Search

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.)

Objectives: We studied patterns of joint inflammation in juvenile idiopathic arthritis (JIA) to assess whether joint activity recurs locally in the same joints., Methods: Joints of 91 patients of the BeSt for Kids study, a treat-to-target trial for children with recent-onset oligoarticular, rheumatoid factor-negative polyarticular and psoriatic JIA, were clinically assessed during 2 years (10 study visits). The association between joint inflammation at baseline and later inflammation in the same joint was assessed using a multilevel mixed-effects logistic regression model at joint level. With a Poisson model, the association between baseline joint inflammation and the number of study visits at which the same joint was recurrently inflamed was tested., Results: Of the 6097 joints studied, 15% (897) was clinically inflamed at baseline. In 42% (377/897) of those joints, inflammation recurred during follow-up. Joint inflammation at baseline was statistically significantly associated with joint inflammation during follow-up in the same joint (OR 3.9, 95% CI 3.5 to 4.4) and specifically with the number of episodes of recurrent joint inflammation (IRR 1.6, 95% CI 1.2 to 2.1)., Conclusion: In JIA, joint inflammation has the tendency to recur multiple times in joints that are clinically inflamed at disease onset. This indicates that local factors might play a role in the processes contributing to the occurrence of JIA flares., Competing Interests: Competing interests: The original BeSt for Kids study received financial support from Pfizer., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Clinical phenotyping and predicting treatment responses in SLE patients is challenging. Extensive blood transcriptional profiling has identified various gene modules that are promising for stratification of SLE patients. We aimed to translate existing transcriptomic data into simpler gene signatures suitable for daily clinical practice., Methods: Real-time PCR of multiple genes from the IFN M1.2, IFN M5.12, neutrophil (NPh) and plasma cell (PLC) modules, followed by a principle component analysis, was used to identify indicator genes per gene signature. Gene signatures were measured in longitudinal samples from two childhood-onset SLE cohorts (n = 101 and n = 34, respectively), and associations with clinical features were assessed. Disease activity was measured using Safety of Estrogen in Lupus National Assessment (SELENA)-SLEDAI. Cluster analysis subdivided patients into three mutually exclusive fingerprint-groups termed (1) all-signatures-low, (2) only IFN high (M1.2 and/or M5.12) and (3) high NPh and/or PLC., Results: All gene signatures were significantly associated with disease activity in cross-sectionally collected samples. The PLC-signature showed the highest association with disease activity. Interestingly, in longitudinally collected samples, the PLC-signature was associated with disease activity and showed a decrease over time. When patients were divided into fingerprints, the highest disease activity was observed in the high NPh and/or PLC group. The lowest disease activity was observed in the all-signatures-low group. The same distribution was reproduced in samples from an independent SLE cohort., Conclusions: The identified gene signatures were associated with disease activity and were indicated to be suitable tools for stratifying SLE patients into groups with similar activated immune pathways that may guide future treatment choices., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Multisystem inflammatory syndrome in children is a rare, potentially life-threatening postinfectious complication in children after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. It is currently unknown if multisystem inflammatory syndrome in children (MIS-C) can recur upon reinfection with SARS-CoV-2. Here, we report on a former MIS-C patient who was reinfected with SARS-CoV-2 without recurrence of MIS-C., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, 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.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Genuine uncertainty on superiority of one intervention over the other is called equipoise. Physician-investigators in randomized controlled trials (RCT) need equipoise at least in studies with more than minimal risks. Ideally, this equipoise is also present in patient-participants. In pediatrics, data on equipoise are lacking. We hypothesize that 1) lack of equipoise at enrolment among parents may reduce recruitment; 2) lack of equipoise during participation may reduce retention in patients assigned to a less favoured treatment-strategy., Methods: We compared preferences of parents/patients at enrolment, documented by a questionnaire (phase 1), with preferences developed during follow-up by an interview-study (phase 2) to investigate equipoise of child-participants and parents in the BeSt-for-Kids-study (NTR 1574). This trial in new-onset Juvenile Idiopathic Arthritis-patients consists of three strategies. One strategy comprises initial treatment with a biological disease-modifying-antirheumatic-drug (DMARD), currently not standard-of-care. Semi-structured interviews were conducted with 23 parents and 7 patients, median 11 months after enrolment., Results: Initially most parents and children were not in equipoise. Parents/patients who refused participation, regularly declined due to specific preferences. Many participating families preferred the biological-first-strategy. They participated to have a chance for this initial treatment, and would even consider stopping trial-participation when not randomized for it. Their conviction of superiority of the biological-first strategy was based on knowledge from internet and close relations. According to four parents, the physician-investigator preferred the biological-first-strategy, but the majority (n = 19) stated that she had no preferred strategy. In phase 2, preferences tended to change to the treatment actually received., Conclusions: Lack of equipoise during enrolment did not reduce study recruitment, mainly due to the fact that preferred treatment was only available within the study. Still, when developing a trial it is important to evaluate whether the physicians' research question is in line with preferences of the patient-group. By exploring so-called 'informed patient-group'-equipoise, successful recruitment may be enhanced and bias avoided. In our study, lack of equipoise during trial-participation did not reduce retention in those assigned to a less favoured option. We observed a change for preference towards treatment actually received, possibly explained by comparable outcomes in all three arms.

Objectives: To evaluate differences in baseline characteristics between etanercept- and adalimumab-treated JIA patients and to reveal factors that influence the choice between these TNF inhibitors, which are considered equally effective in the recent ACR recommendations for JIA treatment., Methods: Biologic-naïve JIA patients with active arthritis who started treatment with adalimumab or etanercept between March 2008 and December 2011 were selected from the Dutch Arthritis and Biologicals in Children register. Baseline characteristics were compared. Focus group interviews with paediatric rheumatologists were performed to evaluate factors determining treatment choices., Results: A total of 193 patients started treatment with etanercept and 21 with adalimumab. Adalimumab-treated patients had longer disease duration prior to the start of biologics (median 5.7 vs 2.0 years) and more often a history of uveitis (71% vs 4%). Etanercept-treated patients had more disability at baseline (median Childhood Health Assessment Questionnaire score 1.1 vs 0.4) and more active arthritis (median number of active joints 6 vs 4). The presence of uveitis was the most important factor directing the choice towards adalimumab. Factors specific for the paediatric population-such as painful adalimumab injections-as well as the physician's familiarity with the drug accounted for the preference for etanercept., Conclusion: Although the two TNF inhibitors are considered equally effective, in daily practice etanercept is most often prescribed; adalimumab is mainly preferred when uveitis is present. In choosing the most suitable biologic treatment, paediatric rheumatologists take into account drug and patient factors, considering newly published data and cautiously implementing this into daily care.

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 immunomodulatory 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., (Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

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.)