What is Hereditary Angioedema?

    Hereditary angioedema (HAE) is an inherited disease that causes repeated episodes of swelling. Angioedema means swelling beneath the surface of the skin. In HAE, the swelling and associated inflammation can be confined to the face, hands, feet, arms and legs. However, dangerous swelling in the airways—trachea (windpipe) or larynx (voice box)—or intestinal tract can also occur.

    Some people with HAE have mild inflammation, which requires no treatment. Others may need to be hospitalized for life-saving treatment.

    There are three types of HAE: type I, II, and III. Each type has its own causes and symptoms.

    Types of HAE and their Causes

    Each type of HAE has a different cause.

    Type I

    Type I HAE is caused by mutations in the SERPING1 gene. This gene makes the protein C1 inhibitor. C1 inhibitor is part of the body’s complement system—small proteins that assist the immune system—and it, specifically, helps control inflammation. People with type I HAE don’t make enough C1 inhibitor and as a result they cannot control inflammation.

    Type II

    People with type II HAE also have a mutation in the SERPING1 gene. They make enough C1, but the C1 doesn’t work properly.

    Type III

    In type III HAE, there is no abnormality found with C1 inhibitor. Instead, it has several potential causes. This condition occurs mainly in women and can be made worse with pregnancy or use of birth control medications. It is also associated with a mutation in the Factor XII gene (F12 gene). This gene makes coagulation factor XII. Factor XII assists in the blood clotting process. However, it can also stimulate inflammation. In people with type III HAE, too much coagulation factor XII is produced.

    How HAE Is Inherited

    HAE mutations are dominant. That means you only need to inherit one copy of a mutated gene to develop HAE. A parent with HAE has a 50 percent chance of passing it on to their child.

    In rare cases, a person will develop HAE when neither parent is affected. This means that a spontaneous gene mutation has occurred. Although technically the person’s HAE isn’t inherited, they will be able to pass it on to their children.

    What Are the Symptoms of HAE?

    The symptoms of HAE are grouped by the area of inflammation. Swelling may affect the abdomen, face, throat, limbs, and intestines. According to the Genetic and Rare Diseases Information Center, an episode of swelling may last for up to four days (GRDIC).

    Symptoms of intestinal swelling include:

    • Severe abdominal pain and cramping
    • dehydration
    • diarrhea
    • shock (in severe cases)

    Symptoms of throat inflammation include:

    • hoarse voice
    • difficulty swallowing
    • difficulty breathing

    Other symptoms include swelling in the:

    These symptoms may also be caused by other conditions. Always seek medical attention if you have unexplained swelling.

    Call 911 immediately if you develop throat swelling, difficulty breathing or talking. These are life-threatening symptoms. They could lead to shock or death.

    Testing for and Diagnosing Hereditary Angioedema

    Blood tests can check the C1 inhibitor level and function.

    Since Cl inhibitor is part of the complement system, blood tests for complement components C4 and C2 may also help diagnose HAE.

    Treatment Options

    There is no cure for HAE. Treatment focuses on relieving symptoms and preventing flare-ups.

    Several types of medication and therapies can be used to treat HAE.

    • Epinephrine is used in life-threatening situations to keep the airway open. It tightens blood vessels and relaxes muscles in the throat. Epinephrine is more effective than antihistamines—antihistamines have not been proven to be as effective in treatment of HAE. It also works more quickly, so is better in emergency situations.
    • C1-inhibitors are a very effective way to treat HAE. However, they are not always available.
    • Fresh frozen plasma might be beneficial in treating the symptoms of HAE.
    • Attenuated androgens (such as danazol) may be able to increase production of C1 inhibitor in people with type I HAE.

    If you have severe throat swelling, you may need respiratory treatments. These are given in a hospital setting.

    How Do I Prevent Flare-ups?

    Several types of medication have been approved to prevent flare-ups from HAE. These drugs are available by prescription only and some must be administered in a controlled health care setting. They include:

    • C1-inhibitors (Cinryze, Berinert)
    • ecallantide (Kalbitor)
    • icatibant (Firazyr)

    Complications of Hereditary Angioedema

    HAE can be life-threatening. Swelling in the throat can cause difficulty breathing and death. Prompt treatment with intubation or tracheotomy can be life-saving. Hypovolemic shock due to loss of blood from blood vessels must be treated promptly with fluid replacement.

    If you have trouble breathing, it is a medical emergency. You need to see a doctor right away.