Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
권호 표지
DOI QR코드

DOI QR Code

Prediction of unresponsiveness to second intravenous immunoglobulin treatment in patients with Kawasaki disease refractory to initial treatment

  • Seo, Euri (Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Yu, Jeong Jin (Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Jun, Hyun Ok (Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Shin, Eun Jung (Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Baek, Jae Suk (Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Kim, Young-Hwue (Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Ko, Jae-Kon (Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine)
  • Received : 2016.05.26
  • Accepted : 2016.08.29
  • Published : 2016.10.15
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: This study investigated predictors of unresponsiveness to second-line intravenous immunoglobulin (IVIG) treatment for Kawasaki disease (KD). Methods: This was a single-center analysis of the medical records of 588 patients with KD who had been admitted to Asan Medical Center between 2006 and 2014. Related clinical and laboratory data were analyzed by univariate and multivariate logistic regression analyses. Results: Eighty (13.6%) of the 588 patients with KD were unresponsive to the initial IVIG treatment and received a second dose. For these 80 patients, univariate analysis of the laboratory results obtained before administering the second-line IVIG treatment showed that white blood cell count, neutrophil percent, hemoglobin level, platelet count, serum protein level, albumin level, potassium level, and C-reactive protein level were significant predictors. The addition of methyl prednisolone to the second-line regimen was not associated with treatment response (odds ratio [OR], 0.871; 95% confidence interval [CI], 0.216-3.512; P=0.846). Multivariate analysis revealed serum protein level to be the only predictor of unresponsiveness to the second-line treatment (OR, 0.160; 95% CI, 0.028-0.911; P=0.039). Receiver operating characteristic curve analysis to determine predictors of unresponsiveness to the second dose of IVIG showed a sensitivity of 100% and specificity of 72% at a serum protein cutoff level of <7.15 g/dL. Conclusion: The serum protein level of the patient prior to the second dose of IVIG is a significant predictor of unresponsiveness. The addition of methyl prednisolone to the second-line regimen produces no treatment benefit.

Keywords

References

  1. Newburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY, Burns JC, et al. 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 2004;114:1708-33. https://doi.org/10.1542/peds.2004-2182
  2. Tremoulet AH, Best BM, Song S, Wang S, Corinaldesi E, Eichenfield JR, et al. Resistance to intravenous immunoglobulin in children with Kawasaki disease. J Pediatr 2008;153:117-21. https://doi.org/10.1016/j.jpeds.2007.12.021
  3. Burns JC, Capparelli EV, Brown JA, Newburger JW, Glode MP. Intravenous gamma-globulin treatment and retreatment in Kawasaki disease. US/Canadian Kawasaki Syndrome Study Group. Pediatr Infect Dis J 1998;17:1144-8. https://doi.org/10.1097/00006454-199812000-00009
  4. Sittiwangkul R, Pongprot Y, Silvilairat S, Phornphutkul C. Management and outcome of intravenous gammaglobulin-resistant Kawasaki disease. Singapore Med J 2006;47:780-4.
  5. Wei M, Huang M, Chen S, Huang G, Huang M, Qiu D, et al. A multicenter study of intravenous immunoglobulin non-response in Kawasaki disease. Pediatr Cardiol 2015;36:1166-72. https://doi.org/10.1007/s00246-015-1138-0
  6. Uehara R, Belay ED, Maddox RA, Holman RC, Nakamura Y, Yashiro M, et al. Analysis of potential risk factors associated with nonresponse to initial intravenous immunoglobulin treatment among Kawasaki disease patients in Japan. Pediatr Infect Dis J 2008;27:155-60.
  7. Koren G, Lavi S, Rose V, Rowe R. Kawasaki disease: review of risk factors for coronary aneurysms. J Pediatr 1986;108:388-92. https://doi.org/10.1016/S0022-3476(86)80878-2
  8. Ichida F, Fatica NS, Engle MA, O'Loughlin JE, Klein AA, Snyder MS, et al. Coronary artery involvement in Kawasaki syndrome in Manhattan, New York: risk factors and role of aspirin. Pediatrics 1987;80:828-35.
  9. Daniels SR, Specker B, Capannari TE, Schwartz DC, Burke MJ, Kaplan S. Correlates of coronary artery aneurysm formation in patients with Kawasaki disease. Am J Dis Child 1987;141:205-7.
  10. Ghelani SJ, Pastor W, Parikh K. Demographic and treatment variability of refractory kawasaki disease: a multicenter analysis from 2005 to 2009. Hosp Pediatr 2012;2:71-6. https://doi.org/10.1542/hpeds.2011-00112
  11. Uehara R, Yashiro M, Oki I, Nakamura Y, Yanagawa H. Re-treatment regimens for acute stage of Kawasaki disease patients who failed to respond to initial intravenous immunoglobulin therapy: analysis from the 17th nationwide survey. Pediatr Int 2007; 49:427-30. https://doi.org/10.1111/j.1442-200X.2007.02389.x
  12. Hashino K, Ishii M, Iemura M, Akagi T, Kato H. Re-treatment for immune globulin-resistant Kawasaki disease: a comparative study of additional immune globulin and steroid pulse therapy. Pediatr Int 2001;43:211-7. https://doi.org/10.1046/j.1442-200x.2001.01373.x
  13. Wallace CA, French JW, Kahn SJ, Sherry DD. Initial intravenous gammaglobulin treatment failure in Kawasaki disease. Pediatrics 2000;105:E78. https://doi.org/10.1542/peds.105.6.e78
  14. Miura M, Tamame T, Naganuma T, Chinen S, Matsuoka M, Ohki H. Steroid pulse therapy for Kawasaki disease unresponsive to additional immunoglobulin therapy. Paediatr Child Health 2011;16: 479-84. https://doi.org/10.1093/pch/16.8.479
  15. Furukawa T, Kishiro M, Akimoto K, Nagata S, Shimizu T, Yamashiro Y. Effects of steroid pulse therapy on immunoglobulin-resistant Kawasaki disease. Arch Dis Child 2008;93:142-6. https://doi.org/10.1136/adc.2007.126144
  16. Teraguchi M, Ogino H, Yoshimura K, Taniuchi S, Kino M, Okazaki H, et al. Steroid pulse therapy for children with intravenous immunoglobulin therapy-resistant Kawasaki disease: a prospective study. Pediatr Cardiol 2013;34:959-63. https://doi.org/10.1007/s00246-012-0589-9
  17. Suzuki H, Terai M, Hamada H, Honda T, Suenaga T, Takeuchi T, et al. Cyclosporin A treatment for Kawasaki disease refractory to initial and additional intravenous immunoglobulin. Pediatr Infect Dis J 2011;30:871-6. https://doi.org/10.1097/INF.0b013e318220c3cf
  18. Mori M, Imagawa T, Yasui K, Kanaya A, Yokota S. Predictors of coronary artery lesions after intravenous gamma-globulin treatment in Kawasaki disease. J Pediatr 2000;137:177-80. https://doi.org/10.1067/mpd.2000.107890
  19. Dallaire F, Dahdah N. New equations and a critical appraisal of coronary artery Z scores in healthy children. J Am Soc Echocardiogr 2011;24:60-74. https://doi.org/10.1016/j.echo.2010.10.004
  20. Kim HK, Oh J, Hong YM, Sohn S. Parameters to guide retreatment after initial intravenous immunoglobulin therapy in kawasaki disease. Korean Circ J 2011;41:379-84. https://doi.org/10.4070/kcj.2011.41.7.379
  21. Lee SM, Lee JB, Go YB, Song HY, Lee BJ, Kwak JH. Prediction of resistance to standard intravenous immunoglobulin therapy in kawasaki disease. Korean Circ J 2014;44:415-22. https://doi.org/10.4070/kcj.2014.44.6.415
  22. Hwang JY, Lee KY, Rhim JW, Youn YS, Oh JH, Han JW, et al. Assessment of intravenous immunoglobulin non-responders in Kawasaki disease. Arch Dis Child 2011;96:1088-90. https://doi.org/10.1136/adc.2010.184101
  23. Research Committee of the Japanese Society of Pediatric Cardiology; Cardiac Surgery Committee for Development of Guidelines for Medical Treatment of Acute Kawasaki Disease. Guidelines for medical treatment of acute Kawasaki disease: report of the Research Committee of the Japanese Society of Pediatric Cardiology and Cardiac Surgery (2012 revised version). Pediatr Int 2014;56:135-58. https://doi.org/10.1111/ped.12317
  24. Ogata S, Bando Y, Kimura S, Ando H, Nakahata Y, Ogihara Y, et al. The strategy of immune globulin resistant Kawasaki disease: a comparative study of additional immune globulin and steroid pulse therapy. J Cardiol 2009;53:15-9. https://doi.org/10.1016/j.jjcc.2008.08.002
  25. Miura M, Ohki H, Yoshiba S, Ueda H, Sugaya A, Satoh M, et al. Adverse effects of methylprednisolone pulse therapy in refractory Kawasaki disease. Arch Dis Child 2005;90:1096-7. https://doi.org/10.1136/adc.2004.062299
  26. Yu JJ. Use of corticosteroids during acute phase of Kawasaki disease. World J Clin Pediatr 2015;4:135-42. https://doi.org/10.5409/wjcp.v4.i4.135

Cited by

  1. Clinical implications in laboratory parameter values in acute Kawasaki disease for early diagnosis and proper treatment vol.61, pp.5, 2016, https://doi.org/10.3345/kjp.2018.61.5.160
  2. A new model for predicting intravenous immunoglobin-resistant Kawasaki disease in Chongqing: a retrospective study on 5277 patients vol.9, pp.None, 2016, https://doi.org/10.1038/s41598-019-39330-y
  3. A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease vol.17, pp.1, 2019, https://doi.org/10.1186/s12969-019-0337-2
  4. Shock and unresponsiveness to repeated courses of intravenous immunoglobulin in Kawasaki disease: a nationwide database study vol.87, pp.5, 2020, https://doi.org/10.1038/s41390-019-0668-1
  5. A Retrospective Cohort Study of Intravenous Immunoglobulin Therapy in the Acute Phase of Kawasaki Disease: The Earlier, the Better? vol.2021, pp.None, 2021, https://doi.org/10.1155/2021/6660407
  6. Kawasaki Disease: A Systematic Review and Meta‐Analysis of Benefits and Harms of Common Treatments vol.3, pp.10, 2021, https://doi.org/10.1002/acr2.11308
  7. Prediction of repeated intravenous immunoglobulin resistance in children with Kawasaki disease vol.21, pp.1, 2021, https://doi.org/10.1186/s12887-021-02876-w