What is the treatment for angioneurotic edema?

Treatment of Angioneurotic Edema

Immediate Airway Assessment is Critical

The first priority in treating angioneurotic edema is immediate assessment for airway compromise, as laryngeal involvement can be life-threatening with historical mortality rates approaching 30%. 1, 2

• Consider elective intubation before complete airway obstruction occurs if the patient exhibits change in voice, loss of ability to swallow, or difficulty breathing 1, 3
• Awake fiberoptic intubation is optimal to reduce risk of worsening edema 3
• Patients with oropharyngeal or laryngeal involvement must be monitored in a facility capable of performing emergency intubation or tracheostomy 1, 2
• Backup tracheostomy equipment should be immediately available if intubation is unsuccessful 1

Determine the Type of Angioedema Immediately

Treatment differs dramatically based on whether the angioedema is histamine-mediated (allergic) versus bradykinin-mediated (hereditary or ACE inhibitor-induced), making rapid differentiation essential. 1, 3

• Obtain medication history immediately, particularly for ACE inhibitors, which are a common cause of bradykinin-mediated angioedema 3
• Check for family history of recurrent angioedema to identify possible hereditary angioedema (HAE) 3
• Recognize that standard allergic treatments (epinephrine, antihistamines, corticosteroids) are completely ineffective for bradykinin-mediated angioedema 1, 2, 3

Treatment Algorithm Based on Angioedema Type

For Histamine-Mediated (Allergic) Angioedema:

Administer epinephrine (0.1%) 0.3 mL subcutaneously or 0.5 mL by nebulizer immediately for significant symptoms or any airway involvement. 1, 2, 3

• Give IV diphenhydramine 50 mg and IV methylprednisolone 125 mg 1, 2
• Add H2 blockers: ranitidine 50 mg IV or famotidine 20 mg IV 1, 2
• Do not delay epinephrine administration in cases of airway compromise 2

For Bradykinin-Mediated Angioedema (Hereditary or ACE Inhibitor-Induced):

First-line treatment is icatibant 30 mg subcutaneously in the abdominal area or plasma-derived C1 inhibitor 1000-2000 U (or 20 IU/kg) intravenously. 1, 2, 3, 4

• Icatibant is FDA-approved for acute HAE attacks in adults ≥18 years 4
• If response is inadequate or symptoms recur, additional icatibant injections may be given at intervals of at least 6 hours, but do not exceed 3 injections in 24 hours 4
• Standard allergic treatments (epinephrine, antihistamines, corticosteroids) are NOT effective and should not be relied upon 1, 2, 3
• Fresh frozen plasma (10-15 mL/kg) may be considered only if specific targeted therapies (icatibant or C1 inhibitor) are unavailable 1, 3

For ACE Inhibitor-Induced Angioedema Specifically:

Immediately and permanently discontinue the ACE inhibitor—never restart it. 1, 2, 3

• Administer icatibant 30 mg subcutaneously as bradykinin-targeted therapy 1, 2, 3
• Patients experiencing angioedema with one ACE inhibitor will typically react to others (class effect) 3
• Switching to an ARB carries modest recurrence risk (2-17%), though most patients tolerate ARBs without recurrence 3

Special Consideration for Alteplase-Associated Angioedema:

If angioedema develops after IV alteplase for stroke, discontinue the alteplase infusion immediately, hold ACE inhibitors, and administer IV methylprednisolone 125 mg, IV diphenhydramine 50 mg, and ranitidine 50 mg IV or famotidine 20 mg IV 5, 1

• If angioedema progresses, administer epinephrine (0.1%) 0.3 mL subcutaneously or 0.5 mL by nebulizer, and consider icatibant 30 mg subcutaneously 1
• This is a potential side effect that may cause partial airway obstruction 5

Supportive Care for All Types

• Provide symptomatic treatment including analgesics, antiemetics, and aggressive hydration for abdominal attacks 1, 2
• Monitor vital signs and neurological status closely 1
• Observe patients for appropriate duration based on severity and location of angioedema 1
• Do not discharge patients with oropharyngeal or laryngeal involvement without adequate observation 1, 2

Prophylaxis for Hereditary Angioedema Patients

Short-Term Prophylaxis (Before Dental/Surgical Procedures):

• Administer plasma-derived C1 inhibitor 1000-2000 U intravenously 2, 3
• Alternative options include attenuated androgens (danazol 2.5-10 mg/kg) or tranexamic acid 2

Long-Term Prophylaxis (For Frequent Attacks):

• Options include androgens (danazol 100 mg on alternate days) 2, 3
• Tranexamic acid (30-50 mg/kg/day) should be considered where first-line treatments are unavailable 2
• Regular monitoring for side effects with blood testing and periodic hepatic ultrasounds is required for patients receiving attenuated androgens 2
• Encourage self-administration of medication when appropriate, as it significantly reduces time to treatment 3

Special Populations

Children:

• Tranexamic acid is the preferred drug for long-term prophylaxis where first-line agents are unavailable 2

Pregnant Patients:

• C1-INH is the only recommended acute and prophylactic treatment 1, 2

Elderly Patients:

• Elderly patients demonstrate increased systemic exposure to icatibant, though differences in efficacy and safety between elderly and younger patients have not been identified 4

Critical Pitfalls to Avoid

• Never delay epinephrine in histamine-mediated angioedema with airway compromise 2
• Never use standard allergic treatments (epinephrine, antihistamines, corticosteroids) as primary therapy for bradykinin-mediated angioedema—they are ineffective 1, 2, 3
• Never discharge patients with oropharyngeal or laryngeal involvement prematurely 1, 2
• Avoid direct visualization of the airway unless necessary, as trauma can worsen angioedema 1
• Recognize that African American patients, smokers, older individuals, and females are at higher risk for ACE inhibitor-induced angioedema 1