Understanding Hereditary Angioedema (HAE)

People with hereditary angioedema (HAE) may spend years searching for answers. The road to an accurate diagnosis can be long and difficult. You may have visited many doctors. You may have been told your swelling is just a bad allergy. HAE is a rare genetic condition. It is not an allergic reaction. Understanding how it works is the first step toward managing your health.^1,2

What is hereditary angioedema (HAE)?

HAE is a condition that causes parts of the body to swell. This swelling (also called edema) often happens in the hands, feet, face, and throat. It can also happen in the stomach. When it happens in the stomach, it causes a lot of pain. When it happens in the throat, it can obstruct the airway, causing breathing problems.^1-3

HAE is caused by a problem with a protein in the blood. This protein is called C1 inhibitor (C1-INH). In most HAE cases, the body does not make enough of this protein. In other cases, the protein is there, but it does not work as it should. This protein is meant to control swelling. Without it, the body cannot stop fluid from leaking into tissues.^1-3

The broken brake: How swelling starts

To understand HAE, think of a car with a broken brake. The C1-INH protein is the brake for your body. It keeps certain chemicals in check. One of these chemicals is called bradykinin. Bradykinin is a peptide (a small protein) that tells your blood vessels to open up. C1-INH is supposed to stop an enzyme called kallikrein from creating too much bradykinin.^1-3

When the C1-INH "brake" is broken, your body makes too much bradykinin. This is called the bradykinin cascade.^1-3

Too much bradykinin makes the walls of your blood vessels very thin. They become leaky. Fluid from the blood leaks out into the space around the vessels. This leads to the heavy swelling you feel during an attack.^1-3

Because this process does not involve histamine, allergy drugs do not work. You need treatments that target the bradykinin system or replace the missing "brake."^1-3

The 3 types of HAE

There are 3 main types of HAE. Each type involves the C1-INH protein or other genetic factors in a different way:^1-3

• Type 1 – This is the most common form. About 85 percent of people with HAE have Type 1. In this type, the body does not make enough C1-INH protein. Levels of the protein in the blood are very low.
• Type 2 – This type affects about 15 percent of people. In Type 2, the body makes a normal amount of C1-INH protein. However, the protein does not work correctly.
• Type 3 – This is now more often called HAE with normal C1-INH. It is very rare. People with this type have normal levels of C1-INH. The protein also works fine. The swelling is caused by genetic mutations. One of them being the F12 gene, encoding coagulation factor XII (Hageman factor).

What triggers an HAE attack?
Swelling attacks often have a specific cause. These causes are called triggers. Knowing your triggers can help you manage your health. Not every person has the same triggers. Common triggers for many people include:^1-3

• Emotional or mental stress
• Physical injury or trauma to the body
• Dental work or medical surgeries
• Illnesses like a cold or the flu
• Hormonal changes, especially in women
• Certain heart drugs called ACE inhibitors

Your comprehensive care plan

A comprehensive care plan is a map for your future health. It helps you and your doctor track your condition. A key part of this plan involves blood tests. These tests are called complement studies.

If you have HAE, doctors look at 3 main things:^1,2

• C4 levels – This is often the first test. C4 is a protein that is usually low in people with HAE, even between attacks. While C4 is a great screening tool for Types 1 and 2, it is important to note that people with HAE with normal C1-INH (Type 3) usually have normal C4 levels.
• C1-INH protein levels – This shows if you have enough protein.
• C1-INH function – This test shows if the C1-INH in the body is working.

Your care plan will also include a strategy for attacks. You will learn about "on-demand" treatments. These are used when an attack starts. You may also talk about "prophylaxis" (preventative treatment). These are medicines you take to stop attacks before they happen. Your doctor will help you decide which path is best for you.^1,2

Moving forward with confidence

A diagnosis of HAE can feel like a heavy weight. But it is also a tool. It gives you the power to find treatments that actually work. Do not be afraid to ask your healthcare team many questions. Reach out to community groups for support. With a solid care plan and an understanding of your body, you can manage HAE. You can live a full and active life.