hereditary angioedema: types, signs and treatment in canada
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signs and symptoms of hereditary andioedema include episodes of swelling in the face, hands, and genitals, often with abdominal pain. breathing difficulties are rare but can be potentially fatal because of asphyxiation.
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hereditary angioedema (hae) is a rare genetic disorder that causes spontaneous episodes of edema or swelling because of excess fluids accumulated in body tissues. the swelling can affect the hands, feet, face, gastrointestinal tract, or airway, and it can last one to five days. the onset can be slow over several hours or rapid. it’s this pattern that helps distinguish hae from other chronic, non-episodic conditions.
the attacks don’t have the itching often seen in allergic reactions, but they come with pain, fatigue and disfigurement. swelling in the gastrointestinal tract can cause severe cramping, whereas swelling in the airway can lead to life-threatening obstruction of breathing. the fluid accumulation happens because of leakage from blood vessels into surrounding tissues, driven by a dysfunction in regulation.
hae occurs in about one in 10,000 to one in 50,000 people, according to hereditary angioedema canada (hae canada). a child has a 50 per cent possibility of inheriting this disease if one of the parents has it. symptoms typically begin in childhood or young adulthood and get worse around puberty. most symptomatic cases occur before age 20, however, young children sometimes remain asymptomatic. because hae is so rare, it can take up to 10 years to get an accurate diagnosis after symptoms are first experienced.
as hae canada notes, “the disease places extraordinary strain on patients emotionally, physically and psychologically. it is common for patients to miss many days of school or work during an attack.”
what causes hereditary angioedema?
the majority of people with hae have a genetic defect that leads to a deficiency in the c1-inhibitor protein which regulates fluid balance. c1-inhibitor is part of a group of proteins in the blood plasma that work alongside the immune system to protect the body from infections. however, hae is also seen in people who have normal levels of c1-inhibitor, which means there are genetic defects in other genes that are responsible for their angioedema.
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another factor that complicates diagnosis is that while hae is an inherited disorder, new variants account for up to 25 per cent of cases without a family history, notes the national organization for rare disorders.
types and signs of hereditary angioedema
hae is classified into three types: type i, the most common (85 per cent of cases), is characterized by abnormally low levels of c1-inhibitor. type ii (15 per cent of cases) results from the production of a dysfunctional c1-inhibitor protein, and type iii (the less common) has normal c1-inhibitor levels and is caused by variants in several different genes.
signs and symptoms include episodes of swelling, often with abdominal pain. breathing difficulties are rare but can be potentially fatal because of asphyxiation. research has shown that several factors can trigger the attacks, such as stress, trauma, infections, certain medications like ace inhibitors or nsaids, and hormonal changes from oral contraceptives and pregnancy.
the signs and symptoms that can happen include the following:
cutaneous angioedema
- affects the face, extremities and genitals most frequently
- swollen areas are non-pitting with ill-defined margins, hard and painful, not red and itchy
- episodes often last one to five days and resolve without treatment
- skin rashes such as urticaria are rarely present and, if noted, may exclude hae from the diagnosis
visceral angioedema
swelling in the gastrointestinal mucosa can lead to:
- severe abdominal pain
- nausea and vomiting
- symptoms mimicking acute abdomen, sometimes leading to unnecessary surgery
swelling of the throat (pharynx) or voice box (larynx) can cause:
- pain
- difficulty swallowing (dysphagia)
- difficulty speaking (dysphonia)
- noisy breathing (stridor)
- laryngeal edema, which is a life-threatening complication from airway obstruction, requires immediate medical attention
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for some people, many hae episodes happen without identifiable triggers, and response to the same trigger can vary significantly between individuals. for example, a specific trigger may cause a severe response in one patient but a mild or negligible response in another.
diagnosis and treatment of hereditary angioedema
diagnosis can be complex, involving assessing c1-inhibitor antigenic and functional levels, c4 complement levels, and potential genetic testing. without proper treatment, hae is highly disabling.
with limited data available on the clinical profile and disease burden of hae in canadians, researchers from the centre hospitalier universitaire de québec looked at the results from a patient survey conducted by the hae patient organization angio-oédeme héréditaire du québec from may 2019 to february 2020. they noted in the journal of immunology research that prior to diagnosis, 69 per cent of participants underwent unnecessary treatments and procedures, with a 10-year delay between first symptoms and diagnosis. before starting their current treatment, 42 per cent experienced weekly hae attacks—most in the abdomen (89 per cent), followed by the larynx and feet (both 66 per cent), hands and face (both 63 per cent).
while most attacks were severe or moderate, almost half of participants waited more than an hour before getting medical attention at their last emergency department visit.
as well, hae was associated with decreased quality of life, impacting personal and professional life. patients with type iii were treated more often with tranexamic acid for long-term prophylaxis, and their condition was less controlled, resulting in more attacks and er visits.
as the authors wrote: “individuals face barriers at each step, from diagnosis to treatment and disease management. this indicates an urgent need for increased awareness and education on hae among canadian physicians, as well as continued advancements in treatment.”
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where are we at with treatment? seven products are currently approved by health canada for preventing and treating hae attacks, affording patients and their physicians options for developing an hae treatment plan tailored to meet each person’s unique needs. while there is no cure, the aim of treatment is to prevent the episodes, reduce their severity and improve quality of life.
but as hae canada explains, a large number of patients report that their frequent and severe abdominal pain was inappropriately diagnosed as psychosomatic, resulting in a referral for psychiatric evaluation. unnecessary exploratory surgery has been performed on patients experiencing gastrointestinal edema, because abdominal hae attacks mimic other diseases such as appendicitis, small bowel obstruction, inflammatory bowel disease, gall bladder disease or diverticulitis.
as well, before therapy became available, the mortality rate for airway obstruction was reportedly as high as 30 per cent.
if you think you may have hae and do not yet have a specialist, the first step is to see a family physician for referral. visit the canadian hae network (chaen) for a list of hae treating physicians who are members of the network.
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