Description

• AE commonly occurs as a part of the presentation of urticaria, but when it presents without wheals, it should be diagnosed as a distinct disease (1).
• 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, both with unique subtypes (1):
  • Acquired AE (AAE): involves all cases that are not considered to be hereditary AE (HAE)
    • Idiopathic histaminergic (IH-AAE): no cause identified, response to antihistamine treatment
    • Idiopathic non-histaminergic (InH-AAE): no cause identified, no response to antihistamine treatment
    • Angiotensin-converting enzyme-inhibitor (ACEI)-related AAE (ACEI-AAE)
    • C1-inhibitor (C1-INH) deficiency-related AAE (C1-INH-AAE)
  • HAE: mediated by changes in the genes that regulate the compliment cascade, also known as bradykinin-mediated AE
    • C1-INH-HAE: caused by C1-INH deficiency
    • FXII-HAE: Patients have a normal C1-INH but a FXII mutation.
    • U-HAE: Patients have a normal C1-INH, unknown cause.
• Synonym(s): angioneurotic edema; Quincke edema

Epidemiology

• Predominant age of onset
  • AAE (1):
    • IH-AAE, InH-AAE, ACEI-AAE: any age
    • C1-INH-AAE: age >40 years
  • HAE: infancy to 2nd decade of life
• Predominant gender: male = female, except FXII-HAE which predominantly affects females

Prevalence

• AAE:
  • IH-AAE: most common form of AE
  • ACEI-AAE: 0.1–2.2% of patients receiving ACEI (1)
    • The incidence of AE related to ACEI use in black individuals is as high as four times that of whites. Note: Race is now recognized as a social, not biological, construct and decisions about initiation of ACEI should not be influenced by self-identified race.
  • C1-INH-AAE: 1:500,000 (1)
• HAE
  • C1-INH-HAE: 1:10,000 to 100,000 (1)
  • C1-INH accounts for 85% of cases of HAE (2)

Etiology and Pathophysiology

• AAE:
  • IH-AAE: due to release of vasoactive substances
  • ACEI-AAE: thought to be due to elevated plasma levels of bradykinin
  • C1-INH-AAE: nongenetic changes to C1-INH function, can be due to autoantibodies
    • Can be associated with other lymphoproliferative conditions like systemic lupus erythematosus
• HAE:
  • Attacks are triggered by prolonged mechanical pressure, cold, heat, trauma, emotional stress, menses, illness, and inflammation.
  • C1-INH-HAE
    • Type I: decreased production of C1-INH
    • Type II: normal or high levels of C1-INH; however, is dysfunctional
  • FXII-HAE
    • normal C1-INH with presence of mutation in coagulation FXII gene
    • Formerly type III HAE
    • Symptoms, often estrogen-dependent, are induced with estrogen administration (hormone replacement therapy or oral contraceptives [OCPs]) or with pregnancy
  • U-HAE
    • Normal C1-INH, without presence of FXII gene mutation

Genetics

• HAE types I and II are autosomal dominant, whereas HAE with normal C1-INH is dominant X-linked.
• Spontaneous genetic mutations responsible for 25% of HAE cases

Risk Factors

• Consuming medications and foods that can cause allergic reactions
• Positive family history

General Prevention

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

Commonly Associated Conditions

• Quincke disease (AE of the uvula)
• Urticaria