What is the treatment for angioedema?

Treatment of Angioedema

For acute attacks of hereditary angioedema (HAE), the first-line treatments are plasma-derived C1 inhibitor (C1INH), icatibant (a bradykinin B2 receptor antagonist), or ecallantide (a plasma kallikrein inhibitor), which should be administered as early as possible in an attack. 1

Types of Angioedema and First-Line Treatments

Hereditary Angioedema (HAE)

• HAE presents with recurrent episodes of non-pruritic, non-pitting angioedema involving extremities, abdomen, genitourinary tract, face, oropharynx, or larynx 1
• Standard angioedema treatments (epinephrine, corticosteroids, antihistamines) are NOT effective for HAE 1
• First-line treatments for acute attacks include:
  • Plasma-derived C1INH (20 U/kg IV) 1
  • Icatibant (30 mg subcutaneously in the abdomen; may repeat at 6-hour intervals if needed, maximum 3 injections in 24 hours) 2
  • Ecallantide (plasma kallikrein inhibitor) 1
• On-demand treatment is most effective when administered early in an attack 1

ACE Inhibitor-Associated Angioedema

• Discontinuation of the ACE inhibitor is the cornerstone of therapy 1
• Antihistamines, corticosteroids, and epinephrine have not been shown to be efficacious 1
• Icatibant and fresh frozen plasma have been described as potentially effective, though no controlled studies have been reported 1
• Patients may continue to experience angioedema for weeks to months after discontinuation 3

Histaminergic Angioedema

• Responds to antihistamines, corticosteroids, and epinephrine 4, 3
• Often accompanied by urticaria but can present as isolated angioedema in approximately 20% of cases 3

Management of Severe and Life-Threatening Angioedema

Oropharyngeal and Laryngeal Attacks

• These are medical emergencies requiring immediate attention 1
• All patients experiencing oropharyngeal or laryngeal attacks should be observed in a medical facility capable of performing intubation or tracheostomy 1
• Monitor closely for signs of impending airway closure:
  • Change in voice
  • Loss of ability to swallow
  • Difficulty breathing 1
• Direct visualization of the airway should be avoided as it may worsen angioedema 1
• If signs of impending airway closure develop, consider elective intubation 1
• Immediate availability of backup tracheostomy is necessary if intubation is unsuccessful 1

Abdominal Attacks

• Require symptomatic treatment:
  • Pain control (narcotic medications may be needed)
  • Antiemetics for nausea and vomiting
  • Aggressive hydration for third-space sequestration of fluid 1
• Caution regarding narcotic addiction risk in patients with frequent attacks 1
• Out-of-hospital use of potent narcotics (fentanyl patches, oxycodone) should be avoided 1

Alternative Treatments When First-Line Options Are Unavailable

• Fresh frozen plasma (FFP) can be used if first-line treatments are not available 1
  • Typically administered as 10-15 ml/kg 1
  • Generally effective but carries risks:
    • May occasionally cause sudden worsening of symptoms
    • Carries inherent risk of viral transmission
    • Transfusion reactions including anaphylaxis have been reported 1
• The decision to use FFP should balance potential benefits against potential harms 1

Prophylactic Treatment Options

Short-term Prophylaxis

• Indicated before procedures likely to trigger HAE attacks (e.g., dental work, invasive medical/surgical procedures) 1
• Options include:
  • C1INH replacement (1000-2000 U or 20 U/kg for children) 1
  • Fresh frozen plasma (2 units or 10 ml/kg for children) administered several hours up to 12 hours before the procedure 1

Long-term Prophylaxis

• Consider for patients with frequent or severe attacks 1
• Options include:
  • Plasma-derived C1INH (starting dose 1000 U every 3-4 days, adjusted based on response) 1
  • 17α-alkylated androgens (efficacy is dose-related, use lowest effective dose) 1
  • Antifibrinolytic drugs (less effective than other options) 1

Important Caveats and Pitfalls

• Standard angioedema treatments (antihistamines, corticosteroids, epinephrine) are ineffective for bradykinin-mediated angioedema like HAE 1
• Delay in appropriate treatment of laryngeal attacks can lead to asphyxiation and death 1
• Abdominal attacks can mimic acute abdomen, leading to unnecessary surgical interventions 1
• When using FFP, be prepared for potential paradoxical worsening of symptoms 1
• Patients with HAE should have an established emergency plan for severe attacks 1