Angioedema

Angioedema and urticaria should be viewed as varying manifestations of the same pathologic process. Postcapillary venule inflammation results in fluid leakage and edema in both conditions. However, angioedema involves vessels in the layers of the skin below the dermis, while urticaria is localized superficial to the dermis. This results in varying clinical presentations.

The subdermal source of angioedema results in well-demarcated, localized, nonpitting edema. Urticaria is localized to the superficial portion of the dermis and is characterized by well-circumscribed wheals with raised erythematous borders and central blanching. These often coalesce to become giant wheals.

These conditions can occur together or separately. Recurrent episodes of one or both conditions for less than a 6-week duration are considered acute, whereas longer-lasting attacks are considered chronic.

Angioedema, with or without urticaria, is classified as allergic, hereditary, or idiopathic. Complications range from dysphonia or dysphagia to respiratory distress, complete airway obstruction, and death.

Pathophysiology

Angioedema involves vascular leakage beneath the dermis and subcutis. This response is mediated by vasoactive mediators, such as histamine, serotonin, and kinins (eg, bradykinins), which cause the arterioles to dilate while inducing a brief episode of vascular leakage in the venules, where the junction between the endothelial cells appears looser than in the capillaries and arterioles.

Frequency

United States

Approximately 15% of the general population is affected by recurrent idiopathic episodes. The most common kind does not have a discoverable cause.

Mortality/Morbidity

Morbidity and mortality are directly related to the severity of airway obstruction.

Race

No specific racial predilection exists.

Sex

Women tend to have more occurrences than men.

Age

Persons who are predisposed have an increase in frequency of attacks after adolescence, with the peak incidence occurring in the third decade of life.

Clinical

History

• General history
  • Urticarial eruptions usually appear at intervals and are intensely pruritic.
  • Patients with angioedema or urticaria should be questioned in detail to identify the offending antigen (in cases of allergic angioedema).
  • Any family history or history of recurrent episodes with the use of particular agents must be sought.
• Drugs associated with urticaria and angioedema include the following:
  • Radiocontrast agents
  • Opiates
  • Dextran
  • Angiotensin-converting enzyme (ACE) inhibitors
  • Aspirin
  • Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Common sources of antigens that cause urticaria and angioedema include the following:
  • Hymenoptera envenomations
  • Food allergies such as fresh berries, shellfish, fish, nuts, tomatoes, eggs, milk, chocolate, food additives, and preservatives
  • Local trauma (eg, dental procedure, tonsillectomy)
  • Exposure to water, sunlight, cold, or heat
  • Animal dander (from scales of shed skin)
  • Emotional stress
  • Post infection or illness, including autoimmune disorders such as thyroid autoimmunity and leukemia
• Chronic urticaria (increasingly associated with Helicobacter pylori bacteria)

Physical

• General examinations
  • Patients usually present with the acute onset of well-demarcated cutaneous edema of distensible tissues (eg, lips, eyes, earlobes, tongue, uvula).
  • The face, extremities, and genitalia are most commonly affected.
• Airway assessment
  • First, determine airway patency.
  • Severe attacks can herald the onset of systemic anaphylaxis, characterized initially by dyspnea.
• Gastrointestinal (GI): Massive edema of the subcutaneous tissue in the abdominal region may present with abdominal distention and signs consistent with bowel obstruction.

Causes

• Immunoglobulin E (IgE)-mediated angioedema/urticaria may result from antigen ingestion (eg, food, drug) or from parenteral exposure (eg, medications, Hymenoptera).
• Complement-mediated angioedema/urticaria:
  • This angioedema involves immune complex–mediated necrotizing cutaneous venulitis manifested as serum sickness.
  • It is characterized by fever, angioedema, arthralgias, urticaria, and palpable purpura.
• Hereditary angioedema
  • This type of angioedema is characterized by recurrent self-limited attacks involving the skin, subcutaneous tissue, upper respiratory tract, or GI tract. Attacks may last from several hours to 2-3 days.
  • GI or upper respiratory tract attacks may be precipitated by local trauma (eg, dental procedures, tonsillectomy).
• Idiopathic angioedema appears to manifest due to direct mast cell–releasing agents in certain compounds (eg, radiocontrast media, opiates, dextran).
  • Other drugs may precipitate attacks by effects on arachidonic acid metabolism (eg, aspirin, NSAIDs, any compounds that are cyclooxygenase inhibitors).
  • ACE inhibitors precipitate attacks by directly interfering with the degradation of bradykinin, thereby potentiating its biological effect.