Kawasaki Syndrome: An Investigation of Recurrence, Atypical Cases, and Treatment Open Access

Maddox, Ryan Allen (2012)

Permanent URL: https://etd.library.emory.edu/concern/etds/sf268609t?locale=en
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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):

  1. Are patients with recurrent KS different from non-recurrent KS patients?
  2. Are there characteristics of physician-diagnosed KS patients who do not meet the KS case definition that may allow for early identification and treatment?
  3. 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 17th 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


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