Clinical Rheumatology

, Volume 35, Issue 11, pp 2771–2776 | Cite as

Prediction of intravenous immunoglobulin resistance in Kawasaki disease in an East China population

  • Yunjia Tang
  • Wenhua Yan
  • Ling Sun
  • Jie Huang
  • Weiguo Qian
  • Yueyue Ding
  • Haitao LvEmail author
Original Article


The objectives of the study were to find the risk factors associated with intravenous immunoglobulin (IVIG) resistance and generate a prediction scoring system of IVIG resistance in patients with Kawasaki disease (KD). We retrospectively reviewed the clinical records of KD patients between January 2006 and December 2014. Multivariate logistic regression was performed to identify the risk factors of IVIG non-responders. The independent risk factors were used to construct a new scoring system and compared with Kobayashi and Egami scoring systems. Multivariate logistic regression analysis identified age <6 months, rash, edema of extremities, % neutrophils, and serum albumin as independent risk factors for IVIG non-responders. We assigned one point for rash, edema of extremities, and % neutrophils ≥80 %. Two points were assigned for age <6 months and serum albumin <35 g/L. Using a cutoff point of three or more, we identified the IVIG non-responders with 71.4 % sensitivity and 76.0 % specificity. The new scoring system had a relatively better performance than Kobayashi and Egami scoring systems in the KD patients in East China. Clinical pediatricians must pay more attention to these high-risk patients, and use of additional therapies early in the course of their illness is necessary.


Children Intravenous immunoglobulin Kawasaki disease Resistance 



This work was financially supported by the Chinese Natural Science Foundation (No. 81370217, No. 81400222, and No. 81570455), the Jiangsu Province Science Foundation (No. BE2013632, No. BRA2015489, and No. BK20150291), and the Suzhou Science and Technology Bureau (No. SZS201411).

Compliance with ethical standards



Ethical standards

The study was approved by the Ethics Committee of Children’s Hospital of Soochow University and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All persons gave their informed consent prior to their inclusion in the study.


  1. 1.
    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 E, Kawasaki D, Council on Cardiovascular Disease in the Y, American Heart A, American Academy of P (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. Circulation 110(17):2747–2771. doi: 10.1161/01.CIR.0000145143.19711.78 CrossRefPubMedGoogle Scholar
  2. 2.
    Kuwabara M, Yashiro M, Kotani K, Tsuboi S, Ae R, Nakamura Y, Yanagawa H, Kawasaki T (2015) Cardiac lesions and initial laboratory data in Kawasaki disease: a nationwide survey in Japan. Journal of epidemiology/Japan Epidemiological Association 25(3):189–193. doi: 10.2188/jea.JE20140128 CrossRefGoogle Scholar
  3. 3.
    Ruan Y, Ye B, Zhao X (2013) Clinical characteristics of Kawasaki syndrome and the risk factors for coronary artery lesions in China. Pediatr Infect Dis J 32(10):e397–e402. doi: 10.1097/INF.0b013e31829dd45e CrossRefPubMedGoogle Scholar
  4. 4.
    Callinan LS, Tabnak F, Holman RC, Maddox RA, Kim JJ, Schonberger LB, Vugia DJ, Belay ED (2012) Kawasaki syndrome and factors associated with coronary artery abnormalities in California. Pediatr Infect Dis J 31(9):894–898. doi: 10.1097/INF.0b013e31825c4d7c CrossRefPubMedGoogle Scholar
  5. 5.
    Tacke CE, Breunis WB, Pereira RR, Breur JM, Kuipers IM, Kuijpers TW (2014) Five years of Kawasaki disease in the Netherlands: a national surveillance study. Pediatr Infect Dis J 33(8):793–797. doi: 10.1097/INF.0000000000000271 CrossRefPubMedGoogle Scholar
  6. 6.
    Saundankar J, Yim D, Itotoh B, Payne R, Maslin K, Jape G, Ramsay J, Kothari D, Cheng A, Burgner D (2014) The epidemiology and clinical features of Kawasaki disease in Australia. Pediatrics 133(4):e1009–e1014. doi: 10.1542/peds.2013-2936 CrossRefPubMedGoogle Scholar
  7. 7.
    Giannouli G, Tzoumaka-Bakoula C, Kopsidas I, Papadogeorgou P, Chrousos GP, Michos A (2013) Epidemiology and risk factors for coronary artery abnormalities in children with complete and incomplete Kawasaki disease during a 10-year period. Pediatr Cardiol 34(6):1476–1481. doi: 10.1007/s00246-013-0673-9 CrossRefPubMedGoogle Scholar
  8. 8.
    Hashino K, Ishii M, Iemura M, Akagi T, Kato H (2001) Re-treatment for immune globulin-resistant Kawasaki disease: a comparative study of additional immune globulin and steroid pulse therapy. Pediatrics international: official journal of the Japan Pediatric Society 43(3):211–217CrossRefGoogle Scholar
  9. 9.
    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(2):131–137. doi: 10.1007/s00431-006-0223-z CrossRefPubMedGoogle Scholar
  10. 10.
    Egami K, Muta H, Ishii M, Suda K, Sugahara Y, Iemura M, Matsuishi T (2006) Prediction of resistance to intravenous immunoglobulin treatment in patients with Kawasaki disease. J Pediatr 149(2):237–240. doi: 10.1016/j.jpeds.2006.03.050 CrossRefPubMedGoogle Scholar
  11. 11.
    Kobayashi T, Inoue Y, Takeuchi K, Okada Y, Tamura K, Tomomasa T, Kobayashi T, Morikawa A (2006) Prediction of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease. Circulation 113(22):2606–2612. doi: 10.1161/CIRCULATIONAHA.105.592865 CrossRefPubMedGoogle Scholar
  12. 12.
    Tremoulet AH, Best BM, Song S, Wang S, Corinaldesi E, Eichenfield JR, Martin DD, Newburger JW, Burns JC (2008) Resistance to intravenous immunoglobulin in children with Kawasaki disease. J Pediatr 153(1):117–121. doi: 10.1016/j.jpeds.2007.12.021 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Fu PP, Du ZD, Pan YS (2013) Novel predictors of intravenous immunoglobulin resistance in Chinese children with Kawasaki disease. Pediatr Infect Dis J 32(8):e319–e323. doi: 10.1097/INF.0b013e31828e887f PubMedGoogle Scholar
  14. 14.
    Akagi T, Rose V, Benson LN, Newman A, Freedom RM (1992) Outcome of coronary artery aneurysms after Kawasaki disease. J Pediatr 121(5 Pt 1):689–694CrossRefPubMedGoogle Scholar
  15. 15.
    Rigante D, Valentini P, Rizzo D, Leo A, De Rosa G, Onesimo R, De Nisco A, Angelone DF, Compagnone A, Delogu AB (2010) Responsiveness to intravenous immunoglobulins and occurrence of coronary artery abnormalities in a single-center cohort of Italian patients with Kawasaki syndrome. Rheumatol Int 30(6):841–846. doi: 10.1007/s00296-009-1337-1 CrossRefPubMedGoogle Scholar
  16. 16.
    Sato S, Kawashima H, Kashiwagi Y, Hoshika A (2013) Inflammatory cytokines as predictors of resistance to intravenous immunoglobulin therapy in Kawasaki disease patients. Int J Rheum Dis 16(2):168–172. doi: 10.1111/1756-185X.12082 CrossRefPubMedGoogle Scholar
  17. 17.
    Muta H, Ishii M, Furui J, Nakamura Y, Matsuishi T (2006) Risk factors associated with the need for additional intravenous gamma-globulin therapy for Kawasaki disease. Acta Paediatr 95(2):189–193. doi: 10.1080/08035250500327328 CrossRefPubMedGoogle Scholar
  18. 18.
    Kuo HC, Liang CD, Wang CL, Yu HR, Hwang KP, Yang KD (2010) Serum albumin level predicts initial intravenous immunoglobulin treatment failure in Kawasaki disease. Acta Paediatr 99(10):1578–1583. doi: 10.1111/j.1651-2227.2010.01875.x CrossRefPubMedGoogle Scholar
  19. 19.
    Terai M, Honda T, Yasukawa K, Higashi K, Hamada H, Kohno Y (2003) Prognostic impact of vascular leakage in acute Kawasaki disease. Circulation 108(3):325–330. doi: 10.1161/01.CIR.0000079166.93475.5F CrossRefPubMedGoogle Scholar
  20. 20.
    Burns JC, Capparelli EV, Brown JA, Newburger JW, Glode MP (1998) Intravenous gamma-globulin treatment and retreatment in Kawasaki disease. US/Canadian Kawasaki Syndrome Study Group. Pediatr Infect Dis J 17(12):1144–1148CrossRefPubMedGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2016

Authors and Affiliations

  • Yunjia Tang
    • 1
  • Wenhua Yan
    • 1
  • Ling Sun
    • 1
  • Jie Huang
    • 1
  • Weiguo Qian
    • 1
  • Yueyue Ding
    • 1
  • Haitao Lv
    • 1
    Email author
  1. 1.The Department of CardiologyChildren’s Hospital of Soochow UniversitySuzhouChina

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