Description

• Angioedema (AE) is an acute, localized swelling of skin, mucosa, and submucosa caused by extravasation of fluid into the affected tissues. It often resolves in hours to days, but it can be life threatening if the upper airway is involved.
• Hereditary AE (HAE) and acquired AE (AAE) are diseases of the complement cascade that result in recurrent episodes of AE of the skin, upper airway, and GI tract.
• Synonym(s): Angioneurotic edema; Quincke edema

Epidemiology

• Predominant age:
  • Allergen, medication, or other triggers can affect all ages.
  • HAE: Infancy to 2nd decade of life
  • AAE: Typically patients in 4th decade of life
• Predominant gender: Male = Female (except type III HAE, which affects more women than men)

• AE occurs in ~15% of the population over a lifetime.
• AE: 0.1–2.2% of patients receiving ACE inhibitors: African Americans have a 4–5 times greater risk of ACE inhibitor–induced AE than Caucasians.
• HAE: 1:10,000–50,000 population in US

Risk Factors

• Consuming medications and foods that can cause allergic reactions
• Pre-existing diagnosis of HAE or AAE

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

General Prevention

• Avoid known triggers.
• Do not use ACE inhibitors in patients with C1 esterase inhibitor (C1 INH) deficiency.

Pathophysiology

• Type 1 hypersensitivity reaction
• Increase in vascular permeability secondary to IgE-mediated mast cell–stimulated histamine release or from activation of the complement system and an elevation in bradykinin (HAE)
• Attacks of HAE are triggered by prolonged mechanical pressure, cold, heat, trauma, emotional stress, menses, illness, and inflammation:
  • Type I HAE is the most common form, caused by decreased production of C1 esterase inhibitor (C1 INH), and has autosomal-dominant inheritance.
  • Type II HAE has functionally impaired C1 INH and autosomal-dominant inheritance.
  • Type III (HAE-FXII) involves mutations in coagulation factor XII gene (occurs more frequently in women, often estrogen-dependent, associated with estrogen administration); also type III HAE-unknown exists.
• AAE is a rare condition:
  • Type I is associated with lymphoproliferative diseases or paraneoplastic diseases.
  • Type II is due to autoimmune disorders (anti-C1 INH antibody).
  • Affected patients have circulating antibodies directed either against specific immunoglobulins expressed on B cells (type I) or against C1 INH (type II).
  • AAE typically presents later in life (>40), and patients lack family history of AE.

Etiology

• Idiopathic
• Medication-induced:
  • ACE inhibitors cause 10–25% of AE cases, mostly occurring within the 1st month of use. However, onset may be delayed by years.
  • Angiotensin-receptor blockers (ARBs) also can cause AE, but more rarely than ACE inhibitors.
• Allergic triggers:
  • Food allergens such as shellfish, nuts, eggs, milk, wheat, soy
  • Medications such as aspirin, NSAIDs, antibiotics, narcotics, and oral contraceptives
  • Latex, venom
• Physically induced: Cold, heat, pressure, vibration, trauma, emotional stress, ultraviolet light
• Hereditary or acquired C1 INH deficiency
• Thyroid autoimmune disease–associated AE

Commonly Associated Conditions

• Quincke disease (AE of the uvula)
• Urticaria