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

ID PMID Title PublicationDate abstract
21149486 18F-FDG PET as a tool to predict the clinical outcome of infliximab treatment of rheumatoi 2011 Jan 18F-FDG PET is a sensitive, promising method for visualizing disease activity in rheumatoid arthritis. This study aimed to assess the association between changes in 18F-FDG joint uptake after 2 wk of infliximab treatment and clinical outcome. METHODS: Scans were obtained at the initiation of treatment and at 2 wk. Uptake in metacarpophalangeal and wrist joints was quantified using standardized uptake values. RESULTS: Changes in mean standardized uptake value at 0-2 wk significantly correlated with the disease activity score (DAS) at 14 and 22 wk and contributed significantly to the prediction of DAS at these time points. No significant correlation was found between changes in acute-phase reactants at 0-2 wk and the DAS at later time points. CONCLUSION: Early changes in 18F-FDG uptake in joints during infliximab treatment of rheumatoid arthritis patients, using PET, may predict clinical outcome.
22198689 The discrepancy between clinical and ultrasonographic remission in rheumatoid arthritis is 2012 Dec To evaluate the clinical remission by means of power Doppler ultrasonographic (PDUS) monitoring in a group of patients with rheumatoid arthritis (RA) in clinical remission (DAS28 < 2.6). The study included 54 patients with RA in therapy with DMARDS, anti-TNF, or no therapy in clinical remission according to ACR criteria and DAS 28 < 2.6 for at least 6 months. All patients had active wrist or hand inflammation in the past. US examination evaluated the presence of active synovitis, power Doppler signal, and synovial hypertrophy on the following bilateral joints: metacarpophalangeal-proximal interphalangeal joints-flexor tendons (on 2°-3° fingers) and wrist (radiocarpal and midcarpal joints). In 19 patients, there was an agreement between clinical and US parameters. However, 35 patients with clinical remission showed a positive ultrasonographic assessment and at least an active parameter. No statistic correlation was found between US examination and antibody assessment (anti-CCP and/or RF). Patients in therapy with anti-TNF or other therapies showed similar US assessment without significant statistical differences. Among eleven patients that presented swollen and tender joints at the latest physical examination, which preceded US exam, just 5 patients had an US confirmation too. In the other patients, the PDUS did not confirm the presence of inflammation in the corresponding swollen and tender joints or showed a positive ultrasonographic assessment in other locations. The remission state is a great therapy target and not only through the biological therapy. Synovial inflammation could persist independently from type of therapy or autoantibody status.
21111998 Rheumatologic disease and the liver. 2011 Feb Rheumatologic diseases such as rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, and scleroderma are immunologically mediated disorders that typically have multisystem involvement. Although clinically significant liver involvement is rare, liver enzyme abnormalities may be observed in up to 43% of patients. The biochemical abnormalities are typically mild and transient and the histologic abnormalities are usually nonprogressive. Such biochemical and histologic findings are typically ascribed to the primary rheumatologic condition and require no specific management. In a subset of patients with rheumatologic conditions and liver test abnormalities, further evaluation identifies a coexisting, primary liver disease or medication-related liver toxicity as the cause of the biochemical abnormality. Liver test abnormalities in patients with a coexisting primary liver disease are more likely to be persistent. In such cases, further workup using serologic tests, appropriate imaging studies and liver biopsy may be needed to accurately identify the cause of liver test abnormalities. This article reviews the spectrum of liver-related abnormalities associated with several rheumatologic diseases. Hepatotoxicity related to medications commonly prescribed in such conditions is also discussed.
21529307 Morning stiffness and other patient-reported outcomes of rheumatoid arthritis in clinical 2011 Morning stiffness has been recognized in traditional approaches to assessment of disease activity in rheumatoid arthritis (RA). Although morning stiffness is not specific to RA, changes in morning stiffness for an individual patient are helpful when monitoring health status. Health professionals can ask about morning stiffness but the most accurate and consistent approach to assessment from one visit to the next appears to be a patient self-report questionnaire. However, quantitative measures of patient-reported data are not an integral part of clinical monitoring in most clinics. No single measure is adequate for all individual patients, so quantitative measurement of patient-reported data should include many elements such as pain, functional status, fatigue, sleep, morning stiffness, work capacity, and physical and emotional well-being. In daily clinical practice, patient-reported outcomes can be collected easily using a standard questionnaire that patients can complete with pencil and paper or electronically on a touch screen in the waiting room. The results are then immediately available to the rheumatologists, to facilitate doctor-patient communication to improve the quality of patient care, leading to better patient outcomes.
23213198 In vivo imaging of cell proliferation enables the detection of the extent of experimental 2013 Jan The aim of this work was to study the feasibility of measuring cell proliferation noninvasively in vivo during different stages of experimental arthritis using the PET proliferation tracer 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT). METHODS: We injected mice with serum containing glucose-6-phosphate-isomerase-specific antibodies to induce experimental arthritis, and we injected control mice with control serum. Animals injected with (18)F-FLT 1, 3, 6, and 8 d after the onset of disease were analyzed in vivo by PET, PET/CT, or PET/MR imaging followed by autoradiography analysis. The (18)F-FLT uptake in the ankles and forepaws was quantified on the basis of the PET images by drawing standardized regions of interest. To correlate the in vivo PET data with cell proliferation, we performed Ki-67 immunohistochemistry of diseased and healthy joints at the corresponding time points. RESULTS: Analysis of the different stages of arthritic joint disease revealed enhanced (18)F-FLT uptake in arthritic ankles (2.2 ± 0.2 percentage injected dose per gram [%ID/g]) and forepaws (2.1 ± 0.3 %ID/g), compared with healthy ankles (1.4 ± 0.3 %ID/g) and forepaws (1.5 ± 0.5 %ID/g), as early as 1 d after the glucose-6-phosphate-isomerase serum injection, a time point characterized by clear histologic signs of arthritis but only slight ankle swelling. The (18)F-FLT uptake in the ankles (3.5 ± 0.3 %ID/g) reached the maximum observed level at day 8. Ki-67 immunohistochemical staining of the arthritic ankles and forepaws revealed a strong correlation with the in vivo (18)F-FLT PET data. PET/CT and PET/MR imaging measurements enabled us to identify whether the (18)F-FLT uptake was located in the bone or the soft tissue. CONCLUSION: Noninvasive in vivo measurement of cell proliferation in experimental arthritis using (18)F-FLT PET is a promising tool to investigate the extent of arthritic joint inflammation.
23342374 Epstein-Barr virus in systemic lupus erythematosus, rheumatoid arthritis and multiple scle 2012 Dec Epidemiological data suggest that the Epstein-Barr virus (EBV) is associated with several autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis. However, it is not clear whether EBV plays a role in the pathogenesis of these diseases, and if so, by which mechanisms the virus may contribute. In this review, we discuss possible viral and immunological mechanisms that might explain associations between EBV and autoimmune diseases and whether these associations represent causes or effects of inflammation and autoimmunity.
21529306 How should morning function in rheumatoid arthritis be assessed? Bibliographic study of cu 2011 In patients with rheumatoid arthritis (RA), symptoms of joint stiffness and pain may be most severe in the morning, resulting in impaired ability to carry out normal morning functions. Although morning stiffness was included in the criteria for classification and remission of RA, defined by the American College of Rheumatology (ACR) in 1987, the approach to assessment of this circadian symptom has not been standardized, and other circadian aspects of the disease (i.e. pain, functional ability) were not included. A bibliographic study of papers published in English in the period January 2007 to January 2010 and reporting morning stiffness, pain or function was undertaken to investigate methods of assessing circadian aspects of RA. A total of 73 studies were identified using Medline, including 62 clinical trials. Full papers were obtained for 52 reports of clinical studies (84%), most of which (44/52, 85%) assessed duration of morning stiffness. Only two studies (4%) specified that severity of morning stiffness was assessed, only three (6%) assessed pain in the morning, and none assessed morning functional ability. These findings suggest the need for consistent reporting of a measure to reflect the impaired morning function, arising from joint stiffness and pain that is commonly experienced by patients.
22088550 Coexisting ankylosing spondylitis and rheumatoid arthritis: a case report with literature 2011 Oct A 30-year-old female patient with coexisting ankylosing spondylitis and rheumatoid arthritis was diagnosed and treated. The human leukocyte antigen (HLA)-B27 is a predisposing factor of ankylosing spondylitis and HLA-DR4 is a predisposing factor of rheumatoid arthritis. This patient was HLA-B27 and HLA-DR4 positive, and ankylosing spondylitis manifested before rheumatoid arthritis. After disease modifying anti-rheumatic drugs successfully arrested ankylosing spondylitis activity the patient conceived and delivered a healthy baby. One year later, she developed peripheral polyarthritis and was diagnosed with rheumatoid arthritis. We hypothesized that pregnancy may be one of the environmental factors that can activate rheumatoid arthritis, and that disease modifying anti-rheumatic drugs play an important role in keeping the disease under control.
21077801 Treatment with low-dose prednisolone is associated with altered body composition but no di 2011 May OBJECTIVES: To determine whether low-dose prednisolone affects body composition and bone mineral density (BMD) in patients with rheumatoid arthritis (RA), also considering inflammation and physical disability. METHODS: This cross-sectional study included 100 patients (50 women) with RA with a median (IQR) disease duration of 8 (4-15) years. Fifty patients had been treated with prednisolone (5-7.5 mg) for at least 2 years (the P-group) and 50 patients matched for gender and age had not (the NoP-group). Body composition and BMD were assessed by dual-energy X-ray absorptiometry (DXA). Disease activity (28-joint Disease Activity Score, DAS28) and physical disability (Health Assessment Questionnaire, HAQ) were assessed. RESULTS: The total patient group had increased fat mass (FM) and a high trunk:peripheral fat ratio, of which 38% had a fat free mass index (FFMI, kg/m²) below the 10th percentile of a reference population. The P-group had significantly higher FM but similar lean body mass (LBM) and BMD compared with the NoP-group. In multivariate analyses, treatment with prednisolone and a higher HAQ score were significantly and independently associated with higher FM but not with LBM. Higher C-reactive protein (CRP) was independently associated with lower LBM. Higher HAQ score and low weight were significantly and independently associated with lower BMD at femoral neck and lumbar spine. CONCLUSIONS: RA patients treated with low-dose prednisolone had significantly higher FM than patients without prednisolone, an effect that was independent of current inflammation. However, there was no association between prednisolone treatment and muscle mass or BMD. Thus, the net effect of prednisolone on body composition and bone is different in inflammatory diseases such as RA.
22903698 Health-related quality of life in Moroccan patients with rheumatoid arthritis. 2012 Oct We aimed to assess the aspects of health-related quality of life (HRQoL) in Moroccan patients with rheumatoid arthritis (RA) and to evaluate the disease-related parameters influencing it. Two hundred fifty-five patients with RA were consecutively included. We assessed sociodemographic characteristics, cigarette smoking status, disease duration, diagnosis delay, joint pain intensity (on a 0-100-mm visual analogue scale), disease activity (by the disease activity score (DAS 28) and biological tests), structural damage (by radiographs scored using the Sharp's method as modified by Van der Heijde), functional disability (by the Health Assessment Questionnaire), extra-articular manifestations, immunological status, and treatments. The Arabic version of the Medical Outcomes Study Short Form 36 Health Survey (SF-36) was applied to assess HRQoL. All domains of SF-36 were deteriorated in a significant way comparing to the general population. The most affected subgroups of SF-36 were role limitation, role emotional, vitality, and social functioning. Women had significantly lower scores of SF-36 compared to men. Patients with decreased levels of education and low socioeconomic status had significantly lower scores of SF-36 (for all p ≤ 0.01). Current and ex-smokers had lower scores in physical domains of quality of life. Patients treated with methotrexate had better scores of mental health. Furthermore, patients receiving biologic agents had better scores of physical and social domains. Decreased scores of SF-36 were significantly correlated with disease duration, joint pain intensity, clinical and biological disease activity, functional disability, and radiographic damage. The level of antibodies against citrullinated peptides had significant correlations with the impairment of physical domains of SF-36. Physical as well as mental aspects of HRQoL in our RA patients were significantly deteriorated. Recognizing complicated relationships between HRQoL and disease-related variables among our RA patients can help to develop further management strategies to improve patients' daily living particularly with the advent of new treatments.
22137918 Co-morbidities in established rheumatoid arthritis. 2011 Aug Co-morbid conditions are common in patients with rheumatoid arthritis (RA). Although the presence of co-morbid conditions can be assessed using standardised indexes such as the Charlson index, most clinicians prefer to simply record their presence. Some co-morbidities are causally associated with RA and many others are related to its treatment. Irrespective of their underlying pathogenesis, co-morbidities increase disability and shorten life expectancy, thereby increasing both the impact and mortality of RA. Cardiac co-morbidities are the most crucial, because of their frequency and their negative impacts on health. Treatment of cardiac risk factors and reducing RA inflammation are both critical in reducing cardiac co-morbidities. Gastrointestinal and chest co-morbidities are both also common. They are often associated with drug treatment, including non-steroidal anti-inflammatory drug and disease-modifying drugs. Osteoporosis and its associated fracture risk are equally important and are often linked to long-term glucocorticoid treatment. The range of co-morbidities associated with RA is increasing with the recognition of new problems such as periodontal disease. Optimal medical care for RA should include an assessment of associated co-morbidities and their appropriate management. This includes risk factor modification where possible. This approach is essential to improve quality of life and reduce RA mortality. An area of genuine concern is the impact of treatment on co-morbidities. A substantial proportion is iatrogenic. As immunosuppression with conventional disease-modifying drugs and biologics has many associated risks, ranging from liver disease to chest and other infections, it is essential to balance the risks of co-morbidities against the anticipated benefits of treatment.
21607559 Serum levels of macrophage migration inhibitory factor are associated with rheumatoid arth 2012 Aug Rheumatoid arthritis (RA) is an inflammatory autoimmune disease of unknown etiology. Many cytokines have been found to be associated with RA pathogenesis and among them is macrophage migration inhibitory factor (MIF). The aim of this study was to determine whether MIF serum levels are associated with RA course, clinical activity, and clinical biomarkers of the disease. MIF levels were determined in serum samples of 54 RA patients and 78 healthy subjects (HS) by enzyme-linked immunosorbent assay (ELISA). Disease activity was evaluated using the DAS28 score. Patients were subgrouped according to disease activity and years of evolution of disease. Statistical analysis was carried out by SPSS 10.0 and GraphPad Prism 5 software. RA patients presented increased levels of MIF as compared to HS. MIF levels were raised on early stages of RA and tend to decrease according to years of evolution. Moreover, MIF levels positively correlated with rheumatoid factor in RA patients and with C reactive protein in all individuals studied. Our findings suggest that MIF plays a role in early stages of RA.
20919947 The presence of rheumatoid nodules at early rheumatoid arthritis diagnosis is a sign of ex 2011 Mar OBJECTIVE: Radiographic damage is an important outcome in rheumatoid arthritis (RA). The disease course varies considerably, and there is a need for simple and reliable prognostic markers. The aim of the study was to determine the utility of early signs of extra-articular disease, manifested as rheumatoid nodules (RN), in predicting radiographic outcome. METHODS: In a cohort (n = 1589) of consecutive, newly diagnosed patients with RA, 112 cases with RN at inclusion (7%) were identified. Each case was compared to two age- and sex-matched controls without nodules from the same cohort. Radiographs of the hands and feet were performed at inclusion, after 1, 2, and 5 years and scored according to the modified Sharp van der Heijde Score (SHS; range 0-448). RESULTS: Fifty-two cases with RN and 139 controls without RN had available radiographs at baseline and after 5 years. Cases were more often rheumatoid factor (RF) positive and anti-cyclic citrullinated peptide (anti-CCP) positive, and had higher disease activity and radiographic damage scores at baseline (7.9 vs. 2.5). After 5 years, there was more extensive radiographic damage among the cases (mean SHS progression 21.7 vs. 13.5). In bivariate analysis, positive RF, positive anti-CCP, SHS, and RN were strong baseline predictors for radiographic progression up to 5 years. In multivariate analysis, positive anti-CCP and SHS at baseline were independently associated with radiographic progression. CONCLUSION: The presence of RN at baseline is a marker of extra-articular involvement and severe disease, and a predictor of subsequent joint damage.
21303541 Diagnostic properties of metabolic perturbations in rheumatoid arthritis. 2011 Feb 8 INTRODUCTION: The aim of this study was to assess the feasibility of diagnosing early rheumatoid arthritis (RA) by measuring selected metabolic biomarkers. METHODS: We compared the metabolic profile of patients with RA with that of healthy controls and patients with psoriatic arthritis (PsoA). The metabolites were measured using two different chromatography-mass spectrometry platforms, thereby giving a broad overview of serum metabolites. The metabolic profiles of patient and control groups were compared using multivariate statistical analysis. The findings were validated in a follow-up study of RA patients and healthy volunteers. RESULTS: RA patients were diagnosed with a sensitivity of 93% and a specificity of 70% in a validation study using detection of 52 metabolites. Patients with RA or PsoA could be distinguished with a sensitivity of 90% and a specificity of 94%. Glyceric acid, D-ribofuranose and hypoxanthine were increased in RA patients, whereas histidine, threonic acid, methionine, cholesterol, asparagine and threonine were all decreased compared with healthy controls. CONCLUSIONS: Metabolite profiling (metabolomics) is a potentially useful technique for diagnosing RA. The predictive value was without regard to the presence of antibodies against cyclic citrullinated peptides.
22545356 Common carotid intima-media thickness in patients with late rheumatoid arthritis; what is 2011 Aug 15 This study aimed to evaluate color Doppler sonographic findings in carotid arteries in RA patients under pharmacological treatments and to compare them with normal population. Forty nine patients with late RA and 48 healthy age and sex-matched controls were recruited. The two groups were matched for other known risk factors of atherosclerosis including serum lipid abnormalities, smoking status, diabetes mellitus and hypertension. High resolution B-mode color Doppler ultrasound with a 7 MHZ transducer was used for measuring the Common Carotid Intima-Medial Thickness (CCIMT) in both sides in all subjects. Presence of atherosclerotic plaque was also investigated. The mean left and maximum CCIMT was significantly higher in the case group (0.72 vs. 0.62 mm for the left artery; p < 0.01; 0.72 vs. 0.64 mm for the maximum reading; p = 0.01). No atherosclerotic plaque was found in common carotid arteries. There were 3 (6.1), 7 (14.3) and 9 (18.4%) plaques in left internal carotid artery, right carotid bulb and left carotid bulb in the case group, respectively with no atherosclerotic plaques in the controls (p = 0.24, 0.01 and < 0.001, respectively). Comparing the findings by gender in the case group with the controls, the mentioned significant differences were only between the male patients and the controls. The process of atherosclerosis in RA patients is similar to that in normal population. However, it is apparently accelerated and more advanced in these patients.
21945064 Multiple rheumatoid bursal cysts that were finally effectively treated by combining surgic 2012 Feb A 71-year-old male who had been diagnosed with rheumatoid arthritis 3 years previously developed multiple subcutaneous cysts on his buttock, elbow, knee, hand and back. The diameters of the cysts were 10-15 cm. The characteristic fluid and pathology of the cysts led to the diagnosis of multiple rheumatoid bursal cyst (MRBC). The patient was keen to treat the cyst on his buttock as it hampered his sitting position. However, it resisted several kinds of sclerotherapies, including absolute alcohol, OK-432, minocycline and dexamethasone. When the cyst grew further, it was resected surgically; however, the cyst recurred immediately. It was finally brought under control by injecting it with OK-432. The thick cyst wall, which resisted the various sclerotherapies, was removed surgically, and a new capsule developed inside the cavity; adding a sclerotant to newly made thin capsule made us possible to treat this resistant large bursal cyst.
22040689 Declining needs for total joint replacements for rheumatoid arthritis. 2011 This millennium brings new views to rheumatology. Total joint replacement surgery is needed less often as active treatment strategies combined with availability of new medications has led to more effective rheumatoid arthritis control. This was beautifully shown in a recent issue of Arthritis Research & Therapy by a Swedish study that uses data from national registers and compares incidence rates for total hip and knee arthroplasties before and after the establishment of biologic agents use for rheumatoid arthritis.
23206619 Power Doppler ultrasonography for assessment of rheumatoid synovitis: comparison with dyna 2013 Jan PURPOSE: The aim of this study was to compare the effectiveness of power Doppler ultrasonography (PDUS) with that of dynamic magnetic resonance imaging (MRI) for detecting active synovitis in the hands of rheumatoid arthritis (RA) patients. MATERIALS AND METHODS: PDUS and dynamic MRI were performed for a total of 220 finger joints with active RA. Each synovial blood flow by PDUS and dynamic MRI was measured and categorized into four grades. RESULTS: Taking dynamic MRI as a reference, PDUS showed a sensitivity of 94%, a specificity of 95%, and an accuracy of 95%. CONCLUSION: PDUS is useful for detection of active synovitis in the overall-grade RA patients.
22113596 ACPA (anti-citrullinated protein antibodies) and rheumatoid arthritis. 2011 Jul It has recently been discovered that anti-citrullinated protein antibodies (ACPA) are present in 50% of patients with early rheumatoid arthritis (RA). Assays for detecting ACPA have been shown to have very good diagnostic and predictive characteristics, and they may facilitate the identification of patients with early arthritis who need aggressive treatment. In addition to their diagnostic and predictive properties, ACPA have also provided new insights into the pathophysiology of RA. The specific association of certain genetic and environmental risk factors with ACPA-positive but not with ACPA-negative RA, has led to new concepts of the underlying pathogenetic mechanisms. The fact that ACPA-positive patients have a more severe disease course with greater joint destruction has also fueled the hypothesis that ACPA themselves may be pathogenic. Although there is no direct proof for this intriguing theory so far, it is clear that ACPA allow the classification of RA patients into two different disease subsets that are associated with distinct pathophysiological mechanisms and clinical outcomes. Rheumatoid arthritis (RA) is a chronic, potentially destructive, arthritis which has a large impact on patients' quality of life(1). It has become clear that in order to be able to prevent disease progression and joint destruction, RA needs to be diagnosed early, which requires diagnostic markers which can reliably predict disease development and progression(2). Some of the most attractive diagnostic markers are autoantibodies. Rheumatoid factor (RF) has long been known to be a marker of future RA development(3), but more recently, a better diagnostic and predictive marker has emerged in the form of anti-citrullinated protein antibodies (ACPA).
21267731 [Pharmacogenetics and pharmacogenomics of methotrexate. Current status and novel aspects]. 2011 Feb Since its introduction as a disease-modifying drug, methotrexate (MTX), a folate antagonist, is regarded as a major pillar of anti-rheumatic pharmacotherapy. This has not been changed in the current era of biologicals based on recombinant proteins. Despite most promising therapeutic progress about half of rheumatoid arthritis patients still display insufficient response to anti-rheumatic drugs. Specifically, about one in four patients on MTX shows lack of sufficient therapeutic efficacy which may lead to drug discontinuation. In addition, adjustment of therapy may be necessary due to individual drug toxicity. In this context and in light of recent advances concerning the use of genetic analysis in clinical practice, the development of novel strategies which implement individualized pharmacotherapy has become a major issue for translational and clinical research. Accordingly, numerous studies have been performed in recent years analyzing genetic polymorphisms of cellular parameters which relate to MTX efficacy and toxicity. Data currently available demonstrate the potential and the limitations of clinical genetic polymorphism analyses.