Understanding HAE

Patient Voice spoke with Dr. Stephen Betschel to learn more about hereditary angioedema (HAE), a condition that involves recurrent attacks of severe swelling. He explains how each type of HAE presents and what patients can do to optimize their mental and physical health.

Photography by Patient Voice.

Dr. Betschel is a Staff Clinical Immunologist and Allergist in the Division of Allergy and Clinical Immunology at St. Michael’s Hospital, part of Unity Health Toronto.

1. What is HAE? How does each type of HAE differ?

Hereditary angioedema (HAE) is a rare genetic disease that affects about one in 50,000 people. It’s autosomal dominant, which means that the child of a parent who has HAE has a 50 percent chance of inheriting the condition.

HAE Type I and Type II affect C1-inhibitor, which is an important protein that regulates the production of bradykinin, a key mediator that can cause swelling. There is also HAE normal, in which all biochemistry testing is normal and may not involve C1-inhibitor.

Approximately 85 percent of HAE patients are Type I, having both low levels of C1 inhibitor and decreased C1 inhibitor function. Patients with HAE Type II, approximately 15 percent of diagnosed patients, have normal or elevated C1 inhibitor levels, but decreased C1 inhibitor function.

It’s relatively easy to diagnose HAE Type I and Type II (it’s identified via a simple blood test), but doctors often don’t think to test for it because it’s so rare and its symptoms overlap with a number of other conditions, like allergies. Due to how exceedingly rare HAE with normal C1 inhibitor is, and because it cannot be diagnosed via blood testing, these patients face significant diagnostic delays and unique therapeutic access challenges.

2. How does an attack typically present?
HAE’s swelling attacks typically affect the hands and feet, and sometimes also the genitals, stomach, face, and/or throat. These attacks are extremely painful and if untreated, they can last for several days. They can be quite debilitating for patients. For example, severe swelling of the hands can make using a phone, pen, or keys nearly impossible. Abdominal swelling can lead to severe abdominal pain, which is typically associated with nausea and vomiting — this typically lands almost all patients in the ER at some point. Facial swelling can be disfiguring, transforming patients’ faces and making them completely unrecognizable.

The most significant concern is swelling of the back of the throat and airway, which puts patients at risk of suffocating and can be fatal. These attacks can come on randomly, such as in the middle of the night, and if left undiagnosed or untreated the mortality rate is very high, at around 35 percent.

Most HAE attacks are random, but in some cases they can be precipitated by things like physical trauma, emotional stress, or certain medications. An undiagnosed patient undergoing a dental surgery, for example, could experience unexpected and life-threatening swelling.

“It’s relatively easy to diagnose HAE (it’s identified via a simple blood test), but doctors often don’t think to test for it because it’s so rare and its symptoms overlap with other conditions.”

3. How can living with HAE impact one’s mental health and well-being?

Living with HAE can have a significant impact on patients’ quality of life. It often causes or contributes to anxiety and depression. Although one might have a diagnosis and access to treatment, never knowing when one might have a life-threatening attack can cause a lot of uncertainty and anxiety. Even when an attack isn’t life-threatening, it can cause a lot of stress for patients. 

Imagine a patient who doesn’t have a diagnosis, and they have an attack that affects their face and that’s completely disfiguring. They won’t be able to go to work or school, and they’ll always be worried that they might have an attack if they’re at a social gathering or travelling. This disease has a tremendous impact on patients, especially if they’re undiagnosed or don’t have access to treatment. 

4. Why is it important to maintain an ongoing and collaborative dialogue with one’s specialist?

It’s important to maintain a dialogue with one’s specialist in order to get the best possible treatment and to optimize one’s quality of life. The treatment landscape in HAE has changed dramatically in the past decade.

A decade ago, we had very limited options for prophylaxis – that is, treatments to prevent attacks. Nowadays, we have newer agents with established safety profiles that can effectively replace C1-inhibitor, as well as agents that are directed to kallikrein specifically, which is where bradykinin comes from. These new types of treatments will help patients to prevent attacks. Other new treatments are currently being studied, and we’re hoping they will all be available in Canada soon.

Many HAE patients have had a very rough go in the health care system over the years, dealing with misdiagnoses, inadequate treatments, and accusations of being drug-seeking. As a result, they tend to not have a lot of faith in the system or to follow up with health care practitioners. But if they have been diagnosed, it’s very important that they stay in touch with their specialist.

5. What are some ways that HAE patients can optimize their health?

The most important thing that HAE patients can do to improve their health and their quality of life is to reduce the number of attacks they experience. Anything that can be done to minimize attacks is helpful — that could be lifestyle changes, identifying and avoiding attack triggers, or being made aware of all treatment options, like prophylaxes to minimize attacks. Patients should also have a treatment available for when they do have an attack, especially if they’re not taking any prophylaxis, which is effective and easy to self-administer.

Another thing that patients can do to improve their health and well-being is to engage with other patients, for example by being involved in patient organizations to share their experiences. 

Although HAE is a terrible condition to have, especially if one is undiagnosed, it’s important to know that if one is diagnosed, one really can live an almost completely normal life, and that’s what the goal is now with new treatments and increased awareness. 

HAE Canada (HAEC) is Canada’s first and only national HAE patient-led non-profit organization. HAEC is dedicated to help ensure equitable access to promising drug therapies, more and better clinical trials in Canada, and in collaboration with the Canadian Angioedema Scholarship Program (CASP), increased investment in HAE research. Please visit to learn more.

This content was supported by BioCryst Canada. This page was developed by Patient Voice, and the supporter did not influence the final article or editorial themes of this content.