Hereditary angioedema (HAE) is a rare condition that often runs in families. HAE causes episodes of symptoms, called attacks, that involve swelling and pain in the gastrointestinal (GI) tract, face, throat, hands, feet, and genitals. HAE attacks often start in childhood and get worse during the teen years.
HAE is usually caused by a mutation to the SERPING1 gene passed from parents to their children. This gene carries the instructions for making a protein called C1 inhibitor (C1-INH), which helps control the flow of fluids in and out of cells.
While some HAE attacks can be linked to specific triggers, episodes can happen without any known cause.
How often attacks happen is different for each person. Some people rarely have attacks. Others get them a couple of times a week. Most untreated people have attacks every 1 to 2 weeks.
Without treatment, symptoms gradually get worse over the first 12 to 36 hours. Attacks usually end and symptoms improve within 2 to 5 days.
There are three types of HAE. Each has different causes:
- Type I. This form of HAE occurs when your body doesn’t make enough C1-INH protein. It occurs in about 85 percent of people with the condition.
- Type II. If you’re among the estimated 15 percent of people with this type of HAE, your body makes C1-INH protein that doesn’t work correctly.
- Type III. In this very rare form of the condition, your C1-INH protein levels are normal but you still have HAE symptoms for an unknown reason.
When you don’t have enough C1-INH or it doesn’t work correctly, small blood vessels in your body leak fluid into the surrounding tissues. The fluid builds up and causes swelling and pain that usually occurs in the skin, GI tract, and upper airway.
Triggers for HAE attacks may include:
- dental procedures
- infections, such as colds and the flu
- hormonal changes, including during menstruation and pregnancy
- medications, such as birth control pills, hormone replacement therapy, and some blood pressure drugs
- physical exertion, such as mowing the lawn
The severity of an HAE attack varies from person to person. Before you experience an attack, you may notice a tingling sensation.
As fluid builds up, the affected area swells up and may be painful. The skin over the swelling can feel tight or tingly.
Swelling can happen in many different parts of your body. The symptoms you have depend on where the swelling is located:
- GI tract: nausea, vomiting, pain, diarrhea
- throat/airway: pain, trouble swallowing, difficulty breathing, noisy breathing
- skin: swelling of the face, hands, feet, or genitals
Swelling in the throat and airway is the most dangerous because it can prevent you from breathing. If you have an attack that affects your throat, it’s important to get medical help right away.
These symptoms are easy to confuse with other conditions. Some people who have belly pain, nausea, and vomiting are mistakenly diagnosed with irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), or appendicitis.
Symptoms of untreated HAE attacks usually last for about 3 to 4 days. Your episodes may be longer or shorter.
Attacks can start without warning. Some people have early signs that an episode is about to happen. These symptoms can include:
- extreme tiredness
- tingling of the skin
- non-itchy rash
- hoarse voice
- sudden mood changes
Once an HAE attack starts, an acute medication stops the processes in your body that cause swelling and pain.
Because an attack can be very serious if it affects your airway, experts recommend keeping at least two doses of acute medication with you at all times.
There are several types of medications that stop an HAE attack:
- C1 esterase inhibitors. Plasma-derived nanofiltered C1INH (Berinert) and recombinant human C1INH (Ruconest) replace the C1-INH that your body is missing or that isn’t working well.
- Bradykinin B2-receptor antagonists. Icatibant (Firazyr) blocks bradykinin. During an HAE attack, a protein called kallikrein triggers the release of bradykinin, which causes your blood vessels to leak fluid.
- Plasma kallikrein inhibitors. Ecallantide (Kalbitor) has the same effect as icatibant, but it works slightly differently. It blocks kallikrein to stop the production of bradykinin.
These medications come as an injection or through an IV. You can give yourself all of these medications except for Kalbitor, which is only administered by a doctor.
You can take one of several medications to prevent HAE attacks. Preventive HAE treatments include:
- berotralstat (Orladeyo)
- C1 esterase inhibitors (Cinryze, Haegarda)
- lanadelumab (Takhzyro)
You can take these medications for short periods of time when you’re at greatest risk of having an attack. For example, you might need one of these treatments during stressful events or before surgery.
Your doctor may recommend taking these medications on a regular basis if you get attacks more than once every 3 months or if your attacks are severe. This can reduce the number and severity of attacks you have.
HAE is a rare condition that often runs in families. It causes fluid to leak out of blood vessels. This leads to attacks that cause swelling and pain in the face, throat, GI tract, and other areas of the body.
Some medications for HAE stop attacks once they start. They may replace the protein C1-INH, which your body is missing. Or they may block bradykinin or kallikrein, both of which lead to swelling. Other medications can be taken proactively to help prevent HAE attacks.