What is Hereditary Angioedema?
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 (Type I) or dysfunctional (Type II) levels of C1 inhibitor, a naturally occurring molecule that is known to inhibit kallikrein, bradykinin, and other serine proteases in the blood1,2. 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 disease1.
Symptoms and Severity of HAE
Symptoms of an HAE attack generally present as edema of one or more organ systems, most commonly affecting the skin, gastrointestinal tract, or respiratory tract. During skin attacks, the edema 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 obstruction1 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 surgeries5. 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.
An additional morbidity associated with HAE is premature labor in pregnant women afflicted with the disease. In a study of one kindred, 60% more premature labor was reported among diagnosed mothers1. It is important that emergency room physicians become familiar with HAE symptoms as HAE patients account for about 15,000 to 30,000 Emergency Room visits annually6. Emergency departments should have a protocol for the management of patients with HAE, which should include seeking the advice of an allergist/immunologist on the plan of treatment. It is also important that allergists work with their patients’ general physicians to ensure that general physicians are aware of all HAE patients within their practice and that appropriate treatment plans are in place5.