What is Hereditary Angioedema (HAE)?

Hereditary angioedema (HAE) is a rare, serious, potentially life-threatening genetic disorder occurring in 1 in 50,000 to 1 in 150,000 people worldwide. In Europe, approximately 10,000 people are affected.1

People with hereditary angioedema (HAE) are unable to make enough of the functional blood protein, C1-esterase inhibitor (C1-INH). Lack of this inhibitor results in overproduction of an inflammatory substance called bradykinin, which causes leakage of fluid from blood vessels and build-up of excessive fluid, which is the cause of localised swelling.2,3

HAE causes repeated episodes of spontaneous angioedema – or swelling – that can occur at any time and in almost any part of the body but more predominantly in the hands, feet, face, airway (throat) and internal organs. Most people experience their first episode in childhood or adolescence. HAE is not an allergy or allergic reaction.5

HAE symptoms can start to occur at a very early age, but there are also examples of this occurring later in life. As incidents of suffocation due to throat swelling can occur within families with HAE, making a timely diagnosis is extra important.4

What causes HAE?

HAE is usually caused by the lack of, or low levels of, a blood protein called C1 esterase inhibitor (C1-INH), or sometimes this protein doesn’t work properly.6 In rare cases, the cause of HAE is unknown. DNA contains genes which carry the information for the C1 INH protein defect, which explains why HAE runs in families. If one parent has HAE, their children (male and female) will have a 50% chance of inheriting the condition.7

The absence of family history does not rule out an HAE diagnosis because there can be spontaneous changes to the C1 inhibitor gene. These patients can also pass on the defective gene to their offspring.7

Symptoms and triggers

Emotional factors (e.g., exam stress, relationship problems), small surgical procedures (e.g., dental work) and hormonal fluctuations (e.g., during pregnancy, puberty, or menstruation) are sometimes enough to trigger a swelling episode.8-10 It is also possible that medicines used to lower blood pressure, called angiotensin converting enzyme (ACE) inhibitors, can prompt an episode.11 Other potential triggers include infections, insect bites, certain foods, heat and cold. Often, the exact cause of an episode is unknown.8

Warning signs and symptoms of an HAE episode

Accidental injury

Infection (e.g. cold or flu)

Emotional stress

Surgery, particularly dental surgery

Hormonal fluctuations

Check your signs and symptoms:

Some people have warning signs and symptoms that an episode is coming, which may appear as early as 16 hours beforehand.4 Knowing your own warning signs can help you to make sure you are treated as early as possible. Discomfort at the site of the swelling and a non-itchy, spreading rash with a wavy border are two examples.2-3
Other warning signs and symptoms may include:

Fatigue / weakness / lack of energy

Mood swings





Joint or muscle pain

HAE episodes

The frequency of HAE episodes varies between people and tends to be unpredictable: some people may have very few episodes, while others may have episodes every few days.2 Episodes may start in one part of the body and spread to another before they disappear.14 Swelling typically builds up over the first 24 hours,14 and episodes can last for 2-5 days if not treated.2 They may affect any part of the body, but the most common sites are:2,14,15

The severity of symptoms varies among family members and people who start to get symptoms at an early age often have more severe HAE than those who start to develop symptoms at a later age.18

Swelling in the arms and legs is usually less painful; however, abdominal (belly) symptoms may become worse with time, so it is important to treat all episodes as early as possible.19 Prompt treatment is particularly important for people with swelling of the face and/or mouth, even if this seems mild, to make sure the swelling does not spread to the airways and prevent the person from breathing.20

Types of HAE23

Type C1-INH level C1-INH functionality Men/Women Occurrence


Low Normal Equal ~85% of people with HAE


Normal Abnormal Equal ~15% of people with HAE

HAE with normal, functioning C1-INH23

Normal Normal More common in women than men Extremely rare


Due to the complexity of the disease and its potential risks, it is essential that HAE patients receive an accurate diagnosis early in the disease course. The diversity of symptoms and their similarity to other conditions and/or other types of swelling lead to confusion among those doctors who are not familiar with HAE.13,20

Typical symptoms that patients can look out for include:24,25

The diagnosis of HAE is made by a thorough clinical evaluation, a detailed patient history, and blood tests that test levels of the protein called C4 antigen.26 Other protein levels such as C1 and C2 can also be tested for. Ultrasound, CT scans, and X-rays may be used to demonstrate swelling.27

In Europe, expert centres have sufficient specialised, comprehensive care to make a reliable diagnosis.20 Diagnosis is obtained by laboratory tests performed on a blood sample. The blood of HAE patients shows a decreased concentration of C1-inhibitor and/or reduced activity of C1 inhibitor. The concentration of C4 antigen levels is also usually reduced in people with HAE.26


A timely diagnosis can improve your quality of life!


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