What is the management of angioedema (Angioneurotic Edema)?

From the Guidelines

Management of angioedema requires prompt assessment and treatment based on the underlying cause, with the most recent and highest quality study recommending C1 esterase inhibitor concentrates, icatibant, or ecallantide for hereditary angioedema (HAE) attacks 1. For acute episodes, first secure the airway if there's respiratory compromise, as laryngeal edema can be life-threatening.

• For histamine-mediated angioedema (allergic reactions), administer epinephrine 0.3-0.5 mg IM (1:1000 solution) for severe cases, followed by antihistamines (diphenhydramine 25-50 mg IV/PO) and corticosteroids (methylprednisolone 125 mg IV or prednisone 40-60 mg PO).
• For bradykinin-mediated angioedema, such as hereditary angioedema (HAE) or ACE inhibitor-induced angioedema, standard allergic treatments are ineffective, as stated in the study 1. For HAE attacks, specific treatments include:
• C1 esterase inhibitor concentrates (Berinert, Cinryze)
• Icatibant (30 mg SC)
• Ecallantide (30 mg SC), as recommended by the study 1. For ACE inhibitor-induced angioedema, discontinue the offending medication immediately and provide supportive care. Long-term management of HAE includes prophylactic medications like:
• Danazol (200 mg 2-3 times daily)
• Tranexamic acid (1-1.5 g twice daily)
• Regular C1 inhibitor infusions, as mentioned in the study 1. Patient education about trigger avoidance and having rescue medications readily available is essential for all forms of recurrent angioedema. The different treatment approaches reflect the distinct pathophysiological mechanisms:
• Histamine-mediated angioedema involves mast cell degranulation
• Bradykinin-mediated forms result from excessive bradykinin production or reduced breakdown, as explained in the study 1.

From the FDA Drug Label

The safety and efficacy of BERINERT in the treatment of acute abdominal or facial HAE attacks in subjects with hereditary angioedema were demonstrated in a placebo-controlled, double-blind, prospective, multinational, randomized, parallel-group, dose-finding, three-arm, clinical study, referred to as the randomized clinical trial (RCT) The study objectives were to evaluate whether BERINERT shortens the time to onset of relief of symptoms of an abdominal or facial HAE attack compared to placebo and to compare the efficacy of two different doses of BERINERT Subjects were randomized to receive a single 10 IU/kg body weight dose of BERINERT (39 subjects), a single 20 IU/kg dose of BERINERT (43 subjects), or a single dose of placebo (42 subjects) by slow intravenous infusion (recommended to be given at a rate of approximately 4 mL per minute) within 5 hours of an HAE attack

The management of angioedema with BERINERT involves administering a single dose of 10 IU/kg or 20 IU/kg body weight by slow intravenous infusion within 5 hours of an HAE attack 2. The dose of BERINERT can be repeated if there is no relief or insufficient relief of symptoms by 4 hours after infusion. BERINERT has been shown to shorten the time to onset of relief of symptoms of an abdominal or facial HAE attack compared to placebo 2.

• Key points:
  • Administer BERINERT within 5 hours of an HAE attack
  • Use a single dose of 10 IU/kg or 20 IU/kg body weight
  • Repeat the dose if necessary
  • Monitor for adverse events for up to 7 to 9 days after administration 2

From the Research

Management of Angioedema

• Angioedema is a self-limiting edema of the subcutaneous or submucosal tissues due to localized increase of microvascular permeability whose mediator may be histamine or bradykinin 3.
• The management of angioedema involves initial evaluation of consciousness and vital signs to manage breathing and to support circulation if necessary, followed by a simple approach for a correct diagnosis and treatment 3.
• Forms of edema such as anasarca, myxedema, superior vena cava syndrome, and acute dermatitis should be ruled out, and an effort should be made to differentiate histaminergic from non-histaminergic angioedema 3.

Diagnosis and Treatment

• Concomitant urticaria and pruritus suggest a histaminergic origin, while exposure to allergens and drugs (mainly ACE inhibitors and non-steroidal anti-inflammatory drugs) should be investigated, as well as a family history of similar symptoms 3.
• Allergic histaminergic angioedema has a rapid course (minutes), whereas non-histaminergic angioedema is slower (hours) 3.
• Therapeutic options for angioedema due to C1-inhibitor deficiencies are C1-inhibitor concentrates, icatibant, and ecallantide, while fresh frozen plasma can be considered if these drugs are not available 3.
• Histamine-mediated angioedema should be treated with epinephrine intramuscularly, antihistaminergic medications, and steroids, whereas bradykinin-mediated angioedema does not respond to these treatments 4.

Specific Treatments

• C1-INH protein replacement, kallikrein inhibitor, and bradykinin receptor antagonists are other medications used to treat angioedema, although evidence is controversial concerning their efficacy in acute episodes 4.
• Airway management is the most important intervention when indicated, and airway intervention may require fiberoptic or video laryngoscopy, with preparation for cricothyrotomy 4.
• The efficacy of treatment of ACEI-induced angioedema with bradykinin antagonists, kallikrein inhibitor, and C1 inhibitor warrants further study, although consistent benefit of these medications has not been demonstrated 5.

Disposition and Follow-up

• Disposition is dependent on the patient's airway and respiratory status, as well as the sites involved 4.
• ED physicians must be aware of the different pathophysiologic pathways that lead to angioedema in order to efficiently and effectively manage these potentially fatal conditions 6.
• New medications that correct imbalances in the kallikrein-kinin system may prove safe and efficacious in the treatment of ACEI-induced angioedema 7.