Diagnosing HAE

Hereditary angioedema (HAE) is a rare disease that is often misdiagnosed because its symptoms mimic those of several common conditions, such as allergic reaction, acute appendicitis, gallbladder attack, submucosal abdominal tumor, diverticulitis, and irritable bowel syndrome.1,2

When a family history is not available, initial misdiagnosis commonly occurs. In these cases, patients are often subjected to non-essential medical procedures, such as laparoscopy; ineffective treatments, such as administration of antihistamines; and/or unnecessary psychiatric referrals (due to "unexplained" recurrent abdominal pain).1,6

HAE can be confirmed with proper blood tests

When HAE is suspected, a referral to an allergist/clinical immunologist 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.8

The Canadian HAE Network of physicians (CHAEN) has a list of Diagnostic labs in Canada along with sample handling instructions under the "about HAE & Diagnosis" heading on their website. Click (here)

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.6

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

Clinical and laboratory findings associated with angioedema of various causes 6

Type of Angioedema Clinical Findings C4 Level Antigenic C1-Inhibitor Level Functional C1-Inhibitor Level C1q Level C3 Level
Hereditary angioedema Recurrent angioedema and abdominal attacks without urticaria; attacks are episodic, with intervals between periods of swelling; onset in childhood or young adulthood, with worsening around the time of puberty; prolonged attacks (typically 72–96 h in duration); family history in 75% of patients; attacks do not respond to antihistamines or corticosteroids. decrease decrease
(in type I)
or
normal
(in type II)
decrease normal normal
Acquired C1-inhibitor deficiency Attacks similar to those in hereditary angioedema; onset in middle age or later; absence of family history; attacks do not respond to antihistamines or corticosteroids. decrease decrease
or
normal
decrease decrease normal
or
decrease
Inherited angioedema with normal C1-inhibitor levels Family history of angioedema; possible preponderance of women among affected persons; may be estrogen-dependent; typically manifested after childhood; face, tongue, and extremities affected more than abdomen; attacks do not respond to antihistamines or corticosteroids. normal normal normal normal normal

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.10

Consult the CHAEN website for labs in canada (under the about HAE & Diagnosis section).

Registration

Register for updated information on HAE disease management.

Diagnosis & treatment tools

Ask simple questions to decide if it’s HAE. Compare the UK and Canadian treatment algorithms. Tools for diagnosis & treatment.

Quality of life with HAE

Patients feel depression, anxiety, and fear of unpredictable attacks, especially if they lack understanding of HAE. Read about quality of life with HAE.