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Angioedema

Angioedema is a medical condition characterised by rapid swelling of the lower layer of skin and tissue just under the skin or mucous membranes. It often occurs in the face, tongue, larynx, abdomen, or extremities and is frequently associated with hives. The onset is typically rapid, occurring over minutes to hours.

Allergic angioedema: this child is unable to open his eyes due to the swelling.
Allergic angioedema: this child is unable to open his eyes due to the swelling.

Signs and Symptoms

The most common sites of swelling are the skin of the face, lips, and mucosa of the mouth and/or throat, as well as the tongue. The swelling can also occur elsewhere, such as the hands. The affected areas might feel itchy or painful, and there may be a slight reduction in sensation due to nerve compression. Hives (urticaria) may co-occur.

In severe cases, airway involvement can lead to stridor, gasping, and wheezing, necessitating tracheal intubation to prevent respiratory arrest and death.

Angioedema of half of the tongue
Angioedema of half of the tongue
Angioedema of the face, most strikingly in the upper lip.
Angioedema of the face, most strikingly in the upper lip.

Pathophysiology

The underlying mechanism involves either histamine or bradykinin. Histamine-mediated angioedema typically results from an allergic reaction to agents like foods or medications, whereas bradykinin-mediated forms may stem from inherited issues such as C1 esterase inhibitor deficiency, ACE inhibitors, or lymphoproliferative disorders.

Bradykinin is a very important mediator in hereditary angioedema (HAE), leading to rapid fluid accumulation in the interstitial tissue. Three types of HAE exist:

  • Type I: decreased levels of C1INH (85%)
  • Type II: normal levels but decreased function of C1INH (15%)
  • Type III: normal C1INH but linked to mutations in the factor XII gene, affecting mostly women.

Diagnosis

Diagnosis is primarily clinical, with routine blood tests and specific investigations like complement levels aiding in determining the cause. In hereditary cases, a family history and reduced complement factor C4 levels can be indicative. Acquired angioedema (AAE) can often be linked to allergies or medication side effects, particularly ACE inhibitors.

Management

Allergic Angioedema

Avoidance of known allergens and antihistamines may prevent future episodes. Cetirizine is commonly prescribed, and severe cases may require desensitisation or epinephrine.

Drug-Induced Angioedema

ACE inhibitors should be discontinued in affected patients, who may be switched to angiotensin II receptor blockers (ARBs), though some patients may still develop angioedema with ARBs.

Hereditary Angioedema

HAE does not respond to antihistamines, corticosteroids, or epinephrine. Acute treatment involves C1-INH concentrate or, in emergencies, fresh frozen plasma. Medications like ecallantide and icatibant can also be used.

Acquired Angioedema

In nonhistaminergic angioedema and HAE types I and II, antifibrinolytics like tranexamic acid may be effective. Cinnarizine can also be used in patients with liver disease.

Prophylaxis

Preventive measures for HAE include androgens like danazol and oxandrolone, which increase aminopeptidase P levels. Lanadelumab, a monoclonal antibody, has been approved for preventing HAE attacks by inhibiting kallikrein.

Epidemiology

In the U.S., angioedema accounts for approximately 80,000 to 112,000 emergency department visits annually and is a leading cause of hospital admissions due to allergic disorders.

History

Heinrich Quincke first described angioedema in 1882. William Osler later noted its hereditary nature in 1888 and coined the term "hereditary angio-neurotic oedema." The association with C1 esterase inhibitor deficiency was established in 1963.


Self-assessment MCQs (single best answer)

What is the primary characteristic of angioedema?




Which of the following is NOT commonly associated with angioedema?




Severe cases of angioedema involving the airway can lead to which of the following symptoms?




Which mediator is primarily involved in histamine-mediated angioedema?




What is the primary treatment for acute hereditary angioedema (HAE) attacks?




Which of the following medications should be discontinued in patients with drug-induced angioedema?




Which of the following is not typically effective in treating hereditary angioedema (HAE)?




Which type of hereditary angioedema (HAE) is associated with normal levels but decreased function of C1INH?




For the prophylaxis of hereditary angioedema (HAE), which of the following is used to increase aminopeptidase P levels?




What is the estimated annual number of emergency department visits in the U.S. due to angioedema?




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