Validation of a semi-quantitative ultrasonography score for knee synovitis in juvenile idiopathic arthritis and its association with clinical findings.

Background:The transition from pediatric to adult care of patients affected by juvenile idiopathic arthritis (JIA) represents a complex process. A recent retrospective study has shown that in an early adulthood...

Ultrasound (US) has been shown to be a sensitive tool for evaluating synovitis in rheumatoid arthritis. However, the validity of US has not yet been established in juvenile idiopathic arthritis (JIA). The purpose of this study was to assess the validity of US for detecting synovitis for both diagnosis and followup in JIA. A systematic literature search in Embase and PubMed was performed before February 25, 2011. Selection criteria included original articles on children, JIA, US, Doppler, synovitis, and management published in the English language. Data were extracted from the articles meeting the inclusion criteria, particularly those focused on the US definition of synovitis, scoring systems used, and metric properties studied. The type and number of joints tested, study design, and quality of the studies were assessed. Twenty studies were identified using US to assess synovitis in JIA. The knee was the joint most commonly studied in these articles. There was heterogeneity regarding the US definition and quantification of synovitis. Synovitis was commonly assessed by using gray scale and only a few studies included the Doppler technique. Construct validity was reported in 80% of articles, including the clinical examination as the main comparator. US demonstrated higher sensitivity in detecting synovitis as compared to clinical examination. Few studies reported US reliability and responsiveness in JIA. US is a valuable tool for detecting synovitis in JIA, and demonstrated higher sensitivity in assessing synovitis as compared to clinical examination. However, further studies are needed for evaluating the reliability and responsiveness to assess synovitis changes over time.

ObjectiveTo 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.MethodsIn a cross-sectional...

Background: Ultrasonography (USG) is a perfect device for analyzing more than one joint in rather brief intervals of time and is well accepted by children with no harmful ionizing radiation, usually does not require sedation, and can be carried out without difficulty in an outpatient setting. Purpose: To demonstrate the ability of ultrasonography (USG) in detecting clinical and subclinical synovitis in children with juvenile idiopathic arthritis (JIA) and compare the USG findings with clinical findings. Methods: 20 patients with JIA diagnosed according to the ILAR criteria were include. A total of 208 joints were examined both clinically and ultrasonographically for detection of synovitis. The presence of subclinical synovitis detected by USG was sought and its effect on the classification of JIA was assessed. USG assessment was done using the High-Resolution Linear probe including both grey scale and Power Doppler assessment. Results: The mean age of patients was 10.2 years with average disease duration of 5.9 months. A total of 49 joints (23.5%) had clinical synovitis and 59 joints (28.4%) had USG synovitis out of a total of 208 joints. A total of 14 joints had subclinical synovitis (8.8% out of the 159 clinically normal joints) upon USG. USG additionally brought about classifying three patients as having poly articular disorder who had been considered as oligo articular upon clinical examination. Conclusion: USG assessment of subclinical synovitis in JIA patients is an essential component of classifying the disease and detects more joints with synovitis than clinical examination; however, both are complimentary and should be used in combination in all patients with JIA.

Comparison of Clinical and Ultrasonographic Evaluations for Peripheral Synovitis in Juvenile Idiopathic Arthritis

Whilst musculoskeletal ultrasound (MSUS) normal values for examination of the hip joint have been established for healthy children, equivalent values for patients with juvenile idiopathic arthritis (JIA), as well as internationally validated MSUS protocols for the optimal evaluation of synovitis are lacking. This study aimed to develop and validate the most sensitive MSUS protocol for the detection of hip synovitis in JIA. In consecutive JIA patients with ≥ 1 clinically affected hip joint, affected and unaffected hips underwent MSUS. Disease, demographic and clinical findings were recorded. Synovitis was graded using the pediatric OMERACT score for B-Mode (BM) and power-Doppler Mode (PD) in the longitudinal and transverse scans and the sensitivity and specificity was analyzed. Additionally anterior recess size (bone to capsula distance), capsula thickness and femoral head cartilage thickness (transverse view) were measured. Published data provided further control data for anterior recess size (children without JIA). Interobserver reliability of BM and PD was tested using Fleiss-Kappa. 60 patients were enrolled who had 76 hips with and 32 without clinical arthritis. BM was positive (grade ≥ 1) in 74/76 of hips with clinical arthritis (97%, sensitivity 0.97 (0.93-1.0), specificity 0.85 (0.74-0.97) versus 2/32 (6%) in hips without arthritis. PD positivity frequency was 6 (8%) in hips with arthritis versus 0 in hips without. Anterior recess size (mean ± SD) was significantly wider in patients with clinical arthritis (9.9 ± 2.5 vs 5.5 ± 1.3, p-value 0.001). Use of the cut-off of ≥ 7.2 mm resulted in an area under the curve of at least 95%, with a sensitivity of 86% and specificity of 94%. Articular capsula and femoral head cartilage thickness did not differ between patients with and without arthritis. Recess size was comparable in the internal and external control groups (n = 449). Interobserver reliability of BM and PD positivity showed excellent agreement (kappa = 0.85). The Pediatric internationally agreed UltraSound hip synovitis protocol (PIUS-hip) could be limited to one longitudinal scan including B-Mode scoring plus measurement of anterior recess size for maximal sensitivity and specificity for synovitis.

AB1023 Bone Erosions Visualized by Magnetic Resonance Imaging in Juvenile Idiopathic Arthritis (JIA) are True Cortical Breaks Visible in High-Resolution Computed Tomography

To characterize ankle magnetic resonance imaging (MRI) features in pediatric and young adult patients with familial Mediterranean fever (FMF) and compare them with those in juvenile idiopathic arthritis (JIA) and chronic nonbacterial osteomyelitis (CNO) in order to identify distinguishing or overlapping imaging features among the three conditions. Twelve ankle MRI examinations from 11 patients with FMF (mean age 12.4 years, 7 females) were retrospectively evaluated and compared with 22 examinations from 17 patients diagnosed with JIA (12 patients/14 ankles, mean age 14.3 years, 8 females) or CNO (5 patients/8 ankles, mean age 10.2 years, 3 females). Calcaneal enthesitis features were assessed at the insertion site of the Achilles tendon, plantar fascia, and the long plantar tendon. Also evaluated were the presence of diffuse calcaneal bone marrow edema (BME), midfoot arthritis, synovitis, and tenosynovitis. Insertional calcaneal BME, an enthesitis-related feature, was more prevalent in FMF patients compared to both JIA and CNO, while among the three evaluated entheses, long plantar tendon enthesitis was significantly more prevalent in FMF patients only compared to those with JIA (p < 0.001). CNO presented a predominantly osseous inflammation pattern with diffuse calcaneal BME (87.5%, p < 0.001) and additional hindfoot BME (75%, p < 0.002), clearly distinct from FMF. Synovitis and tenosynovitis were more commonly observed in JIA patients, although the differences compared to FMF and CNO were not statistically significant. Although imaging features overlap among FMF, CNO, and JIA, distinct MRI patterns emerge: enthesitis predominates in FMF, osteitis in CNO, and synovitis in JIA.

AB0991 Current State of Musculoskeletal Ultrasound in JIA in France and Switzerland

# 1.1 Disease specific divergence of T cell receptor (TCR) oligoclonality in juvenile idiopathic arthritis (JIA) {#article-title-2} We used a highly sensitive molecular heteroduplex technique to track specific clonality of...

Synovial angiogenesis, a critical determinant of juvenile idiopathic arthritis (JIA) pathogenesis, is sustained by various mediators, including vascular endothelial growth factor (VEGF) and osteopontin (OPN). We characterized the contribution of the local hypoxic environment to VEGF and OPN production by monocytic cells recruited to the synovium in JIA. Paired synovial fluid (SF) and peripheral blood (PB) samples were collected from 20 patients with JIA. Mononuclear cells (MC) were isolated, and monocytic cells were purified by adherence, maintained in a hypoxic environment, or subjected to reoxygenation. VEGF and OPN protein concentrations were tested in SF, plasma, and culture supernatants by ELISA, and mRNA expression was assessed in freshly purified and cultured cells by reverse transcriptase-polymerase chain reaction. Synovial tissue was obtained at synovectomy from 4 patients with JIA, and analyzed by immunohistochemistry for VEGF, OPN, CD68, and hypoxia-inducible factor-1alpha (HIF-1alpha). VEGF mRNA expression was increased in SFMC and SF monocytic cells compared to matched PBMC and PB monocytic cells or SF lymphocytes, correlating with significantly higher protein levels in SF relative to plasma samples. Accordingly, OPN mRNA expression in SF monocytic cells was associated with significant increase of SF protein. Immunohistochemistry revealed the presence of both factors in synovial tissues at the level of the lining and sublining layers, which colocalized with intense CD68 and HIF-1alpha staining, suggesting production by hypoxic synovial monocytic cells. VEGF and OPN expression was abrogated upon SF monocytic cell reoxygenation and maintained by exposure to prolonged hypoxia. Hypoxic synovial monocytic cells are a likely source of VEGF and OPN in JIA. These data point to a role for hypoxia in the perpetuation of synovitis in JIA.

BackgroundDouble inversion recovery (DIR) MRI has the potential to accentuate the synovium without using contrast agents, as it allows simultaneous signal suppression of fluid and fat. The purpose of this study was (1) to compare DIR MRI to conventional contrast-enhanced (CE) MRI for delineation of the synovium in the knee in children with juvenile idiopathic arthritis (JIA) and (2) to assess the agreement between DIR MRI and CE-MRI regarding maximal synovial thickness measurements.ResultsIn this prospective study, 26 children with JIA who consecutively underwent 3.0-T knee MRI between January 2018 and January 2021 were included (presence of knee arthritis: 13 [50%]; median age: 14 years [interquartile range [IQR]: 11–17]; 14 girls). Median confidence to depict the synovium (0–100 mm visual analogue scale; scored by 2 readers [consensus based]) was 88 (IQR: 79–97) for DIR MRI versus 100 (IQR: 100–100) for CE-MRI (p value = < .001). Maximal synovial thickness per child (millimeters; scored by 4 individual readers) on DIR MRI was greater (p value = < .001) in the children with knee arthritis (2.4 mm [IQR: 2.1–3.1]) than in those without knee arthritis (1.4 mm [IQR: 1.0–1.6]). Good inter-technique agreement for maximal synovial thickness per child was observed (rs = 0.93 [p value = < .001]; inter-reader reliability: ICC DIR MRI = 0.87 [p value = < .001], ICC CE-MRI = 0.90 [p value = < .001]).ConclusionDIR MRI adequately delineated the synovium in the knee of children with JIA and enabled synovial thickness measurement similar to that of CE-MRI. Our results demonstrate that DIR MRI should be considered as a child-friendly alternative to CE-MRI for evaluation of synovitis in children with (suspected) JIA.

To provide an update from the Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group on the progress for defining ultrasound (US) minimal disease activity threshold at joint level in rheumatoid arthritis (RA) and for standardization of US application in juvenile idiopathic arthritis (JIA). For minimal disease activity, healthy controls (HC) and patients with early arthritis (EA) who were naive to disease-modifying antirheumatic drugs were recruited from 2 centers. US was performed of the hands and feet, and scored semiquantitatively (0-3) for synovial hypertrophy (SH) and power Doppler (PD). Synovial effusion (SE) was scored a binary variable. For JIA, a Delphi approach and subsequent validation in static images and patient-based exercises were used to developed preliminary definitions for synovitis and a scoring system. For minimal disease activity, 7% HC had at least 1 joint abnormality versus 30% in the EA group. In HC, the findings of SH and PD were predominantly grade 1 whereas all grades were seen in the EA cohort, but SE was rare. In JIA, synovitis can be diagnosed based on B-mode findings alone because of the presence of physiological vascularization. A semiquantitative scoring system (0-3) for synovitis for both B-mode and Doppler were developed in which the cutoff between Doppler grade 2 and grade 3 was 30%. The first step has been taken to define the threshold for minimal disease activity in RA by US and to define and develop a scoring system for synovitis in JIA. Further steps are planned for the continuous validation of US in these areas.

Synovial angiogenesis is considered to be an important early step in the pathogenesis of juvenile idiopathic arthritis (JIA). In this study we assessed levels of angiogenic markers in serum or synovial fluid and their possible relevance to disease activity or degree of ultrasound signs of synovial inflammation and angiogenesis in early JIA. The concentration of vascular endothelial growth factor (VEGF), its soluble receptors 1 and 2 (sVEGF-R1, sVEGF-R2), and angiopoietins 1 and 2 (ANG-1, ANG-2) were evaluated in 43 JIA patients and 23 healthy controls. Synovial angiogenesis was assessed by means of Power-Doppler Ultrasonography (PDUS), according to the fourth-grade vascularity scale. VEGF and its receptors' (sVEGF-R1, sVEGF-R2) serum levels were significantly higher in JIA patients (p = 0.002). We found large variation in serum ANG-1 and ANG-2 levels. The PDUS imaging identified increased synovial microvascular blood flow in 15 (35.7%) examined JIA children. Intensity of joint vascularization correlated with higher serum VEGF and its levels was lowest in grade 0 and highest in grade 3 (p < 0.007 and p < 0.001, resp.). In conclusion, the high correlation between synovial microvascular blood flow, serum angiogenic proteins, and symptoms of synovitis may indicate its important role in pathogenesis of JIA.

Juvenile Idiopathic Arthritis (JIA) frequently affects children's hips, causing severe progression, but early hip synovitis lacks obvious symptoms and is hard to detect via conventional ultrasound, delaying diagnosis. magnetic resonance imaging (MRI), though accurate, is costly and inaccessible for routine use. This study aims to develop an automatic identification system for the early diagnosis of hip synovitis in JIA through the integration of deep learning and radiomics techniques. A YOLO-JIA model specifically designed for the automatic segmentation of hip ultrasound images was developed. Radiomic features were extracted from these segmented regions. Subsequently, feature selection was performed using the analysis of variance (ANOVA) test followed by least absolute shrinkage and selection operator (LASSO) regression. Based on the selected features, a Random Forest (RF) classification model was constructed and evaluated separately on an internal and an external validation set. The YOLO-JIA model demonstrated high precision (0.98) and recall (1.00) in object detection tasks, with a mean average precision at 50-95% (mAP50-95) for mask (M) reaching 0.86. The RF classification model achieved an area under the curve (AUC) of 0.88 on the internal validation set and 0.81 on the external validation set. Decision curve analysis further confirmed the clinical utility of our proposed system. Finally, the models were integrated and deployed locally. This study successfully developed a system for the early diagnosis of JIA hip synovitis based on deep learning and radiomics. The system offers an effective and reliable means for early screening, enhancing diagnosis rates, and ultimately reducing the risk of severe joint damage in JIA patients.