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ID PMID Title PublicationDate abstract
20046016 [Is rheumatoid arthritis without anti-citrullinated peptide antibody a genetically distinc 2009 Dec These days, rheumatoid arthritis (RA) is reported to be subclassified into two subsets by anti-citrullinated peptide antibody (ACPA) positivity. Clinically, ACPA positive RA tends to develop more severe arthritis than ACPA negative RA. In addition, a lot of reported susceptibility genes to RA (ie. HLA-DRB1(*)04, PTPN22, TRAF1/C5, CTLA4) are found to be associated only with ACPA positive RA but not with ACPA negative RA. It is getting clear that HLA-DRB1(*)04, which was believed to be primarily associated with RA, is not a primary risk factor but ACPA is. Then, a hypothesis for the disease mechanism of ACPA positive RA is set as follows; citrullination possibly due to smoking, etc, provokes ACPA production in individuals who have susceptibility alleles of genes including HLA, followed by joint inflammation in autoantibody-dependent manner. The search for susceptibility genes for ACPA negative RA is slowly progressing, but only a few genes are so far reported: HLA-DRB1(*)03 for Caucasian, HLA-DRB1(*)09 for Japanese, IRF5 and STAT4. When we investigate the disease mechanisms of RA, we should manage independently the two disease subsets : ACPA positive and ACPA negative RA.
20698446 Rheumatoid forefoot reconstruction. 2010 Jun Management of the patient with rheumatoid forefoot deformity requires a multidisciplinary integrated approach for a successful outcome. Despite recent advances in the pharmacological management of rheumatoid arthritis and its impact upon disease progression, forefoot deformity and pain remain common manifestations requiring input from orthopaedic surgeons. The typical deformities encountered include hallux valgus, with subluxation or frank dislocation at the lesser metatarsophalangeal (MTP) joints. Surgical intervention is directed at correcting and decompressing these deformities, with the ultimate goal of a stable, painless, functional plantigrade foot. Although a variety of surgical options exist, fusion of the 1st MTP joint with lesser MTP joint excision arthroplasty remains the gold standard, upon which newer procedures should be judged. This article reviews the pathophysiology of forefoot deformity in rheumatoid arthritis with special emphasis on recent advances in surgical management.
20515283 Biomarkers for rheumatoid arthritis: making it personal. 2010 Effective treatment of rheumatoid arthritis (RA) has been hampered by the heterogeneity of the disease. Although early intervention can result in disease remission, it requires early diagnosis - and current diagnostic tests are not sufficiently accurate or sensitive in the early stages of RA. As a result, RA is typically diagnosed only once damage to the joints has already begun, a time at which the window for optimal treatment may have been missed. Furthermore, a significant proportion of RA patients do not respond to any given therapeutic. Research efforts are increasingly focused on discovery of biomarkers that enable early diagnosis and stratification of RA, and thus the implementation of timely, targeted therapy. Biomarkers have the potential to transform the management of RA by enabling not only early diagnosis, but also assessment and prediction of disease severity, selection of therapy, and monitoring of response to therapy. In this mini review, we discuss the development of molecular biomarkers for RA.
19578391 The serological diagnosis of rheumatoid arthritis: antibodies to citrullinated antigens. 2009 Mar BACKGROUND: This article provides an overview of modern serological diagnostic testing for rheumatoid arthritis (RA) involving the detection of antibodies against citrullinated peptides/proteins (ACPA). Recommendations are also given for differential diagnosis and sequential testing in rheumatoid arthritis, with a view towards improving early diagnosis, so that irreparable joint damage can be avoided. METHODS: Selective literature research, with consideration of the authors' own publications. RESULTS: Two different, adequately evaluated testing systems, involving the detection of anti-CCP antibodies and of anti-MCV antibodies, are now commercially available and enable routine, relatively highly specific diagnostic testing for RA. Two point-of-care tests (POCT) for the early diagnosis of RA constitute the latest development in serologic diagnostic testing. CONCLUSIONS: The two ACPA assays now on the market are equally useful for the diagnosis of rheumatoid arthritis. The correlation between RA disease activity and stratification with ACPA has only been demonstrated to date through the detection of anti-MCV antibodies.
21031164 Targeting IKKβ for the treatment of rheumatoid arthritis. 2010 Oct Activation of the nuclear factor-κB (NF-κB) family of transcription factors results in the expression of numerous genes involved in the regulation of the innate and adaptive immune responses, and has been implicated as a key mechanism in chronic inflammatory diseases including rheumatoid arthritis (RA). The IκB kinases (IKKs) are key components in the signaling pathway by which proinflammatory stimuli, such as lipopolysaccharide and tumor necrosis factor-α lead to the activation of NF-κB. The most widely studied of the IKKs is IKKβ. Inhibitors of the kinase activity of IKKβ offer opportunities for intervention in RA, as well as other inflammatory disorders. Some examples for which the most extensive data are available will here be reviewed.
21062513 The association between rheumatoid arthritis and periodontal disease. 2010 Chronic, plaque-associated inflammation of the gingiva and the periodontium are among the most common oral diseases. Periodontitis (PD) is characterized by the inflammatory destruction of the periodontal attachment and alveolar bone, and its clinical appearance can be influenced by congenital as well as acquired factors. The existence of a rheumatic or other inflammatory systemic disease may promote PD in both its emergence and progress. However, there is evidence that PD maintains systemic diseases. Nevertheless, many mechanisms in the pathogenesis have not yet been examined sufficiently, so that a final explanatory model is still under discussion, and we hereby present arguments in favor of this. In this review, we also discuss in detail the fact that oral bacterial infections and inflammation seem to be linked directly to the etiopathogenesis of rheumatoid arthritis (RA). There are findings that support the hypothesis that oral infections play a role in RA pathogenesis. Of special importance are the impact of periodontal pathogens, such as Porphyromonas gingivalis on citrullination, and the association of PD in RA patients with seropositivity toward rheumatoid factor and the anti-cyclic citrullinated peptide antibody.
19683077 The Wnt signaling pathway and rheumatoid arthritis. 2010 Feb The Wnt signaling pathways play a key role in cell renewal, and there are two such pathways. In patients with rheumatoid arthritis (RA), the synovial membrane expresses genes such as Wnt and Fz at higher levels than those observed in patients without RA. The Wnt proteins are glycoproteins that bind to receptors of the Fz family on the cell surface. The Wnt/Fz complex controls tissue formation during embryogenesis, as well as throughout the process of limb development and joint formation. Recent studies have suggested that this signaling pathway plays a role in the pathophysiology of RA. Greater knowledge of the role of the Wnt signaling pathway in RA could improve understanding of the differences in RA clinical presentation and prognosis. Further studies should also focus on Wnt family members as molecular targets in the treatment of RA.
19835638 Developments in the scientific understanding of rheumatoid arthritis. 2009 Rheumatoid arthritis (RA) is recognized to be an autoimmune disease that causes preclinical systemic abnormalities and eventually leads to synovial inflammation and destruction of the joint architecture. Recently identified genetic risk factors and novel insights from animal models of spontaneous arthritis have lent support to the concept that thymic selection of an autoreactive T-cell repertoire is an important risk factor for this disease. With advancing age, defects in the homeostatic control of the T-cell pool and in the setting of signaling thresholds lead to the accumulation of pro-inflammatory T-effector cell populations and loss of tolerance to neo-antigens, such as citrullinated peptides. As the breakdown of tolerance to modified self-antigens can precede synovitis by decades, repair of homeostatic defects may open a unique window of opportunity for preventive interventions in RA. The end result of RA, destruction of cartilage and bone, appears to be driven by cytokine- and cell contact-induced activation of synoviocytes and monocytic cells, some of which differentiate into tissue-destructive osteoclasts. Targeting mediators involved in this process has greatly improved the management of this chronic inflammatory syndrome.
19233050 Non-drug therapies in early rheumatoid arthritis. 2009 Feb Non-pharmacological treatment modalities are often used as an adjunct to drug therapy in patients with rheumatoid arthritis (RA). The aim of this overview is to summarize the available evidence on the effectiveness of these modalities in early RA. The few available randomized controlled trials that have specifically investigated patients with early RA support the effectiveness of dynamic exercise and cognitive behavioural interventions, and to a lesser extent of joint protection programmes and foot orthoses. The effectiveness of multidisciplinary team-care programmes, specialist nurse care, electro-physical modalities (including passive hydrotherapy), wrist orthoses, and dietary interventions have not been studied in patients with early RA. Current recommendations on the usage of non-pharmacological treatment modalities in sets of guidelines on the management of early RA vary with respect to their scope, strength and level of detail. The results of this review indicate a need for further investigation into the most clinically effective and cost-effective strategies to deliver non-pharmacological treatment modalities as well as comprehensive arthritis care models in early RA.
19233041 What have we learnt from early rheumatoid arthritis cohorts? 2009 Feb Longitudinal and observational studies have provided valuable information on the course, clinical outcomes, and prognostic markers in rheumatoid arthritis (RA). They reflect a complete spectrum of disease in 'true-to-life' settings, and can identify aspects of RA such as long-term outcomes and predictive markers which are not easily obtained from clinical trials. Profiles of drug therapies gained over time from these studies complement those of short-term randomized studies. Comparisons of results from early-RA cohorts show both similarities and considerable differences.
19233048 The economics of treatment in early rheumatoid arthritis. 2009 Feb Recent years have witnessed a shift in the therapeutic approach for patients with early rheumatoid arthritis (RA). The focus of interest has been the improved outcomes achieved through the use of early aggressive disease-modifying therapy, including the use of biologic agents. Such strategies have acquisition costs which typically exceed those of older anti-rheumatic strategies. However, improved outcomes might lead to fewer hospitalizations and physician visits and improved employability, leading to future cost savings. This is in addition to the health benefits which patients value as improvements in quality of life. With many services competing to spend often limited health-care budgets, information on the relative benefits and costs of new approaches for treating RA can be useful in deciding on efficient allocation and treatment decisions.
20485228 The Cochrane review of assistive technology for rheumatoid arthritis. 2010 Jun AIM: The aim of this systematic review is to summarise the available evidence on the effectiveness of assistive technology for adults with rheumatoid arthritis in terms of improving functional ability and reducing pain, and to assess potential adverse effects related to device use. METHODS: In this review, randomised controlled trials, clinical controlled trials, controlled before and after studies and interrupted time series available through systematic searches (electronic databases, grey literature, contact with authors, reference lists) up to October 2008 were included. Two reviewers independently selected trials for inclusion, assessed the validity of included trials, and extracted data. Investigators were contacted to obtain missing information. RESULTS: Out of 7177 hits, 13 articles were reviewed in full text and only one trial was finally included (N.=29). The study was a randomised crossover trial, in which the use of an eye drop device was compared to a standard bottle in people with rheumatoid arthritis suffering from persistent dry eyes. The results show that the eye drop device improved application of eye drops and prevented adverse effects in terms of touching the eye with the bottle tip. The study was considered to have low quality of evidence. CONCLUSION: Since only one trial met the inclusion criteria for this review, there is very limited evidence for the effect of assistive technology for adults with rheumatoid arthritis. There is an urgent need for high-quality research in this field, in order to reach sufficient evidence on the effectiveness of this commonly used intervention.
19563609 The vasculature in rheumatoid arthritis: cause or consequence? 2009 Jun The expansion of the synovial lining of joints in rheumatoid arthritis (RA) necessitates an increase in the vascular supply to the synovium, to cope with the increased requirement for oxygen and nutrients. New blood vessel formation -'angiogenesis'- is recognized as a key event in the formation and maintenance of the pannus in RA, suggesting that targeting blood vessels in RA may be an effective future therapeutic strategy. Although many pro-angiogenic factors have been demonstrated to be expressed in RA synovium, vascular endothelial growth factor (VEGF) has been demonstrated to a have a central involvement in the angiogenic process in RA. Nevertheless, it is unclear whether angiogenesis - whether driven by VEGF and/or other factors - should be considered as a 'cause' or 'consequence' of disease. This ongoing 'chicken vs. egg' debate is difficult, as even the success of angiogenesis inhibition in models of RA does not provide a direct answer to the question. This review will focus on the role of the vasculature in RA, and the contribution of different angiogenic factors in promoting disease. Although no data regarding the effectiveness of anti-angiogenic therapy in RA have been reported to date, the blockade of angiogenesis nevertheless looks to be a promising therapeutic avenue.
19447938 Anakinra for rheumatoid arthritis: a systematic review. 2009 Jun OBJECTIVE: To perform a systematic review of clinical effectiveness and safety of anakinra in rheumatoid arthritis (RA). METHODS: We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, and the reference lists of included articles for randomized controlled trials comparing anakinra to placebo in adults with RA. RESULTS: Five trials involving 2846 patients, 781 randomized to placebo and 2065 to anakinra, were included. There was a significant improvement in the number of participants achieving American College of Rheumatology (ACR)20 (38% vs 23%) treated with anakinra 50-150 mg daily versus placebo after 24 weeks. ACR50 (18% vs 7%), ACR70 (7% vs 2%), Health Assessment Questionnaire, visual analog scale for pain, Larsen radiographic scores, and erythrocyte sedimentation rate all demonstrated significant improvement with anakinra versus placebo as well. There were no statistically significant differences noted in the number of withdrawals, deaths, adverse events (total and serious), and infections (total and serious). An increase in incidence of serious infections in anakinra versus the placebo group (1.8% vs 0.6%) was noted that may be clinically significant. Injection site reactions were significantly increased, occurring in 71% of anakinra versus 28% of placebo group. CONCLUSION: Anakinra is a relatively safe and modestly efficacious biologic therapy for RA. More studies are needed to evaluate safety and efficacy, especially in comparison to other therapies, and adverse event data for the longterm use of anakinra have yet to be assessed.
19822039 Differences in pathophysiology between rheumatoid arthritis and ankylosing spondylitis. 2009 Jul Rheumatoid arthritis and ankylosing spondylitis are common and severe chronic inflammatory skeletal diseases. Recognizing the differences rather than emphasizing similarities is important for a better understanding of the disease processes, the identification of specific therapeutic targets and in the long-term better treatment options for the individual patients. We discuss a number of pathophysiological differences between rheumatoid arthritis and ankylosing spondylitis by looking at the anatomical characteristics, differences and similarities in the autoimmune and autoinflammatory reactions, association with other immune mediated inflammatory diseases, structural outcome, and their potential significance for further therapeutic developments. Further research into the differences between these diseases should focus on the specific nature of the immune/inflammatory components, the role of resident cells in the joint and joint-associated tissues, the types and mechanisms of tissue remodeling and the characteristics of the articular cartilage. Better insights into their individual characteristics may lead to better therapeutic strategies, specific targets and useful biomarkers.
19439037 Rheumatoid cachexia: a complication of rheumatoid arthritis moves into the 21st century. 2009 Rheumatoid cachexia, loss of muscle mass and strength and concomitant increase in fat mass, is very common in patients with rheumatoid arthritis (RA). Despite great advances in the treatment of RA, it appears that rheumatoid cachexia persists even after joint inflammation improves. Rheumatoid cachexia may be an important risk factor for cardiovascular disease and excess mortality in RA. In this issue of Arthritis Research & Therapy, Elkan and colleagues demonstrate a link between rheumatoid cachexia and metabolic syndrome, further reinforcing the need for therapy directed beyond inflammation and at the metabolic consequences of RA.
19728748 Elderly onset rheumatoid arthritis: differential diagnosis and choice of first-line and su 2009 Elderly onset rheumatoid arthritis (EORA) has been considered a benign form of rheumatoid arthritis (RA). However, it most probably encompasses different subsets of patients with distinct outcomes. According to data reported in the most recent studies directly comparing older and younger RA patients, it seems that, overall, the prognosis of EORA patients is not very different from that of other patients with this disease. However, some cases with negative rheumatoid factor and polymyalgia-like symptoms appear to be a distinct subset with a different genetic basis and a more benign course. The differential diagnosis of EORA from other rheumatological disorders that are prevalent in this stratum of the population, such as polymyalgia rheumatica, crystal-induced arthritis or osteoarthritis, may be complicated because these disorders can present with signs and symptoms similar to those of RA in some circumstances. A prompt diagnosis of true RA is important because early treatment should be implemented. It is recommended that therapy of EORA be tailored according to disease activity, with the aim of achieving clinical remission or the lowest possible level of disease activity in order to minimize potential functional sequelae. Co-morbidities and drug toxicity profiles are major considerations when choosing the most suitable therapy for EORA patients. Prudent use and careful follow-up of all treatments are also required because of the increased risk of adverse events in elderly patients. However, no special contraindications to the use of disease-modifying antirheumatic drugs in this age group apply, and use of biological therapies currently used in younger RA patients has also been described in these patients. Therefore, a therapeutic strategy for first-line and subsequent treatment that is in accordance with the disease activity of patients with EORA is suggested.
20576221 The assessment of disease activity in rheumatoid arthritis. 2010 May Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by progressive damage of diathrodial joints, with variable extra-articular manifestations. Joint damage begins early in the course of the disease as a consequence of the active inflammation, and can lead to progressive and irreversible disability. Successful treatment relies on patients attaining low disease activity or a state of remission, which have become achievable goals since the improved use of methotrexate (MTX) and the introduction of biological agents, especially tumor necrosis factor (TNF) inhibitors. To allow physicians to evaluate the indication and effect of particular therapies, accurate assessment of disease activity is necessary. Disease states in RA can be evaluated by a number of measures. These include signs and symptoms, such as counts of tender and swollen joints; laboratory measures like the acute phase response, which is a direct reflection of the underlying inflammatory activity; and patient-focused variables to measure pain and global assessment of disease activity. Some of these (and additional) measures are used in composite indices to assess disease activity or a disease activity state at any point in time and can inform the physician (and patient) about improvement (or deterioration) in disease activity from or states at a particular level at baseline, to that seen at any specific time point. The accurate assessment of disease is, therefore, an important part of the care of patients with RA. However, it can be complex to perform in the clinical setting, so new and simplified measures have evolved. Next to disease activity, the disease outcome is of utmost importance, in particular disability and quality of life, which are assessed using patient reported questionnaires. Radiographic assessment of structural changes is also an important outcome of RA and mirrors joint damage. The latest developments in the field are discussed and will help to identify patients who can benefit most from today's opportunities of pharmacotherapy, allowing optimization of patient care.
20691813 The role of adenosine receptors in rheumatoid arthritis. 2010 Dec Rheumatoid arthritis (RA), is the most common inflammatory musculoskeletal disease inducing diminished quality-of-life in the affected individuals and having major impact on society due to decrease work ability. Early diagnosis and immediate, effective therapy are crucial in order to prevent unfavorable outcome. Treatment of RA has progressed during the past two decades thanks to the advent of a large number of new agents targeting different specific molecules and pathways involved in the modulation of the inflammation. In this scenario an important role is covered by adenosine, a purine nucleoside released from a variety of cells in response to metabolic and inflammatory stress, which is considered to be a potent endogenous regulator acting through its interaction with 4 cell surface receptors named as A(1), A(2A), A(2B) and A(3). Adenosine receptor stimulation has complex effects on the release of pro-inflammatory cytokines depending on selective receptor engagement. Recent data show the involvement of adenosine pathways in RA and its potential therapeutic implications.
19772831 The role of toll-like receptors in rheumatoid arthritis. 2009 Oct An increasing body of data supports the role of the innate immune system in the pathogenesis of rheumatoid arthritis (RA). Toll-like receptors (TLRs) are expressed by cells within the RA joint and various endogenous TLR ligands are present within the inflamed joints of patients with RA. Further, various animal models suggest that TLR signaling is important in the pathogenesis of disease. Overall, the data suggest that activation by endogenous TLR ligands may contribute to the persistent expression of proinflammatory cytokines by macrophages and the joint damage to cartilage and bone that occurs in RA. The data support a potential role for suppression of TLR signaling as a novel therapeutic approach in patients with RA.