Research advances on risk factors of coronary artery lesion in Kawasaki disease / 中国小儿急救医学

Kawasaki disease is an acute febrile rash disease with systemic vasculitis as the main lesion, which can lead to coronary artery lesion(CAL)in some children.Early diagnosis of Kawasaki disease can effectively prevent CAL.Previous studies on the risk factors of CAL in Kawasaki disease focused on leukocyte, neutrophil percentage, erythrocyte sedimentation rate, C-reactive protein, serum albumin, etc.In recent years, many new biomarkers have been found.This review summarized the newly studied risk factors, aiming to provide reference for timely treatment of Kawasaki disease and prevention of CAL.

Analysis of risk factors for duration of small or medium-sized coronary artery aneurysms in children with Kawasaki disease / 中华实用儿科临床杂志

Objective:To analyze risk factors for duration of small or medium-sized coronary artery aneurysms (CAA) in children with Kawasaki disease (KD) so as to provide clinical guidance for early and full course treatment.Methods:The clinical data of 68 children diagnosed with KD in the Department of Pediatrics, the First Affiliated Hospital of Xinxiang Medical University from January 2018 to January 2021 were retrospectively analyzed.According to duration of CAA, all cases were divided into 2 groups, duration of CAA ≥ 8 weeks group and duration of CAA <8 weeks group.Risk factors associated with CAA duration were screened using univariate analysis, and then independent risk factors for CAA duration in children with KD were analysed using multiple Logistic regression analysis. Results:A total of 68 cases were enrolled in this study.Among these cases, 45 cases (66.18%) were male and 23 cases (33.82%) were female.The onset age was from 3 months to 10 years old, and the median onset age was 1.59 (1.02-3.19). There were 31 cases in the group with CAA duration ≥8 weeks and 37 cases in the group with CAA duration <8 weeks.Univariate analysis showed that patients with the total fever course >10 days[45.16%(14/31 cases) vs.21.62%(8/37 cases)], time of treatment with intravenous immunoglobulin (IVIG)>10 days[54.84%(17/31 cases) vs.16.22%(6/37 cases)], platelet (PLT)>600×10 9/L[32.26%(10/31 cases) vs.10.81%(4/37 cases)], hypersensitive C-reactive protein (HsCRP) >100 mg/L[38.71%(12/31 cases) vs.13.51%(5/37 cases)] (all P<0.05 ) in the group with CAA duration ≥8 weeks were significantly more than those in the group with CAA duration <8 weeks.However, there were no significant differences in gender, age, type of KD, etiology evidence, hormone application, duration of fever before IVIG application, IVIG sensitivity, IVIG application way, urine leukocytes, white blood cells, hemoglobin, percent of neutrophilic granulocyte, erythrocyte sedimentation rate, glutamic-pyruvic transaminase between the 2 groups (all P>0.05). Multivariate Logistic regression analysis showed that the course of IVIG before application >10 days ( OR=6.589, 95% CI: 1.678-25.867, P=0.007)and HsCRP >100 mg/L ( OR=7.949, 95% CI: 1.947-32.461, P=0.004)were independent risk factors for predicting the duration of KD complicated with small and medium-sized CAA ≥8 weeks. Conclusions:The course of IVIG before application >10 days and HsCRP>100 mg/L are independent risk factors for KD complicated with small and medium-sized CAA lasting ≥8 weeks.

Aneurisma gigante de la arteria coronaria derecha, reporte de un caso y revisión de la literatura / Giant aneurysm of the right coronary artery, report of a case and review of the literature

Resumen Los aneurismas de las arterias coronarias se definen como una dilatación localizada que excede el diámetro normal en 1.5 veces. Esta es una condición poco frecuente, su incidencia varía del 0.3 hasta el 5.3% de las angiografías coronarias. Los aneurismas que exceden cuatro veces el diámetro del vaso normal se consideran gigantes. Estos son aún más raros y se presentan en el 0.02 a 0.2% de todos los casos. Existe controversia en cuanto a su fisiopatología, sin embargo, hasta el 50% de los casos se relacionan con la aterosclerosis. Se diagnostican más frecuentemente entre la sexta y séptima décadas de vida. Las principales manifestaciones clínicas están relacionadas con la cardiopatía isquémica. Respecto a su tratamiento, no existe un consenso del manejo en los pacientes adultos, las opciones son: médico, quirúrgico o intervencionismo. Reportamos la presencia de un aneurisma gigante de la coronaria derecha y ectasia gigante del sistema izquierdo con trombosis activa en un hombre con antecedentes de un aneurisma en la aorta abdominal, tratado por vía endovascular, e infarto agudo al miocardio sin elevación del segmento ST no reperfundido. Requirió de estudio de angiotomografía coronaria, el cual permitió la identificación de las características anatómicas de esta enfermedad.

Abstract Coronary artery aneurysms are described as a localized dilatation that exceeds the normal diameter by 1.5 times. This is a rare condition; its incidence varies from 0.3% up to 5.3% of all coronary angiographies. Those aneurysms that exceed 4 times the diameter of a normal artery are considered giant aneurysms, which are even more uncommon, presenting between 0.02% and 0.2% of all cases. There is controversy regarding its pathophysiology, however, up to 50% of the cases are related to atherosclerosis. They are diagnosed more frequently between the sixth and seventh decade of life. The main clinical manifestations are related to ischemic heart disease. Regarding their treatment, there is no general consensus towards its management in adult patients. The options are medical, surgical or percutaneous treatment. We report the presence of a giant aneurysm of the right coronary artery and giant ectasia of the left coronary system with active thrombosis in a man with history of an abdominal aortic aneurysm, with endovascular treatment and a non-ST segment elevation myocardial infarction with no reperfusion strategy, who required a coronary computed tomography, identifying the anatomical characteristics of this disease.

Analysis on high risk factors for early coronary artery aneurysms early complicated with Kawasaki disease in inpatients by single-center analysis for 6 years / 中华实用儿科临床杂志

Objective@#To investigate the high risk factors for early coronary artery aneurysms(CAA)early complicated with Kawasaki disease (KD) in inpatient children.@*Methods@#Totally 679 inpatient children with KD from January 2005 to December 2011 in Children′s Hospital of Chongqing Medical University were enrolled in this study.These data were analyzed by Chi-square test to analyze the possible risk factors for CAA.Multiple Logistic regression analysis was performed to estimate the OR and 95%CI for the risk factors.@*Results@#There were 385(56.70%) male and 294(43.30%) female cases with the onset ages of 2 months to 15 years and 7 months.There were 32 cases (4.71%) of CAA, among them, 8 cases resistant to intravenous immunoglobulin (IVIG). In total 32 cases of CAA, 25 cases were treated with 2 g/(kg·time) IVIG for 1 to 3 times, and 2 cases were also treated by methylprednisolone.The other 7 cases of CAA were treated with IVIG less than or equal to 1 g/(kg·time) for 4 to 7 times.There were 6 recu-rrent KD cases (0.88%), occurred on the 2nd-18th month after the onset of the illness, including 1 case complicated with CAA.There was no death case during the acute stage.The monofactor analysis showed that male, duration of fever ≥ 10 d, time of treatment with IVIG ≥7 d, hemoglobin < 100 g/L, erythrocyte sedimentation rate ≥100 mm/1 h, serum albumin < 30 g/L were associated with early complicated CAA(all P<0.05). However, the age, white blood cells, platelets, C-reactive protein were not associated with early complicated CAA(all P>0.05). The multiple Logistic regression analysis showed that hemoglobin <100 g/L (OR=2.99, 95%CI: 1.01-8.75, P=0.04), duration of fever ≥ 10 d (OR=6.67, 95%CI: 1.57-22.54, P=0.01), time of treatment with IVIG ≥7 d(OR=3.57, 95%CI: 1.12-11.02, P=0.02) were the independent risk factors for CAA.@*Conclusions@#The levels of hemoglobin<100 g/L, duration of fever ≥ 10 d and time of treatment of IVIG ≥7 d are the independent risk factors for CAA.

Analysis on high risk factors for early coronary artery aneurysms early complicated with Kawasaki disease in inpatients by single-center analysis for 6 years / 中华实用儿科临床杂志

Objective To investigate the high risk factors for early coronary artery aneurysms (CAA)early complicated with Kawasaki disease (KD) in inpatient children.Methods Totally 679 inpatient children with KD from January 2005 to December 2011 in Children's Hospital of Chongqing Medical University were enrolled in this study.These data were analyzed by Chi-square test to analyze the possible risk factors for CAA.Multiple Logistic regression analysis was performed to estimate the OR and 95％ CI for the risk factors.Results There were 385 (56.70％) male and 294(43.30％) female cases with the onset ages of 2 months to 15 years and 7 months.There were 32 cases (4.71％) of CAA,among them,8 cases resistant to intravenous immunoglobulin (IVIG).In total 32 cases of CAA,25 cases were treated with 2 g/(kg · time) IVIG for 1 to 3 times,and 2 cases were also treated by methylprednisolone.The other 7 cases of CAA were treated with IVIG less than or equal to 1 g/(kg · time) for 4 to 7 times.There were 6 recurrent KD cases (0.88％),occurred on the 2nd-18th month after the onset of the illness,including 1 case complicated with CAA.There was no death case during the acute stage.The monofactor analysis showed that male,duration of fever ≥ 10 d,time of treatment with IVIG ≥7 d,hemoglobin＜ 100 g/L,erythrocyte sedimentation rate ≥ 100 mm/1 h,serum albumin ＜ 30 g/L were associated with early complicated CAA (all P ＜ 0.05).However,the age,white blood cells,platelets,C-reactive protein were not associated with early complicated CAA (all P ＞ 0.05).The multiple Logistic regression analysis showed that hemoglobin ＜ 100 g/L (OR =2.99,95％ CI:1.01-8.75,P =0.04),duration of fever ≥ 10 d (OR =6.67,95 ％ CI:1.57-22.54,P =0.01),time of treatment with IVIG ≥ 7 d (OR =3.57,95 ％ CI:1.12-11.02,P =0.02) were the independent risk factors for CAA.Conclusions The levels of hemoglobin ＜100 g/L,duration of fever ≥ 10 d and time of treatment of IVIG ≥7 d are the independent risk factors for CAA.

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 characteristics and therapy of Kawasaki disease with giant coronary artery and thrombosis / 中华实用儿科临床杂志

Objective To summarize the clinical characteristics of children with coronary artery aneurysms (CAA) and thrombosis in Kawasaki disease (KD),in order to explore the safe and effective thrombolytic therapy and its prognosis.Methods The clinic,treatment and follow-up data of 210 patients with KD between January 2006 and December 2016 were retrospectively reviewed in the Department of Pediatrics,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology.The clinic signs and laboratory data for CAA with thrombosis were analyzed.The characteristics of CAA were monitored by tltrasound.All KD patients with thrombus received intravenous antithrombotic therapy,including urokinase,heparin,and oral Warfarin,and anti-platelet treatment.The effectiveness of antithrombotic treatment was evaluated by measuring the ability to dissolve the thrombus.Results Fourteen cases in 210 patients with KD developed CAA,and had associated thrombosis.In these 14 patients,the largest diameter of CAA was 18.5 mm,and the average value was 12.6 mm.There was no special blood analysis in CAA with thrombus.Moreover,typical KD symptoms and acute myocardial infarction were not found in CAA with thrombosis.Thrombus occurred in giant aneurysms,and 2 patients had multiple thrombosis.After thrombolytic therapy,12 cases in the 14 patients had successful thrombolysis,2 patients had thrombus organization and coronary artery stenosis.Conclusions Neither clinical features nor laboratory data could reliably predict CAA associated thrombosis.Thrombus was easily formed in giant CAA.Frequent and periodly follow-up are important to detect thrombosis in KD patients with giant coronary artery.Therapy with adequate intravenous antithrombotic therapy and anti-platelet treatment earlier can effectively dissolve thrombus in KD patients,and avoid deterioration.

Immunopathogenesis of Kawasaki Disease

Kawasaki disease (KD) is an acute, self-limiting, small-vessel vasculitis with an unknown cause that affects children between the ages of 6 months and 5 years. It is the most common cause of acquired coronary artery disease in childhood. Acute myocardial infarction and coronary artery aneurysm are major complications. Although an infectious agent is highly suspected, the etiology of KD is unknown. Significant progress has been, however, toward understanding the natural history of this disease, and therapeutic interventions have been developed that halt the immune-mediated destruction of the vascular system. The pathology of the necrotizing vaculitis of KD suggests a primary role for monocytes-macrophages and T lymphocytes in the acute vascular injury observed. KD fits nicely in the spectrum between an infectious disease and a true autoimmune disease, with an infectious trigger leading to a prolonged self-directed immune response. This review focuses on recent data concerning the immunopathogenesis of vascular damage, and the involvement of CD4+CD25+ regulatory T cells (Treg) in KD.