Angioedema most often affects the lips, eyes, tongue, throat, arms, and legs. It is the swelling of the lower layer of tissue just under the skin or mucous membranes, where fluid builds and vessels dilate. Angioedema may become serious and even life-threatening if it occurs in the throat, lungs, or gastrointestinal tract.
Angioedema is often caused by an allergy but can also be triggered by a non-allergic drug reaction, an infection, cancer, genetics, and even stress. Treatment depends on the underlying cause but may include antihistamines, steroids, and the avoidance of the known triggers.
This article explains the symptoms and possible causes of angioedema. It also covers diagnosis and treatment options for the condition.
Angioedema Symptoms
Angioedema is swelling under the skin that often happens as an allergic reaction. Symptoms of angioedema include swelling of the eyes, lips, hands, feet, legs, or genitals. The swelling may begin within minutes or develop over hours.
Other common angioedema symptoms include:
- Dizziness
- Patchy welts
- Rash
- Redness
- Upset stomach
Less common angioedema symptoms include:
- Breathing difficulties
- Itching, tingling, burning, or numbness
- Trouble chewing or swallowing
- Diarrhea
Angioedema symptoms range in severity but are rarely life-threatening. Swelling can last for several hours to days. When the swelling resolves, the affected skin will usually appear normal with no flaking, peeling, scarring, or bruising.
Certain types of angioedema can be far more serious, particularly if they extend beyond the extremities, face, or trunk. Among the complications:
- Angioedema of the gastrointestinal tract can cause violent vomiting, severe pain in the midsection, and dehydration (due to the inability to keep fluids down).
- Angioedema of the lungs can cause wheezing, shortness of breath, and airway obstruction.
- Angioedema of the larynx (voice box) can lead to asphyxiation and death.
Angioedema vs. Hives
Angioedema and hives share some of the same underlying causes, although symptoms often differ.
A case of hives (urticaria), characterized by raised wheals with clearly defined borders, involves the outermost layers of skin (called the dermis and epidermis).
By contrast, angioedema occurs in the subcutaneous tissue beneath the outermost layers. As such, it causes a deeper, generalized swelling that tends to last longer than hives.
Angioedema Causes
From a broad perspective, angioedema is caused by an abnormal response of the immune system in which chemicals known as histamine or bradykinins are released into the bloodstream.
Histamine, which forms part of the immune defense, causes the dilation of blood vessels so that immune cells can get closer to the site of an injury. Bradykinins also cause blood vessels to dilate but do so to regulate body functions such as blood pressure and respiration. When released abnormally, either on their own or together, these compounds can cause the swelling we recognize as angioedema.
Hereditary Angioedema
Hereditary angioedema (HAE) is usually an autosomal dominant disorder, meaning that you can inherit the problematic gene from just one parent. The gene mutations typically result in the overproduction of bradykinins and can affect all organ systems, including the skin, lungs, heart, and gastrointestinal tract.
While HAE can be triggered by stress or injury, most attacks have no known cause. Recurrence is common and can last anywhere from two to five days. ACE inhibitors and estrogen-based contraception, both of which can affect bradykinin levels, are known to increase the frequency and severity of attacks.
HAE is rare, occurring in only one in 50,000 people worldwide. It is is most often suspected when antihistamines or corticosteroids fail to provide the relief of symptoms.
Diagnosing Angioedema
Angioedema can often be diagnosed based on its clinical appearance and a review of your medical history and accompanying symptoms.
If an allergy is suspected, your healthcare provider may suggest that you undergo allergy testing to identify the causal trigger (allergen). This may involve a skin prick test (in which a tiny amount of a suspected allergen is injected beneath the skin), a patch test (using an adhesive patch infused with the allergen), or blood tests to check whether allergic antibodies are in your blood.
Blood tests can also be used to diagnose HAE. If all other causes of angioedema have been excluded, your healthcare provider may decide to check the level of a substance called C1 esterase inhibitor, which regulates bradykinins, in your blood. Those with HAE are less able to produce this protein, so a low level of C1 esterase inhibitor is considered a strong indication of this type of angioedema.
Angioedema Treatment
Among the best ways to prevent future attacks is to avoid any known trigger. If this is not achievable, treatment would be focused on tempering the immune response to reduce the levels of histamine or bradykinins in your blood.
Among the options:
- Oral antihistamines are typically prescribed to treat allergy-associated angioedema.
- Depending on the cause, some cases may respond well to systemic corticosteroids. Prednisone is one of the more commonly prescribed options but is only used for short-term relief due to the risk of side effects.
- HAE can be treated with the drugs Kalbitor (ecallantide) or Firazyr(icatibant). Kalibor blocks enzymes that stimulate the production of bradykinins, while Firazyr prevents bradykinins from attaching to receptors on targeted cells. Nausea, fatigue, headache, and diarrhea are common side effects.
- People with HAE may also find relief by taking androgens (male hormones) such as methyltestosterone and danazol. These work by suppressing the levels of bradykinins circulating in the blood. Long-term use can cause masculinizing effects in women (including male pattern baldness and facial hair) and breast enlargement (gynecomastia) in men.
- Severe angioedema of the larynx should be treated with an emergency injection of epinephrine (adrenaline). People with a known severe allergy often need to carry a preloaded epinephrine injector, called an EpiPen, in the event of an attack.
Summary
Angioedema swelling can happen anywhere on the body, but most often affects the face (lips, eyes), tongue, throat, arms, and legs. Fluid builds and vessels dilate in the lower layer of tissue under the skin or mucous membranes. Angioedema can result from allergic or drug reactions, an infection, cancer, genetics, and stress events but sometimes no cause can be found.
Angioedema symptoms can be severe or recurrent but are rarely life-threatening. Swelling can last for several hours to days. Treatment depends on the underlying cause but may include steroids, antihistamines, and the avoidance of known triggers.
If angioedema is believed to be allergy-related, keeping a daily record of foods eaten and any likely environmental allergen exposures may help to pinpoint and avoid triggers.
If swelling of the throat develops accompanied by breathing difficulty of any kind, call 911 or seek help at the nearest emergency room.