25
Researchers at Pennsylvania State University College of
Medicine conducted 2 systematic reviews of prodromal
symptoms in the medical literature.
58,59
They also sent a
questionnaire on prodromal symptoms preceding HAE
attacks to 158 patients. Of 46 patients returning the
survey, 40 (87.0%) reported the occurrence of prodromal
symptoms before their recent attack, and 44 (95.7%)
reported having had prodromal symptoms before previous
attacks.
60
The prevalence of these prodromal symptoms
was 0% to 100%, and reproducibility varied. The authors
concluded that symptoms were highly variable in mani-
festation, prevalence, reproducibility, and duration.
59
The most common prodromal symptoms were:
60
•
Erythema marginatum-like, nonpruritic rash
•
Parasthesias (tingling, itching, tightness, or pain)
•
Flu-like symptoms
•
Headache
•
Irritability
•
Abdominal discomfort
•
Mood changes
•
Urticaria
•
Hyperactivity
•
Fatigue
•
Thirst
•
Malaise
•
Nausea.
3.2 Establishing the Diagnosis of HAE
Diagnosis of HAE is based on the clinical and family history,
signs and symptoms, and laboratory tests.
5,8,11
3.21 Clinical Signs of HAE
An International Consensus Algorithm for the Diagnosis,
Therapy, andManagement of HAE was published in 2010.
11
Experts agree that any of the following signs, symptoms, or
clinical history may be suspicious of a diagnosis of HAE:
5,8,11
•
Recurrent, nonpitting, nonpruritic angioedema
without urticaria
•
Recurrent episodes of cramping and abdominal pain
that mimic acute abdomen
•
Angioedema that does not respond dramatically to
antihistamines or corticosteroids
•
Laryngeal edema
•
History of similar symptoms in relatives or diagnosis
of HAE in a family member.
3.22 Laboratory Criteria to Corroborate
the Diagnosis
For suspected HAE, the International Consensus Algorithm
recommends laboratory screening with:
11
•
Serum C4
•
C1-INH antigenic protein.
C4 levels are decreased between swelling attacks in
nearly all individuals with HAE. However, because of the
wide range of “normal” C4 values in many laboratories,
significant consumption of C4 can occur during an attack
and values may test in the “low normal” range. If C4
levels are decreased, C1-INH protein and function can help
confirm the diagnosis of HAE.
8,11
In HAE-I, serum C4 and C1-INH antigenic proteins are
both low. The International Consensus Algorithm panel
recommends repeating the tests to confirm the diagnosis of
HAE-I. To confirm the diagnosis of HAE-I – or if C4 levels are
normal or low and C1-INH antigenic protein is normal – the
International Consensus panel recommends:
•
C1-INH functional assay.
HAE
