Diagnosis of Hereditary AngioedemaNext Topic
Although HAE can be detected using a simple blood test, often the disease is misdiagnosed because many HAE symptoms are associated with a range of common conditions such as allergies, headaches, colic, appendicitis, or other gastrointestinal illnesses. If symptoms are not recurrent or do not recur in the same physical location, diagnosis is difficult from the outset.
Diagnosis of HAE is often delayed by as much as 10 or more years. Be sure your doctor is aware of your family medical history, signs and symptoms, onset and duration of angioedema, and triggers of attacks. This will allow other causes of angioedema to be ruled out. (See Other cause of angioedema.) Ruling out other causes is important because the treatment of HAE is different from treatment of other causes of angioedema. Proper diagnosis will avoid inappropriate treatment with ineffective medical approaches. Patients with abdominal symptoms have sometimes been subjected to unnecessary abdominal surgery.
Differential Diagnosis of HAE
Although almost all cases of allergic angioedema produce hives (urticaria) and itching (pruritus), these two symptoms usually do not appear in bradykinin-mediated forms of angioedema, such as HAE and ACE-inhibitor–induced angioedema.
The diagnosis of HAE is suggested by clues such as episodes of swelling without hives and unexplained attacks of severe cramping and abdominal pain. Most patients with HAE also have a personal or family history of mild recurrent attacks of angioedema or abdominal pain. In approximately 20% to 25% of cases, however, a family history of HAE is absent. These cases are thought to be due to a new spontaneous mutation.
Patients with HAE typically experience their first episode of angioedema during adolescence or early adulthood, though many patients have mild attacks beginning in childhood. Episodes of angioedema may develop without any prior trauma, but most patients are able to identify a potential triggering event.
Common precipitating factors include minor injury, dental or surgical procedures, vigorous exercise, emotional stress, alcohol consumption, infections, and oral contraceptive use. In patients with HAE, skin swelling (which may affect the extremities, face, genital area, and the trunk) is the most common symptom of angioedema. Abdominal pain is also frequently present.
With suspicion from signs and symptoms, your doctor can diagnose HAE with blood tests to measure the levels of C1-INH concentration, C1-INH activity, and a related enzyme called C4 (see diagram below).
| Blood tests for different types of angioedema |
| HAE type |
C1-INH concentration |
C1-INH activity |
C4 |
| Type 1 |
Low |
Low |
Low |
| Type 2 |
Normal |
Low |
Low |
| Type 3 |
Normal |
Normal |
Normal |
ACE-inhibitor–induced Angioedema
ACE-inhibitor–induced angioedema does not have symptoms of hives (urticaria) or itching (pruritus). About half of the patients who develop angioedema while taking an ACE inhibitor will have started on the drug during the week prior to occurrence of angioedema symptoms. However, this drug-induced adverse effect can also occur after several years of ACE inhibitor therapy. ACE-inhibitor–induced angioedema commonly involves the head, neck, mouth, tongue, and upper airway. Intestinal edema may also occur, causing sudden abdominal pain, vomiting, and diarrhea.
Next Topic