What is the initial evaluation and treatment for a patient presenting with angioedema?

Initial Evaluation and Treatment of Angioedema

Immediately assess airway patency and breathing status, as laryngeal involvement can be life-threatening and requires urgent intervention including possible intubation or tracheostomy. 1, 2

Immediate Airway Assessment

• Monitor continuously for signs of impending airway closure: change in voice, loss of ability to swallow, difficulty breathing, or stridor 1
• All patients with oropharyngeal or laryngeal involvement must be observed in a facility capable of performing emergency intubation or tracheostomy 1
• Avoid direct visualization of the airway as trauma from the procedure can worsen angioedema 1
• If signs of impending airway closure develop, proceed with elective intubation by physicians highly skilled in airway management, with immediate backup tracheostomy available 1

Critical Historical Features

• Obtain medication history immediately, specifically asking about ACE inhibitors, ARBs, dipeptidyl peptidase inhibitors, neprilysin inhibitors, tissue plasminogen activators, and NSAIDs 1
• Document presence or absence of urticaria/hives—angioedema WITHOUT hives suggests bradykinin-mediated causes (hereditary angioedema or ACE inhibitor-induced) rather than histamine-mediated 1
• Ask about family history of recurrent angioedema, as this strongly suggests hereditary angioedema 1, 3
• Determine attack characteristics: bradykinin-mediated attacks progress more slowly, last longer (typically days), and more commonly involve the abdomen or require intubation compared to histamine-mediated forms 1

Initial Laboratory Testing

Order C4 level, C1-esterase inhibitor (C1INH) antigen, and C1INH functional activity immediately to exclude hereditary or acquired C1INH deficiency 1, 3, 2

• If acquired C1INH deficiency is suspected (age of onset >40 years), also measure C1q level and anti-C1INH antibodies 1, 3
• Normal C1INH levels do NOT exclude hereditary angioedema with normal C1 inhibitor (HAE-nC1INH), which requires genetic testing 1, 3

Treatment Algorithm Based on Type

For Histamine-Mediated Angioedema (with urticaria/pruritus):

• Administer epinephrine 0.3-0.5 mg intramuscularly immediately 2, 4
• Give H1 antihistamines (up to 4 times standard dose), corticosteroids, and consider H2 blockers 1, 2
• These patients typically respond within hours 4

For Bradykinin-Mediated Angioedema (without urticaria):

Critical pitfall: Epinephrine, antihistamines, and corticosteroids are NOT effective for hereditary angioedema or ACE inhibitor-induced angioedema 1, 2

If Hereditary Angioedema is Suspected or Confirmed:

• First-line treatment: Icatibant 30 mg subcutaneously in the abdomen 2, 5
  • Can repeat at 6-hour intervals if inadequate response or symptom recurrence 5
  • Maximum 3 doses in 24 hours 5
• Alternative: Ecallantide (plasma kallikrein inhibitor) administered by healthcare provider within 8 hours of attack onset 2
• Alternative: Plasma-derived C1 inhibitor concentrate 1000-2000 units intravenously 1, 2

If ACE Inhibitor-Induced Angioedema:

• Discontinue the ACE inhibitor (or ARB) immediately 1, 2
• Understand that swelling can continue for up to 6 weeks after discontinuation 1
• Consider icatibant or ecallantide, as open-label reports suggest benefit, though clinical trials are ongoing 1
• Standard anaphylaxis treatments (epinephrine, antihistamines, corticosteroids) are unreliable 1

Symptomatic Management by Location

Abdominal Attacks:

• Provide narcotic analgesics for severe pain (avoid long-term potent narcotics like fentanyl patches or oxycodone due to addiction risk) 1
• Administer antiemetics for nausea/vomiting 1
• Give aggressive intravenous hydration for third-space fluid sequestration 1

Extremity or Genitourinary Attacks:

• Provide pain medication as needed 1
• Consider urinary catheterization if patient cannot urinate 1

Common Pitfalls to Avoid

• Do NOT rely on antihistamines, corticosteroids, or epinephrine for bradykinin-mediated angioedema—this is the most common treatment error in emergency settings 2
• Do NOT assume normal C1INH levels exclude hereditary angioedema; HAE with normal C1INH exists and requires genetic testing 1, 3
• Do NOT fail to test C1INH function, as this is essential for diagnosing HAE type 2 3
• Do NOT directly visualize the airway in laryngeal attacks, as instrumentation can worsen swelling 1
• For laryngeal attacks, even after administering icatibant, patients must seek immediate medical attention due to potential mortality 2, 5

Disposition

• Admit all patients with laryngeal or oropharyngeal involvement for airway monitoring 1
• Observation duration should be individualized but generally continues until clear improvement is documented 1
• Patients with abdominal or extremity involvement may be discharged if symptoms are controlled and airway is not threatened 4