Angiodema

Angioedema is a deep, short-lived swelling that can occur anywhere below or within the skin. Skin angioedema swellings are usually pale and uncomfortable rather than red and itchy. They generally last longer than superficial weals and often for days. Angioedema can also occur below mucous membranes of the mouth and genitalia. In rare situations, it can affect the bowel and bladder causing pain due to obstruction without being visible. Angioedema may be a feature of urticaria where it is due to histamine release from mast cells and responds to the same treatments as weals. It may also be a feature of anaphylaxis if it causes choking as a result of swelling within the throat. However, if angioedema occurs without weals it may be caused by a completely different mediator called bradykinin.
This may cause abdominal pain or throat swellings, which need completely different treatments from urticaria. Doctors try to understand from the story whether angioedema occurs with or without weals since this helps them to work out whether the swellings are due to histamine or bradykinin but it can be difficult to tell. A proportion of patients with bradykinin-induced angioedema will have inherited their condition. This is known as hereditary angioedema. Three types are currently recognized with different laboratory findings (Type I, II and III). About 50% of the children of affected patients are at risk of carrying the genetic abnormality that results in a reduction in function of an important enzyme inhibitor that controls several pathways necessary for good health.

Diagnosis

The diagnosis of angioedema is primarily clinical but understanding the cause of the angioedema needs laboratory tests to show the specific type of underlying abnormality when kinin causes the swellings. Three types of hereditary angioedema are now recognized and some even less common types of C1 esterase inhibitor deficiency can sometimes be identified in patients with other types of illness that are not hereditary. The simplest and best screening test for all these types of angioedema is the measurement of a blood protein level called C4 complement. The levels are considerably reduced in all except Type III hereditary angioedema whether the disease is active or not. The cause of angioedema in the majority of patients who do not develop weals is usually unknown and their illness is therefore called ‘idiopathic’. Fortunately the majority of patients with idiopathic angioedema respond to treatments for histamine-mediated urticaria.

Management

Attacks of bradykinin-induced angioedema may be frequent or infrequent but usually begin in childhood. They may present with severe abdominal pain due to obstruction of the gut so they are often diagnosed late when there is no family history to guide the correct diagnosis. Of greater concern for patients with the condition is the knowledge that swellings may affect the throat severely so urgent appropriate therapy is required to minimize the risk of choking. The best treatment until recently was an emergency infusion of purified C1 inhibitor into the vein to replace the missing protein. A relatively new inhibitor of bradykinin is now available that is injected under the skin once an attack starts and appears to work as well as C1 inhibitor although studies comparing the two therapies have not been done yet. Patients who develop frequent attacks of hereditary angioedema often benefit from taking medications to prevent them but there is still no perfect preventative measure. It is now recognized that women on oestrogen hormone therapies are at increased risk of angioedema and should be advised to find alternatives whenever possible.
By complete contrast to bradykinin-induced angioedema, idiopathic (histamine-mediated) angioedema responds well in an emergency to adrenaline (epinephrine). Treatment with antihistamines and steroids are often given. However, steroids should only be taken in short courses to minimize the risk of side effects. Antihistamines are sometimes insufficient to prevent angioedema on their own and then other treatments are often given as well.

Coping

Whilst effective treatments are now available for emergencies, the condition can still be stressful for patients because attacks are unpredictable and medical help may be required at very short notice. Because severe attacks of both bradykinin and histamine-induced angioedema involving the throat require injections, patients need to be shown how to self-administer treatment and gain confidence in how to manage an emergency effectively. Less severe attacks settle naturally over days but still cause discomfort and embarrassment if they are on the face and may be a reason for taking days off work or school.