Rheumatoid Arthritis: Gardner-Medwin JM

Gardner-Medwin JM, Irwin G, Johnson K. · Department of Child Health, University of Glasgow, Royal Hospital for Sick Children, Yorkhill, Glasgow, Scotland, UK. · Ann N Y Acad Sci. · Pubmed #19250231 No free full text.

Abstract: The use of MRI in the assessment of the musculoskeletal system in children has important differences from its use in adults. Growth in children has significant impact on the epiphysis and growth plate, which are important structures in the growing child, and there are radiological features that differ from those in adults: disease may alter structures during a period of growth; the pathologies themselves are a distinct group of diseases at variance with adult arthritis and myositis, with a different spectrum of differential diagnoses; and many technical issues are different when imaging a child. These are important considerations in choosing the appropriate imaging. MRI is a powerful and valuable imaging technique in pediatric musculoskeletal pathologies, with considerable potential for future developments to enhance its role in diagnosis, management, and therapeutic intervention for these children.

Killeen OG, Gardner-Medwin JM. · Paediatric Rheumatology, Department of Child Health, RHSC, Glasgow, UK. · Arch Dis Child. · Pubmed #16714734 links to  free full text

This publication has no abstract.

Gardner-Medwin JM, Killeen OG, Ryder CA, Bradshaw K, Johnson K. · Department of Child Health, Royal Hospital for Sick Children, Yorkhill, Glasgow, UK. · J Rheumatol. · Pubmed #16981289 No free full text.

Abstract: OBJECTIVE: A proportion of children with oligoarthritis have an aggressive disease course. Identifying these children at presentation would help guide prognosis and management. We examined if magnetic resonance imaging (MRI) of clinically unaffected joints is more sensitive than clinical assessment in identifying those at risk of developing arthritis in more than one joint. METHODS: Ten children were recruited; they had a mean age of 9.4 (range 5.2-14.2) years at presentation of a monoarthritis. MRI of a clinically unaffected knee was performed within 4 months of presentation, and was reported by 2 pediatric radiologists blinded to the clinical findings. All MR examinations included post-gadolinium sequences. Joints with clinically apparent arthritis were recorded regularly over a median of 37.0 (range 6.6-47.0) months by a median of 6.0 (range 2-8) pediatric rheumatologists blinded to the MR result. RESULTS: Four children developed arthritis in other joints over a median of 3.9 (range 3-6) months after the MRI scan; all had abnormal MRI scans at presentation. Three of these developed clinical features in the previously normal knee 4-11 months after MRI identified small joint effusions, synovial hypertrophy, and lymph node enhancement. One child developed a polyarthritis, but never developed clinical features in the imaged knee over 3.8 years of followup. Four other children had a persistent monoarthropathy with a median followup of 29.5 (range 6.6-42.0) months. All 4 had normal MRI. Two children had reactive arthritis. CONCLUSION: MRI distinguished between patients with a persistent monoarthritis and those who developed further clinical arthritis up to 1 year later. The results suggest a widespread inflammatory process may exist in children whose arthritis extends, and this has implications for our understanding of disease and the design and timing of therapeutic interventions.

Black AP, Bhayani H, Ryder CA, Pugh MT, Gardner-Medwin JM, Southwood TR. · Department of Rheumatology, Division of Immunity and Infection, University of Birmingham, Birmingham, UK. · Arthritis Res Ther. · Pubmed #12932291 links to  free full text

Abstract: The aim of this research was to determine whether all memory T cells have the same propensity to migrate to the joint in patients with juvenile idiopathic arthritis. Paired synovial fluid and peripheral blood mononuclear cell proliferative responses to a panel of antigens were measured and the results correlated with a detailed set of laboratory and clinical data from 39 patients with juvenile idiopathic arthritis. Two distinct patterns of proliferative response were found in the majority of patients: a diverse pattern, in which synovial fluid responses were greater than peripheral blood responses for all antigens tested; and a restricted pattern, in which peripheral blood responses to some antigens were more vigorous than those in the synovial fluid compartment. The diverse pattern was generally found in patients with a high acute phase response, whereas patients without elevated acute phase proteins were more likely to demonstrate a restricted pattern. We propose that an association between the synovial fluid T cell repertoire and the acute phase response suggests that proinflammatory cytokines may influence recruitment of memory T cells to an inflammatory site, independent of their antigen specificity. Additionally, increased responses to enteric bacteria and the presence of alphaEbeta7 T cells in synovial fluid may reflect accumulation of gut associated T cells in the synovial compartment, even in the absence of an elevated acute phase response. This is the first report of an association between the acute phase response and the T cell population recruited to an inflammatory site.

Johnson K, Wittkop B, Haigh F, Ryder C, Gardner-Medwin JM. · Department of Clinical Radiology, Birmingham Children's Hospital, Birmingham, U.K. · Clin Radiol. · Pubmed #12069461 No free full text.

Abstract: AIMS: Early diagnosis of juvenile idiopathic arthritis (JIA) facilitates earlier more aggressive therapy, and improved outcome. Recognition of the features of early, untreated JIA on magnetic resonance imaging (MRI) will improve disease detection and expedite treatment. This study aims to highlight the relevant MRI features. METHODS: MRI examinations of the knee joint were performed on 11 children with clinically confirmed, early, untreated JIA. The MRI images were obtained at a mean of 2 months after symptom onset and independently evaluated by two consultant paediatric radiologists. RESULTS: Abnormalities were found on all MRI examinations. Synovial hypertrophy, joint effusions, popliteal lymph nodes and soft tissue swelling were present in all patients. Gadolinium DTPA enhancement improved the detection of synovial hyperplasia. Metaphyseal splaying and condylar overgrowth were seen in five cases (41%), oedema of the lateral collateral ligament in two cases (18%) and superficial cartilage thinning in one case. Bony erosions and deep cartilage destruction were not demonstrated. CONCLUSION: MRI of the knee joint identifies early joint changes which are distinct from those in later disease. The presence of these features should alert the radiologist to the possible diagnosis of JIA and post gadolinium DTPA sequences should be performed. Gadolinium DPTA enhancement increases the sensitivity for the detection of inflammatory changes in JIA.

Black AP, Bhayani H, Ryder CA, Gardner-Medwin JM, Southwood TR. · MRC Human Immunology Unit, Institute of Molecular Medicine, John Radcliffe Hospital,Headington, Oxford, UK. · Arthritis Res. · Pubmed #12010567 links to  free full text

Abstract: A study was done to determine if the differentiation and activation phenotype of T cells in synovial fluid (SF) from patients with juvenile idiopathic arthritis (JIA) is associated with T-cell proliferation in situ. Mononuclear cells were isolated from 44 paired samples of peripheral blood and SF. Differentiation and activation markers were determined on CD4 and CD8 T cells by flow cytometry. Cell-cycle analysis was performed by propidium iodide staining, and surface-marker expression was also assessed after culture of the T cells under conditions similar to those found in the synovial compartment. The majority of the T cells in the SF were CD45RO+CD45RBdull. There was greater expression of the activation markers CD69, HLA-DR, CD25 and CD71 on T cells from SF than on those from peripheral blood. Actively dividing cells accounted for less than 1% of the total T-cell population in SF. The presence or absence of IL-16 in T-cell cultures with SF or in a hypoxic environment did not affect the expression of markers of T-cell activation. T cells from the SF of patients with JIA were highly differentiated and expressed early and late markers of activation with little evidence of in situ proliferation. This observation refines and extends previous reports of the SF T-cell phenotype in JIA and may have important implications for our understanding of chronic inflammation.

Njeh CF, Shaw N, Gardner-Medwin JM, Boivin CM, Southwood TR. · Department of Nuclear Medicine, Queen Elizabeth Hospital, Birmingham, UK. · J Clin Densitom. · Pubmed #11090232 No free full text.

Abstract: Periarticular osteoporosis around inflammed joints and generalized osteoporosis have been shown to be markers of disease activity and severity in children with juvenile idiopathic arthritis (JIA). Bone mineral density (BMD) in adults can be assessed precisely by dual X-ray absorptiometry (DXA), but this technique has not been used widely in children. Quantitative ultrasound (QUS) may provide an alternative method for assessment of bone status. The aim of this pilot study was to compare QUS to DXA in assessing generalized osteoporosis in a cohort of patients JIA. Twenty-two Caucasian children (15 females, 7 males) with JIA of duration 19-142 months (mean 71 mo) and age 7-17 yr were recruited. Total body and lumbar spine BMD and bone mineral content (BMC) were measured by DXA using standard procedures on a Lunar DPX-L scanner. QUS was performed using Myriad SoundScan 2000. Speed of sound (SOS) was measured at the right midtibia. The DXA results were compared to QUS using linear regression analysis. Spine and total body BMD measured by DXA correlated significantly with tibia SOS (spine: r = 0.57, p < 0.007; total body: r = 0.68, p < 0.001). Spine BMC was similarly related to SOS as BMD (r = 0.58, p < 0.007). Individual patient weight and height were strong predictors of BMD, but only moderate predictors of SOS. The mean spine BMD was lower in the JIA patients compared to the normal ranges (mean Z-score of -1.19). BMD Z-scores were negatively associated with disease duration. Patients taking steroids were associated with lower Z-scores. In conclusion, SOS shows a significant correlation with BMD as measured by DXA, albeit with wide 95% confidence intervals in this small pilot study. QUS was also well tolerated and was technically easy to perform in these children. With the added advantage that it is free from radiation risk, further assessment of this potentially valuable tool for measuring bone status in children is warranted.