Synovitis In Juvenile Idiopathic Arthritis Research Articles

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

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. To assess the equivalence of unenhanced MRI with contrast-enhanced MRI in evaluating synovial thickness. 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. 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. 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.

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

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...

Ultrasonographic Evaluation of Sub-Clinical Synovitis in Juvenile Idiopathic Arthritis: The Disease Classification and Management.

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. 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. 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. 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. 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.

Double inversion recovery MRI versus contrast-enhanced MRI for evaluation of knee synovitis in juvenile idiopathic arthritis

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.

Effect of the Inclusion of the Metacarpophalangeal Joints on the Wrist Magnetic Resonance Imaging Scoring System in Juvenile Idiopathic Arthritis.

To extend the magnetic resonance imaging (MRI) score for assessment of wrist synovitis in juvenile idiopathic arthritis (JIA) by inclusion of the metacarpophalangeal (MCP) joints, and to compare the metric properties of the original and the extended score. Wrist MRI of 70 patients with JIA were scored by 3 independent readers according to (1) the wrist component of the rheumatoid arthritis MRI synovitis score (comprising distal radioulnar, radiocarpal, and combined midcarpal and carpometacarpal joints); and (2) an extended score including the MCP joints. Thirty-eight patients had a 1-year MRI followup. The concordance between the readers [intraclass correlation coefficient (ICC), 95% limits of agreement (LOA), and weighted Cohen's κ], correlations with clinical variables (Spearman's ϱ), and the sensitivity to change [standardized response mean (SRM)] were calculated for both scores. The interreader agreement was moderate for the original score (ICC 0.77; 95% CI 0.68-0.84) and good for the extended score (ICC 0.86; 95% CI 0.80-0.91). Using 95% LOA, the aggregate score variability was less favorable with relatively wide LOA. Weighted Cohen's κ of the individual joints indicated good agreement for the original score and good to excellent agreement for the extended score. Correlations with clinical variables reflecting disease activity improved for the extended score and its SRM was higher compared to that of the original score. The extended score showed better reliability, construct validity, and sensitivity to change than the original. Inclusion of the MCP joints should be considered for a more accurate assessment of disease activity and treatment efficacy in JIA.

The OMERACT Ultrasound Group: A Report from the OMERACT 2016 Meeting and Perspectives.

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.

Establishing percentile charts for hip joint capsule and synovial cavity thickness in apparently healthy children

BackgroundThe usefulness of musculoskeletal ultrasonography (MSUS) in paediatric population is limited by lack of reference values. One of such parameters is hip joint capsule thickness, postulated as an early measure for synovitis. However, the joint capsule is hardly a distinguished structure from slit synovial cavity in patients with little or no fluid collection. Therefore, in patients without effusion, it is more convenient to measure hip joint capsule thickness together with synovial cavity.The aim of the study was to establish percentile chart for hip joint capsule and synovial cavity thickness (HJC&SCT) in apparently healthy children.Material and methodsThe analysis included 816 US of hip joint in 408 children without musculoskeletal disorders, distributed equally throughout the whole developmental period in 18 one-year subgroups. Hip joints US was performed according to standard protocol including measurement of HJC&SCT in a single rheumatology centre by three investigators.ResultsThe 3rd, 10th, 25th, 50th, 75th, 90th, and 97th HJC&SCT percentile curves were depicted in the age and height charts for the combined group of girls and boys. The median HJC&SCT values were increasing with age from 3.7 (C10 - C90: 3.3 – 4.2) mm in the first year of life up to 6.7 (5.8 – 7.3) in 16 years old, and above. In a similar way the increase was seen with height from 3.9 (3.5 – 4.7) mm in shorter than 95 cm to 6.9 (6.2 – 7.4) mm in taller than 169 cm subjects. Intra-observer and inter-observer mean precision was less than 1.8 and 12.5%, respectively.ConclusionThe developed centile chart for hip joint capsule and synovial cavity thickness in the paediatric population is expected to improve detection of hip joint capsule disorders, including synovitis in juvenile idiopathic arthritis.

Serum Angiogenesis Markers and Their Correlation with Ultrasound-Detected Synovitis in Juvenile Idiopathic Arthritis.

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.

A104: Aggressive Erosive Synovitis in Juvenile Idiopathic Arthritis

Background/Purpose:Plain radiographs (x‐rays) are useful in the evaluation of children with JIA. Bone erosions are one of the finding that can be seen on x‐rays. However, they are most often reported in the polyarticular RF+ subtype of JIA and are rare in most other subtypes.Methods:Herein 3 patients with JIA are presented whose diagnoses were questioned after plain x‐rays were obtained. MRI later revealed significant erosive disease in these patients.Results:Case 1: A 14 yo male presented with a monoarthritis of the left wrist. Initial x‐rays were normal. His work‐up was unremarkable. His inflammatory markers were normal. He was thus diagnosed with JIA–oligoarthritis. After 6 months in remission, after the use of an NSAID, he flared in the same joint. Repeat x‐rays showed a radiolucent area with associated sclerosis in the scaphoid of unclear etiology. An MRI was thus requested. It revealed synovitis associated with erosive disease. Post gadolinium injection, a geode in the scaphoid bone with marked synovial enhancement visible within this erosion was detected. He underwent a joint injection which put him into remission. Repeat x‐rays one year later, revealed unchanged findings likely corresponding to the non‐healed erosion.Case 2: An 11 yo HLA B27 + male diagnosed with ERA with polyarthritis of the lower limbs and sacroiliac joints was treated with methotrexate and an NSAID. Investigations ruled out IBD and the arthritis was felt to be well controlled despite persistently elevated inflammatory markers of unclear etiology. He presented with a severe flare in his knees and ankles. X‐rays revealed well‐defined lytic lesions in the anterior aspect of the proximal tibial metaphysis just below the growth plate bilaterally. Given the concern of an infiltrative process, an MRI was obtained. Post gadolinium injection, a large erosion of the tibial plateau with marked synovial enhancement within this erosion was seen, as well as a knee synovitis. Etanercept was started.Case 3: An 8 yo male presented with a monoarthritis of the right wrist evolving for five months after an initial minor trauma. X‐rays revealed advanced bone maturation of the right wrist as well as a sclerotic lesion of the hamate. Given the initial trauma, an MRI was obtained which demonstrated very extensive bone marrow edema, synovitis, tenosynovitis and a large erosion within the hamate. A diagnosis of JIA–oligoarthritis was made. He underwent a joint injection with good disease control.Conclusion:Large erosions are not typical for some JIA subtypes such as oligoarthritis and ERA. Findings on x‐rays led the treating physicians to question the underlying diagnosis however, MRI revealed very aggressive synovitis of the wrist and knee in these patients. MRI was useful to demonstrate the presence of synovial enhancement within the eroded bone and helped rule out another diagnosis. Awareness of this type of aggressive arthritis is needed so that patients are not over‐investigated and prompt treatment can be offered.

FRI0331 Comparison of clinical and ultrasonographic examination of 7200 joints in 100 JIA patients satisfying wallace criteria of inactive disease (ID), suggests to add ultrasonography as a new criteria of ID

Backgroundultrasonography (US) is useful to detect synovial inflammation in JIA but still seldom used by pediatric rheumatologists to confirm the clinical definition of inactive synovitisObjectivesUS and Power Doppler Signal (PDS)...

SAT0510 Grey-Scale Ultrasonography with Power Doppler Technique: an Available Tool for the Assessment of Subclinical Joint Inflammatory Activity in Juvenile Idiopathic Arthritis

BackgroundMusculoskeletal ultrasonography (US) has been routinely used to confirm synovial effusion in children with arthritis. Recent studies show that US is more sensitive than clinical examination in detecting synovitis in...

Reduced joint assessment vs comprehensive assessment for ultrasound detection of synovitis in juvenile idiopathic arthritis

To propose a reduced joint power Doppler US (PDUS) assessment and provide preliminary evidence of its validity, feasibility, reliability and sensitivity to change compared with a comprehensive (i.e. 44 joints) PDUS assessment in evaluating synovitis in JIA. This multicentre study included 42 children with active JIA with ≥4 clinically involved joints requiring modified therapy. At each visit, clinical and PDUS assessments were performed blinded. Each joint was scored for greyscale (GS) synovitis and power Doppler signal according to a 4-point semiquantitative scale with calculation of US composite indices and US composite joint counts. A process of data reduction based on the frequency of US joint involvement was performed to obtain a reduced PDUS assessment. The relationship between the comprehensive and the reduced PDUS assessments was investigated by Spearman's coefficient at all visits, as well as the relationship between changes in the two PDUS assessments during follow-up. In addition, the metric properties of the comprehensive and the reduced PDUS assessments were tested. The 10-joint PDUS assessment, including bilateral knee, ankle, wrist, elbow and the second MCP joints, detected 100% of children with GS synovitis and power Doppler signal. The two PDUS assessments were highly correlated at all visits. The reduced model had a higher responsiveness than the comprehensive model. Intraobserver and interobserver agreement was good for both US findings. The 10-joint PDUS assessment is valid and feasible for assessment of synovitis in JIA in clinical practice.

MRI of the wrist in juvenile idiopathic arthritis: proposal of a paediatric synovitis score by a consensus of an international working group. Results of a multicentre reliability study

MRI is a sensitive tool for the evaluation of synovitis in juvenile idiopathic arthritis (JIA). The purpose of this study was to introduce a novel MRI-based score for synovitis in children and to examine its inter- and intraobserver variability in a multi-centre study. Wrist MRI was performed in 76 children with JIA. On postcontrast 3-D spoiled gradient-echo and fat-suppressed T2-weighted spin-echo images, joint recesses were scored for the degree of synovial enhancement, effusion and overall inflammation independently by two paediatric radiologists. Total-enhancement and inflammation-synovitis scores were calculated. Interobserver agreement was poor to moderate for enhancement and inflammation in all recesses, except in the radioulnar and radiocarpal joints. Intraobserver agreement was good to excellent. For enhancement and inflammation scores, mean differences (95 % CI) between observers were -1.18 (-4.79 to 2.42) and -2.11 (-6.06 to 1.83). Intraobserver variability (reader 1) was 0 (-1.65 to 1.65) and 0.02 (-1.39 to 1.44). Intraobserver agreement was good. Except for the radioulnar and radiocarpal joints, interobserver agreement was not acceptable. Therefore, the proposed scoring system requires further refinement.

Is ultrasound a validated imaging tool for the diagnosis and management of synovitis in juvenile idiopathic arthritis? A systematic literature review

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.

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

The characteristics of synovitis in juvenile idiopathic arthritis (JIA) are important to evaluate, as they define several clinical categories. The metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints are frequently involved. Few studies have investigated peripheral joint evaluation using ultrasonography, a sensitive tool for detecting subclinical synovitis. Our objectives here were to compare clinical and ultrasound evaluations of MCP and MTP joint synovitis and to determine the prevalence of predefined ultrasound abnormalities in JIA patients and healthy controls. Standardized physical and ultrasound assessments of the same joints were done in 31 consecutive patients with JIA and 41 healthy volunteers. Joint pain, motion limitation, and swelling were recorded. Ultrasonography was performed on the same joints by 2 trained sonographers who recorded synovial fluid, synovial hypertrophy, erosion, and power Doppler signal. Intraobserver reproducibility of ultrasonography was assessed. Of 558 peripheral joints examined in JIA patients, 69 (12.5%) had ultrasonographic synovitis and 83 (15%) had abnormal physical findings. All the physical abnormalities were significantly associated with ultrasonographic synovitis (P < 0.0001) but agreement was low between ultrasonographic and physical findings. Ultrasonographic synovitis was most common at the feet (59.4%), where it was detected clinically in only 25% of cases. Ultrasonographic synovitis was associated with the presence of synovial fluid. Cartilage vascularization was found in 2 (4.2%) healthy controls. Ultrasonography is useful for monitoring synovitis in JIA. Subclinical involvement of the MTP joints is common. Clinicians should be aware of the specific ultrasonographic findings in children.

Spectrum of magnetic resonance imaging appearances of juvenile temporomandibular joints (tmj) in non-rheumatic children

Temporomandibular joints (TMJ) are frequently involved in children with juvenile idiopathic arthritis (JIA), and gadolinium-enhanced magnetic resonance imaging (MRI) is the only modality for an early diagnosis. However, only very few data exist on the appearance of contrast-enhanced MRI of normal juvenile TMJ. To define the spectrum of normal MRI findings of juvenile TMJ, and to assess a possible overlap with findings typical for active synovitis in JIA. 96 children (192 TMJ), 51 boys and 45 girls with a median age of 7.8 years (range 3-13 years), underwent a head MRI. The presence of autoimmune disease, including JIA, was excluded via chart history, available laboratory findings, and the absence of known typical pathological MRI changes (degree of synovial enhancement, hyperintense signal on T2-weighted images in the synovia or bone marrow, and morphologic changes of the mandibular condyle) of the TMJ affected by JIA. In 90 (94%) children, the TMJ showed no MRI abnormalities compatible with arthritis. In three children (3%), the only abnormal MRI finding was a small bilateral joint effusion. A further three children (3%) had a mild synovial enhancement seen on both axial and coronal MR planes in one child and only in the axial plane in the other two children. Signal hyperintensity on T2-weighted images and other corresponding characteristics of TMJ inflammation were lacking in all these six patients. The vast majority of juvenile TMJ in non-rheumatic children shows no MRI abnormalities. Exceptions, including a discrete enhancement of the synovial membrane (3%) or small joint effusions (3%), can occur in a minority of patients, but none of them are accompanied by other signs of inflammation or morphological changes of the TMJ.

Comparison of clinical versus ultrasound‐determined synovitis in juvenile idiopathic arthritis

To compare clinical evaluation and ultrasonography (US) in the assessment of joint synovitis in children with juvenile idiopathic arthritis (JIA). Thirty-two patients underwent clinical evaluation of 52 joints by 2 pediatric rheumatologists. Joints were assessed for swelling, tenderness/pain on motion, and restricted motion. The same joints were scanned independently by an experienced sonographer for synovial hyperplasia, joint effusion, and power Doppler (PD) signal. In total, 1,664 joints were assessed both clinically and with US. On clinical examination, 98 joints (5.9%) were swollen, 59 joints (3.5%) were tender, and 40 joints (2.4%) had restricted motion. On US evaluation, 125 joints (7.5%) had synovial hyperplasia, 153 joints (9.2%) had joint effusion, and 53 joints (3.2%) had PD signal. A total of 104 (6.3%) and 167 (10%) joints had clinical and US synovitis, respectively. Of the 1,560 clinically normal joints, 86 (5.5%) had subclinical synovitis (i.e., had synovitis on US). US led to classifying 5 patients as having polyarthritis who were classified as having oligoarthritis or were found to have no synovitis on clinical evaluation. US variables were moderately correlated with clinical measures of joint swelling, but poorly correlated with those of joint tenderness/pain on motion and restricted motion. Overall, correlations were lower for PD signal than for synovial hyperplasia and joint effusion. We found that subclinical synovitis as detected by US is common in children with JIA. This finding may have important implications for patient classification and may affect the choice of the optimal therapeutic strategy in individual patients.

The Hypoxic Synovial Environment Regulates Expression of Vascular Endothelial Growth Factor and Osteopontin in Juvenile Idiopathic Arthritis

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.

Quantitative assessment of synovitis in juvenile idiopathic arthritis using Dynamic Contrast-Enhanced Magnetic Resonance Imaging

Methods In 22 JIA patients 12 wrists and 10 hips were studied with DCE-MRI. A 3D FFE Dynamic sequence was acquired after contrast injection. Two readers delineated independently a region of interest (ROI) in the area of maximal synovial enhancement. Enhancement curves were obtained plotting pixel intensity against time from the ROIs. Maximum level of synovial enhancement (ME), maximum rate of enhancement (MV) and rate of early enhancement (REE) were obtained from the curves. Correlations with clinical parameters of disease activity and with static MRI synovitis score were investigated.

A comparison of clinical vs ultrasound determined synovitis in juvenile idiopathic arthritis (JIA)

Methods In 34 patients, the clinician (SMM) assessed 52 joints and computed count of joints with swelling, pain/tenderness, restricted motion and active disease (AD). A global articular severity score (GASS) was obtained by grading symptoms in each joint (0–3 scale) and summing scores. Clinical assessments included physician's and parent's global ratings, functional ability and acute phase reactants. The sonographer (OE) scanned independently the same 52 joints for synovial hypertrophy (SI), synovial fluid (SF) and power Doppler (PD), each graded on a 0– 3 scale. Agreement and correlations were assessed with Cohen's kappa and Spearman's correlation, respectively (>0.4 = moderate agreement/correlation).