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1.
Lancet ; 383(9930): 1731-8, 2014 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-24572997

RESUMO

BACKGROUND: Kawasaki disease, the most common cause of acquired heart disease in developed countries, is a self-limited vasculitis that is treated with high doses of intravenous immunoglobulin. Resistance to intravenous immunoglobulin in Kawasaki disease increases the risk of coronary artery aneurysms. We assessed whether the addition of infliximab to standard therapy (intravenous immunoglobulin and aspirin) in acute Kawasaki disease reduces the rate of treatment resistance. METHODS: We undertook a phase 3, randomised, double-blind, placebo-controlled trial in two children's hospitals in the USA to assess the addition of infliximab (5 mg per kg) to standard therapy. Eligible participants were children aged 4 weeks-17 years who had a fever (temperature ≥38·0°C) for 3-10 days and met American Heart Association criteria for Kawasaki disease. Participants were randomly allocated in 1:1 ratio to two treatment groups: infliximab 5 mg/kg at 1 mg/mL intravenously over 2 h or placebo (normal saline 5 mL/kg, administered intravenously). Randomisation was based on a randomly permuted block design (block sizes 2 and 4), stratified by age, sex, and centre. Patients, treating physicians and staff, study team members, and echocardiographers were all masked to treament assignment. The primary outcome was the difference between the groups in treatment resistance defined as a temperature of 38·0°C or higher at 36 h to 7 days after completion of the infusion of intravenous immunoglobulin. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00760435. FINDINGS: 196 patients were enrolled and randomised: 98 to the infliximab group and 98 to placebo. One patient in the placebo group was withdrawn from the study because of hypotension before receiving treatment. Treatment resistance rate did not differ significantly (11 [11·2%] for infliximab and 11 [11·3%] for placebo; p=0·81). Compared with the placebo group, participants given infliximab had fewer days of fever (median 1 day for infliximab vs 2 days for placebo; p<0·0001). At week 2, infliximab-treated patients had greater mean reductions in erythrocyte sedimentation rate (p=0·009) and a two-fold greater decrease in Z score of the left anterior descending artery (p=0·045) than did those in the placebo group, but this difference was not significant at week 5. Participants in the infliximab group had a greater mean reduction in C-reactive protein concentration (p=0·0003) and in absolute neutrophil count (p=0·024) at 24 h after treatment than did those given placebo, but by week 2 this difference was not significant. At week 5, none of the laboratory values differed significantly compared with baseline. No significant differences were recorded between the two groups at any timepoint in proximal right coronary artery Z scores, age-adjusted haemoglobin values, duration of hospital stay, or any other laboratory markers of inflammation measured. No reactions to intravenous immunoglobulin infusion occurred in patients treated with infliximab compared with 13 (13·4%) patients given placebo (p<0·0001). No serious adverse events were directly attributable to infliximab infusion. INTERPRETATION: The addition of infliximab to primary treatment in acute Kawasaki disease did not reduce treatment resistance. However, it was safe and well tolerated and reduced fever duration, some markers of inflammation, left anterior descending coronary artery Z score, and intravenous immunoglobulin reaction rates. FUNDING: US Food and Drug Administration, Robert Wood Johnson Foundation, and Janssen Biotech.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Doença Aguda , Adolescente , Anti-Inflamatórios não Esteroides/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Aspirina/uso terapêutico , Criança , Pré-Escolar , Vasos Coronários/patologia , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Infliximab , Masculino , Síndrome de Linfonodos Mucocutâneos/patologia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores
2.
JACC Case Rep ; 26: 102077, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-38094174

RESUMO

The hypercoagulable state in Kawasaki disease (KD) may lead to complex cardiovascular sequelae. We present the case of a 2-month-old infant with complete KD complicated by giant coronary artery aneurysms, coronary sinus thrombosis, and post-myocardial infarction syndrome (Dressler syndrome), resulting in 2 distinct episodes of pericardial effusion. (Level of Difficulty: Intermediate.).

3.
Lancet Child Adolesc Health ; 7(10): 697-707, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37598693

RESUMO

BACKGROUND: Although Kawasaki disease is commonly regarded as a single disease entity, variability in clinical manifestations and disease outcome has been recognised. We aimed to use a data-driven approach to identify clinical subgroups. METHODS: We analysed clinical data from patients with Kawasaki disease diagnosed at Rady Children's Hospital (San Diego, CA, USA) between Jan 1, 2002, and June 30, 2022. Patients were grouped by hierarchical clustering on principal components with k-means parcellation based on 14 variables, including age at onset, ten laboratory test results, day of illness at the first intravenous immunoglobulin infusion, and normalised echocardiographic measures of coronary artery diameters at diagnosis. We also analysed the seasonality and Kawasaki disease incidence from 2002 to 2019 by subgroup. To explore the biological underpinnings of identified subgroups, we did differential abundance analysis on proteomic data of 6481 proteins from 32 patients with Kawasaki disease and 24 healthy children, using linear regression models that controlled for age and sex. FINDINGS: Among 1016 patients with complete data in the final analysis, four subgroups were identified with distinct clinical features: (1) hepatobiliary involvement with elevated alanine transaminase, gamma-glutamyl transferase, and total bilirubin levels, lowest coronary artery aneurysm but highest intravenous immunoglobulin resistance rates (n=157); (2) highest band neutrophil count and Kawasaki disease shock rate (n=231); (3) cervical lymphadenopathy with high markers of inflammation (erythrocyte sedimentation rate, C-reactive protein, white blood cell, and platelet counts) and lowest age-adjusted haemoglobin Z scores (n=315); and (4) young age at onset with highest coronary artery aneurysm but lowest intravenous immunoglobulin resistance rates (n=313). The subgroups had distinct seasonal and incidence trajectories. In addition, the subgroups shared 211 differential abundance proteins while many proteins were unique to a subgroup. INTERPRETATION: Our data-driven analysis provides insight into the heterogeneity of Kawasaki disease, and supports the existence of distinct subgroups with important implications for clinical management and research design and interpretation. FUNDING: US National Institutes of Health and the Irving and Francine Suknow Foundation.


Assuntos
Aneurisma , Síndrome de Linfonodos Mucocutâneos , Estados Unidos , Humanos , Criança , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Imunoglobulinas Intravenosas/uso terapêutico , Proteômica , Análise por Conglomerados , Aneurisma/tratamento farmacológico
4.
Pediatr Infect Dis J ; 35(1): 50-3, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26398742

RESUMO

BACKGROUND: Important therapeutic decisions are made based on the presence or absence of fever in patients with Kawasaki disease (KD), yet no standard method or threshold exists for temperature measurement during the diagnosis and treatment of these patients. We sought to compare surface and internal (rectal or oral) routes of temperature measurement for the detection of fever as a marker of treatment resistance. METHODS: From a randomized, placebo-controlled trial of infliximab as an adjunct to primary intravenous immunoglobulin treatment for acute KD, we collected concurrent (within 5 minutes) axillary and internal temperature measurements and performed receiver-operating characteristic and Bland-Altman analyses. We also determined the ability of surface temperatures to detect treatment resistance defined by internal temperature measurements. RESULTS: Among 452 oral-axillary and 439 rectal-axillary pairs from 159 patients, mean axillary temperatures were 0.25 and 0.43 °C lower than oral and rectal temperatures and had high receiver-operating characteristic areas under curves. However, axillary temperatures ≥ 38.0 °C had limited sensitivity to detect fever defined by internal temperatures. Axillary thresholds of 37.5 and 37.2 °C provided maximal sensitivity and specificity to detect oral and rectal temperatures ≥ 38.0 °C, respectively. CONCLUSIONS: Axillary temperatures are an insensitive metric for fevers defining treatment resistance. Clinical trials should adopt temperature measurement by the oral or rectal routes for adjudication of treatment resistance in KD.


Assuntos
Axila , Temperatura Corporal , Boca , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Reto , Doença Aguda , Adolescente , Criança , Pré-Escolar , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Infliximab/uso terapêutico , Masculino , Síndrome de Linfonodos Mucocutâneos/terapia , Curva ROC , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Resultado do Tratamento
5.
Pediatrics ; 125(2): e234-41, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20100771

RESUMO

OBJECTIVE: The 2004 American Heart Association (AHA) statement included a clinical case definition and an algorithm for diagnosing and treating suspected incomplete Kawasaki disease (KD). We explored the performance of these recommendations in a multicenter series of US patients with KD with coronary artery aneurysms (CAAs). METHODS: We reviewed retrospectively records of patients with KD with CAAs at 4 US centers from 1981 to 2006. CAAs were defined on the basis of z scores of >3 or Japanese Ministry of Health and Welfare criteria. Our primary outcome was the proportion of patients presenting at illness day < or =21 who would have received intravenous immunoglobulin (IVIG) treatment by following the AHA guidelines at the time of their initial presentation to the clinical center. RESULTS: Of 195 patients who met entry criteria, 137 (70%) met the case definition and would have received IVIG treatment at presentation. Fifty-three patients (27%) had suspected incomplete KD and were eligible for algorithm application; all would have received IVIG treatment at presentation. Of the remaining 5 patients, 3 were excluded from the algorithm because of fever for <5 days at presentation and 2 because of <2 clinical criteria at >6 months of age. Two of these 5 patients would have entered the algorithm and received IVIG treatment after follow-up monitoring. Overall, application of the AHA algorithm would have referred > or =190 patients (97%) for IVIG treatment. CONCLUSIONS: Application of the 2004 AHA recommendations, compared with the classic criteria alone, improves the rate of IVIG treatment for patients with KD who develop CAAs. Future multicenter prospective studies are needed to assess the performance characteristics of the AHA algorithm in febrile children with incomplete criterion findings and to refine the algorithm further.


Assuntos
Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/terapia , Adolescente , Algoritmos , Criança , Pré-Escolar , Aneurisma Coronário/etiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações , Guias de Prática Clínica como Assunto , Adulto Jovem
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