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Wang X, Shi X, Guo X, Chen S, Lin X, Yang F. Effectiveness of Initial Corticosteroid Treatment in Kawasaki Disease Children Suspected to be IVIG Resistant. Pediatr Cardiol 2024:10.1007/s00246-024-03657-9. [PMID: 39316082 DOI: 10.1007/s00246-024-03657-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Accepted: 09/17/2024] [Indexed: 09/25/2024]
Abstract
This retrospective study assessed the efficacy of initial treatment with intravenous immunoglobulin (IVIG), aspirin, and corticosteroids in Kawasaki disease (KD) patients at risk for IVIG resistance. Data from pediatric patients with KD between January 2010 and December 2019 were divided into the IVIG-sensitive and IVIG-resistant groups based on treatment response. Risk factors for IVIG resistance were identified through univariate analysis. Outcomes included comparison of fever resolution time, hospital stay, and coronary artery lesion (CALs) incidence at multiple intervals post-treatment. An observational group (January 2020 to December 2022) was given additional methylprednisolone if they exhibited three or more IVIG resistance risk factors. The IVIG-resistant group had a higher proportion of males and significantly elevated inflammatory markers (CRP, ESR, PCT) and TBIL, NT-proBNP compared to the IVIG-sensitive group (all p < 0.05), while showing lower levels of albumin, ARR (AST/ALT ratio), and serum sodium (all p < 0.05). Both the IVIG-sensitive and observational groups had significantly shorter fever resolution times and hospital stays than the IVIG-resistant group (all p < 0.05). CALs incidence was consistently higher in the IVIG-resistant group across all follow-up periods (all p < 0.05), with significant differences observed between the observational group and IVIG-resistant group at 1-month, 3-month, and 6-month post-treatment (all p < 0.05). Notably, prior to treatment, the observational group had a higher CALs incidence compared to the IVIG-sensitive group (all p < 0.05). In children with KD who exhibit ≥ 3 risk factors for IVIG non-response, initial treatment with IVIG, aspirin, and glucocorticoids can effectively reduce fever duration, hospitalization duration, and incidence of CALs and is considered safe.
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Affiliation(s)
- Xiaoli Wang
- Department of Pediatrics, Provincial Clinical Medical College of Fujian Medical University, Fujian, Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Hospital, Dongjie 134, Gulou District, Fuzhou, People's Republic of China, 350001
| | - Xiaosong Shi
- Department of Pediatrics, Provincial Clinical Medical College of Fujian Medical University, Fujian, Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Hospital, Dongjie 134, Gulou District, Fuzhou, People's Republic of China, 350001
| | - Xinxin Guo
- Department of Pediatrics, Provincial Clinical Medical College of Fujian Medical University, Fujian, Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Hospital, Dongjie 134, Gulou District, Fuzhou, People's Republic of China, 350001
| | - Shengwei Chen
- Department of Pediatrics, Provincial Clinical Medical College of Fujian Medical University, Fujian, Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Hospital, Dongjie 134, Gulou District, Fuzhou, People's Republic of China, 350001
| | - Xinyu Lin
- Department of Pediatrics, Provincial Clinical Medical College of Fujian Medical University, Fujian, Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Hospital, Dongjie 134, Gulou District, Fuzhou, People's Republic of China, 350001
| | - Fang Yang
- Department of Pediatrics, Provincial Clinical Medical College of Fujian Medical University, Fujian, Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Hospital, Dongjie 134, Gulou District, Fuzhou, People's Republic of China, 350001.
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Wang Y, Cao Y, Li Y, Zhu F, Yuan M, Xu J, Ma X, Li J. Development of an immunoinflammatory indicator-related dynamic nomogram based on machine learning for the prediction of intravenous immunoglobulin-resistant Kawasaki disease patients. Int Immunopharmacol 2024; 134:112194. [PMID: 38703570 DOI: 10.1016/j.intimp.2024.112194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 04/26/2024] [Accepted: 04/30/2024] [Indexed: 05/06/2024]
Abstract
BACKGROUND Approximately 10-20% of Kawasaki disease (KD) patients suffer from intravenous immunoglobulin (IVIG) resistance, placing them at higher risk of developing coronary artery aneurysms. Therefore, we aimed to construct an IVIG resistance prediction tool for children with KD in Shanghai, China. METHODS Retrospective analysis was conducted on data from 1271 patients diagnosed with KD and the patients were randomly divided into a training set and a validation set in a 2:1 ratio. Machine learning algorithms were employed to identify important predictors associated with IVIG resistance and to build a predictive model. The best-performing model was used to construct a dynamic nomogram. Moreover, receiver operating characteristic curves, calibration plots, and decision-curve analysis were utilized to measure the discriminatory power, accuracy, and clinical utility of the nomogram. RESULTS Six variables were identified as important predictors, including C-reactive protein, neutrophil ratio, procalcitonin, CD3 ratio, CD19 count, and IgM level. A dynamic nomogram constructed with these factors was available at https://hktk.shinyapps.io/dynnomapp/. The nomogram demonstrated good diagnostic performance in the training and validation sets (area under the receiver operating characteristic curve = 0.816 and 0.800, respectively). Moreover, the calibration curves and decision curves analysis indicated that the nomogram showed good consistency between predicted and actual outcomes and had good clinical benefits. CONCLUSION A web-based dynamic nomogram for IVIG resistance was constructed with good predictive performance, which can be used as a practical approach for early screening to assist physicians in personalizing the treatment of KD patients in Shanghai.
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Affiliation(s)
- Yue Wang
- Clinical Laboratory Center, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai 201102, China.
| | - Yinyin Cao
- Cardiovascular Center, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai 201102, China.
| | - Yang Li
- Clinical Laboratory Center, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai 201102, China.
| | - Fenhua Zhu
- Clinical Laboratory Center, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai 201102, China.
| | - Meifen Yuan
- Clinical Laboratory Center, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai 201102, China.
| | - Jin Xu
- Clinical Laboratory Center, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai 201102, China.
| | - Xiaojing Ma
- Cardiovascular Center, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai 201102, China.
| | - Jian Li
- Clinical Laboratory Center, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai 201102, China.
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Huang XB, Zhao S, Liu ZY, Xu YY, Deng F. Serum amyloid A as a biomarker for immunoglobulin resistance in Kawasaki disease. Ann Med 2023; 55:2264315. [PMID: 37870383 PMCID: PMC10836278 DOI: 10.1080/07853890.2023.2264315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 09/21/2023] [Indexed: 10/24/2023] Open
Abstract
BACKGROUND Intravenous immunoglobulin (IVIG) resistance is of prime importance in Kawasaki disease (KD). In this study, we examined the value and mechanism of serum amyloid A (SAA) level in predicting IVIG resistance in patients with KD. METHODS SAA levels were measured in 497 consecutive patients with KD before IVIG therapy in the training set. The patients were divided into two groups (IVIG-responsive and IVIG-resistant) according to the American Heart Association (AHA) definition of IVIG resistance. Demographic, echocardiographic, and laboratory data were also retrospectively analyzed and tabulated to predict IVIG resistance. The predictive value of SAA was validated on test sets of prospective data. Cytokine microarrays were analyzed from 4 patients with resistant to IVIG, 4 patients with responsive to IVIG and 4 healthy volunteers. RESULTS During the training set, 409 patients with KD were enrolled, of whom 43 (10.5%) were resistant to initial IVIG treatment and 47 (11.49%) had coronary artery lesions (CALs). Serum levels of SAA were higher in the IVIG resistant group compared to the IVIG responsive group, (380.00 [204.40-547.25] vs 230.85 [105.40-490.00] mg/L; p = .008). The values of total bilirubin, C-reactive protein, neutrophils, alanine aminotransferase, aspartate aminotransferase, interleukin-6(IL-6), and procalcitonin were significantly higher in the IVIG-resistant group than in the IVIG-responsive group (p < .05); however, the lymphocytes, platelets, serum sodium levels, and duration of fever before IVIG therapy were significantly lower (p < .05). There was no significant difference in SAA levels between patients with KD with and without CALs. Binary logistic regression analysis showed that SAA (p = .008), neutrophils (p < .001), total bilirubin (p = .001), platelet count (p = .004), and serum sodium level (p = .019) were independent factors influencing IVIG resistance. The optimal cutoff value of SAA for IVIG resistance prediction was 252.45 mg/L, with a corresponding clinical sensitivity of 69.8% and specificity of 54.4%. Based on receiver operating characteristic (ROC) curve analyses, the area under the curve (AUC) of combined detection with these five indicators was 0.800, clinical sensitivity was 69.8%, and specificity was 76.2%. In the prospective data, the sensitivity, specificity, and accuracy of SAA for identifying IVIG resistance KD were 77.8%,69.0%, and 70.0%, respectively. Compared with IVIG- responsive group and healthy children, the levels of IL-6 was upregulated significantly in IVIG-resistant group through cytokine microarrays. CONCLUSIONS SAA may be a potential biomarker for predicting IVIG responsiveness to KD, Combined detection of SAA levels, total bilirubin, neutrophil count, platelet count, and serum sodium levels is superior to that of any other single indicator for predicting IVIG resistance in KD. And elevated SAA may accompany with IL-6 in KD patients, its use in clinical practice may be helpful for treatment management.
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Affiliation(s)
- Xiao-bi Huang
- Department of Pediatric Nephrology, Children’s Hospital of Anhui Medical University (Anhui Provincial Children’s Hospital), Hefei, China
- Department of Pediatric Cardiology, Children’s Hospital of Anhui Medical University (Anhui Provincial Children’s Hospital), Hefei, China
| | - Sheng Zhao
- Department of Pediatric Cardiology, Children’s Hospital of Anhui Medical University (Anhui Provincial Children’s Hospital), Hefei, China
| | - Zhi-yuan Liu
- Department of Pediatric Cardiology, Children’s Hospital of Anhui Medical University (Anhui Provincial Children’s Hospital), Hefei, China
| | - Yan-yan Xu
- Department of Pediatric Cardiology, Children’s Hospital of Anhui Medical University (Anhui Provincial Children’s Hospital), Hefei, China
| | - Fang Deng
- Department of Pediatric Nephrology, Children’s Hospital of Anhui Medical University (Anhui Provincial Children’s Hospital), Hefei, China
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Iio K, Hanna H, Beykou M, Gale C, Herberg JA. Role of procalcitonin in predicting complications of Kawasaki disease. Arch Dis Child 2023; 108:862-864. [PMID: 37524408 DOI: 10.1136/archdischild-2023-325787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 07/18/2023] [Indexed: 08/02/2023]
Affiliation(s)
- Kazuki Iio
- Applied Paediatrics MSc course, Imperial College London, London, UK
- Division of Pediatric Emergency Medicine, Tokyo Metropolitan Children's Medical Center, Fuchu, Tokyo, Japan
| | - Heather Hanna
- Section of Paediatric Infectious Disease, Imperial College London, London, UK
| | - Melina Beykou
- Circuits and Systems Group, Centre of Bio-Inspired Technology, Department of Electrical and Electronic Engineering, Imperial College London, London, UK
- Dynamical Cell Systems Group, Division of Cancer Biology, Institute of Cancer Research, London, UK
- Cancer Research UK Convergence Science Centre, London, UK
| | - Chris Gale
- Neonatal Medicine, School of Public Health, Faculty of Medicine, Imperial College London, London, UK
| | - Jethro Adam Herberg
- Section of Paediatric Infectious Disease, Imperial College London, London, UK
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Li SY, Ding Y. [Expression of interleukin-17A in serum of children with intravenous immunoglobulin-resistant Kawasaki disease and its clinical significance]. ZHONGGUO DANG DAI ER KE ZA ZHI = CHINESE JOURNAL OF CONTEMPORARY PEDIATRICS 2023; 25:244-249. [PMID: 36946157 PMCID: PMC10032069 DOI: 10.7499/j.issn.1008-8830.2210151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 03/23/2023]
Abstract
OBJECTIVES To study the expression of interleukin-17A (IL-17A) in the serum of children with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) and its clinical significance. METHODS A total of 143 children with KD who were hospitalized in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, from June 2021 to June 2022 were enrolled in this prospective study, among whom 115 had IVIG-sensitive KD and 28 had IVIG-resistant KD. After matching for sex and age, 110 children with acute respiratory infectious diseases (fever time ≥5 days but without KD) were enrolled as the control group. The enzyme-linked immunosorbent assay was used to measure the serum level of IL-17A. The levels of white blood cell count (WBC), neutrophil count (NE), platelet count, erythrocyte sedimentation rate, and C-reactive protein (CRP) were measured. The receiver operating characteristic curve was plotted to analyze the value of WBC, NE, CRP, and IL-17A in the prediction of IVIG-resistant KD. The multivariate logistic regression analysis was used to evaluate the predictive factors for resistance to IVIG in children with KD. RESULTS Before IVIG treatment, the KD group had a significantly higher serum level of IL-17A than the control group (P<0.05), and the children with IVIG-resistant KD had a significantly higher serum level of IL-17A than those with IVIG-sensitive KD (P<0.05). The receiver operating characteristic curve analysis showed that WBC, NE, CRP, and IL-17A had an area under the curve of 0.718, 0.741, 0.627, and 0.840, respectively, in the prediction of IVIG-resistant KD. With serum IL-17A ≥44.06 pg/mL as the cut-off value, IL-17A had a sensitivity of 84% and a specificity of 81% in the prediction of IVIG-resistant KD. The multivariate logistic regression analysis showed that a high serum level of IL-17A was a predictive factor for resistance to IVIG in children with KD (OR=1.161, P=0.001). CONCLUSIONS Serum IL-17A levels are elevated in children with IVIG-resistant KD, and serum IL-17A level (≥44.06 pg/mL) may have a predictive value for resistance to IVIG in children with KD.
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Affiliation(s)
- Shi-Yu Li
- Department of Pediatric Immunology, Wuhan Children's Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430016, China
| | - Yan Ding
- Department of Pediatric Immunology, Wuhan Children's Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430016, China
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Yamashita K, Kanazawa T, Abe Y, Naruto T, Mori M. Kawasaki disease without changes in inflammatory biomarkers: A case report. World J Clin Cases 2022; 10:13038-13043. [PMID: 36569014 PMCID: PMC9782948 DOI: 10.12998/wjcc.v10.i35.13038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 11/04/2022] [Accepted: 11/18/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Kawasaki disease (KD) is diagnosed based on clinical features. Blood tests and other tests are auxiliary diagnostic tools. Since KD is a disease caused by arterial inflammation, many patients with KD have elevated levels of inflammatory biomarkers, such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and serum amyloid A protein (SAA) in blood tests. We report our experience of a patient with KD who did not have elevated levels of inflammatory biomarkers.
CASE SUMMARY A 1-year-old boy presented with a 3-day history of fever. Five of the six symptoms of KD were observed, except for changes in the lips and oral cavity. Blood tests revealed no elevation in CRP, ESR, or SAA levels. Although the blood test results were atypical, the patient was diagnosed with KD based on clinical symptoms and was admitted to the hospital for treatment. The patient was administered intravenous immunoglobulin (IVIG) and aspirin. Despite commencing treatment, the fever persisted; therefore, additional IVIG was administered, the dosage of aspirin was increased, and ulinastatin was added. Three doses of IVIG were administered and the fever resolved on day 11 of KD symptoms started. Blood tests performed during hospitalization showed normal levels of inflammatory biomarkers. We examined leucine-rich alpha-2-glycoprotein 1 - a protein that is elevated during the acute phase of KD. The protein levels did not increase during hospitalization.
CONCLUSION This case suggests the need to identify criteria and biomarkers for detecting KD conditions that do not require KD treatment.
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Affiliation(s)
- Kosei Yamashita
- Children’s Medical Center, Showa University Koto Toyosu Hospital, Tokyo 135-8577, Japan
| | - Takeru Kanazawa
- Children’s Medical Center, Showa University Koto Toyosu Hospital, Tokyo 135-8577, Japan
| | - Yoshifusa Abe
- Children’s Medical Center, Showa University Koto Toyosu Hospital, Tokyo 135-8577, Japan
| | - Takuya Naruto
- Lifetime Clinical Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
| | - Masaaki Mori
- Lifetime Clinical Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
- Department of Rheumatology, Clinical Immunology and Allergology, St. Marianna University School of Medicine, Kanagawa 216-8511, Japan
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胡 慧, 陈 笑, 张 永, 杜 忠. [Association of liver damage with coronary artery lesion and no response to intravenous immunoglobulin in the acute stage of Kawasaki disease]. ZHONGGUO DANG DAI ER KE ZA ZHI = CHINESE JOURNAL OF CONTEMPORARY PEDIATRICS 2022; 24:681-686. [PMID: 35762436 PMCID: PMC9250406 DOI: 10.7499/j.issn.1008-8830.2112094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 05/06/2022] [Indexed: 06/15/2023]
Abstract
OBJECTIVES To summarize the clinical features of liver damage in children in the acute stage of Kawasaki disease (KD), and to investigate the clinical value of liver damage in predicting coronary artery lesion and no response to intravenous immunoglobulin (IVIG) in children with KD. METHODS The medical data were collected from 925 children who were diagnosed with KD for the first time in Beijing Children's Hospital from January 1, 2016 to December 31, 2017. According to the presence or absence of abnormal alanine aminotransferase (ALT) level on admission, the children were divided into a liver damage group (n=284) and a non-liver damage group (n=641). A logistic regression analysis was used to investigate the clinical value of the indicators including liver damage in predicting coronary artery lesion and no response to IVIG in children with KD. RESULTS Compared with the non-liver damage group, the liver damage group had a significantly earlier admission time and significantly higher serum levels of inflammatory indicators (P<0.05). The liver damage group had a significantly higher incidence rate of coronary artery lesion on admission than the non-liver damage group (P=0.034). After initial IVIG therapy, the liver damage group had a significantly higher proportion of children with no response to IVIG than the non-liver damage group (P<0.001). In children with KD, coronary artery lesion was associated with the reduction in the hemoglobin level and the increases in platelet count, C-reactive protein, and ALT (P<0.05), and no response to IVIG was associated with limb changes, the reduction in the hemoglobin level, the increases in platelet count, C-reactive protein, and ALT, and coronary artery lesion (P<0.05). CONCLUSIONS Compared with those without liver damage, the children in the early stage of KD with liver damage tend to develop clinical symptoms early and have higher levels of inflammatory indicators, and they are more likely to have coronary artery lesion and show no response to IVIG treatment.
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Affiliation(s)
| | - 笑征 陈
- 首都医科大学附属北京妇产医院/北京妇幼保健院儿童保健科北京100006
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Kato T. Using Biomarkers to Predict Unresponsiveness to Initial Immunoglobulin for Kawasaki Disease Patients. Circ J 2022; 86:984-985. [PMID: 34732588 DOI: 10.1253/circj.cj-21-0821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Taichi Kato
- Department of Pediatrics/Developmental Pediatrics, Nagoya University Graduate School of Medicine
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Clinical implications of procalcitonin in Kawasaki disease: a useful candidate for differentiating from sepsis and evaluating IVIG responsiveness. Clin Exp Med 2021; 21:633-643. [PMID: 33839960 PMCID: PMC8036161 DOI: 10.1007/s10238-021-00709-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 03/26/2021] [Indexed: 12/17/2022]
Abstract
OBJECTIVE Kawasaki disease (KD) is an acute systemic vasculitis and suspected to be triggered by several potential infections in which procalcitonin (PCT) experiences an increase to some extent. However, whether PCT can serve as a useful candidate for differentiating KD from sepsis, and even for predicting incomplete KD, intravenous immunoglobulin (IVIG) nonresponsiveness and coronary artery abnormalities (CAAs) remains unclear. METHODS A total of 254 Chinese KD children were enrolled and divided into 6 subgroups, including complete KD, incomplete KD, IVIG-responsive KD, IVIG-nonresponsive KD, KD with CAAs and KD without CAAs. Blood samples were collected from all subjects within 24-h pre- and 48-h post-IVIG infusion, respectively. PCT, C-reactive protein, erythrocyte sedimentation rate and blood cell counts were detected. In addition, both 261 children with sepsis and 251 healthy children sex- and age-matched with KD children were enrolled in the same period. RESULTS (1) PCT experienced the highest increase in sepsis patients before antibiotic therapy, followed by acute KD patients and the healthy controls. (2) The proportion of KD patients with a PCT concentration below 0.25 ng/ml was 11 folds higher than that of sepsis patients. (3) PCT had a sensitivity of 91.7% and a specificity of 30.3% at a cutoff value of > 0.15 ng/ml to predict IVIG nonresponsiveness, and the proportion of IVIG-nonresponders with a PCT concentration of 0.25-0.50 ng/ml was 2 folds higher than that of IVIG-responders. CONCLUSIONS The PCT concentrations below 0.25 ng/ml may be useful for discriminating KD from sepsis, and moreover, the PCT concentrations of 0.25-0.50 ng/ml may be helpful in predicting IVIG nonresponsiveness.
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