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Objectives Although epidemiological surveys of paediatric rheumatic diseases in Japan have been conducted they were single surveys with no continuity. This is the first report of the Pediatric Rheumatology Association of Japan (PRAJ)... more
Objectives Although epidemiological surveys of paediatric rheumatic diseases in Japan have been conducted they were single surveys with no continuity. This is the first report of the Pediatric Rheumatology Association of Japan (PRAJ) registry database, which was established to continuously collect data for paediatric rheumatic diseases. Methods ‘PRICUREv2’ (Pediatric Rheumatology International Collaborate Unit Registry version 2) is a registry database established by the PRAJ. The registry data were analysed for the age of onset, time to diagnosis, sex differences, seasonality, and other factors. Results Our data showed the same trend regarding rates of paediatric rheumatic diseases reported in Japan and other countries. The age of onset was lower in juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM) and higher in systemic lupus erythematosus (SLE) and Sjögren’s syndrome (SS). The time to diagnosis was relatively short in JIA and SLE but longer in JDM and SS. Rhe...
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Table S3. The characteristics and outcomes of alendronate-treated patients with and without bone loss. (DOCX 26 kb)
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Background The European League Against Rheumatism (EULAR) Sjögren Syndrome Disease Activity Index (ESSDAI) has been utilized to assess Sjögren syndrome-related systemic involvement in adult patients. To date, however, the ESSDAI has not... more
Background The European League Against Rheumatism (EULAR) Sjögren Syndrome Disease Activity Index (ESSDAI) has been utilized to assess Sjögren syndrome-related systemic involvement in adult patients. To date, however, the ESSDAI has not been validated in children with primary Sjögren’s syndrome. This study evaluated the applicability of the ESSDAI to Japanese children with primary Sjögren’s syndrome. Methods The medical records of children who had been diagnosed with Sjogren syndrome at age ≤ 16 years between June 2011 and October 2016 were collected, and their ESSDAIs at initial presentation were calculated. Clinical symptoms and treatment regimens were surveyed by questionnaire, and patients were divided into groups based on ESSDAI and glucocorticoid dosages. The associations of ESSDAI scores with treatment regimens were analyzed statistically. Results The study subjects included 31 children (3 boys, 28 girls) with primary Sjögren’s syndrome. Their median age at disease onset was ...
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Abstract There are a considerable number of pediatric patients with Sjögren’s syndrome (SS); however, SS is generally considered rare among children. Pediatric patients with SS report fewer sicca symptoms; therefore, many are... more
Abstract There are a considerable number of pediatric patients with Sjögren’s syndrome (SS); however, SS is generally considered rare among children. Pediatric patients with SS report fewer sicca symptoms; therefore, many are under-diagnosed and cannot access appropriate medical management. Therefore, we propose a newly developed guidance for the diagnosis, treatment, and management of pediatric SS, including epidemiology, clinical features, and diagnostic examination methodology. The aim of this guidance was to standardize the medical care of pediatric SS in Japan, and we published the Japanese version by YODOSHA in 2018. This article is the English version, which is summarized and updated. This guidance will need to be revised in the near future as additional clinical data become available.
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Skin colonization at 6 months of age by S. aureus with functional Agr quorum sensing associates with later atopic dermatitis development in infants.
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Purpose of ReviewMicroRNAs (miRNAs) are short, single-stranded, non-coding RNAs that are increasingly being recognized as important epigenetic regulators. They have been implicated in the pathogenesis of many diseases including cancer,... more
Purpose of ReviewMicroRNAs (miRNAs) are short, single-stranded, non-coding RNAs that are increasingly being recognized as important epigenetic regulators. They have been implicated in the pathogenesis of many diseases including cancer, cardiovascular diseases, connective tissue diseases, and neuromuscular disorders.Recent FindingsA few miRNAs have already been recognized as a core set of miRNAs important in allergic inflammation. These include let-7, miR-21, miR-142, and miR-146.SummaryThis review aims to bring together some of the recent findings on how miRNAs regulate allergic inflammation with special focus on asthma, atopic dermatitis, allergic rhinitis, and eosinophilic esophagitis. We will also touch upon extracellular miRNAs and future perspective of this field of study.
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Background: Maternal carotenoid intake during pregnancy may be associated with decreased infantile atopic dermatitis (AD) odds. This study aimed to elucidate the association between maternal and infant carotenoid levels and AD... more
Background: Maternal carotenoid intake during pregnancy may be associated with decreased infantile atopic dermatitis (AD) odds. This study aimed to elucidate the association between maternal and infant carotenoid levels and AD development. Methods: This prospective study included 267 newborns with a family history of allergies as part of the Chiba High-risk Birth Cohort for Allergy study. Serum was collected from the cord blood of mothers at 36 weeks of gestation and 1-year-old infants, together with post-childbirth colostrum and breast milk samples at 1 and 6 months after birth. These were used to determine total and specific carotenoids, α-tocopherol, and retinol levels, and the results were compared between AD-positive and -negative infants. Univariate and multivariate analyses were conducted, and variables were selected for the multivariate analysis using variable importance in projection scores calculated by partial least squares regression. Results: Specific carotenoid levels ...
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IntroductionThis study established an independent evaluation index for patients with childhood-onset chronic diseases in Japan.MethodsFrom November to December 2020, three Delphi rounds were conducted. Thirty-nine participants completed... more
IntroductionThis study established an independent evaluation index for patients with childhood-onset chronic diseases in Japan.MethodsFrom November to December 2020, three Delphi rounds were conducted. Thirty-nine participants completed at least one survey. We asked them about targets of social independence for 10 types of activities (education/labor/finance/acquisition of necessities/housing/transportation/leisure/social relationship/intimate relationships/sexuality). The Delphi technique was to be repeated until a consensus of over 80% of participants was reached.ResultsThe targets chosen for measuring independence in patients with childhood-onset chronic diseases were as follows: “Graduation from high school,” “Labor for livelihood (including temporary turnover),” “Financially independent (including temporary turnover, excluding students),” “Buy or rent a house and buy the daily necessities and get the public services you need to live,” “Do housework alone,” “Plan alone and use t...
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Systemic juvenile idiopathic arthritis (sJIA) is an autoinflammatory disease caused by high production of inflammatory cytokines. Conventional biomarkers, such as IL-18 are reportedly not always associated with frequent relapses or... more
Systemic juvenile idiopathic arthritis (sJIA) is an autoinflammatory disease caused by high production of inflammatory cytokines. Conventional biomarkers, such as IL-18 are reportedly not always associated with frequent relapses or complication with macrophage activation syndrome (MAS). As few specific biomarkers that can indicate and evaluate the sJIA disease activity have been identified, the discovery of biomarkers is very important. We performed a deep proteomic analysis of serum samples from nine patients with sJIA using highly sensitive mass spectrometry, and identified differentially expressed proteins in various disease phases. We selected 68 proteins (URPs) that were highly expressed in the active phase from total of 2,727 proteins. Pathway analysis revealed that the URPs included proteins related to many immune process and proteasome proteins, which might be associated with the pathogenesis of sJIA. Based on these results, four proteins (leucine aminopeptidase 3; LAP3, gua...
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Objectives The Committee for Support of Transition to Adult Medical Care, Pediatric Rheumatology Association of Japan, has developed a checklist for patients with pediatric rheumatologic diseases to evaluate readiness for transition to... more
Objectives The Committee for Support of Transition to Adult Medical Care, Pediatric Rheumatology Association of Japan, has developed a checklist for patients with pediatric rheumatologic diseases to evaluate readiness for transition to adult medical care. Methods Using checklists for general pediatric chronic diseases developed by researchers at the Ministry of Health, Labour and Welfare, committee members discussed points for modification or addition specific to pediatric rheumatic diseases and pediatric rheumatism clinical practice. Results Three patient-assessment checklists based on patient age and understanding level and a parent-assessment checklist were developed. The checklist for junior high school students and above included a ‘Health Education in Adolescence and Young Adulthood’ section with items related to sexual knowledge and concerns. Also, items on oral medications and subcutaneous injections management in the ‘Self-management of Daily Medical Care,’ domain and next ...
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Matrix metalloproteinases (MMPs) are a class of extra-cellular and membrane-bound proteases involved in a wide array of physiological and pathological processes including tissue remodeling, inflammation, and cytokine secretion and... more
Matrix metalloproteinases (MMPs) are a class of extra-cellular and membrane-bound proteases involved in a wide array of physiological and pathological processes including tissue remodeling, inflammation, and cytokine secretion and activation. MMP-13 has been shown to be involved in lung diseases such as acute lung injury, viral infections, and chronic obstructive pulmonary disease; however, the molecular pathogenesis of MMP-13 in these conditions is not well understood. In this study, we investigated the mechanisms and roles of MMP-13 secretion in human small airway epithelial cells (SAECs) and functional polymorphisms of the MMP13 gene. Polyinosinic-polycytidylic acid (poly(I:C)) and interferon β (IFN-β) stimulated the secretion of MMP-13 from SAECs by more than several hundred-fold. Stimulation of the secretion by poly(I:C) was abolished by SB304680 (p38 inhibitor), LY294002 (PI3K inhibitor), Janus kinase (JAK) inhibitor I, RNA-activated protein kinase (PKR) inhibitor, and Bay 11-...
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ABSTRACT
Research Interests: Incidence Geometry, Asthma, Dermatology, Medicine, Allergy, and 2 moreSensitization and Nose(Sensitization and Nose)
(Sensitization and Nose)
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Allergies are characterized by a hypersensitive immune reaction to originally harmless antigens. In recent decades, the incidence of allergic diseases has markedly increased, especially in developed countries. The increase in the... more
Allergies are characterized by a hypersensitive immune reaction to originally harmless antigens. In recent decades, the incidence of allergic diseases has markedly increased, especially in developed countries. The increase in the frequency of allergic diseases is thought to be primarily due to environmental changes related to a westernized lifestyle, which affects the commensal microbes in the human body. The human gut is the largest organ colonized by bacteria and contains more than 1000 bacterial species, called the "gut microbiota." The recent development of sequencing technology has enabled researchers to genetically investigate and clarify the diversity of all species of commensal microbes. The collective genomes of commensal microbes are together called the "microbiome." Although the detailed mechanisms remain unclear, it has been proposed that the microbiota/microbiome, especially that in the gut, impacts the systemic immunity and metabolism, thus affecting the development of various immunological diseases, including allergies. In this review, we summarize the recent findings regarding the importance of the microbiome/microbiota in the development of allergic diseases and also the results of interventional studies using probiotics or prebiotics to prevent allergies.
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Human parvovirus B19 (HPV-B19) is a DNA virus of the erythrovirus, and causes erythema infectosum, arthritis, and transient marrow aplastic shock, while systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune inflammatory... more
Human parvovirus B19 (HPV-B19) is a DNA virus of the erythrovirus, and causes erythema infectosum, arthritis, and transient marrow aplastic shock, while systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune inflammatory disease of unknown cause, which may involve the skin, joints, kidneys, lungs, and central nervous system. We report the association of prolonged fever, migrating skin rash, and edema of hands and feet with hypocomplementemia and hypoalbuminemia in a 1-year-old girl with HPV-B19 infection. Kawasaki disease should be distinguished from this clinical condition, and this is the earliest case of SLE-like presentation with HPV-B19 infection.
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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... more
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 β-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.
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Immediate allergy to l-asparaginase (ASP) is a major obstacle in treating lymphoid malignancies. ASP-specific immunoglobulin G (ASP-IgG) has been used as a surrogate marker. Recently, the CD203c-basophil activation test (BAT) was found to... more
Immediate allergy to l-asparaginase (ASP) is a major obstacle in treating lymphoid malignancies. ASP-specific immunoglobulin G (ASP-IgG) has been used as a surrogate marker. Recently, the CD203c-basophil activation test (BAT) was found to be useful in diagnosing IgE-mediated allergies. We compared the diagnostic utility of the CD203c-BAT to that of ASP-IgG levels in determining ASP allergies in children. Eight ASP allergic reactions occurred over 75 ASP treatment courses. The sensitivity, specificity and area under the receiver operating characteristic curve of CD203c-BAT were similar to the ASP-IgG levels (0.75 vs. 0.85, 0.82 vs. 0.78 and 0.81 vs. 0.85, respectively). Positive skin prick test results in patients with ASP allergy suggested that ASP-IgE was one of the key players in ASP allergy. A combination of the BAT with the ASP-IgG level had the highest specificity (0.95) and positive predictive value (0.62), which permitted us to identify ASP allergy more effectively.
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Research Interests: Rheumatology, Medicine, Osteoporosis, Humans, Child, and 15 moreInternal Medicine, Autoimmune Disease, Female, Male, Bone Density, Clinical Sciences, Alendronate, Longitudinal Studies, Glucocorticoid, Bone Mineral Density, Bone Loss, Bone remodeling, Rheumatic diseases, Pilot Projects, and Glucocorticoids
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This preliminary prospective study suggests that background factors may differ among allergic diseases. The beneficial interventions for reducing development of allergic rhinitis (AR) are also effective for the prevention of subsequent... more
This preliminary prospective study suggests that background factors may differ among allergic diseases. The beneficial interventions for reducing development of allergic rhinitis (AR) are also effective for the prevention of subsequent onset of bronchial asthma (BA). To determine the risk factors associated with onset of AR in atopic children in a prospective study. All patients with atopic dermatitis (AD) or food allergy with or without BA who visited the Pediatric Unit of Chiba University Hospital from 2005 to 2006 were enrolled in the study and received allergy examinations every 3-6 months. A total of 100 patients were followed up for more than 2 years. Among the 60 patients without BA at entry to the study, 12 developed BA during the follow-up period. Development of AR preceded BA in 10 of the 12 patients (83.3%). In the background factors at the entry, positive sensitization to house dust mite (HDM) was significantly related to development of BA. Among the 48 patients without AR, 20 developed AR. High titers of serum HDM-specific IgE and high eosinophil counts in blood, and detection of eosinophils in nasal smears at the entry were significantly related to development of AR.
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Issues related to transitioning from paediatric to adult healthcare are currently receiving international attention. In Japan, 1000 patients with childhood-onset chronic rheumatological diseases reach adulthood every year and require... more
Issues related to transitioning from paediatric to adult healthcare are currently receiving international attention. In Japan, 1000 patients with childhood-onset chronic rheumatological diseases reach adulthood every year and require transition from care by paediatric to care by adult rheumatologists. Here, we propose a guide for the latter, wherein the adult caregiver poses the clinical questions about transitional support that they need to have answered, and the paediatric caregiver mainly compiles the plans for the transition. To formulate the guide, we sought comments from both the Japan College of Rheumatology and the Pediatric Rheumatology Association of Japan and obtained their approval. Here, we present the outcome of this consultation in the form of a Guide for Supporting Transitional Care, aiming to provide essential knowledge to physicians in the fields of adult internal medicine and orthopaedics who may be involved in treating patients with rheumatic disease during the t...