Hereditary angioedema

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at September 1, 2016
StartDiseasesHereditary angioedema

Hereditary angioedema (HAE) is a rare genetic disorder that is inherited through an autosomal dominant pattern. This disorder causes recurrent attacks of angioedema, that is, swelling or edema that affect different areas of the body, including the face, extremities (limbs), genitals, gastrointestinal tract, and upper respiratory tract.

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Definition & Facts

The severity of attacks can vary from attack-to-attack and/or from person-to-person. Swelling of the throat can be fatal for it can obstruct breathing and must be treated immediately with emergency medical care.

There are different types of hereditary angioedema, based on the genetic mutation involved and how it affects the body.

  • Type I hereditary angioedema is the most common form of the disease and involves an abnormally low amount of C1-inhibitor, a protein which regulates inflammation. It affects as many as 85 percent of patients with hereditary angioedema.
  • Type II hereditary angioedema occurs in about 15 percent of patients. These patients have normal or raised levels of C1-inhibitor, however the gene does not function properly.
  • Type III hereditary angioedema mostly affects women. It results from mutations in the F12 gene.

This disorder affects approximately one in 10,000–50,000 people. During a survey of over five hundred untreated persons with hereditary angioedema, it was concluded that forty percent of have up to eleven swellings a year.

Symptoms & Complaints

The trademark symptoms of hereditary angioedema are swelling of the extremities, gastrointestinal tract, tongue, and throat (death resulting from untreated swelling of the throat is as high as 30 percent). These symptoms can last from two to five days, and they can occur at any time and without warning.

If a patient does experience swelling of their intestines, then they may also encounter other symptoms such as vomiting, diarrhea, pain, abdominal cramping, dehydration, and shock. If this does occur, the patient should seek medical attention.

Causes

The cause of hereditary angioedema is the inheritance of genetic mutations that control the production of C1-inhibitor or the result of a genetic mutation that occurs spontaneously at conception. Mutations that cause type I and type II hereditary angioedema affect the gene, SERPING1 which creates C1-inhibitor.

Without adequate levels of C1-inhibitor (in cases of type I hereditary angioedema) or C1-inhibitor that functions properly (in cases of type II hereditary angioedema), the bradykinin protein proliferates and causes inflammation. Bradykinin causes blood vessels to become more permeable and to leak fluid, causing rapid swelling.

Mutations in the F12 gene cause type III hereditary angioedema. This gene gives instructions to make coagulation factor XII which in turn makes bradykinin. The defect involved in type III hereditary angioedema causes overproduction of coagulation factor XII and excessive levels of bradykinin.

Most hereditary angioedema attacks occur without warning, and many times without reason. But, there are some conditions that can trigger an attack, such as:

The age at which symptoms appear varies considerably. Over two-thirds of one study's subjects reported symptoms by the age of thirteen, along with an increased frequency of attacks during puberty. Women report that they have more attacks during menstruation and pregnancy.

Diagnosis & Tests

Due to the rarity of hereditary angioedema, patients can go many years without being properly diagnosed. One study showed that patients with this disorder, on average, waited 12-16 years between when they first noticed their symptoms and when they received a diagnosis of hereditary angioedema.

Some patients report undergoing unnecessary surgeries and/or treatments due to excruciating abdominal pain. Blood tests are done for those with a known family history to test C1-inhibitor function and levels.

Treatment & Therapy

Swelling that occurs in relation to hereditary angioedema is not the same as swelling that occurs due to allergic reactions, so they should not receive the same treatment. According to the United States Hereditary Angioedema Association, antihistamines or corticosteroids are not effective.

Since hereditary angioedema symptoms vary from person to person, patients should consult their physician to devise an individualized treatment plan. Treatment necessarily involves prevention of attacks and immediate alleviation of attacks. Androgens such as danazol may be prescribed to reduce the frequency of attacks. Pain associated with hereditary angioedema may be abated with painkillers.

For the attacks themselves, C1-inhibitor replacement drugs are used. Conestat alfa is a C1-inhibitor made from rabbits as opposed to human plasma. Other drugs are derived from blood that is donated. Icatibant is a type of drug that inhibits bradykinin, thereby reducing inflammation. Kallikrein inhibitors may also be prescribed. Ecallantide is one such drug that may be used to treat an acute attack.

If a patient is experiencing an acute hereditary angioedema attack, first aid may also need to be applied. This step can be life-saving, especially if the swelling is located in the neck because that could lead to asphyxiation, and even death. Tracheotomy may be required if the airways are obstructed from swelling.

Prevention & Prophylaxis

Because hereditary angioedema is a hereditary disease, prevention of the disease will prove to be impossible. However, there are steps a person can take to minimize the amount and frequency of attacks they are having. These steps include avoiding situations that cause stress or anxiety, or trauma to the oral cavity.

Patients can also avoid demanding physical activities that place too much stress on their extremities (like jogging). If a patient continues to encounter frequent and severe episodes, and preventative measures have been taken but are not producing a result, then they should consult their physician to discuss other treatment options.