What is the recommended treatment for a patient with angioedema?

Angioedema Treatment

Immediately assess for airway compromise and differentiate between histamine-mediated and bradykinin-mediated angioedema, as treatments are completely different and using the wrong approach wastes critical time and can be fatal. 1

Immediate Airway Assessment

• Evaluate for signs of impending airway closure immediately: change in voice, loss of ability to swallow, difficulty breathing, or stridor. 1, 2
• Consider elective intubation before complete obstruction occurs if any of these warning signs are present, as delayed intubation becomes exponentially more difficult. 1, 2
• Patients with oropharyngeal or laryngeal involvement must be monitored in a facility capable of performing emergency intubation or tracheostomy. 1, 2
• Avoid direct visualization of the airway unless absolutely necessary, as instrumentation trauma can worsen angioedema. 1
• Have backup tracheostomy equipment immediately available if intubation is unsuccessful. 1

Rapid Clinical Differentiation: Critical First Step

The presence or absence of urticaria determines your treatment pathway:

Histamine-Mediated Angioedema (with urticaria/pruritus):

• Approximately 50% of cases present with concurrent urticaria. 1, 3
• Responds to antihistamines, corticosteroids, and epinephrine. 1, 2
• Often triggered by foods, medications, or insect stings. 3

Bradykinin-Mediated Angioedema (no urticaria/pruritus):

• Antihistamines, corticosteroids, and epinephrine are completely ineffective and waste critical time. 1, 2, 4
• Includes hereditary angioedema (HAE), ACE inhibitor-induced angioedema, and acquired C1-inhibitor deficiency. 5, 6
• Obtain medication history immediately—ACE inhibitors account for up to one-third of emergency department angioedema presentations. 5

Treatment Based on Type

For Histamine-Mediated Angioedema (with urticaria):

Immediate pharmacotherapy:

• Administer epinephrine (0.1%) 0.3 mL intramuscularly immediately for significant symptoms or any airway involvement. 1, 2, 7
• Give IV diphenhydramine 50 mg. 1, 2
• Give IV methylprednisolone 125 mg. 1, 2
• Add H2 blocker: ranitidine 50 mg IV or famotidine 20 mg IV. 1, 2

Common pitfall: Delaying epinephrine administration while waiting to see if symptoms progress—this is dangerous. 1

For Bradykinin-Mediated Angioedema (no urticaria):

First-line specific therapies:

• Plasma-derived C1 inhibitor concentrate 1000-2000 U (or 20 IU/kg) intravenously is the preferred treatment for hereditary angioedema. 8, 1, 2
• Icatibant 30 mg subcutaneously (selective bradykinin B2 receptor antagonist) is equally effective. 1, 2
• Fresh frozen plasma 10-15 mL/kg may be considered if specific targeted therapies are unavailable. 1, 2

Critical action for ACE inhibitor-induced angioedema:

• Discontinue the ACE inhibitor permanently and immediately. 8, 1, 2
• Consider icatibant 30 mg subcutaneously for severe or progressive cases. 1, 2
• Symptoms can recur for weeks to months after ACE inhibitor discontinuation. 6
• Never substitute an ARB—the safety is uncertain and cross-reactivity can occur. 8

What NOT to do:

• Do not give antihistamines, corticosteroids, or epinephrine for bradykinin-mediated angioedema—they are completely ineffective. 1, 2, 4
• This is the most common and dangerous error in angioedema management. 1, 2

Supportive Care for All Types

• Provide aggressive IV hydration for abdominal attacks due to third-space fluid sequestration. 1, 2
• Give antiemetics for nausea/vomiting. 1, 2
• Provide appropriate analgesia, but avoid creating narcotic dependence in patients with frequent attacks. 1, 2
• Monitor vital signs and neurological status continuously. 1

Observation and Disposition

• Extended observation is mandatory for oropharyngeal or laryngeal involvement—historical mortality rates for untreated laryngeal attacks approach 30%. 1, 2
• Duration of observation should be based on severity and location of angioedema. 1
• Do not discharge patients with airway involvement until symptoms have significantly improved. 2, 9

Diagnostic Workup (After Stabilization)

For angioedema without urticaria:

• Check C4 level first as a screening test. 1, 6
• If C4 is low, measure C1 inhibitor level and function. 1, 6
• C1q level distinguishes hereditary (normal C1q) from acquired C1 inhibitor deficiency (low C1q). 9
• Consider targeted gene sequencing for HAE with normal C1 inhibitor if clinical suspicion remains high. 1, 6

Prophylaxis for Hereditary Angioedema Patients

Short-term prophylaxis (before dental/surgical procedures):

• Plasma-derived C1 inhibitor 1000-2000 U intravenously is first-line. 8, 2
• Risk of angioedema after dental extraction is 21.5% and after non-dental surgical procedures is 5.7% without prophylaxis. 2

Long-term prophylaxis (for frequent attacks):

• Androgens (danazol 100 mg on alternate days, titrated to lowest effective dose). 2
• Tranexamic acid 30-50 mg/kg/day as alternative. 2
• Regular monitoring with blood tests and periodic hepatic ultrasounds required for patients on androgens. 2

Special Populations

Children:

• Tranexamic acid is the preferred long-term prophylaxis where first-line C1-INH replacement is unavailable. 2, 9
• Attenuated androgens carry high side effect burden in children. 2, 9

Pregnant patients:

• C1-INH is the only recommended treatment for both acute attacks and prophylaxis during pregnancy. 2
• Attenuated androgens are contraindicated. 2