What is the treatment for angioedema?

Treatment of Angioedema

Treatment of angioedema depends critically on distinguishing between histamine-mediated (allergic) and bradykinin-mediated (hereditary or ACE inhibitor-induced) forms, as standard antiallergic therapies are completely ineffective for bradykinin-mediated angioedema. 1, 2

Immediate Airway Assessment (All Types)

• Assess for airway compromise immediately as the first critical step in managing any patient with angioedema 1, 2, 3
• Monitor patients with oropharyngeal or laryngeal involvement in a facility capable of performing intubation or tracheostomy 2, 3
• Consider elective intubation if signs of impending airway closure develop: voice change, inability to swallow, or difficulty breathing 2, 3
• Avoid direct visualization of the airway unless necessary, as trauma can worsen angioedema 2
• Keep backup tracheostomy equipment immediately available if intubation fails 2

Treatment Algorithm Based on Angioedema Type

Histamine-Mediated (Allergic) Angioedema

For allergic angioedema with significant symptoms or airway involvement:

• Administer epinephrine 0.3 mL (0.1%) subcutaneously or 0.5 mL by nebulizer 2, 3
• Give IV diphenhydramine 50 mg and IV methylprednisolone 125 mg 2, 3
• Add H2 blockers: ranitidine 50 mg IV or famotidine 20 mg IV 2, 3
• For chronic management, use high-dose second-generation H1 antihistamines (fourfold the standard dose), adding montelukast if antihistamines alone fail 3

Hereditary Angioedema (HAE) - Bradykinin-Mediated

First-line acute treatment options (choose one):

• Plasma-derived C1 inhibitor: 1000-2000 U intravenously 1, 2, 3
• Icatibant: 30 mg subcutaneously 1, 2, 3
• Ecallantide: 30 mg subcutaneously 1, 4

Critical pitfall: Standard treatments (epinephrine, corticosteroids, antihistamines) are NOT effective for HAE 1, 2, 3, 5

• If specific targeted therapies are unavailable, consider fresh frozen plasma 10-15 mL/kg 2, 3
• Early treatment is critical and most effective when administered as early as possible in an attack 1
• Encourage self-administration of medication when appropriate, as this significantly reduces time to treatment 1

ACE Inhibitor-Induced Angioedema - Bradykinin-Mediated

• Immediately discontinue the ACE inhibitor permanently 1, 2, 3
• Consider icatibant 30 mg subcutaneously as bradykinin pathway-targeted therapy 1, 2, 3
• Standard antiallergic medications (epinephrine, corticosteroids, antihistamines) are ineffective 1, 5
• Higher risk populations include African Americans, smokers, older individuals, and females 2

Prophylaxis for HAE Patients

Short-Term Prophylaxis (Before Dental/Surgical Procedures)

• Plasma-derived C1 inhibitor: 1000-2000 U intravenously 1, 3
• Alternative: Danazol 2.5-10 mg/kg or tranexamic acid 1, 3
• If first-line therapies unavailable, consider attenuated androgens, fresh frozen plasma, or combination 3

Long-Term Prophylaxis (For Frequent Attacks)

• Danazol 100 mg on alternate days 1, 3
• Tranexamic acid 30-50 mg/kg/day 1, 3
• Implement regular monitoring with blood testing and periodic hepatic ultrasounds for patients receiving attenuated androgens 3

Supportive Care (All Types)

• Provide analgesics, antiemetics, and aggressive hydration for abdominal attacks 1, 2
• Monitor vital signs and neurological status closely 2
• Observe patients for appropriate duration based on severity and location of angioedema 2

Special Populations

Children

• Tranexamic acid is the preferred drug for long-term prophylaxis where first-line agents are unavailable 1, 3
• Fresh frozen plasma should be considered for acute treatment and short-term prophylaxis where first-line agents unavailable 3
• Attenuated androgens may exceptionally be considered but side effect burden is likely high 3

Pregnant Patients

• C1-INH is the only recommended acute and prophylactic treatment for pregnant patients with HAE 2, 3

Critical Pitfalls to Avoid

• Never delay epinephrine administration in cases of airway compromise with histamine-mediated angioedema 2, 3
• Never use standard angioedema treatments (epinephrine, corticosteroids, antihistamines) for bradykinin-mediated angioedema—they are completely ineffective 1, 2, 3, 5
• Do not discharge patients with oropharyngeal or laryngeal involvement without adequate observation 2, 3
• Recognize that laryngeal attacks are potentially life-threatening with historical mortality rates of approximately 30% or higher 3
• Avoid narcotic addiction risk in HAE patients who experience frequent attacks 2
• Do not miss ACE inhibitor-induced angioedema—this relationship is often underestimated and can occur even after long-term treatment 6, 7