Hereditary angioedema is a rare inherited condition that causes repeated attacks of sudden swelling in the skin, the gut and sometimes the airway, caused by a build-up of a natural body chemical called bradykinin rather than by an allergy [1,2].
This page provides general information. It does not replace advice from a doctor or another qualified healthcare professional.
Hereditary angioedema causes repeated attacks of swelling deep under the skin and in the lining of the gut and the airway. The swelling does not itch and does not come with hives [1].
The cause is a natural body chemical called bradykinin, which makes small blood vessels leak fluid into surrounding tissue. A protein called C1 inhibitor normally keeps bradykinin in check. In hereditary angioedema that control fails, bradykinin builds up, and fluid leaks [1,2].
There are two main groups. With C1 inhibitor deficiency, the protein is either in short supply, called type 1, or present but not working, called type 2. With normal C1 inhibitor, the protein tests normal and the problem lies elsewhere. That group used to be called type 3, a name the guidelines have retired [1,2].
Two things are often confused with it. Allergic swelling involves histamine, usually itches, often comes with hives, and does respond to antihistamines and adrenaline. Swelling from ACE inhibitor blood-pressure tablets also involves bradykinin, so allergy medicines do not help there either, yet it is a drug side effect rather than something inherited [1,3]. Acquired C1 inhibitor deficiency is a third, non-inherited form [1].
Hereditary angioedema is rare, and nobody knows the exact figure.
The 2025 international guidelines put estimates at between 1 in 50,000 and 1 in 100,000 people. For the C1 inhibitor deficiency form, a review of published studies reported a worldwide prevalence of roughly 1 in 67,000, which would mean more than 100,000 people affected globally [1,24]. Prevalence means how many people live with a condition at one time. Incidence, the number of new cases each year, is not reliably known here.
Patient organizations often quote a wider range, 1 in 10,000 to 1 in 50,000, and a United States genetics resource gives about 1 in 50,000 [2,5,9]. These figures do not agree, and the guidelines state that underdiagnosis is likely to be high, so the real number is probably larger than the counted one [1].
No difference between ethnic groups has been confirmed, which is not the same as rates being identical everywhere, since counted cases depend on access to testing [1].
A gene is a set of instructions your body uses to make a protein. Hereditary angioedema with C1 inhibitor deficiency is caused by a change, or variant, in a gene called SERPING1, which carries the instructions for making C1 inhibitor [2].
It is inherited in an autosomal dominant pattern, which means one changed copy of the gene, from either parent, is enough to cause the condition. A parent who has it has a 50 percent chance of passing it to each child [2,5]. Some people are the first in their family, because the change happened newly in the egg or sperm [2]. When one person is diagnosed, the guidelines recommend offering testing to close relatives [1].
Where C1 inhibitor is normal, the gene found most often is F12. Several other genes account for smaller numbers, and in many people testing finds nothing [1,2].
Most attacks happen for no identifiable reason. Recognized triggers include injury, dental work, surgery, infections, emotional stress, estrogen-containing contraceptives and ACE inhibitor tablets. In the form linked to F12, symptoms usually begin after puberty and are closely tied to estrogen [1].
Attacks build over hours rather than seconds, are often lopsided, and settle over about three to five days if untreated. They do not itch and do not come with hives. Untreated, people average an attack every 7 to 14 days, though frequency varies widely [1,2,4].
Swelling can occur almost anywhere [1,4]:
Gut attacks affect between 70 and 90 percent of people, and the pain can look so much like a surgical emergency that people have had unnecessary operations. About one third, mostly children, get a flat, non-itchy, ring-shaped rash called erythema marginatum. More than half have their first symptoms before age 10, and puberty often makes attacks worse [1,2]. Many notice warning signs beforehand, such as tiredness, tingling or nausea [1,4].
When to seek urgent help. Swelling of the throat or airway is a medical emergency. Fewer than 1 in 100 attacks involve the throat, yet around half of people have at least one at some point. Take your on-demand medicine as early as possible and get emergency help at the same time [1]. Call emergency services if the lips, mouth, tongue or throat swell, if breathing or swallowing becomes hard, or if the voice changes [1,3]. In people not yet diagnosed, the risk of death from a throat attack has been estimated at 20 to 25 percent [1,30].
A family doctor usually refers on to an immunologist or allergy specialist, and many people first come to attention in an emergency department [1,28].
Diagnosis starts with blood tests [1]:
All three come back normal where C1 inhibitor is normal and in swelling caused by ACE inhibitor tablets, so a normal result does not close the question. In acquired C1 inhibitor deficiency all three are low. Where results and symptoms do not fit together, testing should be repeated [1].
Genetic testing helps in particular situations, including babies under one year old, whose levels are naturally low and can mislead, testing relatives, and borderline results [1].
Diagnosis is often slow, taking about 7 to 10 years on average, down from 21 years in the 1970s [1].
There is no cure. Treatment has three parts: treating attacks, preventing attacks around procedures, and preventing them day to day. Guidance has changed a great deal recently [1,29].
Treating an attack. Everyone diagnosed should keep on-demand medicine at home, even if attacks are rare, and enough for at least two attacks. Treating early works better than waiting. The first choices are C1 inhibitor into a vein, icatibant injected under the skin, or sebetralstat taken by mouth [1,21,22,23]. Sebetralstat is the first tablet for attacks, approved in the United States on 3 July 2025 and authorized in the European Union [12,16,25]. Ecallantide is still approved in the United States, though it has to be given by a health professional and is not available in Europe. Antihistamines, steroids and adrenaline do not work and should not be used in their place [1,4].
Prevention before a procedure. Dental work, surgery and anything involving the airway can set off an attack, and up to 3 in 10 people have one afterward. The first choice is C1 inhibitor into a vein within six hours beforehand, with on-demand medicine still to hand [1].
Day-to-day prevention. Five treatments are first choice: C1 inhibitor injected under the skin, lanadelumab, garadacimab, donidalorsen, and berotralstat, a daily capsule [1,15,19,20]. Garadacimab is given monthly and donidalorsen every four to eight weeks, both approved in the United States during 2025 and authorized in the European Union [13,14,17,18,27]. Whether to start, continue or stop is reviewed at least yearly, and self-injection at home is an option for all five [1].
Danazol and why it is used far less. Danazol is a weakened male hormone that raises C1 inhibitor levels and was a mainstay for decades. Doses are now capped at 200 mg a day to limit harm, which also limits how well it works. It is strongly linked with masculinizing effects in women, changes in blood fats, liver damage and liver tumors, and cannot be used in pregnancy or by children. It is now a second choice [1].
Availability differs by country. Even in wealthier countries only about half of those who could benefit from day-to-day prevention receive it, and cost limits access elsewhere, where plasma products, low-dose danazol or tranexamic acid are used [1]. In England, the body that appraises new medicines recommends berotralstat [11].
Care is usually shared between a specialist team and a family doctor, with a written plan setting out what to take and where to go [1,8].
Be ready. Carry on-demand medicine at all times, including while on prevention treatment, along with an emergency card explaining the condition and your medicines. HAE International publishes cards in many languages [1,6]. Self-injection training works well from around age 8 with help [1].
Everyday life. Progesterone-only contraception is preferred over estrogen-containing products, and another blood-pressure medicine is chosen instead of an ACE inhibitor where one is needed. Time lost to attacks is common, so teachers and employers need clear information, and medicine should be reachable at school and on trips. Anxiety and low mood are more common in people with frequent attacks, and much of the burden comes from not knowing when the next attack will come [1,8].
Pregnancy. Pregnancy makes attacks worse for some people and better for others. C1 inhibitor made from plasma has the best evidence in pregnancy and while breastfeeding, and danazol must not be used. Birth is best planned in hospital with on-demand medicine available [1].
Clinical trials test whether a treatment works and is safe. Hereditary angioedema is a busy research area, so studies do come up [1]. Deciding is personal, and it helps to take it in steps.
Be clear on what a study involves:
Every trial has rules about who can take part, called eligibility criteria. Some describe who can join, others who cannot. For a hereditary angioedema study they might include a confirmed diagnosis, a specific type such as C1 inhibitor deficiency or normal C1 inhibitor, a minimum number of attacks in the months before joining, an agreement to stop or continue an existing prevention medicine, an age range, and rules about pregnancy.
trialport’s medifit helps people consider information related to possible medical suitability. It does not diagnose a condition, confirm eligibility or replace formal screening by the study team.
Explore hereditary angioedema clinical trials through trialport
A study can look right on paper and still be hard in practice. Worth thinking through:
trialport’s readifit helps people reflect on their understanding, motivation, time, routines, support, emotions and practical arrangements.
Useful questions to put to a research team:
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The main areas being worked on are:
Study status checked: 3 August 2026. Research moves quickly, so this list will date, and none of the treatments named here is approved anywhere. For current information, search at app.trialport.com.
Globally, HAE International is the umbrella body for national organizations, with plain-language explanations, printable emergency cards and member groups across 107 countries [5,6].
In the United States, the US Hereditary Angioedema Association offers a toolkit for emergency departments, a way to find experienced doctors, and guides on travel and pregnancy [7,8].
In the United Kingdom, HAE UK covers diagnosis and treatment, with sections for children, young people and women [4], and the NHS page on angioedema explains the other causes of swelling [3].
In Canada, HAE Canada covers triggers, work and school, and access to treatment [9]. In Australia and New Zealand, HAE Australasia provides patient and carer resources [10].
Coverage is thinner in many low- and middle-income countries, and HAE International is the best starting point for finding what exists locally [1,5].
Why doesn’t an antihistamine or an adrenaline pen help?
Those medicines work on histamine, the chemical behind allergic swelling. Hereditary angioedema is driven by bradykinin instead, so they do not relieve it, and reaching for them can delay treatment that does [1,4].
Will my children have it?
Each child of a parent with the condition has a 50 percent chance of inheriting it. Relatives can be tested, and a negative result means they cannot pass it on [2,5].
Is this the same as the swelling caused by blood-pressure tablets?
No, although the two are related. Swelling from ACE inhibitor tablets also involves bradykinin, so allergy medicines do not help, yet it is a side effect rather than an inherited condition. Anyone on those tablets with repeated swelling should still be tested [1].
Do I need treatment before dental work or surgery?
Often yes. Up to 3 in 10 people have an attack after an invasive procedure, so preventive treatment beforehand is recommended. Tell every dentist, surgeon and anesthetist about the diagnosis [1].
Can it be cured?
Not at present. Treatment controls it well, and some people on preventive treatment go years without an attack. Gene-editing research aims at lasting control from a single dose, though nothing of that kind is approved [1,26].
Why did it take so long to get diagnosed?
The condition is rare, gut attacks look like other things, and swelling has many causes. The average delay is now about 7 to 10 years [1].
Written by: trialport editorial team
Reviewed by: Keith Berelowitz, Founder and CEO, trialport
Reviewed on: 3 August 2026
Next review due: 3 August 2027
References last checked: 3 August 2026