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ID PMID Title PublicationDate abstract
19829943 Transient thyrotoxicosis as an initial presentation of rheumatoid arthritis: a case report 2009 Jul 16 INTRODUCTION: Few reports in the literature describe the association of rheumatoid arthritis and transient thyrotoxicosis. We report a case of rheumatoid arthritis and painless thyroiditis presenting simultaneously and acutely with a cluster of symptoms that initially made the diagnosis of rheumatoid arthritis very challenging. CASE PRESENTATION: A 41-year-old Caucasian male presented with complaints of malaise and decreased range of motion in the left elbow. Physical examination and laboratory evaluation established the diagnosis of rheumatoid arthritis and painless thyroiditis. CONCLUSIONS: When patients with rheumatoid arthritis present with numerous "extra articular" and constitutional symptoms, evaluation of thyroid disorder with thyroid function test should be considered to help establish the correct diagnosis.
19946450 Felty's syndrome as an initial presentation of rheumatoid arthritis: a case report. 2009 Nov 18 INTRODUCTION: Felty's syndrome is an uncommon but severe extra-articular manifestation of rheumatoid arthritis. Felty's syndrome is characterized by the triad of rheumatoid arthritis, neutropenia, and splenomegaly. The lifetime risk of Felty's syndrome for a rheumatoid arthritis patient is less than 1% and there are only few case reports of Felty's syndrome with neutropenia preceded clinical evidence of arthritis. We present a case which is atypical presentation of Felty's syndrome without arthritis. CASE PRESENTATION: We present a case of 31-year-old man who presented with fever and skin infection, found to have neutropenia. The work up showed splenomegaly and other evidences support Felty's syndrome diagnosis without arthritis presentation. CONCLUSION: Patients with unexplained, continuous neutropenia without arthritis but with high level of rheumatoid factor and positive antibodies to cyclic citrullinated peptides should be suspected of developing Felty's syndrome as an initial presentation of rheumatoid arthritis.
20666701 Does the p38 MAP kinase inhibitor pamapimod have potential for the treatment of rheumatoid 2010 Oct Methotrexate alone or in combination with other agents is the standard treatment for moderate-to-severe rheumatoid arthritis. As biological agents are expensive, they are not usually used until methotrexate has failed to give a good response. Thus, there is scope for the development of cheaper drugs that can be used instead of methotrexate or in addition to methotrexate. Pamapimod is a p38α inhibitor being developed for use in the treatment of rheumatoid arthritis. The objective of this review was to evaluate the recent clinical trials of pamapimod in subjects with rheumatoid arthritis. There is no clear-cut evidence that pamapimod alone or in the presence of methotrexate is efficacious in subjects with rheumatoid arthritis but it does cause adverse effects. It is unlikely that pamapimod will be useful in the treatment of rheumatoid arthritis.
20003451 Local expression of tumor necrosis factor-receptor 1:immunoglobulin G can induce salivary 2009 INTRODUCTION: Tumor necrosis factor is a pleiotropic cytokine with potent immune regulatory functions. Although tumor necrosis factor inhibitors have demonstrated great utility in treating other autoimmune diseases, such as rheumatoid arthritis, there are conflicting results in Sjögren's syndrome. The aim of this study was to assess the effect of a locally expressed tumor necrosis factor inhibitor on the salivary gland function and histopathology in an animal model of Sjögren's syndrome. METHODS: Using in vivo adeno associated viral gene transfer, we have stably expressed soluble tumor necrosis factor-receptor 1-Fc fusion protein locally in the salivary glands in the Non Obese Diabetic model of Sjögren's syndrome. Pilocarpine stimulated saliva flow was measured to address the salivary gland function and salivary glands were analyzed for focus score and cytokine profiles. Additionally, cytokines and autoantibody levels were measured in plasma. RESULTS: Local expression of tumor necrosis factor-receptor 1:immunoglobulin G fusion protein resulted in decreased saliva flow over time. While no change in lymphocytic infiltrates or autoantibody levels was detected, statistically significant increased levels of tumor growth factor-beta1 and decreased levels of interleukin-5, interleukin-12p70 and interleukin -17 were detected in the salivary glands. In contrast, plasma levels showed significantly decreased levels of tumor growth factor-beta1 and increased levels of interleukin-4, interferon-gamma, interleukin-10 and interleukin-12p70. CONCLUSIONS: Our findings suggest that expression of tumor necrosis factor inhibitors in the salivary gland can have a negative effect on salivary gland function and that other cytokines should be explored as points for therapeutic intervention in Sjögren's syndrome.
19492031 Hypertrophic obstructive cardiomyopathy in rheumatoid arthtritis - coincidence or associat 2009 Spring A 60-year-old woman with a history of rheumatoid arthritis was admitted to the hospital for investigation of dyspnea on exertion (New York Heart Association class II), polyarthralgias and mild fever. An echocardiogram revealed asymmetric hypertrophy of the interventricular septum with signs of subaortic obstruction.The coexistence of rheumatoid arthritis and hypertrophic cardiomyopathy could be connected with the human lymphocyte antigen DR4, which is common in both conditions. Further studies are necessary to assess whether a true association of the above diseases exists.
21234291 Tocilizumab: a review of its safety and efficacy in rheumatoid arthritis. 2010 Dec 19 Recent years have seen many exciting developments in the treatment of rheumatoid arthritis. Tocilizumab (TCZ) is a monoclonal antibody which inhibits the interleukin-6 receptor. After initial studies in Japan, it has been extensively studied in five multicentre clinical trials. This report summarises the key efficacy and toxicity findings from the major clinical trials. TCZ works quickly and effectively in rheumatoid arthritis either as monotherapy or in combination with other agents in early disease, DMARD inadequate responders, seronegative disease and after anti-TNF failure. The toxicity profile is manageable but includes infections (most notably skin and soft tissue), increases in serum cholesterol, transient decreases in neutrophil count and abnormal liver function tests (especially in combination with methotrexate). In summary, there is sufficient evidence to make TCZ a first line biologic therapy for rheumatoid arthritis especially for those who are unable to take methotrexate or who fail anti-TNF therapy.
27789984 The clinical efficacy and safety of certolizumab pegol (CZP) in the treatment of rheumatoi 2009 Rheumatoid arthritis can cause chronic pain, disability, fatigue and loss of productivity both in the workplace and at home. Fatigue, not joint pain, swelling or that there may be radiographic damage, is frequently mentioned by patients as their most debilitating problem. In the era prior to biologic therapy in rheumatoid arthritis, it was reported that 40% to 50% of individuals reported work loss within 10 years of the onset of their disease. Rheumatoid arthritis is not just associated with chronic pain and inability to function normally; there is a significant economic burden caused by the disease which affects society as well the individual. Work disability in individuals with rheumatoid arthritis occurs early and increases over time. Early, aggressive treatment has now become the norm in clinical practice with changes of medication dictated by measuring the presence of continued disease activity. The combination of adequately dosed methotrexate and a biologic agent, especially a TNFα inhibitor, has been shown to be far more effective than traditional disease modifying anti-rheumatic drugs in early and long-standing disease, with respect to clinical, radiologic and functional outcomes. Unfortunately, not all patients respond to all medications equally; indeed a patient may fail a number of medications, either alone or in combination, and then respond to another medication. For this reason, there is room in our therapeutic armamentarium for additional effective agents such as certolizumab pegol. The results of up to 100 weeks of treatment with certolizumab pegol with an emphasis on functional outcomes, is the focus of this review.
21794600 [Characterization of patients with rheumatoid arthritis according to the health care level 2009 Jul OBJECTIVE: To characterize rheumatoid arthritis patients seen in Rheumatology Units at different health care levels. MATERIAL AND METHODS: Questionnaire and clinical examination of rheumatoid arthritis patients seen as outpatients in Rheumatology Units from Primary Care, county Hospitals and Reference Hospitals. Demographic, social, labour and disease data were collected. Statistical study included a description of the variables and a multiple correspondence analysis to define patient profiles. RESULTS: Eight hundred and twelve patients with rheumatoid arthritis were included. There were significant differences in patient profiles at the different care level. In Primary Care, patients were older, with basic studies, and with short duration and generally mild rheumatoid arthritis. In local hospitals the typical patient was a man, qualified worker, with low income, and an erosive disease with extraarticular manifestations. At reference Hospitals prevailing patients were young women with a long duration disease and requiring biological therapy. CONCLUSION: There are significant differences in rheumatoid arthritis patient profiles at different health care levels.
19814865 Therapeutic index of methotrexate depends on circadian cycling of tumour necrosis factor-a 2009 Oct OBJECTIVES: Rheumatoid arthritis is an autoimmune disorder of unknown aetiology. Morning stiffness, a characteristic feature of rheumatoid arthritis, shows a 24-h rhythm. Noticing this rhythm, we hypothesized the presence of a similar rhythm for a rheumatoid arthritis indicator, in addition to dosing-time dependency of the anti-rheumatic effect of methotrexate in arthritis induced by collagen in rats and mice, which reflect the symptomatology of rheumatoid arthritis patients. METHODS: To measure tumour necrosis factor (TNF)-alpha concentration, blood was taken at different times (2, 6, 10, 14, 18 or 22 h after the light was turned on (HALO)) in collagen-induced arthritic mice. Methotrexate was administered at two different dosing times based on these findings to estimate arthritis. KEY FINDINGS: The arthritis score was significantly lower in the 22 HALO-treated group than in the control and 10 HALO-treated groups in collagen-induced arthritic rats and mice. Plasma TNF-alpha concentrations showed obvious 24-h rhythms, with higher levels at light phase and lower levels at dark phase after rheumatoid arthritis crisis. Arthritis was relieved after administration of methotrexate during the dark phase in synchronization with the 24-h rhythm. CONCLUSIONS: Our findings suggest that choosing an optimal dosing time associated with the 24-h cycling of TNF-alpha could lead to effective treatment of rheumatoid arthritis by methotrexate.
19707411 B cell reductive therapy with rituximab in the treatment of rheumatoid arthritis. 2009 The approach to treating autoimmune disorders is currently undergoing a significant change in focus. As therapies are developed that are more precise in targeting the pathogenesis for these diseases, patients experience significantly fewer side effects. At the same time, as more precise therapies are discovered, the etiologies of these diseases become further elucidated. It is now widely accepted that B-lymphocytes play a significant role in the pathogenesis of various autoimmune diseases, the extent of which continues to be the focus of ongoing research. Rheumatoid arthritis is one such disease process that has been the focus of various B-lymphocyte-directed therapeutic trials. In this paper we review the current research available on rituximab as treatment for rheumatoid arthritis. This review details results from four main studies, as well as others, which used rituximab in at least one of the arms in treatment of rheumatoid arthritis. The results are promising and will likely lead to longer term studies as well as a potential focus on B cell subsets.
18830907 Brain-derived neurotrophic factor and nerve growth factor correlate with T-cell activation 2009 Jan OBJECTIVES: Identification of factors associated with disease activity and B and T cell activation is a challenge in primary Sjogren's syndrome (pSS). Neurotrophins (NTs), recently reported as B cell antiapoptotic, and T-cell activation factors seem to be implicated in autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: Samples from 18 pSS patients and 12 control subjects were studied to determine serum levels of nerve-growth factor (NGF) and brain-derived neurotrophic factor (BDNF), and their relationships with T- and B-cell activation and disease activity. Peripheral blood mononuclear cells (PBMCs) from patients with pSS and controls were examined by flow cytometry for HLA-DR expression by activated T cells. B cell activation was evaluated by B cell activating factor (BAFF) serum levels measured by enzyme-linked immunosorbent assay (ELISA) and immunoglobulin (Ig) and free light chain (FLC) levels. RESULTS: Mean serum levels of BDNF in pSS patients were significantly higher than in healthy controls and correlated directly with disease activity. NGF levels were associated with the subgroup of patients with hypergammaglobulinaemia. The pSS group was characterized by peripheral CD4+ and CD8+ T cell activation that correlated positively with BDNF and NGF levels, respectively. CONCLUSION: NT levels are potential biomarkers for lymphocyte activation in pSS patients.
19830115 Autologous chondrocyte implantation for rheumatoid arthritis of the knee: a case report. 2009 Apr 3 INTRODUCTION: Although pharmacologic treatment remains the mainstay for treating rheumatoid arthritis, there is an increasing need for a method that biologically regenerates arthritic knee lesions as patient longevity continually increases. CASE PRESENTATION: We treated rheumatoid arthritis of the right knee in a 35-year-old female Korean patient using autologous chondrocyte implantation. Twelve months after surgery, the patient could walk without pain. CONCLUSION: Autologous chondrocyte implantation appears to be effective for treating rheumatoid arthritis of the knee.
19222863 Blockade of lymphotoxin-beta receptor signaling reduces aspects of Sjögren's syndrome in 2009 INTRODUCTION: The lymphotoxin-beta receptor (LTbetaR) pathway is important in the development and maintenance of lymphoid structures. Blocking this pathway has proven beneficial in murine models of autoimmune diseases such as diabetes and rheumatoid arthritis. The aim of this study was to determine the effects of LTbetaR pathway blockade on Sjögren syndrome (SS)-like salivary gland disease in non-obese diabetic (NOD) mice. METHODS: The course of SS-like disease was followed in NOD mice that were given lymphotoxin-beta receptor-immunoglobulin fusion protein (LTbetaR-Ig) starting at 9 weeks of age. Treatment was given as a single weekly dose for 3, 7, or 10 weeks. Age-matched NOD mice treated with mouse monoclonal IgG1, or not treated at all, were used as controls. The severity of inflammation, cellular composition, and lymphoid neogenesis in the submandibular glands were determined by immunohistochemistry. Mandibular lymph nodes were also studied. Saliva flow rates were measured, and saliva was analyzed by a multiplex cytokine assay. The salivary glands were analyzed for CXCL13, CCL19, and CCL21 gene expression by quantitative polymerase chain reaction. RESULTS: Treatment with LTbetaR-Ig prevented the increase in size and number of focal infiltrates normally observed in this SS-like disease. Compared with the controls, the submandibular glands of LTbetaR-Ig-treated mice had fewer and smaller T- and B-cell zones and fewer high endothelial venules per given salivary gland area. Follicular dendritic cell networks were lost in LTbetaR-Ig-treated mice. CCL19 expression was also dramatically inhibited in the salivary gland infiltrates. Draining lymph nodes showed more gradual changes after LTbetaR-Ig treatment. Saliva flow was partially restored in mice treated with 10 LTbetaR-Ig weekly injections, and the saliva cytokine profile of these mice resembled that of mice in the pre-disease state. CONCLUSIONS: Our findings show that blocking the LTbetaR pathway results in ablation of the lymphoid organization in the NOD salivary glands and thus an improvement in salivary gland function.
19584494 Adult-onset Still's disease: a review. 2009 May OBJECTIVE: This article is an attempt to review recent literature regarding pathogenesis and clinical and laboratory findings in adult-onset Still's disease (AOSD). MATERIALS AND METHODS: A search was conducted in PubMed and Ovid for English language publications, using individual or linked search terms "adult-onset Still's disease," "adult Still's disease," "Still's disease," "AOSD," and other related terms, from 1996 to 2009, and the clinically relevant articles were subsequently selected. RESULTS: More than 1000 titles were reviewed by the authors, and the most important concepts were selected from 143 full-text articles. CONCLUSION: Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology and pathogenesis, usually presenting with high spiking fever accompanied by systemic manifestations. The disease is an entity with heterogeneous pathology; and diverse suggested etiologies, clinical manifestations and prognoses. There is no single diagnostic test for AOSD; rather, the diagnosis is based on a set of criteria, the most important of which are indeed clinical, but they also include paraclinical ones. Treatment aims at both minimizing inflammation and halting disease progression. For the former, nonsteroidal anti-inflammatory drugs have limited efficacy; so glucocorticoids in conjunction with disease-modifying antirheumatic drugs are also used. Novel therapeutic approaches such as anti-tumor necrosis factor blockade and monoclonal antibodies are promising.
20016797 Patient preferences and satisfaction in the treatment of rheumatoid arthritis with biologi 2009 Nov 29 Significant advances in the treatment of rheumatoid arthritis (RA) have been made over the past 10 years with the introduction of biologic therapies, such as the TNF inhibitors. With these medications, many patients with RA have seen significant improvement in symptoms, function, and quality of life. However, with the introduction of the biologics, decision-making for this chronic disease that affects up to 1% of the population has become even more complex. Patient preferences for mode and frequency of administration, and for certain risks vs benefits as well as medication beliefs are central to uptake and adherence to these medications. This review examines the current literature on patient satisfaction, adherence, and preference for biologic therapy in RA.
21769257 A case of rheumatoid arthritis with bucillamine-induced yellow nail syndrome initially man 2010 We report a case of a 67-year-old woman with rheumatoid arthritis with yellow nail syndrome (YNS) that was caused by bucillamine. All three signs (yellow fingernails, lymphatic edema, and bronchiectasis) of YNS manifested, with characteristic timing, first with the nails turning yellow after when bronchiectasis was noticed. We reviewed 10 case reports from Japan and compared the periods until the appearance of yellow nails after starting bucillamine treatment, as well as those until lung disease and leg edema appeared.
23105835 Uric acid a better scavenger of free radicals than vitamin C in rheumatoid arthritis. 2009 Apr Uric acid an endogenous aqueous antioxidant in normal humans is present in much higher concentrations than vitamin C and has been known to cover 2/3(rd) of the free radical scavenging capacity in plasma. In the present study average uric acid levels of patients of rheumatoid arthritis were found to be close to the normal individuals. A unique feature was observed after classifying the patients on the basis of the duration of suffering, the patients having longer duration of disease had least uric acid levels as compared to those suffering from relatively lesser period, similar trend was observed in the ascorbic acid estimations. The decline in uric acid values with progression of the disease was much more than what was observed in case of ascorbic acid suggesting the significant role of uric acid in scavenging of free radicals. Too much lowering of Uric Acid should be checked and vitamin C should be supplemented in diet for maintaining the balance between pro oxidant and antioxidant forces to check pro oxidant insult in rheumatoid arthritis.
19655827 Patterns of biologic agent use in older males with inflammatory diseases: an institution-f 2009 BACKGROUND: Little investigation has focused on use of biologic agents in elderly patients with rheumatoid arthritis, spondyloarthropathies, inflammatory bowel disease or psoriasis. Furthermore, studies of drugs for autoimmune diseases that do include elderly populations have tended to include a preponderance of female patients. OBJECTIVE: To evaluate the pattern of biologic agent use in older males with inflammatory diseases, including rheumatoid arthritis, the spondyloarthropathies (ankylosing spondylitis, psoriatic arthritis and reactive arthritis), inflammatory bowel disease and psoriasis. METHODS: All prescriptions of biologic agents dispensed by a US Department of Veterans Affairs Medical Center pharmacy in Dallas, Texas, USA, between 1 January 1999 and 31 December 2007 were analysed. Comprehensive chart reviews were undertaken on all non-cancer patients treated with six biologic agents (infliximab, etanercept, adalimumab, abatacept, rituximab and anakinra) to determine the tolerability of the medication and rates of stopping or switching each drug. RESULTS: A total of 428 patients (mean +/- SD age 59 +/- 12 years) with rheumatoid arthritis (49%), spondyloarthropathy (37%), inflammatory bowel disease (7%) or psoriasis (7%) were treated with biologics at some point over the 9-year study period. The mean number of biologics used was highest in patients with spondyloarthropathies (1.5) [p = 0.003], with the mean stop/switch rate for the first biologic agent being lowest in patients with rheumatoid arthritis (47.4%) [p = 0.02]. The mean length of time patients remained on their first biologic agent before stopping or switching was greatest in patients with rheumatoid arthritis (21.1 months) [p = 0.26]. The biologic with the highest rate of continuation was etanercept for all groups except inflammatory bowel disease. CONCLUSION: This experience with biologic agents in older males with inflammatory diseases revealed that the mean number of agents used when rheumatologists managed rheumatoid arthritis and spondyloarthropathies was higher than when gastroenterology or dermatology specialists treated inflammatory bowel disease and psoriasis. The stop/switch rates were lowest among rheumatoid arthritis patients. Rheumatologists treating rheumatoid arthritis tended to keep patients on the first biologic for a longer period of time before stopping/switching. For those patients who remained on their first biologic agent, etanercept was the most commonly continued drug.
21886749 Multiple eruptive periungual pyogenic granulomas during anti-CD20 monoclonal antibody ther 2010 Dec 19 BACKGROUND: New targeted therapies have been developed for inflammatory and neoplastic diseases. MAIN OBSERVATION: We report on a 73-year-old woman who developed multiple eruptive periungual and subungual pyogenic granulomas. Because of severe rheumatoid arthritis the patient was treated with monoclonal anti-CD20 antibodies. Eruptive granuloma pyogenicum developed after the second antibody application and remained more than 8 weeks after targeted therapy was over. New lesions, however, did not appear. CONCLUSION: Eruptive granuloma pyogenicum of the nail apparatus is a possible new rare adverse effect of targeted therapies. To the best of our knowledge this is the first case in association with anti-CD20 antibody treatment.
20018001 Association of KCNB1 to rheumatoid arthritis via interaction with HLA-DRB1. 2009 Dec 15 With the rapid development of large-scale high-throughput genotyping technology, genome-wide association studies have become a popular approach to mapping genes underlying common human disorders. Some genes are discovered, but many more have not been. Because these genes were not initially identified, it is reasonable to assume that their main effect is weak. We propose a method to accommodate such a situation. It is applied to the Genetic Analysis Workshop 16 Problem 1 case-control data in which shared-epitope alleles of HLA-DRB1 show very strong association with rheumatoid arthritis. Because some previous functional studies have reported association of gene KCNB1 to rheumatoid arthritis, we evaluate whether the gene KCNB1 contributes to the genetics of rheumatoid arthritis in this data set. Fifteen single-nucleotide polymorphisms from this gene were chosen. The association of KCNB1 gene to rheumatoid arthritis seems to be moderate.