Adjunctive therapies in Kawasaki disease.
Ontology highlight
ABSTRACT:
SUBMITTER: Tremoulet AH
PROVIDER: S-EPMC5777888 | biostudies-literature | 2018 Jan
REPOSITORIES: biostudies-literature
Publications
Adjunctive therapies in Kawasaki disease.
International journal of rheumatic diseases 20171027 1
Despite the administration of intravenous immunoglobulin (IVIg) at a dose of 2 g/kg, approximately 3-5% of children with acute Kawasaki disease (KD) may develop coronary artery aneurysms. IVIg-resistance, defined as recrudescence of fever more than 36 h after IVIg completion, is a risk factor for coronary artery abnormalities. Thus, several adjunctive therapies are being evaluated for use in IVIg-resistant KD patients and in patients with coronary artery abnormalities. In this review the role of ...[more]
Similar Datasets
Project description:ObjectiveTo determine the safety and pharmacokinetics of etanercept (Amgen, Thousand Oaks, California) a tumor necrosis factor-? receptor blocker, in children with acute Kawasaki disease (KD). Standard therapy of acute KD includes intravenous immunoglobulin (IVIG) and high-dose aspirin, but a substantial number of patients are refractory and require additional treatment. Tumor necrosis factor-? levels are elevated in children with KD, suggesting a role for etanercept in treatment.Study designWe performed a prospective open-label trial of etanercept in patients with KD (age range, 6 months-5 years; n = 17) meeting clinical criteria and with fever ? 10 days. All received IVIG and high-dose aspirin. They received etanercept immediately after IVIG infusion and then weekly two times. For the initial safety evaluation, the first 5 patients received 0.4 mg/kg/dose. Subsequent subjects received 0.8 mg/kg/dose.ResultsFifteen patients completed the study. The pharmacokinetics were similar to that in older children in published series. No serious adverse events related to etanercept occurred. No patient demonstrated prolonged or recrudescent fever requiring re-treatment with IVIG. No patient showed an increase in coronary artery diameter or new coronary artery dilation/cardiac dysfunction.ConclusionEtanercept appears to be safe and well tolerated in children with KD. The data support performance of a placebo-controlled trial.
| S-EPMC2970727 | biostudies-literature
Project description:The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19), is a worldwide pandemic, as declared by the World Health Organization (WHO). It is a respiratory virus that infects people of all ages. Although it may present with mild to no symptoms in most patients, those who are older, immunocompromised, or with multiple comorbidities may present with severe and life-threatening infections. Throughout history, nutraceuticals, such as a variety of phytochemicals from medicinal plants and dietary supplements, have been used as adjunct therapies for many disease conditions, including viral infections. Appropriate use of these adjunct therapies with antiviral proprieties may be beneficial in the treatment and/or prophylaxis of COVID-19. In this review, we provide a comprehensive summary of nutraceuticals, such as vitamins C, D, E, zinc, melatonin, and other phytochemicals and function foods. These nutraceuticals may have potential therapeutic efficacies in fighting the threat of the SARS-CoV-2/COVID-19 pandemic.
| S-EPMC7920448 | biostudies-literature
Project description:Sepsis remains an important challenge in pediatric critical care medicine. This review provides an appraisal of adjunctive therapies for sepsis and highlights opportunities for meeting selected challenges in the field. Future clinical studies should address long-term and functional outcomes as well as acute outcomes. Potential adjunctive therapies such as corticosteroids, hemofiltration, hemoadsorption, and plasmapheresis may have important roles, but still require formal and more rigorous testing by way of clinical trials. Finally, the design of future clinical trials should consider novel approaches for stratifying outcome risks as a means of improving the risk-to-benefit ratio of experimental therapies.
| S-EPMC3612267 | biostudies-literature
Project description:Cerebral malaria (CM) is one of the most severe complications of malaria infection characterized by coma and neurological effects. Despite standardized treatment of malaria infection with artemisinin-based combination therapies (ACT), the mortality rate is still high, and it primarily affects pediatric patients. ACT reduces parasitemia but fails to adequately target the pathogenic mechanisms underlying CM, including blood-brain-barrier (BBB) disruption, endothelial activation/dysfunction, and hyperinflammation. The need for adjunctive therapies to specifically treat this form of severe malaria is critical as hundreds of thousands of people continue to die each year from this disease. Here we present a summary of some potential promising therapeutic targets and treatments for CM, as well as some that have been tested and deemed ineffective or, in some cases, even deleterious. Further exploration into these therapeutic agents is warranted to assess the effectiveness of these potential treatments for CM patients.
| S-EPMC10895034 | biostudies-literature
Project description:A 3-month-old infant was transferred to our facility with persistent fever and concerns for septic shock. A 2-D echocardiogram revealed multiple coronary aneurysms and axillary and coronary artery thrombi, and a diagnosis of incomplete Kawasaki disease (KD) was established. Aggressive therapies including intravenous immunoglobulins, enoxaparin, abciximab, aspirin, and alteplase were used to decrease the size of the coronary aneurysms and inhibit further thrombus formation. After minimal change in the size of coronary aneurysms and in thrombus formation, clopidogrel was added. Approximately 2 weeks after initiation of these therapies, a decrease in the coronary aneurysm size was noted with no signs of thrombus. This case documents successful use of thrombolytic and combination anti-platelet agents (i.e., clopidogrel, abciximab, and aspirin) in an infant with KD and cardiovascular sequelae.
| S-EPMC3461989 | biostudies-other
Project description:Background: Kawasaki disease (KD) is an acute self-limited vasculitis and the leading cause of acquired heart disease in children in developed countries. No etiologic agent(s) has been identified, and the processes that mediate formation of coronary artery aneurysms and abatement of fever following treatment with intravenous immunoglobulin (IVIG) remain poorly understood. Results: In an initial survey, we used DNA microarrays to examine patterns of gene expression in peripheral whole blood from 20 children with KD; each was sampled during the acute, subacute, and convalescent phases of the illness. Acute KD was characterized by increased relative abundance of gene transcripts associated with innate immune and proinflammatory responses and decreased abundance of transcripts associated with natural killer cells and CD8+ lymphocytes. There was significant temporal variation in transcript levels during the acute disease phase and stabilization thereafter. We confirmed these temporal patterns in a second cohort of 64 patients, and identified additional inter-individual differences in transcript abundance. Notably, higher levels of transcripts of the gene for carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) were associated with an increased percentage of unsegmented neutrophils, fewer days of illness, higher levels of C-reactive protein, and subsequent non-response to IVIG; this last association was confirmed by quantitative reverse transcription PCR in a third cohort of 33 patients, and was independent of day of illness. Conclusions: Acute KD is characterized by dynamic and variable gene-expression programs that highlight the importance of neutrophil activation state and apoptosis in KD pathogenesis. Our findings also support the feasibility of extracting biomarkers associated with clinical prognosis from gene-expression profiles of individuals with systemic inflammatory illnesses. Whole blood (PAXgene tubes) was obtained from 64 Kawasaki disease patients prior to treatment. RNA was amplified using the MessageAmp kit (Ambion), and reverse transcribed. Each sample was labelled with Cy5, and hybridized to a Lymphochip cDNA array along with amplified human reference RNA labelled with Cy3(Universal Human Reference RNA, Stratagene). Analysis was restricted to those array elements (LUIDs) with signal intensity/background of at least 2.5 in either channel for at least 80% of the samples, and a regression correlation of 0.6. Patterns of gene expression were correlated with clinical parameters, including subsequent response to treatment with intravenous immunoglobulin (IVIG). A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Phenotype: Patient responded (R) or not (NR) to IVIG therapy. Some patients were not classified because they were treated more than 10 days after onset of fever Keywords: disease_state_design
2007-12-13 | GSE9864 | GEO
Project description:ABSTRACT Background. Acute Kawasaki disease (KD) is difficult to distinguish from other acute rash/fever illnesses, in part because the etiologic agent(s) and pathophysiology remain poorly characterized. As a result, diagnosis and critical therapies may be delayed. Methods. We used DNA microarrays to identify possible diagnostic features of KD. We compared gene expression patterns in the blood of 23 children with acute KD and 18 age-matched febrile children with three illnesses that resemble KD. Results. Genes associated with platelet and neutrophil activation were expressed at higher levels in KD patients than in patients with acute adenovirus infections or systemic adverse drug reactions but not in patients with scarlet fever; genes associated with B cell activation were also expressed at higher levels in KD patients than in controls. A striking absence of interferon-stimulated gene expression in the KD patients was confirmed in an independent cohort of KD subjects. We successfully predicted the diagnosis in 21 of 23 KD patients and 7 of 8 adenovirus patients using a set of 38 gene transcripts. Conclusions. These findings provide insight into the molecular features that distinguish KD from other febrile illnesses, and support the feasibility of developing novel diagnostic reagents for KD based on the host response. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Disease State: One of Kawasaki Disease (KD) or control (C) of Scarlet fever (C-sf), adenovirus infection (C-ai) or drug reaction (C-dr) disease_state_design
2010-06-24 | E-GEOD-15297 | biostudies-arrayexpress
Project description:Background: Kawasaki disease (KD) is an acute self-limited vasculitis and the leading cause of acquired heart disease in children in developed countries. No etiologic agent(s) has been identified, and the processes that mediate formation of coronary artery aneurysms and abatement of fever following treatment with intravenous immunoglobulin (IVIG) remain poorly understood. Results: In an initial survey, we used DNA microarrays to examine patterns of gene expression in peripheral whole blood from 20 children with KD; each was sampled during the acute, subacute, and convalescent phases of the illness. Acute KD was characterized by increased relative abundance of gene transcripts associated with innate immune and proinflammatory responses and decreased abundance of transcripts associated with natural killer cells and CD8+ lymphocytes. There was significant temporal variation in transcript levels during the acute disease phase and stabilization thereafter. We confirmed these temporal patterns in a second cohort of 64 patients, and identified additional inter-individual differences in transcript abundance. Notably, higher levels of transcripts of the gene for carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) were associated with an increased percentage of unsegmented neutrophils, fewer days of illness, higher levels of C-reactive protein, and subsequent non-response to IVIG; this last association was confirmed by quantitative reverse transcription PCR in a third cohort of 33 patients, and was independent of day of illness. Conclusions: Acute KD is characterized by dynamic and variable gene-expression programs that highlight the importance of neutrophil activation state and apoptosis in KD pathogenesis. Our findings also support the feasibility of extracting biomarkers associated with clinical prognosis from gene-expression profiles of individuals with systemic inflammatory illnesses. Whole blood RNA (PAXgene tubes) was collected from 20 Kawasaki patients during the acute, sub-acute (post-IVIG treatment) and convalescent phases of the disease. RNA was amplified using the MessageAmp kit (Ambion), and reverse transcribed. Each sample was labelled with Cy5, and hybridized to a Lymphochip cDNA array along with amplified human reference RNA labelled with Cy3(Universal Human Reference RNA, Stratagene). Analysis was restricted to those array elements (LUIDs) with signal intensity/background of at least 2.5 in either channel for at least 80% of the samples, and a regression correlation of 0.6. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Keywords: disease_state_design
2007-12-13 | GSE9863 | GEO
Project description:Kawasaki disease (KD) is a common febrile multisystemic inflammatory illness in children that preferentially affects coronary arteries. Children with KD who develop coronary artery aneurysms have a life-long risk of premature coronary artery disease. Hypothesis of inherent predisposition to KD is supported by epidemiological evidence that suggests increased risk of development of disease in certain ethnicities and in children with a previous history of KD in siblings or parents. However, occurrence of cases in clusters, seasonal variation, and very low risk of recurrence suggests an acquired trigger (such as infections) for the development of illness. Epigenetic mechanisms that modulate gene expression can plausibly explain the link between genetic and acquired predisposing factors in KD. Analysis of epigenetic factors can also be used to derive biomarkers for diagnosis and prognostication in KD. Moreover, epigenetic mechanisms can also help in pharmacogenomics with the development of targeted therapies. In this review, we analysed the available literature on epigenetic factors such as methylation, micro-RNAs, and long non-coding RNAs in KD and discuss how these mechanisms can help us better understand the disease pathogenesis and advance the development of new biomarkers in KD.
| S-EPMC8266996 | biostudies-literature
Project description:Adjunctive therapies have been proposed for use in at least 5 inflammation pathobiology phenotypes in pediatric sepsis-induced multiple organ failure. This article discusses host-pathogen interaction prototypes to facilitate understanding of the rationale for personalized therapy in these phenotypes. The article discusses the literature on adjunctive antiinflammatory and immune modulation therapies that, in addition to traditional organ support and infection source control, might be part of a personalized precision medicine approach to the reversal of each of these inflammatory pathobiology phenotypes.
| S-EPMC5663307 | biostudies-literature