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

ID PMID Title PublicationDate abstract
23271425 Major trends in the manifestations and treatment of rheumatoid arthritis in a multiethnic 2013 Jul We analyzed the epidemiological changes of rheumatoid arthritis (RA) over three decades using patients from a single center in Singapore. All patients who fulfill the 1987 American College of Rheumatology criteria for RA were invited to enroll in a prospective disease registry. We analyzed the patient demographics, disease manifestation, management and patient-reported outcomes, including quality of life (QoL), in the three categories according to the year of disease onset: before 1989 (group I), 1990-1999 (group II) and after 2000 (group III). There were 1,153 patients with 231, 532 and 390 in groups I, II and III, respectively. The mean disease durations were 25, 12 and 4.8 years, respectively. The majority was female (84.1 %) and Chinese (76.6 %) with no socio-demographic differences across the three periods. The age of onset rises and the prevalence of rheumatoid factor falls with the proximity of disease onset. Patients with most recent disease onset had the earliest access to the rheumatologist. They also had the highest tender and swollen joint counts, lowest deformed joint count and highest remission rate. Patients in group I report better mental and emotional QoL though many developed marked disability. We have documented changes of the manifestations of RA that are dependent and independent of improved treatment. Significant differences in accessibility to the rheumatologist, RA activity, functional capacity, quality of life and comorbidities were seen in subsequent cohorts due to treatment evolution and more efficient healthcare delivery.
25524399 Fostering autonomous motivation, physical activity and cardiorespiratory fitness in rheuma 2014 Dec 19 BACKGROUND: People with rheumatoid arthritis are at greater risk of morbidity and mortality from cardiovascular disease than the general population. Sustained physical activity increases cardio-respiratory fitness and reduces cardiovascular disease risk factors. However, little is known about how we can effectively promote long-term participation in physical activity in patients with rheumatoid arthritis. The literature consistently calls for physical activity interventions, and their implementation, to be theoretically-grounded. METHODS/DESIGN: This paper documents the protocol of a randomised control trial that investigates whether a Self-determination Theory-based intervention fosters the adoption and maintenance of physical activity (3, 6 and 12 months) sufficient to provide sustained cardiovascular and personal well-being benefits in patients with rheumatoid arthritis. The cost effectiveness of the intervention will also be determined. The trial is registered as Current Controlled Trials ISRCTN04121489. DISCUSSION: Results from this trial will provide guidance regarding key social environmental factors that can be manipulated to support motivational processes conducive to positive health behaviour change and optimal functioning in patients with Rheumatoid Arthritis.
24997587 A double-blind, randomized controlled trial to compare the effect of biannual peripheral m 2014 Jul 5 BACKGROUND: Permanent joint damage is a major consequence of rheumatoid arthritis (RA), the most common and destructive form of inflammatory arthritis. In aggressive disease, joint damage can occur within 6 months from symptom onset. Early, intensive treatment with conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) can delay the onset and progression of joint damage. The primary objective of the study is to investigate the value of magnetic resonance imaging (MRI) or radiography (X-ray) over standard of care as tools to guide DMARD treatment decision-making by rheumatologists for the care of RA. METHODS: A double-blind, randomized controlled trial has been designed. Rheumatoid and undifferentiated inflammatory arthritis patients will undergo an MRI and X-ray assessment every 6 months. Baseline adaptive randomization will be used to allocate participants to MRI, X-ray, or sham-intervention groups on a background of standard of care. Prognostic markers, treating physician, and baseline DMARD therapy will be used as intervention allocation parameters. The outcome measures in rheumatology RA MRI score and the van der Heijde-modified Sharp score will be used to evaluate the MRI and X-ray images, respectively. Radiologists will score anonymized images for all patients regardless of intervention allocation. Disease progression will be determined based on the study-specific, inter-rater smallest detectable difference. Allocation-dependent, intervention-concealed reports of positive or negative disease progression will be reported to the treating rheumatologist. Negative reports will be delivered for the sham-intervention group. Study-based radiology clinical reports will be provided to the treating rheumatologists for extra-study X-ray requisitions to limit patient radiation exposure as part of diagnostic imaging standard of care. DMARD treatment dose escalation and therapy changes will be measured to evaluate the primary objective. A sample size of 186 (62 per group) patients will be required to determine a 36% difference in pharmacological treatment escalation between the three groups with intermediate dispersion of data with 90% power at a 5% level of significance. DISCUSSION: This study will determine if monitoring RA and undifferentiated inflammatory arthritis patients using MRI and X-ray every 6 months over 2 years provides incremental evidence over standard of care to influence pharmacotherapeutic decision-making and ultimately hinder disease progression. TRIAL REGISTRATION: This trial has been registered at ClinicalTrials.gov: NCT00808496 (registered on 12 December 2008).
24295183 Skewness of TCR Vβ of peripheral blood and synovial fluid of patients with rheumatoid art 2014 To date, the complete mechanism of rheumatoid arthritis (RA) remain unclear, T cells have been proposed to play an important role in the disease initiation and progression. Presently, some researchers have reported that there were skewed TCR Vβ in different samples of experimental animals or RA patients, such as in the peripheral blood, joints or synovial fluid, however, most of the results were not coincident or even conflict with each other. In this article, with real-time fluorescence quantitative PCR with DNA melting curving technique, we detected the bias of TCR Vβ of RA patients, and found that although most of TCR Vβ usage were different between peripheral blood and synovial fluid, the overview of all the Vβ skewness was similar between the two samples.
24217669 Testicular vasculitis: a rare manifestation of rheumatoid arthritis. 2013 Aug Testicular vasculitis is a very rare extra-articular manifestation of rheumatoid arthritis (RA). We describe the case of a 53-year-old man diagnosed with RA for eight years, who was poorly controlled and developed rheumatoid vasculitis, which manifested as leg ulcers and peripheral polyneuropathy. The patient also had acute neutrophilic meningitis and was treated with antibiotics and intravenous pulse therapy with methylprednisolone (500 mg daily) for three days, followed by oral cyclophosphamide (2 mg/kg daily) and prednisone. Overall improvement was observed, and the patient was discharged. But 15 days later, the meningitis recurred, and the patient was readmitted and treated again with antibiotics. Three days later, he developed pain and enlargement of his left testicle with gangrene. Unilateral orchiectomy was performed, revealing lymphocytic vasculitis. The patient died two days later due to aspiration pneumonia. This case illustrates a rare and severe manifestation of rheumatoid vasculitis.
24129131 The when and how of biologic agent withdrawal in rheumatoid arthritis: learning from large 2013 Jul There has been great interest lately concerning the possibility that in the treatment of rheumatoid arthritis, biologic agents might be withdrawn for patients who achieve desirable targets, such as low disease activity or remission. While there are a number of reasons why such a treatment paradigm might be desirable, there is a paucity of relevant data at present to guide clinicians about embarking on such a treatment change. Data is starting to emerge, much of it from controlled trials, that can provide some guidance as to which patients might be the best candidates for such an approach. These data will provide answers to the key questions that remain concerning this important potential paradigm shift in the treatment of rheumatoid arthritis as well as other systemic inflammatory autoimmune diseases.
24725498 Translation and validation of the Turkish language version of the Rheumatoid Arthritis Dis 2017 Dec AIM: The purpose of this study was to translate the Rheumatoid Arthritis Disease Activity Index-5 (RADAI-5), which is a tool for measuring disease activity in rheumatoid arthritis (RA) patients, into Turkish language and prove its validity, reliability and sensitivity to changes. METHODS: Translation from the original German version was performed according to the standardized methods. One hundred and two patients with RA completed in the Turkish RADAI-5 twice within 3 days interval. Internal consistency and test-retest reliability was investigated by calculating Cronbach's alpha and intra-class correlation coefficients (ICC), respectively. Validity was assessed by analyzing the correlations between the Turkish RADAI-5 and some measurement tools evaluating the disease activity, functional status and quality of life. To test the scale's responsiveness to the changes, another 23 patients with uncontrolled disease activity and three newly diagnosed RA patients completed the RADAI-5 before and after a biologic agent or methotrexate treatment. RESULTS: There were no floor or ceiling effects. Cronbach's alpha (0.91) and ICC (0.997) values certified the Turkish version's reliability. Strong correlations between the Turkish questionnaire and Disease Activity Score-28 (DAS28), DAS28-CRP, DAS28-three variables, Health Assessment Questionnaire, Rheumatoid Arthritis Quality of Life questionnaire, patient's and doctor's global assessments, tender joint count proved the convergent validity of the scale. Effect size (3.08) demonstrated that the Turkish RADAI-5 is sensitive to the changes. CONCLUSION: The Turkish RADAI-5 is a feasible, reliable and valid questionnaire and sensitive to changes; thus it can be used to monitor disease activity in Turkish RA patients.
24847749 Max Schüller and an alleged microbial cause of rheumatoid arthritis. 2014 Jun Max Schüller (1843-1907) was a German surgeon and microbiologist. From 1884 to 1905, he published histopathologic and bacteriological research on bacterial infection of human joints. Beginning in 1892, he focused on a bacterium he had identified in joints of patients with rheumatoid arthritis and surmised that he had discovered the cause of this disease. He persisted in conducting various experiments, some original at the time, with which he convinced himself of the validity of his discovery, without considering the possibility that he was working on contaminants. Contemporaneous attempts to confirm Schüller's findings gave inconsistent results. A century of microbiological research with ever more sensitive techniques has not definitively answered the etiologic question. This history is a cautionary tale of the difficulty of disproving an erroneous premise.
23645652 A rheumatoid nodule in an unusual location: mediastinal lymph node. 2013 May 2 Rheumatoid arthritis (RA) is a multisystem inflammatory disease characterised by destructive synovitis and varied extra-articular involvement. Rheumatoid lung nodules are the most common pulmonary manifestations of RA. Rheumatoid nodules in mediastinal lymph nodes are extremely uncommon. We describe a male patient with long-standing RA and subcutaneous rheumatoid nodules presenting with multiple lung nodules and mediastinal lymphadenopathies. Definite histopathology of a lymph node was consistent with necrobiotic granuloma due to RA. Clinicians should be aware of rheumatoid nodules as a potential cause of mediastinal lymphadenopathies, mainly in advanced rheumatoid arthritis.
24673827 The -308 G/A polymorphism in the tumor necrosis factor-α gene is not associated with deve 2016 May AIM: A polymorphism in the tumor necrosis factor-alpha (TNF-α) promoter region has been associated with disease susceptibility and progression in rheumatoid arthritis (RA). The presence of an adenosine (TNF2 allele) instead of a guanine (TNF1 allele) at position -308 may be responsible for a general increase in the transcriptional activity of the TNF-α gene. Our aim was to evaluate the association of the TNF2 allele with the risk of disease development and/or progression of RA in an Argentine population cohort. METHODS: Two hundred and twenty-three consecutive patients with RA according to the 1987 criteria of the American College of Rheumatology were included in the study. Clinical variables, Disease Activity Score 28, Health Assessment Questionnaire and Rheumatoid Arthritis Quality of Life were recorded. The radiographic erosions were determined by the method of Sharp/van der Heijde. A group of 111 healthy subjects matched by sex and age was used as a control. All samples were genotyped for the -308 G/A TNF-α polymorphism. RESULTS: No significant differences were observed either in the frequency of the TNF2 allele or in the genotypic distributions of the -308 G/A TNF-α polymorphism (P > 0.05) between the control group and the RA patients. No association was found between the TNF2 allele and the variables related to the course and outcome of the disease (P > 0.05). CONCLUSION: In this cohort of Argentinean patients with RA, the TNF2 allele was neither associated with susceptibility to the disease nor was it associated with the variables related to the course and outcome of the disease.
24719046 Three months of moderate-intensity exercise reduced plasma 3-nitrotyrosine in rheumatoid a 2014 PURPOSE: Rheumatoid arthritis (RA) patients display high levels of oxidative stress. Transient exercise-induced increases in oxidative stress are thought to be adaptive in healthy populations. This study investigated the effect of exercise on markers of oxidative stress in RA, following acute exercise and a period of exercise training. METHODS: Acute exercise study: RA patients (N = 12, age: 56 ± 11) undertook a bout of exercise (30-40 min, 70 % VO2MAX), and blood samples were taken before and after exercise to assess markers of oxidative stress. Training study: RA patients (N = 19, age: 56 ± 10) were randomised into either a control or exercise group, who undertook 3 exercise sessions per week (30-40 min @70 % VO2MAX) for 3 months. Plasma markers of oxidative stress (protein carbonyls (PC), lipid hydroperoxides (LOOH), 3-nitrotyrosine (3-NT), total antioxidant capacity (TAC) and catalase (CAT) activity), inflammation (interleukin-8 (IL-8) and C-reactive protein (CRP)) and nitric oxide metabolites (NOx) were assessed before and after training. RESULTS: Acute exercise study: Protein carbonyls (PC) (+18 %) and NOx (+27 %) were significantly increased following exercise. Training study: 3-nitrotyrosine (3-NT) decreased (2.18 ± 1.78 to 1.10 ± 0.93 μM) in the exercise group only, alongside increases in aerobic fitness (24.45 ± 4.98 to 27.10 ± 4.51 ml/kg/min(-1)) and reductions in disease activity score (DAS: 3.47 ± 1.17 to 2.88 ± 0.76). PC, LOOH, TAC, IL-8, CRP and NOx concentrations, and CAT activity were unchanged in both groups. CONCLUSIONS: Aerobic exercise training did not increase markers of oxidative stress in RA patients. 3-Nitrotyrosine and disease activity were decreased following exercise training.
24701711 [Complications and systemic manifestations of rheumatoid arthritis]. 2014 Mar 12 Rheumatoid arthritis (RA), in addition to the traditional joint damage can affect all organs as a systemic disease. Extra-articular manifestations of RA are highly variable ranging from rheumatoid nodules (most common) to rheumatoid vasculitis presenting a significant morbidity and mortality (49% at 5 years). With the new algorithms of treatment (earlier) and the use of biologics, the incidence of severe extra-articular manifestations decreases. Regarding the treatment of rheumatoid vasculitis, rituximab looks promising. RA also increases cardiovascular risk and the risk of osteoporosis. It is therefore important to identify these risks and, if appropriate, treat them. Collaboration with the general practitioner is essential in this situation.
23578823 Sexual disparities in the incidence and course of SLE and RA. 2013 Nov Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) disproportionately affect females compared to males, with female to male prevalence ratios of 7-9:1 for SLE and 2-3:1 for RA. Interestingly, epidemiologic studies indicate that men that develop SLE may have more morbidity than women, but the same is not true for RA. Given the sex and age bias of SLE and RA, sex hormones may influence the pathogenesis of these diseases. However, the ways in which, and to what degree, sex hormones affect disease incidence and severity remain unclear and is the topic of ongoing research. Recent findings have implicated interactions between sex hormones, the immune system, genetic factors, and epigenetic modifications in influencing SLE and RA disease activity. This article reviews current hypotheses regarding the potential impact of sex hormones and genetics on disease pathogenesis, incidence, and severity of SLE and RA.
24514915 Persisting eicosanoid pathways in rheumatic diseases. 2014 Apr An unmet clinical need exists for early treatment of rheumatic diseases and improved treatment strategies that can better maintain remission with reduced ongoing subclinical inflammation and bone destruction. Eicosanoids form one of the most complex networks in the body controlling many physiological and pathophysiological processes, including inflammation, autoimmunity and cancer. Persisting eicosanoid pathways are thought to be involved in the development of rheumatic diseases, and targeting this pathway might enable improved treatment strategies. Several enzymes of the arachidonic acid cascade as well as eicosanoid receptors (all part of the eicosanoid pathway) are today well-recognized targets for anti-inflammatory drugs that can reduce symptoms of inflammation in rheumatic diseases. In this Review, we outline the evidence supporting pivotal roles of eicosanoid signalling in the pathogenesis of rheumatic diseases and discuss findings from studies in animals and humans. We focus first on rheumatoid arthritis and discuss the upregulation of the cyclooxygenase and lipoxygenase pathways as most data are available in this condition. Research into the roles of eicosanoids in other rheumatic diseases (osteoarthritis, idiopathic inflammatory myopathies, systemic lupus erythematosus and gout) is also progressing rapidly and is discussed. Finally, we summarize the prospects of targeting eicosanoid pathways as anti-inflammatory treatment strategies for patients with rheumatic diseases.
24771380 Apoptosis regulator proteins: basis for the development of innovation strategies for the t 2014 Jan Apoptosis markers (p53, PUMA, p21, and Mdm2) were studied in patients with rheumatoid arthritis at the early and late stages of disease on bone marrow smears and frozen sections of the articular synovial membrane. The target molecules were found in all patients. The early stage was characterized by maximum expression of antiapoptotic (Mdm2) molecule and the minimum expression of proapoptotic molecules (p53, PUMA, and p21). The proapoptotic proteins predominated in patients with the late stage of rheumatoid arthritis, while the antiapoptotic factor (Mdm2) was depressed significantly. These data suggested total suppression of apoptosis at the early stage of rheumatoid arthritis and recommended the Mdm2 molecule as a prospective target for the development of new drugs.
24647026 Rheumatoid meningitis presenting with stroke-like episodes. 2014 Apr 29 Neurologic symptoms in patients with rheumatoid arthritis (RA) are most often caused by osseous compression, affecting the cervical spine or peripheral neurologic structures. CNS involvement in RA is infrequent, consisting of CNS vasculitis or meningitis with or without meningeal nodules.(1) When meningeal infiltration is seen, symptoms of presentation can include focal neurologic deficits, seizure, cranial nerve dysfunction, or altered consciousness.(1) Here we describe a patient with an unusual presentation of rheumatoid meningitis.
24607326 Alterations of plasma glycosaminoglycan profile in patients with rheumatoid arthritis in r 2014 Jun 10 BACKGROUND: Qualitative and quantitative evaluation of plasma glycosaminoglycans (GAGs) of rheumatoid arthritis (RA) patients in relation to disease activity estimated by DAS28 score was evaluated. METHODS: GAGs were quantified by hexuronic acid assay and electrophoretic fractionation. Keratan sulfate (KS) and hyaluronic acid (HA) were measured by immunoassay. RESULTS: Chondroitin/dermatan sulfate (CS/DS) and heparan sulfate/heparin (HS/H) in plasma of healthy subjects and RA patients were stated. Total GAGs, CS, HS/H and HA levels were higher in patients with high and moderate disease activity than in controls. Total GAGs and CS levels in patients with high disease activity were elevated in comparison to patients with low disease activity. HS/H levels in patients with high and moderate activity were elevated in comparison to those with low disease activity. KS levels were increased in all patient groups in comparison to controls. Total GAGs, CS, HS/H and HA levels were positively correlated with DAS28 and CRP. CONCLUSIONS: Structural tissue damage/remodeling of the extracellular matrix occurs in RA, which is reflected in the qualitative and quantitative changes of plasma GAGs. The above changes depend on DAS28 and may contribute to systemic changes in the properties of the extracellular matrix.
24589910 Gene expression analysis in RA: towards personalized medicine. 2014 Apr Gene expression has recently been at the forefront of advance in personalized medicine, notably in the field of cancer and transplantation, providing a rational for a similar approach in rheumatoid arthritis (RA). RA is a prototypic inflammatory autoimmune disease with a poorly understood etiopathogenesis. Inflammation is the main feature of RA; however, many biological processes are involved at different stages of the disease. Gene expression signatures offer management tools to meet the current needs for personalization of RA patients' care. This review analyses currently available information with respect to RA diagnostic, prognostic and prediction of response to therapy with a view to highlight the abundance of data, whose comparison is often inconclusive due to the mixed use of material source, experimental methodologies and analysis tools, reinforcing the need for harmonization if gene expression signatures are to become a useful clinical tool in personalized medicine for RA patients.
24347286 MR and CEUS monitoring of patients with severe rheumatoid arthritis treated with biologica 2014 Jun PURPOSE: This study was done to propose a study protocol for patients with rheumatoid arthritis (RA) treated with biological agents, by evaluating the contribution of contrast-enhanced magnetic resonance (CE-MR) imaging, a software programme that calculates the volume of synovitis on CE-MR images, and contrast-enhanced ultrasound (CEUS). MATERIALS AND METHODS: Sixteen patients with RA receiving treatment with biologics were analysed. The patients underwent clinical examination, CE-MR imaging and CEUS on the same day. Images were postprocessed with the software and evaluated independently by three physicians in terms of RAMRIS (Rheumatoid Arthritis Magnetic Resonance Imaging Score), SAMIS (Simplified Rheumatoid Arthritis Magnetic Resonance Imaging Score) and CEUS grade. The techniques were correlated statistically. RESULTS: The RAMRIS and SAMIS scores were found to correlate statistically. CE-MR imaging correlated with the clinical data (p < 0.05), whereas CEUS did not. The data provided by the software did not correlate statistically with the other techniques. The most painful joint was consistently found to be the joint with most synovitis. CONCLUSIONS: CE-MR imaging may be used prior to treatment and for long-term follow-up. CEUS might be useful in the short-term follow-up, as it seems to provide an indication of the presence or absence of disease, though not of its severity. The software is a very useful tool that can supplement, but not replace, the other techniques.
25406507 Increased nocturnal periodic limb movements in rheumatoid arthritis patients meeting quest 2014 Nov 18 BACKGROUND: Based on questionnaire criteria, the sensorimotor disorder restless legs syndrome (RLS) has been reported to have a higher prevalence in rheumatoid arthritis (RA) patients than in the general population. There has been some speculation that peripheral arthritic symptoms may allow false positive responses to questionnaire criteria. This study evaluates whether RA patients meeting RLS questionnaire criteria also have objective evidence of increased periodic limb movements (PLMs) characteristic of RLS. METHODS: Participants were recruited from RA clinic. Questionnaire data collected at study entry included: pain scores, rheumatoid arthritis disease activity index, Epworth sleepiness scale, Pittsburgh sleep quality index and RLS diagnostic criteria. Each participant was provided a PAM-RL actigraphic monitor, which attached to the ankle. This device was worn for two consecutive nights then returned for data download. Laboratory data including hemoglobin, iron studies, renal function and C-reactive protein levels were collected. RESULTS: Of the 57 participants, 23 met RLS diagnostic criteria. Those who met RLS criteria demonstrated higher mean frequency of nocturnal PLMs (19.63/hour; SD:21.13) than those who did not meet RLS criteria (11.13/hour; SD:12.10; p=0.033). There were no significant differences between groups in terms of patient characteristics, disease activity or duration measures. Patients meeting RLS criteria did have poorer sleep quality measures (p <0.001). CONCLUSIONS: RA patients who met RLS diagnostic criteria demonstrated higher frequencies of nocturnal PLMs than RA patients who did not meet criteria for RLS. This finding supports use of the RLS diagnostic criteria in helping to differentiate between RA arthritic symptoms and RLS.