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ID PMID Title PublicationDate abstract
20638761 Lung sarcoidosis induced by TNF antagonists in rheumatoid arthritis: a case presentation a 2011 Apr We report on a 72 year-old woman with long-standing rheumatoid arthritis diagnosed as granulomatosis due to pulmonary sarcoidosis after 49 months of treatment with etanercept. A clinical and radiological improvement was seen after tumor necrosis factor (TNF) antagonist withdrawal plus a course of steroids. Currently, 27 cases of histological proven sarcoidosis with pulmonary involvement have been reported in relation to anti-TNF therapy, with etanercept being more frequent in comparison with the anti-TNF monoclonal antibodies infliximab and adalimumab. Potential pathogenic mechanisms of the paradoxical effect of anti-TNF treatment is discussed. It is important for clinicians to be aware of this potential and uncommon complication of biological therapy with TNF antagonists.
21620893 IL-15 promotes osteoclastogenesis via the PLD pathway in rheumatoid arthritis. 2011 Sep 30 Osteoclastogenesis plays an important role in joint destruction in rheumatoid arthritis (RA). IL-15 is a pleiotropic proinflammatory cytokine that appears to help mediate the pathological bone loss. This study was undertaken to explore the signaling molecules essential for osteoclastogenesis mediated by IL-15 in rheumatoid synovial fibroblasts. Expression of phospholipase D1 (PLD1) and osteoclast-related gene expression in synovial tissues and their modulation by treatment with IL-15 and different inhibitors in synovial fibroblasts of RA patients were evaluated using immunohistochemistry and quantitative polymerase chain reaction. The levels of IL-15 in serum and synovial fluid were measured by ELISA. The effects of IL-15 and phosphatidic acid (PA) on osteoclast formation were evaluated in cocultures of rheumatoid synovial fibroblasts and peripheral blood monocytes or monocytes alone in the presence of M-CSF and RANKL. The levels of RANKL and PLD1 but not PLD2 were upregulated significantly by IL-15, and the RANKL level was significantly upregulated by PA in rheumatoid synovial fibroblasts. Blocking PA production with 1-butanol and siRNA against PLD1 significantly inhibited the IL-15-stimulated expression of RANKL and PLD1. IL-15 levels were significantly higher in serum and synovial fluid from patients with RA than in osteoarthritis patients and healthy controls. IL-15 and PA induced osteoclast formation through the mitogen-activated protein kinases (MAPKs) and NF-κB signaling pathways. Activation of PLD1 contributes to IL-15-mediated osteoclastogenesis via the MAPKs and NF-κB signaling pathways in rheumatoid synovial fibroblasts. Our data suggest that PLD1 might be an efficient therapeutic strategy for preventing bone destruction in rheumatoid arthritis.
21764596 The -1082A/G polymorphism in the Interleukin-10 gene and the risk of rheumatoid arthritis: 2011 Nov A large number of studies have shown that the -1082A/G polymorphism (rs1800896) in the Interleukin-10 gene (IL-10) is implicated in the susceptibility to rheumatoid arthritis (RA). However, the results are inconsistent and inconclusive. The aim of this study is to analyze the association between the -1082A/G polymorphism in the IL-10 gene and the RA risk by meta-analysis. A total of 1480 cases and 1413 controls in 10 case-control studies were included in this meta-analysis. The results indicated that the G allele carriers (GG+GA) had a 25% decreased risk of RA, when compared with the homozygote AA (odds ratio (OR)=0.75, 95% confidence interval (CI): 0.59-0.93). In the analysis in Europeans, significant decreased risks were associated with the G allele carriers (OR=0.73 and 95% CI: 0.57-0.93 for GG+GA vs. AA). The results from this meta-analysis provide evidence for the association between the IL-10 -1082A/G polymorphism and the risk of RA. To further evaluate gene×gene and gene×environment interactions between the polymorphisms in the IL-10 gene and RA risk, more studies with large groups of patients are required.
23121982 In vivo imaging implicates CCR2(+) monocytes as regulators of neutrophil recruitment durin 2012 Jul The infiltration of neutrophils and monocytes is a prominent feature of inflammatory diseases including human rheumatoid arthritis. Understanding how neutrophil recruitment is regulated during pathogenesis is crucial for developing anti-inflammatory therapies. We optimized the K/B×N serum-induced mouse arthritis model to study neutrophil trafficking dynamics in vivo using two-photon microscopy. Arthritogenic serum was injected subcutaneously into one hind footpad to induce a local arthritis with robust neutrophil recruitment. Using this approach, we showed that the depletion of monocytes with clodronate liposomes impaired neutrophil recruitment specifically at the transendothelial migration step. The depletion of CCR2(+) monocytes with the monoclonal antibody MC-21 reproduced these effects, implicating CCR2(+) monocytes as key regulators of neutrophil extravasation during arthritis initiation. However, monocyte depletion did not prevent neutrophil extravasation in response to bacterial challenge. These findings suggest that anti-inflammatory therapies targeting monocytes may act in part through antagonizing neutrophil extravasation at sites of aseptic inflammation.
23146852 Diagnostic utility of anti-citrullinated protein antibody and its comparison with rheumato 2012 Nov OBJECTIVE: To assess the diagnostic utility of anti-citrullinated protein antibody (anti-CCP) in rheumatoid arthritis (RA) and compare it with rheumatoid factor (RF). STUDY DESIGN: Analytical study. PLACE AND DURATION OF STUDY: Section of Chemical Pathology, Department of Pathology and Microbiology and Medicine, the Aga Khan University, Karachi, from January to May 2010. METHODOLOGY: A review of medical records of patients presenting to the clinics with complaints of muscular or joint pains and who were tested for their serum anti-CCP was done. Inclusion criteria were presence of clinical synovitis in at least one joint and an absence of alternative diagnosis. Patients with arthralgia alone or with missing acute phase reactants information were excluded. Scoring and classification of RA was done using the 2010 RA Classification Criteria by the American College of Rheumatology (ACR). RESULTS: Out of the 98 charts reviewed, ACR criteria showed 54 cases with RA. The mean age of the group was 46 ± 15 years, 82.7% being females. High titers of anti-CCP corresponded with the ACR scores. The sensitivity and specificity of anti-CCP and RF reactivity for the diagnosis of RA were 54.7% and 95.5% versus 59.3% and 88.4% respectively. CONCLUSION: Anti-CCP is useful for the diagnosis of RA due to its higher specificity as compared to RF and can predict disease severity.
22209159 Costs related to hip disease in patients eligible for total hip arthroplasty. 2012 Aug This study was designed to estimate direct and indirect costs incurred by hip disease in patients eligible for total hip arthroplasty (THA). Before THA, 2635 patients completed a questionnaire regarding the use of resources because of their hip disease. Costs were assigned using official statistical sources or market prices. Annual costs amounted to US$ 7666 per patient. In a regression analysis, higher annual costs were associated with working age, female gender, comorbidity, and operation waiting time more than 90 days (P < .005). The burden of disease for THA candidates is extensive, where loss of productivity is the principal cost. Long wait for surgery is associated with increased costs. This study provides baseline cost data, which will be useful for further health economic analyses and could provide guidance for health care decision makers.
22344961 Effects of infertility, pregnancy loss, and patient concerns on family size of women with 2012 May OBJECTIVE: Women with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have fewer children on average than other women. We sought to determine the roles of infertility, pregnancy loss, and personal choice on family size in women with these diseases. METHODS: A reproductive history questionnaire was completed by women with RA and SLE participating in a longitudinal observational study. Within each disease cohort, participants were divided into 3 groups: those interested in having children at symptom onset who had either fewer children than planned (group A) or the same number as planned (group B), and those no longer interested in having children at diagnosis (group C). RESULTS: Of the 578 RA and 114 SLE women surveyed, >60% were in group C. Of those interested in having children, 55% with RA and 64% with SLE had fewer children than originally planned. Among women with RA, group A had 1 less pregnancy, 1 less live birth, and an infertility rate 1.5 times higher than group B; the miscarriage rate was similar in both groups. Compared to SLE group B, SLE group A had a similar number of pregnancies, but a 3-fold higher rate of miscarriage and 1 less live birth. Concerns about child health and personal welfare were associated with a lower pregnancy rate. CONCLUSION: In this population, more than one-half of young women with RA or SLE had fewer biologic children than desired. While patient choice plays a role, infertility in RA patients and miscarriage in SLE patients are also important.
22669023 The absence of typical pneumonia symptoms in a patient with rheumatoid arthritis during to 2012 May 23 A 78-year-old woman with rheumatoid arthritis while being treated with tocilizumab and steroid treatment presented with pharyngeal pain and general malaise. She felt chills and vomited while waiting in the waiting room, in addition to urinary incontinence. An immediate evaluation of her condition indicated that she was in shock and a physical examination revealed moist rales in the right lung field. Her white cell count and C reactive protein level were within normal limits; however, a radiological study indicated pneumonia. Antibiotic treatment resulted in improvement of her condition. Blood culture later revealed bacteraemia due to Streptococcus pneumoniae. The anti-inflammatory effect of tocilizumab and steroid treatment may mask the typical symptoms and signs of infection, so physicians must be aware of the potential for hidden infection when such patients present with an unidentified complaint.
22292554 The 2010 patent landscape for spleen tyrosine kinase inhibitors. 2012 May Discovery of small molecular inhibitors for treatment of rheumatoid arthritis is a major ongoing effort within the pharmaceutical industry. Spleen tyrosine kinase (SYK) is one of leading small molecular targets with regard to clinical development primarlly due to efforts by Rigel and Portola. In this review, we provide a comprehensive overview of the SYK patent landscape. The patent literature we evaluated relates to any organization that has filed applications that imply that SYK is the intended target. The interest in SYK was initiated in the early 2000's with many organizations, including several large pharmaceutical companies, and has been active for years. In general, the structural theme of most of the compounds in these applications is a traditional ATP competitive inhibitor with each organization having a different hinge binding element. In general, the attachment to the hinge is an aryl amine that is decorated with a solubilizing group. The other substituents are broadly variable across the numerous companies indicating that SYK has significant flexibility in its interactions in that portion of the kinase. This overview of the SYK patent literature and the learnings of the inhibitors' substitution patterns would be an important reference for anyone working in this area.
22114888 Managing the adverse effects of nonsteroidal anti-inflammatory drugs. 2011 Sep Conventional medical treatment for rheumatoid arthritis and osteoarthritis includes the use of NSAIDs (traditional and selective inhibitors of cyclooxygenase [COX]-2), because they provide unmistakable and significant health benefits in the treatment of pain and inflammation. However, they are associated with an increased risk of serious gastrointestinal (GI) and cardiovascular (CV) adverse events. Both beneficial and adverse effects are due to the same mechanism of action, which is inhibition of COX-dependent prostanoids. Since CV and GI risk are related to drug exposure, a reduction in the administered dose is recommended. However, this strategy will not eliminate the hazard owing to a possible contribution of individual genetic background. Further studies will be necessary to develop genetic and/or biochemical markers predictive of the CV and GI risk of NSAIDs.
20950247 Antimalarial cutaneous side effects: a study in 209 users. 2011 Mar BACKGROUND: Antimalarial agents are commonly used drugs that may have skin side effects. OBJECTIVE: To study the prevalence of cutaneous side effects in antimalarial users. METHODS: We studied the prevalence of cutaneous manifestations in 209 antimalarial users, 127 with systemic lupus erythematosus (SLE) and 82 with rheumatoid arthritis (RA). As control we included 200 patients from the gynecologic and ophthalmologic departments who did not have antimalarial use. Patients were submitted to a structured questionnaire for demographic data, type of antimalarial drug used, and treatment time as well as skin complaints. Physical examination was performed by a dermatologist. RESULTS: In 159 of 209 (76%) of the antimalarial users, there were cutaneous findings. The most frequent was xerosis, followed by skin hyperpigmentation and pruritus. In 4.8% of the antimalarial users, allergic reactions led to drug withdrawal. When comparing them with the control group, skin hyperpigmentation and xerosis were more prevalent (p < .0001 for both), but pruritus was not (p = .39). No relationship could be found between the skin side effects and ethnic background, gender, antimalarial type, or treatment duration. Hair depigmentation was more common in SLE patients than in RA patients. CONCLUSION: Cutaneous side effects in antimalarial users are frequent. Xerosis and hyperpigmentation are the most common findings.
22179728 Factors associated with absenteeism, presenteeism and activity impairment in patients in t 2012 Feb OBJECTIVES: To understand the impact of the early years of RA on all aspects of work productivity, and determine how this is related to clinical markers. Previous research on work productivity has examined predominantly early retirement and absenteeism. The impact of reduced work performance (presenteeism) and activity impairment is less well understood in early RA populations. METHODS: Working patients enrolled in an RA inception cohort were recruited into a nested study. A questionnaire incorporating the Work Productivity and Activity Impairment (WPAI) instrument was administered with a number of clinical outcomes, including the Multidimensional Health Assessment Questionnaire (MD-HAQ) and scales for pain, fatigue and patient assessment of disease patient global assessment (PtGA). RESULTS: Analysis included 150 RA patients, with the mean age at onset being 48 years (s.d. 10 years) and disease duration from symptom onset being 49 months. Patients had relatively mild disease: MD-HAQ (0.6), pain (3.6), PtGA (3.6) and fatigue (4.6). Of the 92% patients working for pay, 19% reported missing work (absenteeism) in the past week due to their health, accounting for 46% of their working time. Even while at work, ∼25% of actual hours was lost due to poor health, while outside work 33% of patients' regular daily activities were prevented. In multivariate analyses, disease severity was associated with the presence of absenteeism, presenteeism and activity impairment. Patients able to self-schedule their work had lower presenteeism and activity impairment. CONCLUSIONS: Productivity loss is common in patients in the first years of RA who are in paid work and was associated with work characteristics and adverse clinical outcomes.
22334975 Nodular regenerative hyperplasia of liver--a rare cause of portal hypertension in patients 2011 Sep Nodular regenerative hyperplasia of liver (NRHL) is a rare entity and is infrequently associated with collagen vascular disease. Clinically patients present with recurrent abdominal pain, non-specific symptoms of underlying systemic disease and signs of portal hypertension. This entity is usually diagnosed by MRI and liver biopsy. Prognosis is usually good.
21221592 The Th17/Treg imbalance and cytokine environment in peripheral blood of patients with rheu 2012 Apr Broken Th17/Treg balance has been reported contributing to several inflammatory autoimmune diseases. The objective of the study was to investigate whether the Th17/Treg balance was impaired in the peripheral blood of patients with rheumatoid arthritis (RA). The frequencies of Treg cells and Th17 cells and mRNA expression of transcription factor RORγt and FoxP3 in peripheral blood of RA patients (n = 37) and healthy controls (n = 30) were determined by flow cytometry and real-time PCR, respectively. Eleven serum cytokines were analyzed by using cytometeric bead array (CBA). The results demonstrated that active RA patients exhibited increased peripheral Th17 cells, Th1- and Th17-related cytokines and RORγt expression while decreased Treg cells and FoxP3 expression. In addition, Th17/Treg ratios were positively correlated with serum concentrations of Th1- and Th17-related cytokines. In conclusion, our results indicated that Th17/Treg balance was broken in peripheral blood, which may play an important role in the development of RA.
21921096 Canadian Rheumatology Association recommendations for pharmacological management of rheuma 2012 Aug OBJECTIVE: The Canadian Rheumatology Association (CRA) has developed recommendations for the pharmacological management of rheumatoid arthritis (RA) with traditional and biologic disease-modifying antirheumatic drugs (DMARD) in 2 parts. Part 1 is reported here. METHODS: The CRA Therapeutics Committee assembled a national working group of RA clinical experts, researchers, patient consumers, and a general practitioner. Treatment questions were developed a priori based on results of a national needs assessment survey. A systematic review of all clinical practice guidelines and consensus statements regarding treatment with traditional and biologic DMARD in patients with RA published between January 2000 and June 2010 was performed in Medline, Embase, and CINAHL databases, and the grey literature. Guideline quality was assessed by 2 independent reviewers, and guideline characteristics, recommendations, and supporting evidence from observational studies and randomized controlled trials were synthesized into evidence tables. The full working group reviewed the evidence tables and developed recommendations using a modified Delphi technique. RESULTS: Five overarching principles and 26 recommendations addressing general RA management strategies and treatment with glucocorticoids and traditional and biologic DMARD were developed for rheumatologists, other primary prescribers of RA drug therapies, and patients with RA. CONCLUSION: These recommendations were developed based on a synthesis of international guidelines, supporting evidence, and expert consensus considering the Canadian healthcare context with the intention of promoting best practices and improving healthcare delivery for persons with RA.
21989284 Safety of biologic therapy in rheumatoid arthritis. 2011 Oct 11 Biologic therapies have revolutionized the treatment of rheumatic diseases in the past decade. As with any drugs, however, a variety of important safety concerns affect the choice and use of these agents. Several issues, such as the risk of infection, malignancy, or administration reactions, apply to all of these compounds, although some conditions that affect patient selection and management within these categories seem to be specific to particular biologic treatments. Other safety concerns with biologic agents, such as congestive heart failure, demyelinating disease, and hyperlipidemia, are associated with individual agents. Despite all these concerns, the therapeutic indices for biologic agents remain fairly high in relation to non-biologic DMARDs. Available safety data for all biologic agents approved for the treatment of rheumatoid arthritis are reviewed in this manuscript. With careful patient selection and appropriate vigilance on the part of treating physicians and other care providers, these compounds can be safely integrated into the therapeutic plan.
22939655 [Palindromic rheumatism]. 2013 Jan Palindromic rheumatism is characterized by episodes of arthritis or para-arthritis leaving no residual or radiographic changes. Several diseases should be ruled out in the differential diagnosis. Evolution to rheumatoid arthritis is common, especially in patient with positive rheumatoid factor and anticitrullinated peptides. In seronegative patients, palindromic rheumatism could be part of the spectrum of autoinflammatory diseases because of a high frequency of MEFV mutations. Treatment remains discussed. The use of antimalarials could delay the development of rheumatoid arthritis or another connective tissue disease.
23190682 The role of inflammation, the autonomic nervous system and classical cardiovascular diseas 2012 Nov 28 INTRODUCTION: Evidence indicates that rheumatoid arthritis (RA) patients have increased susceptibility to myocardial ischaemia that contributes to myocardial infarction. The subendocardial viability ratio (SEVR) can be measured using pulse wave analysis and reflects myocardial oxygen supply and demand. The objective of the present study was to examine specific predictors of SEVR in RA patients, with a specific focus on inflammation and classical cardiovascular disease (CVD) risk factors. METHODS: Two patient cohorts were included in the study; a primary cohort consisting of 220 RA patients and a validation cohort of 127 RA patients. All patients underwent assessment of SEVR using pulse wave analysis. Thirty-one patients from the primary cohort who were about to start anti-inflammatory treatment were prospectively examined for SEVR at pretreatment baseline and 2 weeks, 3 months and 1 year following treatment. Systemic markers of disease activity and classical CVD risk factors were assessed in all patients. RESULTS: The SEVR (mean ± standard deviation) for RA in the primary cohort was 148 ± 27 and in the validation cohort was 142 ± 25. Regression analyses revealed that all parameters of RA disease activity were associated with SEVR, along with gender, blood pressure and heart rate. These findings were the same in the validation cohort. Analysis of longitudinal data showed that C-reactive protein (P < 0.001), erythrocyte sedimentation rate (P < 0.005), Disease Activity Score in 28 joints (P < 0.001), mean blood pressure (P < 0.005) and augmentation index (P < 0.001) were significantly reduced after commencing anti-TNFα treatment. Increasing C-reactive protein was found to be associated with a reduction in SEVR (P = 0.02) and an increase in augmentation index (P = 0.001). CONCLUSION: The present findings reveal that the SEVR is associated with markers of disease activity as well as highly prevalent classical CVD risk factors in RA, such as high blood pressure and diabetes. Further prospective studies are required to determine whether the SEVR predicts future cardiac events in RA.
22922344 Immunosuppressant discovery from Tripterygium wilfordii Hook f: the novel triptolide analo 2012 Sep The Chinese traditional herb Tripterygium wilfordii Hook f (TwHF) has been widely used in the treatment of autoimmune and inflammatory diseases. Over the past few decades, great efforts have been made to explore modern preparations of TwHF with higher efficacy, solubility, and lower toxicity. In this study, we reviewed several examples both of naturally occurring compounds and their derivatives in TwHF, and summarized the preclinical evaluations with regard to autoimmune and inflammatory diseases. All of the candidate compounds described herein have been or are currently in clinical trials. Although some studies encountered problems, the data still provided valuable references for future studies. (5R)-5-hydroxytriptolide (LLDT-8, Leitengshu) is a novel triptolide derivative with potent immunosuppressive and anti-inflammatory activities developed at Shanghai Institute of Materia Medica. Indeed, a Phase I clinical trial for this compound has been completed in rheumatoid arthritis patients. The results will provide the basis for the further exploration of this ancient herb and encourage the research and development of valuable traditional Chinese medicine.
21461651 The association of Raynaud's syndrome with rheumatoid arthritis--a meta-analysis. 2011 Aug Rheumatoid arthritis (RA) has traditionally been included among the diseases associated with Raynaud's syndrome (RS). The prevalence of RS in patients with RA is not well defined. The objective of this paper was to assess the prevalence of RS in patients with RA-a meta-analysis of published data was performed. The PubMed database of the National Library of Medicine and ISI Web of Knowledge was used for studies dealing with RS and RA. The studies provided sufficient data to estimate the prevalence of RS in patients with RA. A forest plot was determined by the revealed prevalences. Statistical analysis was based on methods for a random effects meta-analysis and a finite mixture model for proportions. Publication bias was investigated with the linear regression test (Egger's method). A meta-regression was conducted by the year of publication. Twenty-eight eligible studies, contributing data on 3,730 subjects, were included in this meta-analysis. For RA, a pooled prevalence of 12.3% and 95% CI = 0.093-0.157 were obtained. A mixture model analysis found five latent classes. Statistically and graphically, publication bias was present (p = 0.031). In the meta-regression, the estimated prevalence decreased within the observation period (1977-2010) from 11.2% to 9.4%. Despite some heterogeneity, there is a possible indication of an association for RS and patients with RA.