RESUMO
BACKGROUND: There is still no definite treatment for refractory Kawasaki disease (KD). In this pilot study, we evaluated the safety and efficacy of a new protocol consisting of sivelestat sodium hydrate (SSH) combined with additional i.v. immunoglobulin (IVIG) for KD resistant to initial IVIG therapy. METHODS: This study is a prospective non-randomized, open-label and single-arm study undertaken in a population of refractory KD patients at Chiba University Hospital from December 2006 to March 2016. The subjects had KD resistant to initial IVIG (2 g/kg) and received SSH (0.2 mg/kg/h for 5 days) combined with additional IVIG (2 g/kg) as a second-line therapy. We evaluated the safety and efficacy of the treatment during the study period. RESULTS: Forty-six KD patients were enrolled in this study and no serious adverse event was noted. Of these, 45 patients were evaluated for the incidence of coronary artery lesions, which occurred in one patient (2.2%; 95% CI: 0.5-15.2). Twenty-eight (62.2%) responded promptly and were afebrile after the therapy. The median total duration of fever was 8 days (range, 6-28 days). CONCLUSIONS: Additional IVIG combined with SSH as a second-line therapy for KD refractory to initial IVIG therapy was safe and well tolerated and could be a promising option for severe KD. Further investigations are expected to clarify the safety and timing of SSH treatment for KD.
Assuntos
Glicina/análogos & derivados , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Inibidores de Serina Proteinase/uso terapêutico , Sulfonamidas/uso terapêutico , Adolescente , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Glicina/uso terapêutico , Humanos , Lactente , Masculino , Projetos Piloto , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Altered regulatory immune responses to microbial stimuli and intestinal colonization of beneficial bacteria early in life may contribute to the development of allergic diseases (e.g., atopic dermatitis [AD]). However, few reports have investigated these factors simultaneously. The purpose of this study was to analyze neonatal immune responses to microbial stimuli as well as intestinal colonization of beneficial bacteria, in relation to the development of AD in a birth cohort. METHODS: Pregnant women were recruited, and their infants were followed up until 7 months of age. Levels of interleukin (IL)-10 released from cord-blood mononuclear cells (CBMCs) stimulated with heat-killed gram-positive bacteria (Bifidobacterium bifidum and Lactobacillus rhamnosus GG) and Lactobacillus-derived peptidoglycan were measured. Fecal Bifidobacterium counts at 4 days and 1 month were quantified using real-time polymerase chain reaction. The development of AD was determined by means of a questionnaire at 7 months of age. RESULTS: The levels of released IL-10 were significantly lower in infants with AD (n = 17) than in infants without AD (n = 53) for all stimuli. In infants with fecal Bifidobacterium, the incidence of AD was inversely associated with the release of IL-10 from cord blood mononuclear cells. CONCLUSION: Our findings suggest that impaired IL-10 production in response to microbial stimuli at birth may be associated with an increased risk of developing infantile AD, even in infants with early colonization of intestinal bifidobacteria.
Assuntos
Infecções por Bifidobacteriales/imunologia , Bifidobacterium/fisiologia , Dermatite Atópica/imunologia , Sangue Fetal/fisiologia , Leucócitos Mononucleares/imunologia , Células Cultivadas , Estudos de Coortes , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Interleucina-10/metabolismo , Masculino , Mães , Gravidez , Estudos Prospectivos , Fatores de RiscoRESUMO
The Japanese Guideline for the Diagnosis and Treatment of Allergic Diseases 2017 (JAGL 2017) includes a minor revision of the Japanese Pediatric Guideline for the Treatment and Management of Asthma 2012 (JPGL 2012) by the Japanese Society of Pediatric Allergy and Clinical Immunology. The section on child asthma in JAGL 2017 provides information on how to diagnose asthma between infancy and adolescence (0-15 years of age). It makes recommendations for best practices in the management of childhood asthma, including management of acute exacerbations and non-pharmacological and pharmacological management. This guideline will be of interest to non-specialist physicians involved in the care of children with asthma. JAGL differs from the Global Initiative for Asthma Guideline in that JAGL emphasizes diagnosis and early intervention of children with asthma at <2 years or 2-5 years of age. The first choice of treatment depends on the severity and frequency of symptoms. Pharmacological management, including step-up or step-down of drugs used for long-term management based on the status of asthma control levels, is easy to understand; thus, this guideline is suitable for the routine medical care of children with asthma. JAGL also recommends using a control test in children, so that the physician aims for complete control by avoiding exacerbating factors and appropriately using anti-inflammatory drugs (for example, inhaled corticosteroids and leukotriene receptor antagonists).
Assuntos
Asma/diagnóstico , Asma/terapia , Guias de Prática Clínica como Assunto , Fatores Etários , Antiasmáticos/administração & dosagem , Antiasmáticos/uso terapêutico , Asma/epidemiologia , Asma/etiologia , Criança , Diagnóstico Diferencial , Gerenciamento Clínico , Progressão da Doença , Humanos , Japão , Mortalidade , Educação de Pacientes como Assunto , Fenótipo , Prevalência , Prognóstico , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
Cutaneous polyarteritis nodosa (cutaneous PAN) is a form of necrotizing vasculitis of small- and medium-sized arteries, primarily involving the skin. In juvenile cases, cutaneous PAN is known to be frequently associated with Group A ß-hemolytic Streptococcus (GAS) infections. We herein describe the first reported juvenile case of GAS-associated recurrent cutaneous PAN successfully improved with tonsillectomy. To avoid the use of steroids and immunosuppressive drugs, especially in juvenile cases, tonsillectomy is a possible treatment for GAS-associated recurrent cutaneous PAN.
Assuntos
Poliarterite Nodosa/cirurgia , Infecções Estreptocócicas/cirurgia , Tonsilectomia , Pré-Escolar , Feminino , Humanos , Poliarterite Nodosa/complicações , Infecções Estreptocócicas/complicações , Streptococcus , Resultado do TratamentoRESUMO
The consumption of probiotics by pregnant and lactating women may prevent the onset of allergic disorders in their children by increasing the concentrations of immunoactive agents such as cytokines in breast milk. Prebiotics such as fructo-oligosaccharides (FOS) increase the number of beneficial organisms such as bifidobacteria. Thus, prebiotics may have an effect similar to that of probiotics. The objective of the present study was to carry out a comprehensive analysis of mRNA expression in human milk cells to identify changes in the concentrations of cytokines in breast milk after the consumption of FOS (4 g × 2 times/d) by pregnant and lactating women. The microarray analysis of human milk cells demonstrated that the expression levels of five genes in colostrum samples and fourteen genes in 1-month breast milk samples differed more than 3-fold between the FOS and control groups (sucrose group). The mRNA expression level of IL-27, a cytokine associated with immunoregulatory function, was significantly higher in 1-month breast milk samples obtained from the FOS group than in those obtained from the control group. In addition, the protein concentrations of IL-27 in colostrum and 1-month breast milk samples were significantly higher in the FOS group than in the control group. In conclusion, the consumption of FOS by pregnant and lactating women increases the production of IL-27 in breast milk. Future studies will address the association of this phenomenon with the onset of allergic disorders in children.
Assuntos
Interleucina-27/metabolismo , Lactação/metabolismo , Leite Humano/metabolismo , Oligossacarídeos/farmacologia , Prebióticos , Gravidez/efeitos dos fármacos , Adulto , Método Duplo-Cego , Feminino , Humanos , Lactação/imunologia , Leite Humano/imunologia , Oligossacarídeos/imunologia , Gravidez/imunologia , Gravidez/metabolismo , RNA Mensageiro/metabolismoRESUMO
No studies showed specific antibody levels against all serotypes covered by 13-valent pneumococcal conjugate vaccine (PCV13) among polyclonal intravenous immunoglobulin (IVIG) products. Our study aimed to assess whether we could expect the efficacy of IVIG therapy for invasive pneumococcal disease (IPD) and to clarify the age group which should be recommended for IVIG therapy in case of IPD. Serotype-specific immunoglobulin G (IgG) levels against PCV13 serotypes were measured in four IVIGs which were produced from Japanese donors who were not immunized with any pneumococcal conjugate vaccines (PCVs), and in the serum of 160 non-PCV immunized Japanese subjects, by enzyme-linked immunosorbent assay. The functional opsonic activities of the IVIGs against serotypes 6B and 19A were assessed by a multiplexed opsonophagocytic killing assay. Japanese infants aged <2 years had a geometric mean IgG concentration of <0.35 µg/ml against several serotypes. Serotype-specific IgG concentrations varied among IVIGs. In general, IgG antibodies against serotypes 6A, 14 and 19A were higher in each IVIG. Although opsonization indices also varied among preparations, each IVIG had the ability to opsonize both serotypes 6B and 19A. This study suggests that routine immunization with PCV is important for prevention of IPD, especially for children <2 years old and IVIGs might be effective for IPD patients.
Assuntos
Anticorpos Antibacterianos/sangue , Imunoglobulina G/sangue , Imunoglobulinas Intravenosas/imunologia , Vacinas Pneumocócicas/imunologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Japão/epidemiologia , Vacinas Pneumocócicas/administração & dosagem , Estudos Soroepidemiológicos , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/imunologia , Adulto JovemRESUMO
The 7-valent pneumococcal conjugate vaccine (PCV7) and Haemophilus influenzae type b (Hib) vaccine reduce nasopharyngeal carriage of vaccine-type bacteria, which may in turn influence the presence of other nasopharyngeal bacterial pathogens. To investigate this possibility, nasopharyngeal carriage of potential pathogens was examined before and after official financial support was provided to offer the PCV7 and Hib vaccines in healthy children attending a day care centre in Japan during 2011-2012. Despite a virtual disappearance of PCV7 serotypes over time, the overall pneumococcal carriage rate remained unchanged. Although others have reported an increase in PCV13 serotypes following PCV7 vaccination, only non-PCV13 serotypes were observed to have increased in this study. The majority of H. influenzae isolates were non-typeable and Hib was not found. Our data identified an unexpected pattern of pneumococcal serotype replacement following PCV7. Continuous monitoring of pneumococcal carriage is important for decisions regarding the future of national vaccination policy in Japan.
Assuntos
Portador Sadio/microbiologia , Vacinas Anti-Haemophilus/administração & dosagem , Haemophilus influenzae/isolamento & purificação , Nasofaringe/microbiologia , Vacinas Pneumocócicas/administração & dosagem , Streptococcus pneumoniae/isolamento & purificação , Portador Sadio/epidemiologia , Criança , Creches , Pré-Escolar , Feminino , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Vacinas Anti-Haemophilus/economia , Vacina Pneumocócica Conjugada Heptavalente , Humanos , Lactente , Japão/epidemiologia , Masculino , Moraxella catarrhalis/isolamento & purificação , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/microbiologia , Vacinas Pneumocócicas/economiaRESUMO
Human herpesvirus 6 (HHV-6) is the only virus known to integrate into human chromosomes and be transmitted from parents to offspring. Less than 1% of the population carries integrated HHV-6 in their genomes. Here, we report the case of a 9-year-old Japanese girl with an extraordinarily high copy number of HHV-6B in her genome. The integrated virus genome was detected by real-time polymerase chain reaction (PCR) in cerebrospinal fluid and serum during the treatment of meningoencephalitis and pneumonia caused by Mycoplasma pneumoniae infection. Furthermore, the HHV-6B genome was detected in hair follicle, plasma, and whole blood in the patient and her mother, but not in the patient's father. Fluorescence in situ hybridization revealed that the viral genome was integrated into chromosome 22. Therefore, these results emphasize the importance of screening for chromosomally integrated HHV-6 prior to starting unnecessary antiviral therapies, particularly for patients harboring HHV-6 with a high copy number.
Assuntos
Cromossomos Humanos/genética , Cromossomos Humanos/virologia , Herpesvirus Humano 6/genética , Infecções por Mycoplasma/virologia , Integração Viral/genética , Criança , Feminino , Humanos , Imunocompetência , Transmissão Vertical de Doenças Infecciosas , Mycoplasma pneumoniaeRESUMO
Asthma is a complex phenotype influenced by genetic and environmental factors. We conducted a genome-wide association study (GWAS) with 938 Japanese pediatric asthma patients and 2,376 controls. Single-nucleotide polymorphisms (SNPs) showing strong associations (P<1×10(-8)) in GWAS were further genotyped in an independent Japanese samples (818 cases and 1,032 controls) and in Korean samples (835 cases and 421 controls). SNP rs987870, located between HLA-DPA1 and HLA-DPB1, was consistently associated with pediatric asthma in 3 independent populations (P(combined)â=â2.3×10(-10), odds ratio [OR]â=â1.40). HLA-DP allele analysis showed that DPA1*0201 and DPB1*0901, which were in strong linkage disequilibrium, were strongly associated with pediatric asthma (DPA1*0201: Pâ=â5.5×10(-10), ORâ=â1.52, and DPB1*0901: Pâ=â2.0×10(-7), ORâ=â1.49). Our findings show that genetic variants in the HLA-DP locus are associated with the risk of pediatric asthma in Asian populations.
Assuntos
Povo Asiático/genética , Asma/genética , Predisposição Genética para Doença/genética , Antígenos HLA-DP/genética , Adolescente , Alelos , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Frequência do Gene , Estudo de Associação Genômica Ampla , Cadeias alfa de HLA-DP/genética , Cadeias beta de HLA-DP/genética , Haplótipos , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Langerhans cell histiocytosis (LCH) is a rare proliferative disease accompanied by the accumulation of pathological Langerhans cells, which often spreads into multi-site and multi-organ systems. We here describe a girl with a history of Kawasaki disease and cervical lymphadenopathy who presented with occipital LCH. Adrenal tumor was detected on staging evaluation of LCH and was diagnosed as neuroblastoma on resection using laparoscopic surgery. Neither tumor relapsed following chemotherapy for LCH and resection of neuroblastoma. Although LCH often spreads into multi-organ lesions, invasive biopsy may be needed for tumors with atypical localization for LCH in consideration of the synchronous occurrence of malignancies.
Assuntos
Neoplasias das Glândulas Suprarrenais/complicações , Histiocitose de Células de Langerhans/complicações , Neuroblastoma/complicações , Feminino , Histiocitose de Células de Langerhans/patologia , Humanos , LactenteRESUMO
Streptococcus gallolyticus subsp. pasteurianus was formerly classified as S. bovis biotype II/2, which is recognized as a rare cause of neonatal sepsis and meningitis. Since the taxonomy classification change, there have not been many reports of meningitis due to S. gallolyticus subsp. pasteurianus. Moreover, the pathogenesis of late onset S. gallolyticus subsp. pasteurianus meningitis in infants is unclear. Here we report a case of meningitis in a 5-week-old infant with preceding diarrhea. S. bovis biotype II/2 was isolated from the blood, cerebrospinal fluid and stool, and then was identified as S. gallolyticus subsp. pasteurianus on 16S rRNA gene sequencing. Isolates from all three sample types had identical profiles on pulsed-field gel electrophoresis. The intestinal tract was thought to be the source of the infection.
Assuntos
Meningites Bacterianas , Infecções Estreptocócicas , Sequência de Bases , Humanos , Lactente , Masculino , Dados de Sequência Molecular , Streptococcus/classificação , Streptococcus/genéticaRESUMO
A new version of the Japanese pediatric guideline for the treatment and management of bronchial asthma was published in Japanese at the end of 2011. The guideline sets the pragmatic goal for clinicians treating childhood asthma as maintaining a "well-controlled level" for an extended period in which the child patient can lead a trouble-free daily life, not forgetting the ultimate goal of obtaining remission and/or cure. Important factors in the attainment of the pragmatic goal are: (i) appropriate use of anti-inflammatory drugs; (ii) elimination of environmental risk factors; and (iii) educational and enlightening activities for the patient and caregivers regarding adequate asthma management in daily life. The well-controlled level refers to a symptom-free state in which no transient coughs, wheezing, dyspnea or other symptoms associated with bronchial asthma are present, even for a short period of time. As was the case in the previous versions of the guideline, asthmatic children younger than 2 years of age are defined as infantile asthma patients. Special attention is paid to these patients in the new guideline: they often have rapid exacerbation and easily present chronic asthmatic conditions after the disease is established.
Assuntos
Asma/terapia , Guias de Prática Clínica como Assunto , Adolescente , Criança , Pré-Escolar , Humanos , LactenteRESUMO
The Japanese Guideline for the Diagnosis and Treatment of Allergic Diseases 2013 (JAGL 2013) describes childhood asthma after the Japanese Pediatric Guideline for the Treatment and Management of Asthma 2012 (JPGL 2012) by the Japanese Society of Pediatric Allergy and Clinical Immunology. JAGL 2013 provides information on diagnosis by age group from infancy to puberty (0-15 years of age), treatment for acute exacerbations, long-term management by anti-inflammatory drugs, daily life guidance, and patient education to allow non-specialist physicians to refer to this guideline for routine medical treatment. JAGL differs from the Global Initiative for Asthma Guideline (GINA) in that JAGL emphasizes early diagnosis and intervention at <2 years and 2-5 years of age. A management method, including step-up or step-down of long-term management drugs based on the status of asthma control levels, as in JAGL, is easy to understand, and thus the Guideline is suitable as a frame of reference for routine medical treatment. JAGL has also introduced treatment and management using a control test on children, recommending that the physician aim at complete control by avoiding exacerbation factors and by appropriate use of anti-inflammatory drugs.
RESUMO
A food allergy is defined as "a phenomenon in which adverse reactions are caused through antigen-specific immunological mechanisms after exposure to given food." Various symptoms of food allergy occur in many organs. Food allergies are classified roughly into 4 clinical types: (1) neonatal and infantile gastrointestinal allergy, (2) infantile atopic dermatitis associated with food allergy, (3) immediate-type food allergy (urticaria, anaphylaxis, etc.), and (4) food dependent exercise-induced anaphylaxis and oral allergy syndrome (i.e., specific forms of immediate food allergy). The therapy for food allergies includes treatment of and prophylactic measures against hypersensitivity such as anaphylaxis. A fundamental prophylactic measure is the elimination diet. However, elimination diets should be used only if necessary because of the patient-related burden. For this purpose, it is very important that causative foods be accurately identified. There are a number of means available to identify causative foods, including the history taking, a skin prick test, detection of antigen-specific IgE antibodies in the blood, the basophil histamine release test, the elimination diet test, and the oral challenge test, etc. Of these, the oral challenge test is the most reliable. However, it should be conducted under the supervision of experienced physicians because it may cause adverse reactions, such as anaphylaxis.
RESUMO
The Japanese Guideline for the Diagnosis and Treatment of Allergic Diseases 2013 (JAGL 2013) describes childhood asthma after the Japanese Pediatric Guideline for the Treatment and Management of Asthma 2012 (JPGL 2012) by the Japanese Society of Pediatric Allergy and Clinical Immunology. JAGL 2013 provides information on diagnosis by age group from infancy to puberty (0-15 years of age), treatment for acute exacerbations, long-term management by anti-inflammatory drugs, daily life guidance, and patient education to allow non-specialist physicians to refer to this guideline for routine medical treatment. JAGL differs from the Global Initiative for Asthma Guideline (GINA) in that JAGL emphasizes early diagnosis and intervention at <2 years and 2-5 years of age. A management method, including step-up or step-down of long-term management drugs based on the status of asthma control levels, as in JAGL, is easy to understand, and thus the Guideline is suitable as a frame of reference for routine medical treatment. JAGL has also introduced treatment and management using a control test on children, recommending that the physician aim at complete control by avoiding exacerbation factors and by appropriate use of anti-inflammatory drugs.
Assuntos
Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Fatores de Tempo , Adolescente , Asma/diagnóstico , Criança , Pré-Escolar , Progressão da Doença , Diagnóstico Precoce , Humanos , Lactente , Recém-Nascido , Japão , Educação de Pacientes como AssuntoRESUMO
A food allergy is defined as "a phenomenon in which adverse reactions are caused through antigen-specific immunological mechanisms after exposure to given food." Various symptoms of food allergy occur in many organs. Food allergies are classified roughly into 4 clinical types: (1) neonatal and infantile gastrointestinal allergy, (2) infantile atopic dermatitis associated with food allergy, (3) immediate-type food allergy (urticaria, anaphylaxis, etc.), and (4) food dependent exercise-induced anaphylaxis and oral allergy syndrome (i.e., specific forms of immediate food allergy). The therapy for food allergies includes treatment of and prophylactic measures against hypersensitivity such as anaphylaxis. A fundamental prophylactic measure is the elimination diet. However, elimination diets should be used only if necessary because of the patient-related burden. For this purpose, it is very important that causative foods be accurately identified. There are a number of means available to identify causative foods, including the history taking, a skin prick test, detection of antigen-specific IgE antibodies in the blood, the basophil histamine release test, the elimination diet test, and the oral challenge test, etc. Of these, the oral challenge test is the most reliable. However, it should be conducted under the supervision of experienced physicians because it may cause adverse reactions, such as anaphylaxis.
Assuntos
Alérgenos/imunologia , Hipersensibilidade Alimentar/diagnóstico , Alimentos , Administração Oral , Alérgenos/administração & dosagem , Alérgenos/efeitos adversos , Alimentos/efeitos adversos , Hipersensibilidade Alimentar/dietoterapia , Humanos , Imunização , Japão , Testes Sorológicos , Testes CutâneosRESUMO
BACKGROUND: There are reports that the maternal diet during pregnancy may affect development of babies' eczema. We sought to investigate the association between the maternal diet during pregnancy and the risk of eczema in infancy in Japan. METHODS: A birth cohort was set up at 2 hospitals in Chiba city. Dietary habits concerning fish, butter, margarine, yogurt and natto during pregnancy was obtained from mothers just after delivery. The intake frequencies of these foods were classified into four groups: 1) daily, 2) 2-3 times a week, 3) once a week and 4) once a month or less. Diagnosis of eczema at 6 months of age was made by the presence of an itchy rash that persisted more than two months. RESULTS: Valid data on 650 mother-baby pairs were obtained. No relationship between frequencies of the maternal intake of fish, margarine and yogurt during pregnancy and the onset rate of the babies' eczema were observed. For butter consumption, the incidence of babies' eczema was significantly higher in the group with daily intake than in those with an intake 2-3 times a week or less (p = 0.044). For natto, incidence of babies' eczema was significantly lower in the group with everyday intake than those eating it 2-3 times a week or less (p = 0.020). CONCLUSIONS: High frequency intake of natto during pregnancy possibly reduces the incidence of eczema in children at 6 months of age.