Increasing the etanercept dose in a treat-to-target approach in juvenile idiopathic arthritis: does it help to reach the target? A post-hoc analysis of the BeSt for Kids randomised clinical trial.

Background: Etanercept has been studied in doses up to 0.8 mg/kg/week (max 50 mg/week) in juvenile idiopathic arthritis (JIA) patients. In clinical practice higher doses are used off-label, but evidence regarding the relation with outcomes is lacking.

Patterns of clinical joint inflammation in juvenile idiopathic arthritis.

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.

A multidisciplinary care pathway improves quality of life and reduces pain in patients with fibrous dysplasia/McCune-Albright syndrome: a multicenter prospective observational study.

Background: Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) may cause pain, impaired ambulation and decreased quality of life (QoL). International guidelines advocate management of FD/MAS in a tertiary multidisciplinary care pathway, but no longitudinal data are available to support this recommendation. This multicenter prospective observational study aimed to evaluate effects of 1 year of treatment in the FD/MAS care pathway in 2 tertiary clinics on QoL and pain, assessed by change in Short Form 36 and Brief Pain Inventory between baseline and follow-up.

Gene signature fingerprints stratify SLE patients in groups with similar biological disease profiles: a multicentre longitudinal study.

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.

Nailfold capillary scleroderma pattern may be associated with disease damage in childhood-onset systemic lupus erythematosus: important lessons from longitudinal follow-up.

Objectives: To observe if capillary patterns in childhood-onset SLE (cSLE) change over time and find associations between a capillary scleroderma pattern with disease activity, damage or scleroderma-like features.

Methods: Clinical and (yearly) capillaroscopy data from a longitudinal cohort of patients with cSLE (minimum of four Systemic Lupus International Collaborating Clinics (SLICC) criteria, onset <18 years) were analysed. Disease activity was measured by Systemic Lupus Erythematosus Activity Index (SLEDAI) and disease damage by SLICC Damage Index.

Siglec-1 expression on monocytes is associated with the interferon signature in juvenile dermatomyositis and can predict treatment response.

Objective: JDM is a rare chronic immune-mediated inflammatory disease with a predominant role for type I IFN responses. We aimed to determine the potential of Siglec-1 expression on monocytes as a novel IFN-inducible biomarker for disease activity monitoring and prediction of treatment response in patients with JDM.

Methods: Siglec-1 was measured by flow cytometry on circulating monocytes of 21 newly diagnosed JDM patients before start of treatment and, for 10 of these, also during follow-up.

Reliable detection of subtypes of nailfold capillary haemorrhages in childhood-onset systemic lupus erythematosus.

Objectives: In systemic lupus erythematosus (SLE), it is necessary to obtain biomarkers that predict cardiovascular complications due to premature atherosclerosis, which is related to endothelial dysfunction. Nailfold capillary abnormalities might be a biomarker for endothelial dysfunction. In adults and children with SLE, nailfold capillary haemorrhages have shown to be significantly correlated with disease activity.

Dutch patients, caregivers and healthcare professionals generate first nationwide research agenda for juvenile idiopathic arthritis.

Background: Involving the end-users of scientific research (patients, carers and clinicians) in setting research priorities is important to formulate research questions that truly make a difference and are in tune with the needs of patients. We therefore aimed to generate a national research agenda for Juvenile Idiopathic Arthritis (JIA) together with patients, their caregivers and healthcare professionals through conducting a nationwide survey among these stakeholders.

Methods: The James Lind Alliance method was used, tailored with additional focus groups held to involve younger patients.

Nailfold capillary abnormalities in childhood-onset systemic lupus erythematosus: a cross-sectional study compared with healthy controls.

Objectives: For selection of high-risk systemic lupus erythematosus (SLE) patients it is necessary to obtain indicators of disease severity that predict disease damage. As in systemic sclerosis, nailfold capillary abnormalities could be such a biomarker in SLE. The primary objective of this cross-sectional study is to describe capillary abnormalities in childhood-onset SLE (cSLE) cohort (onset < 18 years) and compare them with matched healthy controls.

Macrophage activation syndrome in a newborn: report of a case associated with neonatal lupus erythematosus and a summary of the literature.

Background: Macrophage activation syndrome (MAS) is a life-threatening hyperinflammatory syndrome and is caused by a severely dysregulated immune response. It has rarely been associated with neonatal lupus.

Case Presentation: We present a female neonate with MAS born to a mother who had cutaneous lupus erythematosus with circulating anti-nuclear antibodies (ANA), anti-SSA, anti-SSB and anti-extractable nuclear antigen (anti-ENA) antibodies.

Update on the treatment of nonsystemic juvenile idiopathic arthritis including treatment-to-target: is (drug-free) inactive disease already possible?

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.

Endothelial and Inflammation Biomarker Profiles at Diagnosis Reflecting Clinical Heterogeneity and Serving as a Prognostic Tool for Treatment Response in Two Independent Cohorts of Patients With Juvenile Dermatomyositis.

Objective: Juvenile dermatomyositis (DM) is a heterogeneous systemic immune-mediated vasculopathy. This study was undertaken to 1) identify inflammation/endothelial dysfunction-related biomarker profiles reflecting disease severity at diagnosis, and 2) establish whether such biomarker profiles could be used for predicting the response to treatment in patients with juvenile DM.

Methods: In total, 39 biomarkers related to activation of endothelial cells, endothelial dysfunction, and inflammation were measured using multiplex technology in serum samples from treatment-naive patients with juvenile DM from 2 independent cohorts (n = 30 and n = 29).

Pharmacological conditioning for juvenile idiopathic arthritis: a potential solution to reduce methotrexate intolerance.

Background: Methotrexate (MTX) therapy has proven to be a successful and safe treatment for Juvenile Idiopathic Arthritis (JIA). Despite the high efficacy rates of MTX, treatment outcomes are often complicated by burdensome gastro-intestinal side effects. Intolerance rates for MTX in children are high (approximately 50%) and thus far no conclusive effective treatment strategies to control for side effects have been found.

MRP8/14 and neutrophil elastase for predicting treatment response and occurrence of flare in patients with juvenile idiopathic arthritis.

Objective: To study two neutrophil activation markers, myeloid-related protein (MRP) 8/14 and neutrophil elastase (NE), for their ability to predict treatment response and flare in patients with JIA.

Methods: Using samples from two cohorts (I and II), we determined MRP8/14 and NE levels of 32 (I) and 81 (II) patients with new-onset, DMARD-naïve arthritis and compared patients who responded to treatment (defined as fulfilling ≥ adjusted ACRpedi50 response and/or inactive disease) with non-responders (defined as fulfilling < adjusted ACRpedi50 response and/or active disease) at 6 and 12 months. Secondly, we compared biomarker levels of 54 (I) and 34 (II) patients with clinically inactive disease who did or did not suffer from a flare of arthritis after 6 or 12 months.

Galectin-9 and CXCL10 as Biomarkers for Disease Activity in Juvenile Dermatomyositis: A Longitudinal Cohort Study and Multicohort Validation.

Objective: Objective evaluation of disease activity is challenging in patients with juvenile dermatomyositis (DM) due to a lack of reliable biomarkers, but it is crucial to avoid both under- and overtreatment of patients. Recently, we identified 2 proteins, galectin-9 and CXCL10, whose levels are highly correlated with the extent of juvenile DM disease activity. This study was undertaken to validate galectin-9 and CXCL10 as biomarkers for disease activity in juvenile DM, and to assess their disease specificity and potency in predicting the occurrence of flares.

Participation in a single-blinded pediatric therapeutic strategy study for juvenile idiopathic arthritis: are parents and patient-participants in equipoise?

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.

Treat to target (drug-free) inactive disease in DMARD-naive juvenile idiopathic arthritis: 24-month clinical outcomes of a three-armed randomised trial.

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.

Identification of an Amino Acid Motif in HLA-DRβ1 That Distinguishes Uveitis in Patients With Juvenile Idiopathic Arthritis.

Objective: Uveitis is a visually debilitating disorder that affects up to 30% of children with the most common forms of juvenile idiopathic arthritis (JIA). The disease mechanisms predisposing only a subgroup of children to uveitis are unknown. This study was undertaken to identify genetic susceptibility loci for uveitis in JIA, using a genome-wide association study in 522 children with JIA.

Neonatal carnitine palmitoyltransferase II deficiency: failure of treatment despite prolonged survival.

Carnitine palmitoyltransferase (CPT) deficiencies are disorders of mitochondrial fatty acid oxidation (FAO). In fatty acid oxidation, long-chain fatty acids need the carnitine cycle to be transported from the cytosol to the mitochondria. In CPT II deficiency, long-chain acylcarnitines cannot be metabolised to carnitine and acyl-CoA, leading to accumulation of toxic long-chain acylcarnitines.