Hereditary angioedema (HAE) is a rare genetic condition that causes swelling in the skin and mucous membranes. It affects the face, hands, feet, and gastrointestinal tract.

The condition develops due to a mutation in a gene called C1NH, which provides instructions for producing a protein called C1 inhibitor. The mutation in this gene causes a biochemical imbalance that leads to repeated swelling attacks.

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Infographic by Diego Sabogal

HAE is rare. Experts estimate that it affects around 1 in every 50,000–150,000 people worldwide. The condition appears to affect males and females equally.

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Infographic by Diego Sabogal

There are three types of HAE:

  • Type 1: This accounts for about 85% of cases. It is due to C1 inhibitor deficiency.
  • Type 2: This accounts for about 15% of cases. It is due to C1 inhibitor dysfunction.
  • Type 3: This is very rare. Experts believe that it is due to other genetic mutations.

HAE attacks are characterized by swelling episodes in the skin and various other parts of the body. They last for about 3 days, on average. Severity and frequency vary significantly.

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HAE attacks most often occur in the:

  • face
  • lips
  • hands
  • feet
  • genitalia
  • stomach, intestines, and bladder, which causes abdominal pain, nausea, and vomiting
  • the upper airway, including the larynx (voice box), tongue, and throat

If these symptoms restrict breathing, the condition becomes a medical emergency.

When do the symptoms start?

Symptoms usually begin by age 13 years. Approximately 50% of people experience their first episode before the age of 10 years. Symptoms may increase around puberty and last a lifetime.

Doctors diagnose HAE using a blood test that measures C4 and C1 esterase inhibitor levels.

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One online survey found that the average time to diagnosis was 8.3 years. It also revealed that around 65% of people with HAE initially received a misdiagnosis.

Doctors often misdiagnose HAE as another more common condition. Some examples of these include:

  • allergic reactions
  • contact dermatitis
  • urticaria
  • appendicitis
  • irritable bowel syndrome

Most HAE attacks are unpredictable, but triggers may include:

  • stress or anxiety
  • an injury
  • a surgery
  • a dental procedure
  • intense physical activity
  • hormonal changes, such as those that occur during pregnancy or menopause
  • an illness, such as a cold or the flu
  • certain medications, including ACE inhibitors and contraceptives
  • an intolerance to foods such as nuts or dairy

If an attack occurs, a person should receive one of the following HAE medications immediately:

  • C1 esterase inhibitor, human (Berinert)
  • C1 esterase inhibitor, recombinant (Ruconest)
  • ecallantide (Kalbitor)
  • icatibant (Firazyr)

People with HAE due to C1 inhibitor deficiency should always have access to at least two standard doses of a HAE medication.

Some preventive treatments for HAE attacks include:

  • IV C1 esterase inhibitor (Cinryze)
  • subcutaneous C1 esterase inhibitor (Haegarda)
  • lanadelumab (Takhzyro)
  • berotralstat (Orladeyo)