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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
20658831 Interplay of concurrent positive and negative interpersonal events in the prediction of da 2010 Jul OBJECTIVE: The purpose of this study was to examine the interaction of daily concurrent positive interpersonal events (PIE) and negative interpersonal events (NIE) on the daily experience of negative affect and fatigue in a sample of men and women with rheumatoid arthritis. Two hypotheses were made. The blunting hypothesis predicted that NIE would nullify the beneficial influence of PIE on outcome measures, and the buffering hypothesis predicted that PIE would offset the adverse influence of NIE. DESIGN: Participants completed up to 30 consecutive daily diaries. Multilevel modeling was used to examine the day-to-day dependencies among study variables. MAIN OUTCOME MEASURES: The primary outcomes were daily negative affect and fatigue. RESULTS: In support of the blunting hypothesis, on days when NIE were diminished, PIE were associated with a greater reduction in fatigue. In contrast, consistent with the buffering hypothesis, on days when PIE were elevated, NIE were associated with a lesser increase in negative affect. CONCLUSION: The examination of concurrent PIE and NIE provides a unique perspective on the role of interpersonal events in affective and physiological outcomes, beyond that which can be gained from the examination of either type of event in isolation.
19321515 Advance and unmet need of health care for patients with rheumatoid arthritis in the German 2009 Jun OBJECTIVES: To assess the quality of health care for RA patients in the general population of Germany. METHODS: A three-stage population survey was conducted to identify individuals with RA using a health care access panel (18-79 years; n = 70,112). A 20-item postal screening questionnaire of musculoskeletal symptoms and diagnoses was followed by a detailed questionnaire for those who indicated the possibility of having RA. Respondents who fulfilled the modified ACR decision tree, who reported an RA diagnosis, care by a rheumatologist or the use of DMARDs were asked to participate in a clinical examination by rheumatologists who diagnosed the participants and rated the adequacy of treatment. RESULTS: RA could not be ruled out in 1177 cases, of which 643 agreed to participate in the clinical examination, which was finally attended by 317 participants. Attendees did not differ with regard to any health or treatment measure from those who did not attend. Forty-one RA patients were detected. Of them, 93% had seen a rheumatologist at least once and 63% within the last 12 months. A total of 73% had received DMARD therapy at some time and 59% were currently receiving it. An unmet need for DMARDs was discovered in 29% of the RA attendees. It pertained almost exclusively to the seronegative cases of which 29% had a need to start and 17% to increase a DMARD therapy according to the opinion of the examining rheumatologist. CONCLUSION: Health care for RA patients has improved significantly since the last German RA survey in 1989. However, DMARD prescription still does not meet clinical recommendations, specifically in RF-negative patients. Since seronegative RA is a treatable disease, this group should not be overlooked.
18685882 Infrared sauna in patients with rheumatoid arthritis and ankylosing spondylitis. A pilot s 2009 Jan To study the effects of infrared (IR) Sauna, a form of total-body hyperthermia in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients were treated for a 4-week period with a series of eight IR treatments. Seventeen RA patients and 17 AS patients were studied. IR was well tolerated, and no adverse effects were reported, no exacerbation of disease. Pain and stiffness decreased clinically, and improvements were statistically significant (p < 0.05 and p < 0.001 in RA and AS patients, respectively) during an IR session. Fatigue also decreased. Both RA and AS patients felt comfortable on average during and especially after treatment. In the RA and AS patients, pain, stiffness, and fatigue also showed clinical improvements during the 4-week treatment period, but these did not reach statistical significance. No relevant changes in disease activity scores were found, indicating no exacerbation of disease activity. In conclusion, infrared treatment has statistically significant short-term beneficial effects and clinically relevant period effects during treatment in RA and AS patients without enhancing disease activity. IR has good tolerability and no adverse effects.
19026580 Visceral leishmaniasis in a rheumatoid arthritis patient treated with methotrexate. 2009 Jul Visceral leishmaniasis (VL) is a relatively rare occurrence in rheumatoid arthritis (RA) patients treated with tumor necrosis factor-alpha (TNF-alpha) antagonists, corticosteroids and methotrexate, or methotrexate alone. A review of the literature revealed that only one case of VL in an RA patient treated with methotrexate has been previously published. We describe an additional case, that of a 65-year-old female with RA being treated with methotrexate, who presented with fever, abdominal discomfort, splenomegaly and pancytopenia. A diagnosis of VL was ultimately established, after a splenectomy was performed. Because RA is characterized by immune cell dysfunction and dysregulation, which potentially predisposes patients to infection, it is unclear whether this serious opportunistic infection can be solely attributable to the methotrexate, an immunosuppressive medication that also increases the risk of infection.
20480164 A fatal case of acute exacerbation of interstitial lung disease in a patient with rheumato 2012 Dec A 68-year-old man, who was a patient with established rheumatoid arthritis (RA) with RA-associated interstitial lung disease (RA-ILD) and pulmonary emphysema, began taking tocilizumab. Subsequently, he developed dyspnea parallel to improvement of RA. At 10 months after the administration of tocilizumab, he was urgently admitted because of exacerbation of ILD. He died despite receiving steroid pulse therapy and antibiotic therapy on a respirator. This is the first case report to describe the exacerbation of ILD during treatment with tocilizumab in the postmarketing surveillance (PMS) period.
20722245 Rheumatoid arthritis in elderly patients. 2009 Sep Rheumatoid arthritis (RA) in the geriatric population presents a unique challenge to treating clinicians. It can present as preexisting disease that may have been present for years or as a de novo onset of the illness. Diagnosis and management requires a detailed knowledge of the disease, its differential diagnoses, and the therapeutic options. A number of other diseases can mimic the illness and must be thoroughly evaluated to avoid serious consequences. New agents to treat RA are available that have shown promise in clinical trials and practice. Aggressive RA treatment should not be withheld in the geriatric population just because of advanced age, rather, treatment should be individualized, especially considering comorbidities and other factors that can specifically affect a patient's quality of life. Coordination of care among geriatricians and rheumatologists is the key to achieving optimal outcome.
18495732 Clinical significance of synovial lymphoid neogenesis and its reversal after anti-tumour n 2009 May OBJECTIVE: To investigate the clinical significance of lymphoid neogenesis (LN) in rheumatoid arthritis (RA), the clinicopathological correlates of this process and its evolution after anti-tumour necrosis factor (TNF)alpha therapy in a large series of synovial tissues were analysed. METHODS: Arthroscopic synovial biopsies from 86 patients with RA were analysed by immunohistochemistry. LN was defined as the presence of large aggregates of lymphocytes with T/B cell compartmentalisation and peripheral node addressin (PNAd) positive high endothelial venules. Clinical variables at baseline and after prospective follow-up were compared in LN positive and negative RA subsets. The evolution of LN and its correlation with the clinical course in a subgroup of 24 patients that underwent a second arthroscopic biopsy after anti-TNFalpha therapy was also analysed. RESULTS: LN was present in 49% of RA synovial tissues. Patients with LN had a significantly higher disease duration and a higher previous use of anti-TNFalpha agents. During prospective follow-up, the proportion of patients achieving good or moderate European League Against Rheumatism (EULAR) 28-joint Disease Activity Score (DAS28) responses was significantly lower in patients who were LN positive despite a significantly higher use of anti-TNFalpha agents. By multivariate logistic regression analysis, LN remained as an independent negative predictor of response to therapy. In the subgroup of patients rebiopsied after anti-TNFalpha therapy, reversal of LN features occurred in 56% of the patients and correlated with good clinical responses. CONCLUSIONS: Synovial LN in RA predicts a lower response to therapy. LN features can be reversed after a short period of anti-TNFalpha therapy in parallel to good clinical responses.
20170034 [Rheumatoid arthritis and ankylosing spondylitis-rheumatologic highlights 2009]. 2010 Jan 20 In this year rheumatology highlights, we will especially note a new treatment, the tocilizumab, an interleukin-6 targeting therapy, effective and adequately safe for the treatment of rheumatoid arthritis. New classification criteria for axial spondylarthropathy have also been published, criteria that should facilitate earlier diagnosis, a diagnosis that should be pursue like a diagnosis of rheumatoid arthritis even in the absence of an inflammatory biological syndrome.
19886117 Rheumatoid hands. 2009 Oct Rheumatoid hands are a common clinical finding and subject for post graduate exams. The following explores some of its more unusual cases.
21167010 Are Th17 cells an appropriate new target in the treatment of rheumatoid arthritis? 2010 Dec Th17 cells play crucial roles not only in host defense but also in many human autoimmune diseases and corresponding animal models. Although many of the fundamental principles regarding Th17 biology have been rapidly elucidated in mice, there remain numerous controversies regarding the differentiation, plasticity, and pathogenicity of human Th17 cells. In this review, we consider these open questions in comparison to what has already been clarified in mice, and discuss the potential impact of discoveries related to the Th17 pathway on the development of new therapeutic strategies in Th17 driven autoimmune diseases, specifically rheumatoid arthritis.
20701312 1H NMR spectroscopy-based interventional metabolic phenotyping: a cohort study of rheumato 2010 Sep 3 1H NMR spectroscopy-based metabolic phenotyping was used to identify biomarkers in the plasma of patients with rheumatoid arthritis (RA). Forty-seven patients with RA (23 with active disease at baseline and 24 in remission) and 51 healthy subjects were evaluated during a one-year follow-up with assessments of disease activity (DAS-28) and 1H NMR spectroscopy of plasma samples. Discriminant analysis provided evidence that the metabolic profiles predicted disease severity. Cholesterol, lactate, acetylated glycoprotein, and lipid signatures were found to be candidate biomarkers for disease severity. The results also supported the link between RA and coronary artery disease. Repeated assessment using mixed linear models showed that the predictors obtained from metabolic profiles of plasma at baseline from patients with active RA were significantly different from those of patients in remission (P=0.0007). However, after 31 days of optimized therapy, the two patient groups were not significantly different (P=0.91). The metabolic profiles of both groups of RA patients were different from the healthy subjects. 1H NMR-based metabolic phenotyping of plasma samples in patients with RA is well suited for discovery of biomarkers and may be a potential approach for disease monitoring and personalized medication for RA therapy.
18688673 Positiveness of purified protein derivatives in rheumatoid arthritis patients who are not 2009 Jan In recent years, biological agents have emerged as the most popular drugs for the treatment of rheumatoid arthritis (RA). The most frightening side effects of biological agents are infections, with tuberculosis being the leader. On account of the fact that biological agents have been used widespread, a number of algorithms have been developed to search latent tuberculosis. Among these algorithms, the most popular is the purified protein derivatives (PPD) test which is based upon late sensitivity reaction. The objective of this trial is to investigate the relevance of PPD response for the disease in RA patients. A total of 149 subjects (80 patients, 69 healthy), 35 RA patients who have not been treated before, 23 RA and 22 AS patients who are candidates for biological agents and being treated with immunosuppressive drugs, and 69 healthy subjects, have been included in this trial. Swelling joints, number of tender joints, visual analog scale, erythrocyte sedimentation rate, C-reactive protein, and rheumatoid factor were recorded. PPD was performed using the Mantoux method and was measured 72 h later. Statistically significant lower PPD values were determined in untreated RA patients compared to PPD values of treated RA and AS patients and healthy subjects. No correlation was determined between disease activity score 28 activity and PPD values in untreated and treated groups. Similarly, there was no correlation between acute phase reactants and PPD. Lower PPD responses in patients not being treated with immunosuppressive are due to the disease itself, rather than to the drugs being used. It is also important to interpret PPD results in early RA patients with suspicion, when it is intended to start anti tumor necrosis factor therapy.
19376737 Double extensor pollicis longus tendon in independent extensor compartments: a case report 2009 Jun The authors report the case of an anatomical variation with a double extensor pollicis longus tendon found during a dorsal approach to the wrist for rheumatoid arthritis. The accessory tendon was located in an additional separate wrist dorsal compartment, which is an extremely rare arrangement.
20059781 Cost-effectiveness of real-world infliximab use in patients with rheumatoid arthritis in S 2010 Jan OBJECTIVES: The objective of this study was to estimate the cost-effectiveness of infliximab use in patients with rheumatoid arthritis (RA) in Swedish clinical practice, based on patient-level data from the Stockholm TNF-alpha follow-up registry (STURE). METHODS: Real-world patient-level data on infliximab use from the STURE registry were implemented in a Markov cohort model, in which health states of functional status were classified according to the Health Assessment Questionnaire Disability Index (HAQ-five categories) and twenty-eight joint count Disease Activity Score (DAS28). The transition probabilities between HAQ and DAS28 states during treatment, as well as discontinuation rates were modeled based on data from the registry for patients using infliximab as their first-line biological treatment. The transition probabilities in the comparator arm, that is, disease progression without biologic treatment, as well as mortality rates, costs, and utilities were based on published literature. The analysis had a societal cost perspective. RESULTS: Infliximab was associated with an incremental gain in quality-adjusted life-years of 1.02 and an incremental cost of 23,264 euros per patient compared with progression without biologic treatment, producing an incremental cost-effectiveness ratio (ICER) of 22,830 euros (SEK211,136 or US$31,230). Sensitivity analyses of input parameters and model assumptions produced ICERs in the range from 18,000 euros to 47,000 euros. CONCLUSIONS: Results from base-case and sensitivity analyses fell well below established benchmarks for cost-effectiveness in Sweden. The results, therefore, indicated that infliximab treatment for RA has provided good societal value for money in Swedish clinical practice, compared with a scenario of no biological treatment.
19843752 Rheumatoid arthritis and tuberculous arthritis: differentiating MRI features. 2009 Nov OBJECTIVE: The purpose of our study was to determine the MRI findings of rheumatoid arthritis (RA) and tuberculous arthritis, with emphasis on differential diagnostic features. MATERIALS AND METHODS: MR images of 63 joints in 62 patients with clinically or pathologically proven RA (36 joints in 35 patients) or tuberculous arthritis (27 joints in 27 patients) were evaluated retrospectively with regard to pattern and degree of synovial thickening, size of bone erosions, rim enhancement at bone erosions, degree of bone marrow and periarticular soft-tissue edema, and presence and number of extraarticular cystic masses. MRI findings were compared between RA and tuberculous arthritis by statistical analysis using kappa statistics, the Mann-Whitney U test, linear-by-linear association, and the chi-square test. RESULTS: Nonuniform and greater degree of synovial thickening was more frequent in RA (p < 0.01); the thicker the synovial membrane, the greater the likelihood of RA (p < 0.01). Bone erosions of tuberculous arthritis were larger (p < 0.01), and the likelihood of tuberculous arthritis increased proportionally to the increment of size of the bone erosions (p < 0.01). Rim enhancement at bone erosion was more frequent in tuberculous arthritis (p < 0.01). Extraarticular cystic masses were more frequently seen and more numerous in tuberculous arthritis (p < 0.01). CONCLUSION: Uniform synovial thickening, large size of bone erosion, rim enhancement at site of bone erosion, and extraarticular cystic masses were more frequent and more numerous in tuberculous arthritis. MRI may be helpful in the differentiation between RA and tuberculous arthritis.
21261114 [Activity of the hypothalamic-pituitary-adrenal axis in patients with rheumatoid arthritis 2010 Dec The controlled data accumulated so far support only subtle alterations in hypothalamic-pituitary-adrenal (HPA) axis function in rheumatoid arthritis (RA), mainly at the adrenal level, and particularly in a subset of premenopausal onset women. Consequences of the subtle HPA alterations in RA for the disease development remain unclear. From a broader perspective, the unresponsiveness of the HPA axis to chronic inflammation in RA can be simply considered an ongoing adaptation to chronic disease.
19723995 Three-dimensional kinematics of the rheumatoid wrist after partial arthrodesis. 2009 Sep BACKGROUND: Partial arthrodesis of the wrist, such as radiolunate and radioscapholunate arthrodesis, is intuitively more appealing for the treatment of the rheumatoid wrist than total arthrodesis is because it preserves some motion. However, wrist kinematics after partial arthrodesis are incompletely understood. The purpose of the present study was to evaluate the kinematics of the radiocarpal and midcarpal joints of rheumatoid wrists with use of three-dimensional computed tomography before and after partial arthrodesis. METHODS: We selected ten wrists that were affected by rheumatoid arthritis in which the radiolunate joint was severely damaged but the midcarpal joint congruities were relatively well preserved. Six radiolunate and four radioscapholunate arthrodeses were then performed, with preservation of the joint congruity between the scaphoid, lunate, and capitate. We acquired in vivo three-dimensional kinematic data during wrist flexion-extension preoperatively and postoperatively with use of computed tomography and a markerless bone-registration technique. Postoperative midcarpal joint congruity and range of motion were compared with preoperative values. RESULTS: The mean range of global wrist motion was 48 degrees +/- 21 degrees after radiolunate arthrodesis and 47 degrees +/- 14 degrees after radioscapholunate arthrodesis. Midcarpal joint congruities and motion between the scaphoid, lunate, and capitate were well preserved in all ten wrists. The postoperative range of capitate motion relative to the lunate was 109% of the preoperative value after radiolunate arthrodesis and 88% after radioscapholunate arthrodesis. The directions of capitate motion relative to the lunate after both types of partial arthrodesis were significantly more oblique than before the arthrodeses, changing from radiodorsal to ulnopalmar along the so-called dart-throwing motion plane (p < 0.05). CONCLUSIONS: The results of this kinematic analysis, which showed that midcarpal motion occurred in the dart-throwing motion plane, may support the use of radiolunate and radioscapholunate arthrodeses as an alternative to total wrist arthrodesis in patients with symptomatic rheumatoid arthritis of the wrist.
20214567 Hypoxia-inducible factor-1 as regulator of angiogenesis in rheumatoid arthritis - therapeu 2010 Angiogenesis plays an important role in the pathogenesis of inflammatory diseases, including rheumatoid arthritis (RA). The site and extent of inflammation and subsequent joint destruction in the rheumatoid synovium is dependent on the development of new vasculature. Inhibition of angiogenesis, extensively studied in cancer, might therefore be of interest as treatment option for RA. Hypoxia-inducible factor-1 (HIF-1) has been reported to play a critical role in the regulation of hypoxia driven angiogenesis. HIF-1 is a transcription factor that is constitutively expressed in many cells. It gains transcriptional activity in hypoxic cells leading to the expression of genes involved in angiogenesis. The synovium is hypoxic, but also in an inflammatory environment such as seen in RA, inflammatory cytokines may be important inducers of HIF-1 expression and/or activation. Many drugs currently used in the treatment of RA have anti-angiogenic effects, which are exerted at different levels. Blocking of TNF-alpha, for instance, reduces TNF-alpha induced VEGF production. Studies aiming at direct inhibition of pro-angiogenic factors, such as inhibiting VEGF- or FGF-receptor signalling or blocking VEGF by monoclonal anti-VEGF antibody therapeutics, are in progress. Inhibition of HIF-1 expression or activation, either by blocking signal transduction pathways leading to HIF-1 induction or by inhibiting accumulation of HIF -1 protein, represents a new strategy, which is of interest for the treatment of RA. This review will concisely summarize the general knowledge on the molecular control of gene expression by HIF-1, its involvement in RA, and potential for therapeutic intervention at the level of HIF-1 activity.
19858780 Gene-gene interactions in folate and adenosine biosynthesis pathways affect methotrexate e 2009 Dec OBJECTIVE: As no single nucleotide polymorphism has emerged as pivotal to predict the lack of efficacy and dose-limiting toxicities to methotrexate (MTX), we evaluated the contribution of gene-gene interactions to the effects of this prodrug in rheumatoid arthritis. METHODS: A total of 255 patients treated with MTX for at least 3 months were evaluated with efficacy assessed using the European League Against Rheumatism response criteria or a physician's assessment of patient's response to MTX visual analog scale. Gastrointestinal and neurological idiosyncrasies were recorded in 158 patients. Fourteen single nucleotide polymorphisms in folate and adenosine biosynthesis pathways were measured and detection of gene-gene interactions was performed using multifactor-dimensionality reduction, a method that reduces high-dimensional genetic data into a single dimension of predisposing or risk-genotype combinations. RESULTS: Efficacy to MTX (53% responders) was associated with high-order epistasis among variants in inosine-triphosphate pyrophosphatase, aminoimidazole-carboxamide ribonucleotide transformylase, and reduced folate carrier genes. In the absence of predisposing genotype combinations, a 3.8-fold lower likelihood of efficacy was observed (vs. in their presence, 95% confidence interval: 2.2-6.4; P<0.001). Increasing MTX polyglutamate concentrations tended to partially overcome this selective disadvantage. Idiosyncrasies occurred in 29% of patients. In the presence of risk-genotype combinations among variants in methylene tetrahydrofolate reductase, γ-glutamyl-hydrolase, thymidylate synthase, serine hydroxymethyltransferase, and inosine-triphosphate pyrophosphatase genes, an 8.9-fold higher likelihood to exhibit toxicities was observed (vs. in their absence, 95% confidence interval: 3.6-21.9; P<0.001). False-positive report probabilities were below 0.2, thereby indicating that true signals were likely detected in this cohort. CONCLUSION: These data indicate that gene-gene interactions impact MTX efficacy and tolerability in rheumatoid arthritis.
19638703 [Biochemical markers of bone turnover. New aspect. Therapy of rheumatoid arthritis for bon 2009 Aug Rheumatoid arthritis (RA) is characterized by inflammatory synovitis, erosive arthritis and joint destruction. Recent evidence indicates that inflammatory cytokines such as TNF-alphaor IL-6 plays a pathological role in joint destruction and osteoporosis and that anti-cytokine therapy provides significant protection against the process. In this article, we described our findings that TNF-alphablocking therapy decreased urinary crosslinked N-telopeptide of type I collagen and increased serum bone alkaline phosphatase in RA patients.