Diagnosing HAE is not difficult in principle; however patients frequently get a wrong diagnosis primarily because of its rarity, with many doctors not coming across a single patient with this clinical picture in their entire career. Furthermore, HAE is difficult to diagnose due to its non-specific symptoms, which often resemble those of an allergy, intestinal colic or appendicitis and can lead physicians to a wrong conclusion easily. As a result, it can take a relatively long time for HAE to be diagnosed correctly. However, while the disease remains undetected, the patient could be at risk of suffocation due to acute swelling in the larynx in a severe attack or, in the case of intestinal edema, of undergoing unnecessary endoscopy or even having their appendix removed.(2,12)
Angioedema is a common symptom and most cases of angioedema are due to an allergic reaction. As a nonallergic form of angioedema, symptoms of HAE do not typically present with urticaria and are not caused by the common triggers of an allergic response or do not respond to treatments used in histamine-mediated allergic reactions, i.e. antihistamines, glucocorticoids and epinephrine.
Ultimately, a diagnosis of HAE is confirmed by laboratory tests indicating either a reduced concentration of C1-INH and/or depressed C1-INH activity. A measure of C4 antigen concentration is also important as this parameter is decreased in both HAE types I and II. Assaying C1q concentrations is necessary to differentiate between HAE and acquired angioedema, a non –inherited form of angioedema associated with a C1-INH deficiency due to a chronic and/or serious illness.(2,11,21,25)
Diagnosis is difficult in patients who only have episodes of swelling in the intestine. Initially, further information is obtained by establishing whether anyone else in the patient’s family has had the disease (known as family history). However, only a laboratory analysis can provide final confirmation.
At what age does HAE attacks start?
The age of HAE onset varies considerably, however, in one study, half of the patients reported onset of their symptoms by the age of seven, and over two thirds became symptomatic by the age of thirteen. There also seems to be an increased frequency of attacks during puberty or adolescence.