HAE: The Always-on Threat

Hereditary angioedema (HAE) is a bradykinin-mediated disease that produces unpredictable swelling in various parts of the body, including the face, gastrointestinal tract, extremities, genitals, and airway (larynx).

What is HAE?

HAE is a rare genetic disease that affects only about one person in 50,000 worldwide.

The sudden and painful swelling can last for days if left untreated and can be disabling, making HAE physically and emotionally hard for people to live with. HAE is unique to each person. While one person may have many attacks in a month, another person may go months without an attack.

Because HAE is so rare, healthcare providers may not have heard of it.  The swelling HAE causes may be mistaken for an allergic reaction or other conditions, such as appendicitis, when involving the abdomen. This can lead to delays in getting the right diagnosis, not getting the proper treatment, and having unnecessary medical procedures.

Forms of HAE

Hereditary Angioedema due to C1-INH Deficiency (HAE-C1-INH)  Type 1 and Type 2

The most common forms of HAE are caused by variants in the SERPING1 gene, leading to reduced C1-INH activity, a key regulator of bradykinin production.

Some variants result in reduced C1-INH (Type 1)
Others result in the C1-INH not working correctly (Type 2)

Suspicion of HAE Type 1 and Type 2—whether due to recurring symptoms, family history, and/or a lack of response to medications used to treat allergies—can be confirmed through laboratory tests that evaluate C1-INH levels and function.

Hereditary Angioedema with Normal C1-INH (HAE-nC1-INH)

Variants in other genes (such as those encoding for coagulation factor XII, plasminogen, kininogen, angiopoietin, etc.) may not directly reduce the activity of C1-INH, but still result in excess signaling through bradykinin-activated bradykinin B2 receptors, leading to HAE.

Suspicion of HAE-nC1-INH can be confirmed by medical and family history together with laboratory tests and genetic testing.

HAE due to unknown mutation (HAE-UNK)

In a number of people with HAE, no genetic variants can be identified and pathogenesis remains to be characterized.

Real person living with HAE.

There is no cure for HAE, though there are several ways to manage it, including infusions, injections, and oral medications. 

What happens during an attack?

For the vast majority of patients with HAE, the disease is caused by an inherited gene defect in the body’s system for regulating bradykinin.

When too much bradykinin is produced and activates the bradykinin B2 receptor in excess, it leads to an uncontrolled leakage of fluid into nearby tissues that causes extreme swelling, discomfort, and pain.

What triggers HAE attacks?

The inconsistency of triggers is one of the most frustrating things about managing HAE, and what makes it so unpredictable. Commonly reported triggers include physical trauma, surgical procedures, anxiety, changes in hormones, certain foods, and even changes in the weather.

Many times, though, attacks occur without any identifiable trigger at all, and something that seemed to trigger an attack once may not the next time. In fact, the number and severity of attacks can change over time.

What are the symptoms of an HAE attack?

It depends on what specific part of the body is being affected.

Before an attack, some patients may notice early warning signs, called prodromes, such as tingling, rash, fatigue, or nausea.

Face

Can draw unwanted attention and cause immense emotional impact
Poor vision from swollen face causing eyes to close

Throat/Airway

Shortness of breath
Difficulty speaking
Choking and fear of death from being unable to breathe
Highest emotional impact compared to other attack locations
Hospitalization more likely to occur

Hands & Arms

Lack of ability to hold objects (phone, pen, glass or cup)
Difficulty texting or typing
May make it difficult to give oneself an injectable or IV HAE medication

Stomach

Mild to severe stomach pain with nausea, vomiting, and/or diarrhea
Abdominal pain can restrict ability to move

Genitals

More frequent attacks during periods and breastfeeding
Estrogen-containing birth-control pills can trigger HAE attacks
Potential attacks after childbirth

Legs & Feet

Difficulty walking or running
Cannot fit into shoes

C1-INH, C1-inhibitor.