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Question: Which is the best strategy to achieve (drug-free) inactive disease in juvenile idiopathic arthritis (JIA)?Methods: In a randomised, single-blinded, study in disease-modifying anti-rheumatic drug (DMARD)-naive patients with JIA, three treatment-strategies were compared: (1) sequential DMARD-monotherapy (sulfasalazine or methotrexate (MTX)), (2) combination therapy MTX + 6 weeks prednisolone and (3) combination therapy MTX +etanercept. Treatment-to-target entailed 3-monthly DMARD/biological adjustments in case of persistent disease activity, with drug tapering to nil in case of inactive disease.After 24 months, primary outcomes were time-to-inactive-disease and time-to-flare after DMARD discontinuation. Secondary outcomes were adapted ACRPedi30/50/70/90 scores, functional ability and adverse events.Results: 94 children (67 % girls) aged median (IQR) 9.1 (4.6-12.9) years were enrolled: 32 in arms 1 and 2, 30 in arm 3. At baseline visual analogue scale (VAS) physician was mean 49 (SD 16) mm, VAS patient 53 (22) mm, erythrocyte sedimentation rate 12.8 (14.7), active joints median 8 (5-12), limited joints 2.5 (1-4.8) and Childhood Health Assessment Questionnaire score mean 1.0 (0.6).After 24 months, 71% (arm 1), 70% (arm 2) and 72% (arm 3) of patients had inactive disease and 45% (arm 1), 31% (arm 2) and 41% (arm 3) had drug-free inactive disease. Time-to-inactive-disease was median 9.0 (5.3-15.0) months in arm 1, 9.0 (6.0-12.8) months in arm 2 and 9.0 (6.0-12.0) months in arm 3 (p=0.30). Time-to-flare was not significantly different (overall 3.0 (3.0-6.8) months, p=0.7). Adapted ACR pedi-scores were comparably high between arms. Adverse events were similar.Conclusion: Regardless of initial specific treatments, after 24 months of treatment-to-target aimed at drug-free inactive disease, 71% of recent-onset patients with JIA had inactive disease (median onset 9 months) and 39% were drug free. Tightly controlled treatment-to-target is feasible.Trial Registration Number: 1574. [ABSTRACT FROM AUTHOR]

Background aims. Infusion of mesenchymal stromal cells (MSCs) has been reported to be an effective treatment modality for acute graft-versus-host disease, and MSCs have been considered for use in the treatment of patients with autoimmune diseases. Before contemplating clinical studies with MSCs in patients with systemic juvenile idiopathic arthritis (sJIA), the immunomodulatory capacity of MSCs in this setting needs to be explored. A comparative analysis of bone marrow-derived MSCs from children with sJIA and healthy pediatric controls was performed. Methods. MSCs were successfully expanded from 11 patients with sJIA and 10 controls. The phenotype, differentiation and iinmunomodulatory capacity of these MSCs were compared. The effect of immunosuppressive drugs on MSC function was also investigated. Results. MSCs from patients with sJIA and controls showed no differences in their suppressive effect using control peripheral blood mononuclear cells. Furthermore, the suppression of the response of peripheral blood mononuclear cells from patients with sJIA by autologous sJIA MSCs and allogeneic control MSCs was comparable. The immunosuppressive effect of both groups of MSCs was diminished in the presence of indomethacin (P < 0.05). MSCs from patients with sJIA and controls suppressed interleukin-2-induced natural killer cell activation to a similar extent. In addition, MSCs of patients with sJIA and controls inhibited the differentiation of monocytes to dendritic cells. Conclusions. This is the first explorative study in a significant cohort of patients with sJIA to evaluate the effect of MSCs on adaptive and innate immune responses. The comparable immunosuppressive characteristics of MSCs derived from patients with sJIA to age-matched controls support the potential use of patient-derived MSCs in the treatment of sJIA. [ABSTRACT FROM AUTHOR]

Over the past decades, the intestinal microbiota has increasingly gained attention in studies addressing the pathophysiology of (pediatric) autoimmune diseases, including inflammatory joint diseases, inflammatory bowel disease (IBD), and type 1 diabetes. In this study, we have analyzed the composition of gut microbiota of newly diagnosed juvenile idiopathic arthritis (JIA) patients, prior to initiation of disease-modifying antirheumatic drugs (DMARDs). Fecal microbiota profiles of 8 JIA patients (median age: 11.1 years, 6 girls) were compared with 22 healthy age-matched controls using IS-pro, a 16S-23S interspacer (IS) region-based, eubacterial molecular detection technique. By partial least squares discriminant analysis (PLS-DA), microbiota profiles of JIA and controls could significantly be discriminated based on a limited set of species belonging to the phylum Bacteroidetes (Fig. 2), but not within other phyla, with a sensitivity of 88%, specificity of 73% (Fig. 3), and area under the curve (AUC) 0.87 (95% CI: 0.73-0.87). These discriminative species have been considered to be part of the microbial core in healthy children. Conclusion Our findings add to the increasing notion that the gut microbiota may be involved in the pathophysiology of JIA. Species involved in the discrimination between JIA and controls are members of the microbial core in the healthy state. Expanding knowledge on JIA-specificmicrobial signatures and host interactions may open avenues to explore options to develop individualized, microbiota-based preventive, and therapeutic interventions in JIA. [ABSTRACT FROM AUTHOR]

Nocturnal crying in toddlers has a broad spectrum of causes, including psychosocial and somatic causes, whereby the majority are self-limiting and do not need referral to specialist medical care. Although uncommon, atypical presentations of nocturnal crying-such as spondylodiscitis-require referral to specialist medical care, especially when combined with discomfort. In this case report, we present a case of a 15-month-old girl with an atypical presentation of nocturnal crying in combination with back pain., Competing Interests: Conflicts of interest None to report. The authors would like to thank the patients’ parents for providing their consent for this case report. The authors would also like to thank M. Reijnierse, A.J. van der Molen, V. Fejzovic, B. Boekestijn, D.A.W. Eijspaart, Y. Tank, J.L. Bloem (Department of Radiology, Leiden University Medical Centre) and L.F. de Geus-Oei (Department of Nuclear Medicine, Leiden University Medical Centre) for their radiological assessments., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: This review concerns the outcome for nonsystemic juvenile idiopathic arthritis (JIA) with emphasis on treatment-to-target (T2T) and treatment strategies aiming at inactive disease by giving an overview of recent articles., Recent Findings: More efficacious therapies and treatment strategies/T2T with inactive disease as target, have improved the outcome for JIA significantly. Recent studies regarding treatment strategies have shown 47-68% inactive disease after 1 year. Moreover, probability of attaining inactive disease at least once in the first year seems even higher in recent cohort-studies, reaching 80%, although these studies included relatively high numbers of oligoarticular JIA patients. However, 26-76% of patients flare upon therapy withdrawal and prediction of flares is still difficult., Summary: Remission can be achieved and sustained in (some) JIA patients, regardless of initial treatment. Cornerstone principles in the management of nonsystemic JIA treatment are early start of DMARD therapy, striving for inactive disease and T2T by close and repeated monitoring of disease activity. T2T and tight control appear to be more important than a specific drug in JIA. Next to inactive disease, it is important that patients/parents are involved in personal targets, like reduction of pain and fatigue. Future studies should focus on predictors (based on imaging-methods or biomarkers) for sustained drug-free remission and flare.

Two adolescents, on immunosuppressive therapy for graft-versus-host disease, developed hemophagocytic lymphohistiocytosis (HLH) after varicella zoster virus (VZV) reactivation. In the absence of dermatome restricted characteristic skin lesions, VZV reactivation was not immediately recognized and treatment with acyclovir was delayed. The first patient developed optical neuritis and died 2 months after the VZV episode due to massive intracranial hemorrhage. The second patient presented with severe abdominal pain and pancreatitis, followed by atypical skin eruptions, which prompted a faster diagnosis. Both patients recovered from their HLH, the first patient being successfully treated with immunosuppressive agents and the second with VZV treatment only. These two cases demonstrate the difficulties in recognizing VZV reactivation, and in order to start adequate and timely treatment, the need to consider VZV as a possible cause of HLH in severely immunocompromised patients., ((c) 2009 Wiley-Liss, Inc.)