Hereditary Angioedema (HAE)

What is it?

Hereditary Angioedema (HAE) is a rare inherited disease that causes significant swelling (often referred to as edema) in the tissues of the body, like the abdomen or face. Depending on the severity of the disease, some people will have many attacks each month, while others can go years without a swelling attack. Minor trauma or stress may trigger an attack, but swelling often occurs without a known trigger. HAE can affect the gastrointestinal system and can cause severe abdominal pain, nausea, and vomiting. This disease can also affect the airway  and can restrict breathing leading to life-threatening obstruction of the airway if an intervention does not occur.

Symptoms of hereditary angioedema typically begin in childhood and worsen during puberty. On average, untreated individuals have an attack every 1 to 2 weeks, and most episodes last for about 3 to 4 days. The frequency and duration of attacks vary among people with hereditary angioedema, even among people in the same family.

What causes it?people

HAE patients have a defect in the gene that controls a blood protein known as the C1 Inhibitor. The genetic defect results in production of either inadequate or a dysfunctional C1-Inhibitor protein. Normal C1-Inhibitor helps to regulate the interactions between certain blood vessels that assist in disease fighting, inflammation, and coagulation. Because a defective C1-Inhibitor protein cannot function correctly, a biochemical imbalance can occur which results in a production of unwanted proteins that cause small blood vessels called capillaries to release fluids into surrounding tissue, thereby causing edema.

Who does it affect?

Hereditary Angioedema is called hereditary because the genetic defect is passed down through families. The defect is autosomal dominant. This means that if a parent has HAE then their child has a 50% chance of inheriting the disease. However, the absence of the disease in the family does not completely rule out the HAE diagnosis since some cases occur as a result of a spontaneous mutation of the C1-inhibitor gene. These patients can then pass the improper functioning gene down to their children.

 What are the symptoms?

  • Throat swelling
  • Sudden hoarseness
  • Repeat episodes of abdominal cramping without obvious cause
  • Diarrhea
  • Vomiting
  • Swelling in the arms, legs, lips, eyes, tongue, or throat
  • There absence of itching or hives.

What causes an attack?

Most attacks occur with no apparent reason. However, anxiety, stress, minor trauma, surgery, and illnesses like a cold or flu can be triggers. Dental procedures or any trauma to the oral cavity can make HAE patients susceptible to airway attacks. The following have been shown to increase the risk of an attack:

  • Anxiety or stress
  • Trauma
  • Surgery
  • Respiratory Illnesses
  • Menstruation
  • Pregnancy
  • Certain medications: specifically ACE Inhibitors (a medication used for high blood pressure) and oral contraceptives

How is it diagnosed?

The diagnosis of HAE is confirmed by a blood test or genetic test. There are two specific tests, C1-inhibitor quantitative and C1-inhibitor functional, that confirm HAE. Other lab tests including a C4 level can identify the presence of HAE during an attack. C4 levels should be elevated during an attack, decreased immediately following an attack, and normal in between attacks.  There are three main types of HAE that can be determined based on genetic and laboratory studies. They are as follows:

  • Type I: In type I HAE, the C1-INH level is low but functional. About 85% of people with HAE have type I, thus making it the most common type.
  • Type II: In type II HAE, the C1-INH levels are normal, but they do not function properly. About 15% of people with HAE have type II.
  • Type III: In type III HAE, all C1-INH lab tests are normal, but the person still has symptoms of HAE. This is an extremely rare type, and is not entirely understood. This type is found primarily in women.

How is it treated?

The treatment of HAE requires a dual approach in which preventing HAE attacks and treating acute attacks are addressed. Patients with HAE should learn to recognize the symptoms of HAE attacks and should seek treatment immediately. Patients should work with their provider to choose the best treatment plan. The following information about disease treatment is important patients to know.


  • Androgens: Androgens are male hormones that can help prevent attacks. The androgens that are most commonly prescribed are danazol, stanozolol, and oxandrin. These androgens are attenuated, which means that the hormone is not as strong as some other male hormones. However, these medicines are normally not suitable for children and have a lot of side effects.
  • C1-INH product for prevention: C1-INH (complement 1 esterase inhibitor) therapy replaces the C1-INH protein in patients that have a deficiency.  These C1-INH infusions can be given twice weekly. Side effects from the treatment include: sinusitis, rash, headache, and upper respiratory tract infection.
  • Antifibrinolytics: These medicines are used less often in the treatment of HAE. These medicines have lots of side effects so their use is normally limited to people who have frequent and/or severe attacks and have failed other medications.

Acute Treatment

  • C1-INH product for acute attacks: C1-INH (complement 1 esterase inhibitor) therapy works by replacing the C1-INH protein in patients with a C1-INH deficiency. C1-INH for acute attacks is given when the first sign of an attack occurs. The most common side effects are nausea, diarrhea, abdominal pain, and muscle spasms.
  • Kallikrein Inhibitors: A kallikrein inhibitor works by blocking the generation of kallikrein and its byproduct, bradykinin, which is thought to cause HAE attacks. The most common side effects are dizziness, fatigue, headache, nausea, and vomiting.

There are many options available when it comes to treatment and patients should work with their provider to develop a treatment plan that works with their needs and lifestyle.

Jul 7, 2014   2393   Paul Barker    Conditions
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