Hereditary Angioedema: What’s Going On Inside the Body

HAE is a rare genetic disease that’s almost always caused by a deficiency or malfunction of C1-inhibitor (C1-INH) proteins. The job of these proteins is to help control the body’s inflammatory response. In particular, C1-INH helps keep a pro-inflammatory peptide called bradykinin in check.

Typically, bradykinin isn’t harmful: Your body produces it to increase blood flow, which also helps reduce blood pressure. But in people with HAE, the regulation of bradykinin becomes dysfunctional. The location and severity of an HAE attack can be significantly influenced by how much bradykinin is present in the body at any given moment, triggering increased vascular permeability of the blood vessels and leading excess fluid to leak through them into other areas of the body.

This buildup of fluid causes swelling during an HAE attack.

A very small percentage of people with HAE have normal C1-INH but still release too much bradykinin, resulting in severe swelling during an HAE attack.

The swelling can last from two to five days, and about 25 percent of people experience a flat, nonitchy red rash either before or during the attack, according to the US Hereditary Angioedema Association.

Attacks may involve one area of the body or a combination, per the Genetic and Rare Diseases Information Center. Gastrointestinal swelling can be particularly painful, as can swelling in the hands and feet, keeping you from participating in your daily activities. While HAE attacks in these areas can be debilitating, they’re usually not considered dangerous. But when the swelling occurs in the mouth or the throat — as it does less than 3 percent of the time, according to research — it’s an emergency, as the swelling can block your airway, affecting your ability to breathe.

Swelling and other HAE symptoms can range from mild to severe, and can involve different parts of the body. Symptoms tend to affect the limbs or face, particularly the eyes and lips. But symptoms may also vary from person to person and from attack to attack.

In severe cases, HAE can cause asphyxiation.

Although the risk is rare, if the upper airway swells enough to cut off oxygen, it can be life-threatening. Everyone who has HAE should be aware of this.

There’s no way to predict if or when an HAE attack might affect the airway, says Paula Busse, MD, a professor of clinical immunology at the Icahn School of Medicine at Mount Sinai in New York City. “A person could always have abdominal attacks and then all of a sudden have an airway attack one day,” she says.

Most people who inherit HAE begin to experience symptoms around age 13, according to the US Hereditary Angioedema Association. Attacks tend to worsen during puberty. These attacks can be brought on by physical trauma, infection, and emotional stress, but they often have no known triggers.

When you first experience an attack, it may cause swelling in only one part of the body. The frequency and duration of attacks vary greatly among individuals, but if HAE is untreated, swelling episodes may occur every one to two weeks, with episodes lasting three to four days, according to MedlinePlus.

Without treatment, HAE attacks are likely to become increasingly more frequent and severe. So if you’re diagnosed with the condition, it’s vital to follow the treatment plan your doctor prescribes.

Medications for HAE work in various ways to relieve attacks or prevent them from occurring:

• Increasing the levels and activity of C1-INH in the body
• Stopping the production of bradykinin
• Blocking bradykinin from binding to certain receptors

Medicines are given by either injection or IV infusion, and there are currently two oral drugs.

There are also promising treatments for HAE on the horizon, including gene therapies, which alter a person’s genetics to cure a condition, says Busse.

Work together with your doctor to develop the right treatment plan to ward off HAE activity in your body and keep symptoms at bay.