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

ID PMID Title PublicationDate abstract
23675020 Expression of Retinoic Acid Receptor (RAR) α Protein in the Synovial Membrane from Patien 2007 Mar Retinoic acid receptors (RAR) are expressed in inflammatory cells and, through ligand binding, play an important role in cell proliferation and differentiation, as well as in regulation of cytokine and matrix metalloproteinase (MMP) production. Inflammatory cytokines and MMPs play a significant role in cartilage destruction in osteoarthritis (OA) and in joint destruction in rheumatoid arthritis (RA), the prototype of inflammatory arthritis. To determine if RARα is expressed in the synovial membrane (SM) of patients with OA and compare it with RA, SM biopsy samples were used in this study which were from 31 patients with late OA and 14 patients with late RA. Cryostat sections were studied by immunochemistry using a RARα-specific antibody. All SM samples from OA and RA patients exhibited cellular localization for RARα. Immunoreactivity was present in mononuclear inflammatory cells, endothelial cells, synovial lining cells, and fibroblasts. Inflammatory infiltrates were interstitial and nodular. Roughly one half of mononuclear cells in the inflammatory nodules in OA and RA were positive for RARα. The conclusion is that the presence of RARα in SM of patients with OA and RA suggests that RARs may play a role in the immunomodulation of synovial inflammation and therefore can be a potential target of therapeutic intervention in these arthritides.
18557533 [Adult onset Still's disease]. 2008 Apr 23 Adult onset Still's disease (AOSD) is a rare systemic inflammatory disorder affecting mainly young adults. AOSD is characterized clinically by spiking fever, arthritis, evanescent rash, sore throat, enlargement of lymph nodes and splenomegaly, and biologically by neutrophilic leukocytosis, high levels of ferritine and elevated liver enzymes. None of these features are specific, and although several classification criteria have been proposed, AOSD remains a diagnosis by exclusion. Its causes and pathomechanism are still unknown, although there is increasing evidence of dysregulated innate immune response. Treatment mainstays are systemic corticosteroids and methotrexate. Blockade of proinflammatory cytokines may be effective in the substantial proportion of patients with poor response to classical immunosuppressants.
16362444 Juvenile rheumatoid arthritis and bronchiolitis obliterans organized pneumonia. 2007 Feb Diverse pleuropulmonary manifestations, including pleural effusion, rheumatoid nodulosis, fibrosis, obliterans brochiolitis, bronchiectasias, vasculitis, drug-induced lung disease, and obliterans bronchiolitis with organized pneumonia, have been described in patients with rheumatoid arthritis (RA). Bronchiolitis obliterans organized pneumonia (BOOP) is an uncommon condition described in patients with RA but not in juvenile RA (JRA). We described a patient with JRA who developed a BOOP.
18466451 A Bayesian genome-wide linkage analysis of quantitative traits for rheumatoid arthritis vi 2007 Rheumatoid arthritis is a complex disease caused by a combination of genetic, environmental, and hormonal factors, and their additive and/or non-additive effects. We performed a linkage analysis to provide evidence of rheumatoid factor IgM on linkage, based on Bayesian variable selection coupled with the new Haseman-Elston method. For statistical inferences to estimate unknown parameters, we utilized the perfect sampling algorithm, an emerging simulation technique that alleviates concerns over convergence and sampling mixing. Our methods provide powerful and conceptually simple approaches to simultaneous genome scans of main effects and all possible pairwise interactions. We apply them to the Genetic Analysis Workshop 15 data (Problem 2) provided by the North American Rheumatoid Arthritis Consortium (NARAC).
21794426 [Rheumatoid arthritis and myocardiopathy. A patient awaiting a heart transplant]. 2007 Jul Cardiovascular pathology is common in rheumatoid arthritis. However, myocardial affection is unusual and clinical disease is rare. We report a case of dilated cardiomyopathy in a patient with rheumatoid arthritis and progressive heart failure that required inclusion into a heart transplantation list.
17009016 Is measurement of IgM and IgA rheumatoid factors (RF) in juvenile rheumatoid arthritis cli 2007 Feb The prevalence and clinical relevance of IgM and IgA RF detected by ELISA were studied in 91 patients with juvenile rheumatoid arthritis (JRA) and 45 healthy children. IgM and IgA RF were detected, respectively, in 33 and 44% of the patients, compared to 6.7 and 15.6% of the healthy children (p = 0.001 and 0.0006, respectively). The frequency of IgM RF was significantly higher in patients with polyarticular (52%) as compared to systemic onset JRA (21%; p = 0.04). Five out of ninety-one patients and none of the control group were IgM RF positive by the latex test. High levels of IgM RF were detected more frequently in patients with active disease (p = 0.01) and positive latex agglutination test (p < 0.001) and had a marginally significant association with severe radiological deformities (p = 0.05). The presence of IgA RF was associated with active disease in polyarticular onset JRA children (p = 0.04). In conclusion, high levels of IgM RF and the detection of IgA RF can be useful in assessing clinical activity in a subset of patients with JRA.
23105680 A clinical study on cortisol and certain metabolites in some chronic psychosomatic disorde 2007 Sep Present clinical study involved two groups of psychosomatic disorders, bronchial asthma and rheumatoid arthritis. In the study, the levels of plasma cortisol, blood glucose, total cholesterol and triglycerides were estimated in 125 clinical subjects, (50 normal controls, and 40 having bronchial asthma and 35 suffering from rheumatoid arthritis. The results showed a significant change in the levels of plasma cortisol and blood glucose in both the stressed clinical groups' vis-à-vis normal controls. The levels of atherogenic lipids (total cholesterol and triglycerides) were found quite elevated in both the diseased groups. However, in rheumatoid arthritis, the physiological changes were relatively more pronounced. The findings of this study indicate that rheumatoid arthritis is a relatively more chronic and late onset disorder as the functional performance of hypothalamopituitary-adrenocortical axis gradually declines with passage of time and the ability of the adrenocortical response to return to normalcy becomes impaired.
19707430 Review of tocilizumab in the treatment of rheumatoid arthritis. 2008 Mar Constitutively overproduced in proliferating synovial tissues, interleukin-6 (IL-6) is deeply involved in the pathology of rheumatoid arthritis (RA). Tocilizumab is a humanized anti-human IL-6 receptor antibody that binds to soluble and membrane-bound IL-6 receptor, and at detectable levels in blood, tocilizumab is capable of almost completely blocking the transmembrane signaling of IL-6. In clinical trials for patients with RA in Japan, tocilizumab monotherapy has shown clinical efficacy equaling that of tumor necrosis factor (TNF) inhibitor in combination with methotrexate, and in an extension study in patients who responded to tocilizumab, almost no patients showed a decrease in the efficacy of tocilizumab. Evidence obtained in a phase III study in Japan demonstrated that tocilizumab monotherapy had a sig-nificant inhibitory effect on the progression of structural joint damage compared with that of conventional disease modifying antirheumatic drugs (DMARDs). Furthermore it has been shown that tocilizumab has an excellent ability to suppress serum amyloid A levels and could therefore be an important therapeutic strategy in amyloid A amyloidosis secondary to rheumatic diseases. The safety profile of tocilizumab appears to be satisfactory. However, several serious infections were also reported, and careful monitoring is therefore important during use.
18516269 Shared decision-making based on different features of risk in the context of diabetes mell 2007 Dec There is an increased awareness about patients' involvement in the clinical decision process where uncertainty is an unavoidable condition. The impact of psychological factors like risk aversion, risk aversion and time, asymmetry in risk aversion, and risk and control on shared decision-making is discussed. In addition to differences in risk estimates, doctors and patients may exhibit a difference in perception of time perspectives, and losses versus gains.A summary of valuation factors in shared decision-making is presented: (a) the doctors tend to follow expected value combinations more closely, while the patient is more risk aversive; (b) unwillingness to take risks increases for rare outcomes; (c) there is an increased tendency to take risks with delayed outcomes of the decisions; (d) the doctor is generally well informed about risk and time aspects for different diseases, whereas this might not always be the case with the patient; (e) rheumatoid arthritis and diabetes mellitus are chronic diseases, and both create a vulnerability to a variety of complications over time; (f) rheumatoid arthritis demands different combinations of treatments sequentially over time, whereas diabetes mellitus is treated with insulin; (g) many diseases, like rheumatoid arthritis and diabetes mellitus, are not completely affected by control, as the disease may constantly progress.
29793290 Pharmacogenomics in the treatment of rheumatoid arthritis: clinical implication and perspe 2006 May Rheumatoid arthritis (RA) is a chronic inflammatory disease. The inflammatory process of the joint destroys articular architecture and causes a significant disability. The efficacy of disease modifying antirheumatic drugs such as methotrexate, sulfasalazine and biological response modifiers, is widely accepted. However, the outcome of the treatment with these agents is known to vary among patients. The application of the pharmacogenomics is expected to reduce toxicities and enhance the desirable effects of therapeutic agents for RA. Recently, pharmacogenomic studies on methotrexate, sulfasalazine and tumor necrosis factor-α inhibitors have been reported. These investigations suggest that the pharmacogenomic approach is useful for the treatment of RA, although there are points to be considered before the translation of the pharmacogenomic data into clinical practice. This review focuses on the latest information on the pharmacogenomics of antirheumatic drugs and its clinical implication in the treatment of RA.
16384777 Etanercept and demyelinating disease in a patient with psoriasis. 2006 Jan The tumor necrosis factor-alpha antagonist (TNF-alpha) etanercept has been approved for the treatment of rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and psoriasis. Earlier reports on the use of etanercept or infliximab in patients with rheumatoid arthritis, psoriatic arthritis, or juvenile rheumatoid arthritis suggested an increased risk of demyelinating disease. It is imperative that dermatologists have a keen awareness of this possible adverse event given the increased use of this class of drugs. We report a case of demyelinating disease occurring in a patient treated for psoriasis. The relation of TNF-alpha antagonist therapy to demyelinating disease/multiple sclerosis is explored. It is recommended that patients be diligently screened before starting TNF-alpha antagonist therapy and that vigilance for symptoms of demyelinating disease/multiple sclerosis be included in follow-up examinations during treatment with these drugs.
17992595 Conventional therapy of Sjogren's syndrome. 2007 Jun Sjogren's syndrome (SS) is a chronic autoimmune disorder affecting mainly middle-aged women. It is characterized by lymphocytic infiltration and destruction of the exocrine glands (mainly the salivary and lacrimal glands), resulting in dry mouth and eyes. Symptoms of SS are chronic and sometimes devastating, compromising the quality of life at a major extent. Despite its autoimmune nature, evidence for the use of immunosuppressive agents, which are the mainstay of therapy of diseases of autoimmune origin, is limited. Keratoconjunctivitis sicca (KCS), the main ocular manifestation of SS, is managed with tear substitutes, as well as local and systemic stimulators of tear secretion and supportive surgical procedures. Management of oral manifestations includes intense oral hygiene, prevention and treatment of oral infections, use of saliva substitutes, and local and systematic stimulation of salivary secretion. Cholinergic agents, such as pilocarpine and cevimeline are the cornerstone of current therapy in SS. Corticosteroids, cyclophoshamide, and nucleoside analogues are reserved for severe extraglandular manifestations of SS. The role of anti-B-cell therapy is a promising option for glandular and extraglandular manifestations of the disease, as well as for the management of SS-associated lymphoma.
21221183 Abatacept: the evidence for its place in the treatment of rheumatoid arthritis. 2008 Feb 29 INTRODUCTION: Rheumatoid arthritis (RA) is the most common inflammatory joint disease in adults with a prevalence of 0.5-1%. The development of targeted therapies, especially anti-TNF (tumor necrosis factor) treatment, has improved disease outcome during the last decade. But despite this progress 25-30% of patients still show unsatisfactory response. Abatacept is a costimulation blocker that inhibits T-cell activation and interrupts the process that leads to inflammation in RA. AIMS: The purpose of this article is to review the clinical trials of abatacept and to discuss how it will fit into the treatment of RA. The medical literature was reviewed for appropriate articles and 123 articles have been identified containing the search terms "abatacept OR CTLA4-Ig AND rheumatoid." All clinical trials were reviewed with respect to clinical and radiologic outcome, quality of life, and safety of patients with RA receiving abatacept therapy. EVIDENCE REVIEW: There are seven (phase II or phase III) clinical trials that have clearly demonstrated efficacy and safety of this new drug. Furthermore, radiographic data show that abatacept also inhibits the progression of joint destruction, one of the important burdens of RA. Abatacept can be used concomitantly with conventional disease-modifying antirheumatic drugs or as monotherapy. Due to an increased risk of infections and malignancies but without an important enhancement of efficacy, simultaneous treatment with abatacept and other biologic response modifiers is not recommended. PLACE IN THERAPY: With its different mechanism of action, abatacept may be an alternative therapy for patients with an inadequate response to other arthritis therapies, especially for those patients with RA refractory to anti-TNF treatment. Cost effectiveness is dependent on underlying disease progression.
19707447 Prevention of bone mineral density loss in patients with rheumatoid arthritis treated with 2008 Dec This review focuses on recent advances in the effect of anti-TNFalpha therapy on bone metabolism and bone mineral density (BMD) in rheumatoid arthritis (RA). RA is a chronic disease characterized by inflammation of the synovial joint, cartilage degradation, and subsequent bone destruction. Bone damage is often manifested as erosions, localized juxta-articular bone loss, or generalized bone loss. Thus, blockade of TNFa not only serves to block inflammation, but also halts the erosive nature of RA and generalized/localized juxta-articular bone loss. Here, we review recent findings showing that anti-TNFa therapy is also effective on halting systemic bone loss. In vitro, TNFa reduces osteoblast activity and increases osteoclast activity through RANKL-RANK pathway. In arthritis animal models, an imbalance between bone formation and resorption is observed. In humans, this coupling of destruction is restored by anti-TNFalpha therapy early on, but only for a few months. Thus, anti-TNFalpha prevents the BMD loss in RA patients. In summary, TNFa blockade is not only able to prevent joint destruction, but it is also able to prevent bone loss in RA patients. Future studies are needed to address if TNFa blockers have an effect on bone fractures.
18460272 Rheumatoid factors and anticyclic citrullinated peptide antibodies in pediatric rheumatolo 2008 Apr Juvenile idiopathic arthritis (JIA) is a heterogenous childhood disease without reliable biomarkers for monitoring disease progression. Immunoglobulin (Ig) M rheumatoid factor (RF) is used to define a subset of JIA patients, but its significance in JIA is dependent on the method of measurement. In addition to IgM RF, IgA RF has been implicated in determining disease severity in JIA, including functional disability and joint damage. Anticyclic citrullinated peptide (anti-CCP) antibodies have been a valuable diagnostic tool in rheumatoid arthritis, with varied results in their significance in JIA patients. Recent studies have demonstrated the possible usefulness of isotypes of anti-CCP antibodies in monitoring JIA patients to determine disease outcome. Overall, RF isotypes and anti-CCP isotypic antibodies have demonstrated increasing importance in the evaluation of JIA patients to determine which patients may have more aggressive or severe disease and to aid in possible treatment plans to prevent joint damage and disability.
17603463 The value of synovectomy of the knee in the treatment of rheumatoid arthritis. 2006 Feb 28 The goal of the present study is to evaluate the usefulness of synovectomy of the knee joint in patients with rheumatoid arthritis. Synovectomy of the knee is the most common lower limb operation performed in patients with rheumatoid arthritis. Depending on the stage of the disease, the symptoms, and the degree of intra-articular changes in the radiological image, there are indications for performing both early and late synovectomy. The progress of the disease is not dependent on its duration, but on the aggressiveness and dynamics of the rheumatoid process. The authors present the advantages of early synovectomy, which halts the progress of the disease and protects the joint from destruction. After early synovectomy one obtains an average of 75% good outcomes, while after late synovectomy the percentage of positive outcomes is about 70%. The authors point out the effectiveness and low level of invasiveness of arthroscopic synovectomy, thanks to which the progress of the disease can be checked and monitored. Another possible therapy is chemical synovectomy, with the specific action of radioisotopes: synoviorthosis with laser irradiation. The authors emphasize that an important factor in obtaining good outcome after every synovectomy is rehabilitation, during which the range, frequency of exercise, and physicotherapeutic procedures are established, depending on the stage of advancement of the rheumatoid process.
18973686 Adalimumab induced mononeuritis multiplex in a patient with refractory rheumatoid arthriti 2008 Oct 30 BACKGROUND: Anti tumor necrosis factor agents are a valuable addition to the armamentarium against rheumatoid arthritis but have some serious side effects which clinicians should be aware about. CASE PRESENTATION: We present a case of a 54 year old Caucasian male with refractory rheumatoid arthritis who developed mononeuritis multiplex four weeks after starting adalimumab therapy. CONCLUSION: Complete resolution of neurological and electromyography findings was seen upon stopping therapy. These agents can be a double-edged sword in the management of rheumatological illnesses. Though they help treat refractory disease, their potential side effects can include mononeuritis multiplex which can be recognized by means of clinical features, electromyography and nerve biopsy as depicted in our case.
17179701 Macrophage activation syndrome in juvenile rheumatoid arthritis successfully treated with 2006 Dec Macrophage activation syndrome (MAS) is one of the serious complications of juvenile rheumatoid arthritis (JRA) and recently, cyclosporine A has been found to be effective in patients with corticosteroid-resistant MAS. A 29-yr-old male was admitted with high fever and jaundice for one month. He was diagnosed as juvenile arthritis 16 yr ago. Physical and laboratory results showed hepatosplenomegaly, high fever, pancytopenia and impaired liver and renal function tests, elevated triglyceride and serum ferritin levels. Bone marrow biopsy showed hyperplasia of histiocytes with active hemophagocytosis. He was diagnosed as MAS associated with juvenile rheumatoid arthritis and managed with high-dose corticosteroids initially, but clinical symptoms and laboratory findings did not improve immediately. Finally, he completely recovered after treatment with cyclosporine A (3 mg/kg/day).
16909773 [Ultrasonography in diagnosing Lyme arthritis of the knee joints in correlation with anti- 2006 Lyme disease, a multi-system disorder may be associated with arthritis. Lyme arthritis most commonly affects the knee joints. Ultrasonography can show the inflammation changes of the knee joint and can be a usefull method in diagnosis of Lyme arthritis. The most freguent ultrasonographic finding was knee joint effusion. Because of Lyme arthritis similarities to rheumatoid arthritis, a serologic test antibodies against cyclic cytrulinated peptid (anty CCP) can be helpfull in distinguishing of these two diseases.
19209259 Interleukin-6 inhibitors in the treatment of rheumatoid arthritis. 2008 Aug Recent developments in understanding the immunopathogenesis of rheumatoid arthritis (RA), combined with progress in biopharmaceutical development, have facilitated the introduction of novel immune modulating therapies for this progressive debilitating disorder. Efficacy achieved with certain agents, particularly the TNF inhibitors, has spurred the development of additional biologic agents targeting other components of the dysregulated immune response relevant to the etiology and sustenance of immune driven systemic inflammation characteristic of RA. Among these other potential targets is IL-6, a cytokine with effects on numerous cell types, including those involved in the pathogenesis of RA. Based on its activities, IL-6 appeared to be a viable target for autoimmune disease. Inhibitors of IL-6 were successful in animal models of autoimmune disease paving the way for subsequent studies in humans. The greatest experience to date has been with tocilizumab, a humanized monoclonal antibody specific for the IL-6 receptor (IL-6R). Beginning with open label studies, and progressing through larger and more rigorous controlled trials, tocilizumab has been shown to have significant Efficacy in patients with RA. Additional studies analyzing its effects in varied populations of RA patients, as well as greater detail concerning its longer-term tolerability and safety, will help define the ultimate role of tocilizumab and other future inhibitors of IL-6 activity as potential therapies for RA.