What is the treatment for angioedema?

Treatment of Angioedema

The treatment of angioedema must be tailored to the specific type: histamine-mediated angioedema responds to antihistamines, corticosteroids, and epinephrine, while bradykinin-mediated angioedema requires targeted therapies such as C1 esterase inhibitor, icatibant, or fresh frozen plasma. 1

Classification and Initial Assessment

Angioedema can be classified into two main types:

1. Histamine-mediated angioedema:

   • Usually presents with urticaria (hives)
   • Often associated with allergen exposure
   • Common triggers: food allergens, medications, insect stings 2

2. Bradykinin-mediated angioedema:

   • Does not present with urticaria
   • Includes:
     • Hereditary angioedema (HAE)
     • Acquired C1 inhibitor deficiency
     • ACE inhibitor-associated angioedema 1, 3

Emergency Management

Airway Assessment (Priority)

• Early elective intubation if signs of airway compromise develop
• Higher risk factors for intubation: edema involving larynx, palate, floor of mouth, or oropharynx with rapid progression (within 30 min)
• Maintain oxygen saturation above 92%
• Be prepared for emergency tracheotomy if intubation fails 1

Treatment Based on Type

For Histamine-Mediated Angioedema:

• H1 antihistamines (e.g., diphenhydramine 50 mg IV)
• Corticosteroids (e.g., methylprednisolone 125 mg IV)
• Epinephrine for severe cases or laryngeal involvement 1, 2

For Bradykinin-Mediated Angioedema (HAE, Acquired C1-INH deficiency, ACE inhibitor-induced):

• First-line treatments:

  • Icatibant 30 mg subcutaneously (may repeat at 6-hour intervals, not exceeding 3 injections in 24 hours) 1, 4
  • Plasma-derived C1 esterase inhibitor (20 IU/kg) 1

• Alternative therapy (when first-line treatments unavailable):

  • Fresh frozen plasma (10-15 ml/kg) - note: may potentially worsen some attacks due to additional contact system substrates 5, 1

• Important: Epinephrine, corticosteroids, and antihistamines are not efficacious for bradykinin-mediated angioedema 5, 6

Specific Management for ACE Inhibitor-Induced Angioedema

• Immediate discontinuation of the ACE inhibitor
• Lifetime discontinuation of all renin-angiotensin inhibitors may be warranted 1
• Consider icatibant for acute attacks 7

Long-Term Prophylaxis (for recurrent angioedema)

Decision factors for prophylaxis:

• Attack frequency and severity
• Impact on quality of life
• Access to acute care
• Comorbid conditions 1

Options include:

1. Plasma-derived C1INH replacement (starting dose of 1000 U every 3-4 days, adjustable based on response) 5
2. Lanadelumab 1
3. Attenuated androgens (lowest effective dose to minimize side effects) 5, 1
4. Antifibrinolytic agents (e.g., tranexamic acid 15-25 mg/kg 2-3 times daily) 5, 1

Special Considerations

Pregnancy

• Androgens are contraindicated
• Plasma-derived C1INH is preferred
• Attacks may increase during pregnancy but typically decrease during delivery
• Risk increases during postpartum period 5, 1

Women with HAE

• Avoid estrogen-containing contraceptives as they can increase attack frequency 5, 1

Common Pitfalls to Avoid

1. Misdiagnosis: Failing to distinguish between histamine and bradykinin-mediated angioedema, leading to ineffective treatment 6

2. Delayed recognition of airway compromise: All patients with oropharyngeal or laryngeal angioedema should be observed in a facility capable of emergency airway management 1

3. Continuing ACE inhibitors: After an episode of angioedema, ACE inhibitors should be discontinued permanently 1, 8

4. Relying on standard angioedema treatments for all types: Standard treatments (antihistamines, corticosteroids, epinephrine) are ineffective for bradykinin-mediated angioedema 5, 6

5. Missing the connection between ACE inhibitors and angioedema: The relationship is often missed because it's not an allergic reaction and can occur after years of use 8