What is the treatment for angioedema?

Treatment of Angioedema

Treatment of angioedema depends critically on identifying the underlying mechanism—histamine-mediated versus bradykinin-mediated—because standard allergy treatments (epinephrine, antihistamines, corticosteroids) are completely ineffective for bradykinin-mediated forms and waste critical time in life-threatening situations. 1, 2

Immediate Airway Assessment (All Types)

Assess for airway compromise immediately as the first critical step in any patient presenting with angioedema. 2, 3

• Examine for oropharyngeal or laryngeal involvement by checking for voice changes, difficulty swallowing, stridor, or respiratory distress 2, 3
• Monitor patients with oropharyngeal or laryngeal involvement in a facility capable of performing emergency intubation or tracheostomy 2, 3
• Consider elective intubation early if signs of impending airway closure develop—do not wait for complete obstruction 2, 3
• Laryngeal attacks carry historical mortality rates approaching 30% without proper treatment 2, 3

Determine Angioedema Type

The presence or absence of urticaria is the key clinical distinguishing feature: 4

Histamine-Mediated (Allergic) Angioedema

• Accompanied by urticaria, pruritus, and often occurs in context of anaphylaxis 3, 4
• Responds to standard allergy treatments 3, 4

Bradykinin-Mediated Angioedema

• No urticaria or pruritus present 3, 4
• Includes hereditary angioedema (HAE), acquired C1 inhibitor deficiency, and ACE inhibitor-induced angioedema 1, 4
• Does NOT respond to antihistamines, corticosteroids, or epinephrine 1, 2

Treatment by Type

Histamine-Mediated Angioedema

Administer intramuscular epinephrine (0.3 mL of 0.1% solution) immediately for significant symptoms or any airway involvement. 2, 3

• Give IV diphenhydramine 50 mg plus IV methylprednisolone 125 mg as adjunctive therapy 2
• Add H2 blockers such as ranitidine 50 mg IV or famotidine 20 mg IV 2
• For chronic management, use high-dose second-generation H1 antihistamines (fourfold the standard dose), with addition of montelukast if antihistamines alone fail 2

Common pitfall: Delaying epinephrine administration in cases with airway compromise can be fatal 2, 3

Hereditary Angioedema (HAE)

For acute HAE attacks, administer plasma-derived C1 inhibitor concentrate (1000-2000 U intravenously) OR icatibant 30 mg subcutaneously as first-line therapy. 1, 2, 5

• Ecallantide (plasma kallikrein inhibitor) is an alternative first-line option 1
• If specific targeted therapies are unavailable, fresh frozen plasma (10-15 mL/kg) may be considered, though it can occasionally worsen attacks 1, 2
• For icatibant: if response is inadequate or symptoms recur, additional 30 mg injections may be given at intervals of at least 6 hours, with maximum of 3 injections in 24 hours 5
• Patients may self-administer icatibant upon recognition of an HAE attack 5

Critical distinction: Epinephrine, corticosteroids, and antihistamines are NOT efficacious and are NOT recommended for HAE treatment 1

HAE Prophylaxis

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

• Plasma-derived C1 inhibitor (1000-2000 U intravenously) is preferred 1, 2
• Alternative: attenuated androgens (danazol 2.5-10 mg/kg) or tranexamic acid 1, 2

Long-term prophylaxis (for frequent attacks):

• Plasma-derived C1 inhibitor provides effective and safe long-term prophylaxis 1
• Attenuated androgens (danazol 100 mg on alternate days) are effective but require monitoring for hepatotoxicity with blood tests and periodic hepatic ultrasounds 1, 2
• Tranexamic acid (30-50 mg/kg/day) is somewhat effective but generally less effective than androgens 1, 2
• In children, tranexamic acid is preferred for long-term prophylaxis where first-line C1-INH replacement is unavailable 2, 3
• In pregnant patients, C1-INH is the only recommended acute and prophylactic treatment 2

Adjunctive strategies: Avoid ACE inhibitors, avoid estrogen therapy when feasible, and implement stress reduction 1

Acquired C1 Inhibitor Deficiency

Treatment is similar to HAE with important differences: 1

• Acute attacks: C1INH replacement therapy, ecallantide, or icatibant 1
• Patients with high levels of C1INH autoantibodies may be resistant to C1INH replacement therapy 1
• Antifibrinolytic drugs (tranexamic acid) are MORE effective than in HAE 1
• Androgens are LESS effective than in HAE 1
• Treat underlying disease (lymphoma, monoclonal gammopathy) as this may lead to remission 1
• For autoantibody-positive patients, consider rituximab, plasmapheresis, cyclophosphamide, or high-dose intravenous immunoglobulin 1

ACE Inhibitor-Induced Angioedema

Immediately and permanently discontinue the ACE inhibitor—this is the cornerstone of therapy. 1, 6

• Observe in a controlled environment capable of emergency intubation, as there may be significant time lag between drug discontinuation and resolution of angioedema propensity 1
• Icatibant (30 mg subcutaneously) has described efficacy for acute attacks, though no controlled studies exist 1, 6
• Fresh frozen plasma has described efficacy but lacks controlled trial support 1, 6
• Antihistamines, corticosteroids, and epinephrine have NOT been shown to be efficacious 1

Switching to ARBs: Most patients who experienced ACE inhibitor-induced angioedema can safely use ARBs without recurrence, though a modest risk (2-17%) of recurrent angioedema exists 1, 6

Risk factors for ACE inhibitor-induced angioedema: African American race (substantially higher risk), smoking, increasing age, female sex 1

Symptomatic Management (All Types)

• Provide aggressive IV hydration for abdominal attacks 2, 3
• Administer antiemetics for nausea/vomiting 2, 3
• Give appropriate analgesia for pain control, but avoid creating narcotic dependence in patients with frequent attacks 3

Observation and Disposition

• Observe until symptoms have significantly improved before discharge 3
• Extended observation is mandatory for laryngeal attacks given the high mortality risk 2, 3
• Never discharge patients with oropharyngeal or laryngeal involvement without adequate observation 2, 3

Critical Pitfalls to Avoid

• Never use standard allergy treatments (epinephrine, corticosteroids, antihistamines) for confirmed or suspected bradykinin-mediated angioedema—they are completely ineffective and waste critical time 1, 2, 6, 3
• Never delay epinephrine in histamine-mediated angioedema with airway involvement 2, 3
• Never prescribe ACE inhibitors to patients with any form of angioedema, especially HAE 3
• Avoid direct visualization of the airway unless absolutely necessary, as trauma can worsen angioedema 3