Mary Rooney

EULAR-PReS points to consider for the use of imaging in the diagnosis and management of juvenile idiopathic arthritis in clinical practice

To develop evidence based points to consider the use of imaging in the diagnosis and management of juvenile idiopathic arthritis (JIA) in clinical practice. The task force comprised a group of paediatric rheumatologists, rheumatologists experienced in imaging, radiologists, methodologists and patients from nine countries. Eleven questions on imaging in JIA were generated using a process of discussion and consensus. Research evidence was searched systematically for each question using MEDLINE, EMBASE and Cochrane CENTRAL. Imaging modalities included were conventional radiography, ultrasound, MRI, CT, scintigraphy and positron emission tomography. The experts used the evidence obtained from the relevant studies to develop a set of points to consider. The level of agreement with each point to consider was assessed using a numerical rating scale. A total of 13 277 references were identified from the search process, from which 204 studies were included in the systematic review. Nine points to consider were produced, taking into account the heterogeneity of JIA, the lack of normative data and consequent difficulty identifying pathology. These encompassed the role of imaging in making a diagnosis of JIA, detecting and monitoring inflammation and damage, predicting outcome and response to treatment, use of guided therapies, progression and remission. Level of agreement for each proposition varied according to the research evidence and expert opinion. Nine points to consider and a related research agenda for the role of imaging in the management of JIA were developed using published evidence and expert opinion.

IL7RA polymorphisms and chronic inflammatory arthropathies.

The C allele of a single nucleotide polymorphism (SNP), rs6897932, located in the interleukin-7 receptor alpha chain (IL7RA) was recently found to be associated with multiple sclerosis and Type I diabetes. We analysed 13 SNPs in the IL7RA gene in a combined cohort of patients with chronic inflammatory arthropathies (rheumatoid arthritis and juvenile idiopathic arthritis; 368 patients and 532 unaffected subjects). No significant associations with disease were found with the exception of the non-synonymous SNP rs6897932. This SNP showed modest enrichment of the TT genotype in arthritic patients compared with controls [P = 0.02; OR 1.72 (95% CI 1.08-2.75)]. Our data are suggestive for a role of rs6897932 in predisposition to chronic inflammatory arthropathies.

Knee disease in juvenile idiopathic arthritis (JIA): correlation between clinical and ultrasonographic findings.

Methods We are undertaking a five year prospective study of children with newly diagnosed JIA who have knee involvement. Review is three monthly with clinical assessment and US of knee(s) at each visit. Knee swelling is graded 0– 4. US scans were performed by an experienced rheumatologist MR using a Sonosite 180 Plus (L38 5–10 MHZ linear transducer) or Esaote MyLab25 scanner (LA523E 7.5–12 MHZ linear transducer). The scans have been scored independently by 2 observers unaware of the clinical findings (graded 0–3).

THU0318 A prospective comparative study of three methods of assessment of the knee joint in juvenile idiopathic arthritis: Clinical examination, ultrasound and MRI. (a newly developed knee mri scoring system)

Background Juvenile Idiopathic Arthritis (JIA) is the main cause of chronic arthritis in children, and it can lead to joint damage and disability. Detecting early articular involvement in JIA is therefore of crucial importance to prevent cartilage and bone damage in these young patients. Since 2004 we have undertaken a prospective study of children with newly diagnosed JIA with knee involvement, and we noted that, not infrequently, knees deemed clinically normal had appreciable effusion on ultrasound (US). Objectives We wished to prospectively compare agreement between clinical, US and MRI assessments of the knee joints in children with JIA, and to develop an MRI scoring system that allows assessment of disease activity and progression in children with JIA and compare it with US examination. Methods Three hundred and thirty one knees from 48 children, affected by JIA with knee arthritis, were assessed clinically and ultrasonographically on the same day, using a semi-quantitative scoring system from 0 to 3 for swelling and effusion, respectively. A subgroup of these children (25) with a total of 40 knees had matching MRI scans obtained within 0 to 14 days from clinical and US examinations. For those, US and MRI scans (T2 weighted images) were scored 0-3 for effusion, synovial hypertrophy, bone oedema and bone erosions, using our newly developed knee MRI scoring system. An open 0.2 Tesla scanner without administration of gadolinium was used. Results A moderate agreement for effusion was found between the 331 knees assessed clinically and ultrasonographically (K 0.54). Out of the 260 knees without swelling, 30 (11.5%) had mild to moderate effusion on US (Table). In the subgroup of 40 knees that had matching US and MRI scans it was demonstrated a good agreement for effusion (K 0.66) and a moderate agreement for synovial hypertrophy (K 0.47) between the two methods of assessments. The inter-observer reliability for US was very good for effusion (K 0.87), and good for synovial hypertrophy (K 0.68). The intra-observer reliability for MRI was good for effusion (K 0.73) and very good for synovial hypertrophy (K 0.85). Moreover, US tends to be more sensitive than MRI at detecting joint effusion (US scored on average 0.08 higher on the scoring system than MRI), maybe due to the lower sensitivity of MRI as T2 weighted images rather than contrast with gadolinium was used. Conclusions A significant number of knee joint effusions are missed on clinical examination. Therefore US of this joint should be used as an adjunct to clinical examination to avoid under-diagnosis, especially when joint injections are being considered, when clinical examination is negative and symptoms are equivocal for active arthritis, at follow-up to assess treatment’s efficacy. We have developed a reproducible scoring system for MRI of the knee. US appeared to be more sensitive than MRI at detecting effusions, however this is probably due to the absence of using gadolinium in MRI. It does however highlight the benefits of MSUS in paediatric rheumatology units where scans can be obtained at the same time as clinical assessment. Disclosure of Interest None Declared

THU0314 Plasma IL-6 Levels Correlate with Ultrasound Measures of Disease Activity in Lupus Arthritis

Background The role of specific cytokines in lupus arthritis has not been elucidated1. This is in stark contrast to rheumatoid arthritis (RA) where an abundance of research has culminated in an advancing era of novel biologic drugs. Objectives To analyse the cytokine profile in SLE patients with erosive, non-erosive arthritis and arthralgia as classified by ultrasound (US). Methods 50 SLE patients, and 40 RA patients had an US scan of their hand as per standardised protocols2-3. US scores per patient were expressed per joint and as a total ‘ultrasound activity’ score, (sum of Power Doppler (PD) and Grey Scale Synovial Hypertrophy scores in all joints) and a total erosion score. SLE disease activity was assessed (BILAG and SELENA SLEDAI). Plasma levels of IL-6, TNF-alpha and BLyS were measured using sandwich ELISA kits (Quantikine® kits, R & D). Results On the basis of the ultrasound results the SLE patients were divided into three groups, those with erosive arthritis (n = 24), those with non-erosive arthritis (n = 14) and those with a normal ultrasound scan (n = 12). CRP and IL-6 levels between the erosive lupus group and the RA group were not significantly different (p = 0.3 and p = 0.2 respectively). Conclusions This is the first study to examine levels of specific cytokines in a cohort of SLE patients stratified in terms of joint disease by ultrasound where the most significant finding is that IL-6 levels correlated with both clinical and ultrasound measures of arthritis disease activity. There is preliminary evidence that IL-6 blockade may be a potential treatment for SLE4 and if arthritis specific outcome measures were included in future clinical trials more robust evidence could be generated. References Jacob N & Stohl W. Cytokine disturbances in Systemic Lupus Erythematosus. Arthritis Research & Therapy 2011; 13 (4): 244 Wakefield RJ et al. Musculoskeletal ultrasound including definitions for ultrasonographic pathology. J Rheum 2005;32(12):2485-87. Szkudlarek M et al. Interobserver agreement in ultrasonography of the finger and toe joints in rheumatoid arthritis. A & R 2003;48(4):955-62. Illei G et al. Tocilizumab in systemic lupus erythematosus: data on safety...... A & R 2010;62(2):542-52. Disclosure of Interest None Declared

THU0288 Proteomic profiling of the synovial membrane in early untreated juvenile idiopathic arthritis

Background Juvenile idiopathic arthritis (JIA) is the one of the most common chronic childhood diseases with a prevalence of around 1/1000 [1]. Over time JIA can result in persistent joint inflammation leading to chronic pain and stiffness, joint deformity and damage. Disease aetiology remains unknown. Investigation of disease pathology at the level of the synovial membrane (SM) is required if we want to begin to understand the disease at the molecular and biochemical level. Objectives Proteomics enables us to better understand the disease process. Thus we undertook proteomic analysis of the SM from early disease-stage, treatment naïve JIA patients in order to identify protein expression profiles that could define JIA subgroups and help explain disease pathology. Methods SM biopsies were acquired from 16 newly diagnosed, untreated JIA patients (8 polyarticular and 8 oligoarticular) under general anaesthetic. After a 2 year follow up none of patients in the oligoarticular group had extended and so this group of patients were termed persistent oligoarticular. Protein was extracted from SM in lysis buffer. Each SM sample was minimally labeled with either Cy5 or Cy3 fluorescent dyes and an internal pooled standard (Cy2) was included on each gel. Proteins were separated by 2-D Fluorescence Difference Gel Electrophoresis (2D DIGE). Gel images were analysed and proteins displaying a 2-fold or greater change in expression levels between oligoarticular and polyarticular patients were identified by mass spectrometry (MS) with expression further verified by Western blotting. Proteins were then localised within the SM by immunohistochemistry. Results 2D DIGE analysis revealed an average of 460 spots per pH 4-7, 11cm gel which were matched across all 16 gels. ANOVA revealed 21 spots that were differentially expressed (2 fold or more change in expression levels) between polyarticular and oligoarticular patients (p≤0.05); 14 spots were expressed at 2-fold or higher in the oligoarticular group and 7 were expressed at 2-fold or higher in the polyarticular group. Principal component analysis (PCA) indicated that the synovial membrane proteome forms 2 distinct groups of patients in an unsupervised fashion. Hierarchical cluster analysis (HCA) was used to examine protein expression patterns and Pearson ranked correlation revealed two distinctive clusters of proteins. Conclusions The data indicates that SM proteome profiles could be used to stratify patients based on disease subgroup. The ability to identify, quantify and localise these specific target proteins in our patient samples would not only provide a novel insight into JIA disease pathology but may also provide potential therapeutic targets which could in turn be used to guide diagnosis and treatment. References Symmons DP, Jones M, Osborne J, Sills J, Southwood TR, Woo P. Pediatric rheumatology in the United Kingdom: data from the British Pediatric Rheumatology Group National Diagnostic Register. The Journal of rheumatology 1996;23(11):1975-1980. Disclosure of Interest None Declared

Early untreated juvenile idiopathic arthritis: predictors of outcome

Methods We are undertaking a five-year prospective study of children with newly diagnosed and untreated JIA. At least one knee was involved requiring intra-articular steroid injection. Detailed clinical, imaging, and laboratory parameters were measured at T0 and 3/12 for 2 years. At outset we obtained synovial biopsies. We report the outcome on those children for whom data is available for one year.