Hereditary Angioedema (HAE) is an autosomal dominant disease characterized by painful, unpredictable, recurrent attacks of inflammation affecting the hands, feet, face, abdomen, urogenital tract, and the larynx. The inflammation can be disfiguring, debilitating, or in the case of laryngeal attacks, life-threatening. HAE is estimated to occur in at least 6,000 people in the US and is caused by deficient or dysfunctional levels of C1 inhibitor, a naturally occurring molecule that is known to modulate the inflammatory cascade. If left untreated, HAE can result in a mortality rate as high as 40% primarily due to upper airway obstruction.
As with other autosomal dominant diseases, patients with HAE generally inherit one normal gene and one abnormal gene (heterozygous). Thus, the child of an affected parent has a 50% chance of inheriting the abnormal gene. The genetic defect may also be caused by spontaneous mutations, and it is estimated that 20% to 25% of all HAE cases occur in patients with no family history of the disease.
Symptoms and Severity of HAE
Symptoms of an HAE attack generally present as swelling of one or more organ systems, most commonly affecting the skin, gastrointestinal tract, or respiratory tract. During skin attacks, the swelling is generally non-pitting with poorly defined margins and typically involves areas of the face such as the lips, eyelids, and tongue. Patients who experience gastrointestinal attacks typically present with significant abdominal pain and vomiting usually resulting from intestinal obstruction caused by swelling in the gut. Gastrointestinal patients may also experience attacks of acute abdominal pain that can mimic other acute surgical conditions, leading to unnecessary abdominal surgeries. More severe symptoms of HAE include laryngeal and upper airway edema that may lead to respiratory tract compromise and potential death from asphyxiation. Patients with no previous history of upper airway involvement are still at risk for asphyxiation as there is no correlation between anatomical location of previous attacks and likely location of future attacks. In acute laryngeal attacks, death may result in as quickly as 20 minutes.
HAE attacks account for approximately 15,000 to 30,000 emergency department (ED) visits per year. And, because symptoms of HAE can mimic a surgical emergency, about one-third of patients with undiagnosed HAE have been reported to have undergone unnecessary surgery during abdominal attacks, because the symptoms very closely resemble appendicitis and other medical conditions that frequently require surgery.
Frequency of HAE Attacks
HAE is unpredictable in nature with substantial variation in the frequency and the age of onset of attacks. Attack patterns vary with age and may affect a single site or multiple sites. Most attacks of HAE last 2 to 5 days, resulting in 20 to 100 days of incapacitation per year. Episodes of HAE often occur without warning and often may be precipitated by a trigger. Common triggers include:
- Dental procedures
- Emotional stress
- Oral contraceptive use
There is little correlation between the symptoms of attack and the type of genetic defect present, even within the same family. Furthermore, age and past attack patterns do not predict the site, severity, or speed of future attacks.
For more information on HAE, visit the U.S. HAE Association’s website at: www.haea.org