Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
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27869626 | Primary Linked Semiconstrained Total Elbow Arthroplasty for Rheumatoid Arthritis: A Single | 2016 Oct 19 | BACKGROUND: Elbow arthroplasty is the treatment of choice for end-stage rheumatoid arthritis (RA). The purpose of this study was to determine the long-term outcome of a linked semiconstrained elbow arthroplasty implant design in patients with RA. METHODS: Between 1982 and 2006, 461 primary total elbow arthroplasties using the Coonrad-Morrey prosthesis were performed in 387 patients with RA. Fifty-five of the arthroplasties were performed to treat concurrent traumatic or posttraumatic conditions. There were 305 women (365 elbows, 79%) and 82 men (96 elbows, 21%). Ten patients (10 elbows) were lost to follow-up, 9 patients (10 elbows) died, and 6 patients (6 elbows) underwent revision surgery within the first 2 years. For the 435 elbows (362 patients, 94%) with a minimum of 2 years of follow-up, the median follow-up was 10 years (range, 2 to 30 years). RESULTS: At the most recent follow-up, 49 (11%) of the elbows had undergone component revision or removal (deep infection, 10 elbows; and mechanical failure, 39 elbows). Eight additional elbows were considered to have radiographic evidence of loosening. For surviving implants followed for a minimum of 2 years, the median Mayo Elbow Performance Score (MEPS) was 90 points. Bushing wear was identified in 71 (23%) of the surviving elbows with a minimum of 2 years of radiographic follow-up; however, only 2% of the elbows had been revised for isolated bushing wear. The rate of survivorship free of implant revision or removal for any reason was 92% (95% confidence interval [CI] = 88% to 94%) at 10 years, 83% (95% CI = 77% to 88%) at 15 years, and 68% (95% CI = 56% to 78%) at 20 years. The survivorship at 20 years was 88% (95% CI = 83% to 92%) with revision due to aseptic loosening as the end point and 89% (95% CI = 77% to 95%) with isolated bushing exchange as the end point. Risk factors for implant revision for any cause included male sex, a history of concomitant traumatic pathology, and implantation of an ulnar component with a polymethylmethacrylate surface finish. CONCLUSIONS: Elbow arthroplasty using a cemented linked semiconstrained elbow arthroplasty provides satisfactory clinical results in the treatment of RA with a reasonable rate of survivorship free of mechanical failure at 20 years. Although bushing wear was identified on radiographs in approximately one-fourth of the patients, revision for isolated bushing wear was uncommon. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. | |
26546613 | Functional implications of disease-specific variants in loci jointly associated with coeli | 2016 Jan 1 | Hundreds of genomic loci have been associated with a significant number of immune-mediated diseases, and a large proportion of these associated loci are shared among traits. Both the molecular mechanisms by which these loci confer disease susceptibility and the extent to which shared loci are implicated in a common pathogenesis are unknown. We therefore sought to dissect the functional components at loci shared between two autoimmune diseases: coeliac disease (CeD) and rheumatoid arthritis (RA). We used a cohort of 12 381 CeD cases and 7827 controls, and another cohort of 13 819 RA cases and 12 897 controls, all genotyped with the Immunochip platform. In the joint analysis, we replicated 19 previously identified loci shared by CeD and RA and discovered five new non-HLA loci shared by CeD and RA. Our fine-mapping results indicate that in nine of 24 shared loci the associated variants are distinct in the two diseases. Using cell-type-specific histone markers, we observed that loci which pointed to the same variants in both diseases were enriched for marks of promoters active in CD14+ and CD34+ immune cells (P < 0.001), while loci pointing to distinct variants in one of the two diseases showed enrichment for marks of more specialized cell types, like CD4+ regulatory T cells in CeD (P < 0.0001) compared with Th17 and CD15+ in RA (P = 0.0029). | |
25399388 | Does socioeconomic status affect outcomes in early inflammatory arthritis? Data from a can | 2015 Jan | OBJECTIVE: To assess the effect of socioeconomic status (SES) on outcomes in patients with early inflammatory arthritis, using data from the Canadian Early Arthritis Cohort (CATCH) study. METHODS: In an incident cohort, 2023 patients were recruited, and allocated to low SES or high SES groups based on education and income. Outcomes at baseline and 12 months were analyzed in relation to SES including the 28-joint Disease Activity Score (DAS28), Simplified Disease Activity Index (SDAI), pain, patient's global assessment scale (PtGA), the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the SF12-v2 Health Survey, using the ANOVA, chi-squared test, and regression analyses. RESULTS: The CATCH population had 43% with high school education or less and 37% in the low-income group (< 50,000 Can$ per annum household income). The low-education group had higher DAS28 at baseline (p = 0.045), becoming nonsignificant at 12 months and lower physical component score on SF12-v2 at baseline (p = 0.022). Patients in the low-income group presented with higher HAQ-DI (p = 0.017), pain (p = 0.035), PtGA (p = 0.004), and SDAI (p = 0.022). Low-income versus high-income groups were associated with an OR above the median for HAQ-DI (1.20; 95% CI 1.00-1.45), PtGA (1.27; 95% CI 1.06-1.53), and SDAI (1.25; 95% CI 1.02-1.52) at baseline. The association with low income persisted at 12 months for HAQ-DI (OR 1.30; 95% CI 1.02-1.67), but not for other variables. CONCLUSION: Low SES was initially associated with higher disease activity, pain, and PtGA, and poorer function. At 1 year, outcomes were similar to those with high SES, with the exception of HAQ-DI. | |
26767827 | Calprotectin (S100A8/A9) and S100A12 are associated with measures of disease activity in a | 2016 Jul | OBJECTIVES: The pro-inflammatory proteins calprotectin (a heterocomplex of S100A8/A9) and S100A12 have been associated with disease activity in rheumatoid arthritis (RA). The aim of this study was to compare their potential as biomarkers in a prospective study of RA patients starting with infliximab as their first biological disease-modifying anti-rheumatic drug (DMARD). METHOD: Thirty-nine RA patients were examined and serum samples collected when starting with infliximab and after 3, 6, and 12 months. Calprotectin and S100A12 were analysed by enzyme-linked immunosorbent assays (ELISAs) and, together with C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), measured at all time points. A disease activity score of 28 joints (DAS28) was calculated. Radiographs of the hands, wrists, and feet were taken at baseline and after 3 years, and assessed according to the modified Sharp/van der Heijde (SvH) score. Responsiveness was evaluated according to the European League of Associations for Rheumatology (EULAR) response criteria based on 28 joints. RESULTS: Both S100 proteins were significantly higher in seropositive than in seronegative patients (p = 0.01). Calprotectin correlated significantly with CRP (Ï = 0.51-0.75), ESR (Ï = 0.32-0.52), and DAS28 (Ï = 0.32-0.62). S100A12 correlated with calprotectin (Ï = 0.62-0.77) and CRP (Ï = 0.32-0.63). The S100 proteins, and especially calprotectin (Ï = 0.23-0.39), showed weak associations with radiographic progression, unlike CRP/ESR. None of the S100 proteins could predict responsiveness. CONCLUSIONS: Calprotectin showed the strongest correlation with measures of disease activity and may be better than S100A12 when evaluating disease activity in RA patients. More extensive studies are needed to further compare the predictive value of the S100 proteins relative to radiographic progression. | |
26063454 | Attainment and characteristics of clinical remission according to the new ACR-EULAR criter | 2015 Jun 11 | INTRODUCTION: This study evaluated various remission criteria in abatacept plus methotrexate (MTX)-treated patients with early rheumatoid arthritis (RA). We aimed to investigate the time to, and sustainability of, remission, and to evaluate the relationship between remission, function and structure. METHODS: Post hoc analyses were performed from the 12-month, double-blind period of the Abatacept study to Gauge Remission and joint damage progression in methotrexate (MTX)-naive patients with Early Erosive rheumatoid arthritis (AGREE) in patients with early RA (≤2 years) and poor prognostic factors, comparing abatacept plus MTX (n = 210) versus MTX alone (n = 209). RESULTS: At month 12, Disease Activity Score 28, Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index and Boolean remission rates were, for abatacept plus MTX versus MTX alone: 47.6 % versus 27.3 %, 33.3 % versus 12.4 %, 34.3 % versus 16.3 %, and 23.8 % versus 5.7 %, respectively. Cumulative probability demonstrated higher proportions achieving first remission and first sustained remission for abatacept plus MTX versus MTX alone (e.g., 23.3 % [95 % confidence interval (CI): 17.6, 29.1] vs 12.9 % [8.4, 17.5] for first SDAI remission over 0-6 months). For patients in SDAI remission at month 3, mean Health Assessment Questionnaire-Disability Index at month 12 was 0.20 versus 0.50 for abatacept plus MTX versus MTX alone. Mean changes in radiographic score from baseline to month 12 were minimal for patients in SDAI remission at month 3 in both groups, while less structural damage progression was seen, 0.75 versus 1.35, respectively, for abatacept plus MTX versus MTX alone for patients with moderate/high disease activity at month 3 (adjusted mean treatment difference: -0.60 [95 % CI: -1.11, -0.09; P < 0.05]). CONCLUSIONS: High proportions of abatacept plus MTX-treated patients achieved stringent remission criteria. Remission was associated with long-term functional benefit; dissociation was seen between clinical and structural outcomes for abatacept. These findings highlight the impact of reaching stringent remission targets early, on physical function and structural damage, in MTX-naïve biologic-treated patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00122382. Registered 19 July 2005. | |
27906042 | What is the impact of biologic therapies on common co-morbidities in patients with rheumat | 2016 Dec 1 | Biologic therapies have revolutionised disease control in patients with rheumatoid arthritis (RA). Theoretically, they have the potential to influence co-morbid disease associated with RA through better control of systemic inflammation. Conversely, co-morbidity may occur as an adverse effect of the drugs. The latest evidence from observational data shows an increased risk of infection in the first 6Â months of treatment with tumour necrosis factor inhibitor (TNFi) therapies and potentially other biologic therapies. Rates of infection after the first 6Â months decrease and become comparable to patients with RA treated with conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs). TNFi also appear to reduce the risk of cardiovascular disease in these patients, in particular ischaemic heart disease. TNFi treatment may be associated with a small increase in the risk of developing squamous cell carcinoma of the skin; in terms of other cancers, rates appears to be no different to those seen in patients treated with csDMARDs. There is a paucity of data on the impact of other biologic therapies and the effect of all biologic therapies on other common co-morbidities. | |
26934116 | Clinical and structural remission rates increased annually and radiographic progression wa | 2016 Nov | OBJECTIVE: To evaluate the clinical and structural efficacy of tocilizumab (TCZ) during its long-term administration in patients with rheumatoid arthritis (RA). METHODS: In total, 693 patients with RA who started TCZ therapy were followed for 3 years. Clinical efficacy was evaluated by DAS28-ESR and Boolean remission rates in 544 patients. Joint damage was assessed by calculating the modified total Sharp score (mTSS) in 50 patients. RESULTS: When the reason for discontinuation was limited to inadequate response or adverse events, the 1-, 2-, and 3-year continuation rates were 84.0%, 76.8%, and 72.2%, respectively. The mean DAS28-ESR was initially 5.1 and decreased to 2.5 at 6 months and to 2.2 at 36 months. The Boolean remission rate was initially 0.9% and increased to 21.7% at 6 months and to 32.2% at 36 months. The structural remission rates (ΔmTSS/year ≤ 0.5) were 68.8%, 78.6%, and 88.9% within the first, second, and third years, respectively. The structural remission rate at 3 years (ΔmTSS ≤ 1.5) was 66.0%, and earlier achievement of swollen joint count (SJC) of 1 or less resulted in better outcomes. CONCLUSIONS: TCZ was highly efficacious, and bone destruction was strongly prevented. SJC was an easy-to-use indicator of joint destruction. | |
27758986 | The Value of Biomarkers as Predictors of Outcome in Patients with Rheumatoid Arthritis-Ass | 2016 Oct 7 | BACKGROUND: Because of the highly variable clinical course of rheumatoid arthritis-associated usual interstitial pneumonia (RA-UIP), the prediction of patient prognosis is important. OBJECTIVE: The aim of this study was to investigate the role of blood biomarkers as prognostic predictors in the patients with RA-UIP. METHODS: The blood levels of biomarkers (Krebs von den Lungen-6 [KL-6], surfactant protein-A [SP-A], matrix metalloproteinase-7 [MMP-7], interleukin-6 [IL-6], and interleukin-32 [IL-32]) were retrospectively compared with the clinical courses of 62 patients with RA-UIP. RESULTS: The median follow-up period was 33.4 months. RA-UIP progressed in 15 patients (45.2%) during one year of follow-up. We found that KL-6 and IL-6 were significant predictors of short-term (1 year) prognosis. Multivariate logistic regression analysis showed that the odds ratio (OR) for KL-6 was 1.001 (95% confidence interval [CI]: 1.000-1.003, p = 0.077) and that the OR for IL-6 was 1.040 (95% CI: 1.002-1.080, p = 0.039) for short-term disease progression. The addition of KL-6 and IL-6 to the clinical parameters (concordance index [C-index]: 0.958, p = 0.053) predicted short-term disease progression better than the clinical parameter alone (C-index: 0.853). In addition, patients with high levels of KL-6 (≥933 U/mL) had shorter survival than those with low levels of KL-6 (<933 U/mL) (median survival: 51 vs. 96 months, p = 0.019). CONCLUSIONS: The results of this retrospective study suggested that KL-6 and IL-6 could be used as predictors of short-term disease progression. In addition, high levels of KL-6 could be used as a predictor of mortality. Additional studies involving a larger patient cohort are warranted. | |
26743639 | Tocilizumab and multiple sclerosis: a causal relationship? Clinical Commentary on the case | 2016 Feb | This clinical commentary discusses on the potential relationship between multiple sclerosis (MS) and tocilizumab in a patient with rheumatoid arthritis who developed MS while on treatment with this anti-interleukin-6 agent. | |
26329343 | Factors Associated with the Use of Complementary and Alternative Medicine for Korean Patie | 2015 Nov | OBJECTIVE: Rheumatoid arthritis (RA) is a chronic autoimmune disease that is often painful and debilitating. Patients with RA are increasingly receiving complementary and alternative medicine (CAM). We aimed to identify the patient characteristics and disease-specific factors associated with Korean patients with RA who decide to start treatment with CAM. METHODS: Among the total 5371 patients with RA in the KORean Observational study Network for Arthritis (KORONA), 2175 patients who had no experience with CAM were included in our study. In our study, we assessed the frequency of new incident CAM use, its patterns, and the predictive factors of new CAM use. RESULTS: Of the 2175 patients, 229 patients (10.5%) newly started receiving CAM within a year of enrolling in the cohort. Of those who started treatment with CAM, 17.0% received only herbal medicine, 54.6% only acupuncture treatments (7.0% used a combination of both), and 21.4% "Other" (e.g., physical therapy and placental extract injections). Women (OR 1.89, 95% CI 1.13-3.14) and patients with depression (OR 3.52, 95% CI 1.65-7.50) were significantly more likely to be treated with CAM. Regarding household types, patients who lived in an extended family (OR 1.78, 95% CI 1.08-2.95) or as part of a couple (OR 1.55, 95% CI 1.07-2.24) were more likely to be treated with CAM than patients living in a nuclear family. CONCLUSION: Our study found, within a year, an incidence rate of 10.5% for new CAM use among patients with no previous experience with CAM. Sex, depression, and household type were significantly associated with new CAM use. | |
27009825 | Marked underdiagnosis and undertreatment of hypertension and hypercholesterolaemia in rheu | 2016 Jul | OBJECTIVE: To investigate the prevalence of underdiagnosis and undertreatment of traditional cardiovascular risk factors in RA patients. METHODS: RA patients ⩽70 years of age without cardiovascular disease (CVD) or diabetes mellitus were included. Systolic blood pressure and a fasting lipid profile were measured. The 10-year CVD risk was estimated using the Dutch Cardiovascular Risk Management (CVRM) guideline and EULAR modifications of the Systemic Coronary Risk Evaluation tables. RESULTS: A total of 327 patients were included (female gender: 68%). The mean age was 53 (11) years [mean (s.d.)]. The median disease duration was 7 years (inter quartile range: 2-14 years). According to the CVRM guideline, 52% of the patients had a CVD risk ⩾20% and according to the EULAR guidelines, 18% of the patients had a CVD risk ≥ 20%. Low-density lipoprotein cholesterol (LDL-C) >2.5 mmol/l was found in >80% of the patients with a CVD risk ⩾10% as estimated by both the CVRM and EULAR guidelines, and 32-42% of the patients with a CVD risk ⩾10% had a systolic blood pressure >140 mmHg, depending on the risk model used. Statins were used in 6% and antihypertensives in 23-25%, and 50-86% of these patients did not reach the recommended treatment targets. CONCLUSION: Regardless of the adapted risk assessment model used, untreated hypertension and hypercholesterolaemia were frequently found in RA patients with increased CVD risk. Treatment of these cardiovascular risk factors deserves more attention in RA. TRIAL REGISTRATION: The Dutch Trial Register, www.trialregister.nl, NTR3873. | |
26159110 | Elevated serum and synovial fluid levels of interleukin-37 in patients with rheumatoid art | 2015 Dec | OBJECTIVES: To measure the serum and synovial fluid (SF) levels of interleukin (IL)-37 in patients with rheumatoid arthritis (RA) and to investigate the effect of recombinant human (rh)IL-37 on inflammatory cytokine production (tumor necrosis factor [TNF]-α, IL-6, IL-17 and IL-10) by peripheral blood mononuclear cells (PBMCs) in RA patients. METHODS: An enzyme-linked immunosorbent assay (ELISA) was used to analyse the serum and SF IL-37 levels. RhIL-37 was used to stimulate RA patient PBMCs. The supernatant TNF-α, IL-17, IL-6 and IL-10 levels were detected with ELISAs. RESULTS: The serum IL-37 levels in RA patients were significantly increased compared with those of osteoarthritis (OA) and healthy controls (HC), and they were especially elevated in RA patients with positive rheumatoid factor (RF) and anti-citrullinated peptide antibody (CCP) levels. Furthermore, the serum IL-37 levels were positively correlated with RF values. In 20 matched RA SF and serum samples, the SF IL-37 levels were much higher than those in the serum. After anti-TNF-α therapy, the serum IL-37 levels significantly decreased. Additionally, rhIL-37 significantly down-regulated TNF-α, IL-17 and IL-6 production by RA patient PBMCs. CONCLUSIONS: IL-37 is an important anti-inflammatory cytokine in the control of RA pathogenesis by suppressing inflammatory cytokine production. Thus, IL-37 administration may be a novel therapy for RA. | |
27796844 | The Complex Role of the Lung in the Pathogenesis and Clinical Outcomes of Rheumatoid Arthr | 2016 Nov | While the primary manifestation of rheumatoid arthritis (RA) is articular disease, extra-articular disease may also occur. In particular, pulmonary disease is a frequent extra-articular manifestation of seropositive RA and a leading cause of morbidity and mortality in this population. This review will highlight studies published in the last several years and will, in particular, discuss the relationship of antibodies to citrullinated protein/peptide antigens (ACPA) and lung disease in patients with RA. We will also review the data regarding the potential role of the lung and generation of RA-related autoantibodies in a period of disease development termed "preclinical RA." Finally, we will discuss the role of ACPA and other Abs in non-RA pulmonary diseases and discuss a research agenda for next steps in the understanding and management of the lung in RA. | |
27118209 | TCR-CD3ζ gene polymorphisms and expression profile in rheumatoid arthritis. | 2016 Nov | OBJECTIVES: Recent evidence has demonstrated that CD3ζ (also called CD247) play a vital role in multiple autoimmune diseases. In this study, we explored the association between CD247 gene single-nucleotide polymorphisms (SNPs) and rheumatoid arthritis (RA) in a Chinese Han population. We also evaluated the CD3ζ expression profile in peripheral blood mononuclear cells (PBMCs) from patients with RA and health controls. METHODS: Three CD247 polymorphisms (rs704853, rs1214611 and rs858554) were studied in 612 patients with RA and 848 controls in a Chinese population. Genotyping was performed using the Fluidigm 192.24 Dynamic Array™ Integrated Fluidic Circuit (IFC). For gene expression study, CD3ζ mRNA levels of 36 patients with RA and 39 healthy individuals were assessed by real-time polymerase chain reaction (RT-PCR). Data were analyzed by SPSS 11.5 software. RESULTS: A significant association between rs858554 polymorphism and RA was found under all genetic models (all p < 0.05). Moreover, we found the genotype distribution and allele frequency of rs858554 were significant associated with ACCP(+) and RF(+) phenotype as compare to health controls (all p < 0.05). Unfortunately, we did not detect any significant associations between rs704853, rs1214611 and RA susceptibility and autoantibody profiles (all p > 0.05). The gene expression assays showed that CD3ζ mRNA levels were downregulated in PBMCs of patients with RA when compared to healthy controls. CONCLUSIONS: Our results, the first reported for distinct Chinese populations, support a role of the CD247 gene in the susceptibility to RA. Further studies with more sample size are necessary to clarify the exact role of CD247 gene in the pathogenesis of RA. | |
26083391 | Quality of life and drug compliance: their interrelationship in rheumatic patients. | 2015 Oct | RATIONALE, AIMS AND OBJECTIVES: In rheumatic disorders, one of the treatment objectives is to improve the patient's quality of life (QoL). Similar to other chronic conditions, drug compliance is poor, but necessary for successful treatment. The relationship between drug compliance and QoL has never been tested. The aim of this study was to elucidate the relationship between drug compliance and QoL in patients with different rheumatic disorders. METHOD: A cross-sectional study was conducted and patients ≥18 years of age with rheumatoid arthritis (RA), spondyloarthritis (SA), juvenile idiopathic arthritis (JIA) and systemic scleroderma (SSc) were recruited. Data were collected by questionnaires including the Short Form 36 version 2, Compliance Questionnaire Rheumatology (CQR), Health Assessment Questionnaire and by a general questionnaire that focused on demographic characteristics. RESULTS: The questionnaires were completed by 289 patients. Of the respondents, 61.6% (178) were treated for RA, 16.3% (47) for SA, 14.2% (41) for SSc and 8% (23) for JIA. The median of CQR score ranged from 66.7 (JIA) to 82.5 (RA), with 51.6% of patients reaching a score <80. QoL was decreased mainly in the physical component, with the lowest rate for patients with SSc. Higher compliance was observed in patients with decreased QoL (physical component), nevertheless, statistical significance of the relationship was reached only in JIA and SA patients. CONCLUSION: Doctors caring for rheumatic patients should focus their efforts on strengthening drug compliance in patients with higher QoL where it seems that lower compliance is more likely. | |
27643663 | Therapeutic potential of Oroxylin A in rheumatoid arthritis. | 2016 Nov | Excessive inflammation contributes greatly to the pathogenesis and development of rheumatoid arthritis (RA). Oroxylin A (OA) is a natural anti-inflammatory flavonoid compound. In this study, we investigated the effects of OA on collagen-induced arthritis (CIA) and human RA fibroblast-like synoviocytes (FLS). CIA was induced in DBA/1 mice and mice were intraperitoneally treated with OA (10mg/kg) for 10days. Arthritis severity was evaluated every day and the histopathologic examination of joints was done. Serum levels of anti-collagen II antibodies (anti-CII Abs) and cytokines were determined by ELISA. Frequency of regulatory T cells (Tregs) and Th17 cells in draining inguinal lymph nodes (ILN) was quantified by flow cytometry. FLS from patients with active RA were treated with varying doses of oroxylin A, followed by stimulation with tumor necrosis factor (TNF)-α (10ng/mL). The production of cytokines was measured by ELISA. Signal transduction proteins were examined by western blot. OA significantly diminished the arthritis and histological damage. Serum anti-CII Abs, IL-1β, IL-6, TNFα, and IL-17 were significantly diminished by OA treatment. Analysis of CD4+T cell populations in OA-treated mice showed an increase in Tregs and reduction in Th17 cells in the ILN. In vitro, OA decreased the secretion of IL-1β and IL-6 from TNFα-stimulated RA FLS in a dose-dependent manner. TNFα-induced p38 MAPK, ERK1/2 and NF-κB signaling pathways were suppressed by OA. Our results indicate that OA exerts an anti-inflammatory activity and may have therapeutic potential for human RA. | |
26123453 | Is this still just sarcoidosis, or should we a-DRESS a different diagnosis? | 2015 Jun 29 | An Afro-Caribbean woman presented with worsening breathlessness, weight loss, lethargy and fevers, developing a bilateral florid erythematous rash on her legs. She was recently diagnosed with rheumatoid arthritis and bilateral hilar lymphadenopathy was found on thoracic CT imaging. She was tachycardic and investigations revealed pancytopenia, eosinophilia, raised serum ACE, acute kidney injury and deranged liver function tests. Biopsy of the lymphadenopathy revealed mixed lymphoid cells and liver biopsy revealed extramedullary haematopoiesis, with hypercellular marrow found on bone marrow biopsy. Cardiac MRI was normal, excluding cardiac sarcoid. The patient developed status epilepticus and phenytoin was started. She subsequently developed skin desquamation, in keeping with toxic epidermal necrosis. Skin biopsies revealed atypical granulomas and multinucleated giant cells, which subsequently resolved on steroid treatment. This case highlights an overlap syndrome, with an unclear diagnosis between sarcoidosis, drug reaction or rash with eosinophilia and systemic symptoms and/or hypereosinophilic syndrome and Still's disease. Hence varied serological and clinical features can complicate the distinction between diagnoses. | |
26838521 | [Lung cancer and rheumatoid arthritis. An interdisciplinary challenge]. | 2016 Feb | Lung cancer is a frequently occurring disease, particularly in the elderly; however, within the last 10 years the pharmaceutical treatment of lung cancer has been significantly improved. Due to a better understanding of the pathophysiological events and the identification of molecular subgroups of lung tumors, new therapeutic drugs have been developed that significantly prolong survival of patients with the respective molecular pattern. In particular immunotherapeutic agents, such as programmed death-ligand 1 (PD-L1) and programmed death 1 (PD1) antibodies have shown promising clinical results in a subgroup of lung cancer patients. Due to the high incidence of both lung cancer and rheumatic diseases they often occur together, which necessitates an interdisciplinary management. The success of improved therapy of lung cancer has led to a greater focus on the treatment of comorbidities; however, interventions into the immune system by immune checkpoint inhibitors can lead to new challenges when an autoimmune disease is simultaneously present. The possibility of an effective screening for lung cancer in the future also presents the prospect of an improvement in mortality, which raises the question of the optimal monitoring of patients with rheumatoid arthritis (RA) under immunosuppressive therapy. The aim of this review is to discuss the interaction between lung cancer and RA with respect to the currently available data. | |
27125521 | How well do ACPA discriminate and predict RA in the general population: a study based on 1 | 2017 Jan | OBJECTIVE: Anti-citrullinated protein antibodies (ACPA) are highly specific for rheumatoid arthritis (RA), but the diagnostic accuracy of ACPA in the general population has not been thoroughly assessed. We aimed to assess the diagnostic accuracy of ACPA for RA in the general population and to further characterise the citrullinated peptide recognition pattern. METHODS: Serum samples from a large population-representative twin cohort consisting of 12 590 individuals were analysed for the presence of ACPA using anti-CCP2 ELISA. All ACPA-positive samples were further tested on ELISAs for four peptide-specific ACPA. RA cases were identified by linkage to the Swedish National Patient Register at inclusion and after a median follow-up of 37 months (IQR 31-49). RESULTS: 350 out of 12 590 individuals had a positive anti-CCP2 test, measuring ACPA. Of these, 103 had an RA diagnosis at the time of blood donation and inclusion. During a median follow-up of 3 years, an additional 21 of the remaining 247 ACPA-positive individuals developed RA. Overall, a positive anti-CCP2 test had a positive predictive value of 29% for prevalent RA at inclusion (negative predictive value of 99.6%). High titres (>3× cut-off) of anti-CCP2 increased the positive predictive value to 48% (negative predictive value of 99.5%). ACPA-positive individuals without RA had lower anti-CCP2 titres and fewer peptide-specific ACPA than ACPA-positive patients with RA and higher C reactive protein levels than ACPA-negative individuals without RA. CONCLUSION: Presence of ACPA and especially high titres of anti-CCP2 have a high diagnostic accuracy for an RA diagnosis in a population setting. | |
26449852 | Non-adherence to disease-modifying antirheumatic drugs is associated with higher disease a | 2015 Oct 8 | INTRODUCTION: Non-adherence to disease-modifying antirheumatic drugs (DMARDs) hampers the targets of rheumatoid arthritis (RA) treatment, obtaining low disease activity and decreasing radiological progression. This study investigates if, and to what extent, non-adherence to treatment would lead to a higher 28-joint count disease activity score (DAS28) in the first year after diagnosis. METHODS: Adult patients from an ongoing cohort study on treatment adherence were selected if they fulfilled the EULAR/ACR2010 criteria for RA, and were to start with their first DMARDs. Clinical variables were assessed at baseline and every 3 months. Non-adherence was continuously electronically measured and was defined as the proportion of days with a negative difference between expected and observed openings of the medication container out of the 3-month period before DAS28 measurement. Generalized linear mixed models were used to investigate whether the DAS28 related to non-adherence. Covariates included were age, sex, baseline DAS28, rheumatoid factor positivity, anti-cyclic citrullinated peptide antibodies (ACPA) positivity, anxiety, depression, weeks of treatment, number of DMARDs used, education level, use of subcutaneous methotrexate and biological use. RESULTS: One hundred and twenty patients met the inclusion criteria for RA. During the study period 17 patients became lost to follow-up. There was a decline in adherence over time for all DMARDs except for prednisone. Non-adherence is a predictor of disease activity in the first 6 months of therapy, adjusted for weeks of treatment, baseline DAS28, and baseline anxiety. CONCLUSIONS: Non-adherence relates to disease activity. Therefore, interventions towards enhancing adherence can improve disease outcome. |