Rheumatoid Arthritis: United Kingdom

Deighton C, O'Mahony R, Tosh J, Turner C, Rudolf M, Anonymous00075. · Department of Rheumatology, Derbyshire Royal Infirmary, Derby DE1 2QY. · BMJ. · Pubmed #19289413 No free full text.

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Luqmani R, Hennell S, Estrach C, Basher D, Birrell F, Bosworth A, Burke F, Callaghan C, Candal-Couto J, Fokke C, Goodson N, Homer D, Jackman J, Jeffreson P, Oliver S, Reed M, Sanz L, Stableford Z, Taylor P, Todd N, Warburton L, Washbrook C, Wilkinson M, Anonymous00069, Anonymous00070. · Nuffield Orthopaedic Centre, University of Oxford, Oxford, UK. · Rheumatology (Oxford). · Pubmed #19174570 No free full text.

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Zhang W, Doherty M, Leeb BF, Alekseeva L, Arden NK, Bijlsma JW, Dincer F, Dziedzic K, Hauselmann HJ, Kaklamanis P, Kloppenburg M, Lohmander LS, Maheu E, Martin-Mola E, Pavelka K, Punzi L, Reiter S, Smolen J, Verbruggen G, Watt I, Zimmermann-Gorska I, Anonymous00031. · Dr W Zhang, Academic Rheumatology, University of Nottingham, Clinical Sciences Building, City Hospital, Nottingham NG5 1PB, UK. · Ann Rheum Dis. · Pubmed #18250111 No free full text.

Abstract: OBJECTIVES: To develop evidence-based recommendations for the diagnosis of hand osteoarthritis (OA). METHODS: The multidisciplinary guideline development group, representing 15 European countries, generated 10 key propositions regarding diagnosis using a Delphi consensus approach. For each recommendation, research evidence was searched for systematically. Whenever possible, the sensitivity, specificity and likelihood ratio (LR) were calculated; relative risk and odds ratios were estimated for risk factors for hand OA. Quality of evidence was categorised using the European League Against Rheumatism (EULAR) hierarchy, and strength of recommendation was assessed by the EULAR visual analogue scale. RESULTS: Diagnostic topics included clinical manifestations, radiographic features, subgroups, differential diagnosis, laboratory tests, risk factors and comorbidities. The sensitivity, specificity and LR varied between tests depending upon the cut-off level, gold standard and controls. Overall, no single test could be used to define hand OA on its own (LR <10) but a composite of the tests greatly increased the chance of the diagnosis. The probability of a subject having hand OA was 20% when Heberden nodes alone were present, but this increased to 88% when in addition the subject was over 40 years old, had a family history of nodes and had joint space narrowing in any finger joint. CONCLUSION: Ten key recommendations for diagnosis of hand OA were developed using research evidence and expert consensus. Diagnosis of hand OA should be based on assessment of a composite of features.

Foster H, Davidson J, Baildam E, Abinun M, Wedderburn LR, Anonymous00192. · School Clinical Medical Science (Rheumatology), Medical School, Newcastle University, Framlington Place, Newcastle-upon-Tyne, UK. · Rheumatology (Oxford). · Pubmed #17077155 links to  free full text

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Chakravarty K, McDonald H, Pullar T, Taggart A, Chalmers R, Oliver S, Mooney J, Somerville M, Bosworth A, Kennedy T, Anonymous00010, Anonymous00011. · Harold Wood Hospital, BHR NHS Trust, Romford, Essex RM7 OBE, UK. · Rheumatology (Oxford). · Pubmed #16940305 No free full text.

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Luqmani R, Hennell S, Estrach C, Birrell F, Bosworth A, Davenport G, Fokke C, Goodson N, Jeffreson P, Lamb E, Mohammed R, Oliver S, Stableford Z, Walsh D, Washbrook C, Webb F, Anonymous00231, Anonymous00232. · Nuffield Orthopaedic Centre, Windmill Road, Oxford OX3 7LD, UK. · Rheumatology (Oxford). · Pubmed #16844700 links to  free full text

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Kennedy T, McCabe C, Struthers G, Sinclair H, Chakravaty K, Bax D, Shipley M, Abernethy R, Palferman T, Hull R, Anonymous00199. · Royal Liverpool and Broadgreen University Hospital, UK. · Rheumatology (Oxford). · Pubmed #15728419 links to  free full text

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Ledingham J, Deighton C, Anonymous00040. · Queen Alexandra Hospital, Portsmouth, UK. · Rheumatology (Oxford). · Pubmed #15637039 links to  free full text

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Davies K, Woo P, Anonymous00129. · Department of Rheumatology, Great Ormond Street Hospital, London WC1N 3EJ, UK. · Rheumatology (Oxford). · Pubmed #12154212 links to  free full text

Abstract: OBJECTIVES: To establish opinion and clinical practice of senior clinicians working with children with rheumatic diseases with regard to immunization and to determine whether or not this is in accordance with current recommendations. To review published guidelines on the subject and examine the evidence base supporting them. METHODS: A questionnaire was sent to all consultant members of the British Paediatric Rheumatology Group. Information on a variety of issues relating to immunization practice in children with rheumatic diseases was collected. A review of published guidelines and the medical literature on the subject was undertaken to assess current recommendations for immunization in patients on immunosuppressive agents and the evidence supporting these. RESULTS: A number of different sources of information are being used to decide whether or not to immunize patients with rheumatic diseases. Clinical practice varies between individuals. Areas of discordance include the doses of corticosteroids and disease-modifying drugs at which significant immunosuppression is felt likely to occur, the level of immunosuppression conferred by rheumatological diseases themselves and whether or not vaccination should be deferred in the presence of active disease. There was also variation in policy with regard to immunizations not part of the routine recommended schedule. CONCLUSIONS: There is variation in both opinion and clinical practice regarding immunization in children with rheumatic diseases amongst senior clinicians working in the field of paediatric rheumatology. This reflects the lack of consistency between various sets of published guidelines and their non-specificity for rheumatic diseases and their treatment, and the lack of published evidence on the safety and efficacy of different vaccines in these situations. Further research is indicated in the hope that more specific guidelines may be developed for this not uncommonly encountered area of uncertainty.

Hull RG, Anonymous00033. · Queen Alexandra Hospital, Cosham, Portsmouth, Hampshire PO6 3LY, UK. · Rheumatology (Oxford). · Pubmed #11709617 links to  free full text

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Barnes PJ, Adcock IM. · National Heart and Lung Institute, Imperial College, London, UK. · Lancet. · Pubmed #19482216 No free full text.

Abstract: Glucocorticoid resistance or insensitivity is a major barrier to the treatment of several common inflammatory diseases-including chronic obstructive pulmonary disease and acute respiratory distress syndrome; it is also an issue for some patients with asthma, rheumatoid arthritis, and inflammatory bowel disease. Several molecular mechanisms of glucocorticoid resistance have now been identified, including activation of mitogen-activated protein (MAP) kinase pathways by certain cytokines, excessive activation of the transcription factor activator protein 1, reduced histone deacetylase-2 (HDAC2) expression, raised macrophage migration inhibitory factor, and increased P-glycoprotein-mediated drug efflux. Patients with glucocorticoid resistance can be treated with alternative broad-spectrum anti-inflammatory treatments, such as calcineurin inhibitors and other immunomodulators, or novel anti-inflammatory treatments, such as inhibitors of phosphodiesterase 4 or nuclear factor kappaB, although these drugs are all likely to have major side-effects. An alternative treatment strategy is to reverse glucocorticoid resistance by blocking its underlying mechanisms. Some examples of this approach are inhibition of p38 MAP kinase, use of vitamin D to restore interleukin-10 response, activation of HDAC2 expression by use of theophylline, antioxidants, or phosphoinositide-3-kinase-delta inhibitors, and inhibition of macrophage migration inhibitory factor and P-glycoprotein.

Lomax AR, Calder PC. · Institute of Human Nutrition, School of Medicine, University of Southampton, Tremona Road, Southampton SO16 6YD, UK. · Curr Pharm Des. · Pubmed #19442167 No free full text.

Abstract: A number of studies have been performed examining the influence of various probiotic organisms, either alone or in combination, on immune parameters, infectious outcomes, and inflammatory conditions in humans. Some components of the immune response, including phagocytosis, natural killer cell activity and mucosal immunoglobulin A production (especially in children), can be improved by some probiotic bacteria. Other components, including lymphocyte proliferation, the production of cytokines and of antibodies other than immunoglobulin A appear less sensitive to probiotics. Probiotics, including lactobacilli and bifidobacteria, administered to children can reduce incidence and duration of diarrhoea, but the precise effects depend upon the nature of the condition. Probiotic supplementation can reduce the risk of travellers' diarrhoea in adults, but does not affect duration. The effect of probiotics on other infectious outcomes is less clear. Probiotics may benefit children and adults with irritable bowel syndrome and adults with ulcerative colitis; studies in Crohn's Disease are less clear. Probiotics have little effect in rheumatoid arthritis. Probiotic supplementation, especially with lactobacilli and bifidobacteria, can reduce risk and severity of allergic disease, particular atopic dermatitis; early supplementation appears to be effective. Overall, the picture that emerges from studies of probiotics on immune, infectious and inflammatory outcomes in humans is mixed and there appear to be large species and strain differences in effects seen. Other reasons for differences in effects seen will include dose of probiotic organism used, duration of supplementation, characteristics of the subjects studied, sample size, and technical differences in how the measurements were made.

Clarke R, Derry S, Moore RA, McQuay HJ. · Pain Research and Nuffield Department of Anaesthetics, University of Oxford, West Wing (Level 6), John Radcliffe Hospital, Oxford, Oxfordshire, UK, OX3 9DU. · Cochrane Database Syst Rev. · Pubmed #19370600 No free full text.

Abstract: BACKGROUND: Etoricoxib is a selective cyclo-oxygenase-2 (COX-2) inhibitor prescribed for the relief of chronic pain in osteoarthritis and rheumatoid arthritis, and acute pain. The drug is believed to be associated with fewer upper gastrointestinal adverse effects than conventional non-steroidal anti-inflammatory drugs (NSAIDs). A number of studies in acute postoperative pain have now been published. OBJECTIVES: To assess the analgesic efficacy and adverse effects of a single oral dose of etoricoxib for moderate to severe postoperative pain. SEARCH STRATEGY: We searched Cochrane CENTRAL, MEDLINE, EMBASE, and the Oxford Pain Database, and reference lists of articles. Date of the most recent search: December 2008. SELECTION CRITERIA: Randomised, double-blind, placebo-controlled clinical trials of single dose, oral etoricoxib for acute postoperative pain in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion in the review and quality, and extracted data. The area under the pain relief versus time curve was used to derive the proportion of participants prescribed etoricoxib or placebo with at least 50% pain relief over six hours, using validated equations. Relative risk (RR) and number needed to treat to benefit (NNT) were calculated. Information on use of rescue medication was used to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. Information on adverse effects was also collected. MAIN RESULTS: Five studies (880 participants) were included in the review. All five studies reported on 120 mg, with 655 participants in a comparison with placebo. At least 50% pain relief was reported by 64% with etoricoxib 120 mg and 10% with placebo (NNT 1.9 (1.7 to 2.1)). For dental studies only the NNT was 1.6 (1.5 to 1.8). Two studies also reported on higher doses of 180 and 240 mg, with 249 participants. At least 50% pain relief was reported by 79% with etoricoxib 120 mg and 12% with placebo (NNT 1.5 (1.3 to 1.7)).Significantly fewer participants used rescue medication when taking etoricoxib 120 mg than those taking placebo (NNT to prevent remedication 2.4 (2.1 to 2.9)), and the median time to use of rescue medication was 20 hours. Adverse events were reported at a similar rate to placebo, with no serious events. AUTHORS' CONCLUSIONS: Single dose oral etoricoxib produces high levels of good quality pain relief after surgery. The 120 mg dose is as effective as, or better than, other commonly used analgesics.

Goëb V, Buch MH, Vital EM, Emery P. · Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, Leeds LS7 4SA, UK. · Curr Opin Rheumatol. · Pubmed #19342956 No free full text.

Abstract: PURPOSE OF REVIEW: To describe the mechanisms of action of abatacept (CTLA4-Ig) and summarize the evidence of its efficacy and safety in rheumatoid arthritis (RA) and other rheumatic diseases such as juvenile idiopathic arthritis (JIA). RECENT FINDINGS: Several studies have demonstrated the clinical efficacy (disease activity, quality of life, prevention of structural damage) of abatacept in patients with RA who have failed to respond to standard disease-modifying antirheumatic drugs (DMARDs) and antitumour necrosis factor-alpha biologic agents. Selective modulation of T-cell costimulation may also be an alternative therapy for children with JIA who are resitant to conventional DMARDs or biologics. SUMMARY: T-cell activation is critical to the onset and maintenance of RA. Abatacept (CTLA4-Ig), the first selective T-cell costimulation modulator has shown to be effective in RA and JIA. Recent 2-year data from the 'AIM' trial suggests an increased and sustained effect of blocking of T cell signalling on the inhibition of RA structural damage progression over time. Abatacept's safety profile in combination with DMARDs also seems to be favourable but should be avoided in combination with other biologics.

Freeston JE, Bird P, Conaghan PG. · Chapel Allerton Hospital, University of Leeds, UK. · Curr Opin Rheumatol. · Pubmed #19339918 No free full text.

Abstract: PURPOSE OF REVIEW: This review describes the important role of MRI in rheumatoid arthritis (RA), exploring recent reliability and validity work, as well as the current use of MRI in clinical trials and practice. RECENT FINDINGS: Both bone oedema and erosions on MRI have been confirmed as representing osteitis and cortical bone defects, respectively, adding to what was already known about the validity of contrast enhanced synovium representing synovitis. An increasing number of studies have used MRI as an outcome measure with interest moving from disease-modifying antirheumatic drugs (DMARDs) to biological therapies and a more technical focus on dynamic imaging. In addition, low-field extremity MRI has been developed as a well tolerated, comfortable and convenient method for imaging assessment in clinical practice. SUMMARY: This review has highlighted both recent research advances as well as the future potential for MRI in RA, with the aim that MRI will become part of standard measures for RA clinical trials. With respect to extremity imaging, further work is required to provide useful clinical algorithms.

de Pablo P, Chapple IL, Buckley CD, Dietrich T. · Rheumatology Research Group, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Edgbaston Birmingham, UK. · Nat Rev Rheumatol. · Pubmed #19337286 No free full text.

Abstract: Periodontitis is a chronic inflammatory disease that is characterized by loss of the periodontal ligament and alveolar bone, and is a major cause of tooth loss. Results from clinical and epidemiologic studies have suggested that periodontitis and tooth loss are more prevalent in individuals with rheumatoid arthritis (RA). However, the strength and temporality of the association are uncertain. Several biologically plausible causal and noncausal mechanisms might account for this association between periodontitis and RA. There is evidence to suggest that periodontitis could indeed be a causal factor in the initiation and maintenance of the autoimmune inflammatory response that occurs in RA. If proven, chronic periodontitis might represent an important modifiable risk factor for RA. In addition, patients with RA might show an increased risk of developing periodontitis and tooth loss through various mechanisms. Moreover, exposure to common genetic, environmental or behavioral factors might contribute to a noncausal association between both conditions.

Meenagh G, Filippucci E, Delle Sedie A, Riente L, Iagnocco A, Scirè CA, Montecucco C, Bombardieri S, Valesini G, Grassi W. · Antrim Hospital, United Kingdom. · Clin Exp Rheumatol. · Pubmed #19327222 No free full text.

Abstract: The field of inflammatory arthritis owes much to the advances in imaging technology which have enlightened not only clinical specialists but also researchers worldwide. The most exciting developments in recent decades have centred upon rheumatoid arthritis (RA) and more specifically the ultrasound (US) and magnetic resonance imaging (MRI) findings at various stages of the natural history of this condition. Investigation of RA using the standard techniques of plain radiography (x-ray) and more sophisticated computerised tomography (CT) have now been superseded by the exponential growth of use of US and MRI and this has been born out by the profusion of scientific papers published on these subjects.This paper aims to review the array of imaging modalities available as investigative tools to the rheumatologist when presented with various clinical scenarios by patients with RA.

Choy E, Sattar N. · Sir Alfred Baring Garrod Clinical Trials Unit, Academic Department of Rheumatology, King's College, London, UK. · Ann Rheum Dis. · Pubmed #19286905 No free full text.

Abstract: In severe untreated rheumatoid arthritis (RA), reductions in high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol and total cholesterol have been noted; this is in line with findings in other pathologies/conditions associated with inflammation or infection, such as sepsis, cancer, trauma or the postoperative period. Although the precise mechanisms remain to be established, cytokine-induced activation of the reticuloendothelial system is potentially critical to such changes. Consequently, dampening of inflammation in severe RA-as occurs with several biologics-may lead to increases, not only in high-density lipoprotein-cholesterol, but also with other lipid moieties, including total and low-density lipoprotein-cholesterol and, perhaps, triglycerides. This concept is consistent with findings following antitumour necrosis factor treatment and interleukin-6 receptor inhibition in patients with RA. At the same time, it is increasingly apparent that potent dampening of inflammation, however achieved, broadly reduces the risk of cardiovascular disease in RA. Therefore, changes in lipid profiles, particularly increases in cholesterol and triglycerides that occur with treatments for severe inflammation, may not represent increased cardiovascular risk as in the usual understanding of lipid-level elevations in individuals without significant inflammation. Rather, changes in lipid levels, in part or largely, may represent a predictable response to attenuation of inflammation. These observations are increasingly important clinically and should aid in the understanding and interpretation of lipid changes under inflammatory conditions, as well as in the context of potent anti-inflammatory interventions.

Firth J, Siddle H. · School of Healthcare, University of Leeds. · Nurs Stand. · Pubmed #19275023 No free full text.

Abstract: Patients with rheumatoid arthritis (RA) are at increased risk of developing foot ulceration. A multidisciplinary approach to the assessment, management and treatment of foot ulceration is essential to improve patient outcomes and reduce recurrence rates of ulceration. This article outlines the management and prevention of foot ulceration in patients with RA and promotes best practice.

Nistala K, Wedderburn LR. · Rheumatology Unit, Institute of Child Health, University College London, London, UK. · Rheumatology (Oxford). · Pubmed #19269955 No free full text.

Abstract: Inflammatory T cells are thought to be central to the pathology of autoimmune arthritis. Th17 cells, CD4 T cells that secrete the pro-inflammatory cytokine IL-17 play a critical role in murine models of arthritis. Recent evidence from human studies suggests that Th17 cells may be important players in several autoimmune diseases, including seronegative arthritis in adults, childhood arthritis [juvenile idiopathic arthritis (JIA)]. It was surprising to find that the development of Th17 cells is closely related to that of an immunoregulatory subset called regulatory T cells (Tregs). Tregs are important in the maintenance of immune homeostasis. Defects in Treg function or reduced numbers have been documented in several human autoimmune diseases, including RA and JIA. Conditions that typically favour the development of Tregs and promote tolerance can be subverted by inflammatory signals towards supporting the generation of Th17 cells. In animal models, the enhancement of Th17 cell differentiation is at the expense of Tregs, and these combined changes trigger autoimmunity. Several mechanisms have come to light that control this reciprocal relationship between Tregs and Th17 cells, including the action of pro-inflammatory cytokines such as IL-1beta. Anti-rheumatic biologic therapies may offer a means of restoring the Th17/Treg balance in favour of Tregs and thereby re-establishing immune tolerance.

Kubassova O, Boesen M, Peloschek P, Langs G, Cimmino MA, Bliddal H, Torp-Pedersen S. · Image Analysis Ltd., University of Leeds, 5-7 Cromer Terrace, Leeds, West Yorkshire, UK. · Ann N Y Acad Sci. · Pubmed #19250239 No free full text.

Abstract: Traditional imaging, represented by radiographs, provides a very concise description of anatomical pathology of bony structures. Both degenerative and inflammatory joint diseases are characterized by progressive joint destruction, and valid, reproducible measures of disease impact are available. Much effort has been expended to develop scoring systems for joint destruction in both osteoarthritis and rheumatoid arthritis, and the most common internationally accepted semiobjective scores are presented. The anatomical pathology mirrors the past activity of the disease, and advanced imaging gives an impression of the actual disease processes, which subsequently lead to the damage. Such information is required to facilitate the development of efficient therapy against arthritis. Newer technology, exemplified by MRI and ultrasound Doppler, supplements images of structural change with functional data of ongoing disease activity. This chapter focuses on the possibilities for quantification of images in MRI and ultrasound, in which postcontrast enhancement and Doppler information, respectively, are of special interest for the evaluation of the inflammatory changes of arthritis. To save time and eliminate human bias, automation is mandatory. In ultrasound, semiautomatic evaluations are coming that allow for a real-time, reproducible estimate of disease activity. With MRI fully automated algorithms have been developed for processing of data of bony structures, cartilage, and soft tissue, and are currently being implemented into everyday clinical practice.

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.

John H, Kitas G, Toms T, Goodson N. · Department of Rheumatology, Dudley Group of Hospitals NHS Trust, UK. · Best Pract Res Clin Rheumatol. · Pubmed #19233047 No free full text.

Abstract: Rheumatoid arthritis (RA) is associated with increased morbidity and mortality due to cardiovascular disease (CVD), mostly accelerated atherosclerotic CVD, and there is evidence that this occurs early in the inflammatory disease process. Both traditional and novel CVD risk factors as well as the effects of the RA disease process and its treatment interact and contribute to the development of CVD in RA. In this review we discuss the evidence for co-morbid CVD complicating early RA. This includes examining studies of mortality outcome and CVD events in cohorts of early RA patients as well as studies using surrogate markers for atherosclerotic CVD in RA. The evidence for shared risk factors for RA and CVD is presented. Screening and modification of CVD risk factors should be an integral part of care for any patient diagnosed with RA. Novel methods to diagnose CVD in high-risk asymptomatic RA patients need to be evaluated.

Pratt AG, Isaacs JD, Mattey DL. · Musculoskeletal Research Group, Institute for Cellular Medicine, School of Clinical Medical Sciences, Newcastle University, Newcastle, UK. · Best Pract Res Clin Rheumatol. · Pubmed #19233044 links to  free full text

Abstract: Rheumatoid arthritis (RA) is a systemic inflammatory disease with a predilection for symmetrically distributed diarthroidal joints. It is clinically heterogeneous, with particular disease phenotypes defined according to a complex interplay of genes and the environment. In this chapter we first summarize current knowledge of RA genetic susceptibility, a field which has been transformed in recent years by powerful modern genotyping technologies. The importance of a recently described subclassification for the disease based upon the presence or absence of circulating autoantibodies to citrullinated peptides has further informed genetic studies, and we consider the implications for our understanding of RA pathogenesis. We then review the cellular and molecular processes that initiate and perpetuate joint destruction.

Raza K, Filer A. · Rheumatology Research Group, Division of Immunity and Infection, Institute of Biomedical Research, MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK. · Best Pract Res Clin Rheumatol. · Pubmed #19233043 No free full text.

Abstract: The rapidity with which bone and cartilage damage occurs in patients with rheumatoid arthritis (RA), and the increasing body of evidence for the effectiveness of early intervention in RA, mean that there is a great need for approaches to accurately predict the development of RA in patients with early undifferentiated arthritis. We will review developments in the prediction of outcome on the basis of clinical and laboratory features, including measures of anti-citrullinated protein/peptide antibody status. Although accurate predictions are possible in the majority of patients using recently developed predictive algorithms which utilize clinical and serological variables, there remains a group of patients for whom it is very difficult to predict the development of RA. The utility of new strategies for prediction will be discussed, including recently discovered genetic associations of RA, an assessment of material from the primary site of pathology (the joint), and assessment using the highly sensitive imaging modalities of ultrasound and magnetic resonance imaging.