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Predictors of Intravenous Immunoglobulin Nonresponse and Racial Disparities in Kawasaki Disease

Clark, Daniel E., MD, MPH*; Denby, Kara J., MD*; Kaufman, Laura M., MD; Fill, Mary-Margaret A., MD; Piya, Bhinnata, MPH§; Krishnaswami, Shanthi, MBBS, MPH§; Fonnesbeck, Christopher, PhD; Halasa, Natasha, MD, MPH§

The Pediatric Infectious Disease Journal: December 2018 - Volume 37 - Issue 12 - p 1227–1234
doi: 10.1097/INF.0000000000002019
Original Studies
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Background: Kawasaki disease (KD) is the most common cause of acquired heart disease in American children. Intravenous immunoglobulin (IVIG) nonresponse is a known risk factor for cardiac sequelae. Previously reported risk factors for nonresponse include age, male sex and laboratory abnormalities. We set out to identify additional risk factors for IVIG nonresponse in a racially diverse KD population.

Methods: We conducted a retrospective chart review at a referral center in the Southeastern United States of children meeting ICD-9 (International Statistical Classification of Disease and Related Health Problems) criteria for KD and being treated with IVIG.

Results: Four-hundred and fifty-nine children met inclusion criteria, 67 were excluded for subsequent rheumatologic diagnosis, unknown race, or failure to meet the American Heart Association guideline criteria. Our final cohort consisted of 392 subjects, with median age of 2.7 years, 65.1% male, 66.1% White, 24.2% Black, 4.9% Asian and 82.9% responded to a single dose of IVIG. Coronary ectasia or aneurysm developed in 27%; 7.4% developed aneurysms and 2.3% giant coronary aneurysms. Nonresponders were more likely to be Black, have higher white blood cell, erythrocyte sedimentation rate and C-reactive protein, lower hemoglobin, develop ectasia or aneurysm and require critical care and hospital readmission. Responders achieved echocardiographic normalization more often compared with nonresponders (81.3% vs. 60.9%, P = 0.002) and coronary artery pseudonormalization (87.2% vs. 69.7%, P = 0.03) at 1 year. Black nonresponders had the slowest normalization at 1 year (52.9%, P = 0.02).

Conclusions: Nonresponders have higher rates and greater severity of coronary involvement than responders. Our study uniquely demonstrates Black race as a risk factor for nonresponse and for delayed normalization of cardiac involvement at 1-year follow-up.

From the *Departments of Internal Medicine and Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee

Greater Lawrence Family Health Center, Lawrence, Massachusetts

Tennessee Department of Health

§Division of Pediatric Infectious Disease, Department of Pediatrics, Vanderbilt University Medical Center

Department of Biostatistics, Vanderbilt University, Nashville, Tennessee.

Accepted for publication February 26, 2018.

This work was supported by Investigator-initiated grant from Baxalta and the CTSA award (Clinical and Translational Science Award) UL1TR000445 from the National Center for Advancing Translational Sciences. Its contents are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences or the National Institutes of Health.

The authors have no conflicts of interest to disclose.

Address for correspondence: Kara J. Denby, MD, Department of Internal Medicine-Pediatrics, Vanderbilt University, 1215 21st Ave South, Medical Center East, 7th Floor, North Tower, Suite II, Nashville, TN 37232. E-mail: k.denby@vanderbilt.edu.

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