Expression of interleukin-17A in serum of children with intravenous immunoglobulin-resistant Kawasaki disease and its clinical significance / 中国当代儿科杂志

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.

Multisystemic inflammatory syndrome in children after severe acute respiratory syndrome coronavirus 2 infection: a clinical analysis of four cases / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical features and treatment strategies of multisystemic inflammatory syndrome in children (MIS-C) after severe acute respiratory syndrome coronavirus 2 infection.@*METHODS@#A retrospective analysis was performed on the medical data of four children with MIS-C who were admitted to the Department of Cardiology, Xuzhou Children's Hospital, Xuzhou Medical Universityfrom January to February 2023.@*RESULTS@#All four children had multiple organ involvements and elevated inflammatory markers, with a poor response to standard therapy for Kawasaki disease after admission. Two children were treated with intravenous immunoglobulin therapy pulse therapy twice, and all four children were treated with glucocorticoids. The children had a good prognosis after the treatment.@*CONCLUSIONS@#MIS-C often appears within 4-6 weeks or a longer time after severe acute respiratory syndrome coronavirus 2 infection, and anti-inflammatory therapy in addition to the standard treatment regimen for Kawasaki disease can help to achieve a favorable treatment outcome.

Role and mechanism of platelet-derived growth factor BB in thrombocytosis in Kawasaki disease / 中国当代儿科杂志

OBJECTIVES@#To study the role and mechanism of platelet-derived growth factor BB (PDGF-BB) on platelet production in Kawasaki disease (KD) mice and human megakaryocytic Dami cells through in vitro and invivo experiments.@*METHODS@#ELISA was used to measure the expression of PDGF in the serum of 40 children with KD and 40 healthy children. C57BL/6 mice were used to establish a model of KD and were then randomly divided into a normal group, a KD group, and an imatinib group (30 mice in each group). Routine blood test was performed for each group, and the expression of PDGF-BB, megakaryocyte colony forming unit (CFU-MK), and the megakaryocyte marker CD41 were measured. CCK-8, flow cytometry, quantitative real-time PCR, and Western blot were used to analyze the role and mechanism of PDGF-BB in platelet production in Dami cells.@*RESULTS@#PDGF-BB was highly expressed in the serum of KD children (P<0.001). The KD group had a higher expression level of PDGF-BB in serum (P<0.05) and significant increases in the expression of CFU-MK and CD41 (P<0.001), and the imatinib group had significant reductions in the expression of CFU-MK and CD41 (P<0.001). In vitro experiments showed that PDGF-BB promoted Dami cell proliferation, platelet production, mRNA expression of PDGFR-β, and protein expression of p-Akt (P<0.05). Compared with the PDGF-BB group, the combination group (PDGF-BB 25 ng/mL + imatinib 20 μmol/L) had significantly lower levels of platelet production, mRNA expression of PDGFR-β, and protein expression of p-Akt (P<0.05).@*CONCLUSIONS@#PDGF-BB may promote megakaryocyte proliferation, differentiation, and platelet production by binding to PDGFR-β and activating the PI3K/Akt pathway, and the PDGFR-β inhibitor imatinib can reduce platelet production, which provides a new strategy for the treatment of thrombocytosis in KD.

Predictive value of peripheral blood lymphocyte subsets for children with intravenous immunoglobulin-resistant Kawasaki disease / 中国当代儿科杂志

OBJECTIVES@#Based on peripheral blood lymphocyte subsets and common laboratory test indexes, this study aimed to construct a predictive scoring system for intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD).@*METHODS@#Children hospitalized in Tianjin Children's Hospital from January 2021 to March 2023 were included in the study (185 cases of IVIG-sensitive KD and 41 cases of IVIG -resistant KD). Forty-six healthy children matched for age and gender were selected as controls. The relative percentage and absolute counts of peripheral lymphocyte subsets were measured by flow cytometry. Multivariate logistic regression was used to identify the predictive factors for IVIG-resistant KD and to construct a predictive scoring system for predicting IVIG-resistant KD.@*RESULTS@#The multivariate logistic regression analysis showed that CD4+ T cell absolute count, natural killer cell absolute count, serum sodium level, globulin level, and total bilirubin level were identified as predictive factors for IVIG-resistant KD (P<0.05). The predictive scoring system based on these factors achieved a sensitivity of 70.7% and a specificity of 83.8% in predicting IVIG-resistant KD.@*CONCLUSIONS@#Peripheral blood lymphocyte subsets can serve as predictive indicators for IVIG-resistant KD in children. The introduction of this indicator and the establishment of a scoring system based on it can provide a higher accuracy in predicting IVIG-resistant KD in children.

Características clínicas, tratamiento y evolución de una serie de niños con síndrome inflamatorio multisistémico asociado a SARS-CoV-2 hospitalizados en dos centros de salud / Clinical characteristics, treatment and evolution of a series of children with multisystemic inflammatory syndrome associated with SARS-CoV-2 hospitalized in two health centers / Características clínicas, tratamento e evolução de uma série de crianças com síndrome inflamatória multissistêmica associada ao SARS-CoV-2 internadas em dois centros de saúde

Introducción: en marzo del 2021 se registró el pico de incidencia de COVID-19 en Uruguay y un aumento de la infección en pediatría. Objetivo: describir las características clínicas, el tratamiento y la evolución de una serie de menores de 15 años con SIM-Ped S hospitalizados en dos centros de salud. Metodología: estudio descriptivo, retrospectivo, de los niños hospitalizados entre el 1/3 y el 31/6 de 2021 que cumplieron los criterios diagnósticos de SIM-Ped de la OMS. Se analizan variables clínicas, paraclínicas, tratamiento y evolución. Resultados: se incluyeron 12 niños, mediana de edad 7 años (22 meses-10 años). Se presentaron complicación posinfecciosas en 8 y en el curso de la infección en 4. Las manifestaciones fueron: fiebre (media 6 días, rango 3-10), digestivas 10 y mucocutáneas 7. Se presentaron como enfermedad Kawasaki símil 5 y como shock 2. La infección por SARS CoV-2 se confirmó por PCR en 6, serología 4 y test antigénico 2. Recibieron tratamiento en cuidados moderados 8 e intensivos 4: inmunoglobulina 9, corticoides 11, heparina 7 y ácido acetilsalicílico 7. Presentaron dilatación de arterias coronarias 2, alteraciones valvulares 2, disminución de la FEVI 2 y derrame pericárdico 2. Todos evolucionaron favorablemente. Conclusiones: en estos centros, los primeros casos de SIMS-Ped S coincidieron con el pico de incidencia de COVID-19 en el país. Predominaron las formas postinfecciosas en escolares con manifestaciones digestivas. Este estudio puede contribuir al reconocimiento de esta entidad y adecuar los algoritmos nacionales de manejo.

Introduction: in March 2021, there was a peak incidence of COVID-19 and an increase in pediatric infections in Uruguay. Objective: describe the clinical characteristics, treatment and evolution of a group of children under 15 years of age with SIM-Ped S hospitalized in two health centers. Methodology: descriptive, retrospective study of children hospitalized between 3/1 and 6/31 of 2021 who met the WHO diagnostic criteria for SIM-Ped. Clinical and paraclinical variables, as well as treatment and evolution were analyzed. Results: 12 children were included, median age 7 years (22 months-10 years). Eight of them showed post-infectious complications and 4 of them had complications during the course of the infection. The manifestations were: fever (mean 6 days, range 3-10), digestive symptoms 10 and mucocutaneous 7. Five of them presented a Kawasaki-like disease and 2 of them shock. SARS CoV-2 infection was confirmed by PCR in 6 cases, serology in 4 and antigenic test in 2. Eight of them received treatment in moderate care and 4 of them in intensive care: immunoglobulin 9, corticosteroids 11, heparin 7 and acetylsalicylic acid 7. Two of them presented dilated arteries coronary , valvular alterations 2, decreased LVEF 2 and pericardial effusion 2. All progressed favorably. Conclusions: in these centers, the first cases of SIMS-Ped S coincided with the peak incidence of COVID-19 in the country. Post-infectious forms predominated in schoolchildren who showed digestive manifestations. This study may contribute to the recognition of this entity and to the adaptation of national management algorithms.

Introdução: em março de 2021, foi registrado no Uruguai um pico de incidência da COVID-19 e um aumento dos casos da infecção pediátrica. Objetivo: descrever as características clínicas, tratamento e evolução de uma série de crianças menores de 15 anos com SIM-Ped S internadas em dois centros de saúde. Metodologia: estudo descritivo, retrospectivo, de crianças internadas entre 1/3 e 31/6 de 2021 que preencheram os critérios diagnósticos da OMS para o SIM-Ped. Foram analisadas variáveis clínicas e para-clinicas, tratamento e evolução. Resultados: foram incluídas 12 crianças, com idade média de 7 anos (22 meses-10 anos). Oito delas apresentaram complicações pós-infecciosas e 4 delas durante o curso da infecção. As manifestações foram: febre (média de 6 dias, intervalo 3-10), digestivas 10 e mucocutânea 7. Cinco delas apresentaram doença de Kawasaki-like e 2 delas sofreram Shock. A infecção por SARS CoV-2 foi confirmada por PCR em 6, sorologia em 4 e teste antigênico em 2. Oito delas receberam tratamento em cuidados moderados e 4 delas em cuidados intensivos: imunoglobulina 9, corticosteroides 11, heparina 7 e ácido acetilsalicílico 7. Duas delas apresentaram artérias coronárias dilatadas 2, alterações valvares 2, diminuição da FEVE 2 e derrame pericárdico 2. Todas evoluíram favoravelmente. Conclusões: nesses centros, os primeiros casos de SIMS-Ped S coincidiram com um pico de incidência de COVID-19 no país. As formas pós-infecciosas predominaram em escolares com manifestações digestivas. Este estudo pode contribuir para o reconhecimento desta entidade e adaptar algoritmos nacionais de gestão.

Retrospective analysis of infliximab in the treatment of Kawasaki disease / 中华儿科杂志

Objective: To investigate the efficacy and safety of infliximab (IFX) therapy for children with Kawasaki disease. Methods: Sixty-eight children with Kawasaki disease who received IFX therapy in Children's Hospital of Fudan University from January 2014 to April 2021 were enrolled. The indications for IFX administration, changes in laboratory parameters before and after IFX administration, response rate, drug adverse events and complications and outcomes of coronary artery aneurysms (CAA) were retrospectively analyzed. Comparisons between groups were performed with unpaired Student t test or Mann-Whitney U test or chi-square test. Results: Among 68 children with Kawasaki disease, 52 (76%) were males and 16 (24%) were females. The age of onset was 2.1 (0.5, 3.8) years. IFX was administered to: (1) 35 children (51%) with persistent fever who did not respond to intravenous immunoglobulin (IVIG) or steroids, 28 of the 35 children (80%) developed CAA before IFX therapy; (2) 32 children (47%) with continuous progression of CAA; (3) 1 child with persistent arthritis. In all cases, IFX was administered as an additional treatment (the time from the onset of illness to IFX therapy was 21 (15, 30) days) which consisted of second line therapy in 20 (29%), third line therapy in 20 (29%), and fourth (or more) line therapy in 28 (41%). C-reactive protein (8 (4, 15) vs. 16 (8, 43) mg/L, Z=-3.38, P=0.001), serum amyloid protein A (17 (10, 42) vs. 88 (11, 327) mg/L, Z=-2.36, P=0.018) and the percentage of neutrophils (0.39±0.20 vs. 0.49±0.21, t=2.63, P=0.010) decreased significantly after IFX administration. Fourteen children (21%) did not respond to IFX and received additional therapies mainly including steroids and cyclophosphamide. There was no significant difference in gender, age at IFX administration, time from the onset of illness to IFX administration, the maximum coronary Z value before IFX administration, and the incidence of systemic aneurysms between IFX-sensitive group and IFX-resistant group (all P>0.05). Infections occurred in 11 cases (16%) after IFX administration, including respiratory tract, digestive tract, urinary tract, skin and oral infections. One case had Calmette-Guérin bacillus-related adverse reactions 2 months after IFX administration. All of these adverse events were cured successfully. One child died of CAA rupture, 6 children were lost to follow up, the remaining 61 children were followed up for 6 (4, 15) months. No CAA occurred in 7 children before and after IFX treatment, while CAA occurred in 54 children before IFX treatment. CAA regressed in 23 (43%) children at the last follow-up, and the diameter of coronary artery recovered to normal in 10 children. Conclusion: IFX is an effective and safe therapeutic choice for children with Kawasaki disease who are refractory to IVIG or steroids therapy or with continuous progression of CAA.

Association of liver damage with coronary artery lesion and no response to intravenous immunoglobulin in the acute stage of Kawasaki disease / 中国当代儿科杂志

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.

Association between duration of fever before treatment and intravenous immunoglobulin resistance in Kawasaki disease / 中国当代儿科杂志

OBJECTIVES@#To examine the association between duration of fever before intravenous immunoglobulin (IVIG) treatment and IVIG resistance in children with Kawasaki disease (KD).@*METHODS@#A retrospective analysis was performed on the medical data of 317 children with KD who were admitted from January 2018 to December 2020. According to the duration of fever before IVIG treatment, they were divided into two groups: short fever duration group (≤4 days) with 92 children and long fever duration group (>4 days) with 225 children. According to the presence or absence of IVIG resistance, each group was further divided into a drug-resistance group and a non-drug-resistance group. Baseline data and laboratory results were compared between groups. A multivariate logistic regression analysis was used to identify the influencing factors for IVIG resistance.@*RESULTS@#In the short fever duration group, 19 children (20.7%) had IVIG resistance and 5 children (5.4%) had coronary artery aneurysm, and in the long fever duration group, 22 children (9.8%) had IVIG resistance and 19 children (8.4%) had coronary artery aneurysm, suggesting that the short fever duration group had a significantly higher rate of IVIG resistance than the long fever duration group (P<0.05), while there was no significant difference in the incidence rate of coronary artery aneurysm between the two groups (P>0.05). In the short fever duration group, compared with the children without drug resistance, the children with drug resistance had a significantly lower level of blood sodium and significantly higher levels of procalcitonin, C-reactive protein, and N-terminal B-type natriuretic peptide before treatment (P<0.05). In the long fever duration group, the children with drug resistance had significantly lower levels of blood sodium and creatine kinase before treatment than those without drug resistance (P<0.05). The multivariate logistic regression analysis showed that a reduction in blood sodium level was associated with IVIG resistance in the long fever duration group (P<0.05).@*CONCLUSIONS@#IVIG resistance in children with KD varies with the duration of fever before treatment. A reduction in blood sodium is associated with IVIG resistance in KD children with a duration of fever of >4 days before treatment.

Pediatric expert consensus on the application of glucocorticoids in Kawasaki disease / 中国当代儿科杂志

Kawasaki disease (KD) is one of the common acquired heart diseases in under-5-year-old children and is an acute self-limiting vasculitis. After nearly 60 years of research, intravenous immunoglobulin combined with oral aspirin has become the first-line treatment for preventing coronary artery aneurysm in the acute stage of KD. However, glucocorticoid (GC), infliximab, and other immunosuppressants are options for the treatment of KD patients with a high risk of coronary artery aneurysm, no response to intravenous immunoglobulin and a confirmed diagnosis of coronary artery aneurysm. At present, there are still controversies over the use of GC in the treatment of KD. With reference to the latest research findings of KD treatment in China and overseas, this consensus invited domestic pediatric experts to fully discuss and put forward recommendations on the indications, dosage, and usage of GC in the first-line and second-line treatment of KD.

Kawasaki-Like Disease, a New Phenotype in Sars-CoV-2?

Abstract The coronavirus disease (COVID-19), that assumed pandemic proportions in March 2020, mainly affects the respiratory tract, causing severe interstitial pneumonia in adults. Worldwide data indicate that COVID-19 tends to be more benign in children, which is evidenced by a high incidence of asymptomatic or mild upper airways' infection cases in this population. However, recent studies have been associating Kawasaki-like symptoms as a nonclassical presentation of coronavirus disease in pediatrics. It is suggested that the intense cytokine cascade, promoted by the SARS-CoV-2 infection, can trigger a multisystem inflammatory response as an atypical Kawasaki form in genetically predisposed individuals. In this context, patients may develop more severe clinical features with a greater predisposition to myocardial involvement, Macrophage Activation Syndrome, and Kawasaki Disease Shock Syndrome. Despite critical conditions, patients usually respond to conventional treatment of Kawasaki Disease with intravenous immunoglobulin. This article intends to provide an approach to the association between Kawasaki-Like Syndrome and COVID-19.

Doença de Kawasaki: Preditores de Resistência à Imunoglobulina Intravenosa e Complicações Cardíacas / Kawasaki Disease: Predictors of Resistance to Intravenous Immunoglobulin and Cardiac Complications

Resumo Fundamento: A doença de Kawasaki (DK) é a principal causa de cardiopatia adquirida em idade pediátrica nos países desenvolvidos. Objetivos: Identificar fatores preditores de resistência à imunoglobulina intravenosa (IGIV), calcular a eficácia dos modelos preditores japoneses e caracterizar as complicações cardíacas. Métodos: Análise retrospectiva dos casos de DK entre janeiro de 2006 e julho de 2018 em um hospital pediátrico português. Foram construídas curvas ROC para encontrar fatores preditores de resistência e utilizada regressão logística multivariada para elaborar o modelo preditor. O nível de significância utilizado foi de 5%. Resultados: Foram incluídos 48 pacientes com mediana de idade de 36 meses. Verificou-se resistência à IGIV em 21%. Ocorreram alterações ecocardiográficas em 46%, com envolvimento coronário em 25%. Como variáveis preditoras de resistência, a proteína C-reativa (PC-R) apresentou uma AUC ROC = 0,789, ponto de corte = 15,1 mg/dL, sensibilidade (S) = 77,8% e especificidade (E) = 78,9%. A velocidade de sedimentação (VS) apresentou uma AUC ROC = 0,781, ponto de corte = 90,5 mm/h, S = 66,7% e E = 85,7%. O modelo com as duas variáveis apresentou valor p = 0,042 e AUC ROC = 0,790. O modelo Kobayashi apresentou S = 63,6% e E = 77,3%; Egami, S = 66,7% e E = 73,1%; e Sano, S = 28,6% e E = 94,1%. Conclusão: A PC-R e a VS são variáveis independentes que mostraram tendência preditora de resistência à IGIV com pontos de corte ótimos de 15,1 mg/dL e 90,5 mm/h, respectivamente. Cerca de metade dos pacientes teve algum tipo de envolvimento cardíaco. Os modelos japoneses não têm utilidade nessa população. (Arq Bras Cardiol. 2021; 116(3):485-491)

Abstract Background: Kawasaki disease (KD) is the leading cause of acquired cardiac disease in children, in developed countries. Objectives: To identify predictive factors for resistance to intravenous immunoglobulin (IVIG), calculate the effectiveness of Japanese predictive models and characterize cardiac complications. Methods: Retrospective analysis of KD cases admitted in a Portuguese paediatric hospital between january 2006 and july 2018. ROC curves were used to determine predictive factors for resistance and the multivariate logistic regression analysis was used to develop the predictive model. A significance level of 5% was used. Results: 48 patients with a median age of 36 months were included. The IVIG resistance was 21%. Echocardiographic anomalies were noted in 46%, with coronary involvement in 25% of the sample population. As predictive variable of resistance, the C-reactive protein (CRP) presented an AUC ROC = 0.789, optimal cut-off value 15.1 mg/dL, sensitivity (Sn) 77.8% and specificity (Sp) 78.9%. The erythrocyte sedimentation rate (ESR) presented an AUC ROC = 0.781, optimal cut-off value 90.5 mm/h, Sn 66.7% and Sp 85.7%. The model with the two variables showed p = 0.042 and AUC ROC = 0.790. Predictive strength of Japanese models were: Kobayashi (Sn 63.6%, Sp 77.3%), Egami (Sn 66.7%, Sp 73.1%), Sano (Sn 28.6%, Sp 94.1%). Conclusion: CRP and ESR are independent variables that were related to IVIG resistance, with optimal cut-off points of 15.1 mg/dL and 90.5 mm/h, respectively. About half of the patients had some form of cardiac involvement. The Japanese models appeared to be inadequate in our population. (Arq Bras Cardiol. 2021; 116(3):485-491)

Diagnostic value of the reaction at the bacillus calmette-guérin vaccination site in kawasaki disease / Utilidade diagnóstica da reação do sítio de vacinação bacillus calmette-guérin na doença de kawasaki

ABSTRACT Objective: To describe the case of an infant - diagnosed with incomplete Kawasaki disease - who developed BCG scar reactivation. Case description: A 6-month-old patient was admitted to hospital with fever associated with ocular hyperemia, cervical lymphadenopathy, and hyperemic lips, and remained hospitalized for 12 days. The physical examination revealed an inflammatory reaction at the site of the BCG scar, leading to the diagnosis of incomplete Kawasaki disease. The patient was treated with venous immunoglobulin, but presented recurrence of Kawasaki disease, with subsequent onset of coronary artery disease. Comments: BCG scar reactivation is an important finding in countries where the vaccine is routinely given and may be a useful marker for early diagnosis of Kawasaki disease, especially in its incomplete form.

RESUMO Objetivo: Descrever o caso de um lactente - com diagnóstico de Doença de Kawasaki incompleta - que desenvolveu reativação da cicatriz da vacina BCG. Descrição do caso: Um paciente de 6 meses de idade foi admitido no hospital com febre, associada à hiperemia ocular, linfadenomegalia cervical e fissuras labiais, permanecendo hospitalizado por 12 dias. Apresentava, no exame físico, reação inflamatória no local da cicatriz da vacina BCG, tendo sido feito o diagnóstico de Kawasaki incompleto. O paciente foi tratado com imunoglobulina venosa, mas apresentou recorrência da doença, com posterior surgimento de coronariopatia. Comentários: A reativação da BCG é um achado importante na doença de Kawasaki em países onde a vacina é aplicada de forma rotineira e pode ser um marcador útil para o diagnóstico precoce da doença de Kawasaki, principalmente em sua forma incompleta.

Resveratrol alleviates Kawasaki disease-induced myocardial injury via inhibition of apoptosis and autophagy / 中南大学学报(医学版)

OBJECTIVES@#To explore the effect of resveratrol (Res) on Kawasaki disease (KD)-induced myocardial injury and to evaluate its effect on apoptosis and autophagy.@*METHODS@#Forty-eight juvenile male Sprague Dawley rats were randomly divided into a control group, a Res group, a lactobacillus casei cell wall extract (LCWE)-induced Kawasaki disease group (KD group), and a LCWE-induced Kawasaki disease + Res treatment group (Res+KD group). The control group was intraperitoneally injected with saline. The Res group was intraperitoneally injected with resveratrol (100 mg/kg). The KD group was intraperitoneally injected with 0.5 mL LCWE (1 mg/mL). The Res+KD group was intraperitoneally injected with 0.5 mL LCWE (1 mg/mL) and resveratrol (100 mg/kg). After 4 weeks, the left ventricular ejection fraction (LVEF) and short axis shortening rate (LVFS) were detected by echocardiography. The apoptotic rate was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) staining. The levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), microtubule-associated protein 1 light chain 3β (LC3B), Beclin-1, autophagy related 5 (Atg5) and sequestosome-1 (p62) were detected by Western blotting. The formation of autophagosome was observed under transmission electron microscope.@*RESULTS@#There was no significant difference in the above-mentioned indexes between the control group and the Res group (all @*CONCLUSIONS@#Res can attenuate the KD-induced myocardial injury via inhibiting the apoptosis and autophagy.

Estudio multicéntrico retrospectivo de los aspectos epidemiológicos, clínicos y terapéuticos de la enfermedad de Kawasaki en niños de Panamá

Resumen Antecedentes: La enfermedad de Kawasaki (EK) representa la principal causa de cardiopatía pediátrica adquirida en muchos países; sin embargo, hay pocos estudios publicados en Latinoamérica. Objetivo: Describir la epidemiología, los aspectos clínicos y el tratamiento de EK en niños en Panamá como parte del estudio de vigilancia de REKAMLATINA-2 en Latinoamérica. Pacientes y Métodos: Estudio retrospectivo, descriptivo, de pacientes internados con diagnóstico de EK, atendidos en tres hospitales pediátricos de Panamá del 1-enero-2009 al 31-diciembre-2013. Resultados: Se analizaron 111 pacientes, 61(54,9%) eran hombres. Todos fueron hospitalizados, siendo la media de hospitalización de 5,8 (4-7) días. La mediana de edad al ingreso fue de 28,9 (12-38) meses. Un 63,9% recibió antimicrobianos recientemente por otros posibles diagnósticos. Recibieron inmunoglobulina intravenosa (IGIV) 105 (94,6%) pacientes; de éstos, 10 (9,5%) fueron resistentes. Un 11,7% tuvo alteraciones cardiovasculares en el ECO inicial, de las cuales las lesiones coronarias se detectaron en 3 (2,9%) pacientes. Conclusiones: Los datos sugieren que EK en Panamá tiene una incidencia cercana a 2,05 x 100,000 bajo 15 años de edad y una frecuencia 2,6 veces mayor bajo 3 años de edad. Se observó un alto porcentaje de uso de antimicrobianos ambulatoriamente antes de la confirmación diagnóstica, lo cual sugiere reconocimiento tardío de EK en Panamá.

Abstract Background: Kawasaki disease (KD) is the leading cause of pediatric acquired heart disease in many countries, however, there are few published studies from Latin America (LA). Aim: To describe the epidemiology, clinical aspects, and treatment of KD in children from Panama as part of the REKAMLATINA-2 in LA. Methods: Retrospective descriptive review of hospitalized patients diagnosed with KD, attended at three main pediatric hospitals of Panama from January-1-2009 to December-31-2013. Results: 111 patients were analyzed, 61(54.9 %) were male. All children were hospitalized, and had a mean length of hospitalization of 5.8 (4-7) days. Median age at admission was 28.9 (12-38) months. Prior to KD final diagnosis, 63.9% patients received antibiotics for other presumed diagnoses. 105 (94.6%) patients received IGIV, 10 (9.5%) were resistant. On initial echocardiogram, 11.7% of cardiovascular complications were reported, of which coronary artery lesions (CALs) were detected in 3 (2.9 %) patients. Conclusion: The data suggest that KD in Panama has an incidence of about 2.05 x 100,000 in children under 15 years of age, and with a frequency 2.6 times higher in children under 3 years. A high rate of antibiotic misuse on outpatient prior to diagnostic confirmation was observed, suggesting KD unawareness and late recognition in Panamá.

Manifestaciones cardiacas en la etapa aguda de la enfermedad de Kawasaki en un hospital pediátrico de tercer nivel en la Ciudad de México / Cardiac manifestations in the acute phase of Kawasaki disease in a third level children's hospital in Mexico City

Resumen Objetivo: Describir las manifestaciones cardiacas en la etapa aguda de la enfermedad de Kawasaki en pacientes atendidos en un hospital de tercer nivel de la Ciudad de México, México. Métodos: Estudio retrospectivo, descriptivo en pacientes con diagnóstico de enfermedad de Kawasaki de agosto de 1995 a diciembre del 2016 en el Instituto Nacional de Pediatría, México. Se estudio la demografía de los pacientes, características clínicas, tratamiento empleado y desarrollo de complicaciones cardiacas en la etapa aguda de la enfermedad. Resultados: Se estudiaron 508 casos de enfermedad de Kawasaki. La edad media al diagnóstico fue de 37.64 ± 35.56 meses. Predominio de pacientes masculinos del 65.4%, con una relación masculino/femenino de 1.88:1. La mayoría de los casos (79.2%) tuvo una presentación completa. La gammaglobulina intravenosa fue administrada en 92.4% de los casos. Veintiocho pacientes (5.5%) desarrollaron arritmias, se presentaron cambios en el segmento ST en 29 pacientes (5.6%) y 5 pacientes desarrollaron isquemia miocárdica. En el ecocardiograma inicial, 51 pacientes (9.9%) presentaron datos de miocarditis, 72 pacien- tes (14%) datos de pericarditis y 77 casos tuvieron derrame pericárdico (15%). Se detectaron alteraciones en las arterias coronarias en 169 casos (32.9%). Cuatro pacientes fallecieron en la etapa aguda de la enfermedad por complicaciones cardiacas de la enfermedad de Kawasaki. Conclusiones: En México cada vez existen más casos de enfermedad de Kawasaki con un alto porcentaje de manifestaciones cardiacas al diagnóstico. Se requiere de un mayor conocimiento de la enfermedad en México, para poder establecer cuál es la evolución cardiológica de los pacientes en el país.

Abstract Objectives: To describe the cardiac manifestations in the acute phase of patients with Kawasaki disease treated in a third level Children's hospital in Mexico City, Mexico. Methods: A cross-sectional study was conducted in patients with a diagnosis of Kawasaki disease treated in this hospital from August 1995 to December 2016. Information included patient demographics, clinical features, treatment used, electrocardiographic findings, extra-coronary echocardiographic findings, and the development of coronary artery aneurysms in the acute phase of the disease. Results: The study included 508 cases of Kawasaki disease, with a mean age at diagnosis of 37.64 ± 35.56 months (range from 2 to 200 months). Almost two-thirds (65.4%) of the patients were male, with a male/female ratio of 1.88:1. Complete Kawasaki disease was diagnosed in 79.2% of cases. Almost all cases (92.4%) received intravenous immunoglobulin. Twenty-eight patients (5.5%) developed arrhythmias, ST changes developed in 29 patients (5.6%), and 5 patients presented with ischaemic changes. In the initial echocardiographic evaluation, 51 patients (9.9%) were diagnosed with myocar- ditis, 72 patients (14.0%) with pericarditis and 77 cases (15.0%) developed pericardial effusion. Coronary artery anomalies were detected in 169 cases (32.9%). 32 cases were diagnosed as giant coronary aneurysms. Four patients died from cardiac complications in the acute phase of the disease. Conclusions: There has been an increase in the diagnosis of Kawasaki disease in Mexico. They presented with more cardiac complications than reported in literature. An increased knowledge of Kawasaki disease is required in Mexico in order to establish the cardiac outcomes of this group of patients.

Clinical Outcomes of Low-Dose Methotrexate Therapy as a Second-Line Drug for Intravenous Immunoglobulin-Resistant Kawasaki Disease

PURPOSE: Intravenous immunoglobulin (IVIG) is the standard treatment for Kawasaki disease (KD). However, there is still no standard treatment for IVIG-resistant KD. This study aimed to evaluate the efficacy of low-dose methotrexate (MTX) as a treatment for IVIG-resistant KD. MATERIALS AND METHODS: We retrospectively analyzed 10-year data for patients with IVIG-resistant KD who were administered MTX at Severance Children's Hospital. RESULTS: The subjects included 75 patients with KD aged 5 months to 9.2 years who had been administered MTX. Their maximum body temperatures decreased significantly within 24 h of therapy. The patients' C-reactive protein levels were significantly lower 1 week after administering the first dose of MTX than those before treatment. No adverse effect for MTX was observed. CONCLUSION: MTX treatment of IVIG-resistant KD resulted in rapid defervescence, improvement of clinical symptoms, and normalization of acute-phase reactants in all patients. Thus, MTX could be a candidate treatment for IVIG-resistant KD.

Caracterización de la enfermedad de Kawasaki en cuatro hospitales privados de Guatemala / Characterization of Kawasaki disease in four private hospitals in Guatemala

Antecedentes: La enfermedad de Kawasaki es una vasculitis sistémica aguda que involucra principalmente vasos de mediano calibre. Se ha convertido en la primera causa de enfermedad cardiaca adquirida en niños. Su frecuencia es mayor en <5 años. No se conoce agente etiológico. En Guatemala no ha sido descrita previamente. Objetivo: Determinar la presentación clínica, diagnóstico, tratamiento y resultados en papeletas de los niños de 0 a 12 años diagnosticados con enfermedad de Kawasaki en Guatemala. Resultados: Durante el período enero 2003 a diciembre 2013 se identificaron 26 casos diagnosticados como enfermedad de Kawasaki en el grupo de estudio. Todos los casos a excepción de 1 fueron en menores de 5 años. Todos los pacientes tenían historia de fiebre, aunque solo 11 la presentaron al ingreso al hospital.

Eficacia y seguridad de la inmunoglobulina intravenosa en el tratamiento inicial de pacientes con enfermedad de kawasaki en la fase aguda / Efficacy and safety of intravenous immunoglobulin in the initial treatment of patients with acute phase kawasaki disease

INTRODUCCÇÃO: Antecedentes: El presente informe expone la evaluación de la inmunoglobulina intravenosa como primera línea de tratamiento de pacientes con diagnóstico de enfermedad de Kawasaki debut y activa con alteraciones de las arterias carótidas. Aspectos Generales: La enfermedad de Kawasaki (EK), previamente conocida como síndrome linfo-mucocutâneo, es una de las vasculitis más comunes de la infancia. Es una condición médica tipicamente auto-limitada, con fiebre y manifestaciones de inflamaciónaguda de una duración promedio de 12 dias sin tratamiento. Tecnología Sanitaria de Interés: La inmunoglobulina es un producto biológico que se deriva del plasma de donantes humanos y es usada en el tratamiento de múltiples condiciones médicas, incluyendo los estados de inmunodeficiencia primaria y secundaria, y una variedad de enfermedades inflamatorias. METODOLOGÍA: Estregia de Búsqueda: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad de la inmunoglobulina intravenosa para el tratamiento de primera línea de los pacientes con enfermedad de Kawasaki activa y anormalidades de las arterias coronarias. Esta búsqueda se realizó utilkizando los meta-buscadores: Translating Research into Practice (TRIPDATABASE), National Lbrary of Medicine (Pubmed-Medline) y Health Systems Evidence. RESULTADOS: Sinopsis de la Evidencia: Se realizó la busqueda bibliográfica y de evidencia científica para el sustento del uso de IGIV como tratamiento de primera línea en pacientes con enfermedad de Kawasakicon anormalidades de las arterias carótidas. CONCLUSIONES: No se identificaron estudios que hayan comparado los efectos del tratamiento con IGIV con los de Aspirina en pacientes con EK en fase aguda. En su lugar, se ha evaluado los efectos de la adición de IGIV a la apirina, en varios ensayos clínicos aleatorizados y controlados; pero la evidencia es insuficientes y no concluyente respecto ao beneficio que ofrece la aspirina al tratamiento con IGIV. El Instituto de Evaluación de Tecnologías Sanitarias -IETSI, aprueba por el periodo de 2 años a partir de la fecha de publicación del presente dictamen preliminar, el uso de IGIV para el tratamiento de pacientes pediátricos con EK en fase aguda con o sin anormalidades de las arterias carótidas, ya que se ha demostrado su eficacia en la reducción de anormalidades de las arterias carótidas y consecuentemente disminución de la morbimortalidad en la fase aguda y a largo plazo.