Differential Diagnosis

Hereditary angioedema (HAE) is a rare disease that is often misdiagnosed because its symptoms mimic several common conditions such as allergic reaction, acute appendicitis, gallbladder attack, submucosal abdominal tumor, diverticulitis, and irritable bowel syndrome (Frank, et al. 1976).

When a family (e.g., hereditary) history is not available, initial misdiagnosis commonly occurs. In these cases, patients are often subjected to non-essential medical procedures, such as laparoscopies, ineffective treatments, such as administration of antihistamines, and/or unnecessary psychiatric referrals (due to "unexplained" recurrent abdominal pain).

HAE can be confirmed with proper blood tests.

When HAE is suspected, a referral to an allergy/clinical immunologist specialist for definitive diagnostic procedures and treatment is appropriate, because not all physicians have experience with HAE, and not all laboratories are equipped to handle the necessary blood specimens.

Patients should have serum levels of C4 measured. A low serum C4 level (C4<30% of mean normal level) is an excellent screening test, because C4 levels are invariably low in untreated patients with either type I or type II HAE.

When these values are low (C4<30% of mean normal level), antigenic C1-INH levels should be tested:

• If antigenic C1-INH is low, this confirms HAE Type I.
• If antigenic C1-INH levels are normal or elevated, a C1-INH functional assay should be performed. If this value is low, HAE Type II is confirmed.

Caution: Not all labs are able to measure functional C1-INH accurately, and the sample should be processed within 48 hours. If HAE is suspected, use a laboratory that can measure this level effectively, and follow-up by having the diagnosis confirmed by a clinical immunologist.

For more information about diagnosis and treatment of HAE see: