HAE Causes and Risk Factors

Hereditary Angioedema (HAE) is a rare genetic condition. It causes severe episodes of swelling in the body. This swelling can affect the face, hands, feet, and belly. It can also affect the throat, which can make it hard to breathe or swallow.^1,2

Living with HAE can be hard for people who have the condition and their caregivers. The swelling can cause severe pain and disrupt daily life. Knowing why this swelling happens can help you manage the condition.

What causes hereditary angioedema?

A change in certain genes causes HAE. This change is called a mutation. Most people with HAE have a mutation in a gene called the SERPING1 gene. This gene helps the body make a protein called C1 inhibitor (C1-INH).^1-3

The C1-INH protein controls inflammation and swelling in your body. When the gene has a mutation, the body does not make enough protein. Or, the protein does not work the way it should. This problem leads to a buildup of another protein called bradykinin.^1-3

Too much bradykinin makes blood vessels leak fluid into nearby tissues. This extra fluid builds up and causes severe swelling. The swelling often lasts for 3 to 4 days if left untreated. ^1-3

Types of HAE

People with HAE have 1 of 3 different types. They include:^1-3

• Type 1 – This is the most common type. In this type, the body does not make enough C1 inhibitor protein.
• Type 2 – This is less common. In this type, the body makes enough protein, but it does not work the way it is supposed to.
• HAE with normal C1-INH – Also known as type 3, this is the rarest type. It occurs with normal levels of C1 inhibitor protein. Mutations in other genes, like the FXII (Factor 12) gene, cause this type. These mutations make other proteins easier to activate. This activation also leads to too much bradykinin in the body. More research is needed to understand this rare form of HAE.

What are the risk factors for HAE?

Family history is the primary risk factor for this condition. HAE is passed down from parents to children in an autosomal dominant pattern. This term means a child only needs 1 copy of the changed gene. A parent with HAE has a 50 percent chance of passing it to a child.^1-3

HAE affects men and women equally. It affects people of all races and ethnicities around the world. Symptoms often begin during childhood or young adulthood. The swelling episodes can get worse when a child reaches puberty.^1-3

Some people with HAE have no family history of the condition. About 25 percent of cases come from a new genetic change. This change happens by chance during early development. These people can still pass this abnormal gene to their children.²

Common triggers of an HAE attack

People with HAE have genes that cause the condition. However, certain everyday events can trigger an attack. Triggers do not cause the disease itself. They just cause a sudden episode of swelling to start.^1-3

Triggers can vary from person to person. An event that triggers swelling in 1 person might not affect another. Some attacks happen without any clear cause.^1-3

Common triggers for HAE swelling include the following items:^1-3

• Physical injury or minor trauma can cause swelling.
• Dental work or surgery can start an attack.
• Emotional stress and anxiety can trigger episodes.
• Viral infections like a cold can lead to swelling.
• Activities like typing, hammering, or shoveling can cause a reaction.
• Changes in hormone levels during pregnancy can affect attacks.
• Certain drugs, like specific blood pressure medicines, can trigger swelling.

It might be helpful to track your daily activities and when swelling occurs so you can pinpoint potential triggers. This can help you prepare for the future.

Work with your healthcare team

Many everyday events can trigger swelling attacks. These events include stress, illness, and physical trauma. Understanding your causes and triggers can help you manage HAE. Work with your healthcare team to create a safe treatment plan.³