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ID PMID Title PublicationDate abstract
20381399 A comparative review of the different techniques to assess hand bone damage in rheumatoid 2010 May Inflammatory related hand bone damage in rheumatoid arthritis is characterized by erosions and periarticular osteoporosis and can lead to substantial clinical disability. So far, conventional radiograph has been considered to be the gold standard for detecting bone damage and monitoring disease progression, but it lacks sensitivity. So other techniques have been recently developed to identify erosions earlier, to be able to change therapy; if necessary. This report reviews, in its first part, the different ways of detecting erosions such as conventional radiograph, magnetic resonance imaging or imaging ultrasonography and, in its second part, the techniques used for the assessment of hand periarticular osteoporosis like dual-X-ray absorptiometry, digital-X-ray radiogrammetry or quantitative ultrasonography.
19392574 RNA interference-based gene therapy for successful treatment of rheumatoid arthritis. 2009 May BACKGROUND: RNA interference (RNAi) is a powerful endogenous process initiated by short double-stranded RNAs, which results in sequence-specific posttranscriptional gene silencing. The possibility of blocking the expression of any protein carries huge expectations for potential therapeutic applications in a wide range of diseases. For clinical development, however, the use of RNAi-based therapeutics has to overcome major obstacles, mainly targeted delivery and safety issues. OBJECTIVE/METHODS: In this short review, we provide an overview of specifications for RNAi-based gene therapy in rheumatoid arthritis (RA) and discuss recent progresses in the development of efficient silencing, focusing on expression of short hairpin RNAs. RESULTS/CONCLUSIONS: Combining advances in RNAi methodology with gene therapy technology opens avenues for rapid applications to RA.
19337288 The cholinergic anti-inflammatory pathway: towards innovative treatment of rheumatoid arth 2009 Apr The efferent vagus nerve can regulate inflammation via its principal neurotransmitter acetylcholine (ACh), a concept referred to as the 'cholinergic anti-inflammatory pathway'. ACh interacts with members of the nicotinic acetylcholine receptor (nAChR) family, in particular with the alpha7 subunit (alpha7nAChR), which is expressed not only by neurons but also macrophages and other cells involved in the inflammatory response. In these inflammatory cells, the stimulation of alpha7nAChR by ACh and other alpha7nAChR-specific agonists suppresses the release of proinflammatory cytokines. Recent work has suggested that alpha7nAChR could represent a new target for the treatment of rheumatic diseases. In this Perspective, we describe the cholinergic anti-inflammatory pathway and the therapeutic potential of modulating this pathway in rheumatoid arthritis.
19174392 Impact of smoking as a risk factor for developing rheumatoid arthritis: a meta-analysis of 2010 Jan OBJECTIVES: To assess whether smoking is a risk factor for developing rheumatoid arthritis (RA). DESIGN: Meta-analysis. DATA SOURCES: were observational studies that examined the association between smoking history and the risk of developing RA identified through Medline and EMBASE (from 1966 to December 2006), relevant books and a reference search. Two authors independently extracted the following: authors' names, publication year, sample size, participant characteristics, odds ratios (OR) or relative risks, adjustment factors, study design and area where the study was conducted. Data syntheses were based upon random effects model. Summarised syntheses effects were expressed by OR. RESULTS: Sixteen studies were selected from among 433 articles. For men, summary OR for ever, current and past smokers were 1.89 (95% CI 1.56 to 2.28), 1.87 (1.49 to 2.34) and 1.76 (1.33 to 2.31), respectively. For rheumatoid factor-positive (RF+) RA, summary OR for ever, current and past smokers were 3.02 (2.35 to 3.88), 3.91 (2.78 to 5.50) and 2.46 (1.74 to 3.47), respectively. Summary OR for 20 or more pack-years of smoking was 2.31 (1.55 to 3.41). For women, summary OR for ever, current and past smokers were 1.27 (1.12 to 1.44), 1.31 (1.12 to 1.54) and 1.22 (1.06 to 1.40), respectively. For RF+ RA, summary OR for ever, current and past smokers were 1.34 (0.99 to 1.80), 1.29 (0.94 to 1.77) and 1.21 (0.83 to 1.77). Summary OR for 20 or more pack-years of smoking was 1.75 (1.52 to 2.02). CONCLUSION: Smoking is a risk factor for RA, especially RF+ RA men and heavy smokers.
19490601 The value of animal models in predicting genetic susceptibility to complex diseases such a 2009 For a long time, genetic studies of complex diseases were most successfully conducted in animal models. However, the field of genetics is now rapidly evolving, and human genetics has also started to produce strong candidate genes for complex diseases. This raises the question of how to continue gene-finding attempts in animals and how to use animal models to enhance our understanding of gene function. In this review we summarize the uses and advantages of animal studies in identification of disease susceptibility genes, focusing on rheumatoid arthritis. We are convinced that animal genetics will remain a valuable tool for the identification and investigation of pathways that lead to disease, well into the future.
20094746 Rheumatoid arthritis among Nigerians: the first 200 patients from a rheumatology clinic. 2010 Jun Rheumatoid arthritis has uncommonly been reported among Africans and rarely among West Africans. Most of the reported cases have been from Southern Africa. A recent awareness of increased reports of RA among Nigerians necessitated this study. The objective of this retrospective study was to identify the clinical presentations, laboratory characteristics as well as treatment regimens of Nigerians presenting with rheumatoid arthritis to a private rheumatology clinic in Lagos, Nigeria. This is a retrospective study of consecutive rheumatoid arthritis patients seen over a period covering 7 years and 10 months diagnosed using the ARA Criteria for RA. Laboratory tests and radiographic investigations were carried out. Treatment was with NSAIDs, prednisolone, disease modifying anti-rheumatic drugs (DMARDs), and biologics. RA accounted for 12.3% of a total of 1,623 patients presenting to the clinic with rheumatologic complaints over the study period. Females were mostly affected (F:M-2.4:1) and mean age is 46.9 years. Duration of symptoms before presentation was 4-264 months with a mean of 63.4 months. The proximal interphalangeal joints were mostly involved. Subcutaneous nodules were seen in 29.5% of the cases while rheumatoid factor was found in 38.5% of the subjects. ESR was mostly elevated and radiographic changes were mostly mild with 29.2% showing erosive changes on radiographs of the hands. Treatment was variously with non-steroidal antiinflammatory drugs (NSAIDs), prednisolone, and DMARDs. Rheumatoid arthritis is not uncommon among Nigerian; and clinical, serologic acumen are necessary for early diagnosis and appropriate referral.
19585131 [Tissue retention of T cells as a therapeutic target in rheumatoid arthritis]. 2009 Oct Autoreactive T cells are instrumental for the induction and chronification of autoimmune diseases. While immigration of T cells into inflamed tissue is strongly enhanced during acute inflammatory phases, retention of antigen specific T cells rather than subsequent recruitment of recirculating effector cells appears to contribute to the inflammatory infiltrate seen during chronic inflammation. Patients suffering from rheumatoid arthritis also show accumulation of oligoclonal T cells within the inflamed synovia, where environmental signals seem to promote the prolonged survival of these chronically activated T cells. The survival signals and mechanisms controlling retention of T cells within the inflamed synovia are poorly characterized. However, the specific interference with these mechanisms could be a therapeutic approach in chronic inflammatory diseases like rheumatoid arthritis that are accompanied by a strong local accumulation of immune cells.
20510233 Leveraging human genetics to develop future therapeutic strategies in rheumatoid arthritis 2010 May The purpose of this article is to place these genetic discoveries in the context of current and future therapeutic strategies for patients with RA. More specifically, this article focuses on (1) a brief overview of genetic studies, (2) human genetics as an approach to identify the Achilles heel of disease pathways, (3) humans as the model organism for functional studies of human mutations, (4) pharmacogenetic studies to gain insight into the mechanism of action of drugs, and (5) next-generation patient registries to enable large-scale genotype-phenotype studies.
19785789 [The vicious circle that leads to rheumatoid arthritis; experimental evidence of the steps 2009 Rheumatoid arthritis (RA) is characterized by chronic inflammation of the joints and the presence of anti-citrullinated protein autoantibodies (ACPA). ACPA are very specific for RA and are involved in its pathophysiology. Five steps, all of which are supported by experimental evidence, can be distinguished during the development of the chronic inflammation in RA. Step 1: During inflammation a large influx of inflammatory cells takes place. These cells will ultimately die via apoptosis. When the dying cells are not cleared efficiently, citrullinated proteins and citrullinating enzymes are released into the extracellular space. Step 2: Extracellular proteins are citrullinated by these enzymes. Step 3: Only individuals with a certain genetic background produce ACPA. Step 4: Arthritis is induced by the formation of immune complexes of ACPA and citrullinated proteins. Step 5: These immune complexes stimulate the inflammation, which leads to the recruitment of new inflammatory cells. This establishes a vicious cycle, the RA cycle.
20827876 Cardiovascular disease in rheumatoid arthritis: disease and treatment interactions and the 2010 Mar Cardiovascular disease is highly prevalent in rheumatoid arthritis patients, contributing to significant morbidity and mortality. Few randomized trials are available to guide risk assessment and intervention in these complex patients. This paper discusses traditional atherosclerotic and rheumatoid-related risk factors for cardiovascular disease in these patients, reviews the effect of treatment of cardiovascular risk factors on rheumatoid arthritis activity, and describes the effect of rheumatoid arthritis treatment on risk factors for cardiovascular disease. The authors reviewed the existing literature by cross-referencing topics such as cardiovascular disease, rheumatoid arthritis, various risk factors for cardiovascular disease and their treatments, and treatments for rheumatoid arthritis, using Medline and PubMed, reviewing references from 1983-2009. Traditional and rheumatoid-related risk factors (including active inflammation/disease activity and some medications) contribute to this high prevalence of cardiovascular disease in rheumatoid arthritis. Evidence supports aggressive therapy for traditional cardiovascular risk factors, reducing rheumatoid activity, and limiting pro-atherosclerotic medications.
20704614 Assessment of endothelial function as a marker of cardiovascular risk in patients with rhe 2010 Aug The endothelium is a major regulator of cardiovascular function and maintains an atheroprotective role through several mechanisms, including vasodilatation, inhibition of platelet aggregation, having anticoagulant and profibrinolytic effects, and having an anti-inflammatory effect. Early changes in the normal functioning of the endothelium are key initiating factors in the development and progression of atherosclerosis. These changes are present well before the presentation of clinical symptoms. Thus, researchers have focused much attention on developing methods for reliable non-invasive testing of endothelial function to allow early detection and monitoring and progression of subclinical atherosclerosis. To date, there is a wide range of methods in use to assess endothelial function, each with its own advantages and limitations. Ideally, the tests should be non-invasive to allow repeated measurements and be applicable in normal healthy subjects and also in children. Given the wide range of regulatory functions of the endothelium, it is not surprising that there is no single measure of endothelial function that provides all the necessary information regarding vascular integrity in different vascular beds. Therefore, a combination of tests examining different components of the vascular system is more appropriate. Since patients with rheumatoid arthritis have increased mortality due to cardiovascular disease, assessment of endothelial function could prove to be useful tools in the identification and monitoring of cardiovascular risk. The purpose of this review is to give a brief overview of some of the commonly used techniques for assessment of endothelial function, and in particular on those that have been used in studies of patients with rheumatoid arthritis.
20191498 Evidence for predictive validity of remission on long-term outcome in rheumatoid arthritis 2010 Jan 15 OBJECTIVE: Remission is rapidly becoming a key end point in rheumatoid arthritis (RA) clinical trials, but its definition is not satisfactory. Although it is generally believed that achieving a state of remission will lead to better structural outcome, this has not been studied systematically. As part of an undertaking to redefine remission, the current review describes the relationship between remission and long-term structural outcome. METHODS: A systematic literature search of PubMed, EMBase, and The Cochrane Library intersected 3 groups of terms: RA, remission, and long-term outcome. The search identified 1,138 records, of which 14 were relevant to the research question. RESULTS: All of the studies included in this review showed a relationship between remission and long-term structural damage or disability. Patients that achieved a state of remission, defined in various ways, showed less deterioration of function and radiographic progression compared with patients who did not reach a state of remission. CONCLUSION: Patients who achieved a state of remission were less likely to show deterioration of function and radiographic progression compared with patients who did not reach a state of remission.
21068083 Cardiovascular morbidity and mortality in patients with rheumatoid arthritis: vascular alt 2011 Jan Mortality in patients with rheumatoid arthritis (RA) is higher than in the general population, which is due mainly to premature cardiovascular disease. Traditional cardiovascular risk factors cannot entirely explain the higher level of cardiovascular complications, and there is growing evidence that chronic inflammation is the main culprit. The aims of this review of the literature are to (i) summarize aspects of vascular alterations found in the cardiovascular system of RA patients and to relate them to the clinically relevant cardiovascular morbidity and mortality and (ii) evaluate what these abnormalities and complications might in the end imply for clinical management. A number of abnormalities in the cardiovascular system of RA patients have been identified, on the molecular level, in endothelial function, arterial stiffness, arterial morphology and, finally, in the clinical presentation of cardiovascular disease. Cardiovascular risk assessment should be part of the care of RA patients. While a great deal of data is published demonstrating abnormalities in the cardiovascular system of these patients, it is much less clear what specific interventions should be performed to reduce the incidence of cardiovascular complications. Cardiovascular care should be delivered in accordance with recommendations for the general population. Whether specific drugs (e.g. statins, aspirin) are of particular benefit in RA patients needs further investigation. Control of inflammation appears to be of benefit. Methotrexate and tumor necrosis factor-α blocking agents might reduce the number of cardiovascular events. Leflunomide, cyclosporine, non-steroidal anti-inflammatory drugs and cyclo-oxygenase-2 inhibitors may worsen cardiovascular outcome. The role of glucocorticoids in active RA remains to be determined.
20408459 [Rheumatoid arthritis, methothrexate, and pulmonary fibrosis: which evidences?]. 2010 Mar 17 Pulmonary fibrosis is an extraarticular manifestation of rheumatoid arthritis (RA), which appears between 20 to 40% of cases. MTX is an ordinary treatment used for patients with RA. It has been suggested in some studies that a link between the use of MTX and the appearance of pulmonary fibrosis exists. Furthermore, the chronic use of MTX has been associated with the development of hepatic cirrhosis. Adenosine, a key molecule in the anti-inflammatory action of MTX seems to have a pro-fibrotic effect in some experimental models, thereby suggesting a mechanism through which MTX could lead to a fibrotic process. However, in spite of these experimental models, clinical studies have not permitted to confirm the pathogenic role of MTX in pulmonary fibrosis.
20306616 Rheumatoid arthritis: coping with disability. 2010 Mar This article explains the components of disability as related to rheumatoid arthritis (RA) using an expansion of Nagi's Model of Disability (Jette, 2006) and the World Health Organization's (WHO) International Classification of Functioning, Disability, and Health (ICF). In addition, suggestions for ways in which nurses can offer patients choices in physical functional therapy and psychosocial aspects of coping with the chronicity of RA are discussed. Understanding how RA relates to the holistic management of the patient will allow nurses to modify and suggest additional measures to enhance the outcomes of patient-centered care. Many degrees of disability exist that affect the physical and psychosocial domains of RA. Nurses should identify the primary issues influencing disability and assemble supporting resources or a multidisciplinary team to manage a person's disabilities. As nurses develop and maintain relationships with patients, they are able to follow through with the care plan continuum and recognize when modifications are needed.
19446472 Unraveling the genetics of complex diseases: susceptibility genes for rheumatoid arthritis 2009 Dec Talk of numerous genetic risk factors for rheumatoid arthritis (RA) and psoriasis has been percolating for years, but with the exception of the human leukocyte antigen (HLA) region, none have been definitively identified. Recently the results of multiple, well powered, genetic case-control studies have begun to appear providing convincing statistical evidence for at least ten non-HLA related risk genes or loci (C5/TRAF1, CD40, CTLA4, KIF5A/PIP4K2C, MMEL1/TNFRSF14, PADI4, PRKCQ, PTPN22, STAT4, and TNFAIP3/OLIG3) for RA and six (IL12B, IL13, IL23R, STAT2/IL23A, TNFAIP3, and TNIP1) for psoriasis. These initial, novel findings are beginning to shed light on the molecular pathways pertinent to the individual diseases and highlight the pleiotropic effects of several risk factors as well as the allelic heterogeneity underlying susceptibility to these and other autoimmune diseases.
20553633 Bacterial and human peptidylarginine deiminases: targets for inhibiting the autoimmune res 2010 Peptidylarginine deiminases (PADs) convert arginine within a peptide (peptidylarginine) into peptidylcitrulline. Citrullination by human PADs is important in normal physiology and inflammation. Porphyromonas gingivalis, a major pathogen in periodontitis, is the only prokaryote described to possess PAD. P. gingivalis infection may generate citrullinated peptides, which trigger anti-citrullinated peptide antibodies. In susceptible individuals, host protein citrullination by human PADs in the joint probably perpetuates antibody formation, paving the way for the development of chronic arthritis. Blockades of bacterial and human PADs may act as powerful novel therapies by inhibiting the generation of the antigens that trigger and sustain autoimmunity in rheumatoid arthritis.
19435478 The inextricable link between atherosclerosis and prototypical inflammatory diseases rheum 2009 The increased burden of cardiovascular disease in patients with rheumatoid arthritis and systemic lupus erythematosus has recently become the focus of intense investigation. Proatherogenic risk factors and dysregulated inflammation are the main culprits, leading to enhanced atherosclerosis in subgroups of patients with inflammatory diseases. Common molecular pathways shared by atherosclerosis and inflammatory disease may be involved. In this review we map the key determinants of the increased incidence of cardiovascular disease in patients with inflammatory diseases at each step of the atherogenesis.
19531746 Declines in erythrocyte sedimentation rates in patients with rheumatoid arthritis over the 2009 Aug OBJECTIVE: To analyze baseline erythrocyte sedimentation rates (ESR) in cohorts of patients with rheumatoid arthritis (RA), which had been included in a review concerning longterm mortality, in reports published between 1973 and 2008, with baseline observations between 1954 and 2000. METHODS: A computer search and complementary review of the literature had identified 84 unique cohorts with RA for which mortality over 5-40 years was reported. Baseline ESR data were available for 23 of the 84 cohorts. Mean and median ESR, age, disease duration, and rheumatoid factor (RF) status were compiled and analyzed in tertiles according to first year of patient recruitment. RESULTS: Among 7 cohorts recruited initially between 1954 and 1980, median ESR at baseline was 47 mm/h (mean 50 mm/h, range 43-66), compared to median 38 mm/h (mean 41 mm/h, range 34-64) among 8 cohorts recruited between 1981 and 1984, and median 36 mm/h (mean 35 mm/h, range 28-42) among 8 cohorts recruited between 1985 and 1996. The lowest mean ESR among 7 cohorts with baseline in 1980 or earlier was 43 mm/h, and the highest reported mean ESR among 8 cohorts recruited after 1985 was 42 mm/h. In 3 cohorts recruited after 1985 from Sweden, Finland, and Spain, mean baseline ESR was < 30 mm/h. CONCLUSION: Mean ESR fell by 30% in cohorts of patients with RA recruited before 1981 compared to cohorts recruited after 1984. This decline may reflect changes in both the natural history and approaches to therapy of RA.
19946022 The effect of methotrexate on cardiovascular disease in patients with rheumatoid arthritis 2010 Feb OBJECTIVES: Patients with RA have an increased prevalence of cardiovascular disease (CVD). This is due to traditional risk factors and the effects of chronic inflammation. MTX is the first-choice DMARD in RA. We performed a systematic literature review to determine whether MTX affects the risk of CVD in patients with RA. METHODS: We searched Medline, Embase, Cochrane database, database of abstracts of reviews of effects, health technology assessment and Science Citation Index from 1980 to 2008. Conference proceedings (British Society of Rheumatology, ACR and EULAR) were searched from 2005 to 2008. Papers were included if they assessed the relationship between MTX use and CVD in patients with RA. Two reviewers independently assessed each title and abstract for relevance and quality. RESULTS: A total of 2420 abstracts were identified, of which 18 fulfilled the inclusion criteria. Two studies assessed the relationship between MTX use and CVD mortality, one demonstrated a significant reduction in CVD mortality and the second a trend towards reduction. Five studies considered all-cause CVD morbidity. Four demonstrated a significant reduction in CVD morbidity and the fifth a trend towards reduction. MTX use in the year prior to the development of RA decreased the risk of CVD for 3-4 years. Four studies considered myocardial infarction, one demonstrated a decreased risk and three a trend towards decreased risk with MTX use. CONCLUSION: The current evidence suggests that MTX use is associated with a reduced risk of CVD events in patients with RA. This suggests that reducing the inflammation in RA using MTX not only improves disease-specific outcomes but may also reduce collateral damage such as atherosclerosis.