3. Documentation and Monitoring

   • Obtain photos or imaging evidence to confirm true angioedema 3
   • Measure C4, C1INH antigen, and C1INH function to exclude C1INH deficiency 3
   • Regular follow-up to assess treatment efficacy

Common Pitfalls to Avoid

• Misdiagnosis: Failing to distinguish between histaminergic and bradykinin-mediated angioedema 5
• Inappropriate treatment: Using steroids and antihistamines for bradykinin-mediated angioedema 5
• Delayed diagnosis: Not considering HAE in recurrent angioedema without urticaria 6
• Medication-induced causes: Not identifying ACE inhibitors or NSAIDs as potential triggers 7

By following this structured approach and selecting medications based on the underlying mechanism, recurrent angioedema can be effectively managed in most patients.