Hereditary angioedema (HAE) is a rare genetic condition that causes repeated episodes of severe swelling throughout the body. It affects the hands, feet, stomach, genitals, face, throat, and tongue. Avoiding triggers and taking preventive medications can help reduce the frequency and severity of HAE attacks.
HAE attacks are often painful and can last for a few days. They can be life threatening if a person’s breathing is obstructed.
Stress, minor illnesses, and physical trauma are common triggers. Sometimes, however, an attack can occur without an obvious trigger.
There is currently no cure for HAE, but medications can treat the swelling once an episode starts. People with HAE can also speak with a doctor about steps they can take to prevent attacks. These steps may include minimizing triggers and taking preventive (prophylactic) medications.
In this article, learn more about what causes HAE attacks and how to help prevent them.
HAE is most commonly caused by mutations in the C1NH gene. This gene provides instructions for producing a protein called C1 inhibitor, which regulates the flow of fluids into and out of cells.
There are three types of HAE, each with a different cause:
- Type 1 is due to a deficiency of C1 inhibitor.
- Type 2 is due to dysfunction of C1 inhibitor.
- Type 3 is not related to C1 inhibitor mutations, but experts think that it may be related to other genetic mutations.
HAE attacks occur when plasma kallikrein becomes more active. This leads to an overproduction of the peptide bradykinin, which causes blood vessels to leak fluids.
A buildup of fluids outside of blood vessels can result in various symptoms, depending on where it occurs. These symptoms might include skin swelling, severe abdominal pain, or airway obstruction.
Some HAE treatments replace the C1 inhibitor that the body is lacking. Others block kallikrein or bradykinin.
Although HAE attacks are often spontaneous, they may be linked to certain triggers. Understanding these factors may help people with HAE better manage the condition.
HAE triggers are different for everyone. Some common triggers include:
- intense physical activity
- infections, such as a common cold or the flu
- physical injury or trauma
- dental procedures
- hormone fluctuations, such as those that occur during menstruation, menopause, and pregnancy
- certain medications, including ACE inhibitors, oral contraceptives, and hormone replacement therapy
- emotional stress or anxiety
Keeping a journal of one’s episodes can help people with HAE identify their triggers so that they can take steps to avoid them in the future. The journal should include:
- a description of the attack
- the treatment method
- the response to treatment
- any potential triggers
It is not possible to avoid all triggers, but making a few lifestyle changes may help minimize exposure to them. Some examples of lifestyle changes to try include:
- receiving yearly influenza vaccinations
- asking a loved one to help out with physically demanding tasks, such as yard work
- prioritizing sleep and self-care
- avoiding very strenuous exercise
- engaging in enjoyable physical activity that does not trigger symptoms and helps relieve stress
- practicing proper daily dental hygiene habits to reduce the need for dental surgery
Prophylactic treatments are medications that people take to prevent or minimize episodes. Not everyone with HAE requires prophylactic treatment, however. Anyone with HAE should talk with a doctor to create a detailed treatment plan.
A person’s treatment plan should be individualized based on a variety of factors, including their:
- access to emergency care
- HAE triggers
- personal preferences
The goal of prophylactic treatment is to decrease the number and severity of HAE attacks. This is known as long-term prophylaxis.
A doctor may also prescribe a short-acting prophylactic treatment to reduce the likelihood of HAE attacks before any potential exposure to likely triggers, such as surgery.
There are four prophylactic treatments with Food and Drug Administration (FDA) approval for HAE. The sections below will look at these in more detail.
C1 esterase inhibitors (Cinryze and Haegarda)
Cinryze and Haegarda are both C1 esterase inhibitors approved for prophylaxis against HAE attacks in adults and children aged 6 years and older.
People take these medications twice weekly. Cinryze comes as an IV infusion, which is an injection into a vein that is slowly dripped over time. Haegarda comes as a subcutaneous injection, which is an injection just under the skin.
People with HAE can receive injections at a doctor’s office. Alternatively, a doctor or pharmacist can teach a person or their caregiver how to administer the medications at home.
Lanadelumab (Takhzyro) is a plasma kallikrein inhibitor approved as a prophylaxis to prevent HAE attacks in adults and adolescents aged 12 years and older.
The medication comes as a subcutaneous injection that a person will receive once every 2 weeks or once every 4 weeks. A doctor or pharmacist can train a person with HAE or their caregiver on how to self-inject the medication at home.
Berotralstat (Orladeyo) is a selective inhibitor of plasma kallikrein. It is the first oral therapy for HAE attacks.
The medication has approval to prevent attacks in adults and adolescents aged 12 years and older. People take it by mouth once per day.
Prophylactic treatments do not prevent all HAE attacks, which can be unpredictable. If an attack occurs, a person should receive on-demand medications immediately.
On-demand treatments for HAE include:
- C1 esterase inhibitor, human (Berinert): This is a plasma-derived C1 inhibitor concentrate for IV use.
- C1 esterase inhibitor, recombinant (Ruconest): This is a plasma-free recombinant C1 inhibitor concentrate for IV use.
- Ecallantide (Kalbitor): This is a kallikrein inhibitor that comes as a subcutaneous injection. It is the only HAE treatment that a person must receive from a healthcare professional.
- Icatibant (Firazyr): This is a bradykinin B2 receptor antagonist that people receive as a subcutaneous injection.
The US Hereditary Angioedema Association recommends that people with HAE due to C1 inhibitor deficiency should always have access to at least two standard doses of an FDA-approved medication for HAE.
Although most attacks are treatable outside of a medical setting, people with HAE should be prepared to access a healthcare facility during an attack.
It is important to know that people living with HAE will not respond to medications for allergic reactions, such as epinephrine, antihistamines, or corticosteroids.
Preventing HAE attacks includes both understanding and avoiding potential triggers and taking preventive medications.
People with HAE should also understand the differences between on-demand and prophylactic medications, how to store the medications, who will administer the medications, and signs they need to seek additional assistance.
Managing triggers can help prevent attacks, but HAE attacks are often unpredictable. Anyone with HAE should take care to refill their medications on time so that they are prepared for any subsequent attack.