An Overview of Angioedema

Allergy is only one of the many possible causes

Show Article Table of Contents

Angioedema is the swelling of the lower layer of tissue just under the skin or mucous membranes. The swelling mostly affects the face, tongue, lips, throat, arms, and legs but 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.

Symptoms

While angioedema is closely related to hives (urticaria) in that they share the same underlying causes, symptoms differ.

Angioedema occurs in the subcutaneous tissue beneath the outermost layers of skin (called the dermis and epidermis). As such, it causes a deeper, generalized swelling that tends to last longer than hives. By contrast, urticaria involves the epidermis and dermis and is characterized by raised wheals with clearly defined borders.

With angioedema, the swelling can begin within minutes or develop over the course of hours. The swollen area of skin is usually not itchy (unless accompanied by urticaria) but can often have a burning, tingling, or numb sensation. The swelling can last for several hours or days. When the swelling finally resolves, the 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.

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.

Angioedema is typically classified into one of two groups:

Acquired Angioedema

Acquired angioedema (AAE) can be caused by immunologic (related to the immune system) and non-immunologic causes. They include:

There will also be cases that have no known cause. These are referred to as idiopathic angioedema.

Chronic idiopathic angioedema is a condition that affects women more than men. Some have hypothesized that it is related to the menstrual cycle, wherein rises in estrogen are often accompanied by rises in bradykinins.

Hereditary Angioedema

Hereditary angioedema (HAE) is 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 of 50,000 people, and is most often suspected when antihistamines or corticosteroids fail to provide the relief of symptoms.

Diagnosis

Angioedema can be often be diagnosed based on its clinical appearance and a review of your medical history and accompanying symptoms.

If an allergy is suspected, your doctor 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 doctor 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.

Treatment

Among the best way 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. Zyrtec (cetirizine) is particularly effective for acute attacks but can also be taken as a lower, nightly dose for sustained relief.
  • If allergy testing confirms that you are hypersensitive to certain allergens, allergy shots may be prescribed to gradually reduce your sensitivity.
  • Chronic cases may respond well to systemic corticosteroids delivered by intramuscular injection. 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.

A Word From Verywell

Angioedema can be distressing, particularly if the swelling is severe or recurrent. Even if there are no other visible symptoms, you should see a doctor if the swelling persists for more than a couple of days.

If the angioedema is believed to be allergy-related but you don't know the cause, keep a diary to record any foods you have eaten or environmental allergens you may have been exposed to. Doing so may help narrow the search and help you avoid problematic triggers.

On the other hand, if you develop swelling of the throat accompanied by breathing difficulty of any sort, call 911 or have someone rush you the nearest emergency room.

View Article Sources