Introduction to HAE: 10 Things Patients Need to Know

This article is taken from an extensive feature on the 2023 HAEi Regional Conference APAC, published in Global Perspectives #1 2023

The iconic Professor Bruce Zuraw opened his presentation with cosmology. Prof. Zuraw likened his awe at seeing an image of a black hole in his lifetime with the advances made in HAE. He told the audience that he had been working in HAE for more than 40 years and didn’t think so much progress could be made so fast.

He introduced his talk as giving the 10 things patients need to know; to help them be better advocates and help themselves, their families, and the entire HAE community.

Why me?

Prof. Zuraw made clear this is something that everybody asks at some point. The answer, he said, started at the genes. With HAE, you have a mutation. If you have C1-inhibitor deficiency, one gene has mutated, so C1-inhibitor either doesn’t work or can’t get out of the cell. That’s what causes most types of HAE.

We now know seven genes that may be mutated but don’t know the mechanism. With more work, this will become clearer for all.

Am I in danger?

Unfortunately, he told the audience, yes, and we must deal with that. Prof. Zuraw illustrated that airway and intestinal swelling looked remarkably similar, and the mechanism is the same: fluid leakage from blood vessels into the tissue.

Prof. Zuraw cautioned: “Anybody, no matter your history, could have a laryngeal attack, and we must be prepared to treat that.”

Prof. Zuraw referenced the work of HAEi and its CEO, Tony Castaldo, in demonstrating that there is a lot of illness with HAE, and people continue to die from laryngeal attacks. The study by Tony and colleagues showed that 100% of patients felt that HAE prevented them from advancing in life. 50% missed work or school. 80% said that an extremity attack caused severe dysfunction.

“We concluded that all attacks matter,” Prof. Zuraw said.

What about my family?

HAE runs in families, said Prof. Zuraw. If somebody in the family inherits the gene, each of their children has a 50:50 chance of getting HAE. It affects males and females equally, though females tend to have slightly worse disease. The genetics are simple, easy to predict, and hard to escape.

The death rate for HAE was far higher in undiagnosed people. Prof. Zuraw stressed that all family members of somebody diagnosed with HAE must be screened. “Please, go back to your families; if anybody has refused to get screened, convince them. It’s important. That applies to children, too.”

What causes attacks?

Prof. Zuraw showed a study by Dr. Hilary Longhurst, which showed that the level of C1-inhibitor people had directly correlated to the risk of attack. People were at very high risk at 20% of the normal level. Control was more possible at levels above 40%.

The immediate cause of attacks can be diverse. Emotional stress is a factor, so consider protecting yourself during stressful periods. Even mild trauma in an untreated patient can lead to an attack. People with HAE should not be given ACE inhibitor drugs for blood pressure as these can provoke an attack. Other medicines containing estrogens, such as contraception or hormone replacement, may worsen your disease.

Can I treat attacks?

Prof. Zuraw now turned his attention to treatment. On-demand (or rescue) treatment is there to eliminate the attack once it starts, before it can cause harm. There are helpful treatment guidelines, and Prof. Zuraw appreciated there is medication variation across the world.

One crucial point was that antihistamines, steroids, and epinephrine do not work. Prof. Zuraw cautioned: “You have to help yourself. Doctors who don’t specialize in this don’t understand it. Unfortunately, it falls on you.”

Prof. Zuraw concluded that the earlier you treat an attack, the faster it will resolve. You shouldn’t wait to know if they’re severe because the medicine won’t work as well if you wait that long. Treat early and treat every attack, he said.

Can I prevent attacks?

Prof. Zuraw stated, “I think it’s much better to prevent than treat if we can,” and again referenced treatment guidelines. He also made it clear that there is no formula for who should be on preventative therapy. This must be individualized based on improving quality of life.

How do I find the right doctor?

Quoting Voltaire, Prof. Zuraw explained that perfect is the enemy of good. You don’t need to find the world’s best expert; you need to find a good doctor willing to listen, learn, and treat you as a core decision-maker. Working with your doctor, you can develop and regularly update a management plan that covers which medicine, where to get it, what happens when you travel, etc.

Who can I turn to for help?

Prof. Zuraw outlined that it is vital to know that HAEi are patients just like you, who understand and work for you. It is an unbiased source of information and help. HAEi understands the need to deliver life-saving medicines to everybody in the world.

Prof. Zuraw highlighted how HAEi has worked to overcome the perspectives of others outside the community, particularly that the costs of ignoring adequate treatment are far higher than insurers and governments recognize. Effectively treating patients is a fiscally sound decision.

Is there a cure?

In the past, the idea of a cure might’ve seemed a cruel joke. However, Prof. Zuraw indicated, “Good management of HAE leads to full control. We should see no deaths and no disruption in your life. If it leads to a normal life, I would argue while it’s not perfect, it is a functional cure”.

Looking to the future, Prof. Zuraw outlined three possible answers to a better cure. One is gene editing to correct your DNA. The second would be gene therapy, inserting extra DNA into your cells to get you producing enough C1-inhibitor. The third would be ‘protein rescue,’ which works to get more of your existing C1-inhibitor to escape your cells.

What can I do to help?

Echoing Prof. Maurer, Prof. Zuraw mentioned registries. By participating in registries, you will ensure data is available to identify important information, such as whether people with HAE have fewer heart attacks than the rest of the population or that they have an increased risk of kidney disease.

Do you believe?

This question was for the audience. Prof. Zuraw encouraged his audience to believe. Quoting Eleanor Roosevelt, he said: “The future belongs to those who believe in the beauty of their dreams.” He felt sure that the dream of a cure would be achieved. He encouraged everyone to never settle for good enough but to keep pushing for a better future. And he hoped that he’d be able to help people get there.