Prediction of intravenous immunoglobulin resistance in patients with Kawasaki disease according to the duration of illness prior to treatment
Risk factors predicting intravenous immunoglobulin (IVIG) resistance in patients with Kawasaki disease (KD) were assessed according to the duration of illness prior to treatment. Of 555 KD patients included between 2008 and 2014, 362 were IVIG responders (65.2%) and 193 were IVIG non-responders (34.8%). The risk of IVIG resistance was inversely correlated with the duration of illness prior to treatment. Neutrophil dominance (≥ 80%) was significantly higher in IVIG non-responders regardless of the duration of pre-IVIG illness. While there were no differences between IVIG responders and non-responders who were diagnosed at < 3 days, increasing platelet count and decreasing liver enzyme levels were seen over time in IVIG responders, but not in IVIG non-responders. Multivariable analysis showed that, in addition to neutrophil levels ≥ 80%, risk factors for IVIG resistance were age ≤ 12 months for patients who were diagnosed at ≤ 3 days, and platelet count ≤ 300 × 103/μL and aspartate aminotransferase level ≥ 100 IU/L for patients who were diagnosed at ≥ 6 days.
What is Known:
• Several systems have been developed to predict IVIG resistance in patients with KD but the sensitivity and specificity of these tools are insufficient and ethnic variations have been reported.
What is New:
• Predictors of IVIG resistance differ depending on the duration of illness prior to treatment.
• Risk assessment according to the duration of pre-treatment illness may improve the ability to predict IVIG resistance.
KeywordsIntravenous immunoglobulin Kawasaki disease Resistance Risk factor
Coronary artery abnormalities
Coronary artery aneurysm
Coronary artery dilatation
We thank Dr. Soon-Young Hwang (Biostatistical consulting unit, Medical Science Research Center, College of Medicine, Korea University) for statistical assistance.
KSH, KCL and JL designed the study, and collected and analyzed the data. JL drafted the initial and final manuscript. All authors participated in critical review and approved the final manuscript as submitted.
Compliance with ethical statements
Conflict of interest
The authors have no conflicts of interest to disclose.
This study is a retrospective and observational study and does not contain any studies with human participants or animals. With the approval of the institutional review board of the Korea University Medical Center, no informed consent was asked.
- 2.Cha Y (2006) Classification and diagnosis of red blood cell diseases. In: Cha Y (ed) Hematology, 2nd edn. Panmun Education, SeoulGoogle Scholar
- 10.Nathan D, Oski F (1998) Nathan and Oski’s Hematology of Infancy and Childhood. 7th edn, Saunders, PhiladelphiaGoogle Scholar
- 11.Newburger JW, Takahashi M, Burns JC, Beiser AS, Chung KJ, Duffy CE, Glode MP, Mason WH, Reddy V, Sanders SP, Shulman ST, Wiggins JW, Hicks RV, Fulton DR, Lewis AB, Leung DYM, Colton T, Rosen FS, Melish ME (1986) The treatment of Kawasaki syndrome with intravenous gamma globulin. N Engl J Med 315:341–347. https://doi.org/10.1056/NEJM198608073150601 CrossRefPubMedGoogle Scholar
- 12.Newburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY, Burns JC, Shulman ST, Bolger AF, Ferrieri P, Baltimore RS, Wilson WR, Baddour LM, Levison ME, Pallasch TJ, Falace DA, Taubert KA, Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association (2004) Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the committee on rheumatic fever, endocarditis, and Kawasaki disease, council on cardiovascular disease in the young, American Heart Association. Pediatrics 114:1708–1733. https://doi.org/10.1542/peds.2004-2182 CrossRefGoogle Scholar
- 13.Research Committee of Kawasaki disease (1984) Report of subcommittee on standardization of diagnostic criteria and reporting of coronary artery lesions in Kawasaki disease. Ministry of Health and Welfare, TokyoGoogle Scholar
- 14.Rigante D, Andreozzi L, Fastiggi M, Bracci B, Natale MF, Esposito S (2016) Critical overview of the risk scoring systems to predict non-responsiveness to intravenous immunoglobulin in Kawasaki syndrome. Int J Mol Sci 17:278. https://doi.org/10.3390/ijms17030278 CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Sano T, Kurotobi S, Matsuzaki K, Yamamoto T, Maki I, Miki K, Kogaki S, Hara J (2007) Prediction of non-responsiveness to standard high-dose gamma-globulin therapy in patients with acute Kawasaki disease before starting initial treatment. Eur J Pediatr 166:131–137. https://doi.org/10.1007/s00431-006-0223-z CrossRefPubMedGoogle Scholar
- 16.Sleeper LA, Minich LL, McCrindle BM, Li JS, Mason W, Colan SD, Atz AM, Printz BF, Baker A, Vetter VL, Newburger JW, Pediatric Heart Network Investigators (2011) Evaluation of Kawasaki disease risk-scoring systems for intravenous immunoglobulin resistance. J Pediatr 158:831–835 e833. https://doi.org/10.1016/j.jpeds.2010.10.031 CrossRefPubMedGoogle Scholar