Author: Vanessa Ngan, staff writer, 2006.

What is angioedema?

Angioedema is a skin reaction similar to hives or urticaria. It is most often characterised by an abrupt and short-lived swelling of the skin and mucous membranes. All parts of the body may be affected but swelling most often occurs around the eyes and lips. In severe cases the internal lining of the upper respiratory tract and intestines may also be affected.

What's the difference between angioedema and urticaria?

Angioedema and urticaria are very similar in many ways and can co-exist and overlap. Urticaria occurs more commonly and is less severe than angioedema as it only affects the skin layers whereas angioedema affects the tissues beneath the skin (subcutaneous tissue). The main differences between urticaria and angioedema are shown in the following table.

Tissues involved Subcutaneous and submucosal surfaces (beneath the dermis) Epidermis (outer layer of skin) and dermis (inner layer of skin)
Organs affected Skin and mucosa, particularly the eyelids and lips Skin only
Duration Transitory (usually lasts between 24-48 hours) Transitory (usually lasts < 24 hours)
Physical signs Red or skin coloured swellings occurring below the surface of the skin Red patches and weals on the surface of skin
Symptoms May or may not be itchy. Often accompanied by pain and tenderness. Usually associated with an itch. Pain and tenderness uncommon.

What causes angioedema?

The causes of angioedema depend on the type of angioedema a patient has. Angioedema can be classified into at least four types, acute allergic angioedema, non-allergic drug reactions, idiopathic angioedema, hereditary angioedema (HAE) and acquired C1 inhibitor deficiency.

Angioedema typeCauses
Acute allergic angioedema
(almost always occurs with urticaria within 1-2 hours of exposure to the allergen)
Non-allergic drug reaction
(onset may be days to months after first taking the medication)
  • Angiotensin-converting enzyme (ACE) inhibitors
  • Cascade of effects via kinin production, arachidonic acid metabolism and nitric oxide generation
Idiopathic angioedema
(frequently chronic and relapsing and usually occurs with urticaria)
  • In most cases the cause of angioedema is unknown
  • Recent research indicates that 30-50% of this type of angioedema may be associated with some types of autoimmune disorders including systemic lupus erythematosus (SLE)
Hereditary angioedema
(very rare autosomal dominant inherited disease)
  • Inherited abnormal gene that causes a deficiency of a normal blood protein
  • 3 types: Type 1 and II mutation of C1NH (SERPING1) gene on chromosome 11, encoding C1 inhibitor protein; Type III mutation in F12 gene on chromosome 12, encoding coagulation factor XII.
  • Type 1 results in low levels and function of circulating C1 inhibitor; Type II has normal levels of C1 inhibitor protein but reduction in function
  • Occurs in 1 in 50,000 males and females; Type III more severe in women.
  • Decreased C1 inhibitor activity leads to excessive kallikrein, which in turn produces bradykinin, a potent vasodilator
Acquired C1 inhibitor deficiency
  • Acquired during life rather than inherited
  • May be due to B-cell lymphoma or antibodies against C1 inhibitor

Whatever the cause of angioedema, the actual mechanism behind the swelling is the same in all cases. Small blood vessels in the subcutaneous and/or submucosal tissues leak watery liquid through their walls and cause swelling. This same mechanism occurs in urticaria but just closer to the skin surface.

What are the clinical features of angioedema?

Symptoms and signs of angioedema may vary slightly between the different types of angioedema but in general some or all of the following occur.

Some features specific to the different types of angioedema are listed below.

Angioedema typeClinical features
Acute allergic
  • Almost always occurs with urticaria
  • Angioedema and urticaria both usually occur within 1-2 hours of exposure to allergen (exception is ACE inhibitor induced angioedema that usually occurs within the first week of treatment but can occur weeks to months later)
  • Reactions are usually self-limiting and subside within 1-3 days
  • Reactions will recur with repetitive exposures or exposure to cross-reactive substances
Non-allergic drug reaction
  • ACE inhibitor induced angioedema occurs without urticaria
  • Similar to acute allergic but angioedema keeps on recurring and often no known cause is found
  • Patients often experience no symptoms until they reach puberty
  • Swellings can occur without any provocation or induced by precipitating factors, including local trauma, vigorous exercise, emotional stress, alcohol, and hormonal factors (menstruation, pregnancy, oestrogen)
  • Some patients may get a transitory prodromal non-itchy rash, headache, visual disturbance or anxiety
  • Face, hands, arms, legs, genitals, digestive tract and airway may be affected; swellings spread slowly and may last for 3-4 days
  • Abdominal cramps, nausea, vomiting, difficulty breathing and rarely urinary retention from swelling of internal tracts
  • Urticaria (wealing) does not occur
  • The tendency to angioedema is less pronounced in adults

How is the diagnosis made?

A detailed medical history is invaluable in diagnosing angioedema.

Skin prick testing may be performed to try and identify any allergens. If hereditary angioedema is suspected, blood tests to check for levels and function of specific complement blood proteins may be done.

What is the treatment for angioedema?

Treatment of angioedema depends on the severity of the condition. In cases where the respiratory tract is involved the first priority is to secure the airway. Patients may need emergency hospital care and require intubation (placement of a tube in the throat to keep the airway open).

Patients with mild acute angioedema can usually be treated the same way as those with an allergic reaction (see urticaria). In many cases the swelling is self-limiting and resolves spontaneously after a few hours or days. In more severe cases where there is persistent swelling, itchiness or pain the following medications may be used.

Chronic angioedema with chronic autoimmune or chronic idiopathic urticaria is often difficult to treat and response to medication variable. The following treatment steps are recommended. Each step is added to the previous one if inadequate response is obtained.

Step 1: non-sedating antihistamines, e.g. cetirizine
Step 2: sedating antihistamines, e.g. diphenhydramine
Step 3: a) oral corticosteroids, e.g. prednisone
b) immunosuppressants e.g. ciclosporin or methotrexate

Omalizumab, an anti-IgE monoclonal antibody, has been reported to be effective in some refractory cases of angioedema.

The goal of treatment for chronic angioedema is to reduce itch, swelling, tenderness and pain to a tolerable level to maintain function (e.g. work, school, sleep).

Acute episodes of hereditary angioedema do not respond to adrenaline, antihistamine and corticosteroids. Fortunately most acute episodes of Type I and II hereditary angioedema are non life-threatening.

The chance of an attack can be reduced with the following medications:

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