Description

• Angioedema (AE) is acute, localized swelling of skin, mucosa, and submucosa caused by extravasation of fluid into the affected tissues.
• AE develops in minutes to hours and resolves in hours to days but can be life-threatening if the upper airway is involved.
• Two major classifications of AE exist:
  • Histamine- or immune-mediated AE (HIAE) with urticarial
  • Bradykinin-mediated AE without urticaria; both with unique subtypes
• Synonym(s): angioneurotic edema; Quincke edema

Epidemiology

• Predominant age
  • HIAE or idiopathic AE (IAE): any age
  • Hereditary AE (HAE): age of onset infancy to 2nd decade of life
  • Acquired AE (AAE): often patients >40 years
• Predominant gender: male = female (except HAE with normal compliment: women > men)

• AE occurs in 15% of the population over a lifetime.
• AE: 0.1–2.2% of patients receiving angiotensin-converting enzyme (ACE) inhibitors: African Americans have a 4 to 5 times greater risk of ACE inhibitor–induced AE than Caucasians.
• HAE: 1:10,000 to 50,000 population in the United States

Etiology and Pathophysiology

• HIAE with urticarial (1):
  • Allergy to food (shellfish, nuts, eggs, milk, wheat soy), latex, venom, or medication (aspirin, NSAIDs, antibiotics, narcotics, and OCPs)
  • Acute and chronic spontaneous urticaria
  • Other urticarial/AE syndromes: cold urticaria, urticarial vasculitis, exercise-induced urticaria or anaphylaxis, episodic eosinophilia with AE, vibration-induced urticaria
  • IAE
• Bradykinin-mediated AE without urticarial (1):
  • Attacks are triggered by prolonged mechanical pressure, cold, heat, trauma, emotional stress, menses, illness, and inflammation.
  • HAE due to C1 INH deficiency
    • Type I: the most common form, caused by decreased production of C1 esterase inhibitor (C1 INH)
    • Type II: functionally impaired C1 INH
  • HAE with normal C1 INH levels
    • Formerly type III HAE
    • Involves mutations in coagulation factor XII gene, often estrogen dependent, associated with estrogen administration
  • AAE with C1 INH deficiency
    • Rare condition
    • Associated with lymphoproliferative disorders, autoimmune diseases (e.g., lupus)
    • Type I: lack of anti–C1 INH autoantibody
    • Type II: presence of anti–C1 INH autoantibody
  • AE due to medications
    • ACE inhibitors
    • Dipeptidyl peptidase-4 inhibitors
    • Direct renin inhibitor
  • IAE

• HAE types I and II are autosomal dominant, whereas HAE with normal C1 INH is dominant X-linked.
• HAE occurs in 25% of patients as a result of spontaneous genetic mutations.

Risk Factors

• Consuming medications and foods that can cause allergic reactions
• Preexisting diagnosis of HAE or AAE
• Positive family history

General Prevention

• Avoid known triggers.
• Do not use ACE inhibitors in type I or II HAE.

Commonly Associated Conditions

• Quincke disease (AE of the uvula)
• Urticaria