Hereditary angioedema (HAE) is a rare genetic condition that can cause sudden swelling in different parts of the body. The swelling may happen in the hands, feet, face, stomach area, genitals, or throat. It can be painful, but it usually doesn’t come with itching or hives.

Some people have HAE attacks for years before they get a diagnosis. Learning more about HAE can help you understand why attacks happen and how the condition can be treated. Here are six facts about HAE.

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Hereditary angioedema causes episodes of severe swelling that are different from an allergic reaction. HAE swelling happens deeper in the body than swelling from a typical rash or allergy.

HAE usually doesn’t cause hives or itching. Allergy medicines — such as antihistamines, corticosteroids, or epinephrine — don’t work to treat HAE attacks.

Hereditary angioedema affects more than 100,000 people around the world. Because it is rare, it can take years to get the right diagnosis. Some people are first told their symptoms may be caused by allergies, anxiety, or digestive problems.

Symptoms typically begin during childhood or the teen years. About half of people with HAE experience their first swelling attack by age 10. Attacks may worsen after puberty and can continue throughout life.

Most types of HAE are passed down through families. This means a child can inherit HAE from a parent who has the condition. If one parent has HAE, each child has a 50 percent chance of inheriting it.

In up to 25 percent of people with HAE, the gene change happens by chance — even with no family history.

Most HAE cases start with a mutation in the SERPING1 gene. This gene helps the body make a protein called C1 inhibitor, or C1INH. This protein helps control swelling in the body.

When there isn’t enough working C1INH, the body can make too much of a chemical called bradykinin. Bradykinin tells blood vessels to let fluid pass into nearby tissues. When too much fluid leaks out, it can cause the deep swelling seen in HAE.

There are two main types of HAE linked to C1INH. Type 1 HAE is the most common form, accounting for about 85 percent of cases. In this type, the body simply doesn’t produce enough C1INH.

Type 2 HAE makes up about 15 percent of cases. In type 2, the body makes enough C1INH, but the protein doesn’t work properly.

There is also a rarer third form called HAE with normal C1INH. People with this type have normal C1INH levels and function. Instead, the swelling is caused by mutations in completely different genes.

Scientists have linked several different genes to HAE with normal C1INH. This rare form is also closely tied to hormones. Swelling attacks often first appear or worsen during pregnancy or menstruation or when using hormonal contraceptives.

HAE attacks can vary in location, severity, and duration — sometimes even in the same person from one episode to the next. Most attacks worsen over the first 24 hours and resolve over the following two to three days, typically lasting no more than five to seven days.

Skin and Extremity Swelling

The most visible form of an HAE attack is severe swelling of the hands, feet, face, or genitals without noticeable changes in skin color. About 1 in 3 people also experience a flat, nonitchy warning rash called erythema marginatum in the hours before swelling begins. HAE swelling doesn’t typically cause itching or hives — two key differences from an allergic reaction.

Abdominal Pain and Digestive Symptoms

Intestinal swelling happens in around 70 percent to 90 percent of people with HAE at some point in their lives, causing severe abdominal pain along with nausea, vomiting, and diarrhea. Because it resembles appendicitis or another surgical emergency, people with undiagnosed HAE have sometimes undergone unnecessary surgery — including appendectomies — before the right diagnosis was made.

Throat and Airway Swelling

Laryngeal angioedema (swelling of the throat and voice box) affects about half of people with HAE at least once, but it makes up less than 1 percent of all attacks.

Warning signs include voice changes, trouble swallowing, noisy breathing, and shortness of breath. Get emergency care right away for any of these symptoms. In people with undiagnosed HAE, untreated airway attacks may be life-threatening in about 20 percent to 25 percent of cases.

A clear trigger is found in fewer than half of HAE attacks. Without treatment, some people have attacks as often as every one to two weeks.

Common triggers include:

• Emotional stress or anxiety, such as stress before a big event or medical procedure
• Illness or infection, such as the flu or a cold
• Dental procedures, which can trigger swelling that spreads to the throat
• Surgical or medical procedures, including minor and major surgeries that cause physical stress
• Physical injury, sustained pressure, or repetitive activities like typing or manual labor
• Hormonal changes, including increased estrogen from oral contraceptives, pregnancy, menstruation, or menopause hormone therapy (also called hormone replacement therapy)

ACE inhibitors, a type of blood pressure medication, can also increase HAE attack frequency. If you’re taking this medication, it’s important to discuss alternatives with your doctor.

Getting the right diagnosis can take years. Today, people with HAE wait an average of seven to 10 years after symptoms start to get diagnosed. This is shorter than in the 1970s, when the average wait was about 21 years. Still, fewer than 40 percent of people are diagnosed within one to three years of their first symptoms.

Blood tests are needed to confirm an HAE diagnosis. The most common initial screening test checks blood levels of a protein called C4.

In most people with HAE, C4 is constantly used up by the body and runs low. In fact, C4 levels are low in up to 95 percent of people with type 1 and type 2 HAE, even between attacks, making it a highly reliable early signal.

To confirm the diagnosis, doctors rely on two specific follow-up blood tests — a C1INH functional assay (measuring how well the protein works) and a C1INH quantitative assay (measuring the actual amount in the blood).

In some cases, doctors may also perform genetic testing to look for the mutations that cause HAE. This can identify gene defects linked to HAE with normal C1INH.

There is no cure for HAE, but it can be managed with the right care plan. The goals are to treat attacks quickly, help prevent future attacks, and be ready for emergencies.

People with HAE should have enough on-demand treatment for at least two attacks at all times. Some people may also need short-term preventive treatment before dental work, surgery, or other planned procedures.

Every person with HAE should have a written emergency action plan, especially for throat or airway symptoms. Keeping an attack log can also help identify triggers and show whether the care plan needs to be adjusted.

Taking the Next Step

If you have swelling that keeps coming back and doesn’t cause hives, ask your doctor about blood tests for HAE.

If you’ve been diagnosed with HAE, work with an allergist or immunologist on a care plan. Make sure your rescue medicine is current, and talk with close family members about whether they should ask their doctors about testing.

Join the Conversation

On myHAEteam, people share their experiences with hereditary angioedema, get advice, and find support from others who understand.

What was the first sign that your swelling might not be an allergy? Let others know in the comments below.