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BACKGROUND: Non-esophageal eosinophilic gastrointestinal disorder (non-EoE-EGID) is a rare disease in which eosinophils infiltrate parts of the gastrointestinal tract other than the esophagus; however, the number of patients with non-EoE-EGID has been increasing in recent years. Owing to its chronic course with repeated relapses, it can lead to developmental delays due to malnutrition, especially in pediatric patients. No established treatment exists for non-EoE-EGID, necessitating long-term systemic corticosteroid administration. Although the efficacy of dupilumab, an anti-IL-4/13 receptor monoclonal antibody, for eosinophilic esophagitis, has been reported, only few reports have demonstrated its efficacy in non-EoE EGIDs. CASE PRESENTATION: A 13-year-old boy developed non-EoE-EGID with duodenal ulcers, with chicken eggs as the trigger. He was successfully treated with an egg-free diet, proton pump inhibitors, and leukotriene receptor antagonists. However, at age 15, he developed worsening upper abdominal pain and difficulty eating. Blood analysis revealed eosinophilia; elevated erythrocyte sedimentation rate; and elevated levels of C-reactive protein, total immunoglobulin E, and thymic and activation-regulated chemokines. Upper gastrointestinal endoscopy revealed a duodenal ulcer with marked mucosal eosinophilic infiltration. Gastrointestinal symptoms persisted even after starting systemic steroids, making it difficult to reduce the steroid dose. Subcutaneous injection of dupilumab was initiated because of comorbid atopic dermatitis exacerbation. After 3 months, the gastrointestinal symptoms disappeared, and after 5 months, the duodenal ulcer disappeared and the eosinophil count decreased in the mucosa. Six months later, systemic steroids were discontinued, and the duodenal ulcer remained recurrence-free. The egg challenge test result was negative; therefore, the egg-free diet was discontinued. Blood eosinophil count and serum IL-5, IL-13, and eotaxin-3 levels decreased after dupilumab treatment. The serum levels of IL-5 and eotaxin-3 remained within normal ranges, although the blood eosinophil counts increased again after discontinuation of oral prednisolone. CONCLUSIONS: Suppression of IL-4R/IL-13R-mediated signaling by dupilumab may improve abdominal symptoms and endoscopic and histologic findings in patients with non-EoE-EGID, leading to the discontinuation of systemic steroid administration and tolerance of causative foods.

DOI： 10.1186/s13223-023-00859-3

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DOI： 10.1016/j.jpeds.2023.113852

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Language：Japanese   Publisher：(一社)日本小児アレルギー学会  

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Language：Japanese   Publisher：(一社)日本小児アレルギー学会  

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DOI： 10.1056/NEJMc2308512

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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DOI： 10.1056/NEJMicm2214160

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Language：Japanese   Publisher：(公社)日本皮膚科学会  

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OBJECTIVES: To clarify how pediatric rheumatologists treat systemic juvenile idiopathic arthritis (s-JIA) associated macrophage activation syndrome (MAS) in the real world and to assess the efficacy and safety of dexamethasone palmitate (DEX-P) in the treatment of s-JIA-associated MAS. METHODS: This multicenter, retrospective study was conducted at 13 pediatric rheumatology institutes in Japan. This study included 28 patients with s-JIA-associated MAS. Clinical findings, such as treatment details and adverse events, were evaluated. RESULTS: Methylprednisolone (mPSL) pulse therapy was selected as the first-line treatment in more than half of the patients with MAS. Cyclosporine A (CsA) was used as first-line therapy in combination with corticosteroids in half of the patients with MAS. DEX-P and/or CsA were selected as the second-line therapy in 63% of patients with corticosteroid-resistant MAS. Plasma exchange was selected as the third-line therapy for DEX-P and CsA-resistant MAS. All patients improved and there were no characteristically severe adverse events associated with DEX-P. CONCLUSIONS: The first-line treatment for MAS in Japan is mPSL pulse therapy and/or CyA. DEX-P could be an effective and safe therapeutic option for patients with corticosteroid-resistant MAS.

DOI： 10.1111/1756-185X.14681

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BACKGROUND: Kawasaki disease (KD) is a form of pediatric systemic vasculitis. Although the etiology remains unclear, infections have been identified as possible triggers. Children with a later birth order and those who attend childcare are at a higher risk of infections due to exposure to pathogens from their older siblings and other childcare attendees. However, longitudinal studies exploring these associations are limited. Thus, we aimed to elucidate the relationship between birth order, group childcare attendance, and KD, using a nationwide longitudinal survey in Japan. METHODS: In total, 36,885 children born in Japan in 2010 were included. The survey used questionnaires to identify hospitalized cases of KD. We evaluated the relationship between birth order classification, group childcare attendance, and KD prevalence every year, from 6 to 66 months of age. For each outcome, odds ratios (ORs), and 95% confidence intervals (CIs) were estimated after adjusting for child factors, parental factors, and region of residence. RESULTS: Children with higher birth orders were more likely to be hospitalized with KD at 6-18 months of age (second child OR: 1.77, 95% CI: 1.25-2.51; third child OR: 1.70, 95% CI: 1.08-2.65). This trend was stronger for children who did not attend group childcare (second child OR: 2.51, 95% CI: 1.57-4.01; third child OR: 2.41, 95% CI: 1.30-4.43). An increased risk of KD hospitalization owing to the birth order was not observed in any age group for children in the childcare group. CONCLUSIONS: Children with higher birth orders were at high risk for hospitalization due to KD at 6-18 months of age. The effect of birth order was more prominent among the children who did not attend group childcare.

DOI： 10.3389/fped.2023.1127053

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DOI： 10.1111/ped.15460

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Language：Japanese   Publisher：(一社)日本小児感染症学会  

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BACKGROUND: Neonatal hemochromatosis causes acute liver failure during the neonatal period, mostly due to gestational alloimmune liver disease (GALD). Thalassemia causes hemolytic anemia and ineffective erythropoiesis due to mutations in the globin gene. Although neonatal hemochromatosis and thalassemia have completely different causes, the coexistence of these diseases can synergistically exacerbate iron overload. We report that a newborn with εγδβ-thalassemia developed neonatal hemochromatosis, which did not respond to iron chelators and rapidly worsened, requiring living-donor liver transplantation. CASE PRESENTATION: A 1-day-old Japanese boy with hemolytic anemia and targeted red blood cells was diagnosed with εγδβ-thalassemia by genetic testing, and required frequent red blood cell transfusions. At 2 months after birth, exacerbation of jaundice, grayish-white stool, and high serum ferritin levels were observed, and liver biopsy showed iron deposition in hepatocytes and Kupffer cells. Magnetic resonance imaging scans showed findings suggestive of iron deposits in the liver, spleen, pancreas, and bone marrow. The total amount of red blood cell transfusions administered did not meet the criteria for post-transfusion iron overload. Administration of an iron-chelating agent was initiated, but iron overload rapidly progressed to liver failure without improvement in jaundice and liver damage. He underwent living-donor liver transplantation from his mother, after which iron overload disappeared, and no recurrence of iron overload was observed. Immunohistochemical staining for C5b-9 in the liver was positive. Serum hepcidin levels were low and serum growth differentiation factor-15 levels were high prior to living-donor liver transplantation. CONCLUSIONS: We reported that an infant with εγδβ-thalassemia developed NH due to GALD, and that coexistence of ineffective erythropoiesis in addition to erythrocyte transfusions may have exacerbated iron overload. Low serum hepcidin levels, in this case, might have been caused by decreased hepcidin production arising from fetal liver damage due to neonatal hemochromatosis and increased hepcidin-inhibiting hematopoietic mediators due to the ineffective hematopoiesis observed in thalassemia.

DOI： 10.1186/s12887-022-03706-3

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Language：Japanese   Publisher：(一社)日本小児アレルギー学会  

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DOI： 10.1053/j.gastro.2022.08.022

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BACKGROUND: The respiratory syncytial virus (RSV) disease burden is significant, especially in infants and children with an underlying disease. Prophylaxis with palivizumab is recommended for these high-risk groups. Early recognition of a RSV epidemic is important for timely administration of palivizumab. We herein aimed to assess the correlation between national surveillance and Google Trends data pertaining to RSV infections in Japan. METHODS: The present, retrospective survey was performed between January 1, 2018 and November 14, 2021 and evaluated the correlation between national surveillance data and Google Trends data. Joinpoint regression was used to identify the points at which changes in trends occurred. RESULTS: A strong correlation was observed every study year (2018 [r = 0.87, p < 0.01], 2019 [r = 0.83, p < 0.01], 2020 [r = 0.83, p < 0.01], and 2021 [r = 0.96, p < 0.01]). The change-points in the Google Trends data indicating the start of the RSV epidemic were observed earlier than by sentinel surveillance in 2018 and 2021 and simultaneously with sentinel surveillance in 2019. No epidemic surge was observed in either the Google Trends or the surveillance data from 2020. CONCLUSIONS: Our data suggested that Google Trends has the potential to enable the early identification of RSV epidemics. In countries without a national surveillance system, Google Trends may serve as an alternative early warning system.

DOI： 10.1186/s12889-022-13899-y

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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DOI： 10.1038/s41598-022-11823-3

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OBJECTIVES: Histidine-rich glycoprotein (HRG) and high-mobility group box 1 (HMGB1) regulate the activation of neutrophils and vascular endothelium. The aim of this study was to quantify HRG and HMGB1 levels in patients with Kawasaki disease (KD) and evaluate their use in the clinical management of KD. METHODS: This study was prospectively performed. Patients were divided into two groups and analyzed depending on whether KD symptoms improved by day 10 of illness. HRG, HMGB1, and other laboratory variables were measured before the first treatment in all cases and, in most cases, afterwards, for assessing trends. RESULTS: In this prospective study, we enrolled 60 patients with KD and 48 healthy controls. The HRG level in the KD group was significantly lower than that in the healthy control group; HMGB1 levels showed no obvious differences. In the KD group, HRG levels were negatively correlated with white blood cell and neutrophil counts. In the poor responders and responders groups, a tendency for a decrease in HRG and HMGB1 levels, respectively, was observed from pretreatment to post-treatment. CONCLUSIONS: HRG and HMGB1 are related to the pathogenesis of KD; low HRG and high HMGB1 levels cause resistance against KD treatment.

DOI： 10.1093/mr/roac040

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Under normal conditions, fasting results in decreased protein disulfide isomerase (PDI) activity and accumulation of unfolded proteins, leading to the subsequent activation of the unfolded protein response (UPR)/autophagy signaling pathway to eliminate damaged mitochondria. Fasting also induces upregulation of thioredoxin-interacting protein (TXNIP) expression and mice deficient of this protein (TXNIP-KO mice) was shown to develop severe hypoglycemia, hyperlipidemia and liver steatosis (LS). In the present study, we aimed to determine the role of TXNIP in fasting-induced LS by using male TXNIP-KO mice that developed LS without severe hypoglycemia. In TXNIP-KO mice, fasting induced severe microvesicular LS. Examinations by transmission electron microscopy revealed mitochondria with smaller size and deformities and the presence of few autophagosomes. The expression of β-oxidation-associated genes remained at the same level and the level of LC3-II was low. PDI activity level stayed at the original level and the levels of p-IRE1 and X-box binding protein 1 spliced form (sXBP1) were lower. Interestingly, treatment of TXNIP-KO mice with bacitracin, a PDI inhibitor, restored the level of LC3-II after fasting. These results suggest that TXNIP regulates PDI activity and subsequent activation of the UPR/autophagy pathway and plays a protective role in fasting-induced LS.

DOI： 10.1038/s41598-022-08791-z

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Language：Japanese   Publisher：(株)診断と治療社  

症例は全身性エリテマトーデスの18歳女性。タクロリムス(TAC)、ミコフェノール酸モフェチル(MMF)併用下に寛解状態にあった。急性胃腸炎を機に腎機能が低下し、いったん軽快した下痢の再燃および血球減少を認めた。TAC、MMF相互の副作用により両薬剤の血中濃度が上昇し有害事象が出現したと考えられ、TAC減量により症状は改善した。TAC、MMF2剤併用中に胃腸炎に罹患したときには、特異な血中濃度の変動に注意する必要がある。(著者抄録)

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The aim of this study is to describe bilateral optic disc swelling in three consecutive patients with Blau syndrome or cryopyrin-associated periodic syndrome at a single institution. Case 1 was a 30-year-old woman receiving 25 mg etanercept twice weekly who had been diagnosed as early-onset sarcoidosis by biopsy of skin rashes at 5 months old and genetically diagnosed with Blau syndrome with CARD15/NOD2 mutation (N670K) at 13 years old. At 10 years old, she began to have uveitis with optic disc swelling in both eyes, resulting in macular degeneration and optic disc atrophy at 17 years old only when etanercept was introduced. Case 2 was a 21-year-old man receiving adalimumab every 2 weeks who had been diagnosed as early-onset sarcoidosis by biopsy of skin rashes at 1.5 years old and genetically diagnosed as Blau syndrome with CARD15/NOD2 mutation (C495Y) at 5 years old. At 8 years old, around the time of adalimumab introduction, he began to show bilateral optic disc swelling which continued until the age of 16 years when the dose of adalimumab was increased. Case 3 was a 20-year-old woman receiving canakinumab every 8 weeks for systemic symptoms such as fever, headache, vomiting, and abdominal pain and later for sensorineural hearing disturbance on both sides. She had been diagnosed genetically with cryopyrin-associated periodic syndrome with NLRP3 mutation (Y859C) at 7 years old. At 5 years old, she was found to have bilateral optic disc swelling, which continued until the age of 10 years when she began receiving canakinumab (IL-1β inhibitor). Bilateral optic disc swelling might be tentatively designated as a plausible common ocular feature, if it occurred, in autoinflammatory diseases to pay more attention to ophthalmic complications in rare diseases.

DOI： 10.3390/life11121433

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DOI： 10.3390/life111

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OBJECTIVE: High mobility group box-1 (HMGB1) has been reported to be involved in influenza A virus-induced acute respiratory distress syndrome (ARDS). We studied the efficacy of an anti-HMGB1 mAb using an in vitro model of TNF-α stimulation or influenza A virus infection in human pulmonary microvascular endothelial cells (HMVECs). METHODS: Vascular permeability of HMVECs was quantified using the Boyden chamber assay under tumor necrosis factor-α (TNF-α) stimulation or influenza A virus infection in the presence of anti-HMGB1 mAb or control mAb. The intracellular localization of HMGB1 was assessed by immunostaining. Extracellular cytokine concentrations and intracellular viral mRNA expression were quantified by the enzyme-linked immunosorbent assay and quantitative reverse transcription PCR, respectively. RESULTS: Vascular permeability was increased by TNF-α stimulation or influenza A infection; HMVECs became elongated and the intercellular gaps were extended. Anti-HMGB1 mAb suppressed both the increase in permeability and the cell morphology changes. Translocation of HMGB1 to the cytoplasm was observed in the non-infected cells. Although anti-HMGB1 mAb did not suppress viral replication, it did suppress cytokine production in HMVECs. CONCLUSION: Anti-HMGB1 mAb might be an effective therapy for severe influenza ARDS.

DOI： 10.1007/s00011-021-01496-5

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DOI： 10.1136/archdischild-2021-322953

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Language：Japanese   Publisher：(一社)日本環境感染学会  

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Language：Japanese   Publisher：(一社)日本環境感染学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Publishing type：Part of collection (book)   Publisher：Springer Singapore  

DOI： 10.1007/978-981-15-9109-9_12

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DOI： 10.3389/fimmu.2020.5

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Language：Japanese   Publisher：(一社)日本小児腎臓病学会  

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Idiopathic chondrolysis of the hip (ICH), a very rare disorder of unknown etiology, occurs mainly in female adolescents. Characterized by pain, limp, stiffness and radiological narrowing joint space from the rapid destruction of the articular cartilage, ICH sometimes results in ankyloses. We present the case of a 10-year-old girl diagnosed with ICH based on arthroscopic inspection and synovium biopsy. The femoral deformity appeared gradually, like a cam-type femoroacetabular impingement. She was treated with intensive rehabilitation and immunosuppressive drug. We later performed an arthroscopic bumpectomy for residual symptoms. She achieved a favorable outcome as a 15-year-old at the latest follow-up.

DOI： 10.18926/AMO/57957

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BACKGROUND: This study aimed to determine the influence of tocilizumab (TCZ) in modifying the clinical and laboratory features of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (s-JIA). Furthermore, we assessed the performance of the 2016 MAS classification criteria for patients with s-JIA-associated MAS while treated with TCZ. METHODS: A panel of 15 pediatric rheumatologists conducted a combination of expert consensus and analysis of real patient data. Clinical and laboratory features of s-JIA-associated MAS in 12 TCZ-treated patients and 18 untreated patients were evaluated. Possible MAS was defined as having characteristic laboratory features but lack of clinical features of MAS, or atypical MAS, or early treatment that prevented full-blown MAS. RESULTS: Clinically, the TCZ-treated patients with s-JIA-associated MAS were less likely febrile and had significantly lower ferritin, triglyceride, and CRP levels than the untreated patients with s-JIA-associated MAS. Other laboratory features of MAS including lower platelet counts and lower fibrinogen were more pronounced in TCZ-treated patients. The TCZ-treated patients with s-JIA-associated MAS were less likely to be classified as MAS based on the MAS classification criteria (25% vs 83.3%, p < 0.01). This is ascribed to the absence of fever or insufficient ferritin elevation, compared with the untreated patients. CONCLUSION: TCZ could modify the clinical and laboratory features of s-JIA-associated MAS. When evaluating the s-JIA patients while treated with TCZ, it is not applicable to use MAS classification criteria. Care must be taken to not underdiagnose MAS based on the MAS classification criteria.

DOI： 10.1186/s12969-020-0399-1

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Objectives: Genetic analysis of TNFRSF1A can confirm the diagnosis of tumor necrosis factor receptor-associated periodic syndrome (TRAPS), but interpretation of the pathogenesis of variants of unknown significance is sometimes required. The aim of this study was to evaluate the clinical significance of serum soluble tumor necrosis factor receptor type I (sTNFR-I)/II ratio to differentiate TRAPS from other autoinflammatory diseases. Methods: Serum sTNFR-I and sTNFR-II levels were measured using an enzyme-linked immunosorbent assay in patients with TRAPS (n = 5), familial Mediterranean fever (FMF) (n = 14), systemic juvenile idiopathic arthritis (s-JIA) (n = 90), and Kawasaki disease (KD) (n = 37) in the active and inactive phase, along with healthy controls (HCs) (n = 18). Results: In the active phase, the serum sTNFR-I/II ratio in patients with s-JIA, KD, and FMF was significantly elevated compared with that in HCs, whereas it was not elevated in patients with TRAPS. In the inactive phase, the serum sTNFR-I/II ratio in patients with s-JIA and FMF was significantly higher compared with that in HCs, and the ratio was lower in TRAPS patients than in patients with s-JIA and FMF. Conclusions: Low serum sTNFR-I/II ratio in the active and inactive phase might be useful for the differential diagnosis of TRAPS and other autoinflammatory diseases.

DOI： 10.3389/fimmu.2020.576152

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Language：Japanese   Publisher：(一社)日本小児リウマチ学会  

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DOI： 10.1136/annrheumdis-2019-eular.5479

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Acute flaccid myelitis (AFM) is a recently defined clinical disease accompanied by the national outbreak of enterovirus D68 (EV-D68) in the United States during the late summer/fall of 2014; 258 cases of EV-D68 and 59 cases of AFM were reported in Japan during the late summer/fall of 2015. Subsequently, there have been no epidemics of AFM or EV-D68. However, we encountered a patient who had AFM associated with EV-D68 in 2017. This is the first case of AFM caused by EV-D68 after the 2015 epidemic, and the only reported case in 2017. This report indicates that AFM caused by EV-D68 can arise even in non-epidemic situations. If a patient presents with paralysis, AFM caused by EV-D68 should be included in the differential diagnosis, regardless of the absence of an epidemic of EV-D68 infection. (C) 2019 The Authors. Published by Elsevier Ltd.

DOI： 10.1016/j.idcr.2019.e00549

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BACKGROUND: Although there are many reports on Juvenile Idiopathic arthritis-associated uveitis (JIA-U) from various countries, especially from Europe and North America, there are few reports from Asia. Our aim was to investigate the epidemiology, characteristics and predictors of JIA-U in Japan. METHODS: Data were retrospectively collected on 726 patients with JIA from medical records as of April 2016 at 15 medical centers specialized in pediatric rheumatic diseases. Of these, patients with uveitis were further investigated for the specific characteristics of this manifestation. RESULTS: The prevalence of uveitis was 6.1% in the 726 JIA patients examined. Incidence of uveitis was significantly higher in patients with an earlier arthritis onset (2.6-vs.-5.8 years, P < 0.0001), oligoarthritis (16.1%-vs.-1.6%, P < 0.001), or anti-nuclear antibodies. On the contrary, it was significantly less common in patients with rheumatoid factor or anti-cyclic citrullinated peptide antibodies. A history of using methotrexate (MTX), infliximab or adalimumab was also associated with uveitis occurrence. The median age at uveitis diagnosis was 5 years, and the median time from arthritis onset to uveitis diagnosis was 2 years. The occurrence of anterior and bilateral uveitis was 79.3 and 53.7%, respectively. There were no symptoms at uveitis diagnosis in 58.5% of cases. Complications arising between the time of uveitis diagnosis and the last observation increased from 31.7 to 56.1%; in particular, cataract was increased 3-fold. While no patients lost their vision, 61.9% did not recover normal vision (≥ 1.0), and in many cases active uveitis persisted, especially in males. In addition to steroid eye drops (97.6%) and MTX (15.4%), biological agents were used for treating the uveitis in 41.5% of patients. CONCLUSIONS: The epidemiology, characteristics and predictors of JIA-U in Japan are described here for the first time. Although the prevalence of JIA-U in Japan is lower than in predominantly Caucasian cohorts, as reported from North America and Europe, the epidemiology, characteristics and predictors were found to be similar.

DOI： 10.1186/s12969-019-0318-5

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Human pandemic H1N1 2009 influenza virus causes significant morbidity and mortality with severe acute lung injury due to the excessive inflammatory reaction, even with neuraminidase inhibitor use. The anti-inflammatory effect of anti-high-mobility group box-1 (HMGB1) monoclonal antibody (mAb) against influenza pneumonia has been reported. In this study, we evaluated the combined effect of anti-HMGB1 mAb and peramivir against pneumonia induced by influenza A (H1N1) virus in mice. Nine-week-old male C57BL/6 mice were inoculated with H1N1 and treated with intramuscularly administered peramivir at 2 and 3 days post-infection (dpi). The anti-HMGB1 mAb or a control mAb was administered at 2, 3, and 4 dpi. Survival rates were assessed, and lung lavage and pathological analyses were conducted at 5 and 7 dpi. The combination of peramivir with the anti-HMGB1 mAb significantly improved survival rate whereas the anti-HMGB1 mAb alone did not affect virus proliferation in the lungs. This combination therapy also significantly ameliorated histopathological changes, neutrophil infiltration, and macrophage aggregation by inhibiting HMGB1, inflammatory cytokines, and oxidative stress. Fluorescence immunostaining showed that the anti-HMGB1 mAb inhibited HMGB1 translocation from type I alveolar epithelial cells. In summary, combining anti-HMGB1 with conventional anti-influenza therapy might be useful against severe influenza virus infection.

DOI： 10.1002/jmv.25330

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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[This corrects the article DOI: 10.1155/2018/2380179.].

DOI： 10.1155/2019/4025694

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Language：Japanese   Publisher：(株)メディカルレビュー社  

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Language：Japanese   Publisher：(一社)日本小児神経学会  

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OBJECTIVE: To estimate target of treatment for long-term efficacy of the first biologic agent used to treat polyarticular juvenile idiopathic arthritis (pJIA). METHODS: A retrospective cohort of patients with pJIA treated at six medical institutions in Japan between 1 March 2005 and 31 October 2014 was identified. The patients were divided by 2-year treatment periods with the first biologic agent into continuous treatment group and switching group. Three markers were examined: matrix metalloproteinase-3 (MMP-3), erythrocyte sedimentation rate (ESR), and disease activity score (DAS) 28-ESR. RESULTS: Thirty-two pJIA patients (8 boys, 24 girls) from 43 recruited patients were included in this study. The treatment periods with the first biologic agent in continuous treatment group (24 patients, 75%) was 40 months (median, range 24-119) and switching group (8 patients; 25%) was 9.5 months (median, 6-18). Markers [odds ratio (95% confidence interval)] at 3 months were MMP-3 [1.02 (0.99-1.05), p = .219], ESR [1.00 (0.78-1.30), p = .998], and DAS28-ESR [13.9 (2.08-409.82), p = .035]. The cut-off point for DAS28-ESR at 3 months to distinguish the two groups was 2.49 (sensitivity, 87.5%; specificity, 87.5%). CONCLUSION: DAS28-ESR of 2.49 at 3 months after initiating the first biologic agent can be a target of sustained treatment in pJIA patients.

DOI： 10.1080/14397595.2017.1415628

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Encephalopathy is a major cause of influenza-associated child death and severe neurological sequelae in Japan, highlighting the urgent need for new therapeutic strategies. In this study, we evaluated the effects of anti-high mobility group box-1 monoclonal antibody (α-HMGB1) treatment on brain edema induced by influenza A virus (IAV) and lipopolysaccharide in 4-week-old BALB/c female mice. The results showed that administration of 7.5 mg/kg α-HMGB1 1 h after IAV (A/Puerto Rico/8/34) inoculation significantly alleviated brain edema at 48 h after IAV inoculation, as confirmed by the suppression of Evans Blue dye leakage and matrix metallopeptidase-9 mRNA expression in the brain. Moreover, we also observed suppression of oxidative stress and different cytokines in IAV-inoculated mice. The expression of plasminogen activator inhibitor-1 was also attenuated following treatment with α-HMGB1. Notably, α-HMGB1 treatment had no effect on virus propagation in the lung. In summary, anti-HMGB1 treatment may improve the prognosis in cases with influenza-associated encephalopathy by attenuating brain edema and reducing the inflammatory responses induced by HMGB1.

DOI： 10.1002/jmv.25076

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Procalcitonin (PCT) is used as a biomarker in severe infections. Here, we retrospectively investigated levels of serum PCT, C-reactive protein (CRP), and inflammatory cytokines (IL-6, TNF-α, and IFN-γ) in the second phase of patients with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). Nine AESD pediatric patients (4 men, 5 women; AESD group) admitted to Okayama University Hospital from 2010 to 2016 were compared with 10 control patients with febrile seizures (FS) (3 men, 7 women; FS group). Mean PCT concentrations (ng/mL) in the AESD and FS groups were significantly different, at 9.8 ± 6.7 and 0.8 ± 0.9, respectively (p = 0.0011). CRP (mg/dL) were 0.79 ± 0.89 and 1.4 ± 1.0 (p = 0.21), respectively; IL-6 (pg/mL) were 449.7 ± 705.0 and 118.3 ± 145.4 (p = 0.20), respectively; TNF-α (pg/mL) were 18.6 ± 12.5 and 16.6 ± 6.0 (p = 0.67), respectively; and IFN-γ (pg/mL) were 79.6 ± 158.5 and 41.9 ± 63.7 (p = 0.56), respectively. Ratios of PCT to CRP were 27.5 ± 34.2 and 3.2 ± 6.8 (p < 0.0001), respectively. The sensitivity and specificity in the diagnosis of AESD using a cutoff of PCT/CRP ratio of 1.0 were 100% and 80%, respectively. These results suggest that PCT and the PCT/CRP ratio are useful in auxiliary diagnosis of the second stage of AESD, and in AESD, PCT is likely to increase through a different mechanism.

DOI： 10.1155/2018/2380179

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Language：Japanese   Publisher：(一社)日本脳卒中の外科学会  

症例1:9歳女児。左片麻痺で発症し、右内包後脚脳梗塞と診断された。aspirin内服を行い、24ヵ月再発なく外来加療中である。症例2:13歳男児。けいれん発作、意識障害、左片麻痺が生じ、動脈炎として加療開始された。右中大脳動脈領域に脳梗塞を認めたため外減圧術を施行したが、第62病日に頭蓋骨形成術を施行後に意識障害が生じ、けいれん重積状態となった。barbitalを用いた2週間にわたる鎮静・呼吸循環管理にて徐々に改善したが、左不全麻痺の悪化、右不全麻痺を生じた。17ヵ月経過現在、両杖をついた歩行訓練を行っている。症例3:10ヵ月女児。左不全片麻痺で発症し、3日後に意識障害が生じた。右側の血栓性脳梗塞と考えaspirin内服を開始したが、脳梗塞の再発、左側に新規の脳梗塞を来たした。warfarinとaspirinの内科加療を開始し、16ヵ月再発なく経過している。症例4:2歳女児。Klippel-Trenaunay症候群として経過観察されていた。繰り返す左片麻痺とけいれん発作が生じ、右内頸動脈の閉塞ないし狭窄に伴う脳虚血と診断し、aspirin内服加療を開始した。16ヵ月間再発なく経過している。

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Our previous analysis of gene expression profiles in the peripheral blood from patients with influenza A (H1N1) pdm09 pneumonia revealed elevated transcription levels of the vanin-1 (vascular non inflammatory molecule 1, VNN1) gene, which encodes an epithelial ectoenzyme with pantetheinase activity involved in recycling coenzyme A. Here, to elucidate the role of VNN1 in influenza A virus (IAV) H1N1 infection, we investigated the change of VNN1 expression in the context of IAV infection and the effects of its related substances, i.e., its direct substrate pantetheine and its two metabolites pantothenic acid and cysteamine on the replication of IAV in the human alveolar epithelial carcinoma cell line A549. The messenger RNA expression of VNN1 in A549 cells was significantly increased (by 4.9-fold) after IAV infection under an elevated concentration of pantetheine. Moreover, VNN1 mRNA levels were elevated by > 100-fold in response to pro-inflammatory cytokines, especially TNF-alpha and IL-1 beta. Pantetheine significantly reduced the IAV replication and IAV Matrix 1 (M1) mRNA levels when it was administered prior to and during infection. In addition, cysteamine treatment during IAV infection significantly reduced the viral replication and IAV M1 mRNA levels, whereas pantothenic acid did not. These findings suggest that the metabolic pathway catalyzed by VNNI pantetheinase plays a suppressive role in IAV infection in the respiratory tract, especially in severe conditions under hypercytokinemia. (C) 2017 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2017.05.172

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Language：Japanese   Publisher：日本小児感染症学会  

EBV関連血球貪食性リンパ組織球症(EBV-HLH)の児で初発時にCD8陽性T細胞に感染していたが、再燃時にB細胞内に増殖を認めた症例を経験したので報告する。症例は2歳の女児であり、発熱と汎血球減少からEBV-HLHと診断された。EBV-DNA量と感染細胞のプロファイリングを行い、診断時にはEBV-DNA量の増加とCD8陽性T細胞への感染を確認した。本児にはHLH-2004プロトコールに準じて治療を開始した。全血EBV-DNA量は一時的に検出感度未満まで低下したが、治療終了直後に再度増加した。感染細胞のプロファイリングによりB細胞内へのEBV感染が疑われた。EBV-HLHの再発例では造血幹細胞移植を行うこともあるが、感染細胞の同定によりB細胞への感染が考えられたためリツキシマブを使用し、EBV-DNA量は速やかに検出感度未満となった。EBV-DNA定量と感染細胞の同定はEBV-HLHの治療方針の決定に有用であると考えられた。(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Okayama University Medical School  

DOI： 10.18926/AMO/54987

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Language：Japanese   Publisher：(株)日本小児医事出版社  

上腸間膜動脈症候群(superior mesenteric artery syndrome:SMAS)は、十二指腸の水平脚が上腸間膜動脈(superior mesenteric artery:SMA)と腹部大動脈あるいは椎体にはさまれて圧迫されることにより起こる十二指腸の通過障害の症候群である。保存的治療が第一選択とされ、無効の場合は外科的治療の適応となる。しかし、保存的治療の期間について明確な基準は確立されていない。今回、側彎症に対する脊柱矯正固定術後にSMASを発症し、76日間にわたる保存的治療が有効であった11歳女児の1例を経験した。体重の増加が確認できるならば長期の保存的治療は脊柱矯正固定術後に発症したSMASに有用であると考えられた。(著者抄録)

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Bordetella pertussis causes life-threatening apnea in infants. Lymphocytosis is an important clue for diagnosis and for determining the severity of pertussis. Antibiotics do not shorten or ameliorate the disease and only decrease the risk of transmission. Antepartum maternal immunization is important for preventing pertussis in infants.

DOI： 10.1002/ccr3.765

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OBJECTIVE: To compare local and systemic profiles between different disease pathologies (pneumonia and encephalitis) induced by influenza A virus (IAV). METHODS: An IAV pneumonia model was created by intranasal inoculation of C57BL/6 mice with influenza A/WSN/33 (H1N1) virus. Lung lavage and blood collection were performed on day 3 after IAV inoculation. Similarly, an IAV encephalitis mouse model was created by direct intracranial IAV inoculation. Cerebrospinal fluid (CSF) and blood collection were conducted according to the same schedule. Cytokine/chemokine profiles were produced for each collected sample. Then the data were compared visually using radar charts. RESULTS: Serum cytokine profiles were similar in pneumonia and encephalitis models, but local responses between the bronchoalveolar lavage fluid (BALF) in the pneumonia model and CSF in the encephalitis model differed. Moreover, to varying degrees, the profiles of local cytokines/chemokines differed from those of serum in both the pneumonia and encephalitis models. CONCLUSION: Investigating local samples such as BALF and CSF is important for evaluating local immune responses, providing insight into pathology at the primary loci of infection. Serum data alone might be insufficient to elucidate local immune responses and might not enable clinicians to devise the most appropriate treatment strategies.

DOI： 10.1155/2017/2594231

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Language：Japanese   Publisher：(公社)日本小児科学会  

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DOI： 10.1016/j.jns.2016.03.038

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INTRODUCTION: Provision for the emergence of an influenza pandemic is an urgent issue. The discovery of a novel anti-influenza therapeutic approach would increase the effectiveness of traditional virus-based strategies. This study was undertaken to evaluate the therapeutic effects of anti-high mobility group box-1 (HMGB1) monoclonal antibody (mAb) treatment on influenza A virus (H1N1)-induced pneumonia in mice. METHODS: Nine-week-old male C57BL/6 mice were inoculated with H1N1, then anti-HMGB1 mAb or control mAb were administered intravenously at 1, 24 and 48 hours after H1N1 inoculation and the survival rate was analyzed. Lung lavage and histopathological analysis were performed on days 3, 5, 7 and 10 after inoculation. RESULTS: Anti-HMGB1 mAb significantly improved the survival rate of H1N1-inoculated mice (1 out of 15 versus 8 out of 15 deaths in the anti-HMGB1 mAb-treated group versus the control mAb-treated group, p < 0.01), although the treatment did not affect virus propagation in the lungs. The treatment also significantly attenuated histological changes and neutrophil infiltration in the lungs of H1N1-inoculated mice. This was associated with inhibition of HMGB1 and suppression of inflammatory cytokine/chemokine expression and oxidative stress enhancement, which were observed in H1N1-inoculated mice. The expression of receptor for advanced glycation end products and nuclear factor κB was attenuated by the treatment. CONCLUSIONS: Anti-HMGB1 mAb may provide a novel and effective pharmacological strategy for severe influenza virus infection in humans by reducing the inflammatory responses induced by HMGB1.

DOI： 10.1186/s13054-015-0983-9

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Viral infections have been implicated as a cause of complex seizures in children. The pathogenic differences in complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis remain unclear. This study analyzed the gene expression profiles in the peripheral whole blood from pediatric patients with complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis. The gene expression profiles of ten patients (five with seizures and five without) with influenza A(H1N1)pdm09 and six patients (three with seizures and three without) with rotavirus gastroenteritis were examined. Gene expression profiles in the whole blood were different in complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis. Transcripts related to the immune response were significantly differentially expressed in complex seizures with influenza A(H1N1)pdm09, and transcripts related to the stress response were significantly differentially expressed in complex seizures with rotavirus gastroenteritis. Pathway analysis showed that the mitogen-activated protein kinases in the T cell receptor signaling pathway were activated in complex seizures due to influenza A(H1N1)pdm09. Dysregulation of the genes related to immune response or stress response could contribute to the pathogenic differences of the complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis.

DOI： 10.1007/s13365-013-0231-5

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UNLABELLED: : Familial cold autoinflammatory syndrome, Muckle-Wells syndrome (MWS), and chronic, infantile, neurological, cutaneous and articular (CINCA) syndrome are dominantly inherited autoinflammatory diseases associated to gain-of-function NLRP3 mutations and included in the cryopyrin-associated periodic syndromes (CAPS). A variable degree of somatic NLRP3 mosaicism has been detected in ≈35% of patients with CINCA. However, no data are currently available regarding the relevance of this mechanism in other CAPS phenotypes. OBJECTIVE: To evaluate somatic NLRP3 mosaicism as the disease-causing mechanism in patients with clinical CAPS phenotypes other than CINCA and NLRP3 mutation-negative. METHODS: NLRP3 analyses were performed by Sanger sequencing and by massively parallel sequencing. Apoptosis-associated Speck-like protein containing a CARD (ASC)-dependent nuclear factor kappa-light chain-enhancer of activated B cells (NF-κB) activation and transfection-induced THP-1 cell death assays determined the functional consequences of the detected variants. RESULTS: A variable degree (5.5-34.9%) of somatic NLRP3 mosaicism was detected in 12.5% of enrolled patients, all of them with a MWS phenotype. Six different missense variants, three novel (p.D303A, p.K355T and p.L411F), were identified. Bioinformatics and functional analyses confirmed that they were disease-causing, gain-of-function NLRP3 mutations. All patients treated with anti-interleukin1 drugs showed long-lasting positive responses. CONCLUSIONS: We herein show somatic NLRP3 mosaicism underlying MWS, probably representing a shared genetic mechanism in CAPS not restricted to CINCA syndrome. The data here described allowed definitive diagnoses of these patients, which had serious implications for gaining access to anti-interleukin 1 treatments under legal indication and for genetic counselling. The detection of somatic mosaicism is difficult when using conventional methods. Potential candidates should benefit from the use of modern genetic tools.

DOI： 10.1136/annrheumdis-2013-204361

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BACKGROUND: The pathogenic mechanisms underlying influenza A(H1N1)pdm09-associated central nervous system (CNS) manifestations and pneumonia remain unclear. This study examined A(H1N1)pdm09 host responses using gene expression profiles of patients' peripheral blood. METHODS: Sixteen A(H1N1)pdm09-infected children in three groups were examined: a CNS group, with convulsion and altered consciousness (n = 6); a pneumonia (Pneu) group (n = 5); and a group of infected control patients (n = 5). The signal ratios of the acute to recovery phases in CNS or Pneu were analyzed versus those of the control. RESULTS: The CNS (619 transcripts) and Pneu (656 transcripts) groups had significantly increased signal ratios compared to the control group. Regarding the increased ratios of transcripts shown by multiple probes, contactin-associated protein-like 3 transcripts, oleoyl-ACP hydrolase transcripts, and interleukin 1 type 1 receptor were observed in CNS and Pneu. Increased ratios of prostaglandin-endoperoxide synthase 2 and α-synuclein were characteristic of CNS. Alkaline phosphatase and the Fc fragment of IgA receptor were characteristic of Pneu. Regarding enriched gene ontology terms, 'response to lipopolysaccharide', 'innate immune response', and 'intrinsic to membrane' were observed commonly in CNS and Pneu. Enriched gene ontology terms related to 'hemoglobin' and 'hemostasis' were, respectively, characteristic of CNS and Pneu. CONCLUSION: These symptom-associated transcripts might be some clues to the pathogenesis of the A(H1N1)pdm09 infection.

DOI： 10.1111/ped.12139

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BACKGROUND: Acute encephalitis/encephalopathy (AEE) is a devastating cause of severe neurodevelopmental sequelae or death in children. Assessing ongoing brain injury and predicting outcomes using bedside point-of-care testing is expected to be extremely valuable. METHODS: For this study, three brain injury markers, S-100B, glial fibrillary acidic protein (GFAP), and tau protein, were measured in early cerebrospinal fluid samples of children with AEE. Subjects comprised three groups: Group 1 (non-AEE control, n = 27); Group 2 (AEE with normal resolution or mild sequelae, n = 13); and Group 3 (AEE with severe sequelae or death, i.e. "poor outcome," n = 10). RESULTS: All marker levels were significantly higher in Group 3 than in Group 1 or 2. In Group 3, only S-100B was significantly higher in non-survivors than in survivors. For scoring assessment (range: 0-3 points), the predictive accuracies of 3 points for poor outcomes in children with AEE (i.e. Group 2 and 3, n = 23) were 91% (21/23) for S-100B, 74% (17/23) for GFAP, and 78% (18/23) for tau. When the scores were summed up for S-100B, GFAP, and tau (range: 0-9 points), and for S-100B and tau (range: 0-6 points), the patients with poor outcomes were identified more accurately using the respective thresholds of 6 points and 4 points (96% [22/23] and 100% [23/23], respectively). CONCLUSION: Our findings suggest that combined measurement and scoring assessment of the markers, especially S-100B and tau, show promise as predictors of clinical outcomes in children with AEE.

DOI： 10.1111/ped.12094

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DOI： 10.1097/CCM.0b013e3182676352

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DOI： 10.4044/joma.125.109

J-GLOBAL

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Blackwell Publishing Asia Pty  

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Other Link： http://search.jamas.or.jp/link/ui/2012230447

Language：Japanese   Publisher：日本臨床免疫学会  

生物学的製剤の治療導入により、リウマチ疾患群の治療予後は劇的に改善した。一方それに伴う副作用が問題となっている。なかでもinfliximab投与による結核発症の増加が関心を集めている。単球は種々のサイトカイン刺激によりマクロファージ・樹状細胞・破骨細胞・多核球に分化する。なかでもTNF-αはマクロファージ活性化や肉芽腫・多核巨細胞(Langhans-type)形成といった結核菌に対する単球の免疫防御発現にとって不可欠なサイトカインとされている。[目的］肉芽腫病変における多核巨細胞(MNGC; Langhans-type)への分化誘導のメカニズムの検討を行うことにより、生物学的製剤による結核発症のメカニズムの検討を行った。［方法］末梢血から単球を９０％以上の純度で単離。GM-CSF(20ng/mL)・TNF-α(20ng/mL)・IL-4存在下に21日間培養。細胞分析プログラムを用いて多核細胞について形態および機能解析を行った。［結果］GM-CSF+IL-4は樹状細胞にさらにTNF-α刺激が単球を有効に集簇させ多核巨細胞へと分化させた。巨細胞はFAK・Rhoキナーゼの阻害により、細胞癒合が阻止された。また巨細胞形成は、抗TNF-α中和抗体により強力に抑制されたが、TNF-αRIIに対する抗体では影響が無かった。［結論］Langhans巨細胞形成とその維持は細胞内寄生菌である結核菌の免疫防御に重要であり、この機能低下が結核発症（潜在性感染の顕性化）に関与すると推察された。Etanercept/Tocilizmabでは細胞分化への影響は乏しく、結核発症率には影響が少ないと考えられた。各生物学的製剤使用中の結核発症症例数と併せ報告する。

DOI： 10.14906/jscisho.39.0.128.0

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Increases of cytokine in the blood play important roles in the pathogenesis of influenza-associated encephalopathy. TNF-alpha was administered intravenously to wild-type mice, after which blood, CSF and brain tissue were obtained, and changes in BBB permeability, the amounts of MMP-9 and TIMP-1, and the localization of activated MMP were assessed. There was a significant increase in BBB permeability after 6 and 12 hr. MMP-9 was increased after 3 hr in the brain and cerebrospinal fluid, which was earlier than in the serum. TIMP-1 protein in the brain increased significantly after MMP-9 had increased. Activation of MMP-9 was observed in neurons in the cerebral cortex and hippocampus, and in vascular endothelial cells. These findings suggest that an increase in blood TNF-alpha promotes activation of MMP-9 in the brain, and may also induce an increase in permeability of the BBB. Early activation of MMP-9 in the brain may contribute to an early onset of neurological disorders and brain edema prior to multiple organ failure in those inflammatory diseases associated with highly increased concentrations of TNF-alpha in the blood, such as sepsis, burns, trauma and influenza-associated encephalopathy.

DOI： 10.1111/j.1348-0421.2010.00226.x

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OBJECTIVE: Early-onset sarcoidosis (EOS), which occurs in children younger than 5 years of age, is associated with granulomatous lesions and a sporadic genetic mutation of the nucleotide-binding oligomerization domain 2 that causes constitutive NF-kappaB activation. The symptoms of EOS can be uncontrollable, progressive, and associated with profound complications. However, appropriate therapy is still under investigation. The aim of this study was to assess the efficacy of thalidomide in patients with severe EOS, based on etiology supporting an initial role of NF-kappaB in activation of this disease. METHODS: Thalidomide was given to 2 patients with EOS (a 16-year-old girl and an 8-year-old boy) at an initial dosage of 2 mg/kg/day, and the dosage was increased if necessary. To elucidate the mechanism of the drug, peripheral blood monocytes were isolated from the patients and stimulated with cytokines (macrophage colony-stimulating factor, tumor necrosis factor alpha, and interleukin-4), and their ability to form multinucleated giant cells (MGCs) and osteoclasts was measured. RESULTS: Both patients showed dramatic improvement of their clinical symptoms (alleviation of fever and optic nerve papillitis, achievement of a response according to the American College of Rheumatology Pediatric 50 and Pediatric 70 criteria) and laboratory findings. Monocytes from patients with EOS had a greater ability to survive and induce MGCs and osteoclasts than those from healthy control subjects. The formation of MGCs and osteoclasts was inhibited by the presence of thalidomide. CONCLUSION: The ability of thalidomide to improve clinical symptoms and laboratory findings in patients with EOS indicates a central role for NF-kappaB activity in this disorder. Inhibition of IKK might be a pharmacologic action by which thalidomide down-regulates NF-kappaB signaling. Thalidomide may be an effective medication in patients with severe complications of EOS, including ocular involvement.

DOI： 10.1002/art.25035

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Responsible for pages：233-252,371-386   Language：English

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Language：Japanese   Publisher：(一社)日本小児感染症学会  

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Language：Japanese   Publisher：(一社)日本小児アレルギー学会  

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Language：Japanese   Publisher：(一社)日本小児心身医学会  

好酸球性消化管疾患は慢性の嘔吐や腹痛の原因となり、内視鏡検査所見で非特異的な所見を呈する症例や肉眼的な異常を呈さない症例では診断が難しい場合がある。今回、慢性の嘔吐・腹痛があり、心因性の腹痛と考えられていたが、アレルギー素因があることから好酸球性消化管疾患が疑われ、上部消化管内視鏡検査で粘膜生検をすることで、好酸球性消化管疾患と診断することができた症例を経験した。プロトンポンプ阻害薬およびロイコトリエン受容体拮抗薬による治療を開始し、症状の改善を認めた。慢性の消化器症状を有する患者でアレルギー素因がある場合には、好酸球性消化管疾患を鑑別に加える必要があると考えられた。(著者抄録)

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Language：Japanese   Publisher：(一社)日本小児感染症学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：岡山医学会  

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Language：Japanese   Publisher：日本小児感染症学会  

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Language：Japanese   Publisher：(一社)日本小児リウマチ学会  

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Language：Japanese   Publisher：日本小児感染症学会  

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Language：Japanese   Publisher：(一社)日本小児リウマチ学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：日本小児アレルギー学会  

J-GLOBAL

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Language：Japanese   Publisher：日本小児感染症学会  

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Language：Japanese   Publisher：日本小児感染症学会  

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Language：Japanese   Publisher：(一社)医療の質・安全学会  

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Language：Japanese   Publisher：(一社)日本小児リウマチ学会  

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Language：Japanese   Publisher：(一社)日本小児リウマチ学会  

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Language：Japanese   Publisher：(一社)日本小児アレルギー学会  

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Language：Japanese   Publisher：日本小児アレルギー学会  

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Language：Japanese   Publisher：日本小児アレルギー学会  

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Language：Japanese   Publisher：日本小児アレルギー学会  

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Language：Japanese   Publisher：日本小児アレルギー学会  

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Language：Japanese   Publisher：日本小児アレルギー学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY  

Web of Science

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：日本臨床ウイルス学会  

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Language：Japanese   Publisher：(一社)日本小児リウマチ学会  

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Language：Japanese   Publisher：日本臨床ウイルス学会  

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Language：Japanese   Publisher：(一社)日本小児リウマチ学会  

J-GLOBAL

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：日本小児感染症学会  

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Language：Japanese   Publisher：(株)日本小児医事出版社  

症例は14歳女児。発熱、腹痛、下痢で発症し、入院後の大腸内視鏡検査で潰瘍性大腸炎(ulcerative colitis:以下UC)と診断された。全大腸炎型UCであり、臨床的重症度分類では中等症であった。プレドニゾロン、5-アミノサリチル酸製剤により寛解導入を試みたが、治療中に重症化したため、経口タクロリムス療法を併用した。治療開始5日目ころから血便、腹痛が改善し、寛解に導入できた。タクロリムス使用中重大な副作用は認められなかった。また、経過中に酸化ストレスの指標である血清総ハイドロペルオキシド濃度を計測した。その値は病勢に一致して変動しており、UCの病態生理に酸化ストレス亢進が関与することが示唆された。タクロリムスは近年内科領域で難治性のUCに対し使用され、効果をあげている。今後、小児のUCに対する有効な治療選択の1つとして期待される。(著者抄録)

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Other Link： http://search.jamas.or.jp/link/ui/2012267026

Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

J-GLOBAL

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(株)日本小児医事出版社  

無疱性帯状疱疹は皮疹を欠く無疱性の水痘帯状疱疹ウイルス(VZV)感染症であるが、その診断は困難であることが少なくない。今回、急性リンパ性白血病(ALL)の寛解期維持療法中にVZV再活性化により無疱性帯状疱疹と髄膜炎を発症した小児例を経験した。症例は15歳男児で、B前駆細胞性ALLの維持療法中に発熱、嘔吐を来して入院した。経過中、脳脊髄液細胞増加と左末梢性顔面神経麻痺が出現した。皮疹は出現しなかったが、髄液と唾液よりVZV-DNAが検出されたため、VZV再活性化による無疱性帯状疱疹および髄膜炎と診断した。プレドニゾロンとアシクロビルの併用により、諸症状は改善した。白血病の経過中に生じる顔面神経麻痺は、原病の再発と関連する場合が多いが、ウイルスの再活性化に伴う場合もあり、その鑑別診断は適切な治療を行ううえで重要である。(著者抄録)

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Language：Japanese   Publisher：日本臨床免疫学会  

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Language：Japanese   Publisher：(一社)日本小児感染症学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Event date： 2021.6.22

Language：Japanese   Presentation type：Oral presentation (general)  

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