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ID PMID Title PublicationDate abstract
18390910 Quantifying anti-cyclic citrullinated peptide titres: clinical utility and association wit 2009 Feb OBJECTIVE: To determine the significance of quantitative levels of antibodies to cyclic citrullinated peptides (anti-CCP) in a population of patients with rheumatoid arthritis (RA). METHODS: A total of 241 consecutive sera from patients with RA sent from a large rheumatology clinic for laboratory testing were selected for precisely quantifying anti-CCP antibody titres with the anti-CCP2 assay. Patient charts were reviewed for demographic information, smoking history, clinical diagnosis, rheumatoid factor (RF) titre, radiographic information and other laboratory information (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level). Correlations with anti-CCP titre and RF titre, disease parameters and smoking history were assessed. RESULTS: We confirm previous findings that anti-CCP seropositivity is associated with a higher incidence of erosions in patients with RA (56% vs 20% CCP+ vs CCP-, kappa = 0.297, p<0.001). We also found a moderate correlation between anti-CCP titre and RF titre. However, we failed to find an association between anti-CCP titre and presence of erosions, between anti-CCP titre and CRP or ESR level, or between anti-CCP titre and age or disease duration. Interestingly, we did find significantly higher anti-CCP titres in patients with a history of smoking (452 units/ml vs 229 units/ml, smokers vs non-smokers, respectively; p = 0.02). CONCLUSIONS: Although anti-CCP titres were not associated with clinical parameters of disease, they are increased in patients with RA with exposure to tobacco. By contrast, no elevation in RF was noted in patients with a history of smoking. These observations are consistent with a pathogenic contribution of smoking to RA and suggest the immune stimulus for anti-CCP is distinct from that for RF.
20064278 Levels of anti-citrullinated protein antibodies and IgM rheumatoid factor are not associat 2010 INTRODUCTION: To investigate whether baseline levels of anti-citrullinated protein antibody (ACPA) or IgM rheumatoid factor (IgM-RF) and changes in the year thereafter are associated with disease activity, functional and radiographic outcome in early arthritis patients, and provide additional information over baseline autoantibody status. METHODS: In 545 early arthritis patients ACPA and IgM-RF levels, disease activity (DAS28), the Health Assessment Questionnaire (HAQ) and Sharp/Van der Heijde Score (SHS) were assessed annually. Baseline status, levels and first-year changes of the autoantibodies were associated with these measures at the two-year follow-up and sub-analysed according to autoantibody status. RESULTS: The mean age was 52.7 years, 69% was female, at baseline 56% was ACPA positive, 47% IgM-RF positive. At the two-year follow-up the mean DAS28 was 2.88, and the median HAQ and SHS were 0.38 and 1, respectively. At one year, ACPA and IgM-RF levels had decreased by 31% and 56%, respectively. A switch from negative to positive occurred in 2% for ACPA and 3% for IgM-RF. Positive ACPA and RF status were both associated with SHS at two years (P < 0.001), but baseline levels only showed a minor correlation of ACPA with DAS28 and HAQ at two years. Level changes were not associated with the outcome parameters. CONCLUSIONS: Baseline levels and first-year changes of ACPA and IgM-RF are hardly associated with outcome after two years. Seroconversion seldom occurs. Therefore, it does not appear useful to repeat ACPA or IgM-RF measurements.
20520649 Intra-articular lentivirus-mediated delivery of galectin-3 shRNA and galectin-1 gene ameli 2010 Oct Different members of the galectin family may have inhibitory or stimulatory roles in controlling immune responses and regulating inflammatory reactions in autoimmune diseases such as rheumatoid arthritis (RA). A hypothetical model of a cross talk between galectin-1 and galectin-3 has been established in the circumstance of rheumatoid joints. As galectin-3 is a positive regulator and galectin-1 is a negative regulator of inflammation and autoimmune responses, in this study we evaluated the effects of local knockdown of galectin-3 or overexpression of galectin-1 on ameliorating collagen-induced arthritis (CIA) in rats. Lentiviral vectors encoding galectin-3 small hairpin RNA (shRNA) and galectin-1, as well as two control vectors expressing luciferase shRNA and green fluorescent protein, were individually injected intra-articularly into the ankle joints of rats with CIA, and their treatment responses were monitored by measuring the clinical, radiological and histological changes. Our results show that both knockdown of galectin-3 and overexpression of galectin-1 induced higher percentages of antigen-induced T-cell death in the lymph node cells from arthritic rats. Furthermore, these treatments significantly reduced articular index scores, radiographic scores and histological scores, accompanied with decreased T-cell infiltrates and reduced microvessel density in the ankle joints. Our findings implicate galectin-3 and galectin-1 as potential therapeutic targets for the treatment of RA.
19359276 Identification of AF4/FMR2 family, member 3 (AFF3) as a novel rheumatoid arthritis suscept 2009 Jul 1 The concept of susceptibility genes common to different autoimmune diseases is now firmly established with previous studies demonstrating overlap of loci conferring susceptibility to type 1 diabetes (T1D) with both Coeliac disease and multiple sclerosis. Rheumatoid arthritis (RA) is an archetypal autoimmune disease and we, therefore, targeted putative T1D susceptibility loci for genotyping in UK RA cases and unrelated controls. A novel RA susceptibility locus at AFF3 was identified with convincing evidence for association in a combined sample cohort of 6819 RA cases and 12 650 controls [OR 1.12 95% confidence intervals (CI) 1.07-1.17, P = 2.8 x 10(-7)]. Association of two previously described loci (CTLA-4 and 4q27) with RA was also replicated (OR 0.87, 95% CI 0.82-0.94, P = 1.1 x 10(-4) and OR 0.86, 95% CI 0.79-0.94, P = 5.4 x 10(-4), respectively). These findings take the number of established RA susceptibility loci to 13, only one of which has not been associated with other autoimmune diseases.
20416859 [Lipid profile and cardiovascular risk in patients with rheumatoid arthritis: Effect of th 2010 Sep The increased mortality in patients with rheumathoid arthritis (RA) is mainly due to high incidence of cardiovascular (CV) disease. CV morbidity and mortality in RA can be explained by several mechanisms: (1) chronic inflammation, (2) enhanced prevalence of traditional CV risk factors including atherogenic dyslipoproteinemia, (3) a lower use of evidence-based therapy such as statins and (4) chronic treatment for RA such as glucocorticoids. It is difficult to distinguish between the role of pharmacological treatment per se and the severity or duration of the disease since these two parameters are closely interrelated. RA likely influences lipoprotein metabolism leading to quantitative and qualitative alteration of low-density lipoproteins (LDL) and of high-density lipoproteins. Glucocorticoids alter carbohydrate and lipid metabolism. However, by reducing the inflammation level, the net effect on lipid parameters and on the CV risk may be favorable. Data from open follow-up studies would suggest that methotrexate use is associated with a beneficial effect on lipid parameters and with a reduction in the incidence of CV disease. Anti-TNF agents increase LDL-cholesterol in some but not all studies; however the use of anti-TNF agents likely reduce CV risk in patients with RA. The influence of recently developed compounds, anti-CD20, CTLA-4 Ig or anti-IL6 is not well documented. Anti-IL6 seem to increase total and LDL-cholesterol; however these changes are associated with an improvement in the TC/HDL-C ratio.
20921970 A genetic marker at the OLIG3/TNFAIP3 locus associates with methotrexate continuation in e 2012 Apr Whole-genome association studies in rheumatoid arthritis have identified single-nucleotide polymorphisms (SNPs) predisposing to disease with moderate risk. We aimed to investigate the role of these markers in predicting methotrexate (MTX) response, measured by continuation on MTX monotherapy in patients with recent onset inflammatory polyarthritis (IP). In all, 19 SNPs were genotyped in 736 patients treated with MTX following registration, or not more than 3 months before registration, to the Norfolk Arthritis Register. The association of SNPs with MTX continuation by year 1 and by year 2 was investigated using Cox proportional hazard regression models. A SNP within the OLIG3/TNFAIP3 locus (rs6920220) was associated with being less likely to maintain MTX monotherapy at year 1, hazards ratio (HR) 1.73 (1.18, 2.52) and year 2, HR 1.49 (1.11, 2.00); correlating with an increased in adverse events. Weak evidence for an effect at the PTPN22 locus was also observed. These findings require replication in other large datasets.
20659406 Decreased levels of CCR3 in CD4+ lymphocytes of rheumatoid arthritis patients. 2010 Jul OBJECTIVES: To evaluate the expression of CCR3 receptors as well as CCR3 agonists, including eotaxin-2 and RANTES, among patients suffering from rheumatoid arthritis and healthy controls, as a possible pathogenetic mechanism in inflammatory joint disease. METHODS: Twenty-two patients and 13 healthy controls were recruited and clinically evaluated. CCR3 expression on CD4+ lymphocytes and mononuclear cells was evaluated by FACS analysis after staining with human CD4 APC (bioscience) and human CCR3 (CD193)PE. Levels of eotaxin-2 and RANTES were analysed by ELISA. RESULTS: A significant decrease was observed in the level of CD4+ cells expressing the CCR3 receptor in serum of RA patients (0.96+/-0.5) as compared with healthy controls (1.48+/-0.6) (p<0.05). A significant decrease in serum eotaxin-2 levels was evident among RA patients suffering from active disease, defined by a DAS-28 score above 5.5, compared with RA patients with lower activity scores (2.1+/-1.6 vs. 7.0+/-5.1; p=0.01). A significant decrease was evident in the number of CCR3 expressing Monocytes among RA patients treated with steroids and anti TNF-a medications as compared with RA patients not receiving such treatment. CONCLUSIONS: CCR3 is differentially expressed on inflammatory cells in RA, while eotaxin-2, a potent CCR3 agonist, is differentially expressed in active disease. Anti-inflammatory medications may down-regulate CCR3 expression in RA. The CCR3-CCR3 agonist pathway may thus have a pathogenic role in RA and may be a future target for novel treatment modalities.
19736621 Protein arginine deiminase 4 (PAD4): Current understanding and future therapeutic potentia 2009 Sep The protein arginine deiminases (PADs), and in particular PAD4, have emerged as potential therapeutic targets for the treatment of rheumatoid arthritis (RA). In this review, evidence linking dysregulated PAD activity to the onset and progression of RA is presented, and the potential role of such aberrant activity in other human diseases, such as multiple sclerosis and cancer, is discussed. The known physiological roles of the PADs, particularly PAD4, and current knowledge regarding PAD structure, catalysis and inhibition are also described.
19650889 Presence of Mycoplasma fermentans in the bloodstream of Mexican patients with rheumatoid a 2009 Aug 3 BACKGROUND: Increasing evidence incriminates bacteria, especially Mycoplasma fermentans, as possible arthritogenic agents in humans. The purpose of this study was to investigate M. fermentans in the bloodstream of patients with rheumatoid arthritis. METHODS: Two hundred and nineteen blood samples from patients with rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid syndrome, and healthy individuals were screened by bacterial culture and direct PCR in order to detect mycoplasmas; IgM and IgG against M. fermentans PG18 were also detected by ELISA and Immunoblotting assays in patients with rheumatoid arthritis and healthy individuals. RESULTS: Blood samples from patients with antiphospholipid syndrome and healthy individuals were negative for mycoplasma by culture or direct PCR. In blood samples from patients with systemic lupus erythematosus were detected by direct PCR M. fermentans in 2/50 (2%), M. hominis in 2/50 (2%) and U. urealyticum in 1/50 (0.5%). In patients with RA M. fermentans was detected by culture in 13/87 blood samples and in 13/87 by direct PCR, however, there was only concordance between culture and direct PCR in six samples, so M. fermentans was detected in 20/87(23%) of the blood samples from patients with RA by either culture or PCR. Antibody-specific ELISA assay to M. fermentans PG18 was done, IgM was detected in sera from 40/87 patients with RA and in sera of 7/67 control individuals, IgG was detected in sera from 48/87 RA patients and in sera from 7/67 healthy individuals. Antibody-specific immunoblotting to M. fermentans PG18 showed IgM in sera from 35/87 patients with RA and in sera from 4/67 healthy individuals, IgG was detected in sera from 34/87 patients and in sera from 5/67 healthy individuals. CONCLUSION: Our findings show that only M. fermentans produce bacteremia in a high percentage of patients with RA. This finding is similar to those reported in the literature. IgM and IgG against M. fermentans PG18 were more frequent in patients with RA than healthy individuals.
20535788 Rates and predictors of hydroxychloroquine retinal toxicity in patients with rheumatoid ar 2010 Jun OBJECTIVE: Hydroxychloroquine (HCQ) retinopathy is of concern because of the potential seriousness of visual loss and the medicolegal consequences of failure to detect toxicity. However, there have been limited demographic data on which to base recommendations for screening. We have studied the largest unselected series of patients to date to evaluate the risk of toxicity and the relevance of purported risk factors. METHODS: We studied 3,995 patients with rheumatoid arthritis or systemic lupus erythematosus who had used HCQ, including 1,538 current users. We screened for self-reported toxicity, and followed up on positive cases with detailed interviews and specialist confirmation. We categorized cases as "definite or probable" if there was bull's eye maculopathy or visual field loss. RESULTS: Of the lifetime users of HCQ, 6.5% discontinued therapy because of an eye problem, including 1.8% who reported HCQ retinal problems. However, definite or probable toxicity was documented in only 0.65% (95% confidence interval 0.31-0.93). The risk of toxicity was low in the initial 7 years of exposure, and was approximately 5 times greater after 7 years of usage (or 1,000 gm total exposure). Toxicity was unrelated to age, weight, or daily dosage. Eye examinations were obtained annually by 50.5% and every 6 months by 40.4% of patients. CONCLUSION: HCQ toxicity remains uncommon, but increases markedly with the duration of therapy and exceeds 1% after 5-7 years. Toxicity was unassociated with age, daily dosage, or weight. These findings will aid the reformulation of screening guidelines.
19822063 A systematic comparison of rheumatoid arthritis and ankylosing spondylitis: non-steroidal 2009 Jul Non-steroidal anti-inflammatory drugs (NSAIDs) play different roles in the management of patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). In RA there is minimal evidence that NSAIDs are able to alter the course of disease or prevent joint destruction and, therefore, they should mostly be used as a short-term bridging therapy. In contrast to RA, in AS NSAIDs are considered as a cornerstone of the treatment not only because of a high symptomatic efficacy, but also because they might even retard osteoproliferation and radiographic progression. Considering younger age of AS patients and lower prevalence of comorbidities, they are probably at lower risk for cardiovascular and gastrointestinal side effects of short- and long-term NSAID therapy in comparison to RA.
21179282 Engagement of toll-like receptor 3 induces vascular endothelial growth factor and interleu 2010 Dec BACKGROUND/AIMS: Angiogenesis, which is a critical step in the initiation and progression of rheumatoid arthritis (RA), involves pro-angiogenic factors, including interleukin (IL)-8 and vascular endothelial growth factor (VEGF). We investigated the role of Toll-like receptor 3 (TLR3) in the regulation of pro-angiogenic factors in RA fibroblast-like synoviocytes (FLS). METHODS: FLS were isolated from RA synovial tissues and stimulated with the TLR3 ligand, poly (I:C). The levels of VEGF and IL-8 in the culture supernatants were measured using enzyme-linked immunosorbent assays, and the mRNA levels were assessed by semiquantitative reverse transcription-polymerase chain reaction. The expression patterns of VEGF and IL-8 in the RA synovium and osteoarthritis (OA) synovium were compared using immunohistochemistry. RESULTS: The expression levels of TLR3, VEGF, and IL-8 were significantly higher in the RA synovium than in the OA synovium. VEGF and IL-8 production were increased in the culture supernatants of RA FLS stimulated with poly (I:C), and the genes for these proteins were up-regulated at the transcriptional level after poly (I:C) treatment. Treatment with inhibitors of nuclear factor-kappaB (NF-κB), i.e., pyrrolidine dithiocarbamate and parthenolide, abrogated the stimulatory effect of poly (I:C) on the production of VEGF and IL-8 in RA FLS. CONCLUSIONS: Our results suggest that the activation of TLR3 in RA FLS promotes the production of proangiogenic factors, in a process that is mediated by the NF-κB signaling pathway. Therefore, targeting the TLR3 pathway may be a promising approach to preventing pathologic angiogenesis in RA.
20840794 MicroRNA-146a expresses in interleukin-17 producing T cells in rheumatoid arthritis patien 2010 Sep 15 BACKGROUND: Interleukin (IL)-17 is an important factor in rheumatoid arthritis (RA) pathogenesis. MicroRNA (miRNA)s are a family of non coding RNAs and associated with human diseases including RA. The purpose of this study is to identify the miRNAs in the differentiation of IL-17 producing cells, and analyze their expression pattern in the peripheral blood mononuclear cells (PBMC) and synovium from RA patients. METHODS: IL-17 producing cells were expanded from CD4+T cell. MiRNA microarray was performed to identify the miRNAs in the differentiation of IL-17 producing cells. Quantitative polymerase chain reaction was performed to examine the expression patterns of the identified miRNAs in the PBMC and synovium from RA and osteoarthritis (OA) patients. Double staining combining in situ hybridization and immunohistochemistry of IL-17 was performed to analyze the expression pattern of identified miRNA in the synovium. RESULTS: Six miRNAs, let-7a, miR-26, miR-146a/b, miR-150, and miR-155 were significantly up regulated in the IL-17 producing T cells. The expression of miR-146a and IL-17 was higher than in PBMC in the patients with low score of Larsen grade and short disease duration. MiR-146a intensely expressed in RA synovium in comparison to OA. MiR-146a expressed intensely in the synovium with hyperplasia and high expression of IL-17 from the patients with high disease activity. Double staining revealed that miR-146a expressed in IL-17 expressing cells. CONCLUSION: These results indicated that miR-146a was associated with IL-17 expression in the PBMC and synovium in RA patients. There is the possibility that miR-146a participates in the IL-17 expression.
20450789 [Impact of citrullination upon antigenicity of fibrinogen]. 2010 Mar 9 OBJECTIVE: To investigate the impact of citrullination upon the antigenicity of fibrinogen peptides and explore the molecular mechanism of autoimmunity against citrullinated fibrinogen in the pathogenesis of rheumatoid arthritis (RA). METHODS: Human fibrinogen was citrullinated in vitro by peptidylarginine deiminase (PAD). Stimulation of citrullinated fibrinogen on PBMC (peripheral blood mononuclear cell) from RA patients and controls was studied by measuring cellular proliferation. Then the bindings of peptides derived from fibrinogen alpha chain and its citrullinated substitute to HLA-DR4 molecule were analyzed by the prediction software. One peptide was chosen and its arginine residues were altered by citrulline residues. Wild-type and altered peptides were synthesized and their bindings to HLA-DR4 molecules examined by peptide binding assay respectively. The effects of two peptides upon T cells were determined by T cell proliferation assay. RESULTS: Compared with controls, the cellular responses to citrullinated fibrinogen or wild protein were slightly higher in RA patients. However no statistical difference was found (P > 0.05). As predicted, the citrullinated substitute peptide from fibrinogen alpha chain was more prone to bind to HLA-DR4 molecule than wild-type peptide and could induce a stronger proliferation of T cells than wild-type peptide (SI, 2.26 +/- 0.14 vs 1.65 +/- 0.53, P < 0.01) in the experiments of cell lines. CONCLUSIONS: Citrullination can enhance the antigenicity of fibrinogen peptides by increasing the binding of fibrinogen peptides to HLA-DR4 molecules and inducing the specific T cell activation.
19809965 ["TRECID", TNFalpha related chronic inflammatory diseases - a new multiple diseases bridgi 2009 Oct The pro-inflammatory cytokine TNF alpha (TNF) has a key position in the pathogenesis of various infectious and inflammatory diseases. Clarification of its pivotal role in the pathogenesis of rheumatoid arthritis, spondyloarthritis, uveitis, psoriasis and inflammatory bowel disease has resulted in the successful development of TNF- blocking therapies, which have disease-modifying properties that exceed the effects of conventional therapeutic options. For this reason data on the concurrence of several chronic inflammatory diseases have led to the hypothesis of common pathogenetic processes of cytokine dysregulation. The acronym TRECID describes this concept of "TNF RElated Chronic Inflammatory Diseases". Physicians of different specialties have integrated new therapeutic options with TNF-blocking therapies into their strategies for the management of the affected patients. Thus the concept of TRECID can be regarded as a role model for a dynamic, interdisciplinary cooperation based on shared pathophysiological aspects.
20074482 The economic burden of biological therapy in rheumatoid arthritis in clinical practice: co 2009 Oct Rheumatoid arthritis (RA), with a prevalence of 0.46%, is found in about 272,004 patients in Italy. The socioeconomic cost of rheumatoid arthritis in Italy in 2002 has been estimated at Euro 1,600 million. Cost-effectiveness evaluations have been based on the concept that, with treatment, patients will not progress to the next level(s) of disease severity or will take a longer time to progress, thus avoiding or delaying the high costs and low utility associated with more severe disease. Many cost-effective studies have been based on the variation of Health Assessment Questionnaire (HAQ) in clinical trials. The objective of this study is to perform a cost-effective analysis of 86 patients with rheumatoid arthritis in therapy with adalimumab 40 mg every other week and etanercept 50 mg/week for two years in a population of patients observed in clinical practice. The group of patients in therapy with adalimumab had also taken methotrexate, mean dose 12.4+/-2.5 mg/week (22 patients) or leflunomide 20 mg/day (16 patients). The group of patients in therapy with etanercept had also taken methotrexate, mean dose 11.7+/-2.6 mg/week (24 patients) or leflunomide 20 mg/day (24 patients). Incremental costs and QALYs (quality adjusted life years) gains are calculated compared with baseline, assuming that without biologic treatment patients would remain at the baseline level through the year. Conversion HAQ scores to utility were based on the Bansback algorithm. The results after two years showed: in the group methotrexate+adalimumab the QALY gained was 0.62+/-0.15 with a treatment cost of Euro 26,517.62 and a QALY/cost of Euro 42,521.13. In the group methotrexate + etanercept the QALY gained was 0.64+/-0.26 with a treatment cost of Euro 25,020.96 and a QALY/cost of Euro 39,171.76. The result of using etanercept in association with methotrexate is cost-effectiveness with a QALY gained under the acceptable threshold of Euro 50,000. These are important data for discussion from an economic point of view when we choose a biologic therapy for rheumatoid arthritis in clinical practice.
20493751 Economic impact of rheumatoid arthritis (RA) biotherapies in France. 2010 Jul OBJECTIVE: Determining the economic impact of rheumatoid arthritis (RA) biotherapies in France. METHOD: The number of patients on RA biotherapy in France was estimated from the French national medical information system program (PMSI) database using the 2007 hospital data. The cost of each biotherapy was calculated on a theoretical basis (French national health authority (HAS) recommendations) and on real-life setting, using 'real-life' setting data. In order to calculate the economic impact of the biotherapies, the cost of management with each biotherapy was applied to the RA patient population taking into account the market share of each biotherapy. RESULTS: The number of patients with RA estimated was 15,873. Management costs ranged from 11,576 to 21,128 euro for the theoretical management scenario and from 6,451 to 19,618 euro for the real-life scenario. The overall cost was 222 million euro (real-life setting). TNF antagonists (adalimumab, etanercept, infliximab) were prescribed for 82% of the patient population and accounted for 80% of the annual overall cost of theoretical management and 84% of the cost of the real-life setting, respectively. Other biotherapies (abatacept, rituximab) were prescribed for 18% of the patients and accounted for 20 and 16% of the annual overall cost of the theoretical setting and real-life setting. Outpatient biotherapy was prescribed for 61% of the patient population and generated 68 and 71% of the total costs. CONCLUSION: The data constitutes an initial inventory of the economic impact of RA biotherapies in France.
20654699 Disruption of the blood-brain barrier in collagen-induced arthritic mice. 2010 Oct 4 Patients with rheumatoid arthritis (RA) are at higher risk of developing pathological cardiovascular and cerebrovascular events than non-RA subjects. Vascular endothelial dysfunction is involved in the induction of cardiovascular events and this process is also observed in patients with RA. Endothelial dysfunction impairs the integrity of the blood-brain barrier (BBB); this phenomenon also underlies brain damage in cerebrovascular diseases. This study was aimed at evaluating the influence of a chronic inflammatory state on BBB integrity in RA using collagen-induced arthritis (CIA), an animal model of RA. CIA was induced by intradermal injection of type II collagen emulsified with Freund's complete adjuvant at the base of the tail of DBA/1 mice. Cerebrovascular permeability was assessed by measurement of sodium fluorescein (Na-F) content in the brains of CIA mice. The expression level of tight junction proteins was investigated by immunoblotting and immunofluorescence of occludin and zonula occludens-1 (ZO-1). Cerebrovascular permeability to Na-F in the brain was increased in CIA mice. This CIA-induced BBB hyperpermeability was more remarkable in the advanced stage than that in the persistent stage of the arthritis. The expression of occludin, but not that of ZO-1, was decreased by CIA. Our results indicate that the integrity of the BBB could be impaired in the inflammatory pathophysiology of RA.
19212282 [Contrast-enhanced ultrasound in musculoskeletal diseases]. 2009 Jan Contrast-enhanced US (ultrasonography) can be used for the study of musculoskeletal diseases but this application still belongs to clinical research. Despite a theoretical value for the identification of microvascularity, the technical limitations of musculoskeletal US are challenging the use of contrast enhanced US. This can explain the slow development of this application and the reason why it remained limited to the assessment of Doppler signal intensity increase. However, the recent availability of real time contrast-enhanced US imaging and quantification data is very promising. The majority of published papers involves rheumatoid arthritis and demonstrates the value of this technique to improve diagnosis, stage the activity of the disease and follow the patients under therapy. These preliminary studies are extending to other disorders (inflammatory arthritides as well as degenerative disorders). Structures other than articular synovium are undergoing investigations (bone, enthesis). New applications are being developed such as contrast-enhanced US of muscular diseases. This new imaging technique appears to have great potentials for the assessment of musculoskeletal diseases.
20066424 A case of rheumatoid arthritis presenting with postherpetic neuralgia and abdominal-wall p 2012 Jun Postherpetic neuralgia is a common complication, while the postherpetic abdominal-wall pseudohernia (AWP) is a quite rare complication of herpes zoster (HZ). We report a patient >45 years of age with a history of rheumatoid arthritis (RA) who presented with two chronic HZ complications. A 75-year-old woman was admitted with neuralgia following cutaneous herpes zoster 6 weeks before. She was on long-term glucocorticoid, antimalarial and non-steroidal anti-inflammatory treatment. Confluent ulcers began to fill with granulation tissue, crusts, scars and skin discoloration in the area of the left T12-L2 dermatomes and reducible, painless swelling of the left flank, 20 × 20 cm, without palpable defect in abdominal-wall. There were typical joint deformity and positive rheumatoid factor. On neurological examination superficial abdominal reflexes were diminished in the left side, with hypesthesia of the overlying skin. Needle electromyography revealed denervational changes limited to the left-side muscles (on affected dermatomes T12-L2). Thoracoabdominal CT did not reveal the presence of existing hernia. There was an abdominal distension, the left abdominal-wall was thinner than the right side. The patient was treated with an oral preparation containing benfotiamine and vitamins B6 and B12, carbamazepine, amitriptyline, gabapentin, and local lidocaine. Skin rash left with scarring and pigmentary changes and the abdominal-wall swelling resolved within 8 months, however, the pain still persisted. To our best knowledge, this is the first observation of RA-associated postherpetic AWP. This rare motor complication appears to be self-limited with a good prognosis for recovery, while postherpetic neuralgia may require a combination of treatments for adequate pain relief. Older age, female sex, greater rash and acute pain severity are considered as risk factors associated with severe postherpetic neuralgia. In addition, patients with RA, mainly those treated with oral corticosteroids, are also at increased risk of HZ complications.