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ID PMID Title PublicationDate abstract
24517140 Mechanism of the 24-hour rhythm of tumor necrosis factor-alpha formed by onset of rheumato 2014 May OBJECTIVE: Morning stiffness and plasma cytokine levels in rheumatoid arthritis (RA) patients exhibit 24-hour variations. Tumor necrosis factor-α (TNF-α) plays a central role in RA clinical conditions, including the invasion of inflammatory cells, destruction of cartilage, systemic inflammatory response and its levels show a 24-hour rhythm after the onset of RA. In this study, we investigated what cytokines and/or transcriptional factors are involved in the formation of 24-hour variations in TNF-α levels after the onset of RA using MRL/Mpj-Tnfrsf6(lpr) (MRL/lpr) mice. METHOD: Blood was drawn at six different times from MRL/lpr mice to measure cytokines, serum amyloid A (SAA), IgG rheumatoid factor (IgG-RF) and corticosterone levels. Cytokine and transcriptional factor levels at the different times were measured in 10- and/or 15-week-old MRL/lpr mice. The promoter activity of TNF-α by lymphotoxins (LTs) was investigated using a dual-luciferase assay. RESULTS: SAA and TNF-α concentrations clearly exhibited 24-hour rhythms with higher levels at the light phase and lower levels at the dark phase after RA crisis. The expression of LT-α and LT-β showed significant 24-hour rhythms in 15-week-old MRL/lpr mice and the phases of LT-α and LT-β levels were antiphase compared with that of TNF-α. AP-1 binding sites were found in LT-α and LT-β promoter regions, and jun mRNA expression corresponded to LT-α and LT-β levels. TNF-α promoter activity was decreased due to the co-transfection of LT-α and LT-β. CONCLUSION: LT-α and LT-β controls the 24-hour rhythm in TNF-α levels after the onset of RA in order to suppress TNF-α promoter activity.
23709375 Evaluation of selected bone metabolism markers in rheumatoid arthritis patients. 2013 Mar BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic disease of connective tissue characterized by progressive destructive arthritis associated with deformation and impairment of the function of the motor system. RA patients more often present secondary osteoporosis and increased risk of fractures. The aetiology of the process remains not fully understood. A significant role is played by proinflammatory cytokines being common mediators of both inflammatory processes and bone remodelling. OBJECTIVES: The purpose of the study was to evaluate the effect of activity of the inflammation and of applied therapy on osteogenesis marker concentrations in RA patients. MATERIAL AND METHODS: Thirty six female patients with RA, confirmed according to ACR criteria, aged from 35 to 77 years were qualified into the study. A control group included 45 healthy women aged between 34 and 78 years. Clinical evaluation (number of painful and swollen joints, DAS 28) and evaluation of RA laboratory activity (ESR, CRP, blood cell count) and levels of selected bone metabolism markers (osteocalcin, PICP) and serum interleukin 1 levels were performed to carry out the study. X-rays of hands and densitometric scanning of the femoral bone neck and spine were completed in order to assess the advancement of lesions in the bones. RESULTS: Osteocalcin and PICP levels were significantly lower in the RA groups compared to the control group (2.51 ± 0.22 pg/mL vs. 18.65 ± 12.84 pg/mL, p < 0.0001; 0.292 ± 0.047 pg/mL vs. 0.829 ± 0.263 pg/mL, p < 0.0001 respectively). A statistically significant difference was also observed between the levels of osteocalcin and PICP in both sub-groups of RA patients (DAS28 ≤ 5.1 and DAS28 > 5.1) and the control (osteocalcin 2.48 ± 0.23 pg/mL vs. 18.65 ± 12.84 pg/mL, p < 0.0001; 2.52 ± 0.22 pg/mL vs. 18.65 ± 12.84 pg/mL, p < 0.0001 respectively and PICP 0.281 ± 0.053 pg/mL vs. 0.829 ± 0.263 pg/mL, p < 0.0001; 0.298 ± 0.044 pg/mL vs. 0.829 ± 0.263 pg/mL, p < 0.0001 respectively). No correlation was demonstrated between the levels of selected bone metabolism markers and the therapy with methotrexate or cyclosporine. CONCLUSIONS: Analysis of the obtained results confirms the presence of disorders of bone metabolism in RA patients. A chronic inflammatory process favors the development of osteoporosis in RA patients. Reduced levels of bone metabolism markers (osteocalcin, PICP) in the study group, compared to the control, may indicate a reduced pace of osteogenesis in RA patients. No effect of therapy with methotrexate and cyclosporine on bone metabolism in that group of patients was found.
24659118 Anti-cyclic citrullinated peptide antibody and rheumatoid factor isotypes in Iranian patie 2014 Jun In this study we determined the frequency, sensitivity and specificity of anti cyclic citrullinated peptides (anti-CCP) IgG antibody, total rheumatoid factor (RF-T), and RF isotypes in Iranian patients with rheumatoid arthritis (RA) and their association with age, clinical and serological parameters. Anti-CCP and RF-T and RF isotypes level were measured in 418 patients and 399 healthy controls by enzyme-linked immunosurbant assay (ELISA). Additionally, serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), visual analog scale (VAS) and disease activity score (DAS28) were evaluated in RA patients. The anti-CCP was positive in 53.1% of RA patients and 4.7% of controls. The frequency of RF-T was 61.87% and 17.66% in RA patients and controls respectively. The prevalence of RF isotypes in RA patients was 46.52% for RF-IgM, 23.47% for RF-IgA and 21.74% for RF-IgG. 31.39% of RA patients were RF-IgM positive without RF-IgA and RF-IgG and 21.9% were positive for all three RF classes. The anti-CCP positive patients showed increased number of swollen joints. On the other hand, RF-T positive patients exhibited a longer disease duration, lower age of onset and also higher ESR, CRP level and increased swollen joints. RF-T titer was significantly higher in RA patients with active disease compared to remission, low and moderate active groups. The sensitivity and specificity were 53.1, 95.3 for anti-CCP antibody and 61.8, 82.3 for RF-T. Our results support that anti-CCP and RF titer maybe valuable in estimation of disease activity and other inflammatory parameters in RA patients.
23818218 Brief report: deficient thymic output in rheumatoid arthritis despite abundance of prethym 2013 Oct OBJECTIVE: To determine the frequencies of common lymphoid progenitors (CLPs) and recent thymic emigrants (RTEs) in patients with rheumatoid arthritis (RA) and healthy control subjects. METHODS: Flow cytometry was performed to determine the frequencies of CLPs and RTEs in the peripheral blood of 101 control subjects and 51 patients with RA. Thirteen of these patients were also analyzed longitudinally for 6 months after initiation of treatment with a tumor necrosis factor (TNF) inhibitor. RESULTS: A significant correlation between the frequencies of CLPs and RTEs was observed in healthy control subjects. The frequencies of both CLPs and RTEs decreased with age and correlated inversely with absolute lymphocyte numbers in peripheral blood. In patients with RA, the frequencies of RTEs were significantly decreased compared with the frequencies in control subjects. Importantly, the frequencies of CLPs were significantly higher in patients with RA compared with control subjects. Therapeutic TNF blockade further increased the frequency of CLPs, thereby normalizing thymic output, as indicated by an increase in the number of RTEs. CONCLUSION: Thymic insufficiency in RA is not attributable to an inadequate supply of progenitor cells to the thymus. Thus, insufficient numbers of RTEs could result from inadequate thymic T cell neogenesis, or alternatively, could be a consequence of high CD4+ T cell turnover, homeostatic proliferation, and subsequent dilution of the RTE population.
25236839 Evaluation of ascending aorta wall in rheumatoid arthritis by tissue and strain Doppler im 2014 Dec BACKGROUND: Patients with rheumatoid arthritis (RA) are at increased risk of vascular events. Data on the effects of tumor necrosis factor-α (TNF-α) blocking agents on aortic vascular function are still debated. HYPOTHESIS: To evaluate the effects of anti-TNF-α treatment on elastic properties of the ascending aorta (distensibility, stiffness, and tissue Doppler imaging [TDI] strain) in RA patients. METHODS: We prospectively followed 13 patients affected by RA without cardiovascular risk factors for 1 year during anti-TNF-α treatment. Every subject received an echocardiographic examination before starting anti-TNF-α drugs and after 1 year. Aortic elastic properties were calculated from the echocardiographically derived thoracic aortic diameters, and TDI strain was measured on the wall of the ascending aorta 3 cm above the aortic valve. RESULTS: We found lower distensibility (12.9 ± 3.5 vs 21.5 ± 7.5 mm Hg(-1); P <0.001) and a higher stiffness index (21.3 ± 3.6 vs 11.7 ± 1.4; P <0.001) in RA cases at baseline compared with values after 1 year of treatment. Peak systolic (S') and diastolic (E' and A') waves of the aortic wall TDI were similar at baseline and at 1 year follow-up (S' wave: 5.6 ± 2.2 cm/s vs 6.5 ± 2.6 cm/s, E' wave: -4.6 ± 2.9 vs -5.0 ± 1.2 cm/s, A' wave: -5.6 ± 0.19 vs -5.9 ± 2.05 cm/s), whereas TDI strain of the aortic wall was improved after anti-TNF-α treatment (-23.7 ± 1.4% vs -31.6 ± 2.8%, P < 0.001). CONCLUSIONS: Anti-TNF-α treatment after 12 months significantly modifies the elastic properties of the aorta. This may reflect the favorable changes in its elastic tissue after anti-TNF-α treatment in RA patients without cardiovascular risk factors. This suggests a potential cardiovascular risk benefit.
24728880 The impact of hepatitis screening on diagnosis and treatment in rheumatoid arthritis. 2014 Dec Identification of patients with exposure to viral hepatitis is an important part of the care of patients with inflammatory arthritis. This study was conducted to assess the extent of hepatitis B and C screening, and the prevalence of viral hepatitis in a cohort of patients with established rheumatoid arthritis (RA). The medical records of 100 consecutive RA patients were retrospectively analysed for screening of hepatitis B surface antigen, surface antibody and core antibody and hepatitis C antibody. A teaching session was then conducted with the rheumatology team, emphasising the rationale for viral hepatitis testing. We then prospectively analysed 100 more RA patients to see if hepatitis screening improved. In the initial 100 patients (21 % male, mean age 65 years), 85 % were taking methotrexate and 22 % biologic treatments. A complete hepatitis screen was present in 8 %, while 12 % had hepatitis B core antibody checked and 53 % had been tested for hepatitis C.The second cohort of patients was similar to the first in terms of demographics and treatment. A complete hepatitis screen was available in 63 %, while 65 % had hepatitis B core antibody checked and 81 % had been tested for hepatitis C.In total, we identified 4 new cases of positive hepatitis B core antibody, 11 cases of positive hepatitis B surface antibody and 1 case of positive hepatitis C antibody. Even in populations where hepatitis B or C is non-endemic, screening will reveal new cases. Educational initiatives are helpful in teaching staff to screen patients.
24517555 Successful treatment with tocilizumab of pericarditis associated with rheumatoid arthritis 2014 Jul Rheumatoid arthritis (RA) is a systemic inflammatory disease often complicated by vasculitis. Pericarditis is a serious complication caused by vasculitis, resulting in retention of pericardial effusion that sometimes induces cardiac tamponade. We report a patient with RA in whom pericarditis improved after tocilizumab administration. A male patient was diagnosed with RA and chronic renal failure in 1980 and was treated with salazosulfapyridine, but disease activity remained high. In January 2012, at the age of 73 years, he developed organizing pneumonia as a complication and was admitted to our hospital. Treatment with prednisolone 30 mg/day was initiated. However, 20 days after initiation of treatment, chest pain and palpitation developed, and chest computed tomography (CT) and echocardiography (ECG) revealed retention of pericardial effusion without cardiac tamponade. Rheumatoid nodules and interstitial pneumonia were also observed, and serum C3 level was decreased. A diagnosis of pericarditis caused by vasculitis was made based on these findings, and tocilizumab 8 mg/kg was administered. His symptoms improved gradually, and chest CT and ECG showed no pericardial effusion after about 3 weeks. No adverse effects of tocilizumab were observed during the clinical course. Although there are only a few reports of the effects of tocilizumab on vasculitis associated with RA, tocilizumab administration appears worthwhile in RA patients with vasculitis who do not respond to conventional treatment.
24527466 The process of acceptance among rheumatoid arthritis patients in Switzerland: a qualitativ 2014 Mar BACKGROUND: Rheumatoid arthritis (RA) is a chronic, painful disease with many injurious psychological effects. Acceptance is an important component of pain management and is associated with improved quality of life, and lower levels of pain and depression. While studies have begun to identify the stages of acceptance, little is known about factors influencing the ease and speed with which patients pass through these stages. OBJECTIVE: To explore the main stages through which RA patients pass and the strategies they adopt to learn to live with the pain, and to identify factors shaping patients' capacities to achieve acceptance. METHODS: A qualitative study involving 20 semistructured interviews with RA patients in the Italian-speaking region of Switzerland was conducted. Analysis of the data followed the precepts of grounded theory. RESULTS: Although the present study revealed that acceptance is not a smooth or linear process, five main stages in patients' struggles to accommodate the newly imposed limitations were, nonetheless, identified: naming the illness; realizing the illness; resisting the illness; 'hitting the bottom'; and integrating the illness. Diagnosis proved to be an especially tortuous stage in the case of RA, and the effects of delayed diagnosis continued to be felt during the subsequent stages. Patients' understanding of the notion of acceptance and the strategies that they used to achieve it were also explored. CONCLUSIONS: Diagnosis of RA is notoriously difficult. Beyond the clinical difficulties, structural reasons for late diagnosis (symptoms being neglected by patients and medical professionals) were identifed. Delayed diagnosis hindered the acceptance process throughout, and led to more resistant behaviour and to a struggle to achieve the optimal formula for acceptance - accepting the losses of prepain life while still pursuing personal goals.
24988532 Risk of rheumatoid arthritis in patients with type 2 diabetes: a nationwide population-bas 2014 OBJECTIVE: Type 2 diabetes is associated with chronic, low-grade inflammation and could potentially trigger the progression of other, more prominent inflammatory diseases such as rheumatoid arthritis (RA). Therefore, we aimed to investigate the risk of incident RA in Taiwanese patients with type 2 diabetes using a population-based health claims database. METHODS: This nationwide, population-based, case-control study used administrative data to identify 1,416 patients with RA (age ≥20 years) as cases and 7,080 controls that were frequency-matched for sex, 10-year age group, and year of catastrophic illness certificate application date (index year). All subjects were retrospectively traced back, up to 13 years prior to the index year, for their first diagnosis of type 2 diabetes. Logistic regression analysis was conducted to quantify the association between incident RA and type 2 diabetes. RESULTS: The odds of developing RA were significantly higher in female (odds ratio [OR] 1.46, 95% confidence interval [95% CI] 1.24-1.72) but not in male (OR 1.00, 95% CI 0.72-1.37) patients who had previously diagnosed with type 2 diabetes. Subgroup analysis indicated that the odds of developing RA were more prominent in younger females (20 to 44 years of age) with type 2 diabetes. In addition, the odds of developing RA in female patients with type 2 diabetes were higher in those with a shorter time interval between the diagnosis of type 2 diabetes and RA. CONCLUSIONS: This large nationwide, population-based, case-control study showed an elevated risk of RA in female Taiwanese patients with type 2 diabetes. Our findings were consistent with the hypothesis that chronic low-grade inflammation in type 2 diabetes may elicit the development of RA in genetically susceptible individuals.
25359382 Methotrexate in combination with other DMARDs is not superior to methotrexate alone for re 2015 Jan OBJECTIVES: To compare the efficacy and safety of intensive combination strategies with glucocorticoids (GCs) in the first 16 weeks (W) of early rheumatoid arthritis (eRA) treatment, focusing on high-risk patients, in the Care in early RA trial. METHODS: 400 disease-modifying antirheumatic drugs (DMARD)-naive patients with eRA were recruited and stratified into high risk or low risk according to classical prognostic markers. High-risk patients (n=290) were randomised to 1/3 treatment strategies: combination therapy for early rheumatoid arthritis (COBRA) Classic (methotrexate (MTX)+ sulfasalazine+60 mg prednisone tapered to 7.5 mg daily from W7), COBRA Slim (MTX+30 mg prednisone tapered to 5 mg from W6) and COBRA Avant-Garde (MTX+leflunomide+30 mg prednisone tapered to 5 mg from W6). Treatment modifications to target low-disease activity were mandatory from W8, if desirable and feasible according to the rheumatologist. The primary outcome was remission (28 joint disease activity score calculated with C-reactive protein <2.6) at W16 (intention-to-treat analysis). Secondary endpoints were good European League Against Rheumatism response, clinically meaningful health assessment questionnaire (HAQ) response and HAQ equal to zero. Adverse events (AEs) were registered. RESULTS: Data from 98 Classic, 98 Slim and 94 Avant-Garde patients were analysed. At W16, remission was reached in 70.4% Classic, 73.6% Slim and 68.1% Avant-Garde patients (p=0.713). Likewise, no significant differences were shown in other secondary endpoints. However, therapy-related AEs were reported in 61.2% of Classic, in 46.9% of Slim and in 69.1% of Avant-Garde patients (p=0.006). CONCLUSIONS: For high-risk eRA, MTX associated with a moderate step-down dose of GCs was as effective in inducing remission at W16 as DMARD combination therapies with moderate or high step-down GC doses and it showed a more favourable short-term safety profile. EUDRACT NUMBER: 2008-007225-39.
23974102 Metabolic profiling of human CD4+ cells following treatment with methotrexate and anti-TNF 2013 Sep 15 The autoimmune process in rheumatoid arthritis depends on activation of immune cells, which utilize intracellular kinases to respond to external stimuli such as cytokines, immune complexes, and antigens. CD4+ T cells comprise a large proportion of the inflammatory cells that invade the synovial tissue and may therefore be a cell type of pathogenic importance. Both methotrexate and infliximab are effective in the treatment of inflammatory arthritis; however, the biological effects triggered by these treatments and the biochemical mechanisms underlining the cell response are still not fully understood. Thus, in this study the global metabolic changes associated with methotrexate or infliximab treatment of isolated human CD4+ T cells were examined using gas chromatography/mass spectrometry or liquid chromatography/mass spectrometry. In total 148 metabolites involved in selective pathways were found to be significantly altered. Overall, the changes observed are likely to reflect the effort of CD4+ cells to increase the production of cellular reducing power to offset the cellular stress exerted by treatment. Importantly, analysis of the global metabolic changes associated with MTX or infliximab treatment of isolated human CD4+ T cells suggested that the toxicity associated with these agents is minimal when used at clinically relevant concentrations.
24664991 Relationships between driving distance, rheumatoid arthritis diagnosis, and disease-modify 2014 Nov OBJECTIVE: Disease-modifying antirheumatic drugs (DMARDs) are recommended for all patients with rheumatoid arthritis (RA). Some estimate that approximately one-half of patients with RA do not receive DMARDs. We hypothesized that patients with RA living farther from rheumatologists would be less likely to receive RA diagnoses and to receive DMARDs. METHODS: US-based Medicare patients ages >65 years were study eligible. We calculated driving distance from patients' homes to the nearest rheumatologist. Using multivariable logistic regression, we assessed relationships between driving distance and RA diagnosis and between driving distance and DMARD receipt. In one set of analyses, distance was divided into quartiles: 0-2, 2.1-5, 5.1-15.9, and ≥16 miles. In a second set of analyses, we used predefined categories: 0-15, 15.1-30, 30.1-60, and >60 miles. RESULTS: Among 59,426 Medicare beneficiaries, 918 had diagnosed RA. Compared to the first quartile, increased distance was associated with decreased odds of RA diagnosis (odds ratio [OR] 0.96 [95% confidence interval (95% CI) 0.80-1.16] in second quartile, OR 0.88 [95% CI 0.72-1.07] in third quartile, and OR 0.72 [95% CI 0.56-0.93] in fourth quartile; P < 0.01 for trend). Similar results were observed using predefined categories. Among those with RA, increased distance was associated with increased odds of DMARD receipt across quartiles (OR 1.15 [95% CI 1.06-1.25] in second quartile, OR 1.41 [95% CI 1.29-1.54] in third quartile, and OR 1.32 [95% CI 1.18-1.46] in fourth quartile; P = 0.001 for trend). There was no relationship between predefined categories and DMARD receipt (P = 0.45 for trend). CONCLUSION: Increased driving distance to rheumatologists was associated with decreased odds of RA diagnosis. Among those with diagnosed RA, the odds of DMARD receipt rose as distance increased from <2 to 16 miles, but not beyond. Urban residents living closer to rheumatologists may have barriers to DMARD use besides geographic access.
25036563 Pigmented villonodular synovitis developing in a patient with rheumatoid arthritis. 2014 Aug A 56-year-old man developed pigmented villonodular synovitis (PVNS) 3 years after he was diagnosed with rheumatoid arthritis (RA). He had been successfully treated with methotrexate, leflunomide, sulfadiazine, and intra-articular knee injection of etanercept (tumor necrosis factor α inhibitor) in 2010. He stopped all drugs for arthritis 1 year later for disease remission. He was readmitted for right knee pain and swelling in 2013, when the magnetic resonance imaging and arthroscopy of the right knee indicated PVNS. Following surgical resection, the patient was doing well after 1 year. This rare case is the first reported case in English-language literature of PVNS of the knee seen in RA patients and illustrates the importance of differential diagnosis of this condition with synovial cysts, which are commonly found in RA.
24400920 Randomized double-blind study of the effect of dexamethasone and methylprednisolone pulse 2014 May AIM: The objective of this study was to compare the efficacy and safety of dexamethasone and methylprednisolone for pulse therapy of rheumatoid arthritis flare-up. METHODS: This randomized double-blind controlled study was performed in the Emam Reza Educational Hospital of Tabriz University of Medical Sciences, Tabriz, Iran. Thirty rheumatoid arthritis patients who had severely active disease were recruited to the dexamethasone and methylprednisolone pulse groups. Disease activity of all the patients was measured by the Disease Activity Score in 28 joints (DAS28) at baseline, and days 4 and 30. RESULTS: The differences in the DAS28 at days 4 and 30, and the number of patients whose DAS28 obtained less than 3.2 and 2.6 in the dexamethasone and methylprednisolone groups were non-significant. There was not any significant difference between the adverse effects of the treatments in the two groups. CONCLUSIONS: The results of the study suggest that dexamethasone pulse therapy is a safe and effective treatment for severe rheumatoid arthritis flare-up.
25166016 Moving towards personalized medicine in rheumatoid arthritis. 2014 To develop personalized medicine strategies for improvement of patient management in rheumatoid arthritis, the clinical and molecular properties of the individual patients need to be well characterized. A crucial step in this approach is to discover subgroups of patients that are characterized by a good or poor treatment outcome. Dennis and colleagues have identified distinct pretreatment gene expression profiles in affected synovial tissue specimens and a tissue type-related systemic protein pattern which are associated with a positive or negative clinical outcome to monotherapy with adalumimab (anti-TNFα) and tocilizumab (anti-IL-6 receptor). These observations assign biological pathways associated with response outcome and provide evidence for the existence of systemic,easy-to-measure predictive biomarkers for clinical benefit of these biologics.
24501246 Bone erosions in rheumatoid arthritis: ultrasound findings in the early stage of the disea 2014 Jun OBJECTIVE: The objective of this study was to determine the prevalence and distribution of bone erosions detectable by US in patients with early RA (ERA) in comparison with long-standing RA (LSRA), other erosive diseases and healthy controls. METHODS: Thirty patients with ERA and 80 patients with LSRA were consecutively recruited. Thirty patients with PsA, 15 with primary OA, 10 with gout and 20 healthy subjects were included as controls. Bone erosions were investigated at the following anatomical sites: the second and fifth metacarpal heads, the ulnar head and the first and fifth metatarsal heads, bilaterally. Dorsal, volar and lateral aspects were explored on longitudinal and transverse views. RESULTS: At least one US bone erosion was found in 20 (66.7%) of 30 patients with ERA and in 10 (33%) of them it was found on the fifth metatarsal head. Bone erosions were most frequently found on the lateral quadrants of all scanned anatomical sites. If the second and fifth metacarpal heads and the fifth metatarsal head were scanned, an erosive disease could be found in 60% of ERA patients. The first metatarsal head was most frequently involved in the disease control group. CONCLUSION: This study found a high percentage of ERA patients with US bone erosions, with the fifth metatarsal head and the lateral aspects the most frequently involved site and quadrants. US scanning for bone erosions on a few target joints was found feasible and provided information not obtainable with clinical examination.
24530824 Vitamin D receptor gene polymorphism as possible risk factor in rheumatoid arthritis and r 2014 May OBJECTIVE: To study the role of VDR polymorphisms as risk factor for RA and osteoporosis, and whether osteoporosis complicating RA is due to RA or VDR polymorphisms. METHODS: VDR gene polymorphisms ApaI, TaqI, BsmI and FokI were typed by RFLP for 128 RA patients, 30 postmenopausal osteoporotic females and 150 healthy controls. RESULTS: Significant differences were found between patients and healthy controls in the frequency of BsmI and TaqI (Pc<0.05) but no significant associations were found for FokI and ApaI polymorphisms except for aa genotype (Pc<0.001). Titers of RF were higher with aa and bb genotypes. Anti-CCP and CRP levels were higher with aa genotype and more bone loss was associated with Bb genotype. Ff genotype frequency was higher in RA patients with osteoporosis than those without osteoporosis. CONCLUSIONS: The ApaI, BsmI and TaqI polymorphisms may be a susceptibility risk factors for RA and the Ff genotype may be responsible for development of osteoporosis in RA Egyptian patients. However, the present study needs to be replicated in a large number of patients from allover the Egypt and also in multi-ethnic populations.
24406543 Evolution of cost structures in rheumatoid arthritis over the past decade. 2015 Apr OBJECTIVE: To estimate the changes in direct and indirect costs induced by patients with rheumatoid arthritis (RA) in German rheumatology, between 2002 and 2011. To examine the impact of functional status on various cost domains. To compare the direct costs incurred by patients at working age (18-64 years) to patients at an age of retirement (≥65 years). METHODS: We analysed data from the National Database of the German Collaborative Arthritis Centres with about 3400 patients each year. Costs were calculated using fixed prices as well as annually updated cost factors. Indirect costs were calculated using the human capital as well as the friction cost approaches. RESULTS: There was a considerable increase in direct costs: from €4914 to €8206 in patients aged 18-64, and from €4100 to €6221 in those aged ≥65, attributable to increasing prescription of biologic agents (18-64 years from 5.6% to 31.2%, ≥65 years from 2.8% to 19.2%). This was accompanied by decreasing inpatient treatment expenses and indirect costs due to sick leave and work disability. The total growth of cost, on average, was €2437-2981 for patients at working age, and €2121 for patients at retirement age. CONCLUSIONS: The increase in treatment costs for RA over the last decade was associated with lower hospitalisation rates, better functional status and a lower incidence of work disability, offsetting a large proportion of risen drug costs. Since the rise in drug costs has manifested a plateau from 2009 onwards, no relevant further increase in total costs for patients with RA treated in German rheumatology is expected.
23817641 Increased production of IL-6 and IL-17 in lipopolysaccharide-stimulated peripheral mononuc 2013 Sep TLR4-mediated inflammatory responses are important for innate immune functions, thus their alterations may participate in the pathogenesis of rheumatoid arthritis (RA). Cortisol is one of the most potent immunomodulatory hormones involved in control of inflammation. In this study, we analyzed TLR4-mediated responses and cortisol effects on the process in peripheral blood mononuclear cells (PBMC) from RA patients. Lipopolysaccharide-stimulated PBMC from 23 female patients and 15 healthy controls were cultured in the presence or absence of cortisol (1 μM) for 24 h. A panel of 17 inflammatory cytokines was analyzed in the cell culture supernatants. Higher (p < 0.05) concentrations of IL-6, IL-17 and MCP-1 were found in lipopolysaccharide-stimulated PBMC from RA patients compared to controls. After normalization of stimulated cytokine secretion to unstimulated cells, a significantly higher (p < 0.05) IL-6 and G-CSF production was found in RA PBMC. Cortisol induced stronger (p < 0.05) suppression of lipopolysaccharide-stimulated secretion of IL-1β, IL-6, IL-17 and G-CSF in RA group compared to controls. The observed higher production of the key inflammatory cytokines by RA PBMC to lipopolysaccharide stimulation supports involvement of TLR4-mediated processes in RA pathogenesis. The higher sensitivity of LPS-stimulated RA PBMC to immunosuppressive effects of cortisol may reflect adaptive processes to chronic inflammation.
23335586 Sternoclavicular joint involvement in rheumatoid arthritis: clinical and ultrasound findin 2013 Jul OBJECTIVE: To describe the prevalence of sternoclavicular (SC) joint involvement and the relationship between clinical and ultrasound (US) findings in patients with rheumatoid arthritis (RA). METHODS: One hundred three consecutive patients with RA and 103 age- and sex-matched healthy individuals were enrolled. Clinical evaluation and blinded US examinations of the SC joint were performed bilaterally in both groups. The presence of gray-scale synovitis, osteophytes, erosions, and intraarticular power Doppler (PD) was recorded. Interobserver agreement was calculated. RESULTS: A total of 412 SC joints were evaluated: 206 from patients with RA and 206 from healthy controls. In the RA group, 39 joints (19%) were found to be clinically involved (pain/swelling), in contrast to only 4 (1.9%) in the control group (P = 0.0001). In the RA group, US abnormalities were recorded in 89 SC joints (43%) compared with 36 (17%) in the healthy control group (P = 0.0001), comprising osteophytes in 59 (29%) versus 25 (12%; P = 0.0001), synovitis in 31 (15%) versus 5 (2%; P = 0.0001), erosions in 23 (11%) versus none (P = 0.0001), and intraarticular PD in 5 (2%) versus none (P = 0.03). Furthermore, a correlation between the presence of US synovitis (P < 0.001) and intraarticular PD (P < 0.0001) with a higher Disease Activity Score in 28 joints (DAS28) was found. CONCLUSION: In patients with RA, US detected a higher number of involved SC joints than with clinical assessment. Our results indicate that both gray-scale and PD US findings were more prevalent in patients with RA than in healthy controls. US synovitis and synovial hyperperfusion correlated with the DAS28, suggesting that SC joints actively participate in the systemic inflammatory process of RA.