Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Pediatric Rheumatology
Published in: Pediatric Rheumatology 1/2019

Open Access 01-12-2019 | Kawasaki Disease | Research article

Predictive value of serum procalcitonin for both initial and repeated immunoglobulin resistance in Kawasaki disease: a prospective cohort study

Authors: Shuran Shao, Chunyan Luo, Kaiyu Zhou, Yimin Hua, Mei Wu, Lei Liu, Xiaoliang Liu, Chuan Wang

Published in: Pediatric Rheumatology | Issue 1/2019

Login to get access

Abstract

Background

Intravenous immunoglobulin (IVIG) resistance prediction is one pivotal topic of interests in Kawasaki disease (KD) since those patients with KD resistant to IVIG might improve of an early-intensified therapy. Data regarding predictive value of procalcitonin (PCT) for IVIG resistance, particularly for repeated IVIG resistance in KD was limited. This study aimed to testify the predictive validity of PCT for both initial and repeated IVIG resistance in KD.

Methods

A total of 530 KD patients were prospectively recruited between January 2015 and March 2019. The clinical and laboratory data were compared between IVIG-responsive and IVIG-resistant groups. Multivariate logistic regression analysis was applied to determine the association between PCT and IVIG resistance. Receiver operating characteristic (ROC) curves analysis was further performed to assess the validity of PCT in predicting both initial and repeated IVIG resistance.

Results

The serum PCT level was significantly higher in initial IVIG-resistance group compared with IVIG-response group (p = 0.009), as well as between repeated IVIG responders and nonresponders (p = 0.017). The best PCT cutoff value for initial and repeated IVIG resistance prediction was 1.48 ng/ml and 2.88 ng/ml, respectively. The corresponding sensitivity was 53.9 and 51.4%, while the specificity were 71.8 and 73.2%, respectively. Multivariate logistic regression analysis failed to identify serum PCT level as an independent predictive factor for both initial and repeated IVIG resistance in KD.

Conclusions

Serum PCT levels were significantly higher in IVIG nonresponders, but PCT may not be suitable as a single marker to accurately predict both initial and repeated IVIG resistance in KD.
Literature
1.
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(17):e927.PubMedCrossRef
2.
Durongpisitkul K, Soongswang J, Laohaprasitiporn D, Nana A, Prachuabmoh C, Kangkagate C. Immunoglobulin failure and retreatment in Kawasaki disease. Pediatr Cardiol. 2003;24(2):145–8.PubMedCrossRef
3.
Wallace CA, French JW, Kahn SJ, Sherry DD. Initial intravenous gammaglobulin treatment failure in Kawasaki disease. Pediatrics. 2000;105(6):E78.PubMedCrossRef
4.
Sundel RP, Burns JC, Baker A, ., Beiser AS, Newburger JW. Gamma globulin re-treatment in Kawasaki disease. J Pediatr 1993;123(4):657–659.PubMedCrossRef
5.
Kobayashi T, Kobayashi T, Morikawa A, Ikeda K, Seki M, Shimoyama S, et al. Efficacy of Intravenous Immunoglobulin Combined with Prednisolone Following Resistance to Initial Intravenous Immunoglobulin Treatment of Acute Kawasaki Disease. J Pediatr. 2013;163(2):521–6.e1.PubMedCrossRef
6.
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(12):1144–8.PubMedCrossRef
7.
Son MBF, Kimberlee G, Lin M, Baker AL, Sundel RP, Fulton DR, et al. Treatment of Kawasaki disease: analysis of 27 US pediatric hospitals from 2001 to 2006. Pediatrics. 2009;124(1):1–8.PubMedCrossRef
8.
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(1):15–9.CrossRefPubMed
9.
Masayuki T, Hirotaro O, Ken Y, Shoichiro T, Minoru K, Hitoshi O, et al. Steroid pulse therapy for children with intravenous immunoglobulin therapy-resistant Kawasaki disease: a prospective study. Pediatr Cardiol. 2013;34(4):959–63.CrossRef
10.
Tremoulet AH, Sonia J, Preeti J, Susan JF, Pancheri JM, Xiaoying S, et al. Infliximab for intensification of primary therapy for Kawasaki disease: a phase 3 randomised, double-blind, placebo-controlled trial. Lancet. 2014;383(9930):1731–8.PubMedCrossRef
11.
Mary Beth S, Kimberlee G, Burns JC, Elena C, Tremoulet AH, Watson VE, et al. Infliximab for intravenous immunoglobulin resistance in Kawasaki disease: a retrospective study. J Pediatr. 2011;158(4):644–9.e1.CrossRef
12.
Tatsunori H, Masaaki M, Takashi N, Tomoko N, Tomoyuki I, Mari I, et al. Long-term efficacy of plasma exchange treatment for refractory Kawasaki disease. Pediatr Int. 2012;54(1):99–103.CrossRef
13.
Kaori S, Masaaki M, Tatsunori H, Shumpei Y. Infliximab plus plasma exchange rescue therapy in Kawasaki disease. J Pediatr. 2014;164(5):1128–32.e1.CrossRef
14.
Tremoulet AH, Paige P, Alessandra F, Matthew B, Chisato S, Yoshihiro O, et al. Calcineurin inhibitor treatment of intravenous immunoglobulin-resistant Kawasaki disease. J Pediatr. 2012;161(3):506–12.e1.PubMedPubMedCentralCrossRef
15.
Hiroyuki S, Masaru T, Hiromichi H, Takafumi H, Tomohiro S, Takashi T, et al. Cyclosporin a treatment for Kawasaki disease refractory to initial and additional intravenous immunoglobulin. Pediatr Infect Dis J. 2011;30(10):871.CrossRef
16.
Tohru K, Yoshinari I, Kazuo T, Yasunori O, Kazushi T, Takeshi T, et al. Prediction of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease. Circulation. 2006;113(22):2606–12.CrossRef
17.
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(2):237–40.PubMedCrossRef
18.
Sano T, Kurotobi S, Matsuzaki K, Yamamoto T, Maki I, Miki K, et al. Prediction of non-responsiveness to standard high-dose gamma-globulin therapy in patients with acute Kawasaki disease before starting initial treatment. Eur J Pediatr. 2007;166(2):131–7.PubMedCrossRef
19.
Pei-Pei F, Zhong-Dong D, Yue-Song P. Novel predictors of intravenous immunoglobulin resistance in Chinese children with Kawasaki disease. Pediatr Infect Dis J. 2013;32(8):1.
20.
Tang Y, Yan W, Sun L, Huang J, Qian W, Ding Y, et al. Prediction of intravenous immunoglobulin resistance in Kawasaki disease in an East China population. Clin Rheumatol. 2016;35(11):2771–6.PubMedCrossRef
21.
Wang H, Sun Y, Ying W, Fu S, Wei W, Xie C, et al. A new model to predict intravenous immunoglobin-resistant Kawasaki disease. Oncotarget. 2017;8(46):80722–9.PubMedPubMedCentral
22.
Shuai Y, Song R, Zhang J, Li X, Li C. Predictive tool for intravenous immunoglobulin resistance of Kawasaki disease in Beijing. Arch Dis Child. 2019;104(3):262–7.
23.
Rossum AMC. Van, Wulkan RW, Oudesluys-murphy AM. Procalcitonin as an early marker of infection in neonates and children. Lancet Infect Dis. 2004;4(10):620–30.PubMedCrossRef
24.
25.
Okada Y, Minakami H, Tomomasa T, Kato M, Inoue Y, Kozawa K, et al. Serum procalcitonin concentration in patients with Kawasaki disease. J Infect. 2004;48(2):199–205.PubMedCrossRef
26.
Dominguez SR, Martin B, Heizer H, Jone PN, Tong S, Davidson J, et al. Procalcitonin (PCT) and Kawasaki Disease: Does PCT Correlate With IVIG-Resistant Disease, Admission to the Intensive Care Unit, or Development of Coronary Artery Lesions? J Pediatric Infect Dis Soc. 2016;5(3):297–302.PubMedCrossRef
27.
Yoshikawa H, Nomura Y, Masuda K, Koriya C, Arata M, Hazeki D, et al. Serum procalcitonin value is useful for predicting severity of Kawasaki disease. Pediatr Infect Dis J. 2012;31(5):523.CrossRefPubMed
28.
Lee NH, Choi HJ, Kim YH. Clinical usefulness of serum procalcitonin level in distinguishing between Kawasaki disease and other infections in febrile children. Korean J Pediatr. 2017;60(4):112.PubMedPubMedCentralCrossRef
29.
Dallaire F, Dahdah N. New equations and a critical appraisal of coronary artery scores in healthy children. J Am Soc Echocardiogr. 2011;24(1):60–74.PubMedCrossRef
30.
Saji T, Arakaki Y, Fuse S, Hamaoka K, Kato H, Kobayashi T, et al. A new Z -score curve of the coronary arterial internal diameter using the lambda-mu-sigma method inaPediatric population. J Am Soc Echocardiogr. 2016;29(8):S0894731716300013.
31.
Leung DY, Geha RS, Newburger JW, Burns JC, Fiers W, ., Lapierre LA, et al. Two monokines, interleukin 1 and tumor necrosis factor, render cultured vascular endothelial cells susceptible to lysis by antibodies circulating during Kawasaki syndrome. Jexpmed 1986;164(6):1958–1972.CrossRef
32.
Ueno Y, ., Takano N, ., Kanegane H, ., Yokoi T, ., Yachie A, ., Miyawaki T, ., et al. The acute phase nature of interleukin 6: studies in Kawasaki disease and other febrile illnesses. Clinexpimmunol 1989;76(3):337–342.
33.
Oberhoffer M, Stonans I, Russwurm S, Stonane E, Vogelsang H, Junker U, et al. Procalcitonin expression in human peripheral blood mononuclear cells and its modulation by lipopolysaccharides and sepsis-related cytokines in vitro ☆ ☆☆ ★ ★★. J Lab Clin Med. 1999;134(1):49–55.PubMedCrossRef
34.
Suzuki H, ., Uemura S, ., Tone S, ., Iizuka T, ., Koike M, ., Hirayama K, ., et al. Effects of immunoglobulin and gamma-interferon on the production of tumour necrosis factor-alpha and interleukin-1 beta by peripheral blood monocytes in the acute phase of Kawasaki disease. Eur J Pediatr 1996;155(4):291–296.PubMedCrossRef
35.
Yuan YD, Sun J, Peng-Fei LI, Wei CL, Yan-Hui YU, Pediatrics DO. Values of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in predicting sensitivity to intravenous immunoglobulin in Kawasaki disease. Chin J Contemp Pediatr. 2017;19(4):410–3.
36.
Akboga YE, Bektas H, Anlar O. Usefulness of platelet to lymphocyte and neutrophil to lymphocyte ratios in predicting the presence of cerebral venous sinus thrombosis and in-hospital major adverse cerebral events. J Neurol Sci. 2017;380:226–9.PubMedCrossRef
37.
Sleeper LA, Minich LA, Mccrindle BM, Li JS, Mason W, Colan SD, et al. Evaluation of Kawasaki Disease Risk-Scoring Systems for Intravenous Immunoglobulin Resistance. J Pediatr. 2011;158(5):831–5.e3.PubMedCrossRef
38.
Negar A, Masato T, Frederick D, Wilbert M. Risk factors for nonresponse to therapy in Kawasaki disease. J Pediatr. 2008;153(3):365–8.CrossRef
39.
Okada K, Hara J, Maki I, Miki K, Matsuzaki K, Matsuoka T, et al. Pulse methylprednisolone with gammaglobulin as an initial treatment for acute Kawasaki disease. Eur J Pediatr. 2009;168(2):181–5.PubMedCrossRef
40.
Otani T. Efficacy of immunoglobulin plus prednisolone for prevention of coronary artery abnormalities in severe Kawasaki disease (RAISE study): a randomised, open-label, blinded-endpoints trial. Lancet. 2012;379(9826):1613.PubMedCrossRef
41.
Hamada H, Suzuki H, Onouchi Y, Ebata R, Terai M, Fuse S, et al. Efficacy of primary treatment with immunoglobulin plus ciclosporin for prevention of coronary artery abnormalities in patients with Kawasaki disease predicted to be at increased risk of non-response to intravenous immunoglobulin (KAICA): a randomised controlled, open-label, blinded-endpoints, phase 3 trial. Lancet. 2019;393(10176):1128–37.PubMedCrossRef
42.
Kimiyasu E, Hiromi M, Masahiro I, Kenji S, Yoko S, Motofumi I, et al. Prediction of resistance to intravenous immunoglobulin treatment in patients with Kawasaki disease. J Pediatr. 2006;149(2):237–40.CrossRef
43.
Uehara R. 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(2):155.PubMed
44.
Charlotte CP, Marie-Claude A, Martin C, Sylvie G, Dominique G. Lack of value of procalcitonin for prediction of coronary aneurysms in Kawasaki disease. Pediatr Infect Dis J. 2007;26(2):179–80.CrossRef
Metadata
Title
Predictive value of serum procalcitonin for both initial and repeated immunoglobulin resistance in Kawasaki disease: a prospective cohort study
Authors
Shuran Shao
Chunyan Luo
Kaiyu Zhou
Yimin Hua
Mei Wu
Lei Liu
Xiaoliang Liu
Chuan Wang
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Pediatric Rheumatology / Issue 1/2019
Electronic ISSN: 1546-0096
DOI
https://doi.org/10.1186/s12969-019-0379-5

Other articles of this Issue 1/2019

Pediatric Rheumatology 1/2019 Go to the issue

Research article

Infrared thermography in children: a reliable tool for differential diagnosis of peripheral microvascular dysfunction and Raynaud’s phenomenon?

Research article

Orofacial pain in juvenile idiopathic arthritis is associated with stress as well as psychosocial and functional limitations

Research article

Plasma exosomes from children with juvenile dermatomyositis are taken up by human aortic endothelial cells and are associated with altered gene expression in those cells

Research article

Clinical features and characteristics of uveitis associated with juvenile idiopathic arthritis in Japan: first report of the pediatric rheumatology association of Japan (PRAJ)

Case Report

Complexity in unclassified auto-inflammatory disease: a case report illustrating the potential for disease arising from the allelic burden of multiple variants

Research article

Patient and caregiver engagement in research: factors that influence co-enrollment in research