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ID PMID Title PublicationDate abstract
20737189 Dystrophic calcinosis in a patient with rheumatoid arthritis. 2011 Feb We report a rare case of dystrophic calcinosis in a patient with rheumatoid arthritis in bilateral buttock lesions and the right elbow joint. The calcinosis was surgically removed because it caused severe local pain, possible infection, and difficulty in sitting. Because no recommended standard pharmacotherapy exists for dystrophic calcinosis, surgical treatment should be taken into consideration when calcinosis causes severe local pain or restricts activities of daily life.
21338325 Smoking at onset of rheumatoid arthritis (RA) and its effect on disease activity and funct 2011 OBJECTIVES: To assess the effects of smoking on disease outcome in a large cohort of patients with early rheumatoid arthritis (RA). METHODS: Between 1996 and 2004, 1787 adult patients (disease duration ≤ 1 year) were included in the BARFOT early RA study in Sweden. Smoking status was recorded at inclusion in the study. Disease Activity Score using 28 joint counts (DAS28), C-reactive protein (CRP), Health Assessment Questionnaire (HAQ) score, rheumatoid factor (RF), antibodies to cyclic citrullinated peptide (anti-CCP), general health (GH) and pain visual analogue scales (VAS), and drug treatment were registered at inclusion and at follow-up at 3, 6, and 12 months. European League Against Rheumatism (EULAR) response and remission criteria were applied at 3, 6, and 12 months. RESULTS: The proportion of patients who smoked at inclusion in the study fell from 29% in 1996 to 20% in 2004. There were no significant differences in disease activity at inclusion stratified according to smoking status. At 12 months of follow-up, 18% of current smokers at inclusion, 12% of previous smokers, and 11% of never smokers had high disease activity (DAS28 > 5.1, p = 0.005). Significantly fewer current smokers were in remission at 12 months (33%) compared to never smokers (36%) and previous smokers (42%) (p = 0.013). Current smoking at inclusion independently predicted poor EULAR response up to 12 months of follow-up. CONCLUSION: The present study gives some support to earlier data indicating that RA patients who smoke have a more active disease but further studies are needed to confirm this.
22647255 Midlife rheumatoid arthritis increases the risk of cognitive impairment two decades later: 2012 Inflammation has been associated with Alzheimer's disease (AD) and dementia. The association between rheumatoid arthritis (RA) or arthritis and dementia/AD has been investigated in several case-control or hospital- and register-based studies with mixed results. This long-term population-based study investigates the association between presence of joint disorders (RA and other joint disorders) in midlife and cognitive status later in life. 1,449 participants were first evaluated in 1972, 1977, 1982, and 1987 and follow-up was performed after 21 years. A self-administered questionnaire including questions on joint disorders was used at both evaluations. Cognitive status (control, mild cognitive impairment, dementia/AD) was assessed at follow-up. The presence of any joint disorder in midlife was significantly associated with a worse cognitive status later in life: OR (95% CI) in an ordinal logistic regression analysis adjusted for age, gender, follow-up time, education, APOEε4, body mass index, smoking, drug treatment, and diabetes was 1.96 (1.17-3.28). For RA only, OR (95% CI) was 2.77 (1.26-6.10). The correlation remained significant for RA when AD was considered instead of dementia OR (95% CI) 2.49 (1.09-5.67). The presence of joint disorders, especially RA, at midlife seems to be associated with a worse cognitive status later in life. Given the chronic inflammatory component of RA, this study suggests that inflammatory mechanisms may have an important role in increasing the risk of cognitive impairment and dementia/AD.
21298627 Metal-on-metal hip resurfacing in rheumatoid patients. A report on thirteen hips with mini 2011 Jan Rheumatoid disease can be extremely debilitating due to progressive joint destruction and multiple joint involvement. While there are varying results for THR in patients with RA, there is only one report of metal-on-metal resurfacing for rheumatoid patients with hip arthritis. We present preoperative and latest follow-up UCLA scores, SF-12 scores, HHS and range of motion in a series of 13 hips (10 patients). The patients experienced no complications associated with their resurfacing procedure and there have been no failures 3 to 13 years after surgery. Our results show that rheumatoid arthritis patients with hip involvement treated with metal-on-metal resurfacing can have extremely good outcomes.
22941259 Association between vitamin D intake and the risk of rheumatoid arthritis: a meta-analysis 2012 Dec The aim of this study was to summarize published results on the association between vitamin D intake and the development of rheumatoid arthritis (RA) and between serum vitamin D levels and RA activity. Evidence of a relationship between vitamin D intake and the development of RA and between serum vitamin D levels and RA activity was studied by summarizing published results using a meta-analysis approach. Three cohort studies including 215,757 participants and 874 incident cases of RA were considered in this meta-analysis, and eight studies on the association between serum vitamin D levels and RA activity involving 2,885 RA patients and 1,084 controls were included. Meta-analysis showed an association between total vitamin D intake and RA incidence (relative risk (RR) of the highest vs. the lowest group = 0.758, 95 % confidence interval (CI) 0.577-0.937, p = 0.047), without between-study heterogeneity (I(2) = 0 %, p = 0.595). Individuals in the highest group for total vitamin D intake were found to have a 24.2 % lower risk of developing RA than those in the lowest group. Subgroup meta-analysis also showed a significant association between vitamin D supplement intake and RA incidence (RR 0.764, 95 % CI 0.628-0.930, p = 0.007), without between-study heterogeneity. All studies, except for one, found that vitamin D levels are inversely associated with RA activity. One study found no correlation between vitamin D levels and disease activity among 85 RA patients, but these patients had a high incidence of vitamin D deficiency, which might have influenced the study outcome. Meta-analysis of 215,757 participants suggests that low vitamin D intake is associated with an elevated risk of RA development. Furthermore, available evidence indicates that vitamin D level is associated with RA activity.
22577832 Association study of MIA3 rs17465637 polymorphism with cardiovascular disease in rheumatoi 2012 Aug Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis. Melanoma inhibitor protein 3 (MIA3) is required for the export of collagen VlI (COL7A1) from the endoplasmic reticulum and it appears to be a tumor suppressor of malignant melanoma. Genome-wide association studies have described an association between MIA3 rs17465637 A/C polymorphisms and coronary artery disease and myocardial infarction. Because of that, we assessed the MIA3 rs17465637 polymorphism in 1505 RA Spanish patients stratified according to the presence/absence of cardiovascular (CV) disease. Also, a subgroup of patients without CV events was assessed for the presence of subclinical atherosclerosis using carotid ultrasound to establish carotid intima-media wall thickness and carotid plaques and brachial ultrasonography to determine the presence of endothelial dysfunction by flow-mediated endothelium-dependent and independent vasodilatation. MIA3 rs17465637 allele A showed a trend for association with the presence of carotid plaques (odds ratio 1.56, 95% confidence interval [0.96-2.51]; p=0.07). However, apart from an association of the MIA3 rs17465637 A allele with the risk of CV events in RA patients with dyslipidemia (p=0.018), no other significant associations were found between the presence of MIA3 rs17465637 A allele and the risk of suffering CV events or other surrogate markers of atherosclerosis. In conclusion, our results suggest a potential association of the MIA3 rs17465637 with CV disease in dyslipidemic patients with RA. However, additional studies are required to better establish the role of the MIA3 gene in mechanisms leading to the accelerated atherogenesis observed in RA.
22473817 Norisoboldine inhibits the production of interleukin-6 in fibroblast-like synoviocytes fro 2012 Aug Interleukin-6 (IL-6) is a pleiotropic cytokine secreted by macrophages and others and it has been proven to be a potential therapeutic target of RA. Norisoboldine (NOR) is the main isoquinoline alkaloid constituent in the dry roots of Lindera aggregata (Sims) Kosterm. (L. strychnifolia Vill.), which has long been used in traditional Chinese medicine for treating RA and other diseases. Our previous studies indicated that NOR was able to attenuate inflammation and joint destruction in collagen II-induced arthritis of mice. To further recognize the anti-rheumatoid potentials of NOR, the present study addressed whether and how NOR interfered with IL-6 production from fibroblast-like synoviocytes (FLS), key effector cells in the development and progression of RA. FLS, obtained from the synovial tissues of rats with adjuvant arthritis, showed incremental release of IL-6 after stimulated with IL-1β in vitro. NOR (10, 30, and 60 µM) could reduce the production of IL-6 in a concentration-dependent manner. It also down-regulated the phosphorylations of mitogen-activated protein kinases (MAPKs), protein kinase C (PKC), and transcriptional factor nuclear factor-κB (NF-κB)-p65 (ser 276) as well as cAMP response element-binding protein (CREB) in FLS. By using specific inhibitors, PKC was shown to be the upstream protein of MAPKs, and p38 MAPK was at the upstream of CREB. It was concluded that preventing IL-6 release from FLS might be an important mechanism for NOR displaying anti-RA property, and the action of NOR was relative to inhibition of PKC/MAPKs/p65/CREB pathways.
22963664 Emerging concepts on inhibitors of indoleamine 2,3-dioxygenase in rheumatic diseases. 2012 The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) finely regulates both innate and adaptive immune responses through the degradation of the essential amino acid tryptophan into kynurenine and other downstream metabolites, which suppress effector T-cell function and promote the differentiation of regulatory T cells. A novel role for IDO1 as a signaling molecule and a modifier of innate inflammatory responses is now emerging. In particular, IDO1 can either support or antagonize inflammation in a context- and tissuedependent manner. Studies in experimental arthritis have unravelled a previously unappreciated role for IDO in controlling B-cell activation and autoantibody production. IDO dysregulation has been documented in patients with systemic lupus erythematosus, systemic sclerosis and Sjogren's syndrome, as well as in severe sepsis and chronic kidney disease. This article summarizes the contribution of IDO to the pathophysiology of inflammatory/autoimmune disorders, and discusses whether strategies to restore metabolic equilibrium in the kynurenine pathway might be pursued in diseases states such as rheumatoid arthritis and systemic sclerosis.
23007740 Emerging optical and nuclear medicine imaging methods in rheumatoid arthritis. 2012 Dec Molecular and multimodal imaging procedures that complement the use of existing anatomical modalities for the diagnosis and monitoring of rheumatoid arthritis (RA) have undergone substantial developmental advances. These techniques have the potential to greatly improve the management of patients with RA through early diagnosis and maximization of the newly available opportunities for early therapeutic intervention. Quantitative, noninvasive monitoring of biomarkers of the molecular events induced during the onset of RA could be used to guide the initial selection of therapy and for assessment of early therapeutic responses. Biomolecular imaging techniques that can reveal the pathophysiological features of RA--including infrared thermography, near-infrared molecular imaging, and PET--are being used to investigate the earliest cellular and biochemical inflammatory events in the development of the disease. Noninvasive imaging of abnormal specific molecular events in early RA could enable early targeted intervention that could be tailored to optimize patient responses before destructive anatomical changes occur. In this Review, we summarize new advances in biomolecular imaging techniques, with an emphasis on their current state of development in terms of the management of RA.
20955151 Natural products triggering biological targets--a review of the anti-inflammatory phytoche 2011 Mar 1 Inflammation is a natural response of living organisms to the presence of internal and external substances which are recognized by the host as being "non-self" or "foreign invader". It is also a cascade leading to the healing of damaged tissue. Uncontrolled inflammation often results in chronic diseases such as arthritis, autoimmune disorder, cancer, dementia, diabetic, neurodegeneration and vascular disease. The list keeps growing due to the increasing numbers of identified molecular markers that are associated with inflammatory genes or transcription factors. Among various transcription factors, nuclear factor kappa B (NF-kB) is the master switch for proinflammatory genes and transactivates arachidonic acid pathway enzymes when activated. Through evolution, plants have developed vast classes of compounds to fight inflammation. Most of them belong to the chemical group of alkaloids, coumarins, flavonoids, polyphenols and terpenoids. This review article presents and discusses results obtained from literature search on recent findings in plant-derived compounds, which exhibit anti-inflammatory activity in rheumatoid arthritis, allergy and asthma via the suppression of the arachidonic acid pathway. IC(50)s of the compounds obtained from the literature are thus tabulated into six groups of inhibitors based on the enzyme target of phospholipase A2, cyclooxygenase 1 and 2, 5-, 12- and 15-lipoxygenase. Modulation of Th1/Th2 cytokines and histamine/mucus release by some of these enzyme inhibitors are also briefly discussed.
22352108 Presentation of tuberculosis as isolated massive pericardial effusion in a patient with rh 2012 Jan The case of a 60 year old male patient, diagnosed with rheumatoid arthritis presenting with recurrent massive pericardial effusion, and unresponsive to treatment of rheumatoid arthritis is documented. Pericardial biopsy proved Tuberculous pericarditis with positive fluid culture for Mycobacterium Tuberculosis. Anti-tuberculous treatment was started along with corticosteroids. Follow up after three months showed no evidence of pericardial effusion.
21222645 Cytokines as therapeutic targets to reduce cardiovascular risk in chronic inflammation. 2011 Patients with chronic inflammatory diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus, psoriasis and Crohn's disease have an increased atherosclerotic risk which cannot be explained by traditional cardiovascular risk factors alone. Inflammatory pathways are implicated in this increased vascular risk. The involvement of cytokine-related signaling pathways in inflammatory diseases has prompted the development of many therapeutic strategies aimed at their modulation to limit disease severity and progression. Whether modulation of these pathways would similarly alter the inflammatory processes related to accelerated atherosclerosis remains unknown. In this review we will focus on the role of pro-inflammatory cytokines and their inhibitors in RA, and whether they may be causal in the accelerated atherosclerosis seen in these patients.
22964534 Rheumatoid arthritis: Threshold for success in RA drug development. 2012 Oct Determining the potential success of investigational therapies for rheumatoid arthritis early in the development process would enable better allocation of increasingly limited resources. Such ‘go or no-go’ decision-making could be improved by a method of analysing longitudinal clinical trial data to establish a threshold for success of a new drug.
21613330 Increased levels of circulating DNA in patients with systemic autoimmune diseases: A possi 2011 Aug High levels of serum and/or plasma circulating DNA (cDNA) have been described in patients with systemic autoimmune diseases (SADs). However, the role of this molecule has not been clarified. Our aim was to evaluate plasma cDNA levels in 48 systemic lupus erythematosus (SLE) and 44 primary Sjögren's syndrome (SS) patients, as compared with healthy and rheumatoid arthritis (RA) subjects, and to analyse their correlation with disease activity, disease damage and clinical manifestations. Plasma DNA was extracted using Qiagen columns and quantified by real-time quantitative PCR. Disease activity and damage were evaluated in both diseases by analysis of clinical and laboratory findings. Our results showed that plasma cDNA levels were significantly higher in patients with SS (mean ± SE: 32.0 ± 7.3 ng/ml) and with SLE (35.0 ± 9.0 ng/ml) than in controls (5.1 ± 1.1 ng/ml) (p < 0.0001 for both). Disease activity index correlated with cDNA levels in SS (p = 0.02), but not in SLE, and SS subjects with active disease displayed significantly higher cDNA levels with respect to inactive patients (p < 0.05). No correlation was found between plasma cDNA levels and disease damage indexes in either SLE or SS. These results indicate that increased plasma cDNA levels can been demonstrated in SLE and in SS patients with respect to healthy subjects. Interestingly, although cDNA levels did not correlate with indexes of disease damage in these disorders, a significant correlation between cDNA concentrations and disease activity was observed in SS, but not in SLE, suggesting a possible role of cDNA as non-invasive marker of disease activity. The different results obtained in these SADs may be explained by distinct disease pathogenesis or the influence of immunosuppressive and corticosteroid therapy that, unlike in SS, is usually employed in SLE.
22210276 Maximal locomotor depression follows maximal ankle swelling during the progression of arth 2012 Dec It is well established that arthritis depresses locomotion in humans as well as in animal disease models. The K/BxN mouse model resembles rheumatoid arthritis and is widely used for research. Here, we investigate the behavioral alterations of arthritic K/BxN mice during arthritis development with respect to horizontal locomotion. Locomotor activity measurements and the methodology of ankle thickness measurements are compared to demonstrate the feasibility of motion tracking in the K/BxN mouse model. Arthritic K/BxN mice show significantly decreased locomotion compared to their non-arthritis K/BxN littermates. We found an indirect correlation of ankle thickness and locomotor activity. However, both parameters are only partially interdependent resulting in temporal displacement of maximal ankle swelling and maximal depression of locomotion by 1 week. Assessing the impaired movement as a behavioral test appears to be a valuable multifactorial parameter for the evaluation of arthritis in the K/BxN mouse model and provides additional information on disease progression and severity.
21925450 [Rhupus: report of 4 cases]. 2011 Sep We present the clinical and serological characteristics of four patients with rhupus (Simon's definition). The 4 patients with rhupus presented ACR criteria for SLE as well as for RA, ANA positive with titers ranging from 1/80 to 1/5,250, and positive anti-DNA, with the predominance of symmetrical erosive polyarthritis. We found anti-CCP positivity and high titers in 3 of the 4 patients, and positive antiphospholipid antibodies in 2 (anticardiolipin and LA), without manifestation of antiphospholipid syndrome. One patient presented renal affection, and 2 subcutaneous nodules. The 3 patients with RA preceded the manifestations of SLE by an average of 7.7 years. Two patients were refractory to conventional DMAR in combination, requiring biologic and mycophennolate mofetil.
23090655 The DAS28-ESR cutoff value necessary to achieve remission under the new Boolean-based remi 2013 Jan To seek the cutoff value of the 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) that is necessary to achieve remission under the new Boolean-based criteria, we analyzed the data for 285 patients with rheumatoid arthritis registered between May 2008 and November 2009 by the Michinoku Tocilizumab Study Group and observed for 1 year after receiving tocilizumab (TCZ) in real clinical practice. Remission rates under the DAS28-ESR criteria and the Boolean criteria were assessed every 6 months after the first TCZ dose. The DAS28-ESR cutoff value necessary to achieve remission under the new criteria was analyzed by receiver operating characteristic (ROC) analysis. Data were analyzed using last observation carried forward. After 12 months of TCZ use, remission was achieved in 164 patients (57.5 %) by DAS28-ESR and 71 patients (24.9 %) under the new criteria for clinical trials. CRP levels scarcely affected remission rates, and the difference between remission rates defined by DAS28-ESR and by the new criteria was mainly due to patient global assessment (PGA). Improvement of PGA was inversely related to disease duration. ROC analysis revealed that the DAS28-ESR cutoff value necessary to predict remission under the new criteria for clinical trials was 1.54, with a sensitivity of 88.7 %, specificity of 85.5 %, positive predictive value of 67.0 %, and negative predictive value of 95.8 %. A DAS28-ESR cutoff value of 1.54 may be reasonable to predict achievement of remission under the new Boolean-based criteria for clinical trials in patients receiving TCZ.
21879710 Dendrimers to treat rheumatoid arthritis. 2011 Sep 27 In comparison with linear polymers, dendrimers' multivalency and nanostructure confer substantial advantages in drug delivery including rapid cell entry, targetability, and easier passage across biological barriers. Previous work has shown that phosphorus-containing dendrimers capped with anionic azabisphosphonate (ABP) end groups prompt anti-inflammatory activation of human monocytes. By using two mouse models of arthritis mimicking human rheumatoid arthritis (RA), Hayder et al. recently demonstrated that intravenous injection of dendrimer ABP inhibits the secretion of proinflammatory cytokines and osteoclastogenesis--two fundamental monocyte-dependent processes of inflammation and bone erosion in RA. While available biological therapies for RA target only one of the cytokines involved in inflammation or bone erosion, dendrimer ABP, by virtue of its double action on both processes in mice, might become a more active and cost-saving alternative for RA patients. This Perspective highlights this important development and the challenges that lie ahead.
22867935 Gait deviations in individuals with inflammatory joint diseases and osteoarthritis and the 2012 Jun This chapter describes three-dimensional gait analysis and common gait deviations in adults with rheumatoid arthritis (RA) and osteoarthritis (OA). Furthermore, we describe changes in gait deviations following surgical and non-surgical interventions. Gait analysis is used to define gait deviations and to evaluate varying surgical approaches, types of surgeries and non-pharmacologic interventions. Most studies examine gait in adults with knee OA. Limitations of existing studies include small samples, poor selection of controls, sample heterogenecity, lack of baseline gait assessments and inconsistency in measurement. Across studies, time and distance parameters are generally used to provide a global measure of gait deviations. Individuals with RA and OA in the lower extremities exhibit reduced walking speed/cadence and decreased motion and moments in relation to healthy subjects. Future research should include larger sample sizes, the use of proper controls, pre- and post-assessments and identify gait abnormalities early in the disease process to minimise long-term consequences.
22405554 [Bilateral arthrodesis of the medial foot joints in a patient with rheumatoid arthritis]. 2012 Patients with rheumatoid arthritis (RA) often have foot problems. The subtalar and particularly talonavicular joints are affected most frequently. The posterior tibial tendon has an important role in mid-foot stability. In RA patients, chronic inflammation of this tendon or talonavicular joint arthritis can results in posterior tibial tendon rupture. This leads to a collapsed talonavicular joint and forefoot instability, first with talonavicular and later Chopart's joint involvement. This shows as a planovalgus foot, with the forefoot in pronation and the heel in valgus deviation. In a 61-year-old RA patient, ruptures of the posterior tibial tendon due to rheumatoid inflammation occurred bilaterally, with subsequent deviation and instability of the forefoot. Arthrodesis with a medial column screw-Midfoot Fusion Bolt was carried out on the left foot and 4 months later on the right foot. At 7 months after the left and 4 months after the right foot surgery, the patient was free from pain, both feet were stable under loading and the forefoot was firm. The planovalgus deformity was corrected, as well as a valgus deviation of the great toe. Radiography showed a good position of the screws and complete healing of the medial foot joints.