scholarly journals Useful predictors of Kawasaki disease without complications before initial acute-phase treatment

2021 ◽  
Vol 7 (3) ◽  
pp. 018-027
Author(s):  
Toshimasa Nakada
Keyword(s):  
Kawasaki Disease ◽  
Acute Phase ◽  
Systemic Vasculitis ◽  
Rescue Therapy ◽  
Ivig Therapy ◽  
Therapy Resistance ◽  
Albumin Ratio ◽  
Reactive Protein ◽  
Ivig Resistance ◽  
Acute Phase Treatment

Kawasaki disease (KD) is an acute febrile systemic vasculitis that primarily affects children younger than 5 years, with coronary artery lesions (CALs) as its severe complications. Intravenous immunoglobulin (IVIG) therapy resistance has been implicated in CAL development, and its known predictors are as follows: Egami score, Kobayashi score, C-reactive protein (CRP), albumin, CRP-to-albumin ratio, and neutrophil-to-lymphocyte ratio (NLR). However, the most useful predictor for IVIG resistance in patients with KD without complications before initial acute-phase treatment remains unclear. Therefore, this study aimed to determine the most useful predictor for IVIG resistance in such patients. This retrospective study included data from 202 patients with KD who underwent acute-phase treatment from January 2009 to March 2021. Among 46 IVIG-resistant patients, 22 patients required rescue therapy (rescued patients), while the remaining 24 received no rescue therapy for resistance and had no CALs. Among the 6 indices, NLR had the highest sensitivity and specificity for the detection of all IVIG-resistant patients and rescued patients (0.724 and 0.728, respectively), and logistic regression analysis showed that the NLR was the sole independent predictor both for the IVIG-resistant patients and for the rescued patients (P < 0.001 and = 0.002, Odds ratio = 5.797 and 5.814, 95% confidence interval = 2.687–12.504 and 1.954–17.299, respectively). NLR was the useful predictor for all IVIG-resistant patients and rescued patients among those with KD without complications before initial acute-phase treatment.

scholarly journals Outcomes of Kawasaki Disease in Families

2020 ◽  
Vol 2 (5) ◽  
Author(s):  
Toshimasa Nakada
Keyword(s):  
Family History ◽  
Kawasaki Disease ◽  
Rescue Therapy ◽  
Positive Family History ◽  
Ivig Therapy ◽  
Therapy Resistance ◽  
Ivig Resistance ◽  
The Family ◽  
History Of ◽  
Acute Phase Treatment

An epidemiological study showed that a positive family history of Kawasaki disease (KD) was a risk factor for intravenous immunoglobulin (IVIG) therapy resistance, coronary artery lesions (CALs), and KD recurrence. However, real-world outcomes of KD patients with a family history remain unclear. The objective of this study was to elucidate the outcomes of KD patients with a family history in the era of 2 g/kg IVIG therapy. This retrospective study included data from 201 KD patients who underwent acute-phase treatment from January 2009 to June 2020, with 184 (91.5%) receiving 2 g/kg IVIG therapy. The patients were divided into 13 (family group) with and 188 (nonfamily group) without a family history of KD. The rates of IVIG resistance (8.3% vs. 22.1%, P = 0.315), rescue therapy (8.3% vs. 12.8%, P = 1.000), CALs (0.0% vs. 2.7%, P = 1.000), and KD recurrence (0.0% vs. 3.2%, P = 1.000) were similar between the family and nonfamily groups.

scholarly journals Current Real-World Outcomes of Recurrent Kawasaki Disease

2020 ◽  
pp. 87-92
Author(s):  
Toshimasa Nakada
Keyword(s):  
Risk Factor ◽  
Kawasaki Disease ◽  
Real World ◽  
Rescue Therapy ◽  
Ivig Therapy ◽  
Therapy Resistance ◽  
Recurrent Group ◽  
First Onset ◽  
Initial Episode ◽  
Acute Phase Treatment

Studies have shown that recurrent Kawasaki disease (KD) is a risk factor for resistance to initial intravenous immunoglobulin (IVIG) therapy and development of coronary artery lesions (CALs). However, current real-world outcomes of recurrent KD patients remain unclear. The objective of this retrospective study was to elucidate the outcomes of recurrent KD patients in the era of 2 g/kg IVIG therapy. Data were included from 201 KD patients who underwent acute-phase treatment from January 2009 to September 2020, with 184 (91.5%) receiving 2 g/kg IVIG therapy. The patients were divided into 7 with (recurrent group) and 194 without (nonrecurrent group) recurrent KD. At the first onset, the rates of initial IVIG therapy resistance (28.6% vs. 21.5%, P = 1.000), rescue therapy (14.3% vs. 14.4%, P = 1.000), and CALs (0.0% vs. 2.6%, P = 1.000) were similar between the recurrent and nonrecurrent groups. The rates of initial IVIG therapy resistance (14.3% vs. 21.5%, P = 1.000), rescue therapy (14.3% vs. 14.4%, P = 1.000), and CALs (0.0% vs. 2.6%, P = 1.000) were also similar between the recurrent group at the second onset and the nonrecurrent group at the first onset. KD recurrence may no longer be a risk factor for developing CALs in the era of 2 g/kg IVIG therapy, unless CALs appear at the initial episode.

Abstract 12698: Sodium-containing versus Sodium-trace Preparations of Ivig for Children With Kawasaki Disease in Acute Phase

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Takanori Suzuki ◽  
Nobuaki Michihata ◽  
Tetsushi Yoshikawa ◽  
Kazuyoshi Saito ◽  
Kiyohide Fushimi ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Length Of Stay ◽  
Propensity Score ◽  
Acute Phase ◽  
Medical Cost ◽  
Instrumental Variable ◽  
Systemic Vasculitis ◽  
Developed Countries ◽  
Recommended Treatment ◽  
Ivig Resistance

Objectives: Kawasaki disease (KD) is an acute systemic vasculitis that most commonly causes acquired cardiac disease in children in developed countries. The most highly recommended treatment for KD is 2 g/kg intravenous immunoglobulin (IVIG). Hyponatremia in patients with KD in the acute phase is known to be associated with IVIG resistance and coronary artery abnormalities (CAA). There are two types of IVIG, sodium-containing (high Na) and sodium-trace (low Na) preparations. However, few studies have compared the effects of these two preparations for superiority. The purpose of this study was to compare outcomes between high and low Na IVIG preparations in KD children using a national inpatient database in Japan. Methods: We used the Diagnostic Procedure Combination database to identify KD patients treated with IVIG between 2010 and 2017. We identified those receiving high and low Na preparations of IVIG as an initial treatment. Outcomes included proportion of CAA, IVIG resistance, adverse effects, length of stay, and medical cost. Propensity score-matched analyses were conducted to compare the outcomes between the two groups. Instrumental variable analyses were performed to confirm the results. Results: We identified 47,292 patients with KD and created 23646 propensity score-matched pairs between the high and low Na IVIG groups. There were significant differences in proportions of CAA (2.5% vs. 2.9%; p=0.016) and IVIG resistance (23.8% vs. 24.9%; p=0.006) between the two groups. However, there were no significant differences in length of stay or medical cost. The instrumental variable analyses confirmed that high Na IVIG was significantly associated with lower proportion of CAA compared with low Na IVIG (odds ratio, 1.69; p<0.001). Conclusions: The present study suggests that high Na IVIG is potentially effective for reducing the proportion of CAA in KD patients. Prospective studies are warranted to confirm the effectiveness observed in this study.

scholarly journals Kawasaki disease with low C-reactive protein levels

2021 ◽  
Vol 10 (2) ◽  
pp. 241-245
Author(s):  
Toshimasa Nakada
Keyword(s):  
Kawasaki Disease ◽  
Clinical Features ◽  
Initial Treatment ◽  
Systemic Vasculitis ◽  
Ivig Therapy ◽  
C Reactive Protein ◽  
High Group ◽  
Reactive Protein ◽  
Serum Crp ◽  
Low Serum

Kawasaki disease (KD) is an acute febrile systemic vasculitis that primarily affects children, and coronary artery lesions (CALs) are severe complications. Clinical features and outcomes of patients with KD associated with low serum C-reactive protein (CRP) levels (< 3.0 mg/dL) before initial treatment remain unclear. The objective of this retrospective study was to elucidate the clinical features and outcomes of patients with KD and low serum CRP levels. Data were included from 220 patients with KD who underwent acute-phase treatment from January 2009 to February 2021 in our department. Patients were divided into low group (n = 50) and high group (n = 170) according to serum CRP levels before initial treatment. The rates of incomplete KD (48.0% vs. 10.6%, P < 0.001) and serum albumin levels (g/dL) before initial treatment (median 3.60 vs. 3.30, P < 0.001) were significantly different between the groups. The rate of patients who required intravenous immunoglobulin (IVIG) therapy was significantly lower in the low group compared to the high group (74.0% vs. 97.1%, P < 0.001). However, the rates of initial IVIG therapy resistance (10.8% vs. 25.5%, P= 0.055) and CALs (2.0% vs. 4.7%, P= 0.475) were similar between the groups. No patient in the low group experienced CALs one month after KD onset. The severity of the disease in patients with KD and low CRP levels was milder than in those with high CRP levels.

scholarly journals Genetic Polymorphism and Intravenous Immunoglobulin Resistance Relationship in Kawasaki Disease

2021 ◽  
Author(s):  
Yusuf Ziya Varlı ◽  
Ahmet Okay Caglayan ◽  
Kaya Bilguvar ◽  
Murat Gunel ◽  
Kazim Oztarhan
Keyword(s):  
Kawasaki Disease ◽  
Intravenous Immunoglobulin ◽  
Systemic Vasculitis ◽  
Resistance Mechanism ◽  
Artery Aneurysm ◽  
Ivig Therapy ◽  
Nucleotide Polymorphisms ◽  
Ivig Resistance ◽  
Exonic Snps ◽  
Northeast Asian

Abstract Objective Kawasaki disease (KD) is an acute febrile systemic vasculitis and the most common cause of coronary artery aneurysm (CAA) in children. Intravenous immunoglobulin (IVIG) therapy is used to prevent fever and systemic inflammation. However, IVIG resistance is the most important risk factor of morbidity and mortality. It has been identified several single nucleotide polymorphisms (SNPs) related to IVIG resistance and this research aims to analyze these polymorphisms in our study population. Methods Patients diagnosed with KD (n:259) were analyzed retrospectively. Blood samples were taken from a randomized subgroup (n:97). Previously reported IVIG resistance related exonic SNPs at five different gene loci (IL16, TNFSF14, NFATC2, DERL3, SAMD9L) were evaluated by whole exome sequencing (WES). Results Between 2010–2019, 259 patients (male/female: 1,67) with KD were submitted to our clinic. CAA and IVIG resistance rates were 11.6% and 21.6%, respectively. The risk of developing CAA was significantly increased in patients with IVIG resistance (p < 0.001). As a result, IVIG resistance frequency increased in the presence of three SNPs. These are "rs11556218"(p.Asn1147Lys), "rs344560"(p.Lys214Glu), "rs12479626"(p.His446Arg), and are located in IL16, TNFSF14, NFATC2 genes, respectively. Conclusions Until now, KD-related genetic data mostly obtained from studies involving large cohorts from Northeast Asian countries. In the analysis of this largest Turkish cohort in the literature, we found that, similar with previous studies, the IL16 gene may be plays important role in the IVIG resistance mechanism.

scholarly journals Acute Phase Treatment and Medium-Term Outcomes in Kawasaki Disease

2020 ◽  
Vol 2 (4) ◽  
Author(s):  
Toshimasa Nakada
Keyword(s):  
Coronary Artery ◽  
Kawasaki Disease ◽  
Acute Phase ◽  
Coronary Artery Stenosis ◽  
Ivig Therapy ◽  
Initial Therapy ◽  
Artery Stenosis ◽  
Cardiac Events ◽  
Medium Term ◽  
Acute Phase Treatment

An acute phase treatment for prevention of coronary artery stenosis caused by Kawasaki disease (KD) has not been established. The objective of this study was to clarify the medium-term outcomes of patients who received acute phase treatment in our department. This retrospective study included data from 214 patients with KD who received acute phase treatment from January 2009 to May 2020. A total of 196 (92.1%) received an initial single dose of intravenous immunoglobulin (IVIG) therapy. One patient with status epilepticus at presentation received initial IVIG plus steroid therapy. A total of 17 patients did not receive IVIG. The rate of coronary artery lesions (CALs) 1 month and 1 year after KD onset were 1.9% and 0.9%, respectively. Two patients had CAL 1 year after KD onset. However, no patients had coronary artery stenosis. One patient with a right giant CAL had a medium CAL before initial therapy. During a median follow-up period of 3 years and 4 months, no patients had cardiac events that required therapy.

scholarly journals Application of C-reactive Protein/Albumin Ratio (CAR) in Kawasaki Disease

2021 ◽  
Author(s):  
Zhenquan Wang ◽  
Yiping Shao ◽  
Xing Rong ◽  
Huixian Qiu ◽  
Jinxing Wang ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Roc Curve ◽  
Laboratory Data ◽  
Clinical Manifestations ◽  
Curve Analysis ◽  
C Reactive Protein ◽  
Roc Curve Analysis ◽  
Albumin Ratio ◽  
Reactive Protein ◽  
Ivig Resistance

Abstract Objective: To investigate the association between the C-reactive protein/albumin ratio (CAR) and coronary artery lesions (CAL), intravenous immunoglobulin (IVIG) resistance in children with Kawasaki disease (KD).Methods: We retrospectively studied 753 children with KD, categorizing them into the CAL group(n=238) and the No-CAL group(n=515), the IVIG-resistance group(n=61) and the No-IVIG- resistance(n=653) group. The differences in laboratory data, clinical manifestations, the relationship between CAR and CAL as well as IVIG resistance were compared between the two cohort groups.Results: Compared with No-CAL group, KD with CAL had a higher CAR (2.12 vs 1.69, p <0.001). And CAR was significantly higher in KD children with IVIG resistance (2.42 vs 1.85, p<0.001). Multivariable logistic regression analysis demonstrated that higher CAR was a risk factors of CAL(OR=1.198, p<0.001) and IVIG resistance (OR=1.297, p<0.001), respectively. CAL and IVIG resistance interact with each other. ROC curve analysis performed for the prediction of CAL, the best cut-off point for CAR was 1.80(AUC=0.602, sensitivity 64.7%, specificity 54.8%). When predicting IVIG resistance according to the ROC curve analysis, the optimal cutoff point for CAR was 2.20(AUC=0.621, sensitivity 59.0%, specificity 61.1%).Conclusions: CAR is a valid indicator in KD children. Higher CAR may be helpful in predicting CAL and IVIG resistance in KD.

Abstract 16564: Analysis of the Mechanisms of Intravenous Immunoglobulin-Resistant Kawasaki Disease Using iPS Cell Technology

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Kazuyuki Ikeda ◽  
Tomonaga Ameku ◽  
Yui Nomiya ◽  
Masahiro Nakamura ◽  
Satoshi Matsui ◽  
...  
Keyword(s):  
Gene Expression ◽  
Kawasaki Disease ◽  
Intravenous Immunoglobulin ◽  
Expression Profiles ◽  
Systemic Vasculitis ◽  
Dermal Fibroblasts ◽  
Gene Set Enrichment Analysis ◽  
Recurrent Fever ◽  
Ips Cell ◽  
Ivig Resistance

Introduction: Kawasaki disease (KD) is a systemic vasculitis of unknown origin. Although the treatment of intravenous immunoglobulin (IVIG) significantly resolves inflammation, 10-20% of KD patients have persistent or recurrent fever after the administration of IVIG, and IVIG-resistant patients have a particularly high risk of developing coronary artery abnormalities. Hypothesis: The mechanisms of IVIG-resistant KD have been analyzed using the patients’ leukocyte samples. However, vascular endothelial cells (ECs), closely related to the vasculitis of KD, have not been examined in the previous reports. We propose a hypothesis that ECs are mainly involved in the etiology of IVIG-resistance. Methods: The purpose of this study is to establish new in vitro disease models of vasculitis using induced pluripotent stem cell (iPSC) technology, and clarify the mechanisms of IVIG-resistance in KD. Dermal fibroblasts or T cells from 2 IVIG-resistant and 2 IVIG-responsive KD patients were reprogrammed by episomal vectors encoding Oct3/4, Sox2, Klf4, L-Myc, LIN28, and p53 shRNA. The iPSC lines were then differentiated into ECs by using a previously-reported differentiation method, and the EC samples were subjected to the microarray analyses. Results: The KD patient-derived iPSCs could be differentiated into ECs. The gene expression profiles were compared between iPS-derived ECs (iPS-ECs) generated from IVIG-resistant and IVIG-responsive KD patients. We found that 107 genes were at least two fold up-regulated and 101 genes were at least two fold down-regulated in iPS-ECs from IVIG-resistant KD patients compared with those from IVIG-responsive patients. The Principle Component Analysis (PCA) was performed, but the gene expression levels showed no significant differences between the groups. The Gene Set Enrichment Analysis (GSEA) revealed that the gene sets related to IL-6, NRAS (a member of the RAS oncogene family) and breast cancer were up-regulated in iPS-ECs from IVIG-resistant KD patients. Conclusions: Taking into account that the concentration of IL-6 has been reported to be elevated in acute phase of IVIG-resistant KD, our results suggest that the up-regulation of IL-6 related genes in ECs might be involved in the pathogenesis of IVIG-resistant KD.

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