People with hereditary angioedema (HAE) experience episodes of soft tissue swelling. Such instances occur in the hands, feet, gastrointestinal tract, genitals, face, and throat.
This article details the stages of an HAE attack and how to treat it.
During an HAE attack, an inherited genetic mutation results in a cascade of events that lead to swelling. The swelling is different from an allergy attack.
Mutations occur in the SERPING1 gene
Inflammation is your body’s normal response to infection, irritation, or an injury. At some point, your body needs to be able to control the inflammation because too much can lead to problems.
There are three different types of HAE. The two most common types of HAE (types 1 and 2) occur due to mutations (errors) in a gene called SERPING1.
This gene provides instructions for making the C1 esterase inhibitor protein (C1-INH). C1-INH helps reduce inflammation by blocking the activity of proteins that promote inflammation.
C1 esterase inhibitor levels reduce in amount or function
The mutation that causes HAE can lead to a reduction in C1-INH levels in the blood (type 1). It can also result in a C1-INH that doesn’t function properly, despite a normal level of C1-INH (type 2).
The next step in the chain of events leading to an HAE attack involves an enzyme in the blood known as kallikrein. C1-INH suppresses kallikrein.
Without enough C1-INH, the body cannot inhibit kallikrein activity. The kallikrein then separates (cleaves) a substrate known as high-molecular-weight kininogen.
Excessive production of bradykinin
When kallikrein splits kininogen, it results in a peptide known as bradykinin. Bradykinin is a vasodilator, a compound that opens up (dilates) the lumen of blood vessels. During an HAE attack, the body produces excessive amounts of bradykinin.
The blood vessels leak too much fluid
Bradykinin allows more fluid to pass through blood vessels into body tissues. This leakage and the blood vessel dilation it causes result in lower blood pressure.
Fluid accumulates in the body tissues
Without enough C1-INH to control this process, fluid builds up in the body’s subcutaneous tissues.
The excess fluid buildup causes severe swelling.
What happens in type 3 HAE
A third, very rare type of HAE (type 3) happens in a different matter. Type 3 results from a mutation in a different gene located on chromosome 5 called F12.
This gene provides instructions for making a protein called coagulation factor XII. This protein is involved in blood clotting and is also responsible for stimulating inflammation.
A mutation in the F12 gene creates a factor XII protein with increased activity. This, in turn, causes more bradykinin production. Like types 1 and 2, the increase in bradykinin makes blood vessel walls leak uncontrollably, which leads to episodes of swelling.
Without treatment, people may experience an HAE attack every 1 to 2 weeks. Each instance may last for 3 to 4 days.
At some point, your body will need C1-INH to help control inflammation. Some HAE attacks happen without any clear reason. There are also
- repetitive physical activities
- activities that create pressure in one area of the body
- freezing weather or changes in weather
- high exposure to the sun
- insect bites
- emotional stress
- infections or other illnesses
- dental procedures
- hormonal changes
- certain foods, like nuts or milk
- blood pressure-reducing medications, known as ACE inhibitors
The main symptom of an HAE attack is recurrent swelling. The most common locations for this swelling include:
- the face
- intestinal tract
People typically first experience HAE attacks during childhood, and symptoms may worsen throughout adolescence.
As per its name, HAE is a hereditary condition.
It occurs when a genetic defect means a person does not have enough C1-INH in their blood or the protein does not work correctly.
Shortfalls in C1-INH levels, or function, mean that the body cannot regulate some of its inflammatory responses, leading to excessive swelling during attacks.
Knowing what happens during an HAE attack has led to improvements in treatments.
To stop fluid from building up, people with HAE need to take medication. HAE drugs either prevent swelling or increase the amount of C1-INH in the blood.
- a direct infusion of donated fresh frozen plasma, which contains C1 esterase inhibitor
- medications that replace C1-INH in the blood, such as Berinert, Ruconest, Haegarda, and Cinryze
- androgen therapy, such as a drug called danazol, which can increase the amount of C1-INH esterase inhibitor your liver produces
- ecallantide (Kalbitor), which is a medication that inhibits cleavage of kallikrein, thus preventing the production of bradykinin
- icatibant (Firazyr), which stops bradykinin from binding to its receptor, the bradykinin B2 receptor antagonist
An HAE attack occurs differently than an allergic reaction. As a result, drugs that you may use to treat allergic reactions, like antihistamines, corticosteroids, and epinephrine, will not work in an HAE attack.
Hereditary angioedema (HAE) is a hereditary condition that causes recurrent swelling.
HAE occurs due to a C1-INH protein dysfunction. During an attack, these proteins cannot regulate your body’s inflammatory responses as they should, which leads to uncontrolled swelling.
Most people with HAE will cycle between periods of flare ups, where symptoms worsen, and periods of remission, where no swelling occurs.
Typically, HAE flares will occur once every 1 to 2 weeks and last 3 to 4 days at a time.