What Is Hereditary Angioedema (HAE)?

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

HAE only occurs in about 1 in 10,000 to 1 in 50,000 people worldwide. Although HAE is a lifelong disease, there are treatments to help manage the condition.

This protein helps control inflammation in your body.

• Type 1: This is the most common form of HAE, accounting for 85 percent of all cases. People with type 1 have low C1 inhibitor levels.
• 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.
• HAE with normal C1 inhibitor: In this very rare form of HAE, formerly known as type 3, C1 inhibitor levels and function are normal. Research has found that defects in other genes — including factor XII, angiopoietin-1, and plasminogen — can cause HAE. With this type of HAE, the onset of swelling often occurs at a later age, more women are affected, and estrogen may play a role in the disease.

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Each type of HAE produces similar episodes of swelling.

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

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.

HAE is a genetic disorder. It may be caused by changes in the SERPING1 gene (also called the C1NH gene) or in other genes, though in some cases the cause is not yet known.

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.

• 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.

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.

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

• Acquired angioedema: This type of angioedema isn’t hereditary but causes swelling episodes that are similar to those of HAE. It 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 inhibitors, ibuprofen, and angiotensin-2 receptor blockers.
• Cutis laxa: This is a rare, inherited disorder that causes limp, saggy, inelastic skin. It’s often confused with HAE.

There’s no cure for 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.

Medication Options

Preventive medications include:

• Andembry (garadacimab-gxii) is a once-monthly injection for people ages 12 and over.
• Cinryze (C1 esterase inhibitor [human]) is indicated for adults, adolescents, and children ages 6 and older. It’s delivered intravenously and is approved for self-administration.
• Dawnzera (donidalorsen) is an RNA-targeted preventive treatment for HAE that offers the longest time between doses, every four or eight weeks. It can be self-administered via auto-injector.
• Heagarda (C1 esterase inhibitor subcutaneous [human]) is delivered by injection, for routine prevention of HAE attacks in patients ages 6 and older.
• Orladeyo (berotralstat) is an oral, once-daily plasma kallikrein inhibitor indicated for routine prevention of attacks in patients ages 12 and older.
• Takhzyro (lanadelumab-flyo) is a plasma kallikrein inhibitor (monoclonal antibody) indicated for preventing attacks in patients ages 2 and older. It’s an injection approved for self-administration.

Medications for acute attacks include:

• Berinert (C1 esterase inhibitor [human]) is an IV infusion you can administer yourself. It’s approved for adults and children.
• Ekterly (sebetralstat) is an oral, on-demand treatment for acute attacks in people ages 12 and older. It’s designed to treat attacks as soon as symptoms begin.
• Firazyr (icatibant injection) is a bradykinin B2 receptor antagonist for treatment of acute attacks in people ages 18 and older. It’s an injection that can be self-administered.
• Icatibant (generic) is an injectable bradykinin B2 receptor antagonist that treats acute attacks in people ages 18 and older.
• Kalbitor (ecallantide) is indicated for treatment of acute attacks in patients ages 12 and older. It’s delivered by subcutaneous injection and it needs to be administered by a healthcare professional.
• Ruconest (C1 esterase inhibitor [recombinant]) is a plasma-free recombinant C1-inhibitor concentrate for treating attacks in adults and adolescents. It’s an intravenous infusion that is approved for self-administration.

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

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 ClincalTrials.gov.

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

While swelling episodes typically continue throughout a person’s lifetime, they can be controlled with certain treatments. And there are steps you can take to help yourself cope with the 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. The resources and virtual support groups offered by the U.S. Hereditary Angioedema Association are a good place to start.

• Hereditary angioedema is a rare genetic condition characterized by episodes of painful and extreme swelling in various body parts, most dangerously affecting the airways, which can lead to respiratory issues and require emergency medical attention.
• Regular and preventive treatments, including several FDA-approved medications, are crucial in managing HAE symptoms and minimizing the frequency and severity of swelling episodes.
• Diagnosis of HAE can be challenging, often taking years before an accurate assessment, which is why finding a specialist who is experienced in HAE is essential for effective management.
• Triggers for HAE attacks can include stress, hormonal changes, and minor physical trauma, so identifying and recording these triggers can be beneficial in managing the condition.