Hereditary Angioedema (HAE)

What hereditary angioedema is

C1 inhibitor is a protein that keeps several blood systems in check, including the one that produces bradykinin. Without enough working C1 inhibitor, bradykinin builds up during an attack and makes small blood vessels leak fluid into the deep layers of the skin and the lining of the gut and airway.

Because histamine is not the cause, HAE looks different from allergic swelling. There are no hives or itching, the swelling develops over hours rather than minutes, and allergy medicines do not help.

Types of HAE

HAE is passed on in an autosomal dominant pattern: a parent with HAE has a 50 percent chance of passing it to each child. About 1 in 4 people have a new mutation with no family history.

Symptoms of hereditary angioedema

Attacks usually start in childhood and often worsen around puberty. They build over 24 hours and then fade over 2 to 5 days.

• Skin swelling: hands, feet, face, lips, eyelids and genitals. It is firm, pale or skin-colored, not itchy, and can be painful or tight.
• Abdominal attacks: severe cramping belly pain, vomiting and diarrhea from swollen bowel wall. These are often mistaken for appendicitis or a bowel obstruction and can lead to unnecessary surgery.
• Throat (laryngeal) swelling: hoarseness, a change in voice, trouble swallowing and difficulty breathing. More than half of people with HAE have at least one throat attack in their lifetime. Before effective treatment, it was a significant cause of death.
• Warning signs (prodrome): tingling, fatigue, irritability, or a non-itchy, ring-shaped pink rash called erythema marginatum, hours before swelling.

Triggers

Many attacks have no clear trigger. Known triggers include:

• Physical trauma, including dental work, surgery and even typing or carrying heavy bags.
• Emotional stress.
• Infections such as colds and flu.
• Estrogen: combined birth control pills and hormone replacement therapy.
• ACE inhibitor blood pressure medicines, which raise bradykinin levels and must be avoided.
• Menstrual periods and pregnancy, in some women.

How HAE differs from other angioedema

For a general overview of all causes, see angioedema. Allergic swelling with breathing trouble or low blood pressure is anaphylaxis, which is treated differently.

Diagnosis

HAE is often diagnosed years after symptoms start. The key blood tests are:

1. C4 level: low in almost all people with type 1 or 2 HAE, especially during attacks. A good screening test.
2. C1 inhibitor level (antigenic): low in type 1.
3. C1 inhibitor function: low in types 1 and 2.
4. C1q level: normal in HAE, low in acquired C1 inhibitor deficiency, which develops later in life and is linked to lymphoma and autoimmune disease.

When tests are normal but the story is typical, genetic testing for HAE with normal C1 inhibitor may be done. Family members of a person with HAE should be tested, including children.

Treatment for hereditary angioedema

Guidelines recommend that everyone with HAE has on-demand medicine for at least two attacks available at all times, and an individualized plan.

On-demand treatment of attacks

Treat every attack as early as possible, especially any involving the face or throat. Options include:

• C1 inhibitor concentrate given into a vein.
• Icatibant, a bradykinin receptor blocker injected under the skin.
• Ecallantide, a kallikrein inhibitor injected by a health professional.
• Sebetralstat, an oral on-demand kallikrein inhibitor approved in the US in 2025.

Many people learn to self-administer at home. Throat attacks still need emergency assessment after treatment.

Long-term prevention

For people with frequent or severe attacks:

• Lanadelumab, an antibody injected every 2 to 4 weeks.
• Berotralstat, a daily oral capsule.
• C1 inhibitor concentrate given regularly into a vein or under the skin.
• Newer injectable preventives, such as garadacimab and donidalorsen, have been approved more recently.
• Older options such as attenuated androgens (danazol) are now used less because of side effects.

Short-term prevention

Before dental work, surgery or procedures involving the airway, a dose of C1 inhibitor concentrate is usually given beforehand.

Living with HAE

• Carry your on-demand medicine and a written emergency plan.
• Wear medical ID stating "hereditary angioedema: does not respond to epinephrine".
• Avoid ACE inhibitors and estrogen-containing medicines; use progestogen-only or non-hormonal contraception.
• Tell dentists and surgeons in advance.
• In pregnancy, plasma-derived C1 inhibitor is the preferred treatment.

With current treatment, most people with HAE lead full, active lives with few attacks.

Frequently asked questions

What triggers hereditary angioedema attacks?

Common triggers are physical trauma (including dental work and surgery), emotional stress, infections, estrogen in birth control pills or hormone therapy, menstrual periods, and ACE inhibitor blood pressure medicines. Many attacks happen without any obvious trigger.

How is hereditary angioedema diagnosed?

A doctor orders blood tests: C4, C1 inhibitor level and C1 inhibitor function. Low C4 with low C1 inhibitor level or function confirms type 1 or type 2 HAE. If these are normal but symptoms and family history fit, genetic testing can identify HAE with normal C1 inhibitor.

Does epinephrine work for hereditary angioedema?

No. HAE swelling is caused by bradykinin, not histamine, so epinephrine, antihistamines and steroids have little or no effect. Attacks need HAE-specific drugs such as C1 inhibitor concentrate or icatibant. If you are unsure whether swelling is allergic, emergency teams may still give epinephrine.

Can hereditary angioedema be cured?

There is no cure yet, but treatment is very effective. Preventive medicines can reduce attacks by well over 80 percent in many people, and on-demand drugs shorten attacks. Gene-based therapies are being studied in clinical trials.

Is hereditary angioedema life-threatening?

It can be. Swelling of the throat can block the airway, and before modern treatment this caused a significant number of deaths. With on-demand medicine at hand, prompt emergency care and preventive treatment, the risk is now much lower.