26
C1-INH functional activity is decreased in both HAE-I and
HAE-II. If C1-INH antigenic protein levels are normal or
elevated and C1-INH activity is low, the results are consistent
with HAE-II. Again, the panel recommends repeating the
laboratory tests for confirmation.
11
Figure 12 summarizes
the diagnostic algorithm for both HAE-I and HAE-II.
Acquired angioedema (AAE) may be suspected if C4 levels
are low, there is no family history of HAE, and the age at
symptomonset is older than 40 years. This conditionmay be
due to autoantibodies produced in association with chronic
lymphocytic leukemia. If AAE is suspected, the following
test is recommended:
•
C1q antigenic protein
Low C1q antigenic protein levels are typical in about 75%
of patients with AAE.
11
If both C4 antigenic protein and C1-INH protein are normal,
the International Consensus panel recommends repeating
the test during an acute attack.
11
Rarely, ACE inhibitors can trigger angioedema, principally
in the upper half of the body, including the face, tongue,
pharynx, and larynx. These episodes are believed to involve
increased local concentrations of bradykinin, which is
normally inactivated by ACE.
61
The International Consensus Algorithm proposes genetic
testing, while it is usually not necessary to confirm the
diagnosis of HAE, as an option for diagnosing HAE in
children younger than 1 year of age.
11
3.23 Differentiating HAE From Other Types of
Angioedema
Ask 8 to Differentiate
is a diagnostic tool developed by
CSL Behring in collaboration with HAE specialists. It poses
8 questions that help to distinguish angioedema of HAE
frommore commonly seen allergic angioedema, as shown
in Figure 13.
An overview of the differential diagnosis of HAE and other
common types of angioedema is presented in Table 7.
Figure 13 –
Ask 8 to Differentiate
Diagnostic Tool
HAE-I
No HAE
C1-INH
function
C1-INH
function
C4,
C1-INH
C4, C1-INH
C4, C1-INH
during attack
Other type of
angioedema?
•
due to medication
•
HAE with normal
C1-INH
HAE-II
HAE?
Family
history
No family
history
Early age
at onset,
C1q
Acquired
angioedema
Late age
at onset,
C1q
C4, C1-INH
Figure 12 – Diagnostic Algorithm for HAE-I and HAE-II
C1-INH=C1 esterase inhibitor
Adapted from 11.
a
Approximately 9 of 10 HAE patients will have abdominal attacks that cause pain,
dizziness, nausea, vomiting, and/or diarrhea.
31,36
b
75% of patients will have a positive family history for HAE;
de novo
mutations
occur in approximately 25% of patients.
16
1
2
3
4
5
6
7
8
Ask 8 to Differentiate
between
allergic angioedema, acute abdomen, and HAE.
(3 or more
✓
’s add credence to a diagnosis of HAE)
Unexplained edema?
Asymmetrical swelling attacks?
Unexplained abdominal pain?
a
Recurrent attacks?
Family history of similar episodes?
b
Or someone in family “choked to death”?
b
Prodrome (fatigue, tingling, nausea,
or flu-like symptoms) — minutes, hours,
or days before?
Antihistamines, epinephrine, or
corticosteroids provide little relief?
Watery or itchy eyes during attack?
YES
NO
✓
✓
✓
✓
✓
✓
✓
✓
CONSIDER HAE
