What Is Hereditary Angioedema (HAE)? Symptoms, Causes, Diagnosis, Treatment, and More

Hereditary angioedema (HAE) is an uncommon but serious genetic disease that causes swelling in different parts of your body.

Symptoms of HAE usually start in childhood and worsen during the teen years, according to the U.S. Hereditary Angioedema Association. (1)

People with HAE may notice that their hands, feet, face, and throat swell up. Abdominal pain, nausea, and vomiting are also common symptoms if HAE affects a person’s intestinal tract. (1)

Although HAE is a lifelong disease, there are treatments to help manage the condition.

Why Does Hereditary Angioedema Happen?

HAE is caused by a mutation, or defect, in the gene that makes a protein called C1 inhibitor. This protein helps control inflammation in your body. (1)

These mutations are inherited in an “autosomal dominant” pattern, meaning that it takes inheriting only one copy of the gene from a parent to have the disease. If one parent has the gene defect that causes HAE, a child has a fifty-fifty chance of inheriting it. (3)

In most cases of HAE, the gene mutations mean that you either don’t have enough C1 inhibitor or it doesn’t function properly. (5)

Not having a family history doesn’t guarantee you won’t develop HAE. The genetic mutations that cause HAE can also crop up for unknown reasons during conception. In fact, as many as 25 percent of HAE cases result from a spontaneous gene mutation. (1)

Hereditary angioedema (HAE) can cause signs and symptoms that are scary, painful, and disfiguring.

HAE attacks cause swelling in different parts of the body. Attacks can range from mild to severe. The frequency and length of the swelling attacks varies in those with HAE. Typically, people who aren’t receiving preventive treatment for the disease have an attack about every one to two weeks. Most of these episodes last three to four days. (1)

Your symptoms will depend on the type of HAE attack you have.

A subcutaneous attack involves swelling and redness on different areas of your skin.

If you have an abdominal episode, you might experience stomach pain, nausea, diarrhea, or vomiting.

Swelling attacks that involve the face, throat, neck, or tongue are particularly dangerous because they can interfere with breathing. These episodes are usually considered medical emergencies. You may need a breathing tube placed down your throat or into your windpipe to open your airways. Sometimes severe swelling in your throat can even lead to death. (1,6)

What Are the Triggers of an HAE Attack?

Sometimes, people with HAE are able to identify certain triggers that spark the swelling. Other times, these attacks come without warning.

Common triggers of HAE attacks include: (1)

• Anxiety
• Stress
• Minor trauma
• Surgery or even dental work
• Ailments such as colds or flu
• Hormonal changes related to things like puberty or pregnancy

It’s important to identify the first signs of an HAE episode so that you can get treatment quickly.

Learn More About Signs and Symptoms of Hereditary Angioedema

There Are Three Types of HAE

HAE only occurs in about 1 in 10,000 to 1 in 50,000 people worldwide. The three main types are: (1)

• Type 1 This is the most common form of HAE. People with type 1 have low C1 inhibitor levels. Type 1 accounts for about 85 percent of all cases.
• Type 2 With this type, C1 inhibitor levels are normal, but the protein doesn’t work like it should. About 15 percent of occurrences are type 2.
• Type 3 In this very rare form of HAE, C1 inhibitor levels and function are normal. Some instances of type 3 HAE may be due to mutations in the F12 gene, but doctors aren’t sure what causes other cases. (6) Type 3 was once thought to occur only in women, but scientists now know men are also affected. It’s usually diagnosed in adulthood. Type 3 HAE is so rare that scientists aren’t sure exactly how many people have it. (1)

Each type of HAE produces similar episodes of swelling.

Other related disorders can cause similar symptoms. These may include: (8,9)

• Acquired Angioedema (AAE) This type of angioedema isn’t hereditary but causes swelling episodes that are similar to those of HAE. AAE is sometimes linked to an underlying medical condition, such as an autoimmune disorder or cancer.
• Drug-Induced Angioedema Some medicines can cause angioedema attacks, even if you’re not allergic to the drug. Common culprits include angiotensin-converting enzyme (ACE) inhibitors, ibuprofen, and angiotensin-2 receptor blockers (ARBs).
• Cutis Laxa This is a rare, inherited disorder that causes limp, saggy, inelastic skin. It’s often confused with HAE.

The age of diagnosis varies when it comes to HAE, and delays are common.

In one study, one-half of the participants said their symptoms started by age 7. More than two-thirds said they had symptoms by age 15.

Many people report experiencing more attacks around the time of puberty or adolescence.

Research shows that because HAE is rare and often confused with other disorders, which complicates diagnosis. One survey of people with HAE found that it took an average of 8.4 years before they received an accurate diagnosis. (10)

Most experts recommend that, if HAE is known to run in a family, parents wait until a child is at least 1 year old before testing them for the disease.

A misdiagnosis can be inconvenient and dangerous. You might not get the correct treatment, or you may have to undergo unnecessary medical procedures.

A simple blood test can usually detect HAE. Genetic testing is another method, but it’s usually not the preferred option for most people.

Once you do get a correct diagnosis, it’s important to find a specialist who has experience working with HAE patients.

RELATED: Appendicitis in Children: Signs, Symptoms, and More

Learn More About Hereditary Angioedema Diagnosis

There’s no cure for hereditary angioedema (HAE), but certain therapies can help control your symptoms.

Your doctor will recommend a treatment plan based on how often you have HAE attacks, how severe the attacks are, your general health, and other factors.

All HAE patients should have access to an on-demand treatment to take when they have symptoms. Your doctor might also prescribe a preventive medicine to help protect against a future attack.

The U.S. Food and Drug Administration has approved many injectable therapies for HAE over the years, and the first oral therapy was approved in 2020. (11)

Medication like antihistamines or steroids — which are typically used to treat allergic reactions — generally won’t help an HAE episode.

Your healthcare provider can assist you in deciding on the best treatment regimen for your disease.

Some people with HAE are interested in clinical trials, which may provide a new treatment option that isn’t yet available to the general public. You can search for clinical trials at the ClincalTrials.gov website.

Learn More About Hereditary Angioedema Treatment

While there’s no way to predict when an HAE attack will occur, some people report symptoms that seem to signal an attack is near. Others are able to identify certain triggers, such as stress, an infection, or medication, that spark an episode.

It’s a good idea to keep a journal listing any potential triggers that could be causing your attacks.

Family members and close friends should know what to do if you experience an episode. Keep your medical paperwork with you in case you have a severe attack and can’t help yourself.

The U.S. Hereditary Angioedema Association’s medical advisory board also recommends that all patients keep a record of their attacks, the medicines they use, and how they respond to treatment. (11)

RELATED: 15 Quotes to Inspire People With Chronic Illness

Learn More About the Triggers of Hereditary Angioedema

HAE can affect your quality of life. Many people report pain, fatigue, and disfigurement following an attack. Kids may miss school, and adults might have to repeatedly call in sick to work.

Your long-term outlook will depend on the frequency, severity, and location of your HAE attacks.

About one-third of people with HAE report having more than one attack per month. Roughly 40 percent have an average of 6 to 11 attacks per year. About 22 percent only experience attacks from time to time. Some people report attacks that last more than a week. (5)

Typically, swelling episodes continue throughout a person’s lifetime, but they can be controlled with certain treatments. (6)

If you have HAE, it’s important to find a doctor who’s experienced in treating the disease. Immunologists and hematologists are often trained to help people with HAE. (5)

Living with HAE can be overwhelming at times. Unpredictable attacks often interfere with your professional and social life.

If untreated, some attacks can last longer than a week. Many people with HAE miss out on school, work, and other activities.

The good news is there are steps you can take to help cope with your disease. Creating a support system, lowering your stress levels, and connecting with a patient advocate are just some ways to take charge of your illness.

You’ll probably still be able to experience other life events, like pregnancy and traveling, but you might need to take special precautions.

People with HAE can live productive and fulfilling lives. Having a plan in place can help you achieve success.

Learn More About Living With Hereditary Angioedema

It’s possible to live with hereditary angioedema and manage its symptoms. But living with a chronic condition — especially a rare one — can feel isolating. And the treatment required to prevent and manage episodes can be expensive. The good news: Advocates have banded together to offer support, insight, information, and, when necessary, financial help. 

Learn More About Resources for Coping With Hereditary Angioedema