What Is Hereditary Angioedema?
Hereditary angioedema (HAE) is a rare condition that causes fluid to build up throughout your body, triggering sudden and repeated serious swelling.
There are three types of hereditary angioedema:
Hereditary angioedema type I
This is the most common type and happens because of very low levels of certain proteins in your blood called C1 esterase inhibitors (C1-INH). These proteins help control different body functions like the flow of fluids in and out of cells.
Without enough normal C1-INH protein, the body has too much of a peptide called bradykinin, which raises fluid leakage through blood vessel walls into tissues, causing swelling attacks.
Hereditary angioedema type II
Hereditary angioedema type II is less common and happens when your body makes abnormal versions of C1-INH, which also leads to too much bradykinin.
Hereditary angioedema with normal C1 inhibitor
This type of HAE mainly affects women and people assigned female at birth and depends on estrogen. People with this have normal levels and function of C1-INH. Researchers aren’t sure what triggers this type and how it works in the body.
Hereditary Angioedema Causes
People with HAE have an abnormal gene that they got from their parents. Your parents pass down HAE as an autosomal dominant trait. This means you only need one copy of the abnormal gene from one parent to have the condition.
Each child of an affected parent has a 50% chance of getting the abnormal gene regardless of the child's sex.
Factor XII and hereditary angioedema
Most cases of HAE can be traced to mutations in the F12 gene. This gene makes a protein called coagulation factor XII, which plays a role in blood clotting and inflammation.
In these cases, the F12 gene makes a factor XII protein that is more easily triggered, which leads your body to make more bradykinin. Higher levels of bradykinin mean more inflammation and leaky blood vessel walls, which cause swelling attacks.
Hereditary Angioedema Symptoms
The main symptom of HAE is swelling in different parts of the body. This is from a buildup of too much fluid (edema). You’ll typically have hard and painful swelling, but it’s not red or itchy like other types of angioedema. Symptoms can come back and may become more serious.
Early signs of hereditary angioedema
You’ll probably start noticing symptoms of HAE in childhood, and they get worse as you reach puberty.
Hereditary angioedema attacks
Swelling attacks tend to happen every 1 or 2 weeks and last up to a few days. How often these attacks happen and how long they last can be different from person to person, even within the same family.
Hereditary angioedema swelling
The condition can lead to swelling in your:
- Hands
- Feet
- Eyelids
- Lips
- Genitals
- Digestive tract
- Airway
Hereditary angioedema rash
Around one-third of people with HAE will have a skin rash called erythema marginatum. It happens during an attack but isn’t itchy.
Other symptoms
When hereditary angioedema affects your digestive system, symptoms may include:
- Feeling sick to your stomach
- Throwing up
- Stomach pain
Swelling in your throat or voice box can cause:
- Pain
- Trouble swallowing
- Trouble speaking
- Noisy breathing
- Life-threatening choking
Hereditary Angioedema Triggers
Triggers for an HAE attack can include:
- Injury
- Serious pain
- Surgery
- Dental procedures
- Viral illness
- Stress
Hereditary Angioedema Diagnosis
Doctors diagnose HAE by performing a physical exam, learning more about your medical history, and checking your blood for low levels of certain proteins. They’ll likely suggest genetic testing if they suspect you have the condition.
Tests for hereditary angioedema
Here’s what doctors test your blood for to figure out if you have HAE:
Type I HAE
- Low levels of C1-INH protein
- Low C4 level
- Normal C1q level
Type II HAE
- Normal or high, but nonfunctional, C1-INH level
- Low C4 level
- Normal C1q level
HAE with normal C1 inhibitor levels
- Normal C1-INH level
- Normal C1-INH function
- Normal C4 and C1q levels
- Possible Factor XII mutation
Imaging studies
These imaging studies can also help doctors diagnose HAE:
Abdominal X-ray. During a digestive system attack, an X-ray may show signs of a blockage.
Chest X-ray. This type of X-ray can show any fluid that might be in your chest.
Abdominal ultrasound or CT scan. This test may show thickening in the wall of your intestine, fluid around your bowel, and large amounts of free fluid in your abdomen.
Questions for your doctor
An HAE diagnosis can be overwhelming, and you probably have lots of questions for your doctor. Here’s a list you can ask at your next appointment. You may not be able to ask them all, so think about which ones are most important to you:
- How serious is my condition, and how will it affect my day-to-day life?
- What is the outlook for my condition?
- Could another illness be causing my symptoms?
- Which tests should I have?
- What symptoms should I be on the lookout for?
- When should I schedule a follow-up visit?
You can also ask:
- What are the treatment options for my condition?
- How much does treatment cost?
- Is there a generic version of my treatment available?
- Does treatment come with side effects?
- What are the pros and cons of treatment?
- How do I know if the treatment is working?
Hereditary Angioedema Treatment
Treatment for HAE involves medications and other therapies. The goals are to:
- Stop attacks from happening
- Treat symptoms when they appear
- Treat before events that might trigger an attack
Hereditary angioedema drugs
The FDA has approved several drugs to treat HAE:
Berinert. Made from human plasma, this C1 esterase inhibitor treats sudden stomach and face swelling caused by HAE. It’s given intravenously, or through an IV. Berinert is the first FDA-approved treatment for kids with HAE.
Cinryze. This is a C1 esterase inhibitor injection, or shot given into a vein, for teens and adults with HAE. It wards off swelling attacks. It’s the first drug the FDA approved for this purpose.
Danazol. This is a synthetic steroid capsule that helps avoid HAE attacks without needing to normalize C1-INH levels. Don’t take this medication if you’re pregnant because it can harm your unborn baby.
Epsilon-aminocaproic acid or tranexamic acid. You take these pills or injections into a muscle or vein to ward off HAE attacks. But they don’t work as well as other medicines.
Firazyr (icatibant). This treats sudden HAE attacks by blocking the bradykinin B2 receptor, which eases swelling.
Haegarda. A C1-esterase inhibitor injection given under the skin that blocks HAE attacks.
Kalbitor (ecallantide). An under-the-skin injection that treats sudden, severe fluid buildup related to HAE.
Lanadelumab (Takhzyro). This monoclonal antibody is made from immune cells and blocks HAE attacks by targeting an enzyme in your body. It’s given as an under-the-skin injection.
Orlaydeo (berotralstat). A pill you take once a day to ward off HAE attacks.
Ruconest. A C1-esterase inhibitor intravenous injection that treats sudden attacks in people with HAE.
Hereditary angioedema therapy
If fluid loss in your tissues has triggered low blood pressure, you may need large amounts of IV fluids to stay stable. Your doctor may prescribe strong painkillers for stomach pain.
Home remedies for hereditary angioedema
Home remedies can offer relief from swelling. Try ice, a cool shower, or a cool, wet cloth over swollen areas.
When to go to the emergency room
Go to the ER right away if your throat starts to swell. That could block your airway and stop you from breathing. The doctor may make a temporary opening in your throat (tracheotomy) to help you breathe.
Hereditary Angioedema Progression
HAE usually starts in childhood with mild attacks that happen every so often. People who start having HAE attacks at a younger age tend to have a worse outlook than those who start later in life. As you reach puberty, symptoms become more serious. How often attacks happen depend on the person. It could be every week to once a year.
Complications of Hereditary Angioedema
HAE can lead to serious, even life-threatening health problems, including:
Upper airway swelling. Swelling in your throat can block the airway, cutting off oxygen.
Gastrointestinal swelling. Abdomen swelling can cause serious pain, which doctors often mistake for other conditions, leading to needless surgeries and delays in the correct diagnosis.
Skin swelling. This can change how you look or your ability to do certain things, impacting your quality of life.
Seizures. Symptoms affecting your nervous system, including seizures, are also common in people with HAE. One study of people with HAE found that around 17% have epilepsy.
Hereditary angioedema and dental treatment
If you’re having dental work done, you’ll need short-term treatment for HAE to avoid a swelling attack. You may get C1-INH infusions a day or less before your procedure.
Other medicines to help avoid swelling (antifibrinolytics or androgens) are another option. You’ll take them 5 days before the dental procedure and continue for another 2 days afterward.
You might also get an infusion of fresh frozen plasma (FFP) on the day of surgery or the day before.
Taking Care of Yourself
HAE is an illness that you’ll need to manage for most of your life, mostly with medication. But there are other ways to potentially ease painful symptoms.
Hereditary angioedema diet
There’s no special diet for people with HAE, and it’s not necessary to restrict what you eat to control your symptoms.
Managing hereditary angioedema
Watching for changes to your symptoms and medication are your best bets for managing HAE. Research is ongoing, but some people with the condition also find nondrug treatments helpful, including taking care of their mental health.
Lowering your stress levels could be especially useful since stress can trigger HAE or make an attack worse. First, figure out what triggers your stress. Is it relationship problems, work issues, or something else? Then, take steps to control your stress. Here are some tips:
- Manage your time and prioritize the things you need to do. Learn to say no to unimportant commitments.
- Practice relaxation techniques like deep breathing, tai chi, yoga, meditation, mindfulness, or spending time in nature.
- Set aside time for self-care activities that help you relax.
- Keep a healthy lifestyle with a balanced diet, regular exercise, and enough sleep.
- Cut back on screen time.
- Avoid using alcohol or drugs to control stress.
What to Expect
Before scientists developed effective treatments for HAE, the death rate for the condition was around 20% to 30%. Today, the outlook is much better. Medication can treat both short-term and long-term side effects.
You can expect to manage painful swelling attacks that affect different parts of your body and last for up to 72 hours. Common triggers include stress, physical trauma, and hormonal changes like menstruation. You may have warning signs before an attack, such as tingling, mood changes, or fatigue.
Getting Support
Understanding HAE, your treatment options, and lifestyle changes is crucial to managing the condition. Talk to your doctor for support. They could direct you to a specialist or other resources dedicated to hereditary angioedema.
Groups like the U.S. Hereditary Angioedema Association and HAE International are focused on the condition and providing support.
Hereditary Angioedema Takeaways
Hereditary angioedema is a rare genetic disorder that causes sudden, severe swelling in various body parts due to fluid buildup outside blood vessels. Symptoms often start in childhood and get worse during puberty. They include swelling in your hands, feet, face, and airways. Treatments focus on avoiding and managing attacks with medication.
Hereditary Angioedema FAQs
Is hereditary angioedema contagious?
No. You get the condition from your parents through your genes.
Is hereditary angioedema an autoimmune disease?
No, it’s a genetic disease. But a lack of C1-inhibitors can cause your immune system to become overly active and lead to a buildup of immune system molecules in your tissues, which might lead to autoimmune disease.
One study found that compared to those without HAE, people with the condition have a much higher chance of getting an autoimmune disease.
What is the life expectancy of someone with angioedema?
Studies show that the life expectancy of someone with HAE is the same as that of the general population.
Does hereditary angioedema go away?
There’s no cure for HAE, but treatment can shorten an attack, make it less severe, and help you avoid one.
