Hereditary angioedema (HAE) is a rare condition that causes swelling in various parts of the body. Without treatment, the condition can be life threatening.
HAE affects an estimated 1 in 10,000 to 1 in 50,000 people. However, the true number of cases is not well-documented. Reasons for this may include the limited awareness of the condition and the similarity of its symptoms to those of other disorders.
In this article, we discuss HAE in more detail, including its symptoms, causes, and treatment.
Researchers characterize HAE as recurrent, severe swelling of the mucous membranes and skin. It can also occur in the gastrointestinal tract or upper airway.
The swelling may occur on or in the following body parts:
- hands and feet
- face (commonly the lips and eyes)
- upper airway (in the tongue or throat)
HAE is a genetic condition that often passes down from one generation to the next. Children have a 50% chance of inheriting HAE if one of their biological parents has the condition.
Scientists consider the condition hereditary, but up to 25% of cases are the result of a spontaneous mutation at the time of conception. This mutation affects the gene responsible for the production of C1 inhibitor. In those cases, the genetic trait can then pass from a person to their children.
There are two main types of HAE: type 1 and type 2. The third type, HAE with normal C1 inhibitor, is rare and not fully understood.
Type 1 HAE
Type 1 HAE accounts for nearly 85% of all cases. Type 1 occurs when a person has low levels of C1 inhibitor in their blood.
Type 2 HAE
Type 2 HAE accounts for 15% of all cases. In type 2 cases, a person’s C1 inhibitor level is normal or close to normal, but the protein does not function properly.
HAE with normal C1 inhibitor
HAE with normal C1 inhibitor, also known as estrogen-dependent or type 3 HAE, occurs in a very small number of cases. People living with this type of HAE experience symptoms of the condition, but their C1 inhibitor is fully functional and appears at normal levels. The condition primarily affects natal females.
The symptoms of the three main types of HAE are the same or similar. Swelling of the skin occurs most commonly on various areas of the body, including the:
Swelling of the skin can cause loss of function in the area, as well as disfigurement and pain. The effects of the attack typically go away on their own within 2–4 days.
A person may also experience swelling of their abdomen, throat, or other organs. When swelling occurs in the abdomen, it can cause additional symptoms, such as pain, diarrhea, and vomiting. Healthcare professionals often mistake angioedema of the abdomen for a surgical emergency.
Swelling that occurs around the throat can become a life threatening emergency that requires immediate medical attention.
Symptoms typically first appear earlier in life. In most cases, they present no later than the age of 13 years. The symptoms may increase in severity as the person gets older.
A person will likely experience episodes of symptoms that occur at different times. Possible triggers include emotional stress and physical trauma. A person may sometimes experience a spontaneous episode with no known cause.
HAE has two primary causes. According to UC San Diego Health, the two most common causes are an inherited gene defect (about 80% of cases) and a spontaneous mutation in the C1 inhibitor (about 20% of cases).
Type 3 HAE does not occur due to C1 inhibitor mutations. Instead, research has identified an association between symptomatic episodes and an increase in estrogen due to pregnancy or taking birth control pills, among other factors.
There is no cure for HAE. Treatments focus on both preventing attacks from occurring and treating symptoms.
People living with HAE will not respond to medications that often help with other conditions that cause swelling or angioedema. Medications that are ineffective include epinephrine, antihistamines, and corticosteroids.
According to the US Hereditary Angioedema Association (HAEA), doctors currently use seven medications to treat HAE. These are:
- Berinert: This intravenous C1-inhibitor concentrate treats HAE attacks in children and adults.
- Cinryze: This drug is an intravenous C1 esterase inhibitor that helps prevent HAE attacks in children, teens, and adults.
- Haegarda: People self-administer this plasma-derived concentrate of C1-esterase inhibitor.
- Ruconest: Doctors use this plasma-free recombinant C1-inhibitor concentrate to treat HAE attacks in adults and adolescents. They give it to the person intravenously prior to an attack starting.
- Firazyr: Doctors give this B2 bradykinin receptor antagonist in the form of an injection to treat acute HAE attacks in people aged 18 years and older.
- Kalbitor: This kallikrein inhibitor, which a person receives in the form of an injection, treats acute HAE attacks in people aged 12 years and older.
- Takhzyro: Doctors use this plasma kallikrein inhibitor to prevent attacks of HAE in people aged 12 years and older. They give the drug via injection once every 2 weeks.
Parents or caregivers should talk to their child’s doctor about the possibility of them having HAE, particularly if one or both biological parents are living with the condition. The HAEA recommend waiting until the child is at least 1 year old before testing for the condition.
If the child does have HAE, parents or caregivers should talk to their doctor about available treatment options and work with them to create a treatment plan.
People with HAE who are pregnant should also talk to their doctor about their treatment options.
HAE is a rare genetic condition that causes swelling in various areas of the body. When it affects the throat, it can be life threatening. Swelling in the abdomen can cause gastrointestinal symptoms, such as pain, diarrhea, and vomiting.
Medications can treat the swelling, and the symptoms should go away within a few hours to a few days. A person should work with their doctor for a proper diagnosis and an effective treatment plan.