Angioedema

Descriptive text is not available for this image BASICS

Angioedema (AE) is acute, localized swelling of skin, mucosa, and submucosa caused by extravasation of fluid into the affected tissues (1).

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

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