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ID PMID Title PublicationDate abstract
17951300 Calorimetry outside the box: a new window into the plasma proteome. 2008 Feb 15 Differential scanning calorimetry provides a new window into the plasma proteome. Plasma from normal individuals yields a characteristic, reproducible thermogram that appears to represent the weighted sum of denaturation profiles of the most abundant constituent plasma proteins. Plasma from diseased individuals yields dramatically different signature thermograms. Thermograms from individuals suffering from rheumatoid arthritis, systemic lupus, and Lyme disease were measured. Each disease appears to have a distinctive and characteristic thermogram. The difference in thermograms between normal and diseased individuals is not caused by radical changes in the concentrations of the most abundant plasma proteins but rather appears to result from interaction of as yet unknown biomarkers with the major plasma proteins. These results signal a novel use for calorimetry as a diagnostic tool.
18495732 Clinical significance of synovial lymphoid neogenesis and its reversal after anti-tumour n 2009 May OBJECTIVE: To investigate the clinical significance of lymphoid neogenesis (LN) in rheumatoid arthritis (RA), the clinicopathological correlates of this process and its evolution after anti-tumour necrosis factor (TNF)alpha therapy in a large series of synovial tissues were analysed. METHODS: Arthroscopic synovial biopsies from 86 patients with RA were analysed by immunohistochemistry. LN was defined as the presence of large aggregates of lymphocytes with T/B cell compartmentalisation and peripheral node addressin (PNAd) positive high endothelial venules. Clinical variables at baseline and after prospective follow-up were compared in LN positive and negative RA subsets. The evolution of LN and its correlation with the clinical course in a subgroup of 24 patients that underwent a second arthroscopic biopsy after anti-TNFalpha therapy was also analysed. RESULTS: LN was present in 49% of RA synovial tissues. Patients with LN had a significantly higher disease duration and a higher previous use of anti-TNFalpha agents. During prospective follow-up, the proportion of patients achieving good or moderate European League Against Rheumatism (EULAR) 28-joint Disease Activity Score (DAS28) responses was significantly lower in patients who were LN positive despite a significantly higher use of anti-TNFalpha agents. By multivariate logistic regression analysis, LN remained as an independent negative predictor of response to therapy. In the subgroup of patients rebiopsied after anti-TNFalpha therapy, reversal of LN features occurred in 56% of the patients and correlated with good clinical responses. CONCLUSIONS: Synovial LN in RA predicts a lower response to therapy. LN features can be reversed after a short period of anti-TNFalpha therapy in parallel to good clinical responses.
18688673 Positiveness of purified protein derivatives in rheumatoid arthritis patients who are not 2009 Jan In recent years, biological agents have emerged as the most popular drugs for the treatment of rheumatoid arthritis (RA). The most frightening side effects of biological agents are infections, with tuberculosis being the leader. On account of the fact that biological agents have been used widespread, a number of algorithms have been developed to search latent tuberculosis. Among these algorithms, the most popular is the purified protein derivatives (PPD) test which is based upon late sensitivity reaction. The objective of this trial is to investigate the relevance of PPD response for the disease in RA patients. A total of 149 subjects (80 patients, 69 healthy), 35 RA patients who have not been treated before, 23 RA and 22 AS patients who are candidates for biological agents and being treated with immunosuppressive drugs, and 69 healthy subjects, have been included in this trial. Swelling joints, number of tender joints, visual analog scale, erythrocyte sedimentation rate, C-reactive protein, and rheumatoid factor were recorded. PPD was performed using the Mantoux method and was measured 72 h later. Statistically significant lower PPD values were determined in untreated RA patients compared to PPD values of treated RA and AS patients and healthy subjects. No correlation was determined between disease activity score 28 activity and PPD values in untreated and treated groups. Similarly, there was no correlation between acute phase reactants and PPD. Lower PPD responses in patients not being treated with immunosuppressive are due to the disease itself, rather than to the drugs being used. It is also important to interpret PPD results in early RA patients with suspicion, when it is intended to start anti tumor necrosis factor therapy.
18946657 [Surgery of the cervical spine in rheumatoid arthritis. Diagnostics and indication]. 2008 Nov The cervical spine is often affected in rheumatoid arthritis. Beside destructive changes, instabilities can occur, mainly in the upper cervical spine. Typical symptoms are missing so that routine x-ray examinations are needed to prevent severe consequences up to death. AP/lateral cervical spine x-rays and lateral functional x-rays are the standard diagnostic tool. Depending on the findings, further neurological examination and MRI must be initiated. Aim is the early recognition, respectively prevention of myelopathy. Therapy includes stage dependent conservative and surgical measures.
17580546 [Vasculitis in rheumatoid arthritis--case report]. 2006 The presence of positive rheumatoid factor (RF) titer in a patient with rheumatoid arthritis (RA) is of clinical value because its presence tends to correlate with the development of extraarticular manifestations. There is a loose correlation with severity of disease and titer. Extraarticular manifestations includes vasculitis, pericarditis, subcutaneous nodules, pulmonary nodules or interstitial fibrosis, episcleritis and mononeuritis multiplex. The vasculitis is most frequently evidenced as skin infarctions/ulcerations and mononeuritis multiplex. We report a case of rheumatoid vasculitis in a 48 years old women with long history of RA, who developed vasculitis of distal arteries with gangrene of digits of upper and lower extremities.
18270857 The role of anti-cyclic cytrullinate antibodies testing in rheumatoid arthritis. 2008 Feb Rheumatoid arthritis (RA) is a chronic, progressive inflammatory disease, which leads to joint destruction and deformity and is often accompanied by systemic complications. It is generally considered an autoimmune disease characterized by several autoantibodies. The impressive advances made in understanding the biological mechanisms of RA have led to more focused, directed therapies that have joined, and in many cases overcome, more traditional treatments. Along the last decade, the so-called biological anti-TNF-alpha agents have been shown to reduce disease activity, to slow disease progression and to improve patients' quality of life. The clear evidence that an early therapeutic intervention improves the overall outcome of the disease supports the importance of an early diagnosis. In the last years, several studies showed that anti-cyclic citrullinated peptide antibodies (anti-CCP) represent a sensitive and specific serologic marker for RA. Moreover, a large body of evidence has shown that anti-CCP may also serve as an early diagnostic and prognostic marker in RA. The aim of this article is to provide an overview of the current state of knowledge regarding anti-CCP focusing in particular on their clinical specificity and prognostic value in RA.
16821266 Dietary caffeine intake does not affect methotrexate efficacy in patients with rheumatoid 2006 Jul OBJECTIVE: Methylxanthines, like caffeine, have been thought to reverse the antiinflammatory effects of methotrexate (MTX) in rheumatoid arthritis (RA). We investigated whether patients with RA taking MTX with a higher dietary caffeine intake have a worse clinical response to MTX than those with a lower intake. METHODS: Patients with RA enrolled in a prospective cohort study and currently taking MTX were divided equally into low, moderate, and high caffeine consumers. MTX clinical response was defined by the Disease Activity Score (DAS)28, Multidimensional Health Assessment Questionnaire (MDHAQ) score, and duration of morning stiffness. Regression models were used to study the relationship between caffeine intake and MTX response adjusting for age, sex, and other relevant variables at study enrollment. RESULTS: Two hundred and sixty-four patients with RA taking MTX had an average caffeine intake of 211.7 mg and average MTX dose of 16.0 mg/wk. The low caffeine group comprised 87 patients, the moderate 86, and the high 91. In 3 multivariate models, there was no statistical difference in MTX efficacy between groups, as measured by DAS28 score, MDHAQ score, and duration of morning stiffness at study enrollment. Moderate and high caffeine group had higher DAS28 scores, physician's global assessment, and swollen joint counts, but differences were not significant. CONCLUSION: Caffeine intake among patients taking high doses of MTX for RA did not affect MTX efficacy and RA disease activity over time.
17497034 No correlation exists between disease activity and the expression of killer-cell immunoglo 2007 OBJECTIVE: The genes for killer-cell immunoglobulin-like receptors (KIRs) have been cloned and their functions and expression in patients with rheumatoid arthritis (RA) have been partially clarified. However, the correlation between their expression and disease activity has not been analyzed in patients with RA. Thus, we measured KIR expression on lymphocytes in patients with RA, and assessed the correlation between KIR expression and disease activity. PATIENTS AND METHODS: In the cross-sectional study, 15 patients (9 females and 6 males) who fulfilled the diagnostic criteria for RA were assessed. In the longitudinal study, patients who were followed-up for 3 months were assessed. CD158a/b expression on peripheral blood mononuclear cells (PBMC) of RA patients was analyzed using flow cytometry. RESULTS: No significant correlation between KIR expression and CRP, ESR, or IgM-RF was observed. There was no remarkable change in the expression of KIRs between the baseline and after 3 months. Additionally, in the 5 patients whose expression of KIRs particularly changed, the time-related changes in the expression of KIRs were independent from those of inflammation parameters and IgM-RF. CONCLUSION: There was no correlation between KIR expression and disease activity; therefore, the clinical use of KIR expression should be limited, while unnatural KIR expression may be involved in the pathogenesis of RA, but not a recruitment of chronic inflammation to induce joint damage.
16709927 Signaling of vascular endothelial growth factor receptor-1 tyrosine kinase promotes rheuma 2006 Sep 15 Vascular endothelial growth factor (VEGF) and VEGF receptor-1 (VEGFR-1/Flt-1) were shown to be involved in pathological angiogenesis, particularly rheumatoid arthritis (RA). However, the molecular basis of their actions is not fully understood. Here we report that in a murine model of RA, deletion of the tyrosine kinase (TK) domain of VEGFR-1 decreased the incidence and clinical symptoms of RA. Pathological symptoms, such as synovial hyperplasia, inflammatory infiltrates, pannus formation, and cartilage/bone destruction, became milder in Vegfr-1 tk(-/-) mice compared with wild-type (Wt) mice in the human T-cell leukemia virus-1 (HTLV-1) pX-induced chronic models. VEGFR-1 TK-deficient bone marrow cells showed a suppression of multilineage colony formation. Furthermore, macrophages induced to differentiate in vitro showed a decrease in immunologic reactions such as phagocytosis and the secretion of interleukin-6 (IL-6) and VEGF-A. Treatment of this RA model with a small molecule inhibitor for VEGFR TK, KRN951, also attenuated the arthritis. These results indicate that the VEGFR-1 TK signaling modulates the proliferation of bone marrow hematopoietic cells and immunity of monocytes/macrophages and promotes chronic inflammation, which may be a new target in the treatment of RA.
16484508 The gut-joint axis: cross reactive food antibodies in rheumatoid arthritis. 2006 Sep BACKGROUND AND AIMS: Patients with rheumatoid arthritis (RA) often feel there is an association between food intake and rheumatoid disease severity. To investigate a putative immunological link between gut immunity and RA, food antibodies were measured in serum and perfusion fluid from the jejunum of RA patients and healthy controls to determine the systemic and mucosal immune response. METHODS: IgG, IgA, and IgM antibodies to dietary antigens were measured in serum and jejunal perfusion fluid from 14 RA patients and 20 healthy subjects. The antigens originated from cow's milk (alpha-lactalbumin, beta-lactoglobulin, casein), cereals, hen's egg (ovalbumin), cod fish, and pork meat. RESULTS: In intestinal fluid of many RA patients, all three immunoglobulin classes showed increased food specific activities. Except for IgM activity against beta-lactoglobulin, all other IgM activities were significantly increased irrespective of the total IgM level. The RA associated serum IgM antibody responses were relatively much less pronounced. Compared with IgM, the intestinal IgA activities were less consistently raised, with no significant increase against gliadin and casein. Considerable cross reactivity of IgM and IgA antibodies was documented by absorption tests. Although intestinal IgG activity to food was quite low, it was nevertheless significantly increased against many antigens in RA patients. Three of the five RA patients treated with sulfasalazine for 16 weeks had initially raised levels of intestinal food antibodies; these became normalised after treatment, but clinical improvement was better reflected in a reduced erythrocyte sedimentation rate. CONCLUSIONS: The production of cross reactive antibodies is strikingly increased in the gut of many RA patients. Their food related problems might reflect an adverse additive effect of multiple modest hypersensitivity reactions mediated, for instance, by immune complexes promoting autoimmune reactions in the joints.
18270854 Anti-citrullinated protein antibodies in rheumatoid arthritis: as good as it gets? 2008 Feb Anti-citrullinated protein antibodies (ACPAs) have recently emerged as sensitive and specific serological markers of rheumatoid arthritis (RA), providing superior alternative of the rheumatoid factor (RF) test in the laboratory diagnostics of RA. The first members of this autoantibody family were anti-perinuclear factor (APF) and anti-keratin antibodies (AKA). It became evident that both APF and AKA recognize citrullinated epitopes of filaggrin. Citrullination is a post-translational modification of arginine by deimination, physiologically occurring during apoptosis, inflammation or keratinization. The presence of several citrullinated proteins has been demonstrated in the RA synovium. The identification of citrullinated epitopes as targets for anti-filaggrin antibodies led to the development of the first and later second generation anti-cyclic citrullinated peptide (anti-CCP) antibody assays. The widely used anti-CCP2 assays have high diagnostic sensitivity and specificity, and they also show important predictive and prognostic value in RA. The anti-Sa antibody has been identified a decade ago; however, recent studies confirmed that anti-Sa is directed against citrullinated vimentin, hence it is a new member of the family of ACPAs. The newly developed anti-mutated citrullinated vimentin (anti-MCV) assay has similar diagnostic performance than the anti-CCP2 ELISA; however, the diagnostic spectrum of the anti-MCV test is somewhat different from that of anti-CCP2. It's especially useful in the diagnosis of RA in RF and anti-CCP2 seronegative patients. The combined application of anti-CCP2 and anti-MCV assays can improve the laboratory diagnostics of RA. The family of ACPAs is expected to expand; there is an increasing need for developing new diagnostic strategies after careful evaluation of the characteristics of the available assays.
18270850 Antibodies to citrullinated vimentin are a specific and sensitive marker for the diagnosis 2008 Feb BACKGROUND: The last 5 years have seen the emergence and establishment of antibodies to citrullinated antigens as the diagnostic marker for rheumatoid arthritis (RA). Initially, these were detected using a synthetic peptide, which has undergone a number of modifications to give a diagnostic test with a sensitivity of 65-80% and a specificity of >95%. Antibodies to citrullinated vimentin were first described in 1994 as a highly specific marker for RA (anti-Sa). However, no easily performed assay for these antibodies has been available. METHODS: We have examined the use of a ELISA-based assay with a mutated citrullinated vimentin (MCV) antigen (Orgentec, Mainz, Germany) to assess the diagnostic and prognostic utility of this antibody in RA. RESULTS: Antibodies to MCV were detected in the sera of 74% RA patients (specificity 96%), 2% systemic lupus erythematosus, 14% Sjögren's syndrome, and 2% scleroderma. Anti-MCV was not detected in sera from healthy blood donors. There was no difference in the frequency of antibodies detected in RA patients with early (<2 years) or chronic (>2 years) disease. There was no significant variation in anti-MCV antibody concentrations in early RA patients over a 52-week period. No significant change was observed with time between the two treatment groups of methotrexate alone or methotrexate plus infliximab. CONCLUSIONS: Antibodies to MCV are a specific and sensitive marker for the diagnosis of RA.
18254923 Diagnosis of periarticular osteoporosis in rheumatoid arthritis using digital X-ray radiog 2008 Osteoporosis can manifest in two ways in rheumatoid arthritis: generalized bone loss, which may result from immobility, the inflammatory process per se and/or treatments such as steroids; and periarticular demineralization, which is probably due to local release of inflammatory agents. Digital X-ray radiogrammetry (DXR) is an effective and sensitive modality for monitoring periarticular osteoporosis, which is among the earliest features of rheumatoid arthritis, preceding bone erosions. DXR is a promising technique, which can provide quantitative data that allow early diagnosis. During the course of rheumatoid arthritis it can be deployed in combination with established X-ray scoring methods to inform decisions regarding the optimal therapy to prevent joint destruction.
17143096 Smoking as a trigger for inflammatory rheumatic diseases. 2007 Jan PURPOSE OF REVIEW: This review has two purposes: to describe the known effects of cigarette smoking on the development of inflammatory rheumatic diseases, in particular rheumatoid arthritis and systemic lupus erythematosus, and to review recent research aimed at understanding the mechanisms by which smoking may interact with genes and immunity in triggering these diseases. RECENT FINDINGS: Large case-control studies as well as cohort studies have demonstrated that cigarette smoking is a risk factor for RF positive and anti-citrulline antibody with rheumatoid arthritis and that the risk diminishes only several years after cessation of smoking. Evidence exists that smoking is a risk factor also for systemic lupus erythematosus, and that the risk may be related to the presence of anti-dsDNA antibodies. Mechanistic studies are reviewed that suggest that smoking can trigger specific and potentially disease-inducing immune reactions against citrullinated proteins in rheumatoid arthritis, and dsDNA in systemic lupus erythematosus, and it is suggested that the genetic context determines which immune reactions may be triggered by smoking. SUMMARY: Counselling against smoking should be mandatory in rheumatological practice both to patients and to their relatives. Studies on the mechanisms whereby smoking triggers rheumatoid arthritis and systemic lupus erythematosus may provide fundamental new knowledge about the cause and molecular pathogenesis of these diseases.
16222411 Diastolic function abnormalities in active rheumatoid arthritis evaluation by conventional 2006 May OBJECTIVE: The aim of this study was to evaluate left ventricular diastolic function in patients with active rheumatoid arthritis (RA), analyzing conventional Doppler and tissue Doppler echocardiographic imaging (TDI) which is a new echocardiographic application, with special regard to disease duration. METHODS: Fifty-two patients with active RA and 47 healthy persons were included in this study. Duration of disease ranged from 3 to 324 months (mean 76+/-85 months). All patients and the control group were evaluated by M-mod, two-dimensional, conventional Doppler echocardiography and TDI. RESULTS: Among conventional Doppler transvalvular mitral flow parameters, late diastolic flow velocity (A) and deceleration time (DT) values were higher in patients with RA than that in the control group (p<0.001). E (early diastolic flow velocity)/A ratio was found to be lower in patients with RA than that in the control group (p<0.001). Mitral annular early diastolic velocity (E (m)), among TDI parameters, was found to be lower in patients with RA than that in the control group (p<0.001). E (m)/A (m) (mitral annular late diastolic velocity) ratio was found to be lower in RA patients compared with that in the control group (p<0.001). The relation was found between A (r=0.43, p=0.001), DT (r=0.30, p=0.03), E/A ratio (r=0.40, p=0.004), E (m) (r=0.32, p=0.02), E (m)/A (m) ratio (r=0.30, p=0.03), and E/E (m) (r=0.32, p=0.02), with disease duration in patients with RA. CONCLUSION: At present, it is concluded that active RA patients, in the absence of clinical evidence of heart disease, show diastolic dysfunction characterized by impaired E/A ratio, E (m)/A (m) ratio, and DT. The relation between diastolic dysfunction and disease duration suggests a subclinical myocardial involvement.
16856508 [Lethal complications and associated diseases of rheumatoid arthritis--a retrospective cli 2006 Jun 11 OBJECTIVE: Complications and/or associated diseases in rheumatoid arthritis can present atypical clinical manifestations which may lead to an incorrect or delayed diagnosis. The aim of this study was to determine: (1) the complications of rheumatoid arthritis, the accompanying diseases, and the mortality of these, (2) the clinically missed diagnoses of complications and/or associated diseases, (3) the possible links between coexistent complications of rheumatoid arthritis and/or diseases associated with it, furthermore the possible role of these in the mortality of rheumatoid arthritis patients. METHODS: Between 1970 and 1999 10,860 patients died at the National Institute of Rheumatology, and among them 234 with rheumatoid arthritis (diagnosed clinically according to the criteria of the American College of Rheumatology). The associated and basic disease, complication(s), and causes of death were determined on the basis of clinical records and in each case the autopsy findings were confirmed by a review of extensive histological material (50-100 tissue blocks from each patient). RESULTS: The complications of rheumatoid arthritis led to death in 152 (65%) of 234 patients. The complications of RA were clinically recognized in 109 (46.6%, 71.7 rel%) and missed in 43 (18.4% 28.3 rel%) of 152 patients. More than two thirds of lethal complications related to rheumatoid arthritis were diagnosed clinically. The remaining 82 (35%) of 234 rheumatoid arthritis patients died of associated diseases; the cause of death was clinically recognized in 78 (33.3%, 95.1 rel%) of 82 cases. There was a significant and positive correlation (1) between vasculitis and cardiac insufficiency (chi2 = 6.37, p <0.01), vasculitis and tuberculosis (chi2 = 4.18, p <0.04), or miliary tuberculosis (chi2 = 3.86, p <0.04); (2) between tuberculosis and miliary tuberculosis (chi2 = 54.84, p <0.001); and (3) between septic infection and purulent arthritis (chi2 = 97.04, p <0.001). There was a significant and inverse correlation between atherosclerosis and vasculitis (chi2 = 5.10, p <0.02), atherosclerosis and amyloidosis (chi2 = 14.58, p <0.001), or atherosclerosis and septic infection (chi2 = 3.81, p <0.05). There was a significant and inverse correlation between atherosclerosis and lethal cases of vasculitis (chi2 = 9.31, p <0.002), of amyloidosis (chi2 = 6.82, p <0.009), of sepsis (chi2 = 3.81, p <0.05) furthermore, between atherosclerosis with lethal outcome (n = 60 of 106) and vasculitis (chi2 = 12.06, p <0.001), or amyloidosis (chi2 = 13.22, p<0.002), or sepsis (chi2 = 10.82, p <0.001), or purulent arthritis (chi2 = 4.18, p <0.04). CONCLUSION: The most important life threatening complications of rheumatoid arthritis (vasculitis, AA amyloidosis and sepsis) are present and lead to death with higher probability in the younger age group (without atherosclerosis), while in older patients who have atherosclerosis these represent a lower risk of death.
16739183 Primary therapist model for patients referred for rheumatoid arthritis rehabilitation: a c 2006 Jun 15 OBJECTIVE: To estimate the incremental cost-effectiveness (ICE) of services from a primary therapist compared with traditional physical therapists and/or occupational therapists for managing rheumatoid arthritis (RA), from the societal perspective. METHODS: Patients with RA were randomly assigned to the primary therapist model (PTM) or traditional treatment model (TTM) for approximately 6 weeks of rehabilitation treatment. Health outcomes were expressed in terms of quality-adjusted life years (QALYs), measured with the EuroQol instrument at baseline, 6 weeks, and 6 months. Direct and indirect costs, including visits to health professionals, use of investigative tests, hospital visits, use of medications, purchases of adaptive aids, and productivity losses incurred by patients and their caregivers, were collected monthly. RESULTS: Of 144 consenting patients, 111 remained in the study after the baseline assessment: 63 PTM (87.3% women, mean age 54.2 years, disease duration 10.6 years) and 48 TTM (79.2% women, mean age 56.8 years, disease duration 13.2 years). From a societal perspective, PTM generated higher QALYs (mean +/- SD 0.068 +/- 0.22) and resulted in a higher mean cost ($6,848 Canadian, interquartile range [IQR] $1,984-$9,320) compared with TTM (mean +/- SD QALY -0.017 +/- 0.24; mean costs $6,266, IQR $1,938-$10,194) in 6 months, although differences were not statistically significant. The estimated ICE ratio was $13,700 per QALY gained (95% nonparametric confidence interval -$73,500, $230,000). CONCLUSION: The PTM has potential to be an alternative to traditional physical/occupational therapy, although it is premature to recommend widespread use of this model in other regions. Further research should focus on strategies to reduce costs of the model and assess the long-term economic consequences in managing RA and other rheumatologic conditions.
18364651 Clinical evaluation and power Doppler sonography in rheumatoid arthritis: evidence for ong 2008 Mar OBJECTIVE: This study proposed to assess the relationship between power Doppler ultrasound examination and spectral Doppler analysis of hand joints with clinical and laboratory parameters in rheumatoid arthritis. METHODS: Patients receiving disease-modifying antirheumatic drugs or biologics (infliximab) underwent joint examination and were assessed by a Health Assessment Questionnaire, Duruoz's Hand Index, and Hand Function Test. All were categorized for disease activity using the American College of Rheumatology and disease activity score 28-joint (DAS28) criteria. Ten metacarpophalangeal joints and 4 wrist joints (ulnar-carpal and radiocarpal joints) in each patient were examined by power Doppler and spectral Doppler. Flow signal in the synovium was semiquantitatively graded. A cumulative flow signal score (CFS) and mean resistive index (RI) was calculated in each patient. RESULTS: Patients with active disease had significantly higher CFS compared with patients with inactive disease, but the mean RI was similar. Health Assessment Questionnaire, Duruoz's Hand Index, Larsen, and DAS28 scores correlated significantly with CFS, but the erythrocyte sedimentation rate and C-reactive protein scores did not. Mean RI did not correlate with clinical or laboratory parameters. A majority of patients who were in clinical remission according to American College of Rheumatology or DAS28 criteria had ongoing synovial inflammation on power Doppler ultrasound (58% and 62%, respectively). CONCLUSION: Power Doppler examination of rheumatoid hand joints is a practical method to estimate synovial inflammation. A modification of current remission criteria by combining imaging techniques with clinical and laboratory examination may be conceivable. These results underscore the necessity of more sophisticated research, assessing the agreement between long-term Doppler changes and clinical parameters.
18322994 Common polymorphisms in the folate pathway predict efficacy of combination regimens contai 2008 Apr OBJECTIVE: To study genetic polymorphisms in the folate pathway, a site of action of methotrexate (MTX) and sulfasalazine (SSZ), as predictors of efficacy of combination disease modifying antirheumatic drug (DMARD) regimens containing MTX and SSZ in early rheumatoid arthritis (RA). METHODS: Ninety-eight Caucasian patients with early RA received MTX with SSZ, hydroxychloroquine, and folate according to a standardized protocol. Efficacy was evaluated using the Disease Activity Score (DAS28) and European League Against Rheumatism response criteria at 12 months. Nine polymorphisms in 7 genes of the folate pathway were studied. RESULTS: Response to therapy was associated with SLC19A1, MTR, and TYMS polymorphisms. Two favorable allele combinations associated with responder status at 12 months were identified: the MTR 2756A allele in combination with either the SLC19A1 80A allele or the TYMS 3R-del6 haplotype (multivariate analysis, p = 0.0002, p = 0.009 respectively). Seventy of the 72 patients with these allele combinations responded compared to 12/24 patients without [odds ratio (OR) 35.0, 95% confidence interval (CI) 6.9-176, p < 0.0001]. An association with remission (DAS28 < 2.6) was also observed (OR 3.4, 95% CI 1.1-10.0, p = 0.04). When analyzed over 3 years, both the change in DAS score from baseline and the final DAS scores were significantly higher and lower, respectively, with the favorable genotype group (p < 0.0001, p < 0.0001). CONCLUSION: Polymorphic variations in the MTR, SLC19A1, and TYMS genes were associated with better clinical response to combination DMARD regimens containing MTX and SSZ. Allele combinations of these genes may predict response to combination DMARD and assist in treatment decisions in patients with early RA.
18390121 [Recommendations of Czech Rheumatological Society for the treatment of rheumatoid arthriti 2008 Jan Rheumatoid arthritis (RA) is an autoimmune disease of unknown aetiology characterized by presence of chronic symmetric synovitis, which leads to the formation of joint erosions. Generally recommended method for activity assessment of RA is so called Disease Activity Score (DAS). In early RA when low disease activity is present with oligo- or monoarthritis antimalarials are drugs of choice, while sulfasalazine (SAS) is recommended in cases with medium activity without erosions. Initial treatment with methotrexate (MTX) or leflunomide (LEF) should be applied in a very active polyarthritis with a rapid development of erosions. MTX is often combined with other disease modifying drugs (DMARD) and the blockers of tumour necrosis factor alpha (TNF-alpha). LEF is to be administered to the patients in whom the other DMARD are contraindicated or not tolerated. In established RA with oligo- or monoarthritis with permanent low activity SAS is DMARD of choice. In cases with insufficient response and medium activity MTX is used and if it is inefficient LEF or combination of DMARD should be considered. In a very active disease with a rapid evolution of erosions high doses of MTX or LEF are recommended. When extraarticular symptoms of RA are present azathioprine is to be applied and in case of involvement of vital organs cyclophosphamide should be used. When DMARD are failing or contraindicated TNF-alpha blockers are to be applied. When one TNF-alpha blocker is inefficient it should by replaced by another one from the same group or another biological should be used. For indication of biologicals the activity limit is DAS28 5.1 and the decrease of DAS28 more than 1.2 is an efficacy criterion. Nonsteroidal antirheumatic drugs are an important part in the management of RA, and also corticosteroids are often of used in oral or parenteral form. To the complex therapy of RA nonpharmacological means are usually implemented--different physical procedures and various surgeries.