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ID PMID Title PublicationDate abstract
17764011 Successful treatment using tacrolimus plus corticosteroid in a patient with RA associated 2008 Mar We report a case of rheumatoid arthritis (RA) complicated by myelodysplastic syndrome (MDS) successfully treated by tacrolimus. A 57-year-old woman had persistent pain and swelling in bilateral wrist and knee joints, in addition to severe anemia and leukopenia. She was diagnosed with MDS and RA based on the results of bone marrow aspiration and the criteria of RA. Combination therapy with tacrolimus (1.5 mg day(-1)) and prednisolone (10 mg day(-1)) improved her bicytopenia and polyarthralgia.
17499763 Plasma exchange for rheumatoid arthritis. 2007 Apr Rheumatoid arthritis (RA) is the most common inflammatory joint disease. Even though, physiopathology of rheumatoid arthritis remains unclear, the presence of circulating immune complexes and rheumatoid factors had led to the use of plasma exchange (PE). Even though PE procedures have evolved over the last decades, their indications and use in RA must be replaced in the context of the evolution of disease-modifying anti-rheumatic drugs. Results of PE and leukapheresis were disappointing in patients with severe and resistant RA. Conversely, immunoadsorption, and particularly over a Staphylococcus aureus protein A column, has resulted in some good responses in refractory RA patients. But, the emergence of effective biologics has clearly restrained their use and limited their indications to some rare patients with refractory and severe RA.
16462521 Imaging outcomes and their role in determining outcomes in osteoarthritis and rheumatoid a 2006 Mar PURPOSE OF REVIEW: This review describes the advances in knowledge of outcomes that have occurred recently as a result of imaging research in both osteoarthritis and rheumatoid arthritis. RECENT FINDINGS: Recent imaging advances in osteoarthritis have offered insights into fundamental questions including the cause of pain and reasons for disease progression. Although ongoing disease modification clinical drug trials in osteoarthritis mostly use standardized plain radiographs to monitor structural changes in the joint, magnetic resonance imaging is rapidly evolving as a method of monitoring joint structure and with time may become the preferred method of monitoring this feature in osteoarthritis clinical trials. The past decade has seen major advances in the treatment of rheumatoid arthritis in which imaging determines whether individual agents or therapeutic regimens are structure modifying. Although conventional radiography remains the gold standard for assessing structural progression in rheumatoid arthritis, growing work on the performance metrics of magnetic resonance imaging has resulted in its increasing use in trials. Ultrasonography shows preliminary promise as a useful outcome measure. SUMMARY: Recent advances in imaging are improving our understanding of the etiopathogenesis and treatment of persons with osteoarthritis and rheumatoid arthritis. Complex challenges face us over the coming years as clinicians and researchers grapple with the use of these new techniques, the insights they may provide, and their clinical application.
17109060 Prognostic factors of radiographic progression in early rheumatoid arthritis: a two year p 2007 Jul The objective of the study was to analyze the prognostic factors of radiographic progression in a series of patients with early rheumatoid arthritis (RA) after 2 years of therapy with a structured algorithm using disease-modifying antirheumatic drugs (DMARDs) and very low doses of oral glucocorticoids. One hundred and five patients (81% female) with early RA (disease duration <2 years) treated with the same therapeutic protocol using gold salts and methotrexate in a step-up strategy, together with methylprednisolone (4 mg/day), were followed up for 2 years. The outcome variable was radiographic progression after 2 years of DMARD therapy using the modified Larsen method. Clinical, biological, immunogenetic, and radiographic data were analyzed at study entry and after 1 and 2 years of follow-up. Radiographic progression (increase of four or more units in the Larsen score) was observed in 32% of patients after 2 years of follow-up. The percentage of erosive disease increased from 18.3% at baseline to 28.9% at 12 months and 44.6% at 24 months, in spite of a significant improvement in disease activity. New erosions appeared in 33% of patients after 2 years. Several baseline parameters were associated with radiographic progression in the univariate analysis: shared epitope (SE) homozygozity, HLA-DRB*04 alleles, female gender, hemoglobin, erythrocyte sedimentation rate, and anticyclic citrullinated peptide antibodies (anti-CCP). In the multivariate analysis, female gender [odds ratio (OR) 5.5, 95% confidence interval (CI): 1.1-28.2, p = 0.04], DRB1*04 alleles (OR 3.1, 95% CI 1.1-9, p = 0.03) and, marginally, anti-CCP antibodies (OR 3.6, 95% CI 0.9-14.5, p = 0.06), were associated with progression. Female patients with both DRB1*04 alleles and anti-CCP antibodies showed the highest scores in radiographic progression. The presence, but not the titer, of anti-CCP antibodies predicted progression. The positive predictive value of the multivariate model for progression was only 53.9% whereas the negative predictive value was 80.3%. In a series of early RA patients treated with a structured algorithm using DMARDs and very low doses of glucocorticoids, radiographic progression was observed in one third of patients after 2 years. Female gender, DRB1*04 alleles (rather than the SE), and the presence of anti-CCP antibodies at baseline (independently of the titer) were the most important predictors of progression. The utility of these parameters in clinical practice is limited by their relatively low positive predictive value.
17897462 A case-control study of rheumatoid arthritis identifies an associated single nucleotide po 2007 Rheumatoid arthritis (RA) is a chronic inflammatory disease with a heritability of 60%. Genetic contributions to RA are made by multiple genes, but only a few gene associations have yet been confirmed. By studying animal models, reduced capacity of the NADPH-oxidase (NOX) complex, caused by a single nucleotide polymorphism (SNP) in one of its components (the NCF1 gene), has been found to increase severity of arthritis. To our knowledge, however, no studies investigating the potential role played by reduced reactive oxygen species production in human RA have yet been reported. In order to examine the role played by the NOX complex in RA, we investigated the association of 51 SNPs in five genes of the NOX complex (CYBB, CYBA, NCF4, NCF2, and RAC2) in a Swedish case-control cohort consisting of 1,842 RA cases and 1,038 control individuals. Several SNPs were found to be mildly associated in men in NCF4 (rs729749, P = 0.001), NCF2 (rs789181, P = 0.02) and RAC2 (rs1476002, P = 0.05). No associations were detected in CYBA or CYBB. By stratifying for autoantibody status, we identified a strong association for rs729749 (in NCF4) in autoantibody negative disease, with the strongest association detected in rheumatoid factor negative men (CT genotype versus CC genotype: odds ratio 0.34, 95% confidence interval 0.2 to 0.6; P = 0.0001). To our knowledge, this is the first genetic association identified between RA and the NOX complex, and it supports previous findings from animal models of the importance of reactive oxygen species production capacity to the development of arthritis.
16249224 Incidence of lymphoma in a large primary care derived cohort of cases of inflammatory poly 2006 May OBJECTIVE: To determine the risk of lymphoma in a primary care derived cohort of new onset cases of inflammatory polyarthritis and assess the contribution of disease severity and standard immunosuppressive treatment. DESIGN: Prospective cohort study. METHODS: 2105 subjects with new onset inflammatory polyarthritis were recruited to the Norfolk Arthritis Register (NOAR) and followed annually for (median) 8.4 years. Occurrence of lymphoma was determined by annual morbidity review and linkage to the central hospital database serving the NOAR area. Cases of lymphoma were verified by record review. Standardised incidence ratios (SIRs) for lymphoma were calculated compared with the local, age, sex, and calendar year expected rates. Stratified analyses were undertaken for various markers of disease severity and treatment history. RESULTS: There were 11 cases of lymphoma during 15,548 person years of follow up, the majority of which were of large B cell type. Compared with the local population the SIR was 2.4 (95% confidence interval, 1.2 to 4.2). The risks in cases classified as rheumatoid arthritis, ever rheumatoid factor positive, or ever treated with DMARDs were all higher, the highest risk group being those treated with methotrexate: SIR = 4.9 (1.8 to 10.6). CONCLUSIONS: There was a doubling in risk of lymphoma in new onset cases of inflammatory polyarthritis. Patients with the most severe disease were twice as likely as other patients to develop lymphoma. These results need to be taken into account when considering reported increased risks of lymphoma compared to background population risk in users of new biological agents.
18274814 Antioxidant intervention in rheumatoid arthritis: results of an open pilot study. 2008 Jun There is evidence that reactive oxygen species play a causal role in auto-immune diseases, such as rheumatoid arthritis (RA). Despite the supporting evidence for a beneficial effect of antioxidants on clinical characteristics of RA, the right balance for optimal effectiveness of antioxidants is largely unknown. To determine the potential beneficial effects of an antioxidant intervention on clinical parameters for RA, an open pilot study was designed. Eight non-smoking female patients with rheumatoid factor + RA and a Disease Activity Score (DAS 28) higher than 2.5 were enrolled in the study. Patients had to be receiving stable non-steroidal anti-inflammatory drug treatment and/or 'second line' medication for at least 3 months. The pilot group consumed 20 g of antioxidant-enriched spread daily during a period of 10 weeks. The intervention was stopped after 10 weeks and was followed by a 'wash-out' period of 4 weeks. At t = 0, t = 10 weeks and t = 14 weeks, patients' condition was assessed by means of DAS. In addition, standard laboratory analyses were performed, and blood-samples for antioxidants were taken. The antioxidant-enriched spread was well tolerated. All laboratory measures of inflammatory activity and oxidative modification were generally unchanged. However, the number of swollen and painful joints were significantly decreased and general health significantly increased, as reflected by a significantly improved (1.6) DAS at t = 10 weeks. The antioxidant effect was considered beneficial as, compared to the scores at t = 0, the DAS significantly reduced at t = 10 weeks. Increase of the DAS (0.7) after the "wash-out period" at t = 14 confirmed a causal relation between changes in clinical condition and antioxidants. This open pilot study aimed to assess the clinical relevance of an antioxidant intervention as a first step in assessing potential beneficial effects of antioxidants on rheumatoid arthritis. These conclusions need to be validated in a larger controlled study population.
17911418 Profiling meta-analysis reveals primarily gene coexpression concordance between systemic l 2007 Sep Consensus gene expression profiling by meta-analysis of 4,500 cDNA sequence microarray data obtained from patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) was assembled and systematically analyzed. The normalized data were statistically analyzed by the significance analysis of microarray (SAM) program (false discovery rate
17657670 Rheumatoid arthritis: what does it cost and what factors are driving those costs? Results 2007 May OBJECTIVE: We sought to investigate the cost of living with rheumatoid arthritis (RA) and evaluate the influence of both demographics and specific disease characteristics on these costs. METHODS: We used a population-based questionnaire to survey 895 patients living in the city of Malmö, Sweden, during 2002. Data were obtained on direct resource consumption, investments, informal care and work capacity, as well as utility, function and patients' assessment of disease severity and pain. RESULTS: The survey was completed by 613 patients (68%). Their mean age was 66 years, 74% were female and the mean duration of disease was 16.7 years. The total mean annual cost per patient was 108,370 SEK (12,020 EUR). Direct costs represented 41% of that amount and were predominantly for drugs [14% of the participants were receiving treatment with tumour necrosis factor (TNF) blockers], community services and hospitalisation. Function measured with the Health Assessment Questionnaire (HAQ) was the main statistical predictor for all types of costs except sick leave, which was most strongly associated with patients' perception of global health. CONCLUSION: This is the first study in Sweden to include all costs incurred by a group representative of RA in the community. In comparison with previous studies, total costs had increased by more than 40%. Furthermore, direct costs were higher and constituted a great proportion of total costs because of more intensive treatments (i.e. the use of TNF blockers). Future comparisons will enable health economic evaluations on a community level.
17889335 Model-based erosion spotting and visualization in rheumatoid arthritis. 2007 Oct RATIONALE AND OBJECTIVES: A method for the automatic detection and the visualization of erosions caused by rheumatoid arthritis is investigated. Erosion-enhanced viewing is a contribution to the computer-aided diagnosis of rheumatoid arthritis. It supports the clinician by providing the automatic marking of erosions and the visualization of any deviations from intact anatomy for a concise reviewing interface. MATERIALS AND METHODS: A generative appearance model is used to capture the variability of intact bone and erosions. The algorithm marks erosions on hand radiographs using this model, and visualizes these erosions with the help of the residual appearance error after fitting the model built from intact bone texture. The algorithm was evaluated on 17 hand radiographs. The standard of reference was an annotation of the erosions by a musculoskeletal radiologist. RESULTS: Detection results from the algorithm are reported for a set of 17 radiographs of moderately diseased hands. With a specificity of 84%, the detection of unequivocal erosions achieved a sensitivity of 85%. A receiver operating characteristic analysis yields an area under the curve of 0.92. The visualization provided a clear representation of the erosions as determined by two musculoskeletal radiologists. CONCLUSION: The automatic spotting of erosions provides promising results, and the visualization of the deviation from healthy anatomy aids clinicians in the evaluation of the erosions and in the reviewing of automatic detection results.
16670824 Radiographic study of joint destruction patterns in the rheumatoid elbow. 2007 Apr Knowledge of the pattern of joint destruction is important for planning the therapeutic approach to rheumatoid arthritis (RA) of the elbow. Accordingly, we carried out a large-scale radiographic study with the objective of elucidating the joint destruction pattern in rheumatoid elbows. From 2001 through 2003, we examined and took plain X-rays of both elbows of 193 RA patients (i.e., 386 elbows), consisting of 18 men and 175 women, with a mean age of 57.0 years. Radiographic images of the elbow joints were used to classify the degree of bone loss in various zones on the elbow joint surface into four grades of severity, and joint destruction was compared between the left and right elbows. In addition, correlation in the extent of bone loss between each of the zones of the same elbow and differences in the extent of bone loss were analyzed statistically. The results showed direct correlations for destruction of the elbow joint surface among the zones for the left and right elbow joints and in the same elbow joint. However, more severe destruction was observed on the radial side of the humeral trochlea, and it was surmised that destruction of the elbow joint must begin at that site and gradually spread mediolaterally. In addition, in the same elbow joint, the correlation in the degree of bone loss between the trochlea of humerus and the trochlear notch was especially strong, indicating that the bone destruction at both sites represented mirror lesions. We conclude that when performing radiographic diagnosis of the joint damage in the rheumatoid elbow, knowledge of this pattern of joint destruction will be useful for assessing whether there is joint destruction in the initial stage and for deciding the therapeutic approach.
17672067 [Cardiovascular diseases in rheumatoid arthritis]. 2007 AIM: To examine the significance of conventional cardiovascular factors of risk and immunoinflammatory markers in development of vascular atherosclerosis in rheumatoid arthritis (RA). MATERIAL AND METHODS: Conventional cardiovascular risk factors were evaluated in 103 RA patients (85 females and 18 males, mean age 46.3 years, duration of the disease 75 months). Forty six controls (32 females and 14 males) had no rheumatic diseases. Vascular atherosclerosis was diagnosed at ultrasonic scanning of the carotid arteries. Highly sensitive C-reactive protein (hsCRP) concentration in the blood serum was measured with highly sensitive enzyme immunoassay. RESULTS: No differences by the rate of conventional cardiovascular risk factors between the groups were identified except arterial hypertension. Cardiovascular complications (ischemic heart disease, myocardial infarction, transient ischemic attacks) occurred more frequently in RA patients. Intima/media complex (IMC) thickness differences between the groups were not registered. Atherosclerotic plaques were detected more often in RA patients. In RA patients there was a correlation between IMC thickness in the carotid arteries and age (p = 0.00001), systolic blood pressure (p = 0.001) and diastolic blood pressure (p = 0.01), concentration of blood cholesterol (C) (p = 0.03) and total coronary risk (TCR) (p = 0.003). Correlation between carotid artery IMC thickness, duration and activity of the disease, RA systemic manifestations was not detected (p > 0.05). A mean concentration of hsCRP in RA was higher than in the controls: 2.8 (4.4-25.6) mg/l and 1.3 (0.6-2.7) mg/ml, respectively (p = 0.001). A positive correlation existed between concentration of hsCRP and DAS4 (p = 0.0004) and negative--with C concentration (p = 0.01), LDL C, HDL C (p = 0.02). Increased concentration of hsCRP, IMC thickness in the carotid arteries, existence of atherosclerotic plaques and clinical picture of vascular atherosclerosis related insignificantly. CONCLUSION: RA patients often suffer from cardiovascular pathology. Immunological markers of inflammation, primarily, hsCRP, in addition to conventional cardiovascular risk factors are essential in development of vascular atherosclerosis.
16465612 Rheumatoid arthritis: inflammation and bone loss. 2006 Jan Chronic synovial inflammation is usually accompanied by bone erosion. Due to resulting structural damage, bone erosion is a major reason for disability in RA patients. Anti-rheumatic drug therapy is focussed not only on the control of synovial inflammation but also on preserving bone from structural damage. Bone erosion in arthritis is a consequence of synovial osteoclast formation. Therapeutic approaches which interfere with synovial osteoclastogenesis and/or osteoclast activation are therefore of great interest. This review describes the mechanism of inflammatory bone loss, describes its cellular and molecular players and gives insights in current therapeutic tools to inhibit this process.
17965559 Methylenetetrahydrofolate reductase and reduced folate carrier-1 genotypes and methotrexat 2007 Oct We investigated the genotypes of methylenetetrahydrofolate reductase (MTHFR) and reduced folate carrier-1 (RFC-1), and the serum concentrations of methotrexate (MTX) in 100 outpatients with rheumatoid arthritis (RA). Frequencies of MTHFR C677T and A1298C were similar to those reported in Japanese RA patients, while frequencies of RFC-1 G80A genotypes differed from those reported in RA patients in the United States. No correlations were found between these genotypes and serum MTX levels.
16705047 Macrophage migration inhibitory factor and glucocorticoid sensitivity. 2006 Aug Glucocorticoids (GCs) are widely used in the treatment of inflammatory diseases including rheumatoid arthritis (RA). Treatment with GC is associated with significant dose-dependent side-effects. The pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) has emerged in recent years as a candidate factor which could regulate GC sensitivity. MIF is induced by GC, and is able to override anti-inflammatory actions of GCs. In this review, we summarize the pro-inflammatory actions of MIF with respect to RA, describe the interactions between MIF and GC and examine new evidence, which identifies MIF as a specific target for steroid sparing.
18194075 Antigen-specific therapy of rheumatoid arthritis. 2008 Feb BACKGROUND: Immunotherapy offers the promise of antigen-specific suppression of pathological immune responses in conditions such as autoimmunity and organ transplantation. Substantial advances have been made in recent years in terms of understanding basic immunological mechanisms of autoreactivity, as well as clinically implementing immune-based therapies that are antigen nonspecific. OBJECTIVE: To provide an integrated overview of the current state of the art in terms of antigen-specific tolerance induction, as well as to predict future directions for the field. METHODS: Examples of successes and failures of antigen-specific immunotherapy were sought. Particular attention was paid to the well-established collagen II-induced model of arthritis. RESULTS/CONCLUSIONS: Previous failures of antigen-specific immunotherapy were associated with lack of identification of clinically relevant antigens, as well as inappropriate tolerogenic methodologies. The advances in proteomics combined with novel gene-specific immune modulatory techniques place today's translational researchers in a unique position to tackle the problem of antigen-specific immunotherapeutic protocols.
16893550 Soluble human leukocyte antigen: a diagnostic indicator of rheumatoid arthritis? 2006 Aug 31 Early stage rheumatoid arthritis (RA) is often difficult to diagnose because initial symptoms are non-specific. To aid diagnosis, suitable serological diagnostic markers are sought. Elevated levels of soluble MHC class II (soluble human leukocyte antigen; sHLA-DR) in human serum have been associated with rheumatoid and 'rheumatoid-like' autoimmune diseases. As a result, sHLA-DR has been suggested as a specific marker of RA. However, reported levels of sHLA-DR in sera of healthy donors vary significantly and the mechanism of release of HLA-DR into serum is poorly understood. Investigations into the diagnostic potential of this molecule necessitate the development of a sensitive and specific sHLA-DR assay. We have investigated multiple ELISA setups to develop such an assay and false positive signal has been carefully removed using a combination of isotype-matched controls and immuno-depletion. sHLA-DR levels in sera of RA patients were not significantly different from those in healthy donors which suggests sHLA-DR has limited utility in the diagnosis of RA. In RA patients, we detected high levels of sHLA-DR in aspirated synovial fluid (SF), but this did not correlate with sHLA-DR levels in serum.
16582690 Synovial cell activation. 2006 May PURPOSE OF REVIEW: Modern molecular biology offers a unique opportunity to gain a comprehensive picture of gene expression in a disease state. This review presents recent findings in the field of synovial fibroblast biology contributing to knowledge of the pathogenesis of rheumatoid arthritis. RECENT FINDINGS: Recently it has become apparent that innate immune response pathways play a critical role in driving synovial activation and contribute significantly to the turnover of leukocytes in the synovial compartment. In addition, microparticles have been identified as a new class of potent mediators, broadening the known spectrum of cell-derived modulators in the joint. Numerous research groups gained new insights into detailed molecular mechanisms leading to the invasiveness of rheumatoid arthritis synovial fibroblasts, the disturbance in the regulation of apoptosis, and synovial cell-cell and cell-matrix interactions. SUMMARY: The key role of synovial fibroblasts in the pathogenesis of rheumatoid arthritis has been highlighted by the fact that these cells not only are the main executors of cartilage and bone destruction but also modulate numerous interactions in rheumatoid joints. Moreover, it has become evident that integration of a large body of information is indispensable to get a comprehensive outlook on synovial activation in the pathology of rheumatoid arthritis.
18260487 Two methods of atlantoaxial stabilisation for atlantoaxial instability. 2007 Dec Thirty-seven patients, 19 males and 18 females, with a mean age of 37.6 years (range 9-62), underwent atlantoaxial fusion for atlantoaxial instability associated with pseudarthrosis of the odontoid, fixed rotary subluxation, rheumatoid arthritis, and mongolism. Two operative techniques were used: transarticular C1-C2 screws and posterior bone grafts according to Magerl, but without posterior wiring, in 24 patients (group 1), and C1 lateral mass screws/C2 pedicle screws, plates and posterior bone grafts, according to Goel, in 13 patients (group 2). The mean follow-up period was 27.6 months. In both groups 92% of the patients were free of neck pain. In group 1, 4 out of 9 patients with neurological involvement improved one Frankel grade and in group 2, 3 out of 5. The fusion rates were 96% and 100%, respectively; they were superior to the rates mainly seen after a Gallie fusion: 67 to 86%. One vertebral artery injury without sequelae occurred in group 1, and one wound infection, that healed with debridement, in group 2. In conclusion, the results were excellent in both groups, but slightly better in group 2.
17476612 Circulating endothelial progenitor cells as a link between synovial vascularity and cardio 2007 Mar Cardiovascular disease refers to the class of diseases that involve the heart and/or blood vessels (arteries and veins). Most Western countries face high and ever-increasing rates of cardiovascular disease. Each year, more Americans are killed by heart disease than by cancer. Diseases of the heart alone cause 30% of all deaths, with other diseases of the cardiovascular system causing substantial further deaths and disability. Indeed, cardiovascular disease is the major cause of death and disability in the USA and most European countries. The development of the vascular systems requires an intricate interplay of molecules such as vascular endothelial growth factor and endothelial progenitor cells. A defective vascular repair/regeneration is thought to be responsible for propagation of atherosclerosis, a key feature of cardiovascular disease. This is partly attributed to a reduction in the circulating endothelial progenitor cells in peripheral blood. Patients with rheumatoid arthritis (RA) have a higher than average incidence of cardiovascular disease in comparison with the general population, with an increased risk of stroke and myocardial infarction, and an increased risk of fatality following myocardial infarction. This review focuses on the current evidence linking the role played by endothelial progenitor cells to the development of cardiovascular disease and why this might relate to the increased risk observed in RA patients.