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Published in: World Journal of Pediatrics 2/2019

01-04-2019 | Kawasaki Disease | Original Article

Biomarkers of intravenous immunoglobulin resistance and coronary artery lesions in Kawasaki disease

Authors: Wei-Xing Kong, Fei-Yue Ma, Song-Ling Fu, Wei Wang, Chun-Hong Xie, Yi-Ying Zhang, Fang-Qi Gong

Published in: World Journal of Pediatrics | Issue 2/2019

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Abstract

Background

Currently, there are no reliable indicators for predicting intravenous immunoglobulin resistance and coronary artery lesions in the early stage of Kawasaki disease.

Methods

A total of 300 patients with Kawasaki disease were studied retrospectively. Laboratory data were compared between the intravenous immunoglobulin resistant (29 patients) and responsive groups, and between the groups with coronary artery lesions (48 patients) and without coronary artery lesions.

Results

The intravenous immunoglobulin resistant group had significantly higher D-dimer, globulin, interleukin-6 and serum ferritin levels in comparison to the intravenous immunoglobulin responder group. D-dimer level had a sensitivity of 87.0% and a specificity of 56.3% for predicting intravenous immunoglobulin resistance at a cutoff point of 1.09 mg/L. Globulin had a sensitivity of 62.1% and a specificity of 82.3% for predicting intravenous immunoglobulin resistance at a cutoff point of 34.7 g/L. Serum ferritin level had a sensitivity of 42.9% and a specificity of 88.8% for predicting intravenous immunoglobulin resistance at a cutoff point of 269.7 ng/mL. The patients with coronary artery lesions had higher D-dimer and tumor necrosis factor-α level. D-dimer level had a sensitivity of 50% and a specificity of 78.6% for predicting coronary artery lesions at a cutoff point of 1.84 mg/L. Based on analysis by multivariate logistic regression, serum ferritin and globulin were independent risks for intravenous immunoglobulin resistance, D-dimer was independent risk for coronary artery lesions.

Conclusions

Elevated serum ferritin, globulin and D-dimer levels are significantly associated with intravenous immunoglobulin resistance in Kawasaki disease. Moreover, serum D-dimer is significantly increased in Kawasaki disease with coronary artery lesions.
Literature
1.
go back to reference McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association. Circulation. 2017;135:e927–99.CrossRefPubMed McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association. Circulation. 2017;135:e927–99.CrossRefPubMed
2.
go back to reference Egami K, Muta H, Ishii M, Suda K, Sugahara Y, Iemura M, et al. Prediction of resistance to intravenous immunoglobulin treatment in patients with Kawasaki disease. J Pediatr. 2006;149:237–40.CrossRefPubMed Egami K, Muta H, Ishii M, Suda K, Sugahara Y, Iemura M, et al. Prediction of resistance to intravenous immunoglobulin treatment in patients with Kawasaki disease. J Pediatr. 2006;149:237–40.CrossRefPubMed
3.
go back to reference Kobayashi T, Inoue Y, Takeuchi K, Okada Y, Tamura K, Tomomasa T, et al. Prediction of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease. Circulation. 2006;113:2606–12.CrossRef Kobayashi T, Inoue Y, Takeuchi K, Okada Y, Tamura K, Tomomasa T, et al. Prediction of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease. Circulation. 2006;113:2606–12.CrossRef
4.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
5.
go back to reference Beiser AS, Takahashi M, Baker AL, Sundel RP, Newburger JW. A predictive instrument for coronary artery aneurysms in Kawasaki disease. US Multicenter Kawasaki Disease Study Group. Am J Cardiol. 1998;81:1116–1120. Beiser AS, Takahashi M, Baker AL, Sundel RP, Newburger JW. A predictive instrument for coronary artery aneurysms in Kawasaki disease. US Multicenter Kawasaki Disease Study Group. Am J Cardiol. 1998;81:1116–1120.
6.
go back to reference Honkanen VE, McCrindle BW, Laxer RM, Feldman BM, Schneider R, Silverman ED. Clinical relevance of the risk factors for coronary artery inflammation in Kawasaki disease. Pediatr Cardiol. 2003;24:122–6.CrossRefPubMed Honkanen VE, McCrindle BW, Laxer RM, Feldman BM, Schneider R, Silverman ED. Clinical relevance of the risk factors for coronary artery inflammation in Kawasaki disease. Pediatr Cardiol. 2003;24:122–6.CrossRefPubMed
7.
go back to reference Sabharwal T, Manlhiot C, Benseler SM, Tyrrell PN, Chahal N, Yeung RS, et al. Comparison of factors associated with coronary artery dilation only versus coronary artery aneurysms in patients with Kawasaki disease. Am J Cardiol. 2009;104:1743–7.CrossRefPubMed Sabharwal T, Manlhiot C, Benseler SM, Tyrrell PN, Chahal N, Yeung RS, et al. Comparison of factors associated with coronary artery dilation only versus coronary artery aneurysms in patients with Kawasaki disease. Am J Cardiol. 2009;104:1743–7.CrossRefPubMed
8.
go back to reference Wang Y, Wang W, Gong F, Fu S, Zhang Q, Hu J, et al. Evaluation of intravenous immunoglobulin resistance and coronary artery lesions in relation to Th1/Th2 cytokine profiles in patients with Kawasaki disease. Arthritis Rheum. 2013;65:805–14.CrossRefPubMed Wang Y, Wang W, Gong F, Fu S, Zhang Q, Hu J, et al. Evaluation of intravenous immunoglobulin resistance and coronary artery lesions in relation to Th1/Th2 cytokine profiles in patients with Kawasaki disease. Arthritis Rheum. 2013;65:805–14.CrossRefPubMed
9.
go back to reference Takahara T, Shimizu M, Nakagishi Y, Kinjo N, Yachie A. Serum IL-18 as a potential specific marker for differentiating systemic juvenile idiopathic arthritis from incomplete Kawasaki disease. Rheumatol Int. 2015;35:81–4.CrossRefPubMed Takahara T, Shimizu M, Nakagishi Y, Kinjo N, Yachie A. Serum IL-18 as a potential specific marker for differentiating systemic juvenile idiopathic arthritis from incomplete Kawasaki disease. Rheumatol Int. 2015;35:81–4.CrossRefPubMed
10.
go back to reference Yamamoto N, Sato K, Hoshina T, Kojiro M, Kusuhara K. Utility of ferritin as a predictor of the patients with Kawasaki disease refractory to intravenous immunoglobulin therapy. Mod Rheumatol. 2015;25:898–902.CrossRefPubMed Yamamoto N, Sato K, Hoshina T, Kojiro M, Kusuhara K. Utility of ferritin as a predictor of the patients with Kawasaki disease refractory to intravenous immunoglobulin therapy. Mod Rheumatol. 2015;25:898–902.CrossRefPubMed
11.
12.
go back to reference Noto T, Seto H, Fukuhara J, Murabayashi M, Yachie A, Ayusawa M, et al. A case of incomplete Kawasaki disease with extremely high serum ferritin and interleukin-18 levels. BMC Pediatr. 2018;18:386.CrossRefPubMedPubMedCentral Noto T, Seto H, Fukuhara J, Murabayashi M, Yachie A, Ayusawa M, et al. A case of incomplete Kawasaki disease with extremely high serum ferritin and interleukin-18 levels. BMC Pediatr. 2018;18:386.CrossRefPubMedPubMedCentral
13.
go back to reference Mizuta M, Shimizu M, Inoue N, Kasai K, Nakagishi Y, Takahara T, et al. Serum ferritin levels as a useful diagnostic marker for the distinction of systemic juvenile idiopathic arthritis and Kawasaki disease. Mod Rheumatol. 2016;26:929–32.CrossRefPubMed Mizuta M, Shimizu M, Inoue N, Kasai K, Nakagishi Y, Takahara T, et al. Serum ferritin levels as a useful diagnostic marker for the distinction of systemic juvenile idiopathic arthritis and Kawasaki disease. Mod Rheumatol. 2016;26:929–32.CrossRefPubMed
14.
go back to reference Soomro AY, Guerchicoff A, Nichols DJ, Suleman J, Dangas GD. The current role and future prospects of D-dimer biomarker. Eur Heart J Cardiovasc Pharmacother. 2016;2:175–84.CrossRefPubMed Soomro AY, Guerchicoff A, Nichols DJ, Suleman J, Dangas GD. The current role and future prospects of D-dimer biomarker. Eur Heart J Cardiovasc Pharmacother. 2016;2:175–84.CrossRefPubMed
15.
go back to reference Imamura T, Yoshihara T, Yokoi K, Nakai N, Ishida H, Kasubuchi Y. Impact of increased D-dimer concentrations in Kawasaki disease. Eur J Pediatr. 2005;164:526–7.CrossRefPubMed Imamura T, Yoshihara T, Yokoi K, Nakai N, Ishida H, Kasubuchi Y. Impact of increased D-dimer concentrations in Kawasaki disease. Eur J Pediatr. 2005;164:526–7.CrossRefPubMed
16.
go back to reference Masuzawa Y, Mori M, Hara T, Inaba A, Oba MS, Yokota S. Elevated D-dimer level is a risk factor for coronary artery lesions accompanying intravenous immunoglobulin-unresponsive Kawasaki disease. Ther Apher Dial. 2015;19:171–7.CrossRefPubMed Masuzawa Y, Mori M, Hara T, Inaba A, Oba MS, Yokota S. Elevated D-dimer level is a risk factor for coronary artery lesions accompanying intravenous immunoglobulin-unresponsive Kawasaki disease. Ther Apher Dial. 2015;19:171–7.CrossRefPubMed
17.
go back to reference Zhou Y, Wang S, Zhao J, Fang P. Correlations of complication with coronary arterial lesion with VEGF, PLT, D-dimer and inflammatory factor in child patients with Kawasaki disease. Eur Rev Med Pharmacol Sci. 2018;22:5121–6.PubMed Zhou Y, Wang S, Zhao J, Fang P. Correlations of complication with coronary arterial lesion with VEGF, PLT, D-dimer and inflammatory factor in child patients with Kawasaki disease. Eur Rev Med Pharmacol Sci. 2018;22:5121–6.PubMed
18.
go back to reference Righini M, Perrier A, De Moerloose P, Bounameaux H. D-dimer for venous thromboembolism diagnosis: 20 years later. J Thromb Haemost. 2008;6:1059–71.CrossRefPubMed Righini M, Perrier A, De Moerloose P, Bounameaux H. D-dimer for venous thromboembolism diagnosis: 20 years later. J Thromb Haemost. 2008;6:1059–71.CrossRefPubMed
Metadata
Title
Biomarkers of intravenous immunoglobulin resistance and coronary artery lesions in Kawasaki disease
Authors
Wei-Xing Kong
Fei-Yue Ma
Song-Ling Fu
Wei Wang
Chun-Hong Xie
Yi-Ying Zhang
Fang-Qi Gong
Publication date
01-04-2019
Publisher
Childrens Hospital, Zhejiang University School of Medicine
Published in
World Journal of Pediatrics / Issue 2/2019
Print ISSN: 1708-8569
Electronic ISSN: 1867-0687
DOI
https://doi.org/10.1007/s12519-019-00234-6

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