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. In total eight views including measurement of the suprapatellar recess were included. Scoring of synovitis followed the pediatric OMERACT criteria (BM and PD severity grading 0 to 3). Interobserver reliability of BM and PD was tested before study begin. Previously published MSUS protocols for knee synovitis were also identified from the literature and their scan protocols compared to identify differences in sensitivity for synovitis according to the number and specific type of views included. Finally, a clinically applicable MSUS protocol for knee synovitis could be proposed. RESULTS: In 114 patients with clinically active knee inflammation, BM positivity (grading ≥ 1) was most frequently detected in the suprapatellar longitudinal and transverse scans performed in any positioning (frequency 97-99% in suprapatellar longitudinal in 30° or neutral respectively). PD positivity was however higher in these views performed in 30° flexion compared to neutral. Intrasynovial PD positivity (grading ≥ 1) was most frequently detected in the lateral parapatellar (69%, sensitivity 0.68, specificity 0.98), medial parapatellar (frequency 67%, sensitivity 0.67, specificity 1.0), the longitudinal lateral (68%, sensitivity 0.67, specificity 0.98) and suprapatellar transverse in 30° (frequency 64%, sensitivity 0.64, specificity 1.0). A combination of five views was the most sensitive for BM and PD synovitis. The suprapatellar recess size was analyzed by age and gender. For each group, the recess was wider in knees with arthritis than without (p < 0.001). Interobserver reliability of BM and PD positivity showed 85% agreement, with kappa 0.74 (very good). Three published studies with knee synovitis MSUS protocols were identified, which included a range of 1-3 views. Evaluation of the sensitivity of positive PD findings of each of these protocols reached a range of 53-83%; the highest sensitivity (91%) was achieved with the 5 views as identified by this study. These five views were therefore combined to form the Pediatric Internationally agreed Ultrasound (PIUS) knee protocol. CONCLUSION: BM and PD positivity reliably correlated with the identification of pathological findings in knees of patients with JIA. From an internationally agreed protocol of eight images, a combination of five showed the greatest sensitivity for synovitis. This protocol, termed 'PIUS-Knee' performed well when compared to existing protocols.

Imaging in Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA) poses clinical challenges because of its heterogeneous categories of chronic arthritis. Although conventional radiography aids with assessment of joint damage, MRI and ultrasound offer more sensitive evaluation of joint changes related to inflammation and damage in JIA. MRI and ultrasound have the potential to complement clinical assessment, monitor inflammation and damage, guide treatment decisions, and improve outcomes in JIA. Future research aims to enhance standardization and reliability and bolster the predictive value of imaging in clinical practice.

Ultrasound-detected tenosynovitis in ankles with clinical arthritis and short-term outcome of patients with new-onset juvenile idiopathic arthritis.

OBJECTIVES: To determine features and frequency of ultrasound (US)-detected tenosynovitis in ankles with clinically active disease and to investigate whether its detection may affect the achievement of inactive disease in patients with new-onset juvenile idiopathic arthritis (JIA). METHODS: The study included children with new-onset JIA and clinically active disease of the ankle. Based on US, patients were stratified as having isolated arthritis or as having tenosynovitis irrespective of the presence of concomitant arthritis in the ankle. Estimation of patients who were able to achieve clinically inactive disease 6 months after starting treatment was assessed by the Kaplan-Meier method. Cox model was used to calculate hazard ratio (HR) and 95% confidence interval (CI). Reliability of US was tested using kappa statistic. RESULTS: Forty-five patients were recruited. On US, tenosynovitis of the ankle was detected in 28 patients (62.2%); isolated arthritis was found in 17 patients (37.8%). The medial and lateral tendon compartments were the tendon sites most frequently inflamed. Patients with tenosynovitis had similar likelihood of those without tenosynovitis to achieve clinically inactive disease (60.7% and 58.8%, respectively; HR 1.12, 95%CI:0.51-2.45). In the subanalysis excluding patients who were given biologics, the probability of experiencing inactive disease was slightly higher for patients with tenosynovitis compared to those without (64.7% and 54.5%, respectively; HR 1.56, 95%CI: 0.58-4.24). The rate of US reliability was high. CONCLUSIONS: US-detected tenosynovitis is frequent in ankles with clinical arthritis at JIA onset but does not impair the chance of achieving clinically inactive disease in the early disease phase.

The assessment of bone health in children with juvenile idiopathic arthritis; comparison of different imaging-based methods.

BACKGROUND: Osteoporosis is increasingly being recognized in children, mostly secondary to systemic underlying conditions or medication. However, no imaging modality currently provides a full evaluation of bone health in children. We compared DXA, a radiographic bone health index (BHI (BoneXpert) and cone-beam CT for the assessment of low bone mass in children with juvenile idiopathic arthritis (JIA). METHODS: Data used in the present study was drawn from a large multicentre study including 228 children aged 4-16 years, examined between 2015 and 2020. All had a radiograph of the left hand, a DXA scan and a cone-beam CT of the temporomandibular joints within four weeks of each other. For the present study, we included 120 subjects, selected based on DXA BMD and BoneXpert BHI to secure values across the whole range to be tested. RESULTS: One hundred and twenty children (60.0% females) were included, mean age 11.6 years (SD 3.1 years). There was a strong correlation between the absolute values of BHI and BMD for both total body less head (TBLH) (r = 0.75, p < 0.001) and lumbar spine (L1-L4) (r = 0.77, p < 0.001). The correlation between BHI standard deviation score (SDS) and BMD TBLH Z-scores was weak (r = 0.34) but significant (0 = 0.001), varying from weak (r = 0.31) to moderate (r = 0.42) between the three study sites. Categorizing BHI SDS and DXA BMD Z-scores on a 0-5 scale yielded a weak agreement between the two for both TBLH and LS, with w-kappa of 0.2, increasing to 0.3 when using quadratic weights. The agreement was notably higher for one of the three study sites as compared to the two others, particularly for spine assessment, yielding a moderate kappa value of 0.4 - 0.5. For cone-beam CT, based on a 1-3 scale, 59 out of 94 left TMJ's were scored as 1 and 31 as score 2 by the first observer vs. 87 and 7 by the second observer yielding a poor agreement (kappa 0.1). CONCLUSIONS: Categorizing DXA LS and automated radiographic Z-scores on a 0-5 scale gave a weak to moderate agreement between the two methods, indicating that a hand radiograph might provide an adjuvant tool to DXA when assessing bone health children with JIA, given thorough calibration is performed.

Imaging of Juvenile Idiopathic Arthritis.

MRI, ultrasound, and conventional radiography each play distinct roles in the evaluation of juvenile idiopathic arthritis (JIA), with MRI being the preferred imaging modality of choice for assessing both inflammatory and destructive changes. These various imaging modalities provide valuable insights into JIA in pediatric patients. However, challenges persist in terms of achieving precision, ensuring validity, and distinguishing between pathologic findings and normal anatomic variations. Establishing normal reference values and implementing scoring systems can aid in the precise evaluation of disease activity and provide information to assist treatment decisions for children with JIA. Ongoing advancements in imaging techniques and standardization initiatives aim to bolster the accuracy of JIA diagnosis and assessment, ultimately leading to enhanced patient care and treatment outcomes.

The reliability and validity of the juvenile idiopathic arthritis magnetic resonance scoring system for temporomandibular joints.

In children with juvenile idiopathic arthritis (JIA), the temporomandibular joint (TMJ) can be involved. To prevent TMJ damage due to inflammation, early recognition is important, for which contrast-enhanced magnetic resonance imaging (MRI) is the gold standard. In this study, the interobserver reliability and construct validity of the Juvenile Idiopathic Arthritis Magnetic Resonance Scoring System for Temporomandibular Joints (JAMRIS-TMJ) was assessed. Two radiologists independently examined 38 MRIs using the JAMRIS-TMJ scoring system. Inter-observer reliability was assessed by Cohen's (weighted) kappa (κ), 95% confidence intervals (CIs) and absolute agreement (%). Construct validity was assessed by correlation between the JAMRIS-TMJ items and TMJ involvement, active maximum interincisal mouth opening (AMIO), and anterior maximum voluntary bite force (AMVBF). The interobserver reliability for the JAMRIS-TMJ items varied from poor to good (κ = 0.18-0.61). Joint enhancement had the highest reliability (κ = 0.61). Correlations were found between TMJ involvement, AMIO, and the JAMRIS-TMJ items, although variation between radiologists and TMJ side existed. No correlation was found between AMVBF and the JAMRIS-TMJ items for both radiologists. The strongest correlations were found between most of the JAMRIS-TMJ items and AMIO. Our findings support the utility of AMIO as a clinical measure of TMJ status in children with JIA.

Increased adiposity in juvenile idiopathic arthritis - A comparison of the bioelectrical impedance analysis and dual-energy X-ray absorptiometry for the assessment of body composition.

AIM: Higher adiposity and increased risk of cardiovascular diseases have been reported in juvenile idiopathic arthritis (JIA), but body composition measurements have produced inconsistent results. This controlled cross-sectional study assessed body composition with two methods to evaluate adiposity in children with JIA. METHODS: We measured body composition by dual- energy X-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA) from 79 JIA-patients in two Finish university hospitals in 2017-2019. Their age- and sex-matched controls (n = 79) were selected from the Physical Activity and Nutrition in Children- study and through National Registry. RESULTS: Body fat percentage measured by BIA was higher (mean, SD) in patients compared to controls (23.1 ± 9.3% vs. 20.1 ± 7.5%, p = 0.047). Also, using DXA, there was a tendency of higher body fat percentage in patients (27.1 ± 9.1% vs. 24.6 ± 8.6, p = 0.106). BIA and DXA showed strong correlation (r from 0.810 to 0.977) in all body composition variables. CONCLUSION: Increased adiposity was observed in patients with JIA. Evaluation of body composition should be included in the multidisciplinary care of JIA to reduce the possible risk of cardiovascular diseases in adulthood. BIA could be a useful tool for assessing body composition due to its clinical availability and safety.

Optical coherence tomography for the screening of anterior chamber inflammation in paediatric patients diagnosed with juvenile idiopathic arthritis.

OBJECTIVES: To evaluate the effectiveness of the anterior segment optical coherence tomography (AS-OCT) for the screening of anterior uveitis in children diagnosed with juvenile idiopathic arthritis (JIA). METHODS: A cross-sectional, observational, non-randomised study was conducted in JIA patients younger than 18 years. All patients underwent anterior segment (AS-OCT) and macular OCT. RESULTS: A total of 300 eyes of 150 patients diagnosed with JIA were included; 74% were females, and mean age was 11.12 ± 3.51 years old (range 4.13-18.60). In the slit-lamp examination, anterior uveitis was diagnosed in 16 eyes. In the AS-OCT, anterior uveitis was suspected in 27 eyes; cells were detected in 27 eyes and retrokeratic precipitates in 5 eyes. Sensitivity was 0.94 and specificity was 0.96, positive predictive value was 0.59 and negative predictive value was 0.99, and Kappa-Cohen index was 0.71. CONCLUSIONS: AS-OCT could be considered for the screening of anterior segment uveitis in children diagnosed with JIA.

Measuring synovial thickness on knee MRI in pediatric patients with arthritis: is contrast necessary?

BACKGROUND: The use of contrast-enhanced imaging has long been standard for magnetic resonance imaging (MRI) assessments of synovitis in juvenile idiopathic arthritis (JIA). However, advancements in MRI technology have allowed for reliable identification of synovium without contrast. OBJECTIVE: To assess the equivalence of unenhanced MRI with contrast-enhanced MRI in evaluating synovial thickness. MATERIALS AND METHODS: This is an institutional review board approved, retrospective study performed in a tertiary children's hospital. Pediatric JIA patients under 21 years old were included who underwent knee MRI scans (1.5 T or 3 T) without and with contrast between January 2012 and January 2022. Two radiologists independently measured synovial thickness at 6 knee sites on contrast-enhanced and unenhanced sequences. Numerical measurements and ordinal scores based on juvenile idiopathic arthritis magnetic resonance imaging scoring (JAMRIS) system were recorded, and tests of equivalence were conducted, as well as between-reader and within-reader reliability by concordance correlation coefficient (CCC). All tests were considered significant at the 5% level. RESULTS: A total of 38 studies from 35 patients (25 females, median age 14 years; interquartile range 7 to 15.7) were included. Equivalence was demonstrated at each of the 6 sites for both continuous measurements (P-values < 0.05) and ordinal scores (P-values < 0.05) based on the average over readers. Within-reader reliability was moderate to high (CCC 0.50-0.89), except for the cruciate ligaments site. Averaged over the 6 sites, reliability between readers was low for unenhanced (CCC 0.47, with 95% CI: [0.41, 0.53]) and moderate for contrast-enhanced (CCC 0.64, with 95% CI: [0.59, 0.69]) sequences. CONCLUSION: Unenhanced knee MRI is equivalent to contrast-enhanced MRI in assessment of synovial thickness using conventional MRI sequences. Contrast material helped improve inter-reader reliability.

Reliability assessment of the OMERACT whole-body magnetic resonance imaging scoring system for juvenile idiopathic arthritis.

Inter-reader reliability of a new scoring system for evaluating joint inflammation and enthesitis in whole body MRI (WBMRI) in juvenile idiopathic arthritis was tested. The scoring system grades 732 item-region combinations of bone marrow and soft tissue changes for commonly involved joints and entheseal sites. Five radiologists rated 17 WBMRI scans through an online rating platform. Item-wise reliability was calculated for 117 items with non-zero scores in >10 % of readings. Interquartile ranges of the five-reader Kappa reliability coefficients were 0.58-0.73 (range: 0.36-0.88) for the joints, 0.65-0.81 (range: 0.39-0.95) for the entheses, and 0.62-0.75 (range: 0.60-0.76) for chronic nonbacterial osteomyelitis-like lesions.

Provider assessment of the temporomandibular joint in Juvenile idiopathic arthritis: a retrospective analysis from the CARRA database.

BACKGROUND: Temporomandibular joint (TMJ) involvement is an often underrecognized complication of juvenile idiopathic arthritis (JIA) that can cause decreased mandibular growth, altered facial morphology, and orofacial pain. It is estimated that the TMJ is affected in 30-45% of children with JIA. Standardized physical examination and imaging evaluations are important in accurately assessing active TMJ arthritis and sequalae. Little is known about the rate at which providers evaluate TMJ involvement in their clinical practice. METHODS: Data were obtained from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Data fields related to assessment for TMJ arthritis were added in 2019. Patients were included in the study if they had a diagnosis of JIA and had data recorded between January 2020 and August 2021. Standard descriptive statistics were used to describe demographic and clinical features. RESULTS: A total of 17,761 visits were reviewed for a total of 7473 patients with JIA. A total of 52.7% of patients had maximal mouth opening (MMO) recorded as finger breadths or total incisal distance (TID). Only 8% had TID measured. A total of 5.0% had MRI with contrast performed. A total of 939 patients had a diagnosis of TMJ arthritis. Of these, 28.5% had an MRI documented, 83% had an MMO documented, and 40% had TID measured. Few patient-level characteristics were statistically related to having MMO assessed. MRI was more likely to be obtained in older and in female patients. MMO was recorded at a given visit > 80% of the time at 17 sites, and it was recorded < 1% of the time at 8 sites. MRIs were infrequently performed at all sites, with 27 sites having no MRIs obtained and only 7 sites having an MRI obtained at > 10% of visits. CONCLUSIONS: MMO is not consistently measured in patients with JIA, and it is rarely measured quantitatively. Similarly, TMJ MRIs are rarely obtained in patients with JIA. Site of care is more associated with TMJ assessments than patient-level characteristics. These data suggest that provider education is needed to improve the assessment of the TMJ in patients with JIA to enable earlier recognition and prevent long-term complications.

A simple, clinically usable whole-body MRI system of joint assessment in adolescents and young people with juvenile idiopathic arthritis.

OBJECTIVES: To introduce and evaluate a simple method for assessing joint inflammation and structural damage on whole-body MRI (WBMRI) in juvenile idiopathic arthritis (JIA), which is usable in clinical practice. METHODS: The proposed system utilizes post-contrast Dixon WBMRI scans. Joints are assessed for synovitis (grade 0-2) and structural damage (present/absent) at 81 sites. The synovitis grading is based on features including above-normal intensity synovial enhancement, synovial hypertrophy, joint effusion, subarticular bone marrow oedema and peri-articular soft tissue oedema.This system was evaluated in a prospective study of 60 young people (47 patients with JIA and 13 controls with non-inflammatory musculoskeletal pain) who underwent a WBMRI. Three readers (blinded to diagnosis) independently reviewed all images and re-reviewed 20 individual scans. The intra- and inter-reader overall agreement (OA) and the intra- and inter-reader Gwet's agreement coefficients 2 (GAC2) were measured for the detection of a) participants with ≥1 joint with inflammation or structural damage and b) joint inflammation or structural damage for each joint. RESULTS: The inter-reader OA for detecting patients with ≥1 joint with inflammation, defined as grade 2 synovitis (G2), and ≥1 joint with structural damage were 80% and 73%, respectively. The intra-reader OA for readers 1-3 was 80-90% and 75-90%, respectively. The inter-reader OA and GAC2 for joint inflammation (G2) at each joint were both ≥85% for all joints but were lower if grade 1 synovitis was included as positive. CONCLUSION: The intra- and inter-reader agreements of this WBMRI assessment system are adequate for assessing objective joint inflammation and damage in JIA.

Temporomandibular involvement in children and adolescents with juvenile idiopathic arthritis: a 2-year prospective cohort study.

This study aimed to clinically evaluate temporomandibular joint (TMJ) involvement in juvenile idiopathic arthritis (JIA) and the ability to identify and/or predict development of TMJ-deformities over time using cone beam computed tomography (CBCT). The predictive value of self-reported TMJ pain was also assessed. A prospective longitudinal cohort study comprising 54 children with JIA, 39 girls and 15 boys, was performed. All children had active disease at baseline, 50% with the subtype oligoarthritis. Repeated clinical orofacial and CBCT examinations were performed over a two-year period. At baseline, 39% had radiographic TMJ deformities (24% unilateral, 15% bilateral), at 2-year follow-up, 42% (p > 0.05). Both progressing and improving TMJ deformities were observed. An association was found between TMJ-deformities and self-reported TMJ pain at baseline (p = 0.01). Maximum unassisted mouth opening (MUO) was smaller for children with TMJ-deformities (p < 0.05). The prevalence of palpatory muscle pain was high (48-59%) but not predictive of development of TMJ-deformities. TMJ noises increased over time and crepitations were associated with TMJ-deformities (p < 0.05). In conclusion, in children with JIA, self-reported TMJ pain and dysfunction were common and predictive of TMJ deformities. TMJ deformities were associated with smaller MUO and palpatory TMJ pain as well as crepitations. Trial registration. ClinicalTrials.gov Protocol id: 2010/2089-31/2.

Validity of an ultrasonographic joint-specific scoring system in juvenile idiopathic arthritis: a cross-sectional study comparing ultrasound findings of synovitis with whole-body magnetic resonance imaging and clinical assessment.

OBJECTIVE: To assess the validity of an ultrasonographic scoring system in juvenile idiopathic arthritis (JIA) by comparing ultrasound detected synovitis with whole-body MRI and clinical assessment of disease activity. METHODS: In a cross-sectional study, 27 patients with active JIA underwent clinical 71-joints examination, non-contrast enhanced whole-body MRI and ultrasound evaluation of 28 joints (elbow, radiocarpal, midcarpal, metacarpophalangeal 2-3, proximal interphalangeal 2-3, hip, knee, tibiotalar, talonavicular, subtalar and metatarsophalangeal 2-3). One rheumatologist, blinded to clinical findings, performed ultrasound and scored synovitis (B-mode and power Doppler) findings using a semiquantitative joint-specific scoring system for synovitis in JIA. A radiologist scored effusion/synovial thickening on whole-body MRI using a scoring system for whole-body MRI in JIA. At patient level, associations between ultrasound synovitis sum scores, whole-body MRI effusion/synovial thickening sum scores, clinical arthritis sum scores, and the 71-joints Juvenile Arthritis Disease Activity Score (JADAS71) were calculated using Spearman's correlation coefficients (rs). To explore associations at joint level, sensitivity and specificity were calculated for ultrasound using whole-body MRI or clinical joint examination as reference. RESULTS: Ultrasound synovitis sum scores strongly correlated with whole-body MRI effusion/synovial thickening sum scores (rs=0.74,p<0.01) and the JADAS71 (rs=0.71,p<0.01), and moderately with clinical arthritis sum scores (rs=0.57,p<0.01). Sensitivity/specificity of ultrasound in detecting synovitis were 0.57/0.96 and 0.55/0.96 using whole-body MRI or clinical joint examination as reference, respectively. CONCLUSION: Our findings suggest that ultrasound is a valid instrument to detect synovitis, and that ultrasound synovitis sum scores can reflect disease activity and may be an outcome measure in JIA.

Effects of orthopedic treatment (distraction splint) on dentofacial deformities in patients with juvenile idiopathic arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA) frequently affects the temporomandibular joint (TMJ), which can alter mandibular growth and development and result in dentofacial deformities. OBJECTIVE: To assess the outcomes of orthopedic treatment with distraction splint (DS) in patients with JIA-related dentofacial deformity. METHODS: The retrospective study involved 30 patients with JIA and unilateral TMJ involvement, another study group of 20 patients with JIA and bilateral TMJ involvement, and a control group of 18 non-JIA orthodontic patients with Class II and III malocclusions. The inclusion criteria were DS treatment and cone-beam computed tomography (CBCT) scans before (T0) and 2 years after treatment (T1). Dentofacial morphology and deformity were evaluated based on a validated three-dimensional CBCT-based morphometric analysis. Intergroup differences in outcome measures were compared at T0 and T1, and intragroup changes between T0 and T1 were assessed using the Kruskal-Wallis test. RESULTS: Initial evaluations at T0 revealed significant differences between the unilateral and bilateral JIA groups and the control group for three out of eight dentofacial deformity variables: inter-side difference in total posterior mandibular height, mandibular axial angle, and posterior/anterior face height (ratio). At follow-up (T1), significant inter-group differences were only observed in total posterior mandibular height indicating that intergroup differences were less pronounced after splint treatment. Assessing inter-group changes between T0 and T1 showed that all parameters remained constant except posterior/anterior face height ratio, which significantly decreased between T0 and T1. CONCLUSIONS: The findings demonstrate the potential of DS treatment for patients with JIA and unilateral or bilateral TMJ involvement to generally support normal dentofacial growth or at least limit further deterioration of dentofacial deformities.

Machine learning diagnosis of active Juvenile Idiopathic Arthritis on blood pool [ 99M Tc] Tc-MDP scintigraphy images.

PURPOSE: Neural network has widely been applied for medical classifications and disease diagnosis. This study employs deep learning to best discriminate Juvenile Idiopathic Arthritis (JIA), a pediatric chronic joint inflammatory disease, from healthy joints by exploring blood pool images of 2phase [ 99m Tc] Tc-MDP bone scintigraphy. METHODS: Self-deigned multi-input Convolutional Neural Network (CNN) in addition to three available pre-trained models including VGG16, ResNet50 and Xception are applied on 1304 blood pool images of 326 healthy and known JIA children and adolescents (aged 1-16). RESULTS: The self-designed model ROC analysis shows diagnostic efficiency with Area Under the Curve (AUC) 0.82 and 0.86 for knee and ankle joints, respectively. Among the three pertained models, VGG16 ROC analysis reveals AUC 0.76 and 0.81 for knee and ankle images, respectively. CONCLUSION: The self-designed model shows best performance on blood pool scintigraph diagnosis of patients with JIA. VGG16 was the most efficient model rather to other pre-trained networks. This study can pave the way of artificial intelligence (AI) application in nuclear medicine for the diagnosis of pediatric inflammatory disease.

Detection of inflammation by whole-body MRI in young people with juvenile idiopathic arthritis.

OBJECTIVES: To assess the frequency of joint inflammation detected by whole-body MRI (WBMRI) in young people (YP) with JIA and controls, and to determine the relationship between WBMRI-detected inflammation and clinical findings. METHODS: YP aged 14-24 years, with JIA (patients) or arthralgia without JIA (controls), recruited from one centre, underwent a WBMRI scan after formal clinical assessment. Consensus between at least two of the three independent radiologists was required to define inflammation and damage on WBMRI, according to predefined criteria. YP with JIA were deemed clinically active as per accepted definitions. The proportions of YP with positive WBMRI scans for joint inflammation (one or more inflamed joint) as well as serum biomarkers were compared between active vs inactive JIA patients and controls. RESULTS: Forty-seven YP with JIA (25 active and 22 inactive patients) and 13 controls were included. WBMRI detected joint inflammation in 60% (28/47) of patients with JIA vs 15% (2/13) of controls (difference: 44%, 95% CI 20%, 68%). More active than inactive JIA patients had WBMRI-detected inflammation [76% (19/25) vs 41% (9/22), difference: 35% (95% CI 9%, 62%)], and this was associated with a specific biomarker signature. WBMRI identified inflammation in one or more clinically inactive joint in 23/47 (49%) patients (14/25 active vs 9/22 inactive JIA patients). CONCLUSIONS: WBMRI's validity in joint assessment was demonstrated by the higher frequency of inflammation in JIA patients vs controls, and in active vs inactive JIA patients. WBMRI found unsuspected joint inflammation in 49% YP with JIA, which needs further investigation of potential clinical implications.

Diagnostic Accuracy Study of the Pediatric-Specific Ultrasound Scoring System for the Knee Joint in Children With Juvenile Idiopathic Arthritis.

OBJECTIVE: We undertook this study to validate the Pediatric Arthritis Ultrasound Scoring System for the knee joint (PAUSS-knee) in children with juvenile idiopathic arthritis (JIA). METHODS: Children with JIA were enrolled to prospectively receive a musculoskeletal ultrasound (MSUS) examination of the knee and a physical examination to determine presence/absence of clinical arthritis. MSUS images were scored using the PAUSS-knee, a semiquantitative MSUS scoring system (0-3, normal to severe) for B-mode and power Doppler mode. In addition to MSUS, a subset of participants also received magnetic resonance imaging (MRI) of the knee, which was scored according to the combined Juvenile Arthritis MRI Scoring (JAMRIS) system. Spearman's correlations (rs ) were used to calculate associations between variables. Test characteristics of the PAUSS-knee were calculated with MRI as the reference standard. Inflammatory biomarkers were assessed in synovial fluid from involved knees. RESULTS: Eighty children with JIA contributed 112 MSUSs and 25 MRIs of the knee. Of the knees, 41% (n = 46) had clinical evidence of arthritis. The B-mode PAUSS-knee score moderately correlated with clinically determined arthritis (rs = 0.54, P < 0.001) and strongly correlated with the JAMRIS score (rs = 0.75, P < 0.001). Compared with MRI, the area under the curve for the B-mode PAUSS-knee was 0.92. For a cutoff of >1, the B-mode PAUSS-knee had a sensitivity of 83% and specificity of 82%. Biomarker analysis indicates that interleukin-2R levels correlate with PAUSS score. CONCLUSION: Our data indicate that the PAUSS-knee has excellent accuracy for the diagnosis of arthritis when compared with MRI. The PAUSS-knee has the potential to effectively inform JIA medical decision-making in real time.

Quantification of temporomandibular joint space in patients with juvenile idiopathic arthritis assessed by cone beam computerized tomography.

OBJECTIVE: To describe a method to calculate the total intra-articular volume (inter-osseous space) of the temporomandibular joint (TMJ) determined by cone-beam computed tomography (CBCT). This could be used as a marker of tissue proliferation and different degrees of soft tissue hyperplasia in juvenile idiopathic arthritis (JIA) patients. MATERIALS AND METHODS: Axial single-slice CBCT images of cross-sections of the TMJs of 11 JIA patients and 11 controls were employed. From the top of the glenoid fossa, in the caudal direction, an average of 26 slices were defined in each joint (N = 44). The interosseous space was manually delimited from each slice by using dedicated software that includes a graphic interface. TMJ volumes were calculated by adding the areas measured in each slice. Two volumes were defined: Ve-i and Vi , where Ve-i is the inter-osseous space, volume defined by the borders of the fossa and Vi is the internal volume defined by the condyle. An intra-articular volume filling index (IF) was defined as Ve-i /Vi , which represents the filling of the space. RESULTS: The measured space of the intra-articular volume, corresponding to the intra-articular soft tissue and synovial fluid, was more than twice as large in the JIA group as in the control group. CONCLUSION: The presented method, based on CBCT, is feasible for assessing inter-osseus joint volume of the TMJ and delimits a threshold of intra-articular changes related to intra-articular soft tissue proliferation, based on differences in volumes. Intra-articular soft tissue is found to be enlarged in JIA patients.

Serum calprotectin and joint ultrasound in the definition of disease relapse in non-systemic juvenile idiopathic arthritis: a prospective longitudinal study.

OBJECTIVES: The aim of our study was to investigate the role of serum calprotectin (SC) and muscle-skeletal ultrasound (MSUS) as predictive markers of relapse in patients with juvenile idiopathic arthritis (JIA). METHODS: Sixty non-systemic (ns) JIA patients in clinical remission were recruited to evaluate the risk of disease relapse. SC levels and JIA disease activity were assessed at every visit (3, 6, 12 and 18 months). Joint synovitis, characterised by both synovial effusion (SE) and synovial hyperplasia (SH), was measured by US score (sum of SE, SH, power Doppler and bone erosions) given to each examined joint and US ratio (US score/number of joints examined) at every visit. Associations of SC, US score and US ratio with relapse prevalence was studied longitudinally by using generalised estimating equations model. RESULTS: Thirty-one (51.6%) patients relapsed within 18 months. Patients with higher baseline US scores showed higher risk of relapse at 6 months (OR (95% confidence interval (CI)): 1.96 (1.09-3.52)). Additionally, patients with higher SC values at baseline showed higher risk of relapse at 18 months (1.66 (1.13-2.44)). Patients with higher baseline SC values showed an increased overall odds of relapse up to 18 months of follow-up (1.21 (1.08-1.36)). Furthermore, patients with higher US scores showed an increased overall odds of relapse up to 18 months of follow-up (1.96 (1.56-2.46)). Similarly, patients with higher US ratio showed an increased overall odds of relapse up to 18 months of follow-up (16.62 (7.17-38.54)). CONCLUSIONS: SC was able to identify JIA patients with unstable remission and increased risk of relapse. MSUS represents an interesting additional tool to the clinical evaluation, especially in predicting early relapse.