Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
24898046 Comparison of characteristics of international and national databases for rheumatoid arthr 2014 OBJECTIVES: To evaluate current (inter)national registers and observational cohorts in Europe, and to compare inclusion criteria, aims, collected data, and participation in the European League Against Rheumatism (EULAR) repository. METHOD: We performed a systematic search strategy in six literature databases for rheumatoid arthritis (RA). Publications reporting European (inter)national prospective registers/cohorts including > 200 RA patients with at least half a year of follow-up were selected. RESULTS: In total, 417 articles and abstracts were included from four international databases and 39 national databases/cohorts. International databases were of similar design, frequency of data collection and selection criteria and are mostly initiated to monitor and compare clinical patient care among countries. National databases/cohorts vary in aims and inclusion criteria. Half of the national registers are connected to the EULAR repository of databases. CONCLUSIONS: Our findings indicate that, among researchers, there is little awareness of guidelines to set up registers or cohorts and of the existence of the database collaboration network of EULAR.
25193808 Greyscale and power Doppler ultrasonographic evaluation of normal synovial joints: correla 2015 Mar OBJECTIVE: US is a promising tool in evaluating RA synovitis, but abnormal US findings have been reported in small subsets of normal joints in healthy subjects. This study aimed to systematically assess greyscale US (GSUS) and power Doppler US (PDUS) findings in 40 peripheral joints-the 28-joint DAS (DAS28) set, ankles and MTP joints-in healthy subjects. A composite score of abnormal US findings in 40 joints was compared with serum levels of pro-inflammatory cytokines. METHODS: US of 60 standard views in 40 joints was performed in 30 healthy subjects (total 3600 images). GSUS and PDUS were scored semi-quantitatively (0-3). Serum samples were obtained at the time of US and analysed for IL-1α, IL-1β, IL-2, IL-6, IL-8, VEGF, TNF-α and IFN-γ using biochip array technology. RESULTS: GSUS abnormalities were more frequent than PDUS abnormalities [mean total GSUS score = 20.07 (range 6-45; maximum potential score = 180), mean total PDUS score = 4.8 (range 0-13)]. GSUS score increased with increasing age (Spearman's ρ = 0.383, P = 0.037). A PDUS signal >1 was observed only in the wrist (8%) and MTP1 (3%). GSUS scores did not correlate with any pro-inflammatory cytokine level. The total PDUS score correlated significantly with serum VEGF (r = 0.395, P = 0.046). CONCLUSION: PDUS signals >1 are rarely seen in normal synovial joints. GSUS synovitis, but not PDUS, may reflect age-related joint changes. PDUS correlated with VEGF, providing further evidence of a central role for VEGF in synovial neo-angiogenesis.
24844672 Measurement properties of rheumatoid arthritis-specific quality-of-life questionnaires: sy 2014 Dec PURPOSE: This study conducted a systematic review of the methodological quality of the psychometric evaluation process and the quality of measurement properties of rheumatoid arthritis (RA)-specific health-related quality-of-life (HRQOL) questionnaires with the purpose of obtaining the best evidence to help in the selection of the most appropriate instrument for measuring HRQOL in RA patients. METHODS: A systematic literature search was performed to identify RA-specific HRQOL questionnaires in databases. The methodological quality of the studies was assessed using the Consensus-based Standards for the Selection of Health Measurement Instruments checklist. The quality of the measurement properties was assessed using quality criteria. The evidence regarding the measurement properties was pooled using best-evidence synthesis, with considerations of the number and methodological quality of the studies, and the consistency of their findings in terms of the quality of the measurement properties. RESULTS: The search identified 37 studies describing 9 instruments. Best-evidence synthesis suggested that the Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire had the strongest positive evidence, especially with respect to reliability, measurement error, and content validity, and moderate positive evidence with respect to hypothesis testing and responsiveness. CONCLUSIONS: The current evidence suggests that the best-validated instrument among the RA-specific HRQOL measures is the RAQoL questionnaire in terms of both methodological quality in the process of psychometric evaluation and the quality of the measurement properties. However, there is limited evidence regarding internal consistency and structural validity of the RAQoL. Further efforts are warranted to establish the psychometric quality of this questionnaire.
25556282 Paraneoplastic arthritis mimicking rheumatoid arthritis in cervical cancer. 2014 Paraneoplastic arthritis, a subcategory ofparaneoplastic syndrome, presents in a similar manner to rheumatic disorder and usually precedes the detection of the primary tumor by years. Herein, the authors report a case of a patient who was diagnosed with parane- oplastic rheumatoid arthritis (RA)-like arthritis with synchronous cervical cancer. A 38-year-old nulligravida woman was admitted to the gynecology department with a three-month history of irregular vaginal spotting accompanied by severe multiple joint pain. She had a one-year history of RA, for which she had been receiving treatment. During the early stage of treatment, her symptoms were slightly improved by RA treatment; however, after eight months of treatment, she showed absolute resistance to RA treatments and complained of a profuse vaginal discharge with severe foul odor. After colposcopy-directed punch biopsy, she was diagnosed with Stage IIA2 squamous cell carcinoma of the cervix. She underwent radical hysterectomy with lymphadenectomy without complications. After treatment, the multiple joint pain associated with paraneoplastic arthritis spontaneously disappeared. There was no evidence of malignancy according to the follow-up cervical cytology report, magnetic resonance imaging, and positron emission tomography-computed tomography.
24706280 Screening for novel serum biomarker for monitoring disease activity in rheumatoid arthriti 2014 Useful biomarkers, which enable the prediction of drug susceptibility, identification of side effects, and/or evaluation of disease activity during drug treatment, are urgently needed to select adequate drugs for patients. Gene mutation status, protein expression levels in a biopsy, and serum proteins are often used as biomarkers. One of the methods to screen for protein biomarkers involves quantitative proteomic approaches using mass spectrometry. Owing to the development of quantitative proteomic approaches, the efficiency of identifying novel biomarkers from clinical samples has improved. In particular, isobaric tag for relative and absolute quantitation technology, which enables relative comparative analysis of up to eight samples, enables high-throughput analysis of screening for biomarkers at the protein level. Here, we describe the identification of a novel biomarker, which is useful for the evaluation of disease activity in patients with rheumatoid arthritis who were treated with anti-TNF-α therapy.
25084482 Decoy receptor 3 suppresses B cell functions and has a negative correlation with disease a 2014 Sep OBJECTIVES: The decoy receptor 3 (DcR3) is a member of the tumour necrosis factor (TNF) receptor superfamily and may regulate inflammation. The aim of this study was to investigate the role of DcR3 in B cell functions and its correlation to disease activity in patients with rheumatoid arthritis (RA). METHODS: The concentrations of DcR3 and TNF-α were measured by ELISA. B cell proliferation was assessed by quantification of 3H-thymidine uptake. Staphylococcus aureus Cowan (SAC) strain were used to stimulate B cell proliferation and TNF-α production. RESULTS: Compared to the osteoarthritis (OA) patients, the RA group had higher synovial DcR3 levels (3273.6±1623.2 vs. 1594.8±1190.0 pg/ml, p=0.003), which were negatively correlated with the serum erythrocyte sedimentation rate and Disease Activity Score using 28 joint counts (DAS28) scores (r=-0.560, p=0.002; r=-0.579, p<0.001, respectively). Although the RA B cells have more active characteristics, B cell proliferation induced by SAC was successfully suppressed by recombinant DcR3.Fc fusion protein with an average inhibition of 44.8%. Moreover, DcR3.Fc fusion protein was found to suppress SAC-induced TNF-α production by B cells in 8 RA patients (average inhibition 47.0%). CONCLUSIONS: The results of our study indicated that the inhibition of B cell functions by DcR3 may partially explain the negative correlation between DcR3 level and disease activity in RA patients. Our findings imply that DcR3 may be used as a biomarker for disease activity and a potential therapeutic agent in the treatment of RA.
24414744 Serious infections in patients with rheumatoid arthritis and other immune-mediated connect 2014 Jul Data on infections in patients exposed to biologic therapies are mainly focused on rheumatoid arthritis (RA). Little is known about the safety profile in other immune-mediated connective tissue diseases (ICTD). The purpose of this study was to describe and to compare the risk of serious infections (SI) in patients with RA and other ICTD on anti-TNF or rituximab and to identify predictors of SI. We analyzed RA or other ICTD patients on anti-TNF or rituximab included in the Spanish registry BIOBADASER 2.0 (2000-2011). For each disease group, incidence rate (IR), mortality rate (MR) and IR ratio (IRR) of SI with 95% CI were estimated. Risks were then standardized by age and sex to the general population. Risk factors for SI were assessed by Poisson regression models. A total of 3,301 patients on anti-TNF (n = 3,166) or rituximab (n = 135), of which 176 (5%) had ICTD other than RA, were analyzed. IR of SI was higher in non-RA ICTD than in RA, with an IRR of 3.15 (95% CI 1.86, 5.31) before adjustment and 1.96 (95% CI 1.06, 3.65) after adjustment for age, comorbidity and corticoid use. Mortality due to infections was higher in ICTD although it did not reach statistical significance. Age, disease duration, comorbidities, corticosteroids and ICTD different to RA were all independently associated with SI. Patients with ICTD other than RA are at a high risk of SI when prescribed anti-TNF or rituximab, partly due to the excess comorbidity and immunosuppressive co-treatment, but also to the inflammatory disease. When evaluating the risk/benefit ratio of off-label medications in ICTD patients, age, comorbidities and corticoid use should carefully be taken into account, applying adequate preventive measures.
24562719 Interchangeability of 28-joint disease activity scores using the erythrocyte sedimentation 2014 Jun This paper aims to examine the interchangeability of the disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) and DAS28-CRP scores in a diverse sample of rheumatoid arthritis (RA) patients and to evaluate generalizability over gender, age, and disease duration. A sample of 682 patients was drawn from the DREAM registry. Agreement between the two DAS28 scores was analyzed using the intraclass correlation coefficient (ICC), Bland Altman plots, and a matrix of classification agreement over DAS28 disease activity categories. Despite a strong linear correlation between the DAS28 scores and a high ICC value of 0.931, a considerable lack of individual agreement could be observed, with Bland-Altman 95% limits of agreement ranging between -0.85 and +1.25 points. On average, DAS28-CRP scores were 0.20 points lower than DAS28-ESR scores, and data stratification on age and gender showed that this systematic bias was most severe in older women (0.39 points). The overall classification agreement across DAS28 categories was 76.69%, with the agreement being lowest (35.37%) in the low disease activity group. Patients were more easily classified as being in remission when using the DAS28-CRP measure. DAS28-ESR and DAS28-CRP scores are not interchangeable within individuals. The DAS28-CRP tends to yield lower values of disease activity than the DAS28-ESR, resulting in substantial classification differences.
23870279 Total glucosides of paeony prevents juxta-articular bone loss in experimental arthritis. 2013 Jul 21 BACKGROUND: Total glucosides of paeony (TGP) is a biologically active compound extracted from Paeony root. TGP has been used in rheumatoid arthritis therapy for many years. However, the mechanism by which TGP prevents bone loss has been less explored. METHODS: TGP was orally administered for 3 months to New Zealand rabbits with antigen-induced arthritis (AIA). Digital x-ray knee images and bone mineral density (BMD) measurements of the subchondral knee bone were performed before sacrifice. Chondrocytes were observed using transmission electron microscopy (TEM). Histological analysis and mRNA expression of receptor activator of nuclear factor-B ligand (RANKL) and osteoprotegerin (OPG) were evaluated in joint tissues. RESULTS: The BMD value in TGP rabbits was significantly higher compared with that seen in the AIA model rabbits. In addition, the subchondral bone plate was almost completely preserved by TGP treatment, while there was a decrease in bone plate integrity in AIA rabbits. There was less damage to the chondrocytes of the TGP treated group. Immunohistochemical examination of the TGP group showed that a higher percentage of TGP treated chondrocytes expressed OPG as compared to the chondrocytes isolated from AIA treated animals. In contrast, RANKL expression was significantly decreased in the TGP treated group compared to the AIA group. In support of the immunohistochemistry data, the expression of RANKL mRNA was decreased and OPG mRNA expression was enhanced in the TGP group when compared to that of the AIA model group. CONCLUSION: These results reveal that TGP suppresses juxta-articular osteoporosis and prevents subchondral bone loss. The decreased RANKL and increased OPG expression seen in TGP treated animals could explain how administration of TGP maintains higher BMD.
24231065 Interstitial lung diseases induced or exacerbated by DMARDS and biologic agents in rheumat 2014 Apr OBJECTIVE: To review published cases of induced or exacerbated interstitial lung disease (ILD) in rheumatoid arthritis (RA) associated with non-biologic disease-modifying antirheumatic drugs (nbDMARDs) and biologics and to discuss clinical implications in daily practice. METHODS: We performed a systematic literature review from 1975 to July 2013 using Medline, Embase, Cochrane, and abstracts from the ACR 2010-2012 and EULAR 2010-2013 annual meetings. Case reports and series that suggest a causative role of nbDMARDs (methotrexate [MTX], leflunomide [LEF], gold, azathioprine [AZA], sulfasalazine [SSZ], and hydroxychloroquine [HCQ]) and biologic agents (TNF inhibitors [TNFi], rituximab [RTX], tocilizumab [TCZ], abatacept [ABA], and anakinra) in causing ILD or worsening a pre-existing ILD in RA patients were included. Results from observational and postmarketing studies as well as reviews on this topic were excluded from the qualitative analysis but still considered to discuss the implication of such drugs in generating or worsening ILD in RA patients. Comparisons were made between MTX-induced ILD in RA and the cases reported with other agents, in terms of clinical presentation, radiological features, and therapeutic management and outcomes. RESULTS: The literature search identified 32 articles for MTX, 12 for LEF (resulting in 34 case reports), 3 for gold, 1 for AZA, 4 for SSZ, 27 for TNFi (resulting in 31 case reports), 3 for RTX, 5 for TCZ (resulting in 8 case reports), and 1 for ABA. No case was found for HCQ or anakinra. Common points are noted between LEF- and TNFi-related ILD in RA: ILD is a rare severe adverse event, mostly occurs within the first 20 weeks after initiation of therapy, causes dyspnea mostly in older patients, and can be fatal. Although no definitive causative relationship can be drawn from case reports and observational studies, these data argue for a pulmonary follow-up in RA patients with pre-existing ILD, while receiving biologic therapy or nbDMARDs. CONCLUSION: As previously described for MTX, growing evidence highlights that LEF, TNFi, RTX, and TCZ may induce pneumonitis or worsen RA-related pre-existing ILD. Nonetheless, identifying a causal relationship between RA therapy and ILD-induced toxicity clearly appears difficult, partly because it is a rare condition.
25045299 Are glucocorticoid-induced osteoporosis recommendations sufficient to determine antiosteop 2014 Jul BACKGROUND/AIMS: We investigated differences in identifying candidates for antiosteoporotic treatment in rheumatoid arthritis (RA) patients according to two available clinical guidelines. METHODS: We prospectively enrolled 100 female patients aged 50 years or older with RA who visited Hanyang University Hospital for periodic examinations between April 2011 and August 2011. We applied the glucocorticoid-induced osteoporosis (GIOP) recommendations and the National Osteoporosis Foundation (NOF) guidelines to RA patients and examined agreement between the guidelines for identifying candidates for antiosteoporotic treatment. We also analyzed the impact of screening vertebral fractures (VFs) in determining the treatment of osteoporosis in RA patients. RESULTS: The 57 patients taking glucocorticoids were classified into high-risk (n = 23), medium-risk (n = 16), and low-risk (n = 18) groups according to the GIOP recommendations. Based on the NOF guidelines, 36 of 57 patients were candidates for antiosteoporotic treatment and the agreement between two guidelines was high (κ = 0.76). Two of the 18 patients in the low-risk group and 19 of 43 patients not eligible per the GIOP recommendations were classified as candidates for antiosteoporotic treatment by the NOF guidelines. CONCLUSIONS: In determining antiosteoporotic treatment for RA patients, using only the GIOP recommendations is insufficient. Application of the NOF guidelines in patients not eligible for or classified into the low-risk group per the GIOP recommendations and screening for VFs may be helpful in deciding on antiosteoporotic treatment in RA patients.
24979595 Association between periodontal disease and inflammatory arthritis reveals modulatory func 2014 Aug Because there is clinical evidence for an association between periodontal disease and rheumatoid arthritis, it is important to develop suitable experimental models to explore pathogenic mechanisms and therapeutic opportunities. The K/BxN serum model of inflammatory arthritis was applied using distinct protocols, and modulation of joint disruption afforded by dexamethasone and calcitonin was established in comparison to the melanocortin (MC) receptor agonist DTrp(8)-γ-melanocyte stimulating hormone (MSH; DTrp). Wild-type and MC receptor type 3 (MC3)-null mice of different ages were also used. There was significant association between severity of joint disease, induced with distinct protocols and volumes of the arthritogenic K/BxN serum, and periodontal bone damage. Therapeutic treatment with 10 μg dexamethasone, 30 ng elcatonin, and 20 μg DTrp per mouse revealed unique and distinctive pharmacological properties, with only DTrp protecting both joint and periodontal tissue. Further analyses in nonarthritic animals revealed higher susceptibility to periodontal bone loss in Mc3r(-/-) compared with wild-type mice, with significant exacerbation at 14 weeks of age. These data reveal novel protective properties of endogenous MC3 on periodontal status in health and disease and indicate that MC3 activation could lead to the development of a new genus of anti-arthritic bone-sparing therapeutics.
25481549 How undifferentiated arthritis evolves into chronic arthritis. 2014 Aug Undifferentiated arthritis (UA) is a frequently occurring clinical presentation with a variable outcome. While some forms of UA will spontaneously remit, other forms will progress to chronic arthritis; an outcome that would preferably be prevented. Which immunological factors are normally at the basis of resolution of inflammation, and what, on the other hand, causes inflammation to persist? This review provides an overview of the immunological mechanisms involved in these two scenarios, including specific examples of how these mechanisms apply, or can be influenced in rheumatic diseases. Furthermore, what do we know about risk factors for chronic arthritis, such as the development of autoantibodies? The recent years have provided many insights concerning risk factors for autoantibody-positive versus autoantibody-negative rheumatoid arthritis, which are discussed along with a possible pathophysiological model incorporating autoantibodies into the larger process of disease development. Finally, the evolution of the autoantibody response over time is described.
24812286 Anti-CarP antibodies in two large cohorts of patients with rheumatoid arthritis and their 2014 Oct INTRODUCTION: In rheumatoid arthritis (RA), several genetic risk factors and smoking are strongly associated with the presence of anticitrullinated protein antibodies (ACPA), while much less is known about risk factors for ACPA-negative RA. Antibodies against carbamylated proteins (anti-CarP) have been described in both ACPA-positive and ACPA-negative RA patients. In this study, we have analysed the relationships among anti-CarP antibodies, ACPA, genetic risk factors (HLA-DRB1 alleles and PTPN22) and smoking in RA. METHODS: Presence of antibodies to carbamylated fetal calf serum (CarP-FCS) and fibrinogen (CarP-Fib) was determined by inhouse ELISAs among RA cases in the Leiden Early Arthritis Clinic (n=846) and in the Swedish Epidemiological Investigation of Rheumatoid Arthritis (n=1985) cohorts. ORs for associations with different HLA-DRB1 alleles, PTPN22 genotypes and smoking were calculated separately for each cohort as well as in meta-analysis in RA subsets defined by the presence/absence of anti-CarP and anticyclic citrullinated peptide (anti-CCP) antibodies. RESULTS: In both cohorts, anti-CarP antibody positivity was mainly detected in the anti-CCP-positive population (49%-73%), but also in the anti-CCP-negative population (8%-14%). No associations between anti-CarP antibodies and HLA-DRB1 shared epitope alleles could be identified, while there were data to support an association between anti-CarP-FCS and HLA-DRB1*03. Further analyses did not reveal any specific associations of anti-CarP antibodies with other HLA-DRB1 alleles, PTPN22 genotypes or smoking. CONCLUSIONS: Anti-CarP antibodies were present in both ACPA-positive and ACPA-negative RA. There were no significant associations among anti-CarP antibodies and HLA-DRB1 alleles, PTPN22 or smoking. These data suggest that different biological mechanisms may underlie anti-CarP versus anti-CCP antibody formation.
24735586 High levels of memory B cells are associated with response to a first tumor necrosis facto 2014 Apr 15 INTRODUCTION: Tumor necrosis factor inhibitor (TNFi) therapy is effective for rheumatoid arthritis (RA). Some researchers have suggested that TNFi therapy affects B-cell homeostasis. We studied the effect of TNFi therapy on the distribution of peripheral B-cell subsets to elucidate B-cell-related biomarkers to predict the TNFi response. METHODS: Peripheral B cells were analyzed for expression of CD19, CD27, CD38 and immunoglobulin D in 31 healthy donors and 96 RA patients, including 21 patients who were followed 3 months after TNFi initiation. RESULTS: Treatment with steroids significantly altered the distribution of B-cell subsets. After we adjusted for age, sex and steroid dose, we found that patients with RA had B-cell subset proportions similar to controls. B-cell subset distributions did not differ upon use of TNFi at baseline or before or after TNFi introduction. TNFi responders (according to European League Against Rheumatism criteria) at 3 months had significantly higher proportions of CD27⁺ memory B cells at baseline, and ≥26% CD27⁺ cells at inclusion was associated with a relative risk of 4.9 (1.3 to 18.6) for response to TNFi treatment. CD27⁺ cells produced three times more TNFα than did TNFi-naïve B cells and were correlated with interferon γ produced from CD4⁺ cells in patients without TNFi treatment. CONCLUSIONS: In patients with RA, high levels of baseline memory B cells were associated with response to TNFi, which may be related to TNFα-dependent activation of the T helper type 1 cell pathway.
24671921 Linguistic validation into 20 languages and content validity of the rheumatoid arthritis-s 2014 BACKGROUND: Impairments in work productivity and daily activities contribute to the burden of rheumatoid arthritis (RA). It is thus essential to use an instrument assessing both work and daily activity impairments when studying the full impact of RA on individuals. The Work Productivity and Activity Impairment (WPAI) questionnaire is such an instrument. OBJECTIVE: This study aims to linguistically validate the RA-specific WPAI (WPAI:RA) instrument in 20 new languages and to assess its content validity for individuals with RA. METHODS: The linguistic validation of the questionnaire followed a standard methodology that included comprehension test interviews (n = 5 individuals with RA per language) to assess the relevance, understanding and acceptability of the WPAI:RA. Content validity of the instrument was simultaneously investigated. RESULTS: Comprehension testing showed that the WPAI:RA questionnaire was well understood similarly across countries; minor changes were made to ensure fidelity to the original concepts and for ease of comprehension. The majority of interviewees (66/93) considered its content comprehensive and appropriate to measure their ability to work and perform daily activities. CONCLUSION: The WPAI:RA questionnaire is now linguistically validated in 20 new languages [Czech (Czech Republic), Dutch (Belgium), English (Canada and UK), French (Belgium, Canada and France), German (Germany), Hungarian (Hungary), Italian (Italy), Polish (Poland), Portuguese (Brazil), Romanian (Romania), Russian (Russia and Ukraine), Spanish (Argentina, Mexico, Spain and US) and Ukrainian (Ukraine)]. The WPAI:RA questionnaire shows good content validity. It can thus be used in multi-country clinical trials to assess RA-related impact on the patients' ability to work and perform daily activities.
25227117 Oral low-dose glucocorticoids should be included in any recommendation for the use of non- 2015 At present, growing scientific evidence from the medical literature and expert opinion provides strong consideration for a mandatory role of glucocorticoids (GCs) in the management of rheumatoid arthritis (RA). Earlier application strategies were based on initial high doses, with subsequent tapering schedules, resulting in dose-related side effects. Recent low-dose GC schemes are more feasible in routine care, while providing evidence of clinical, functional and structural efficacy. Thus, initial low-dose GC 'bridging' treatment on a disease-modifying antirheumatic drug background should be included in any existing recommendations for RA management, as very recently advocated by the EULAR Task Force 2013 updated guidelines. Long-term low-dose therapy appears to provide acceptable safety, leading to long-standing slowing of structural damage, seen even after GC therapy withdrawal. Gaps in knowledge about the optimal method to taper and possibly discontinue GC treatment remain, and this topic should be addressed in clinical trials and observational studies. Recent efforts in GC medication have also included the introduction of a modified-release drug formulation capable of drug delivery consistent with chronobiological pathogenetic rhythms of disease, which has been quite efficacious in controlling the signs and symptoms related to pathways of circadian cytokines. Long-term data will further clarify the add-on benefits of such modified-release formulations.
23705580 Primary central nervous system malignant lymphoma in a patient with rheumatoid arthritis r 2013 Dec We report the first case of primary central nervous system lymphoma (PCNSL) developing in a patient with rheumatoid arthritis (RA) undergoing low-dose methotrexate therapy (LD-MTX). The characteristic clinical management and course in our experience of the present case illustrate the important points about PCNSL in methotrexate-associated lymphoproliferative disorders (MTX-LPD). The number of cases of MTX-LPD in RA patients may increase in the future, since current treatment strategies for RA recommend starting MTX use in early stage RA, and recent insights have tended to show an increase with higher doses.
24782178 Antibodies to IgG4 hinge can be found in rheumatoid arthritis patients during all stages o 2014 May OBJECTIVE: In rheumatoid arthritis (RA), autoantibodies such as anti-citrullinated protein antibodies (ACPAs) develop in response to neoepitopes that are formed under conditions of chronic inflammation. These autoantibodies may subsequently be fragmented by inflammation-associated proteases, leading to the formation of F(ab')2 fragments. The hinge of F(ab')2 fragments can serve as a neoepitope, and so-called antihinge antibodies (AHAs) can be found in RA patients, which might modulate the function of (fragmented) autoantibodies. We undertook this study to investigate the presence and specificities of AHAs in different stages of RA and to study their function. METHODS: The presence of AHAs was assessed by radioimmunoassay in healthy controls, blood donors who later developed RA, patients with arthralgia, patients with early RA, and patients with established RA. Specificity of the AHAs was analyzed with inhibition assays, and complement-activating ability was studied with a C4b deposition assay. RESULTS: Antibodies to IgG1 hinge, IgG2 hinge, and IgG4 hinge were detected in patients with established RA, with anti-IgG4 hinge antibodies being most specific (appearing in 1% of healthy controls, 3.8% of blood donors who later developed RA, 13% of arthralgia patients, 19% of early RA patients, and 16% of established RA patients). Anti-IgG4 hinge antibodies were subclass specific and were able to restore C4b deposition by IgG4 F(ab')2 fragments. In patients with arthralgia and patients with early RA, anti-IgG4 hinge antibodies were associated with rheumatoid factors and ACPAs. CONCLUSION: Anti-IgG4 hinge antibodies are present in RA patients and have low sensitivity but high specificity for RA. Since a significant proportion of ACPAs can be of the IgG4 subclass, the formation of anti-IgG4 hinge antibodies may represent one mechanism of ACPA-mediated inflammation.
24025293 Indications and early to mid-term results of ulnar head replacement. 2013 Sep INTRODUCTION: The aim of this study was to explore the indications and show the early to mid-term results of ulnar head replacement for the treatment of pathological conditions of the distal radioulnar joint. METHODS: Our study group comprised 52 patients with a mean age of 64 years who had 56 ulnar head replacements. Seven were implanted to salvage an unstable deletive procedure; the rest were for primary treatment of osteoarthritis, rheumatoid arthritis and trauma. Concomitant procedures along with the ulnar head replacement included wrist arthrodesis, joint replacement and tendon transfers. RESULTS: The follow-up duration ranged from 1 year to 11 years (mean: 60 months, median: 60 months). In almost all of the patients, pain improved with a median visual analogue scale score of 2 (mean: 2.2, range: 0-8) and a median DASH (Disabilities of the Arm, Shoulder and Hand) score of 12.5 (mean: 17.9, range: 0-56). Of the 52 patients, 47 reported they would have the same procedure again. CONCLUSIONS: Ulnar head replacement appears to be a reliable and effective procedure solving several pathological problems of the distal radioulnar joint. We present a large patient group with a short to medium-term follow-up duration.