Development and validation of a pediatric internationally agreed ultrasound knee synovitis protocol (PIUS-knee) by the PReS imaging working party.

Objectives: To identify an optimal pediatric musculoskeletal ultrasound (MSUS) protocol for the detection of knee arthritis in patients with juvenile idiopathic arthritis (JIA) including a comparison with existing protocols. Secondary aims were to correlate MSUS-identified B-Mode (BM) and Power Doppler-Mode (PD) synovitis with clinical findings.

Methods: Consecutive JIA patients with confirmed knee arthritis after clinical examination underwent a thorough MSUS study protocol which included views identified and consented by the Pediatric Rheumatology european Society (PReS) Imaging Working Party for the detection of synovitis.

Translation and validation in Italian of the methotrexate intolerance severity score for children and adults with arthritis.

Objectives: Methotrexate (MTX) is the most used drug to treat children and adults with arthritis and its use is burdened by adverse effects. The MTX intolerance severity score (MISS) was developed in English to identify patients who are intolerant to MTX. The aim of this study was to translate and validate the MISS in Italian.

Clinical features, treatment and outcomes of Italian children with enthesitis-related arthritis and juvenile psoriatic arthritis: a cross-sectional cohort study.

Objectives: Limited information is available on the clinical features, treatment modalities and outcomes of the juvenile idiopathic arthritis (JIA) categories of enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA). This study was aimed to describe the characteristics of Italian children with ERA and JPsA and to compare them with those of patients with the other categories of JIA.

Methods: Patients were part of a multinational sample included in a study aimed to investigate the prevalence of disease categories, treatment approaches, and disease status in patients from across different geographical areas (EPOCA Study).

OMERACT International Consensus for Ultrasound Definitions of Tenosynovitis in Juvenile Idiopathic Arthritis: Systematic Literature Review and Delphi Process.

Objective: Synovitis and tenosynovitis are present in juvenile idiopathic arthritis (JIA), both as joint pain and/or inflammation, making them difficult to detect on physical examination. Although ultrasonography (US) allows for discrimination of the 2 entities, only definitions and scoring of synovitis in children have been established. This study was undertaken to produce consensus-based US definitions of tenosynovitis in JIA.

Validity of ultrasonography in detecting enthesitis in children: A systematic literature review.

Objective: A systematic review to assess the value of ultrasonography (US) for detecting enthesitis in juvenile idiopathic arthritis (JIA).

Methods: PubMed and Embase databases were searched for articles published from January 1966 to May 2021; we selected those meeting the inclusion criteria according to the US definition of enthesitis and metric properties studied. We assessed the clinical features of the population, study design, the type and number of entheses examined, the definition and scoring system of US enthesitis and metric properties according to the OMERACT filter (truth, discrimination and feasibility).

Development and Initial Validation of the ONCOREUM Score to Differentiate Childhood Cancer with Arthropathy from Juvenile Idiopathic Arthritis.

Objective: To develop and validate a weighted score, the ONCOREUM score, that aids physicians in differentiation of cancer with arthropathy from juvenile idiopathic arthritis (JIA).

Study Design: Data were extracted from the ONCOREUM Study, a multicenter, cross-sectional investigation aimed at comparing children with cancer and arthropathy to children with JIA. Three statistical approaches were applied to develop the ONCOREUM score and assess the role of each variable in the diagnosis of cancer with arthropathy, including 2 approaches based on multivariable stepwise selection (models 1 and 2) and 1 approach on a Bayesian model averaging method (model 3).

A novel magnetic resonance imaging scoring system for active and chronic changes in children and adolescents with juvenile idiopathic arthritis of the hip.

Background: Hip involvement predicts severe disease in juvenile idiopathic arthritis (JIA) and is accurately assessed by MRI. However, a child-specific hip MRI scoring system has not been validated.

Objective: To test the intra- and interobserver agreement of several MRI markers for active and chronic hip changes in children and young adults with JIA and to examine the precision of measurements commonly used for the assessment of growth abnormalities.

Procedures for the content, conduct and format of EULAR/PReS paediatric musculoskeletal ultrasound courses.

Background: Despite the worldwide increasing request of education on paediatric musculoskeletal ultrasound (PedMSUS), content, conduct and format of PedMSUS courses have never been internationally agreed.

Objectives: To produce educational procedures for the conduct, content and format of EULAR/PReS PedMSUS courses.

Methods: After a systemic literature review and expert opinion collection, a panel of items for the development of procedures on PedMSUS courses was identified.

Pro Nerve Growth Factor and Its Receptor p75NTR Activate Inflammatory Responses in Synovial Fibroblasts: A Novel Targetable Mechanism in Arthritis.

We have recently provided new evidence for a role of p75NTR receptor and its preferential ligand proNGF in amplifying inflammatory responses in synovial mononuclear cells of chronic arthritis patients. In the present study, to better investigate how activation of the p75NTR/proNGF axis impacts synovial inflammation, we have studied the effects of proNGF on fibroblast-like synoviocytes (FLS), which play a central role in modulating local immune responses and in activating pro-inflammatory pathways. Using single cell RNA sequencing in synovial tissues from active and treatment-naïve rheumatoid arthritis (RA) patients, we demonstrated that p75NTR and sortilin, which form a high affinity receptor complex for proNGF, are highly expressed in PRG4 lining and THY1COL1A1 sublining fibroblast clusters in RA synovia but decreased in RA patients in sustained clinical remission.

Linking Joint Impairment and Gait Biomechanics in Patients with Juvenile Idiopathic Arthritis.

Juvenile Idiopathic Arthritis (JIA) is a paediatric musculoskeletal disease of unknown aetiology, leading to walking alterations when the lower-limb joints are involved. Diagnosis of JIA is mostly clinical. Imaging can quantify impairments associated to inflammation and joint damage.

Establishing an Updated Core Domain Set for Studies in Juvenile Idiopathic Arthritis: A Report from the OMERACT 2018 JIA Workshop.

Objective: The current Juvenile Idiopathic Arthritis (JIA) Core Set used in randomized controlled trials (RCT) and longitudinal observational studies (LOS) was developed without the input of patients/parents. At the Outcome Measures in Rheumatology (OMERACT) 2016, a special interest group voted to reconsider the core set, incorporating broader input. We describe subsequent work culminating in an OMERACT 2018 plenary and consensus voting.

Microbiome Analytics of the Gut Microbiota in Patients With Juvenile Idiopathic Arthritis: A Longitudinal Observational Cohort Study.

Objective: To assess the composition of gut microbiota in Italian and Dutch patients with juvenile idiopathic arthritis (JIA) at baseline, with inactive disease, and with persistent activity compared to healthy controls.

Methods: In a multicenter, prospective, observational cohort study, fecal samples were collected at baseline from 78 Italian and 21 Dutch treatment-naive JIA patients with <6 months of disease duration and compared to 107 geographically matched samples from healthy children. Forty-four follow-up samples from patients with inactive disease and 25 follow-up samples from patients with persistent activity were analyzed.

Prediction of inactive disease in juvenile idiopathic arthritis: a multicentre observational cohort study.

Objectives: To predict the occurrence of inactive disease in JIA in the first 2 years of disease.

Methods: An inception cohort of 152 treatment-naïve JIA patients with disease duration <6 months was analysed. Potential predictors were baseline clinical variables, joint US, gut microbiota composition and a panel of inflammation-related compounds in blood plasma.

Correction to: The Italian version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).

The family name of author Francesco La Torre was incorrect in the published article. The correct family name should read as La Torre F.

Imaging of the hip in juvenile idiopathic arthritis.

Hip involvement is common and estimated to occur in approximately 35-63% of children with juvenile idiopathic arthritis (JIA). It is more prevalent in the aggressive systemic subtypes, with irreversible changes occurring as early as within 5 years of diagnosis. Whilst clinical parameters and joint examination can be useful for assessing disease severity, subclinical disease is known to exist and delayed treatment may herald a lifetime of disability and pain.

Juvenile idiopathic arthritis - the role of imaging from a rheumatologist's perspective.

Alongside recent advances in treatment strategies for juvenile idiopathic arthritis (JIA), paediatric rheumatologists have taken increasing interest in the use of imaging. Magnetic resonance imaging (MRI) and musculoskeletal ultrasound, by providing more detailed information on disease activity than clinical examination and conventional radiography (CR), have become helpful diagnostic and managerial tools. The growing skeleton, however, with changing appearances over time, is still challenging in the establishment of valid scoring systems for pathological changes.

Predictors of Flare Following Etanercept Withdrawal in Patients with Rheumatoid Factor-negative Juvenile Idiopathic Arthritis Who Reached Remission while Taking Medication.

Objective: To evaluate the rate of flare after etanercept (ETN) withdrawal in patients with juvenile idiopathic arthritis (JIA) who attained clinical remission while taking medication, and to identify predictors of flare.

Methods: Patients were included with oligo- (oJIA) and rheumatoid factor-negative polyarticular JIA (pJIA) who received a first course of ETN for at least 18 months, maintained clinically inactive disease (CID) for at least 6 months during treatment, and were followed for 12 months after ETN withdrawal. Demographic and clinical features were collected at onset, at baseline (initiation of ETN), and at time of disease flare.

The Italian version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Italian language.The reading comprehension of the questionnaire was tested in 10 JIA parents and patients.

Amendment of the OMERACT ultrasound definitions of joints' features in healthy children when using the DOPPLER technique.

Background: Recently preliminary ultrasonography (US) definitions, in B mode, for normal components of pediatric joints have been developed by the OMERACT US group. The aim of the current study was to include Doppler findings in the evaluation and definition of normal joint features that can be visualized in healthy children at different age groups.

Methods: A multistep approach was used.

Normative ultrasound references for the paediatric wrist; dorsal soft tissues.

Objective: To report novel ultrasound (US) references for the healthy paediatric wrist.

Methods: Healthy children and adolescents had an US examination including Doppler, of the right wrist, using a mid-sagittal image through the radiocarpal (RC)/midcarpal (MC) joints. These features were noted: appearances and depth of the recess, with an additional measurement in the flexed position and number of Doppler signals within the recess in close proximity to the joint.

Imaging in juvenile idiopathic arthritis - international initiatives and ongoing work.

Imaging is increasingly being integrated into clinical practice to improve diagnosis, disease control and outcome in children with juvenile idiopathic arthritis. Over the last decades several international groups have been launched to standardize and validate different imaging techniques. To enhance transparency and facilitate collaboration, we present an overview of ongoing initiatives.

Switched Memory B Cells Are Increased in Oligoarticular and Polyarticular Juvenile Idiopathic Arthritis and Their Change Over Time Is Related to Response to Tumor Necrosis Factor Inhibitors.

Objective: To investigate whether abnormalities in B cell subsets in patients with juvenile idiopathic arthritis (JIA) correlate with clinical features and response to treatment.

Methods: A total of 109 patients diagnosed as having oligoarticular JIA or polyarticular JIA were enrolled in the study. B cell subsets in peripheral blood and synovial fluid were analyzed by flow cytometry.