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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
16429239 Carpal collapse in patients with rheumatoid arthritis. 2006 Nov The inflammation of the wrist and carpal collapse play an important role in the deformity of the rheumatoid hand and leads to functional limitation. The aim of this study was to evaluate carpal collapse and related clinical variables in patients with rheumatoid arthritis (RA). Carpal height ratio (CHR) indicating the degree of carpal collapse was measured in 33 female RA patients with a mean age of 41.9+/-10.3 years and 30 female healthy control subjects with a mean age of 40.5+/-9.2 years. The normal range of the carpal collapse was defined in our study population and the incidence of carpal collapse was determined. The correlation between carpal collapse and clinical and laboratory variables including pain by visual analog scale, Ritchie articular index, erythrocyte sedimentation rate, C-reactive protein, health assessment questionnaire indicating functional status, and Larsen roentgenological evaluation were determined. Subgroup analyses were also performed in patients with and without carpal collapse. The mean disease duration of the patients was 12.4+/-5.5 years. The mean CHR index of the patients was significantly lower than in the control group (0.47+/-4.3 and 0.54+/-1.4 respectively). CHR <0.48 was defined as carpal collapse in our study group. Seventeen patients (51.5%) had carpal collapse in the patient group. None of the clinical or laboratory variables except levels of disease duration and Larsen score was correlated with carpal collapse as represented by CHR. The best related clinical variable with carpal collapse was found as duration of disease. The mean duration of disease and the Larsen score were significantly higher in patients with carpal collapse than those without collapse. Other clinical parameters and functional status were similar between patients with and without carpal collapse. In conclusion, although various clinical parameters and functional disability in patients with RA may not be correlated with radiological malalignment, the carpal collapse may be more common in RA than is generally recognized.
16195159 Rheumatoid factor by laser nephelometry and Waaler-Rose assay: prognostic value in patient 2005 Jul OBJECTIVE: To evaluate the prognostic value of rheumatoid factor (RF), detected in the Waaler-Rose agglutination assay and by nephelometry, in patients with recent-onset rheumatoid arthritis (RA). METHODS: Consecutive patients with new-onset RA between 1993 and 1997 were followed for a median period of 4.7 years. Clinical data at baseline and drug use during the disease course were recorded. Outcome parameters studied were disease process, damage (erosions, joint surgery, extra-articular manifestations, and new co-morbidity), and death. Cut-off levels for RF were >40 IU/mL (nephelometry) and titres 1:160 (Waaler-Rose haemagglutination). RESULTS: RF tests were negative by both methods in 22% of RA patients (RF- group), while 33% were RF positive by nephelometry only (RF+ group) and 45% were positive by Waaler-Rose and nephelometry (RF++ group). Baseline clinical and laboratory findings as well as the number of subsequently used disease-modifying anti-rheumatic drugs (DMARDs), the number of patients starting and the time spent on steroid therapy were similar in the three RF groups. Odd ratios for death (n = 23), erosions (n = 62), and serious extra-articular disease manifestations (EAMs) (n = 13) as well as patient survival, erosion-free or surgery-free survival rates did not differ between the RF groups. Only rheumatoid nodules were more frequent in RF++ patients. CONCLUSION: The baseline presence of RF by either Waaler-Rose or nephelometry was not associated with differences in drug therapy, morbidity other than rheumatoid nodules, or mortality in RA patients in the first 5 years of disease. Being immunoglobulin M (IgM) RF positive thus had little impact on RA patient outcome.
16980218 The role of mesenchymal cells in the pathophysiology of inflammatory arthritis. 2006 Oct Rheumatoid arthritis (RA) is a chronic inflammatory disorder of the joints that can cause severe disability. While the role of inflammatory cells in the pathogenesis of RA has been well established, the specific contribution of resident cells within the synovial membrane, especially those of mesenchymal origin, has become the object of closer scrutiny only recently. The central position of these cells in the disease process of RA is underlined by their involvement in its main pathophysiological features: inflammation, hyperplasia and joint destruction. In this chapter, we provide a characterisation of resident mesenchymal cells, specifically fibroblast-like cells in the rheumatoid synovium, and give an overview of the molecular pathways by which these cells are involved in the initiation and perpetuation of RA.
16249229 Impact of parental history on patients' cardiovascular mortality in rheumatoid arthritis. 2006 Jun BACKGROUND: Patients with rheumatoid arthritis are at increased risk of death from cardiovascular disease (CVD). This risk is influenced by the inflammatory activity of the rheumatoid arthritis as well as by traditional risk factors for CVD. However, little is known about whether or to what extent hereditary factors for CVD contribute additional risk in patients with rheumatoid arthritis. OBJECTIVE: To assess the clinical impact of a parental history of CVD in patients with rheumatoid arthritis. METHODS: Population based cohort study of 10,805 Swedish patients with rheumatoid arthritis aged 16-67 years during follow up (1990-2000). Parents, and cardiovascular deaths among patients and parents, were identified through register linkages. Relative risk of death v the general population was assessed using standardised mortality ratios (SMR), which were compared by Poisson regression. RESULTS: Rheumatoid patients with a parental history of fatal CVD had an SMR of death from CVD of 2.9 (95% confidence interval, 2.5 to 3.4). By contrast, rheumatoid patients without a parental history of fatal CVD had an SMR of 1.7 (1.2 to 2.3). A parental death from CVD was associated with a 70% increase in the risk of fatal CVD in rheumatoid arthritis (SMR ratio = 1.7 (1.2 to 2.4), and an increase in the 10 year mortality from CVD from 5% to 10% in men and from 2% to 4% in women aged 50 to 67 years. CONCLUSIONS: Parental history of death from CVD is an important (and easily assessable) risk factor for fatal CVD in rheumatoid arthritis.
16282041 Targeting cytokines beyond tumor necrosis factor-alpha and interleukin-1 in rheumatoid art 2005 Dec Targeting tumor necrosis factor-a has proven of considerable value in treatment for rheumatoid arthritis, with substantial benefits achieved in a proportion of treated patients. However, a significant number of patients do not achieve sufficient improvement and as a result there remains considerable unmet clinical need. A number of cytokines have recently been described with proinflammatory activity in rheumatoid arthritis synovitis, including interleukin (IL)-6, IL-12, IL-15, and IL-18. We review recent data that support the notion that some or all of these moieties offer therapeutic potential. The possibility that some may be useful in partial responders to tumor necrosis factor blocking agents or in synergy with the latter is discussed.
17002483 The initial validation of a Markov model for the economic evaluation of (new) treatments f 2006 OBJECTIVE: Markov models are increasingly used in economic evaluations of (new) treatments for chronic diseases. In this study we propose a Markov model with health states defined by the disease activity score (DAS) to be used to extrapolate efficacy data from short-term clinical trials in rheumatoid arthritis to longer term cost-effectiveness results. Moreover, we perform an initial validation of this model. METHODS: To test the validity of the model, the expected disease course (according to the model) was first compared with the observed disease course in an inception cohort of newly diagnosed rheumatoid arthritis patients. Then the relationship of the health states with utility and costs was investigated. Finally, costs and QALYs were calculated for usual care of patients in the first 5 years of their disease using the model and compared with the literature. RESULTS: The model seemed to be able to extrapolate 1-year efficacy data as seen by a comparable distribution over the Markov states between the model results and the observational data. The health states had a significant relationship with costs and utility, and population characteristics had only a moderate effect on the cost and utility values of the Markov states. The distribution over the Markov states resulted in 3.266 expected QALYs per patient over 5 years. The expected medical and total costs per patient over 5 years were 6754 euro (1997 values) and 12,641 euro, respectively, for standard rheumatoid arthritis care in The Netherlands. CONCLUSION: The developed Markov model seems a valid model for use in economic evaluations in rheumatoid arthritis. The model produced similar utilities, but lower total costs, to those in previously published studies. Although the steps to develop and validate this Markov model were applied in the context of rheumatoid arthritis, they can be generalised to other chronic diseases.
17200064 Experienced health in older women with rheumatoid arthritis. 2006 This study explored how older women with chronic illness and disability experience their own health. Data were collected in in-depth interviews with ten older women with rheumatoid arthritis. Data analysis and interpretation was carried out within a phenomenological- hermeneutic frame of understanding, which revealed five major themes: health as coping with everyday life, health as freedom, health as absence of inconvenience, health as togetherness and health as mental well-being. For older people with chronic illness and disability, good health found expression in general well-being. It was perceived as a state of equilibrium that the respondents sought to maintain through their own active choices.
16855148 Epidemiological aspects of rheumatoid arthritis: the sex ratio. 2006 Jun Many rheumatic diseases, including rheumatoid arthritis (RA) are more frequent in females than males. The objective of this article was to examine the female versus male perspective regarding prevalence/incidence, etiological factors, disease severity/outcomes, access to therapy and therapeutic responses. We also present results from some new analyses from the patient registers in Oslo to supplement existing literature in this area. We found that the prevalence of RA is higher in females than males, the incidence is 4-5 times higher below the age of 50, but above 60-70 years the female/male ratio is only about 2. Smoking is a consistent predictor of RA in males, but findings have been more inconsistent in females. We could not confirm that health status is worse in females than males when corrections were made for different disease duration and for the underlying tendency of healthy females to report worse subjective health status than males. Some studies and data presented here indicate that females have less access to health services. We also found that female sex reduces the likelihood of achieving treatment response with methotrexate and anti-tumor necrosis factor (anti-TNF) drugs by 30-50%. More research is needed to fully describe the differences between males and females regarding epidemiological data.
15716320 Predictive and potentially predictive factors in early arthritis: a multidisciplinary appr 2005 Apr OBJECTIVES: Rheumatoid arthritis (RA) is characterized by variable degrees of joint inflammation, joint destruction, progressive disability and premature death. Destruction of joint cartilage and bone may occur early during disease, as was shown in longitudinal studies of RA, and there is increasing consent among rheumatologists that early diagnosis and early initiation of therapy with disease-modifying anti-rheumatic drugs (DMARDs) can limit the severity of RA. Unfortunately, the currently used diagnostic and predictive indicators (clinical, laboratory and radiological) are of limited value for making an early diagnosis and prognosis of the disease course at the individual level, thus reducing optimal benefit from present and emerging therapies. Therefore, this review focuses on the multidisciplinary aspects of neuroendocrine-immune changes in RA. METHODS: A Medline search was performed using the search terms 'androgens', 'estrogens', 'sympathetic nervous system', 'sensory nervous system', 'prognosis', 'early rheumatoid arthritis', 'arthritis' and 'studies' in various combinations. For the tabular overview, we only listed clinical studies focusing on endocrine and neuronal aspects. RESULTS: In addition to the currently used predictive indicators, there is an abundant body of literature describing changes of the neuronal, endocrine and immune parameters during inflammatory diseases. Unfortunately, no longitudinal studies concerning neuroendocrine aspects have been done up to now. CONCLUSION: Parameters of the neuroendocrine system should be included in anticipated longitudinal clinical studies to find their true predictive value in early RA.
17162371 Identification of patients with early rheumatoid arthritis: challenges and future directio 2006 Jun Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis that affects the adult population. Early diagnosis and treatment are the cornerstones to prevent joint damage and avoid long-term costs and disability. This article reviews the limitations of the currently available tools for the evaluation of patients with early arthritis, including clinical assessment, serologic markers and imaging modalities. It also discusses gene expression analysis, a newer and potentially promising approach to the early diagnosis of RA.
15946116 Affect and pain in rheumatoid arthritis: do individual differences in affective regulation 2005 Jun BACKGROUND: Individual differences in adaptation to rheumatoid arthritis are not fully accounted for by illness severity or duration of symptoms. PURPOSE: In this study, we assessed differences in affect regulation and affect intensity as variables that might be important for identifying women with rheumatoid arthritis who are resilient versus those who have disrupted moods following pain exacerbations. METHOD: Specifically, affective regulation, affect intensity, active coping, neuroticism and weekly reports of pain, positive affect, and negative affect were assessed in a sample of 81 women diagnosed with rheumatoid arthritis. RESULTS: Our results indicated that affective regulation, affect intensity, and active coping played important but distinct roles in the ebb and flow of negative and positive affect. In particular, active coping was related to positive affect, whereas affective regulation and affect intensity showed interactive effects, moderating the prospective relationship between pain and negative affect and pain and positive affect. CONCLUSION: Overall, this study suggests that recovery from rheumatoid arthritis pain can be swift, except for those women who have difficulty regulating strong unpleasant affect.
15485997 A family based study shows no association between rheumatoid arthritis and the PADI4 gene 2005 Apr BACKGROUND: Autoantibodies to citrullinated proteins (ACPA) are considered a specific marker for rheumatoid arthritis. Peptidylarginine deiminase (PAD) is the enzyme that converts arginyl into citrullyl residues; different isoforms of the enzyme are expressed in mammals. It has been suggested that the PADI4 gene may contribute to genetic susceptibility to rheumatoid arthritis, but conflicting results have been obtained in different populations. OBJECTIVE: To test the hypothesis that the PADI4 gene may confer susceptibility to rheumatoid arthritis in a white French population, using powerful and highly reliable family based association tests. METHODS: DNA samples were analysed from 100 families where one member was affected by rheumatoid arthritis and both parents were available for sampling. Five single nucleotide polymorphisms, located within the PADI4 gene and in its close proximity, were genotyped by restriction fragment length polymorphism, and haplotypes were constructed. The analysis involved use of the transmission disequilibrium test and genotype relative risk. ACPA were detected by ELISA on cyclic citrullinated peptides and on human deiminated fibrinogen. RESULTS: No single SNP or haplotype was associated with the disease, or was preferentially transmitted. No association was found when patients were partitioned according to ACPA positivity. CONCLUSIONS: No PADI4 haplotype is associated with rheumatoid arthritis in a white French population. The role of genes encoding the other PAD isoforms, or modulating tissue expression or enzyme activity, remains to be elucidated.
16855154 Are glucocorticoids DMARDs? 2006 Jun Disease modifying antirheumatic drugs (DMARDs) are drugs used in rheumatoid arthritis (RA) to control the disease and to limit joint damage and improve long-term outcome. The last decade evidence has accumulated that suggests that low dosages of glucocorticoids are indeed able to control the disease and limit the destruction. This role is especially present in early disease and in combination with other drugs. The evidence is carefully evaluated and discussed. The ultimate conclusion is that indeed glucocorticoids are DMARDs and are especially useful in early RA.
16184349 [Research strategies towards a holistic characterization of rheumatoid arthritis--a system 2005 Sep Genome-wide screening methods used in functional genomics (genome, transcriptome, proteome and metabolom analysis) have increasingly been conducted in integrative research platforms to enable a comprehensive holistic characterization of multifactorial polygenic diseases. First results of this research strategy demonstrate that extended data sets are compiled whose quality is ensured by the application of standard operating procedures (SOPs) and the integration of specific laboratory information management systems (LIMS). Experimental data derived from this technology and methodology platform are obtained by applying standardized sampling procedures followed by comprehensive experimental validation and bioinformatic comparisons with the world knowledge publicly available. This research strategy should finally lead to a holistic understanding of the pathogenesis presented in rheumatoid arthritis by identifying disease-associated regulatory networks (pathways) and assigning them to cell populations involved in the disease mechanisms. In addition, it has to be investigated to what extent genetic as well as epigenetic factors direct disease initiation and progression in potential conjunction with environmental impacts (infections, smoking, etc.).
16487554 Tropical pyomyositis in a case of rheumatoid arthritis. 2006 Sep Tropical pyomyositis is very rarely associated with rheumatoid arthritis. We report tropical pyomyositis involving gastrocnemius muscle in both the legs with eosinophilia and elevated serum IgG and IgE levels in a case of rheumatoid arthritis. We suggest that the possibility of pyomyositis should be considered in all cases of rheumatoid arthritis presenting with muscle pain, fever and leucocytosis.
16287585 The evidence for early intervention. 2005 Nov It is believed that rheumatoid arthritis (RA) is the most common, potentially treatable cause of disability in the Western world. A commonsense approach to the management of a persistent, progressive, damaging condition such as RA would seem to be intervention before the onset of damage, at a stage when disease still may be reversible. Such a phase of disease has been described as a "window of opportunity" for intervention. This article discusses the evidence for early intervention in RA.
15963480 The role of Toll-like receptor signalling in the pathogenesis of arthritis. 2005 Feb Recent evidence highlighted the role of Toll-like receptors (TLRs) as key recognition structures of the innate immune system. The activation of TLRs initiates the production of inflammatory cytokines, chemokines, tissue destructive enzymes, and type I interferons. In addition, TLR signalling plays an important role in the activation and direction of the adaptive immune system by the upregulation of costimulatory molecules of antigen presenting cells. Considering the important role of TLR signalling as a critical link between innate and adaptive immunity it has been proposed that a dysregulation in TLR signalling might be associated with autoimmunity. In this review, recent studies on TLR signal transduction pathways activated by corresponding ligands are summarized and evidence for a possible role of TLR signalling in the pathogenesis of rheumatoid arthritis is discussed.
17149060 Rheumatoid arthritis-associated necrotizing scleritis and peripheral ulcerative keratitis 2006 Dec In patients with rheumatoid arthritis (RA), necrotizing scleritis, an ocular manifestation of a systemic vasculitic process, is associated with significant ocular morbidity and high mortality. We present a 60-year-old man with RA who developed necrotizing scleritis and peripheral ulcerative keratitis. The scleritis was refractory to local measures, systemic corticosteroids, and cyclophosphamide but responded rapidly to infliximab. Our case illustrates that biologic agents may be considered in refractory cases of sight- and life-threatening scleritis.
16393766 Psychological stress and rheumatoid arthritis in parents after death of a child: a nationa 2005 Nov OBJECTIVE: To examine the risk of rheumatoid arthritis (RA) in parents after the death of a child. METHODS: All 21,062 parents whose child had died (younger than 18 years) between 1980 and 1996 in Denmark were included in the bereaved (exposed) cohort, and 293 745 parents matched on family structure were selected randomly from the general population for the unexposed cohort. RESULTS: We observed 600 incident RA cases during the follow-up (35 in the exposed cohort, 565 in the unexposed cohort). The relative risk (RR) of first hospitalisation for RA was 0.88 [95% confidence interval (CI) 0.63-1.24]. The RR was close to 1 throughout the 18 years of follow-up. CONCLUSION: Our findings do not support an association between severe psychological stress and RA.
16356195 Osteoclasts; culprits in inflammatory osteolysis. 2006 Periarticular osteolysis, a crippling complication of rheumatoid arthritis, is the product of enhanced osteoclast recruitment and activation. The osteoclast, which is a member of the monocyte/macrophage family, is the exclusive bone resorptive cell, and its differentiation and activation are under the aegis of a variety of cytokines. Receptor activator of NF-kappaB ligand (RANKL) and macrophage colony-stimulating factor are the essential osteoclastogenic cytokines and are increased in inflammatory joint disease. Tumor necrosis factor-alpha, which perpetrates arthritic bone loss, exerts its osteoclastogenic effect in the context of RANKL with which it synergizes. Achieving an understanding of the mechanisms by which the three cytokines affect the osteoclast has resulted in a number of active and candidate therapeutic targets.