Angioedema

What is Angioedema?

Angioedema is a common condition, affecting about 10-20% of people during their life, although some types are more common than others.

Angioedema is swelling in the deeper layers of the skin, often around the face and lips. It's usually a reaction to a trigger, such as a medicine or something you're allergic to. It is not normally serious and it is short-lived (one to three days), but it can be a recurring problem for some people.

Bathe and change your clothes. If pollen or animal contact has triggered your hives in the past, take a bath or shower and change your clothes if you're exposed to pollen or animals.

If it affects your breathing/airways, it's a medical emergency and you need to get help. Stridor of the airway occurs, with gasping or wheezy inspiratory breath sounds and decreasing oxygen levels. Tracheal intubation is required in these situations to prevent respiratory arrest and risk of death.

Angioedema can arise with a raised itchy rash called urticaria (hives) or alone. Most times, the hives are harmless, clear up within a day and don't leave any lasting marks, even without treatment.

Angioedema eventually disappears in most people. It may reappear following infection, when under stress or for no particular reason that can be identified. Angioedema is seldom caused by a serious underlying disease, nor does it make you sick or cause damage to organs such as kidneys, liver or lungs.

Significant risk factors for severe cases of angioedema included older age, Hispanic race, ACEi-induced angioedema type, American Society of Anaesthesiologists class III or above, coexistent cardiopulmonary disease, and a positive smoking history.

What are the symptoms?

The skin of the face, normally around the mouth (face/lips) or throat (larynx/tongue/uvula), swell over a period of minutes to hours. The swelling can also occur elsewhere, typically in the hands/feet, around the eyes, cheeks, or the genital areas. The swelling/puffiness can be itchy, red, painful or feel warm. It can feel like thick firm welts (raised marks.) There may also be slightly decreased sensation in the affected areas due to compression of the nerves. Urticaria (hives) may develop simultaneously.

Occasionally, swelling of internal organs like the oesophagus, (food pipe or gullet that leads to the stomach), stomach, or bowel can trigger chest or stomach pains. You can have digestive problems and/or stomach pain if your intestines are swollen. Angioedema can also cause dizziness or even fainting due to blood pressure changes.

Whilst angioedema may be itchy, tingling, or burning, often there are no symptoms other than the discomfort of the swelling. Sometimes the swelling can be painful, particularly when it occurs over joints. These swellings can be large and may last for days. If swelling is constant rather than coming and going, other possible causes of swelling should be considered.

Angioedema can be dangerous if swelling is in your throat, airways or tongue. That can make it suddenly hard to breathe or cause asphyxiation (not getting enough oxygen to prevent you from passing out), dizziness, fainting or collapsing. Blood pressure may fall suddenly. If this happens, you should get medical help right away.

What are the causes?

For most people who experience acute hives and angioedema, the exact cause can't be identified.

• Angioedema is often the result of an allergic reaction (allergic Angioedema). This is where the body mistakes a harmless substance, such as a certain food, for something dangerous. It releases chemicals into the body to attack the substance, which causes the skin to swell. This could be something you’ve eaten (a food - could be peanuts - or beverage) or touched (as in items made with natural rubber latex eg, medicinal gloves, catheters, balloons, contraceptive devices. In addition, this type of angioedema can occur if an insect or spider bites you. Pollen and other allergens (such as animal dander) that you breathe in can trigger hives, sometimes accompanied by respiratory problems. Histamines released from foods such as cheese, alcohol, shellfish, fish, tomatoes, strawberries, pineapples, nuts, citrus fruits and kiwis, soy, eggs or milk could be linked to the triggering of angioedema attacks. Symptoms usually occur within one to two hours of eating the offending food and disappear within 12 to 24 hours. This type of angioedema is not chronic, or long-term. As soon as the individual identifies which item is causing the allergic reaction, they can avoid it. The role of food intolerance (which is different to allergy) remains controversial. Dietary changes such as avoiding naturally occurring food chemicals and food additives may sometimes be tried, as well as allergy testing under the supervision of suitably experienced medical practitioners and accredited dietitians.

Acute allergic angioedema happens quickly, usually within minutes to about one to two hours after you’ve made contact with the allergen. You almost always have hives along with the swelling.

• a medicine, such as angiotensin-converting enzyme (ACE) inhibitors for high blood pressure - this is known as drug-induced angioedema. The most common group of medications that cause this non-allergic reaction is angiotensin-converting enzyme inhibitors, often called ACE inhibitors or ACEIs. These medications relax your blood vessels, treat heart failure and may lower blood pressure. Nonsteroidal anti-inflammatory medications, like ibuprofen and naproxen, can also cause angioedema. If you are allergic to aspirin, penicillin or similar pain medications, taking them may trigger swelling. One in three people with angioedema, will quickly have their swellings made worse if they take these medications, even if they are not allergic to them. It is therefore better to take paracetamol for pain management. If you are already on aspirin or similar pain medications regularly and without symptoms, then there is no need to stop taking them.

• a genetic fault that you inherit from your parents – this is a rare, lifelong condition that usually starts in childhood called hereditary angioedema. This is rare. It happens when your body doesn’t make enough of a blood protein called C1 esterase inhibitor. That lets fluid from your blood move into other tissues, which brings swelling. You’ll usually have your first bout of this before you turn 12 years old. You may pass the condition on to your children. In hereditary angioedema (HAE), often no direct cause is identifiable, although mild trauma, including dental work and other stimuli, can cause attacks. There is usually no associated itch or urticaria, as it is not an allergic response. Patients with HAE can also have recurrent episodes (often called "attacks") of abdominal pain, usually accompanied by intense vomiting, weakness, and in some cases, watery diarrhoea, and an unraised, non-itchy splotchy/swirly rash. These stomach attacks can last one to five days on average and can require hospitalization for aggressive pain management and hydration. Abdominal attacks have also been known to cause a significant increase in the patient's white blood cell count, usually in the vicinity of 13,000 to 30,000. As the symptoms begin to diminish, the white count slowly begins to decrease, returning to normal when the attack subsides. HAE may also cause swelling in a variety of other locations, most commonly the limbs, genitals, neck, throat and face. The pain associated with these swellings varies from mildly uncomfortable to agonizing pain, depending on its location and severity. Predicting where and when the next episode of angioedema will occur is impossible. Most patients have an average of one episode per month, but there are also patients who have weekly episodes or only one or two episodes per year. The triggers can vary and include infections, minor injuries, mechanical irritation, operations or stress. In most cases, angioedema develops over a period of 12–36 hours and then subsides within 2–5 days. The hereditary form (HAE) often goes undetected for a long time, as its symptoms resemble those of more common disorders, such as allergy or intestinal colic. An important clue is the failure of hereditary angioedema to respond to antihistamines or steroids, a characteristic that distinguishes it from allergic reactions. It is particularly difficult to diagnose HAE in patients whose episodes are confined to the gastrointestinal tract. Besides a family history of the disease, only a laboratory analysis can provide final confirmation.

• Acquired angioedema

Diagnosis.

Your doctor can diagnose angioedema by examining the affected skin and discussing symptoms, triggers, and by taking a family and medical history. However, further tests, such as blood tests or allergy tests, may be required to determine the type of angioedema. These may include:

• a skin prick test to confirm a link to possible allergies, in which the skin is pricked with a very small amount of the allergen that is suspected.

• a blood test to see how the immune system reacts to a certain allergen.

• a blood test to check for C1 esterase inhibitor, low levels of which suggest that the problem is hereditary.

Having been exposed to a common allergen before the occurrence of angioedema means that allergic angioedema is likely. The presence of hives will also point to this type.

You can avoid allergic episodes if you stay away from foods, medications, or other conditions that trigger angioedema. If you don’t know what’s causing your episodes, try to keep a diary to track foods, symptoms, and situations tied to your symptoms.

Your doctor might suggest you take antihistamines every day instead of just when you need them. This can help get rid of episodes, make them happen less often, or be less dangerous. You also won't have to wait for the medicine to start working when you need relief.

Management.

Allergic

In allergic angioedema, avoidance of the allergen and use of antihistamines may prevent future attacks.

Cetirizine is a commonly prescribed antihistamine for angioedema. Some patients have reported success with the combination of a nightly low dose of cetirizine to moderate the frequency and severity of attacks, followed by a much higher dose when an attack does appear. The release of histamine within the skin seems to be the trigger for swelling in most people. Antihistamines block this effect. Since they take one to two hours to reduce symptoms, it is often better to take them regularly, rather than as needed. The aim is to stop the episodes of swelling, or to make them less frequent or less severe. In people with severe angioedema, it is often better to take them every day, stopping every month or two to see if they are needed and restarting them if they are. Different people respond best to different antihistamines.  Non-drowsy antihistamines are available over the counter without prescription. Unfortunately, these are less effective for angioedema than for hives (urticaria), and are often totally ineffective for the non-itchy angioedema, in which histamine appears to play no significant role. Severe angioedema cases may require desensitization to the putative allergen, as mortality can occur. Chronic cases require steroid therapy, which generally leads to a good response. In cases where allergic attack is progressing towards airway obstruction, epinephrine may be life-saving. Avoid aggravating factors. Non-specific measures such as avoiding excessive heat, spicy foods or alcohol are often useful.  Since Aspirin can make swellings worse, it should be avoided unless already being taken without a problem. Avoid any medicines, herbs, or supplements that are not prescribed by a provider.

Drug induction

ACE inhibitors can induce angioedema. ACE inhibitors block the enzyme ACE so it can no longer degrade bradykinin; thus, bradykinin accumulates and can cause angioedema. This complication appears more common in African-Americans. In people with ACE inhibitor angioedema, the drug needs to be discontinued and an alternative treatment needs to be found, such as an ARB, which has a similar mechanism but does not affect bradykinin. However, this is controversial, as small studies have shown some patients with ACE inhibitor angioedema can develop it with ARBs, as well.

Hereditary

In hereditary angioedema, specific stimuli that have previously led to attacks may need to be avoided in the future. It does not respond to antihistamines, corticosteroids, or epinephrine. Acute treatment consists of C1-INH (C1-esterase inhibitor) concentrate from donor blood, which must be administered intravenously. In an emergency, fresh frozen blood plasma, which also contains C1-INH, can also be used. However, in most European countries, C1-INH concentrate is only available to patients who are participating in special programmes. Hereditary angioedema cannot be cured, but medicines can help prevent swelling and quickly treat swelling when it occurs. The swelling is caused by "faulty" genes that are inherited from a person’s parents.

Acquired

In acquired angioedema, HAE types I and II, and nonhistaminergic angioedema, antifibrinolytics such as tranexamic acid or ε-aminocaproic acid may be effective. Cinnarizine may also be useful because it blocks the activation of C4 and can be used in patients with liver disease, whereas androgens cannot.