Serum albumin level predicts initial intravenous immunoglobulin treatment failure in Kawasaki disease

Objectives: Kawasaki disease (KD) is a systemic vasculitis primarily affecting children who are <5 years old. Intravenous immunoglobulin (IVIG) is the standard therapy for KD. However, many patients with KD still show poor response to initial IVIG treatment. This study was conducted to investigate the risk factors for initial IVIG treatment failure in KD. Methods: Children who met KD diagnosis criteria and were admitted for IVIG treatment were retrospectively enrolled for analysis. Patients were divided into IVIG‐responsive and IVIG‐resistant groups. Initial laboratory data before IVIG treatment were collected for analysis. Results: A total of 131 patients were enrolled during the study period. At 48 h after completion of initial IVIG treatment, 20 patients (15.3%) had an elevated body temperature. Univariate analysis showed that patients who had initial findings of high neutrophil count, abnormal liver function, low serum albumin level (≤2.9 g/dL) and pericardial effusion were at risk for IVIG treatment failure. Multivariate analysis with a logistic regression procedure showed that serum albumin level was considered the independent predicting factor of IVIG resistance in patients with KD (p = 0.006, OR = 40, 95% CI: 52.8–562). There was no significant correlation between age, gender, fever duration before IVIG treatment, haemoglobin level, total leucocyte and platelet counts, C‐reactive protein level, or sterile pyuria and initial IVIG treatment failure. The specificity and sensitivity for prediction of IVIG treatment failure in this study were 96% and 34%, respectively. Conclusion: Pre‐IVIG treatment serum albumin levels are a useful predictor of IVIG resistance in patients with KD.     

A meta-analysis on the effect of corticosteroid therapy in Kawasaki disease

The current recommended therapy for Kawasaki disease (KD) is the combination of intravenous immunoglobulin (IVIG) and aspirin. However, the role of corticosteroid therapy in KD remains controversial. Using meta-analysis, this study aimed to investigate the efficacy of corticosteroid therapy in KD by comparing it with standard IVIG and aspirin therapy. We included all related randomized and quasi-randomized controlled trials by searching Medline, the Cochrane Central Register of Controlled Trials, EMBASE, Pub Med, Chinese BioMedical Literature Database, China National Knowledge Infrastructure, and the Japanese database (Japan Science and Technology) as well as hand searches of selected references. Data collection and meta-analysis were performed to evaluate the effect of corticosteroids. Our search yielded 11 studies; 7 of which evaluated the effect of corticosteroid for primary therapy in KD, and 4 investigated the effect of corticosteroid therapy in IVIG-resistant patients. Meta-analysis of these studies revealed a significant reduction in the rates of initial treatment failure among patients who received corticosteroid therapy in combination with IVIG compared to IVIG alone (odds ratio (OR) = 0.50; 95% CI, 0.32~0.79; p = 0.003). Furthermore, the use of corticosteroids reduced the duration of fever and the time required for C-reactive protein to return to normal. Our data did not show any significant increase in the incidence of coronary artery lesions or coronary aneurysms (OR = 0.67; 95% CI, 0.35~1.28; p = 0.23) in the corticosteroid group. Conclusion. Corticosteroid combined with IVIG in primary treatment or as treatment of IVIG-resistant patients improved clinical course without increasing coronary artery lesions in children with acute KD.     

Lower level of serum potassium and higher level of C-reactive protein as an independent risk factor for giant aneurysms in Kawasaki disease

Giant aneurysms are the most serious issue of patients with Kawasaki disease (KD). To clarify risk factors for these giant aneurysms, we conducted a matched case-control study. Among the patients reported in nationwide surveys, 117 patients with giant aneurysms had an unequivocal new diagnosis and presented at the treatment center within 9 d of illness. We obtained clinical information on admission of about 69 patients (case) from the treatment centers. One control was selected for each case, an age- and sex-matched patient without coronary involvement, reported from the same treatment center at about the same time as the case, and we obtained the same clinical information about controls. Fourteen variables were analysed with a conditional logistic regression model: body temperature, hematocrit, hemoglobin, numbers of leukocyte and platelets, concentrations of serum albumin, globulin, total cholesterol, sodium, potassium and chloride, erythrocyte sedimentation rate, C-reactive protein and alanine aminotransferase activity. After adjustment for age, duration of illness before admission and use of intravenous gamma globulin therapy, C-reactive protein [odds ratio (OR) = 1.142, 95% confidence interval (CI) 1.054-1.237], alanine aminotransferase activity (OR = 1.008, 95% CI 1.002-1.014), serum sodium concentration (OR = 0.877, 95% CI 0.770-0.999) and serum potassium concentration (OR = 0.319, 95% CI 0.124-0.822) were significantly related to the risk for giant aneurysms. Further analyses with these four explanatory variables revealed that C-reactive protein (OR = 1.159, 95% CI 1.022-1.315) and serum potassium concentration (OR = 0.222, 95% CI 0.052-0.948) met the significant level. Thus, the values for serum C-reactive protein and potassium are independent risk factors for the development of the giant aneurysms of Kawasaki disease.     

Risk factors associated with the need for additional intravenous gamma-globulin therapy for Kawasaki disease

Aim: To investigate the characteristics of patients with Kawasaki disease who needed intravenous gamma-globulin (IVGG) re-treatment. Methods: Using the database of the 17th nationwide survey in Japan, a total 11 366 patients were identified and analysed (1855 re-treatment patients and 9511 responders). Results: Multivariate logistic regression analysis showed that male sex (odds ratio (OR) 1.26; 95% CI 1.14-1.40), complete cases (OR 1.39; 95% CI 1.07-1.80), recurrence (OR 1.47; 95% CI 1.15-1.88), IVGG treatment within 4 d of illness (OR 2.05; 95% CI 1.84-2.27), daily dose of initial IVGG less than 1000 mg/Kg (OR 0.54; 95% CI 0.48-0.61), exanthema (OR 2.03; 95% CI 1.62-2.56), lips and oral lesions (OR 1.57; 95% CI 1.24-1.98), peripheral extremities changes (OR 1.85; 95% CI 1.54-2.22), and cervical lymphadenopathy (OR 1.89; 95% CI 1.66-2.16) were independent risk factors associated with the need for IVGG re-treatment.

Conclusion: Male sex, recurrence, and treatment with IVGG at a dose of 1000 mg/d or less within 4 d of illness onset are independent risk factors associated with the need for IVGG re-treatment.     

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??Abstract??Objective??This study was aimed at evaluating present randomized controlled trials ??RCT?? regarding the drug therapy for intravenous immunoglobulin ??IVIG?? resistant Kawasaki disease ??KD??. Methods??According to inclusion and exclusion criteria?? articles were selected from medical electronic databases. RCT were then assessed based on the Juni assessment?? and meta-analysis was completed by the Review Manager 4.2 software. Indications to evaluate effects were the change of body temperature and change of coronary artery situation detected by ultrasound-cardiogram. The results were stated as relative risk ??RR?? or odd ratio ??OR???? with a 95% confidence interval ??CI?? and a P < 0.05 significant level. Results??In total?? three RCT were selected. Funel plot analysis showed possible publication bias. Meta-analysis of the three RCT?? including all 59 patients in the 2nd intravenous immunoglobulin treatment group and 66 patients in the glucocorticosteroid treatment control group?? indicated that after their first doses of IVIG treatment?? the temperatures of IVIG resistant KD patients who received 2nd IVIG treatment could be more effectively improved than those who received glucocorticosteroid treatment ??RR = 1.29??95% CI??1.10??1.52??P = 0.002???? but there were no differences on the incidence of coronary artery aneurysm between two groups ??OR = 0.91??95% CI??0.33??2.49??P = 0.85??. Conclusion??The Meta-analysis of currently published RCT demonstrates that the 2nd IVIG can more effectively improve the temperature than glucocorticosteroid in IVIG resistant KD patients?? but there were no differences on the incidence of coronary artery aneurysm between two groups.     

N-terminal Pro-Brain Natriuretic Peptide (NT proBNP) as a Predictive Indicator of Initial Intravenous Immunoglobulin Treatment Failure in Children With Kawasaki Disease: A Retrospective Study

Intravenous immunoglobulin (IVIG) administered in the acute stage of Kawasaki disease (KD) is the standard therapy. Few reports describe nonresponders to initial treatment with IVIG in KD, which remains the most consistent risk factor for coronary artery lesions (CALs). This study aimed to investigate whether the serum level of N-terminal pro-brain natriuretic peptide (NT-proBNP) can be a predictive indicator for identifying patients with KD at higher risk of IVIG treatment failure. In this study, 135 patients with a diagnosis of KD admitted for IVIG treatment were retrospectively enrolled for analysis. Of these 135 patients, 22 were nonresponders who received additional rescue therapy because they had an elevated body temperature 36 h after completion of initial IVIG treatment. The NT-proBNP concentration was significantly higher in the nonresponder group (2,465.36 ± 3,293.24 pg/mL) than in the responder group (942.38 ± 1,293.48 pg/mL) (p < 0.05). The optimal sensitivity and specificity cutoff point for predicted nonresponders was 1,093.00 pg/mL or higher. The sensitivity and specificity for prediction of IVIG response were respectively 70.0 and 76.5 %. The findings show that NT-proBNP is a helpful marker in determining patients at risk for not responding to initial IVIG treatment. The authors suggest that patients with an NT-proBNP level of 1,093.00 pg/dL or higher are likely to fail initial IVIG and may require further rescue therapy.     

Assessment of Risk Factors for Korean Children with Kawasaki Disease

Kawasaki disease (KD) is the most common cause of acquired heart disease in children. Intravenous immunoglobulin (IVIG) is the standard therapy for KD, but more than 10% of KD patients do not respond to IVIG and are at high risk for the development of coronary artery lesions (CALs). To identify clinical and genetic risk factors associated with CAL development and IVIG nonresponsiveness, this study analyzed the clinical data for 478 Korean KD patients. Multivariate logistic regression analysis showed that incomplete KD, IVIG nonresponse, fever duration of 7?days or longer, and the CC/AC genotypes of the rs7604693 single nucleotide polymorphism (SNP) in the PELI1 gene were significantly associated with the development of CALs, with odds ratios (ORs) ranging from 2.06 to 3.04. The risk of CAL formation was synergistically increased by the addition of individual risk factors, particularly the genetic variant in the PELI1 gene. Multivariate analysis also showed that a serum albumin level of 3.6?g/dl or lower was significantly associated with nonresponsiveness to IVIG [OR, 2.76; 95% confidence interval (CI), 1.34-5.68; P?=?0.006]. Conclusively, incomplete KD, IVIG nonresponsiveness, long febrile days, and the rs7604693 genetic variant in the PELI1 gene are major risk factors for the development of CALs, whereas low serum albumin concentration is an independent risk factor for IVIG nonresponsiveness.     

Immunoglobulin Failure and Retreatment in Kawasaki Disease

Several cases of Kawasaki disease (KD) were unresponsive to the initial treatment with intravenous immunoglobulin (IVIG). We retrospectively analyzed all children admitted with KD to determine the occurrence and variables associated with the initial IVIG treatment failure. All patients who fulfilled the criteria for KD and were treated with a single dose (2 g/kg) of IVIG between January 1995 and August 2001 were enrolled. An analysis of the patients who had initially failed to respond to IVIG was performed. A total of 120 patients were enrolled during the study period. There were 68 boys (56.7%). Fourteen patients (11.6%) were found to be unresponsive to initial IVIG treatment. Patients who were anemic (Hb<10 G/DL), HAD A HIGH NEUTROPHIL COUNT (> 75%), a high band count, and low albumin were at risk of failure to respond to a single dose of IVIG. We found no correlation among age, gender, days since starting IVIG treatment, and erythrocyte sedimentation rate (ESR) with failure of the initial IVIG treatment. There were 12 patients (10%) who developed coronary artery aneurysms. The failure of a single dose of IVIG treatment occured in up to 11.6% of our Kawasaki patients. We found that low hemoglobin (<10 G/DL), HIGH NEUTROPHIL COUNT (> 75%), high band count, and a low albumin were associated with the requirement for retreatment with a second dose of IVIG.     

Case–control study of giant coronary aneurysms due to Kawasaki disease: The 19th nationwide survey

Background: The risk factors for recently reported cases of giant coronary aneurysms due to Kawasaki disease have not been elaborated. Methods: Fifty‐three patients with giant coronary aneurysms, diagnosed as Kawasaki disease in 2005 and 2006, were selected from the 19th nationwide survey of the disease in Japan. With all the other patients recorded at the same hospitals as a control group, OR and their 95%CI were calculated to delineate the risk factors. Results: In multivariate analyses, patients aged younger than 1 year (OR compared with 1–2‐year‐olds = 6.57) and those older than 5 years (OR compared with 1–2‐year‐olds = 4.24), those who received additional intravenous immunoglobulin (IVIG) without the use of steroid (OR = 8.38) and those who received steroid administration with or without the additional use of IVIG (OR = 220.51 and 83.83, respectively), showed significantly higher OR for giant coronary aneurysms. As for IVIG therapy, the additional use of IVIG (OR = 14.84), total dosage of IVIG exceeding 2500 mg/kg (OR compared with 1500–2499 mg/kg = 12.26) and the duration of IVIG administration for more than 3 days (OR = 30.12), were found to significantly increase the risk of developing giant aneurysms in univariate analyses that were adjusted for sex and age. Conclusions: The observation of 53 patients with giant coronary aneurysms due to Kawasaki disease among those included in the nationwide survey presented some risk factors, together with considerations about the associated aneurysms.     

儿童再发川崎病临床特征的Meta分析

目的 探讨儿童再发川崎病（KD）的临床特点,以提高对再发KD的认识。方法 检索PubMed、Web of Science、Embase、中国知网、万方医学网和中国科技期刊数据库中关于儿童再发KD与初发时临床特点的对照研究,根据纳入、排除标准筛选文献,采用RevMan 5.3软件进行Meta分析。根据异质性检验结果选择相应效应模型进行数据合并,计算各观察指标合并比值比（OR）或加权均数差（WMD）及其95%CI。结果 最终纳入9个病例对照研究,KD患儿样本总量为12 059例,其中再发KD患儿206例（男127例,占61.7%;女79例,占38.3%）。Meta分析结果显示,与初发时相比,再发时发热时程缩短（WMD=-1.81,95%CI：-2.99~-0.64）,手足硬肿率降低（OR=0.46,95%CI：0.26~0.80）,差异均具有统计学意义（P < 0.05）;KD患儿再发时与初发时冠状动脉病变发生率的比较差异无统计学意义（OR=1.34,95%CI：0.84~2.14,P=0.22）。结论 目前证据显示再发KD患儿热程更短,手足硬肿率较低;KD再发以男童多见;再发患儿冠状动脉病变发生风险未见明显增高。     

糖皮质激素联合免疫球蛋白用于川崎病初始治疗有效性的Meta分析

目的 系统评价糖皮质激素(GCs)联合静脉注射免疫球蛋白(IVIG)用于川崎病(KD)初始治疗的有效性和安全性。方法 计算机检索MEDLINE数据库、PubMed数据库、CNKI、万方数据库、维普电子期刊全文数据库等,收集GCs联合IVIG初始治疗儿童KD的前瞻性对照研究或回顾性对照研究,检索时间为各数据库建库至2016年3月。由 2位研究者独立筛选文献、提取资料并对纳入文献进行质量评价后,采用RevMan5.2软件进行Meta分析。结果 共纳入11篇文献,均为英文文献,其中前瞻性研究7项,回顾性研究4项。Meta分析结果显示:与单用IVIG相比,GCs联合IVIG组的冠状动脉损害(CAL)发生率更低 (OR = 0.44,95%CI: 0.23~0.86,P = 0.02),发热持续时间更短 (MD = -1.66,95%CI: -2.32 ~ -1.01,P < 0.00001),且首次治疗未反应率低于单用IVIG组 (OR = 0.37,95%CI: 0.27~ 0.51,P < 0.00001)。两组复发率和不良反应发生率比较差异均无统计学意义。结论 GCs联合IVIG初始治疗KD能降低患儿CAL发生率及首次治疗未反应率,缩短发热时间,且不增加复发率和不良反应的发生。     

对川崎病患儿静脉注射丙种球蛋白耐药临床预测模型建立的质疑

目的 对川崎病(KD)患儿IVIG耐药预测模型提出质疑。方法 回顾性收集经复旦大学附属儿科医院(我院)首次诊断和治疗的KD病例,全样本人群按7∶3比例随机分为建模组和验证组,通过单因素及多因素Logistic回归分析建立IVIG耐药预测模型并行验证,将KD患儿按性别、年龄、发热天数和KD类型等分层,在不同的分层中单独建模和验证;基于全样本人群验证已发表的11个IVIG耐药预测模型,考察通过临床症状、体征和实验室指标是否能满足临床预测KD患儿IVIG耐药。结果 符合本文纳入和排除标准的1 360例KD患儿进入本文分析。男875例(64.3%);年龄中位数1.8(0.9,3.2)岁;IVIG耐药组和敏感组分别为171和1 189例;建模组和验证组分别为952和408例。建模组和验证组人口学特征、主要临床表现、实验室指标、IVIG耐药率和冠脉病变率差异均无统计学意义(P >0.05);建模组中建立的IVIG耐药模型中,男性、发病年龄≥2岁、N%≥0.75、Hb≥110 g·L^-1各计1分,应用首剂IVIG发热≥5 d、ALB≥34 g·L^-1、Na⁺≥133 mmol·L^-1各计2分,AUC为0.818(95% CI:0.774~0.861),总分≥5时,敏感度和特异度分别为0.767和0.726。验证组中AUC为0.777(95% CI:0.712~0.842),敏感度和特异度分别为0.627和0.776。对11个IVIG耐药预测模型验证,以相应预测界值计算敏感度0.272~0.799,特异度0.412~0.926。结论 基于KD患儿人口学特征、临床症状、体征和实验室指标行KD患儿IVIG耐药预测特异度和敏感度均＜75%,对临床预测KD患儿IVIG耐药作用有限。     

对川崎病患儿静脉注射丙种球蛋白耐药临床预测模型建立的质疑

目的 对川崎病(KD)患儿IVIG耐药预测模型提出质疑。方法 回顾性收集经复旦大学附属儿科医院(我院)首次诊断和治疗的KD病例,全样本人群按7∶3比例随机分为建模组和验证组,通过单因素及多因素Logistic回归分析建立IVIG耐药预测模型并行验证,将KD患儿按性别、年龄、发热天数和KD类型等分层,在不同的分层中单独建模和验证;基于全样本人群验证已发表的11个IVIG耐药预测模型,考察通过临床症状、体征和实验室指标是否能满足临床预测KD患儿IVIG耐药。结果 符合本文纳入和排除标准的1 360例KD患儿进入本文分析。男875例(64.3%);年龄中位数1.8(0.9,3.2)岁;IVIG耐药组和敏感组分别为171和1 189例;建模组和验证组分别为952和408例。建模组和验证组人口学特征、主要临床表现、实验室指标、IVIG耐药率和冠脉病变率差异均无统计学意义(P >0.05);建模组中建立的IVIG耐药模型中,男性、发病年龄≥2岁、N%≥0.75、Hb≥110 g·L^-1各计1分,应用首剂IVIG发热≥5 d、ALB≥34 g·L^-1、Na⁺≥133 mmol·L^-1各计2分,AUC为0.818(95% CI:0.774~0.861),总分≥5时,敏感度和特异度分别为0.767和0.726。验证组中AUC为0.777(95% CI:0.712~0.842),敏感度和特异度分别为0.627和0.776。对11个IVIG耐药预测模型验证,以相应预测界值计算敏感度0.272~0.799,特异度0.412~0.926。结论 基于KD患儿人口学特征、临床症状、体征和实验室指标行KD患儿IVIG耐药预测特异度和敏感度均＜75%,对临床预测KD患儿IVIG耐药作用有限。     

Pulse methylprednisolone with gammaglobulin as an initial treatment for acute Kawasaki disease

Approximately 15–20% of patients with Kawasaki disease (KD) are not responsive to high-dose intravenous gammaglobulin (IVIG). We have previously reported a predictive method for identifying IVIG-non-responsive patients (high-risk KD patients). We determined the safety and effectiveness of pulse methylprednisolone with high-dose IVIG (mPSL+IVIG) as a primary treatment for high-risk KD patients. Sixty-two high-risk KD patients were treated with pulse methylprednisolone 30 mg/kg over 2 h, followed by IVIG 2 g/kg over 24 h (mPSL+IVIG group) and were compared with a historical control group of 32 high-risk patients treated with IVIG 2 g/kg alone at the participating hospitals before this study was opened (IVIG group). High-risk patients were identified with at least two of three predictors (C-reactive protein ≥7 mg/dL, total bilirubin ≥0.9 mg/dL or aspartate aminotransferase ≥200 IU/L). Sixty-six percent (95% confidence interval [CI] 54–78%) of patients had a prompt defervescence in the mPSL+IVIG group compared with 44% (95% CI 26–62%) for the IVIG group (p = 0.048). Coronary artery lesions were observed in 24.2% (95% CI 13.2–35.2%) and 46.9% (95% CI 28.6–65.2%) of patients in the mPSL+IVIG and IVIG groups, respectively (p = 0.025). This is the first report showing that mPSL+IVIG is effective and safe as a primary treatment for high-risk KD patients.     

川崎病延迟诊断的危险因素分析

背景 目前对川崎病(KD)尤其是不典型KD的及时诊断仍面临困难.目的 分析KD患儿延迟诊断的影响因素.设计病例对照研究.方法 采用日本川崎病研究委员会2005年发布的第5版KD诊断标准,6条主要诊断标准中满足≥5条即可诊断KD.纳入2009年1月至2014年12月在浙江大学医学院附属儿童医院住院的KD患儿,发病10 d...     

Coronary artery lesions of incomplete Kawasaki disease: a nationwide survey in Japan

Incomplete Kawasaki disease (KD) is associated with delayed diagnosis and treatment, which in turn can lead to the development of coronary artery lesions (CALs). The aim of this study was to determine the epidemiological features of incomplete KD compared with complete KD and to identify risk factors for CALs from incomplete KD patients using data from a nationwide survey of 2007–2008 in Japan. A total of 23,263 patients were classified according to the number of principal clinical signs: 80% (n = 18,620) had complete forms of KD, 14.2% had four principal signs, 4.6% had three signs, and 1.2% had only one or two signs. In comparison with complete KD cases, the prevalence of CAL development tended to be larger and the proportion receiving initial intravenous immunoglobulin (IVIG) treatment were significantly smaller in patients with incomplete forms. In addition, hospital attendance after 7 days of illness or later was significantly associated with CAL development in all incomplete groups (OR: 2.52 in total patients with incomplete KD, 3.26 in those with one or two principal signs, 2.94 in those with three signs, 2.35 in those with four signs). Conclusion The higher prevalence of CALs in incomplete KD reflects difficulties in diagnosis and delays in treatment. More timely diagnosis and treatment of incomplete KD patients could further prevent the development of cardiac lesions.     

Pulse methylprednisolone therapy in the treatment of immune globulin-resistant Kawasaki disease: case report and review of the literature

A subgroup of patients with Kawasaki disease (KD) did not respond to intravenous immune globulin (IVIG) therapy. Corticosteroid therapy remains a controversial alternative in such cases. We report two young children with KD who failed to respond to three courses of IVIG therapy and subsequently received pulse methylprednisolone as an alternative. One had a satisfactory outcome but the other developed giant coronary aneurysms and had a myocardial infarction 2 months after onset of the illness. A review of relevant literature showed that the timing of initiation of pulse methylprednisolone therapy is important. It is suggested that pulse methylprednisolone therapy should be considered if there is no response to two standard doses of IVIG treatment.     

2012至2016年单中心川崎病流行病学及临床特征研究

目的了解川崎病(KD)患病情况及临床特征,探讨KD冠状动脉损害(CAL)及IVIG耐药的危险因素。方法回顾性分析华中科技大学同济医学院附属同济医院2012年1月1日至2016年12月31日初诊的KD患儿的临床资料,比较分析KD治疗前后,典型和不完全KD,KD伴或不伴CAL,IVIG敏感或耐药的临床特征,分析CAL发生和IVIG耐药的危险因素。结果725例KD患儿进入本文分析,男∶女为1.61∶1,平均年龄（2.7±2.3）岁;不完全KD 206例（28.4%）,典型KD 519例;CAL 216例（29.8%）,IVIG耐药61例（8.4%）;治疗中仅使用阿司匹林者70例（9.6%）。KD伴CAL的危险因素为IVIG耐药（OR=5.138,95%CI：1.835~14.836）和氨基末端脑钠肽前体（NT-proBNP）≥1 000 pg·mL-1（OR=2.723,95%CI：1.110~6.679）。IVIG耐药的危险因素为出现CAL（OR=2.586,95%CI：1.067~6.271）。结论KD患病人数、CAL和IVIG耐药患儿有增加趋势。IVIG耐药和NT-proBNP≥1 000 pg·mL-1为KD伴CAL的危险因素,而发生CAL为IVIG耐药的危险因素。     

Intravenous immune globulin plus corticosteroids in refractory Kawasaki disease

Background: The aim of the present study was to investigate the efficacy of i.v. immune globulin (IVIG) therapy combined with corticosteroids for additional treatment of acute Kawasaki disease (KD) unresponsive to initial IVIG treatment. Methods: In 50 prospective KD patients, six IVIG non‐responders without clinical improvement within 24–48 h after completion of initial IVIG, received 2 g/kg IVIG concurrently with 2 mg/kg i.v. prednisolone sodium succinate (PSL) until normalization of C‐reactive protein level. Treatment was then changed to oral PSL, which was tapered over time. Clinical and coronary artery lesion (CAL) outcomes were compared with those of 13 IVIG non‐responders who received additional heterogeneous therapies in 125 retrospective KD patients. In addition, the scoring system of Kobayashi et al. for prediction of non‐responsiveness to initial IVIG treatment was retrospectively verified in 175 KD subjects, consisting of 50 prospective and 125 retrospective patients in order to evaluate the efficacy of the re‐treatment regimen. Results: Incidence of CAL in the study patients was lower than in the control patients, although differences were not significant both in the acute stage (within 1 month: 1/6, 16.7% vs 7/13, 53.8%; P= 0.177) and in the convalescent stage (after 1 month: 0/6, 0.0% vs 4/13, 30.8%; P= 0.255). According to the non‐responder prediction system, the scores of six study and 13 control patients before initial IVIG treatment were similar (7.2 ± 1.9 vs 5.3 ± 3.1; P= 0.200). No serious adverse effects related to each treatment were noted in patients of either group. Conclusions: Additional IVIG combined with concurrent PSL appears to be safe and worth evaluation for the treatment of acute KD unresponsive to initial IVIG treatment.     

Marker of T‐cell activation is elevated in refractory Kawasaki disease

Background: The aim of this study was to investigate whether T‐cell activation is involved in the pathogenesis of Kawasaki disease (KD) resistant to intravenous immunoglobulin (IVIG) treatment. Methods: Serum samples were obtained from 27 patients who fulfilled the diagnostic criteria for KD. These 27 patients were divided into three groups according to their responses to IVIG: Group A, nine patients who showed no response to either initial IVIG or additional IVIG; Group B, six patients who did not respond to initial IVIG but did respond to additional IVIG; Group C, 12 patients who responded to initial IVIG. Serum samples were obtained before and after initial IVIG. Using a commercial chemiluminescence enzyme immunoassay, we examined the serum levels of two cytokines related to T‐cell activation and the severity of inflammation: soluble interleukin‐2 receptor and interleukin‐6. Results: There were no significant differences in the serum levels of the two cytokines before initial IVIG among the three groups, but significant intergroup differences were evident after initial IVIG in the serum levels of soluble interleukin‐2 receptor (P < 0.01, Group A > C) and interleukin‐6 (P < 0.01, Group A > B > C). Conclusions: Our results show that marker of T‐cell activation is elevated most markedly in KD patients resistant to both initial and additional IVIG, and suggest that T cells may be activated in refractory KD.