Hereditary Angioedema

Hereditary Angioedema (HAE) is a rare hereditary disease that can cause attacks of swelling, and often pain, in specific parts of the body including the stomach, hands, feet, arms, legs, genitals, throat, and face. Depending on the severity of the disease, some people will have many attacks each month, while others will go months without an attack.

People with HAE are missing or have low levels of a protein called C1 esterase inhibitor (C1-INH); in some cases, the C1-INH levels are sufficient, but the protein does not function properly. The defect with C1-INH lies within a person's genetic code, which is why HAE runs in families.

Hereditary Angioedema is classified into three types based on what problem the genetic defect causes.

• Type I - Low levels of C1-INH in the body; this is the most common form of HAE and accounts for ~85% of people with HAE.
• Type II – Normal or elevated levels of C1-INH, but C1-INH is dysfunctional; this accounts for ~15% of people with HAE.
• HAE with Normal C1-INH (formerly known as HAE Type III) - Normal and functioning levels of C1-INH; this type of HAE is extremely rare and not well understood.

Symptoms: HAE Attacks
People with HAE experience recurrent episodes of swelling in the hands, feet, genitals, stomach, face, and/or throat that can last from two to five days. The frequency and severity of attacks may vary dramatically in people affected by HAE, even those in the same family. About 1/3 of people with HAE experience a flat, non-itching red rash that often occurs before or during an HAE attack.

FACE/THROAT
HAE attacks that involve the face or throat are particularly dangerous and can be fatal. Without treatment, throat or tongue swelling can close the airway and cause death by choking. Over 50% of HAE patients experience at least one laryngeal attack in their lifetime. Throat swelling is a medical emergency that always requires immediate medical attention at the first sign of symptoms.

STOMACH/GI AREA
Stomach attacks involve excruciating abdominal pain, nausea, vomiting, and light-headedness caused by swelling in the intestinal wall. These symptoms are distinguishing features of HAE because recurring abdominal pain is rarely seen in other types of angioedema.

HANDS/FEET
Swelling involving feet and hands can be extremely painful and often prevents participation in normal daily activities.

Patients must have ready access to effective on-demand medication to administer at the onset of an HAE attack. An FDA-approved on-demand HAE medication (ecallantide, icatibant, pdC1INH, or rhC1INH) should be used as first-line treatment for attacks whenever possible.

Long-term prophylactic treatment of HAE-C1INH should include first-line medications (IV C1INH, SC C1INH, berotralstat, or lanadelumab).

HAE management plans should include: (A) effective on-demand medication for every patient, (B) consideration of long-term prophylactic medications to prevent HAE attacks, and use of short-term prophylactic medications before medical procedures or other events known to trigger HAE symptoms.