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ID PMID Title PublicationDate abstract
19200388 Variability in depression prevalence in early rheumatoid arthritis: a comparison of the CE 2009 Feb 7 BACKGROUND: Depression is common in rheumatoid arthritis (RA), however reported prevalence varies considerably. Two frequently used instruments to identify depression are the Center for Epidemiological Studies Depression (CES-D) scale, and the Hospital Anxiety and Depression Scale (HADS). The objectives of this study were to test if the CES-D and HADS-D (a) satisfy current modern psychometric standards for unidimensional measurement in an early RA sample; (b) measure the same construct (i.e. depression); and (c) identify similar levels of depression. METHODS: Data from the two scales completed by patients with early RA were fitted to the Rasch measurement model to show that (a) each scale satisfies the criteria of fit to the model, including strict unidimensionality; (b) that the scales can be co-calibrated onto a single underlying continuum of depression and to (c) examine the location of the cut points on the underlying continuum as indication of the prevalence of depression. RESULTS: Ninety-two patients with early RA (62% female; mean age = 56.3, SD = 13.7) gave 141 sets of paired CES-D and HAD-D data. Fit of the data from the CES-D was found to be poor, and the scale had to be reduced to 13 items to satisfy Rasch measurement criteria whereas the HADS-D met model expectations from the outset. The 20 items combined (CES-D13 and HADS-D) satisfied Rasch model expectations. The CES-D gave a much higher prevalence of depression than the HADS-D. CONCLUSION: The CES-D in its present form is unsuitable for use in patients with early RA, and needs to be reduced to a 13-item scale. The HADS-D is valid for early RA and the two scales measure the same underlying construct but their cut points lead to different estimates of the level of depression. Revised cut points on the CES-D13 provide comparative prevalence rates.
19781703 Target organ damage in patients with rheumatoid arthritis: the role of blood pressure and 2010 Mar BACKGROUND: Rheumatoid arthritis (RA) is characterised by increased cardiovascular morbidity and mortality. Even though hypertension (HT) is highly prevalent in RA, the extent of target organ damage (TOD) caused by it remains unknown. Inflammation and sympathetic overdrive may also associate with TOD. We investigated the prevalence and associations of TOD in RA. METHODS: In this cross-sectional, observational study, 251 RA patients with no overt cardiovascular or renal disease had extensive clinical and laboratory evaluations, including a 12-lead electrocardiogram and urine albumin:creatinine ratio. Pulse pressure (PP) was used as a proxy of arterial stiffness and heart rate (HR) of autonomic activity. TOD was defined as described in the European guidelines for the management of arterial hypertension. Binary logistic regression analysis was used to evaluate the independence of the variables that associated with the presence of TOD. RESULTS: TOD prevalence was 23.5% (59/251). Of the 59 patients with TOD, 45.8% had suboptimally controlled HT, whereas 32.3% had undiagnosed HT. In univariable analysis, TOD was significantly associated with higher age (64.2+/-11.7 years vs. 58.0+/-12.4 years, p=0.001), HT prevalence (89.8% vs. 60.4%, p<0.001), systolic blood pressure (SBP) (150.3+/-18.8mmHg vs. 139.7+/-20.7mmHg, p=0.001), PP (70.6+/-16.6mmHg vs. 60.3+/-17.3mmHg, p<0.001), HR (77.1+/-15.4bpm vs. 72.2+/-12.2bpm, p<0.001), serum uric acid (320.6+/-88.8mumol/l vs. 285.0+/-74.9mumol/l, p=0.03) and type 2 diabetes mellitus prevalence (13.6% vs. 4.7%, p=0.019). Binary logistic regression analysis revealed that only hypertension indices and HR associated independently with TOD. CONCLUSIONS: TOD is highly prevalent in patients with RA and associates independently with hypertension, arterial stiffness and heart rate. Further prospective studies are needed to confirm these findings and examine the role of beta-blockers in this particular population.
19939454 Double role of mannose-binding lectin in relation to carotid intima-media thickness in pat 2010 Jan BACKGROUND: Patients with rheumatoid arthritis (RA) have increased risk of atherosclerosis and cardiovascular disease (CVD) that cannot be explained by excess of traditional risk factors. Several studies indicate that mannose-binding lectin (MBL) may modify the development of atherosclerosis; both high and low serum levels of MBL are reported to be associated with CVD. Intima-media thickness of the common carotid artery (ccIMT) is a validated non-invasive anatomic measure of subclinical CVD. We examined the relation between ccIMT and MBL in 114 RA patients. METHODS: In a cross-sectional study MBL2 genotypes and serum concentrations of MBL were assessed; ccIMT was determined by means of ultrasonography; traditional and RA related cardiovascular risk modifiers were measured. RESULTS: The median ccIMT was 0.67 mm. The investigated MBL2 genotypes were not significantly associated with ccIMT. Using a general linear model, ccIMT was not linearly associated with serum MBL but was highly associated with the quadratic term of serum MBL (MBL(2)) (P=0.001) reflecting a U-shaped relation. MBL(2) was also significantly associated with ccIMT in a multivariable analysis adjusting for traditional and RA related cardiovascular risk modifiers (P=0.025). CONCLUSION: In RA patients, a quadratic U-shaped relation between serum MBL and ccIMT was observed independently of the effects of traditional and RA related risk factors for CVD. These results provide further support to the notion that both high and low levels of MBL may be associated with CVD.
18821073 NK and NKT cell dynamics after rituximab therapy for systemic lupus erythematosus and rheu 2009 Feb Biomarkers of clinical response to rituximab (RTX) therapy and early predictors of outcome are still under investigation. We report a flow cytometric immunophenotyping analysis from peripheral blood leukocyte subpopulations of two patients with systemic lupus erythematosus (SLE) associated thrombocytopenia and one patient with rheumatoid arthritis (RA), before and after 6 weeks of treatment with RTX. Our results show a reduced population of CD19(+) expressing cells (B cells) after RTX treatment in all three patients. Increased frequency of peripheral regulatory CD4(+)CD25(high) T cell subset and the CD3(-)CD16(-)CD56(bright) NK cell subset after RTX therapy were also observed in all patients, the latter being more pronounced in the SLE patient with sustained clinical response. In addition, an increased population of NKT cell subsets was observed in the patients with clinical response. This is the first evaluation of NK and NKT cells as biomarkers of clinical response after rituximab therapy in rheumatic diseases.
21080353 Comparative study of the detection of joint injury in early-stage rheumatoid arthritis by 2011 Mar OBJECTIVE: To verify whether magnetic resonance imaging (MRI)-proven joint injury is sensitive as compared with joint injury determined by physical examination. METHODS: MRI of the wrist and finger joints of both hands was examined in 51 early-stage rheumatoid arthritis (RA) patients by both plain and gadolinium diethylenetriaminepentaacetic acid-enhanced MRI. Synovitis, bone edema, and bone erosion (the latter two included as bone lesions at the wrist joints); metacarpophalangeal joints; and proximal interphalangeal joints were considered as MRI-proven joint injury. Japan College of Rheumatology-certified rheumatologists had given a physical examination just before the MRI study. The presence of tender and/or swollen joints in the same fields as MRI was considered as joint injury on physical examination. The association of MRI-proven joint injury with physical examination-proven joint injury was examined. RESULTS: A total of 1,110 sites were available to be examined. MRI-proven joint injury was found in 521 sites, whereas the other 589 sites were normal. Physical examination-proven joint injury was found in 305 sites, which was significantly low as compared with MRI-proven joint injury (P = 1.1 × 10(-12) versus MRI). Joint injury on physical examination was not found in 81.5% of the sites where MRI findings were normal. Furthermore, an association of the severity of MRI-proven joint injury with that of joint injury on physical examination was clearly demonstrated (P = 1.6 × 10(-15), r(s) = 0.469). CONCLUSION: Our present data suggest that MRI is not only sensitive but accurately reflects the joint injury in patients with early-stage RA.
20401724 Pulmonary non-Hodgkin's lymphoma developed during long-term methotrexate therapy for rheum 2012 Nov Methotrexate is effective in treating rheumatoid arthritis (RA). Some reports have discussed the possible association between methotrexate and lymphoma. Here, we report a case of pulmonary non-Hodgkin's lymphoma (NHL) developed after 11 years' methotrexate therapy for RA. Biopsy of the pulmonary mass demonstrated a diffuse large B-cell lymphoma. After withdrawal of methotrexate without any other intervention for 4 weeks, a significant reduction in the size of the lymphoma was observed. The causative relationship between methotrexate and pulmonary lymphoma is suggested by the persistent remission after stopping methotrexate therapy.
19337689 Leukocytapheresis (LCAP) decreases the level of platelet-derived microparticles (MPs) and 2009 Microparticles (MPs) are believed to play an important role in inflammatory diseases such as rheumatoid arthritis (RA). Leukocytapheresis (LCAP) is one of the options available for the treatment of RA. We analyzed the levels of MPs in RA, by flow cytometry, especially in relation to the effect of LCAP. Twenty female patients with RA were recruited into this study. Six of the 20 patients with RA further received LCAP. Plasma levels of platelet-derived MPs were high in patients with RA and are correlated with disease activity. LCAP significantly improved RA in all six patients. The numbers of platelet-derived MPs significantly decreased after the first session of LCAP, which was probably due to direct removal by LCAP. Mean numbers of platelet-derived MPs after four sessions of LCAP markedly decreased. The numbers of granulocyte-derived MPs, which are suggested to have an anti-inflammatory effect, were markedly increased after the first session of LCAP. These data suggest that removal of platelet-derived MPs and increase of granulocyte-derived MPs are novel mechanisms of LCAP as effective treatment in RA.
20305562 Angiogenesis and vasculogenesis in rheumatoid arthritis. 2010 May PURPOSE OF REVIEW: Angiogenesis is the formation of new capillaries from pre-existing vessels, whereas vasculogenesis is de-novo capillary formation from endothelial precursor cells (EPCs). Current understanding of the role of angiogenesis and vasculogenesis in rheumatoid arthritis (RA) and possibilities of therapeutic intervention should be summarized. RECENT FINDINGS: There have been many recent studies on the role of the hypoxia and hypoxia-inducible factor (HIF)-vascular endothelial growth factor (VEGF)-angiopoietin axis in angiogenesis associated with RA. The role of additional growth factors, chemokines, cytokines, matrix components and adhesion molecules has been further characterized. Macrophage migration inhibitory factor (MIF) may link inflammation, angiogenesis and atherosclerosis. Junctional adhesion molecules (JAMs) and focal adhesion kinases (FAKs) have recently been implicated in inflammatory angiogenesis. Novel information regarding the role of serum amyloid A (SAA) and sphingosine kinase has become available. Most of these angiogenic factors have recently been targeted using various techniques and arthritis models. Whereas angiogenesis is abundant in RA, there is defective EPC function and vasculogenesis leading to atherosclerosis and vascular disease in arthritis. Treatment with EPCs already under investigation in vascular diseases may also be attempted in RA. SUMMARY: Targeting angiogenesis and restoration of vasculogenesis may be beneficial for the therapy and outcome of RA.
21050950 Rational use of laboratory testing in the initial evaluation of soft tissue and joint comp 2010 Dec The rational use of laboratory testing to investigate early, undifferentiated joint pain depends heavily on a detailed history and careful physical examination. Nevertheless, several diagnostic tests have some discriminatory function in the initial evaluation of soft tissues and joint complaints, given the correct clinical context. Arthrocentesis frequently gives the best results when compared with other tests in the differential diagnosis of monoarticular and polyarticular joint pain. There is also a role for radiographs, and less frequently, magnetic resonance imaging. Although overuse of an arthritis panel is not recommended, for an appropriately chosen patient, complete blood cell count, serum uric acid, C-reactive protein (or erythrocyte sedimentation rate), rheumatoid factor, antiecyclic citrullinated peptide, and antinuclear antibody titers form a reasonable screening panel when rheumatic disease is suspected based on the clinical condition. Other tests might include a purified protein derivative, anti-Borrelia titers, and antibodies for antistreptolysin O. However, many rheumatic conditions can be diagnosed or at least suspected on clinical grounds alone, and a careful history and physical examination are absolutely essential for the appropriate use of any laboratory testing.
19648303 Can magnetic resonance imaging differentiate undifferentiated arthritis based on knee imag 2009 Sep OBJECTIVE: To compare findings as observed on enhanced magnetic resonance imaging (MRI) of the knee joints, in oligoarticular-undifferentiated arthritis (UA) in those with established rheumatoid arthritis (RA) and spondyloarthropathy (SpA). METHODS: A total of 55 patients with knee arthritis were consecutively recruited for the study, including 25 with undifferentiated oligoarthritis of the knee joint(s), 15 fulfilling the American College of Rheumatology criteria for RA and 15 with SpA. Laboratory investigations included erythrocyte sedimentation rate, C-reactive protein, complete blood count, aspartate aminotransferase, alanine aminotransferase, serum creatinine, and urine analysis. In all patients in the UA and in the RA group, rheumatoid factor and anti-CCP2 antibody (ELISA) were tested. All patients underwent enhanced MRI of the more symptomatic knee. All groups were compared in terms of demographics, laboratory investigations, and MRI findings. RESULTS: Synovial thickness differed significantly in the RA group compared to UA and SpA groups (p < 0.001). The RA group showed a higher rate of bony and cartilaginous erosions and bone marrow edema compared to UA and SpA groups (p < 0.001). Enthesitis was found in all patients in the SpA group (100%) and differed from RA and UA groups (p < 0.001). CONCLUSION: Patients with RA showed more destructive changes in terms of synovial thickening, bone marrow edema, cartilaginous and bone erosions compared to UA and SpA groups. Enthesitis is a common feature on MRI in SpA, while absent in the RA and UA groups. This latter finding may have important clinical implications for classification purposes, and can help to determine the evolving pattern of patients with UA of the knee joint.
20824142 Linking power Doppler ultrasound to the presence of th17 cells in the rheumatoid arthritis 2010 Sep 1 BACKGROUND: Power Doppler ultrasound (PDUS) is increasingly used to assess synovitis in Rheumatoid Arthritis (RA). Prior studies have shown correlations between PDUS scores and vessel counts, but relationships with T cell immunopathology have not been described. METHODOLOGY/PRINCIPAL FINDINGS: PBMC were isolated from healthy controls (HC) or RA patients and stimulated ex vivo with PMA and ionomycin for 3 hours in the presence of Golgistop. Paired synovial fluid (SF) or synovial tissue (ST) were analysed where available. Intracellular expression of IL-17, IFNgamma, and TNFalpha by CD4+ T cells was determined by flow cytometry. Synovial blood flow was evaluated by PDUS signal at the knees, wrists and metacarpophalangeal joints of RA patients. Serum, SF and fibroblast culture supernatant levels of vascular endothelial growth factor-A (VEGF-A) were measured by ELISA. The frequency of IL17+IFNgamma-CD4+ T cells (Th17 cells) was significantly elevated in peripheral blood (PB) from RA patients vs. HC (median (IQR) 0.5 (0.28-1.59)% vs. 0.32 (0.21-0.54)%, p = 0.005). Th17 cells were further enriched (mean 6.6-fold increase) in RA SF relative to RA PB. Patients with active disease had a higher percentage of IL-17+ T cells in ST than patients in remission, suggesting a possible role for Th17 cells in active synovitis in RA. Indeed, the percentage of Th17 cells, but not Th1, in SF positively correlated with CRP (r = 0.51, p = 0.04) and local PDUS-defined synovitis (r = 0.61, p = 0.002). Furthermore, patients with high levels of IL-17+CD4+ T cells in SF had increased levels of the angiogenic factor VEGF-A in SF. Finally, IL-17, but not IFNgamma, increased VEGF-A production by RA synovial fibroblasts in vitro. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate a link between the presence of pro-inflammatory Th17 cells in SF and local PDUS scores, and offer a novel immunological explanation for the observation that rapid joint damage progression occurs in patients with persistent positive PDUS signal.
19843471 Ten years of infliximab: insights from clinical trials in rheumatoid arthritis. 2009 Nov 25 Early animal and open label human studies suggested a pivotal role for tumor necrosis factor (TNF) inhibition in the treatment of rheumatoid arthritis (RA). Subsequent randomized controlled trials with infliximab showed a rapid reduction of signs and symptoms as well as fast normalization of C reactive protein (CRP) in patients responding to treatment. In addition, a synergistic effect of methotrexate (MTX) in combination with infliximab was evident. Infliximab treatment can inhibit progression of structural joint damage, a newly reported outcome of TNF inhibition in rheumatoid arthritis shown to be largely independent of clinical response to infliximab treatment. Early treatment with infliximab in combination with methotrexate in methotrexate-naive patients showed similar inhibition of x-ray progression, and change of the natural course of disease thus became an achievable treatment goal in rheumatoid arthritis. Current clinical practice in rheumatology aims at obtaining low disease activity and remission state. Application of new treatment strategies with tight control of disease activity allows to reach these new treatment goals in many patients. The extended research programs of infliximab have added significant knowledge to our current clinical management of rheumatoid arthritis patients. We also learned, however, that anti-TNF treatment is not without risk, and that careful patient selection, screening, and monitoring are vital to achieve these outcomes in every day clinical practice.
19362081 Anti-human parvovirus B19 nonstructural protein antibodies in patients with rheumatoid art 2009 Jul BACKGROUND: Previous studies have reported the association between the development of NS1-specific IgG and arthropathy after the infection of human parvovirus B19 (B19). However, the role of anti-B19-NS1 IgG in RA is still unclear. This study investigated the role of anti-B19-NS1 antibody in patients with rheumatoid arthritis (RA). METHODS: B19-VP IgM and IgG antibodies, nested PCR, B19-NS1 IgM and IgG antibodies, and anti-cyclic citrullinated peptide (CCP) antibodies were assessed by ELISA and Western blot in this study. RESULTS: Significantly higher prevalence of B19-NS1 IgM and IgG antibodies in patients with recent B19 infection was observed as well as the higher prevalence of B19-NS1 IgM and IgG antibodies in RA patients with seronegative diagnostic patterns. However, no significant variation of both B19-NS1 IgM and IgG was detected in RA patients with different B19 diagnostic patterns. Additionally, significantly higher presence of anti-CCP IgG was observed in RA patients with B19-NS1 IgM. CONCLUSIONS: This study suggests the possibility of anti-B19-NS1 IgM as an indicator for RA diagnosis and indicates the suspense of the higher prevalence of anti-B19-NS1 antibody in RA patients with seronegative B19 diagnostic patterns. However, these results provide clues in understanding the association of anti-B19-NS1 antibody in RA patients.
20498212 A matrix risk model for the prediction of rapid radiographic progression in patients with 2010 Jul OBJECTIVES: To develop a matrix model for the prediction of rapid radiographic progression (RRP) in subpopulations of patients with recent-onset rheumatoid arthritis (RA) receiving different dynamic treatment strategies. METHODS: Data from 465 patients with recent-onset RA randomised to receive initial monotherapy or combination therapy were used. Predictors for RRP (increase in Sharp-van der Heijde score > or =5 after 1 year) were identified by multivariate logistic regression analysis. For subpopulations, the estimated risk of RRP per treatment group and the number needed to treat (NNT) were visualised in a matrix. RESULTS: The presence of autoantibodies, baseline C-reactive protein (CRP) level, erosion score and treatment group were significant independent predictors of RRP in the matrix. Combination therapy was associated with a markedly reduced risk of RRP. The positive and negative predictive values of the matrix were 62% and 91%, respectively. The NNT with initial combination therapy to prevent one patient from RRP with monotherapy was in the range 2-3, 3-7 and 7-25 for patients with a high, intermediate and low predicted risk, respectively. CONCLUSION: The matrix model visualises the risk of RRP for subpopulations of patients with recent-onset RA if treated dynamically with initial monotherapy or combination therapy. Rheumatologists might use the matrix for weighing their initial treatment choice.
20423475 A1298C polymorphism in the MTHFR gene predisposes to cardiovascular risk in rheumatoid art 2010 INTRODUCTION: We determined the contribution of the methylene tetrahydrofolate reductase (MTHFR) 677 C>T and 1298 A>C gene polymorphisms to the susceptibility to rheumatoid arthritis (RA). We also assessed whether these two MTHFR gene polymorphisms may be implicated in the development of cardiovascular (CV) events and subclinical atherosclerosis manifested by the presence of endothelial dysfunction, in a series of Spanish patients with RA. METHODS: Six hundred and twelve patients fulfilling the 1987 American College of Rheumatology classification criteria for RA, seen at the rheumatology outpatient clinics of Hospital Xeral-Calde, Lugo and Hospital San Carlos, Madrid, were studied. Patients and controls (n = 865) were genotyped using predesigned TaqMan SNP genotyping assays. RESULTS: No significant differences in allele or genotype frequencies for the MTHFR gene polymorphisms between RA patients and controls were found. Also, no association between the MTHFR 677 C>T polymorphism and CV events or endothelial dysfunction was observed. However, the MTHFR 1298 allele C frequency was increased in patients with CV events after 5 years (38.7% versus 30.3%; odds ratio = 1.45; 95% confidence interval = 1.00 to 2.10; P = 0.04) and 10 years (42.2% versus 31.0%; odds ratio = 1.62; 95% confidence interval = 1.08 to 2.43; P = 0.01) follow up. Moreover, patients carrying the MTHFR 1298 AC and CC genotypes had a significantly decreased flow-mediated endothelium-dependent vasodilatation (4.3 +/- 3.9%) compared with those carrying the MTHFR 1298 AA genotype (6.5 +/- 4.4%) (P = 0.005). CONCLUSIONS: Our results show that the MTHFR 1298 A>C gene polymorphism confers an increased risk for subclinical atherosclerosis and CV events in patients with RA.
19132790 Symptoms of depression predict the trajectory of pain among patients with early inflammato 2009 Feb OBJECTIVE: To assess the longitudinal relationships, including directionality, among chronic pain, symptoms of depression, and disease activity in patients with early inflammatory arthritis (EIA). METHODS: One hundred eighty patients with EIA completed an examination, including swollen joint count, and were administered the Center for Epidemiological Studies Depression Scale (CES-D) and the McGill Pain Questionnaire (MPQ) at 2 timepoints 6 months apart. Cross-lagged panel path analysis was used to simultaneously assess concurrent and longitudinal relationships among pain, symptoms of depression, and number of swollen joints. RESULTS: Pain, symptoms of depression, and number of swollen joints decreased over time (p < 0.001) and were prospectively linked to pain, symptoms of depression, and number of swollen joints, respectively, at 6 months. Symptoms of depression and pain were correlated with each other at baseline (0.47) and at 6-month followup assessments (0.28). Baseline symptoms of depression significantly predicted pain symptoms at 6 months (standardized regression coefficient = 0.28, p = 0.001), whereas pain and disease activity did not predict the course of any other variable after controlling for baseline values. CONCLUSION: Symptoms of depression predicted the trajectory of pain from baseline to 6 months. In addition, there were reciprocal/bidirectional associations between pain and symptoms of depression over time. More research is needed to better understand the relationship between pain and depressive symptoms and how to best manage patients with EIA who have high levels of both.
21177292 Different stages of rheumatoid arthritis: features of the synovium in the preclinical phas 2011 May BACKGROUND: The aetiology of rheumatoid arthritis (RA), a prototype immune-mediated inflammatory disorder, is poorly understood. It is currently unknown whether the disease process starts in the synovium, the primary target of RA, or at other sites in the body. OBJECTIVE: To examine, in a prospective study, the presence of synovitis in people with an increased risk of developing RA. METHODS: Thirteen people without evidence of arthritis, who were positive for IgM rheumatoid factor and/or anticitrullinated protein antibodies, were included in the study. To evaluate synovial inflammatory changes, all participants underwent dynamic contrast-enhanced MRI and arthroscopic synovial biopsy sampling of a knee joint at inclusion. Results were compared with knee MRI data and synovial biopsy data of 6 and 10 healthy controls, respectively. RESULTS: MRI findings evaluated by measurement of maximal enhancement, rate of enhancement, synovial volume and enhancement shape curve distribution were similar between the autoantibody-positive subjects and the healthy controls. Consistent with these findings, all but one autoantibody-positive subject showed very low scores for phenotypic markers, adhesion molecules and vascularity, all in the same range as those in normal controls. The one person with higher scores had patellofemoral joint space narrowing. CONCLUSION: Subclinical inflammation of the synovium does not coincide with the appearance of serum autoantibodies during the pre-RA stage. Thus, systemic autoimmunity precedes the development of synovitis, suggesting that a 'second hit' is involved. This study supports the rationale for exploring preventive strategies aimed at interfering with the humoral immune response before synovial inflammation develops.
17935920 Intra-articular distribution pattern after ultrasound-guided injections in wrist joints of 2009 Feb OBJECTIVE: To investigate the distribution of an ultrasound-guided intra-articular (IA) injection in the wrist joint of patients with rheumatoid arthritis (RA). METHODS: An ultrasound-guided IA drug injection into the wrist joint was performed in 17 patients with 1 ml methylprednisolone (40 mg/ml), 0.5 ml Lidocaine (5mg/ml) and 0.15 ml gadolinium (Omniscan 0.5 mmol/ml). The drug solution was placed in the central proximal part of the wrist between the distal radius and the lunate bone. Coronal and axial MRI sequences were performed after the injection to visualize the distribution. Carpal distribution (radio-carpal, inter-carpal, and carpo-metacarpal) as well as radio-ulnar distribution was recorded. Full distribution in one compartment was given the value 1, partial distribution 0.5 and no distribution 0. A sum of the total distribution for all four compartments was calculated and correlated to the clinical parameters and the MRI OMERACT scores. RESULTS: No uniform pattern was seen in the distribution of the contrast. Only two patients had full contrast distribution to all four compartments, and the mean distribution count for all patients was 2.4 (range 0.5-4). The distribution count correlated with the MRI OMERACT synovitis score (r=0.60, p=0.014), but not with the erosions, bonemarrow oedema scores or any clinical parameters. CONCLUSION: The distribution of contrast on MRI showed patient specific and random patterns after IA injections in active RA wrist joints. The degree of distribution increased with the MRI synovitis score, while no association was found with the erosion- and bonemarrow oedema score. These results indicate that a single injection into a standard injection site in the proximal part of the wrist cannot be assumed to distribute--and treat--the whole joint.
19847430 Synovial tissue rank ligand expression and radiographic progression in rheumatoid arthriti 2010 Nov The objective of the study was to evaluate synovial tissue receptor activator of nuclear factor-κβ ligand (RANKL) and osteoprotegerin (OPG) as biomarkers of disease activity, progressive joint damage, and therapeutic response, during cytokine blockade in rheumatoid arthritis (RA). Patients with active RA entered a randomized open-label 12-month study of anakinra 100 mg/day, administered as monotherapy or in combination with pegsunercept 800 μg/kg twice weekly. Arthroscopic synovial tissue biopsies were obtained at baseline, at 4 weeks and at the final time point. Following immunohistochemical staining, RANKL and OPG expression was quantified using digital image analysis. Radiographic damage was evaluated using the van der Heijde modification of the Sharp scoring system. Twenty-two patients were randomized. Baseline expression of RANKL, but not OPG, correlated significantly with baseline CRP levels (r = 0.61, P < 0.01). While a significant reduction in OPG expression following treatment was observed in clinical responders at the final time point (P < 0.05 vs. baseline), RANKL levels did not change, and the RANKL:OPG ratio remained unaltered, even at the highest levels of clinical response. When potential predictors of radiographic outcome were evaluated, baseline RANKL expression correlated with erosive progression at 1 year (r = 0.71, P < 0.01). Distinct, though related, pathophysiologic processes mediate joint inflammation and destruction in RA. Elevated synovial tissue RANKL expression is associated with progressive joint erosion, and may be independent of the clinical response to targeted therapy. The potential therapeutic importance of modulating RANKL in RA is highlighted, if radiographic arrest is to be achieved.
19635732 Residual minimal disease activity in rheumatoid arthritis: a simple definition through an 2009 Oct OBJECTIVE: To obtain the simplest definition of minimal disease activity (MDA) and to compare it with published proposed definitions of MDA in patients with RA. METHODS: Two hundred and fourteen patients with long-standing RA (LSRA) were evaluated for clinical and laboratory parameters. Factor analysis was performed to remove redundant variables included in the core set measure for MDA definition stated by the OMERACT. Receiver operating characteristic (ROC) curves analysis allowed to obtain optimal cut-off predictors of a 28-joint disease activity score (DAS28) < or =2.85. These were tested in 112 LSRA and 95 early-onset RA (ERA) patients. RESULTS: Factor and ROC curve analysis showed that the best predictors of a DAS28 < or = 2.85 in LSRA cohort were: (i) ESR <20 mm/h (sensitivity: 80%, specificity: 54%); (ii) swollen joint count (out of 28) < or =2 (sensitivity: 95%, specificity: 74%); (iii) patient global assessment (0-100) < or =15 (sensitivity: 78%, specificity: 78%); and (iv) HAQ (0-3) < or =0.5 (sensitivity: 91%, specificity: 61%). To each of these four criteria we assigned a value of 1 when it was satisfied (score ranging: 0-4). The cut-off with the highest overall accuracy for identifying RA patients with DAS28 < or = 2.85 was a score > or =3. We adopted these four parameters in order to define the residual MDA (RMDA). Comparing RMDA criteria, in distinct 112 LSRA and 95 ERA patients, with OMERACT, Simplified Disease Activity Index and Clinical Disease Activity Index definitions of MDA, we found a good agreement in the LSRA cohort and moderate agreement in the ERA cohort. CONCLUSIONS: HAQ, PaGA, SJC28 and ESR allow identification of RA patients with an RMDA. The RMDA criteria behaves similarly to OMERACT definitions, but appears more simple and feasible.