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ID PMID Title PublicationDate abstract
22441579 Atorvastatin inhibits the inflammatory response caused by anti-M(3) peptide IgG in patient 2012 Oct Experimental and clinical investigations have revealed that statins can down-regulate acute and chronic inflammatory processes. Whether statins express anti-inflammatory activities in the salivary glands in patients with primary Sjögren's syndrome (pSS) is not known. The in vitro and in vivo effect of atorvastatin on rat submandibular gland treated with anti-M(3) peptide IgG purified from SS patients was studied. The anti-inflammatory effects of atorvastatin were assessed by measuring the levels of IL-1β, PGE(2) and MMP-3 by ELISA. Atorvastatin inhibited the increase in the production of IL-1β, PGE(2) and MMP-3 in submandibular glands treated with anti-M(3) peptide IgG. A positive correlation between IL-1β production with accumulation of PGE(2) and MMP-3 was observed. Rats pre-treated orally with atorvastatin (30 mg kg(-1)) or vehicle (phosphate-buffered solution) once a day for three consecutive days impaired the increment in the production of IL-1β, PGE(2) and MMP-3 in the submandibular gland in the presence of anti-M(3) peptide IgG. In conclusion, the anti-inflammatory effects of atorvastatin are dependent upon inhibition of production of a pro-inflammatory cytokine (IL-1β) and pro-inflammatory mediators such as PGE(2) and MMP-3. These data suggest that atorvastatin may constitute an anti-inflammatory effect in SS.
22231568 Evaluation of TRAF6 in a large multiancestral lupus cohort. 2012 Jun OBJECTIVE: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with significant immune system aberrations resulting from complex heritable genetics as well as environmental factors. We undertook to study the role of TRAF6 as a candidate gene for SLE, since it plays a major role in several signaling pathways that are important for immunity and organ development. METHODS: Fifteen single-nucleotide polymorphisms (SNPs) across TRAF6 were evaluated in 7,490 SLE patients and 6,780 control subjects from different ancestries. Population-based case-control association analyses and meta-analyses were performed. P values, false discovery rate q values, and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. RESULTS: Evidence of associations was detected in multiple SNPs. The best overall P values were obtained for SNPs rs5030437 and rs4755453 (P = 7.85 × 10(-5) and P = 4.73 × 10(-5) , respectively) without significant heterogeneity among populations (P = 0.67 and P = 0.50, respectively, in Q statistic). In addition, SNP rs540386, which was previously reported to be associated with rheumatoid arthritis (RA), was found to be in linkage disequilibrium with these 2 SNPs (r(2) = 0.95) and demonstrated evidence of association with SLE in the same direction (meta-analysis P = 9.15 × 10(-4) , OR 0.89 [95% CI 0.83-0.95]). The presence of thrombocytopenia improved the overall results in different populations (meta-analysis P = 1.99 × 10(-6) , OR 0.57 [95% CI 0.45-0.72], for rs5030470). Finally, evidence of family-based association in 34 African American pedigrees with the presence of thrombocytopenia was detected in 1 available SNP (rs5030437) with a Z score magnitude of 2.28 (P = 0.02) under a dominant model. CONCLUSION: Our data indicate the presence of association of TRAF6 with SLE, consistent with the previous report of association with RA. These data provide further support for the involvement of TRAF6 in the pathogenesis of autoimmunity.
24217093 Rheumatoid arthritis. 2013 Nov Rheumatoid arthritis (RA) is a chronic inflammatory disease characterised by joint swelling, joint tenderness and destruction of synovial joints, leading to severe disability. RA is considered an autoimmune disease. A study in the UK found the population minimum prevalence of RA is 1.16% in women and 0.44% in men. In Australia, the estimated prevalence is 0.6%. Using BEACH data from April 2011 to March 2013, we examined the rate of RA and its management in Australian general practice.
24736263 Rheumatoid arthritis associated interstitial lung disease: a review. 2014 Rheumatoid arthritis is a common inflammatory disease affecting about 1% of the population. Interstitial lung disease is a serious and frequent complication of rheumatoid arthritis. Rheumatoid arthritis associated interstitial lung disease (RA-ILD) is characterized by several histopathologic subtypes. This article reviews the proposed pathogenesis and risk factors for RA-ILD. We also outline the important steps involved in the work-up of RA-ILD and review the evidence for treatment and prognosis.
24324289 Rheumatoid factors: clinical applications. 2013 Rheumatoid factors are antibodies directed against the Fc region of immunoglobulin G. First detected in patients with rheumatoid arthritis 70 years ago, they can also be found in patients with other autoimmune and nonautoimmune conditions, as well as in healthy subjects. Rheumatoid factors form part of the workup for the differential diagnosis of arthropathies. In clinical practice, it is recommended to measure anti-cyclic citrullinated peptide antibodies and rheumatoid factors together because anti-cyclic citrullinated peptide antibodies alone are only moderately sensitive, and the combination of the two markers improves diagnostic accuracy, especially in the case of early rheumatoid arthritis. Furthermore, different rheumatoid factor isotypes alone or in combination can be helpful when managing rheumatoid arthritis patients, from the time of diagnosis until deciding on the choice of therapeutic strategy.
24437269 [Rheumatoid arthritis]. 2013 Dec Although many requirements must be met to establish a diagnosis of rheumatoid arthritis (RA), morning stiffness is a characteristic feature of RA. Inflammatory cytokines show high concentrations in human blood and synovial fluid of RA, and excess production of these cytokines plays a central role in the pathogenesis of RA. The inflammatory cytokines in blood also show circadian rhythms peaking from midnight to early morning, which mirrors the timing of morning stiffness. In the treatment of RA, steroids are used to reduce pain and inflammation, and methotrexate are used prior to the development of destructive changes in bones, joints, and organ tissues. In this chapter, I would like to introduce the circadian rhythm of RA and the chronotherapies.
26096095 Infections and arthritis. 2014 Dec Bacteria, viruses, fungi, and parasites can all cause arthritis of either acute or chronic nature, which can be divided into infective/septic, reactive, or inflammatory. Considerable advances have occurred in diagnostic techniques in the recent decades resulting in better treatment outcomes in patients with infective arthritis. Detection of emerging arthritogenic viruses has changed the epidemiology of infection-related arthritis. The role of viruses in the pathogenesis of chronic inflammatory arthritides such as rheumatoid arthritis is increasingly being recognized. We discuss the various causative agents of infective arthritis and emphasize on the approach to each type of arthritis, highlighting the diagnostic tests, along with their statistical accuracy. Various investigations including newer methods such as nucleic acid amplification using polymerase chain reaction are discussed along with the pitfalls in interpreting the tests.
23925924 Education, self-management, and upper extremity exercise training in people with rheumatoi 2014 Feb OBJECTIVE: To evaluate the effectiveness of a brief supervised education, self-management, and global upper extremity exercise training program, supplementing a home exercise regimen, for people with rheumatoid arthritis (RA; the Education, Self-Management, and Upper Extremity Exercise Training in People with Rheumatoid Arthritis [EXTRA] program). METHODS: Adults with RA of ≤5 years' duration were randomized to receive either usual care or the EXTRA program comprising 4 (1-hour) group education, self-management, and global upper extremity exercise training sessions supplementing the first 2 weeks of a 12-week individualized, functional home exercise regimen in addition to usual care. Outcome measures were assessed at baseline, 12 weeks (primary end point), and 36 weeks and included the Disabilities of the Arm, Shoulder, and Hand questionnaire (primary outcome measure), the Grip Ability Test, handgrip strength (N), the Arthritis Self-Efficacy Scale (pain, function, and symptoms subscales), and the 28-joint Disease Activity Score. RESULTS: One hundred eight participants (26 men, mean ± SD age 55 ± 15 years, mean ± SD disease duration 20 ± 19 months) were randomized to receive either usual care (n = 56) or the EXTRA program (n = 52). At 12 weeks, there was a significant between-group difference in the mean change in disability (-6.8 [95% confidence interval (95% CI) -12.6, -1.0]; P = 0.022), function (-3.0 [95% CI -5.0, -0.5]; P = 0.011), nondominant handgrip strength (31.3N [95% CI 9.8, 52.8]; P = 0.009), self-efficacy (10.5 [95% CI 1.6, 19.5]; P = 0.021 for pain and 9.3 [95% CI 0.5, 18.2]; P = 0.039 for symptoms), and disease activity (-0.7 [95% CI -1.4, 0.0]; P = 0.047), all favoring the EXTRA program. CONCLUSION: The EXTRA program improves upper extremity disability, function, handgrip strength, and self-efficacy in people with RA, with no adverse effects on disease activity.
23425964 Extra-articular rheumatoid arthritis. 2013 May PURPOSE OF REVIEW: To discuss recent findings on the epidemiology and pathogenesis of extra-articular manifestations in rheumatoid arthritis (RA), and provide an update on the literature on treatment of patients with extra-articular RA (ExRA) manifestations. RECENT FINDINGS: ExRA is associated with increased comorbidity and mortality. Several surveys suggest that some ExRA manifestations, in particular vasculitis, occur less frequently than previously reported. This is probably due to improved overall control of disease activity. Active RA with high disease activity is associated with increased risk of severe ExRA manifestations. Studies on the impact of treatment with biologics on the occurrence of ExRA are inconclusive. Circulating immune complexes and T cells have been implicated in the pathogenesis of ExRA. The genetic background and related disease mechanisms may be somewhat different in manifestations such as vasculitis and interstitial lung disease. Limited data support a benefit from treatment with cyclophosphamide, TNF-inhibitors or rituximab in patients with severe ExRA. SUMMARY: ExRA remains a major diagnostic and therapeutic challenge in some patients. Further studies of the pathogenesis of systemic involvement and on the effect of treatment on such mechanisms may be helpful for further improvement of the management of RA.
23530652 Rheumatoid arthritis in the elderly and its relationship with periodontitis: a review. 2014 Jan Periodontitis and rheumatoid arthritis are chronic inflammatory diseases commonly seen in the elderly. It has been proposed that the two conditions are interrelated and influence the severity of each other. Recently, the role of Porphyromonas gingivalis, a periodontopathogen, has been explained in the pathogenesis and progression of rheumatoid arthritis. It can be inferred from the present review that the two conditions share a common pathobiology, genetics and environmental risk factors. Furthermore, a thorough understanding of the aforementioned mechanisms might enable the development of conjoint treatment modalities beneficial in treating the geriatric population afflicted by both the disorders.
24568138 Epigenetics in the pathogenesis of rheumatoid arthritis. 2014 Feb 26 An increasing number of studies show that besides the inherited genetic architecture (that is, genomic DNA), various environmental factors significantly contribute to the etiology of rheumatoid arthritis. Epigenetic factors react to external stimuli and form bridges between the environment and the genetic information-harboring DNA. Epigenetic mechanisms are implicated in the final interpretation of the encoded genetic information by regulating gene expression, and alterations in their profile influence the activity of the immune system. Overall, epigenetic mechanisms further increase the well-known complexity of rheumatoid arthritis by providing additional subtle contributions to rheumatoid arthritis susceptibility. Although there are controversies regarding the involvement of epigenetic and genetic factors in rheumatoid arthritis etiology, it is becoming obvious that the two systems (genetic and epigenetic) interact with each other and are ultimately responsible for rheumatoid arthritis development. Here, epigenetic factors and mechanisms involved in rheumatoid arthritis are reviewed and new, potential therapeutic targets are discussed.
25180621 Epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis: A Synopsis. 2014 May Rheumatoid arthritis (RA) is one of the more common autoimmune disorders, affecting approximately 1% of the population worldwide. The exact cause of RA is not known; however, initiation of disease seems to result from an interaction among genetic susceptibility, environmental triggers, and chance. RA is characterized by dysregulated inflammatory processes in the synovium of the joint that eventually leads to the destruction of both cartilaginous and bony elements of the joint, with resulting pain and disability. Systemic inflammation associated with RA is associated with a variety of extra-articular comorbidities, including cardiovascular disease, resulting in increased mortality in patients with RA. RA is also associated with several psychosocial disorders. Classification criteria for RA that were promulgated jointly by the American College of Rheumatology and the European League Against Rheumatism in 2010 emphasize early detection of RA so that effective management can be initiated before pathological changes become irreversible.
25111096 Biologics in rheumatoid arthritis: where are we going? 2014 Aug Biological disease-modifying antirheumatic drugs have significantly improved outcomes for patients with rheumatoid arthritis, but cost limits their use. This article assesses data on patients who have achieved remission or low disease activity with these drugs and the possibility of dose reduction or discontinuation in these patients.
25491208 Rheumatoid arthritis in Saudi Arabia. 2014 Dec The status of rheumatoid arthritis (RA) in Saudi Arabia (SA) was examined from various perspectives based on a systematic literature review and the authors' personal experiences. In this regard, database and journal search were conducted to identify studies on RA in SA, yielding a total of 43 articles. Although efforts have been made to promote RA research in SA, current studies mostly represent only a few centers and may not accurately portray the national status of RA care. Notably, biological therapies were introduced early for almost all practicing rheumatologists in SA (government and private). However, no national guidelines regarding the management of RA have been developed based on local needs and regulations. Also, while efforts were made to establish RA data registries, they have not been successful. Taken together, this analysis can contribute to the planning of future guidelines and directives for RA care in SA. 
23719075 Imaging of rheumatoid arthritis. 2013 Aug Increased awareness of the need for early diagnosis of rheumatoid arthritis and advances in the ability to effectively treat rheumatoid arthritis have made disease remission and maintenance of function a reality for many patients. However, identification of patients who are at risk for erosive disease remains a challenge. As more is learnt about risk factors for disease severity and the role of imaging techniques such as ultrasound and magnetic resonance imaging, the ability to prevent disease progression in the form of joint damage and its attendant deformity and functional limitation will further improve.
24093840 Rheumatoid arthritis and cardiovascular disease. 2013 Oct BACKGROUND: Rheumatic disease and heart disease share common underpinnings involving inflammation. The high levels of inflammation that characterize rheumatic diseases provide a "natural experiment" to help elucidate the mechanisms by which inflammation accelerates heart disease. Rheumatoid arthritis (RA) is the most common of the rheumatic diseases and has the best studied relationships with heart disease. METHODS: A review of current literature on heart disease and RA was conducted. RESULTS: Patients with RA have an increased risk of developing heart disease that is not fully explained by traditional cardiovascular risk factors. Therapies used to treat RA may also affect the development of heart disease; by suppressing inflammation, they may also reduce the risk of heart disease. However, their other effects, as in the case of steroids, may increase heart disease risk. CONCLUSIONS: Investigations of the innate and adaptive immune responses occurring in RA may delineate novel mechanisms in the pathogenesis of heart disease and help identify novel therapeutic targets for the prevention and treatment of heart disease.
24924730 [Sport and rheumatoid arthritis]. 2014 Jun BACKGROUND: Sport is becoming increasingly more important in our society. Due to the changing age spectrum with a greater number of elderly and substantially more active people, an increasing number of people with underlying orthopedic diseases are becoming interested in participating in sport. MATERIAL AND METHODS: This article deals with the possibilities and effects of sporting activities for people with rheumatoid arthritis within the framework of a conservative therapy. A literature search was carried out using medical search engines, in particular PubMed, and also via the recommendations of specialist societies and patient help groups. RESULTS: The quality of life of patients with rheumatoid arthritis consists of physical, mental and social components. Sport as a means of rehabilitation influences all of these components. Sport should be comprehended as a form of therapy and be adapted to the needs of the individual patient. The willingness to actively participate in sport should always be highly rated and encouraged. Sport is therefore an important pillar of therapy in a conservative total concept. The main aspects of sport therapeutic activities are functional, pedagogical and experience-oriented aspects. The clinical symptoms, extent of damage and physical impairment must, however, be evaluated and taken into consideration for the therapeutic concept. CONCLUSION: The amount of data on the complex topic of sport and rheumatoid arthritis is low and is mainly dealt with as retrospective reviews. A prospective randomized study basis is lacking. The aim must therefore be to confirm the currently available recommendations for various types of sport in controlled studies.
24925587 Vaccinations for rheumatoid arthritis. 2014 Aug Patients with rheumatoid arthritis (RA) suffer an increased burden of infectious disease-related morbidity and mortality and have twice the risk of acquiring a severe infection compared to the general population. This increased risk is not only a result of the autoimmune disease but is also attributed to the immunosuppressive therapies that are commonly used in this patient population. Given the increase in infection-related risks in RA, there is great interest in mitigating such risk. A number of vaccines are available to the rheumatologist, with a handful that are of importance for RA patients in the United States. The goal of this paper is to highlight the most recent literature on the key vaccines and the specific considerations for the rheumatologist and their RA patients, with a particular focus on influenza, pneumococcal, and herpes zoster vaccines. It is important for rheumatologist to understand and be aware of which vaccines are live and what potential contraindications exist for giving vaccines to RA patients.
24315049 Can rheumatoid arthritis be prevented? 2013 Aug The discovery of elevations of rheumatoid arthritis (RA)-related biomarkers prior to the onset of clinically apparent RA raises hopes that individuals who are at risk of future RA can be identified in a preclinical phase of disease that is defined as abnormalities of RA-related immune activity prior to the clinically apparent onset of joint disease. Additionally, there is a growing understanding of the immunologic processes that are occurring in preclinical RA, as well as a growing understanding of risk factors that may be mechanistically related to RA development. Furthermore, there are data supporting that treatment of early RA can lead to drug-free remission. Taken as a whole, these findings suggest that it may be possible to use biomarkers and other factors to accurately identify the likelihood and timing of onset of future RA, and then intervene with immunomodulatory therapies and/or risk factor modification to prevent the future onset of RA in at-risk individuals. Importantly, several clinical prevention trials for RA have already been tried, and one is underway. However, while our growing understanding of the mechanisms and natural history of RA development may be leading us to the implementation of prevention strategies for RA, there are still several challenges to be met. These include developing sufficiently accurate methods of predicting those at high risk of future RA so that clinical trials can be developed based on accurate rates of development of arthritis and subjects can be adequately informed of their risk of disease, identifying the appropriate interventions and biologic targets for optimal prevention, and addressing the psychosocial and economic aspects that are crucial to developing broadly applicable prevention measures for RA. These issues notwithstanding, prevention of RA may be within reach in the near future.
23574519 Immunopathology of rheumatoid arthritis. 2013 Rheumatoid arthritis (RA) is one of the most common autoimmune diseases. Genetic and epidemiologic studies point to a relevant role of adaptive T-cell response interactions with environmental factors such as smoking in the immunopathogenesis of the disease. These interactions result in a specific systemic autoantibody response that seems to contribute to the synovial inflammatory process. The reasons for specific localization of the autoimmune proinflammatory process to synovial tissue remain poorly known, but relevant local effector mechanisms have been recently unveiled and successfully targeted by new specific therapies. A relevant role for cytokine networks, where TNF-α displays a pivotal role, has been confirmed. The local pathology is hallmarked by immune cell accumulation and expansion of resident stromal and vascular cells. Crosstalk between these elements generates an aggressive environment that leads to cartilage and bone destruction. RA provides represents a model for systemic T-cell mediated systemic autoimmunity leading to local cellular and autoantibody mediated chronic inflammation. Whereas targeting of these elements with specific antagonists may interfere with the disease process, reestablishing tolerance and preventing further synovial inflammation has not been achieved.