Abstract
Abstract
Kawasaki Syndrome: An Investigation of Recurrence, Atypical
Cases, and Treatment
Kawasaki syndrome (KS), an acute illness of unknown etiology,
is the leading cause of acquired heart disease among children. This
dissertation, in three studies, addresses the following research
questions related to KS patients who may be at increased risk for
coronary artery abnormalities (CAAs):
- Are patients with recurrent KS different from non-recurrent KS
patients?
- Are there characteristics of physician-diagnosed KS patients
who do not meet the KS case definition that may allow for early
identification and treatment?
- Can KS patients who will not respond to initial intravenous
immunoglobulin (IVIG) treatment be predicted?
Studies 1 and 2 used the Centers for Disease Control and
Prevention (CDC) national KS surveillance database (1984-2008) to
evaluate recurrence and patients not meeting the CDC KS case
definition, respectively. Study 1 also applied the CDC case
definition to the 17
th Japanese nationwide KS survey
(2001-2002) to assess recurrence in Japan. In the US, 1.7% of KS
patients were recurrent; in Japan, 3.5% were. Although recurrent
patients were treated earlier than non-recurrent patients, they
were more likely to develop CAAs. In Study 2, KS patients not
meeting the CDC case definition were significantly younger.
Physician-diagnosed KS patients were also more likely to be white
and less likely to be black compared to patients meeting the CDC
case definition, which may reflect quality of care issues.
For Study 3, data abstracted from electronic medical records
for KS patients discharged from two pediatric specialty hospitals
in Atlanta, Georgia from 2006-2008 were analyzed, with a focus on
IVIG treatment response. Of KS patients meeting the CDC KS case
definition, 23.6% did not respond to initial treatment. Based on
logistic regression results, a scoring system was created that
improved upon earlier models in predicting nonresponse to initial
treatment in our population, which varied markedly from populations
evaluated previously.
The three studies emphasize that, until a confirmatory test
for KS is developed, physicians must use their best judgment when
diagnosing and treating the illness. For high-risk KS patients,
more aggressive treatment may be warranted, and further research is
needed to determine the best regimen to apply.
Table of Contents
Table of Contents
1.
Overview................................................................................................
1
2.
Background.............................................................................................
2
2.1
History.................................................................................................
2
2.2 Clinical description and case
definitions......................................................
4
2.2.1 CDC KS case
definition.........................................................................
4
2.2.2 Japanese KS case
definition..................................................................
5
2.2.3 Atypical and incomplete
KS...................................................................
6
2.2.4 Other disease
characteristics................................................................
6
2.3 KS
surveillance......................................................................................
7
2.3.1 US
surveillance...................................................................................
7
2.3.2 Japan
surveillance...............................................................................
7
2.4 KS
epidemiology....................................................................................
8
2.4.1 KS
incidence......................................................................................
8
2.4.2 KS
demographics................................................................................
8
2.4.3 KS
recurrence.....................................................................................9
2.5 Etiology and
transmission.........................................................................9
2.6
Treatment............................................................................................10
2.6.1 Prediction of those at risk for
CAAs........................................................12
2.6.2 Prediction of those at risk for treatment
nonresponse................................13
2.7 Current
research...................................................................................15
2.7.1
Genetics...........................................................................................15
2.7.2 Alternative
treatments........................................................................16
3.
Introduction...........................................................................................17
3.1 Are patients with recurrent KS different from
non-recurrent
patients?..................................................................................................17
3.2 Are there characteristics of physician-diagnosed KS
patients who
do not meet a KS case definition that may allow for
early
identification and
treatment?........................................................................17
3.3 Can KS patients who will not respond to initial IVIG
treatment be
predicted?
...............................................................................................18
4.
Methods................................................................................................19
4.1 Statistical
tests....................................................................................19
4.1.1 Categorical
variables...........................................................................19
4.1.2 Continuous
variables...........................................................................19
4.2 Measures of
association.........................................................................20
4.2.1 Risk
ratio..........................................................................................20
4.2.2 Odds
ratio........................................................................................20
4.3 Logistic regression
modeling...................................................................20
4.4 Assessment of test
performance.............................................................21
4.4.1 Sensitivity and
specificity...................................................................21
4.4.2 ROC curve
analysis............................................................................21
5. Study 1: Kawasaki syndrome recurrence among children in
the
United States and in
Japan.........................................................................22
5.1
Abstract.............................................................................................23
5.2
Introduction........................................................................................24
5.3
Methods.............................................................................................26
5.3.1 US
data...........................................................................................26
5.3.2 Japanese
data..................................................................................28
5.4
Results...............................................................................................29
5.5
Discussion...........................................................................................33
5.6
References..........................................................................................37
6. Study 2: Atypical and physician-diagnosed Kawasaki syndrome
cases
not meeting a Kawasaki syndrome case definition, United
States, 1984-
2008.......................................................................................................47
6.1
Abstract.............................................................................................48
6.2
Introduction........................................................................................49
6.3
Methods.............................................................................................51
6.4
Results...............................................................................................52
6.5
Discussion...........................................................................................54
6.6
References..........................................................................................58
7. Study 3: Kawasaki syndrome treatment response at two
pediatric
specialty hospitals, Atlanta, Georgia,
2006-2008..............................................68
7.1
Abstract.............................................................................................69
7.2
Introduction.........................................................................................71
7.3
Methods..............................................................................................72
7.4
Results................................................................................................75
7.5
Discussion............................................................................................78
7.6
References...........................................................................................81
8.
Discussion.............................................................................................90
8.1 General
conclusions...............................................................................90
8.2
Strengths............................................................................................91
8.3
Limitations...........................................................................................92
8.4 Future
research....................................................................................93
9.
References............................................................................................95
10.
Appendix............................................................................................112
About this Dissertation
Rights statement
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