Treatment and management of HAE attacks

Last updated Oct. 2, 2023, by Marisa Wexler, MS
Fact-checked by Patrícia Silva, PhD

Hereditary angioedema, or HAE, is a genetic disorder that is characterized by attacks of sudden swelling.

A number of therapies are available to help manage such swelling attacks. Some HAE medications can be used as prophylactic (preventive) treatments to reduce the risk of attacks, while others can help to resolve attacks that do occur (on-demand or acute treatments).

What is an HAE attack?

An HAE attack is a sudden bout of swelling in someone with the disease. The swelling can affect most parts of the body, including the hands, feet, limbs, abdomen, genitals, face, or throat. Swelling in the throat is generally the most serious type of attack, as it can compromise a person’s ability to breath.

What causes HAE attacks?

Swelling attacks in HAE are caused by the overproduction of a signaling molecule called bradykinin. Bradykinin causes blood vessels to become leaky and release fluid into the surrounding tissue, ultimately causing swelling.

In the most common forms of HAE (types 1 and 2), bradykinin is overproduced due to mutations that interfere with the production of C1-inhibitor (C1-INH), a protein that normally helps to regulate bradykinin production. Other rarer mutations that cause abnormal bradykinin levels may also cause HAE.

Sometimes, HAE attacks can be triggered by physical injury or exertion, exposure to an allergen, illness, fluctuations in hormone levels (for example, due to menstruation), and emotional stress or changes in the weather. However, HAE attacks often occur without any clear trigger.

How common are HAE attacks?

HAE attacks are usually infrequent and mild in children but generally become more common and more severe during adolescence and puberty. Around half of patients will experience at least one swelling attack before age 10, and virtually everyone with HAE will experience attacks by the time they reach their early twenties.

Without preventive treatment, the average adult with HAE will experience about two swelling attacks per month (one attack every 2 weeks), but rates of swelling attacks can vary widely from person to person. Some patients only rarely experience attacks even without treatment, while others may have attacks every few days when untreated.

Without treatment, HAE attacks will typically get gradually worse over the course of about 12 to 36 hours, and then will usually resolve after a few days. Specific treatments can help to resolve attacks quicker and prevent more serious complications.

What are the symptoms of an HAE attack?

The main symptom that characterizes HAE attacks is swelling. Often, areas of swelling in HAE causes pain, and they usually feel hard to the touch. Unlike in some other types of angioedema, itchiness or rash are uncommon in HAE-related swelling, though some HAE patients do experience redness at the swelling site.

Some patients also experience other HAE attack symptoms that can occur during, before, or after swelling. These may include:

• numbness, tingling, burning, or prickling sensations
• nausea
• fatigue
• flu-like symptoms
• fever
• depression and anxiety
• stomach pain and loose stools
• aches and pains
• headache.

HAE attack treatment

Because HAE attacks can be life-threatening, patients seek answers to the question of how to reduce angioedema swelling. Several therapies are approved to reduce swelling in such attacks, including:

• Berinert, which is approved to treat HAE attacks in adults and children. The therapy contains a version of C1-INH — the bradykinin-regulating protein that is defective in most people with HAE — derived from human blood. It is administered via injection into the bloodstream by a medical professional.
• Firazyr (icatibant injection) is approved to treat acute HAE attacks in adults, 18 and older. The therapy, which works by blocking bradykinin receptors, is administered via a subcutaneous (under-the-skin) injection in the abdomen, which may be done by patients or caregivers at home with appropriate training.
• Kalbitor (ecallantide) is approved for treating HAE attacks in patients 12 and older. It works to block plasma kallikrein, a protein that helps to produce bradykinin. The therapy is administered by subcutaneous injection, which must be given by a medical professional.
• Ruconest contains a recombinant (lab-made) version of the C1-INH protein. It is approved to treat swelling attacks in adults and adolescents with HAE. The therapy is administered via a slow injection into the bloodstream (intravenous injection), which may be done by patients and caregivers at home with appropriate training.

In some situations, particularly in emergency rooms, HAE attacks may be managed by administering fresh frozen plasma — the non-cellular portion of blood — from a healthy donor. The donor plasma can help to restore C1-INH levels to stop swelling.

HAE attack prevention strategies

A few preventive therapies are approved for HAE to reduce the risk of swelling attacks. These include:

• Cinryze, which contains a version of the C1-INH protein and is approved for preventive treatment in HAE patients 6 and older. It is administered by intravenous infusion (into the bloodstream) every three or four days, by a healthcare professional.
• Danocrine (danazol) is an oral medication approved to prevent HAE swelling attacks. The therapy is thought to increase levels of C1-INH protein.
• Haegarda is approved as a treatment to prevent HAE attacks in patients 6 and older. The therapy contains a version of the C1-INH protein, and is administered via subcutaneous injection by patients or caregivers with appropriate training.
• Orladeyo (berotralstat) is a once-daily oral therapy approved to prevent swelling attacks in HAE patients 12 and older. It works by blocking the bradykinin-making protein plasma kallikrein.
• Takhzyro (lanadelumab) is approved to prevent swelling attacks in HAE patients 2 and older. It’s given by subcutaneous injection every few weeks, which can be done by patients or caregivers with appropriate training.
• Winstrol (stanozolol), an oral steroid that can reduce bradykinin levels, may be used as a preventive treatment in HAE.

In addition to prophylactic treatments, taking steps to avoid possible triggers of swelling attacks, such as injury, is an important part of disease management for many people with HAE.

Angioedema News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.