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

Arthritis is one complication of Kawasaki disease (KD); however, the clinical features of arthritis in KD have not been well clarified. We retrospectively investigated the characteristics of persistent arthritis beyond the subacute phase of KD. In this cohort, 49 of 243 patients (20%) developed arthritis, with 33 patients (14%) experiencing persistent arthritis. Among these 33 patients, 31 (94%) had complete KD. Thirty (91%) were resistant to first intravenous immunoglobulin, and 15 (45%) required additional infliximab. Five patients (15%) developed coronary artery lesions, and 24 (73%) had oligoarthritis, mainly in large lower-extremity joints. Twenty-four patients (73%) complained of arthralgia. At arthritis onset, 16 patients (48%) presented with fever, including recurrent fever in 10 patients. Serum C-reactive protein concentration in patients with active arthritis significantly increased compared with after acute KD treatment (2.4 vs. 0.7 mg/dL, p < 0.001). Serum matrix metalloproteinase-3, a biomarker of arthritis, was significantly higher in patients with active arthritis than in remission (93.7 vs. 20.3 ng/mL, p < 0.001). Thirty (91%) and 14 (42%) patients, respectively, were treated with non-steroidal anti-inflammatory drugs and prednisolone, and they completely recovered. To summarize, persistent arthritis is a common complication in refractory KD, and adequate diagnosis and treatment are necessary.

DOI： 10.1038/s41598-023-36308-9

PubMed

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

DOI： 10.1111/ped.15510

PubMed

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

OBJECTIVES: To report the efficacy and safety of canakinumab treatment in Japanese patients with systemic juvenile idiopathic arthritis over a 48-week study period. METHODS: Patients were administered canakinumab 4 mg/kg (maximum dose 300 mg) every 4 weeks, with no dose adjustments. The key outcomes measures included adapted American College of Rheumatology paediatric 30/50/70/90/100 response, proportion of patients with inactive disease, and corticosteroid-tapering. RESULTS: In total, 16/19 (84.2%) patients received canakinumab for ≥96 weeks reaching end-of-study visit without premature discontinuation. Regardless of the level of joint involvement at baseline, high adapted American College of Rheumatology paediatric responses were observed throughout the study; at end-of-study, adapted American College of Rheumatology paediatric 90/100 response rates were 84.2%/63.2%, respectively. The proportion of patients who successfully tapered corticosteroids at end-of-study was 66.7% (12/18), of which 10 patients were steroid-free. The most common adverse events were infections (238.3 events/100 patient-years). Serious adverse events were observed in 52.6%. One event adjudicated as possible macrophage activation syndrome was preceded by sJIA flare. No deaths were reported. CONCLUSIONS: Canakinumab treatment resulted in a sustained treatment response in systemic juvenile idiopathic arthritis patients over 48 weeks and was associated with corticosteroid-tapering in the majority of patients. No new safety findings were reported.

DOI： 10.1093/mr/roac128

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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：(株)日本臨床社  

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

OBJECTIVE: Systemic juvenile idiopathic arthritis (sJIA) is characterized by fever, arthritis, rash, hepatosplenomegaly, and macrophage activation syndrome; however, its pathogenesis is still unclear. Elevated serum interleukin (IL)-18 concentrations and decreased natural killer (NK) cell activity are characteristic of active disease; thus, we examined IL-18 signaling in NK cells from sJIA. METHODS: We analyzed mitogen-activated protein kinase (MAPK) p38 and nuclear factor κ light chain enhancer of activated B cells (NFκB) p65 phosphorylation in NK cells after in vitro recombinant IL-18 (rIL-18) stimulation in 31 patients with sJIA. Associations between clinical features, serum IL-18, and phosphorylation intensity were analyzed. Furthermore, we investigated the effects of high IL-18 concentrations on phosphorylation in NK cells. RESULTS: Patients were divided according to their disease activity: systemic features (n = 8), chronic arthritis (n = 7), remission on medication (n = 10), and remission off medication (n = 6). MAPK p38 and NFκB p65 phosphorylation intensity were the highest in healthy controls, followed by remission off medication, remission on medication (vs. control; MAPK p38, P < 0.01; NFκB p65, P < 0.05), chronic arthritis (P < 0.001, P < 0.001), and systemic features (P < 0.001, P < 0.001). The systemic features group showed a complete defect in phosphorylation. Serum IL-18 was the highest in the systemic features group followed by chronic arthritis, remission on medication (P < 0.01), remission off medication (P < 0.01), and healthy controls (P < 0.01). Phosphorylation intensity was negatively correlated with serum IL-18 (MAPK p38, r2  = 0.42; NFκB p65, r2  = 0.54). Furthermore, healthy control NK cells were cultured with rIL-18; impaired phosphorylation was reproduced in vitro. CONCLUSION: Impaired IL-18 signaling in NK cells correlated with disease activity in sJIA. High serum IL-18 exposure induces impaired MAPK and NFκB phosphorylation in NK cells.

DOI： 10.1002/acr2.11426

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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

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

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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：(公社)日本小児科学会  

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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：(公社)神奈川県医師会  

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

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

INTRODUCTION: Haploinsufficiency of A20 (HA20) is a form of inborn errors of immunity (IEI). IEIs are genetically occurring diseases, some of which cause intestinal dysbiosis. Due to the dysregulation of regulatory T cells (Tregs) observed in patients with HA20, gut dysbiosis was associated with Tregs in intestinal lamina propria. METHODS: Stool samples were obtained from 16 patients with HA20 and 15 of their family members. Infant samples and/or samples with recent antibiotics use were excluded; hence, 26 samples from 13 patients and 13 family members were analyzed. The 16S sequencing process was conducted to assess the microbial composition of samples. Combined with clinical information, the relationship between the microbiome and the disease activity was statistically analyzed. RESULTS: The composition of gut microbiota in patients with HA20 was disturbed compared with that in healthy family members. Age, disease severity, and use of immunosuppressants corresponded to dysbiosis. However, other explanatory factors, such as abdominal symptoms and probiotic treatment, were not associated. The overall composition at the phylum level was stable, but some genera were significantly increased or decreased. Furthermore, among the seven operational taxonomic units (OTUs) that increased, two OTUs, Streptococcus mutans and Lactobacillus salivarius, considerably increased in patients with autoantibodies than those without autoantibodies. DISCUSSION: Detailed interaction on intestinal epithelium remains unknown; the relationship between the disease and stool composition change helps us understand the mechanism of an immunological reaction to microorganisms.

DOI： 10.3389/fcimb.2021.787667

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Language：Japanese   Publisher：神奈川県医師会  

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X-linked inhibitor of apoptosis protein (XIAP) deficiency results in monogenic inflammatory bowel disease. To date, no vasculitis associated with XIAP deficiency has been reported. A 10-year-old boy was diagnosed with Crohn's disease and he responded poorly to conventional treatment for Crohn's disease. He was dependent on corticosteroids and parenteral nutrition. To manage severe colitis, he underwent ileostomy followed by ileocolectomy for an ileo-sigmoid fistula. At the age of 15 years, he developed IgA vasculitis and at the age of 17 years, he developed refractory Takayasu arteritis (TAK), which was resistant to corticosteroid and immunosuppressive therapy. Whole-exome sequencing revealed a novel mutation of the splice acceptor site in XIAP (c.1057-1G > A) at the age of 19 years. Allogeneic hematopoietic stem cell transplantation was successful with subsequent withdrawal of intensive immunosuppressive therapy and clinical remission of both enterocolitis and TAK. This case suggests that patients with XIAP deficiency could develop intractable inflammatory disease involving the intestinal tract and blood vessels.

DOI： 10.1016/j.clim.2020.108495

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Haploinsufficiency of A20 (HA20) causes inflammatory disease resembling Behçet's disease; many cases have been reported, including some that are complicated with autoimmune diseases. This study aims to clarify the immunophenotype of patients with HA20 by analyzing lymphocyte subsets using multicolor flow cytometry. The patients with HA20 previously diagnosed in a nationwide survey were compared by their cell subpopulations. In total, 27 parameters including regulatory T cells (Tregs), double-negative T cells (DNTs), and follicular helper T cells (TFHs) were analyzed and compared with the reference values in four age groups: 0-1, 2-6, 7-19, and ≥20 years. The Tregs of patients with HA20 tended to increase in tandem with age-matched controls at all ages. In addition, patients ≥20 years had increased DNTs compared with controls, whereas TFHs significantly increased in younger patients. In HA20 patients, the increase in DNTs and TFHs may contribute to the development of autoimmune diseases.

DOI： 10.1016/j.clim.2020.108441

Scopus

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Language：Japanese   Publisher：横浜市立大学医学会  

循環不全を伴う川崎病の重症型は川崎病ショック症候群(Kawasaki disease shock syndrome:KDSS)と呼ばれ、KDSSでは急性期の消化器症状の頻度が高いことが知られている。今回、消化器症状が長期に持続したKDSSの症例を経験した。症例は1歳6ヵ月女児。発熱、嘔吐、下痢で発症し、第3病日に川崎病主要症状5/6を認め、診断された。免疫グロブリン大量静注療法(Intravenous immunoglobulin:IVIG)が開始されたが、意識障害、呼吸障害、胆汁性嘔吐を認め、当院に転院搬送となった。来院時にはショックと多臓器不全を伴う播種性血管内凝固症候群を合併していた。ICUにて全身管理を行い、血漿交換療法(plasma exchange:PE)、IVIG、インフリキシマブ、シクロスポリンの追加投与等により、冠動脈の一過性拡張のみで全身炎症は改善した。一方、発症時から胆汁性嘔吐、腹部膨満、腸蠕動音の低下があり、イレウスと判断した。十二指腸チューブでの減圧管理で症状は一旦改善したが、回復期に消化器症状が再燃した。上部消化管造影検査の結果から、機械性腸閉塞の合併が疑われた。川崎病に合併する消化器症状にはイレウスと機械性腸閉塞、ふたつの機序があり、機械性腸閉塞の場合には外科的介入を要することがある。本症例は保存的加療により改善したが、嘔吐、腹痛などの症状が遷延する場合には、消化管造影検査や消化管内視鏡検査等を考慮すべきである。(著者抄録)

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

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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：(株)日本小児医事出版社  

症例は12歳男児。1ヵ月前から持続する発熱で前医に入院となったが熱源が不明であり、当院に転院となった。身体所見に特記すべき所見はなく、血液検査でも非特異的な炎症反応の上昇を認めるのみであった。FDG-PET/CTで左後腹膜に腫瘤性病変を認め、開腹による後腹膜腫瘍摘出術を施行した。病理組織学的に炎症性偽腫瘍(inflammatory pseudotumor:IPT)と診断した。腫瘍摘出後も発熱が持続したため、プレドニゾロン(prednisolone:PSL)を投与し速やかに解熱し、炎症反応も改善した。PSLを漸減終了し、再燃なく経過している。FDG-PET/CTは、発熱以外の症状のない不明熱患者の確定診断に有用である。(著者抄録)

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DOI： 10.1136/annrheumdis-2019-eular.5479

Web of Science

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

<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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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Language：Japanese   Publisher：(一社)日本小児腎臓病学会  

小児ANCA関連血管炎(AAV)は稀である。成人AAVでは、他のリウマチ性疾患合併例が散見されるが、小児の類似報告は殆どない。顕微鏡的多発血管炎(MPA)と多関節型若年性特発性関節炎(pJIA)を合併した2例を報告する。症例1は23歳女性。10歳時にMPAを発症し、メチルプレドニゾロンパルス療法(MPT)とシクロホスファミド静注療法で寛解した。16ヵ月後に関節痛が生じpJIAと診断し、メトトレキサート(MTX)を追加し関節痛は消失した。症例2は14歳女児。11歳時にpJIAを発症し、13歳からプレドニゾロン、MTX、エタネルセプトを開始した。血尿、蛋白尿を認め、14歳時にMPAと診断し、MPT、リツキシマブを開始し改善した。JIAとAAVの併発は稀だが、併発の可能性を考慮した診察や検査を行うべきである。また、両疾患に共通した治療選択が重要であり、とくにMPAに対する治療が、腎予後および生命予後に影響すると考えられた。(著者抄録)

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

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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

小児期発症の全身性エリテマトーデス(SLE)は、成人と比べて急性かつ重篤な経過をたどる。我々は、既存の免疫抑制療法に抵抗性で、再燃に伴い腎機能が低下し、寛解導入に難渋した症例を経験したので報告する。症例は11歳男児、初回の腎生検でISN/RPS分類IV-S(A)であり、ステロイドパルス療法とミコフェノール酸モフェチル(MMF)に加え、経静脈的シクロフォスファミド療法(IVCY)を併用したが寛解に至らなかった。治療開始7ヵ月後にSLEが悪化し、ステロイドパルス療法、タクロリムス、ヒドロキシクロロキンを追加した。その後の腎生検でほぼすべての糸球体に半月体または巣状硬化を認めるIV-G(A/C)と悪化を認め、免疫吸着療法とリツキシマブの投与を行い、再燃から約10ヵ月後に尿所見は正常化した。男性、若年発症、重症ループス腎炎の合併はいずれもSLEの予後不良因子とされている。小児期発症SLEにおいて、男児かつ重症ループス腎炎合併例では早期に寛解導入を目指すべきであり、マルチターゲット療法や免疫吸着療法、リツキシマブ投与も治療の選択肢になり得ると考えた。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J06126&link_issn=&doc_id=20181205350009&doc_link_id=10.34539%2Fpraj.9.1_45&url=https%3A%2F%2Fdoi.org%2F10.34539%2Fpraj.9.1_45&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

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

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

<b>Objectives:</b> Subcutaneous involvement, including calcinosis and panniculitis, is a more common complication in juvenile dermatomyositis (JDM) than in adult dermatomyositis. Magnetic resonance imaging (MRI) is useful for evaluating disease distribution. We investigated the clinical significance of subcutaneous involvement in JDM. <b>Methods:</b> Thighs and hips in 18 newly diagnosed JDM patients were evaluated with fat-suppression MRI. Bilateral muscle, fascial and subcutaneous fat involvement were scored from 0 to 8 points according to the severity of distribution on MRI. Associations between clinical manifestations, serum muscle enzymes, and MRI scores were also evaluated. <b>Results:</b> Abnormal MRI findings in muscle, fascia and subcutaneous fat were observed in 18, 18, and 10 patients, respectively. Subcutaneous fat scores were significantly higher in early-diagnosed JDM patients (diagnosed less than 2 months from onset) than in late-diagnosed JDM patients (diagnosed later) (<i>p</i> = .025). Serum aldolase was elevated in all patients, although only eight demonstrated elevated serum creatine phosphokinase. Serum aldolase was significantly correlated with MRI scores for subcutaneous fat (<i>p</i> < .0001, ρ = .787) and fascia (<i>p</i> = .013 ρ = 0.574), but not muscle. Additionally, serum aldolase was significantly correlated with serum triglycerides (<i>p</i> = .009, ρ = 0.629). <b>Conclusion:</b> Subcutaneous fat involvement is a characteristic finding in early-diagnosed JDM and correlates with elevated serum aldolase.

DOI： 10.1080/14397595.2018.1511026

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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)日本小児リウマチ学会  

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Publishing type：Research paper (scientific journal)  

OBJECTIVE:To validate whether the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (JIA) is practical in the real world. METHODS:A combination of expert consensus and analysis of real patient data was conducted by a panel of 15 pediatric rheumatologists. A total of 65 profiles comprised 18 patients with systemic JIA-associated MAS and 47 patients with active systemic JIA without evidence of MAS. From these profiles, 10 patient data points for full-blown MAS, 11 patient data points for MAS onset, and 47 patient data points for acute systemic JIA without MAS were evaluated. RESULTS:Evaluation of the classification criteria to discriminate full-blown MAS from acute systemic JIA without MAS showed a sensitivity of 1.000 and specificity of 1.000 at the time of full-blown MAS. Sensitivity was 0.636 and specificity was 1.000 at the time of MAS onset. The number of measurement items that fulfilled the criteria increased in full-blown MAS compared to that at MAS onset. At MAS onset, the positive rates of patients who met the criteria for platelet counts and triglycerides were low, whereas those for aspartate aminotransferase were relatively high. At full-blown MAS, the number of patients who met the criteria for each measurement item increased. CONCLUSION:The classification criteria for MAS complicating systemic JIA had a very high diagnostic performance. However, the diagnostic sensitivity for MAS onset was relatively low. For the early diagnosis of MAS in systemic JIA, the dynamics of laboratory values during the course of MAS should be further investigated.

DOI： 10.1002/acr.23482

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

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

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

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Publishing type：Research paper (scientific journal)   Publisher：OMICS Publishing Group  

DOI： 10.4172/1758-4272.1000175

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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：日本小児腎不全学会  

小児有熱性尿路感染症(UTI)では初診時に膿尿を認めない例も存在し、起炎菌の種類が膿尿の有無に影響する可能性がある。本研究では二大起炎菌である大腸菌と腸球菌によるUTIの臨床的特徴を検討した。2010年4月〜2015年11月に単一菌によるUTIと診断された110例を大腸菌群(78例)と腸球菌群(11例)に分け、性別、月齢、UTIの既往歴の有無、先行抗菌薬の有無、有熱期間、血中白血球数、CRP、尿所見、US、VCUGについて比較した。結果、腸球菌群では大腸菌群と比較して血中白血球数が有意に高く(p=0.022)、尿中白血球数が有意に低値となった(p<0.001)。腸球菌性UTIでは膿尿を伴わないことも多く、熱源不明の乳幼児の急性発熱において、迅速にグラム染色が行えない状況では尿培養の追加と抗菌薬の選択を工夫するべきと思われた。(著者抄録)

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Language：Japanese   Publisher：神奈川県医師会  

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

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

<p>【緒言】ベーチェット病（BD）類似の早期発症型自己炎症性疾患を引き起こす常染色体優性遺伝疾患の病因として，TNFAIP3遺伝子のハプロ不全が報告された．TNFAIP3遺伝子がコードする分子A20は，TNF-αシグナル伝達経路上で，その機能を抑制的に制御している．Primary immunodeficiency database in Japan（PIDJ），及び自己炎症性疾患研究班と連携して情報を収集したところ，国内で9家系30症例のA20ハプロ不全症（HA20）症例が判明した．HA20の国内症例について臨床像を調査したので報告する．【結果】9家系で同定された変異はそれぞれの家系で固有のものであり，in vitro機能解析で全て病的変異であることが確認された．また，既報告文献と同様，国内症例においてもTNF-α，IL-1β等の前炎症性サイトカイン産生の増加を認め，Th17細胞への分化過剰も認められたが，Th9への分化過剰は認められなかった．臨床像として，BDの診断基準を満たさない症例が半数程度存在しており，反復性口内炎のみ認める症例等，部分的にBD様症状を認める症例が多く存在していた．またBD様症状以外の症状として自己免疫疾患（自己免疫性肝炎，SLE，橋本病，Graves病，乾癬性関節炎）やネフローゼ症候群，IgA血管炎の併発例を認めている．【結論】HA20患者では自己免疫疾患の発症例が多く認められた．</p>

DOI： 10.2177/jsci.40.304c

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

We report the clinical course and outcome of primary varicella infection in six children with systemic juvenile idiopathic arthritis (sJIA) receiving tocilizumab. None had disseminated or fatal varicella infection, but one patient developed macrophage activation syndrome (MAS) and another had an arthritis relapse. All patients had a significant elevation of serum IL-6 levels, and the two children who developed MAS or arthritis relapse showed high serum IL-18 levels, which could cause a sJIA flare-up.

DOI： 10.1080/14397595.2016.1254314

PubMed

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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)日本小児リウマチ学会  

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Language：Japanese   Publisher：神奈川県医師会  

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Language：Japanese   Publisher：神奈川県医師会  

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

<h4>Background</h4>The aim of this study was to evaluate the performance of two interferon-γ release assays (IGRA), QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB, for pediatric patients with rheumatic disease in Japan and to analyze the frequencies of indeterminate test results with these kits.<h4>Methods</h4>An IGRA was performed in 108 patients <20 years old in order to exclude tuberculosis infection at the time of first application of or change of biological agents and immunosuppressants in Yokohama City University Hospital.<h4>Results</h4>None of the 108 patients tested had active tuberculosis during the 50 month observation period. Indeterminate results of QFT-GIT and T-SPOT.TB tests were obtained in 9.9% and in 0% of cases, respectively. Indeterminate results were obtained significantly more frequently in patients on prednisolone >0.5 mg/kg and in patients with active underlying disease. Use of biologicals and other immunosuppressants had no effect on these measurements.<h4>Conclusions</h4>IGRA are very useful for excluding tuberculosis infection in patients with rheumatic disease before starting new immunosuppressant therapy. Furthermore, the T-SPOT.TB test was suitable for evaluating latent tuberculosis infection even under immunosuppression, when TB tests are generally hard to perform.

DOI： 10.1111/ped.12885

Web of Science

PubMed

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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  

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

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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)日本小児リウマチ学会  

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

<h4>Objective</h4>To examine and delineate inflammatory focus in patients with juvenile idiopathic arthritis (JIA), (18)F-Fluoro-deoxy-glucose (FDG)-positron emission tomography (PET) ((18)F-FDG-PET) was applied to patients with JIA, and the images of these patients were compared.<h4>Methods</h4>Sixty-eight children (59 with systemic JIA (s-JIA) and 9 with polyarticular JIA) were included. The diagnosis of JIA was done to meet the International League of Associations for Rheumatology (ILAR) criteria. After 6-h fasting, whole-body positron emission tomography (PET) scans were acquired 60 min after intravenous injection of 3-5 MBq/kg (18)F-FDG. The interpretation of (18)F-FDG uptake was based on visual characteristics.<h4>Results</h4>Two types of PET images were outstanding in s-JIA; one was (18)F-FDG uptake in red bone marrow, such as the spine, pelvis, and long bones as well as spleen (12 cases), and other type was the uptake in the major joints, such as hips, elbows, wrists, knees, and ankles (8 cases). The former findings were correlated with elevated levels of inflammatory markers, while the latter were with significantly increased levels of MMP-3 (p < 0.05).<h4>Conclusion</h4>There was a noticeable accumulation of (18)F-FDG uptake in bone marrow of s-JIA patients which may indicate the inflammatory focus of this disease and play an important role in the pathogenic basis of arthritis and systemic inflammation of s-JIA.

DOI： 10.3109/14397595.2015.1082686

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PubMed

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

<h4>Purpose</h4>To conduct a national survey of systemic lupus erythematosus (SLE) patients treated with mycophenolate mofetil (MMF). Based on current information on the use of MMF, we aimed to evaluate its efficacy and safety for childhood-onset (c-) SLE.<h4>Target</h4>We evaluated 115 patients by questionnaire on MMF use for c-SLE in medical facilities specializing in pediatric rheumatic and renal diseases.<h4>Results</h4>Average age at SLE onset was 10.6 (range, 2-15) years; average age at the time of starting MMF was 12.3 (range, 2-15) years. Average dose per body surface area was 1,059.3 mg/m(2)/day. Corticosteroid dosing was 20.9 mg/day before treatment but 7.7 mg/day after treatment. Laboratory values before and after MMF treatment were as follows: C3 increased from 67.0 to 84.9 mg/dl (p < 0.001), C4 increased from 10.2 to 15.1 mg/dl (p < 0.001), and anti-DNA antibody decreased from 154.2 to 18.4 IU/ml (p < 0.001). 24 adverse events in 21 cases were reported, but MMF was not discontinued in any.<h4>Conclusions</h4>The amount of MMF for c-SLE in Japan is similar to the standard dose in other countries. Reduction of corticosteroid dose and improvement of laboratory values represent efficacy of MMF. The side effects recorded here indicated tolerability of the drug.

DOI： 10.3109/14397595.2015.1077555

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PubMed

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Language：Japanese   Publisher：神奈川県医師会  

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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  

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

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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)日本小児リウマチ学会  

当科では、若年性線維筋痛症(juvenile fibromyalgia:JFM)に対して、環境分離を主軸とする入院治療を行ってきた。入院の適応は、重症例もしくは社会的因子が病状に強く影響している場合である。入院では、規則正しい生活と院内学級通学、リハビリテーションが治療の中心であり、同時に環境調整(家族や学校との面談)を進め、必要に応じて薬物療法を併用する。2001年3月〜2012年12月までの期間に、当科で入院加療したJFM患児32例について、その効果と実際について検討した。結果は、臨床症状と重症度において、退院時のステージが17例(53%)で改善し増悪は1例のみだった。また、入院中9例(31%)に圧痛点の減少があり、うち6例(19%)は退院時に圧痛点が消失した。入院時に不登校の患児は25例(78%)で、うち9例(36%)が退院後3ヵ月の時点で登校可能となった。入院治療による多面的なアプローチは、JFMの症状改善に有効と考えられた。(著者抄録)

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

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

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

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Language：Japanese   Publishing type：Research paper (scientific journal)  

A 14-year-old boy was admitted in the former hospital with remittent fever, erythematous rash, joint pain, and muscle pain. Antibiotics were ineffectively administered and then, methylprednisolone (mPSL) pulse therapy with methotrexate was introduced under the diagnosis of suspected systemic juvenile idiopathic arthritis (JIA). However, he still had clinical symptoms and signs, and was transferred to our hospital. Re-examination revealed no malignancies including acute leukemia by bone marrow aspiration, no infectious agents by septic work, and no significant increases of antibodies against several viruses including CMV, EBV, HSV, Parvovirus B19, adenovirus, and so forth. FDG-PET demonstrated the accumulation of (18)F-FDG in bone marrows suggesting systemic JIA. Laboratory findings were leukocytosis and granulocytosis, elevated levels of C-reactive protein, D-dimer, ferritin, and interleukin-6. He was finally diagnosed as having severe systemic JIA. Thus, soon after the additional mPSL pulse therapy, tocilizumab (TCZ) was successfully introduced. In conclusion, for systemic JIA patients with severe systemic inflammation, it will be reasonable to introduce tocilizumab earlier than the guideline suggested to reduce side effects of long-term and large amounts of steroids and to protect the transition to macrophage activation syndrome. Further studies will be needed to recommend appropriate timing of tocilizumab introduction.

PubMed

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Language：Japanese   Publishing type：Research paper (scientific journal)  

A 14-year-old boy was admitted in the former hospital with remittent fever, erythematous rash, joint pain, and muscle pain. Antibiotics were ineffectively administered and then, methylprednisolone (mPSL) pulse therapy with methotrexate was introduced under the diagnosis of suspected systemic juvenile idiopathic arthritis (JIA). However, he still had clinical symptoms and signs, and was transferred to our hospital. Re-examination revealed no malignancies including acute leukemia by bone marrow aspiration, no infectious agents by septic work, and no significant increases of antibodies against several viruses including CMV, EBV, HSV, Parvovirus B19, adenovirus, and so forth. FDG-PET demonstrated the accumulation of ¹⁸F-FDG in bone marrows suggesting systemic JIA. Laboratory findings were leukocytosis and granulocytosis, elevated levels of C-reactive protein, D-dimer, ferritin, and interleukin-6. He was finally diagnosed as having severe systemic JIA. Thus, soon after the additional mPSL pulse therapy, tocilizumab (TCZ) was successfully introduced. In conclusion, for systemic JIA patients with severe systemic inflammation, it will be reasonable to introduce tocilizumab earlier than the guideline suggested to reduce side effects of long-term and large amounts of steroids and to protect the transition to macrophage activation syndrome. Further studies will be needed to recommend appropriate timing of tocilizumab introduction. © 2014 The Japan Society for Clinical Immunology.

DOI： 10.2177/jsci.37.176

Scopus

PubMed

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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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J-GLOBAL

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J-GLOBAL

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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)日本リウマチ学会  

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Language：Japanese   Publisher：金原出版(株)  

＜文献概要＞FDG-PETおよびFDG-PET/CTは,不明熱や不明炎症の持続を示す患者の原因検索に有用であり,実臨床で用いられる機会が増えてきた.さまざまな診断技術の進歩に伴い,不明熱の原因としてリウマチ性疾患と類縁疾患の占める割合は相対的に増加している.そのため,それらの代表的疾患の臨床像とFDG-PET所見の理解は有意義である.実際,FDG-PETはしばしば診断に直接的な情報を与え,間接的には 内視鏡検査実施の契機や生検部位の特定に有用である.不明熱の原因精査において,適切な患者にFDG-PET,FDG-PET/CTを行うことは,早期診断や検査の侵襲を減らすことにつながり,診療の質の向上をもたらす.

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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

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Language：Japanese   Publisher：(有)科学評論社  

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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Language：Japanese  

J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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

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

Web of Science

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

Web of Science

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J-GLOBAL

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