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ID PMID Title PublicationDate abstract
26069140 Chemokine Signaling Pathway Involved in CCL2 Expression in Patients with Rheumatoid Arthri 2015 Jul PURPOSE: Rheumatoid arthritis (RA) is an inflammatory joint disorder, the progression of which leads to the destruction of cartilage and bone. Chemokines are involved in RA pathogenesis. In this study, we investigated the chemokine signaling pathway associated with CCL2 in peripheral blood (PB) and synovial tissues (ST) of RA patients based on our previous work about chemokine signaling pathway involved in the activation of CCL2 production in collagen-induced arthritis rat ST. MATERIALS AND METHODS: Total RNA was isolated from PB leukocytes and synovium of the knee joint in both RA patients and control populations. Real-time polymerase chain reaction was used to determine CCL4, CCR5, c-Jun, c-Fos, and CCL2 expressions. Serum level of CCL2 was assessed by enzyme-linked immunosorbent assay, and the production of CCL2 in ST was analyzed immunohistochemically. RESULTS: The expressions of CCL4, CCR5, c-Jun, c-Fos, and CCL2 messenger RNA in RA patients were significantly higher than those in healthy controls, both in ST and on PB leukocyte. Serum CCL2 levels were elevated in RA patients. Histological examination of rheumatoid joints revealed extensive CCL2 expression in RA ST. CONCLUSION: CCL2, CCL4, c-Jun, c-Fos, and CCR5 may play an important role in the recruitment of PB leukocytes into the RA joints. These data provide evidence that the chemokine signaling pathway is involved in CCL2 expression in RA patient tissues, which may contribute to chronic inflammation associated with RA. Targeting this signaling pathway may provide a novel therapeutic avenue in RA.
26158921 Balneotherapy (or spa therapy) for rheumatoid arthritis. An abridged version of Cochrane S 2015 Dec BACKGROUND: Treatment options for rheumatoid arthritis (RA) include pharmacological interventions, physical therapy treatments and balneotherapy. AIM: To evaluate the benefits and harms of balneotherapy in patients with RA. DESIGN: A systematic review. POPULATION: Studies were eligible if they were randomised controlled trials consisting of participants with definitive or classical RA. METHODS: We searched various databases up to December 2014. Balneotherapy had to be the intervention under study, and had to be compared with another intervention or with no intervention. We considered pain, improvement, disability, tender joints, swollen joints and adverse events among the main outcome measures. We excluded studies when only laboratory variables were reported as outcome measures. Two review authors independently selected trials, performed data extraction and assessed risk of bias. RESULTS: This review includes nine studies involving 579 participants. Most studies showed an unclear risk of bias in most domains. We found no statistically significant differences on pain or improvement between mudpacks versus placebo (1 study; N.=45; hand RA; very low level of evidence). As for the effectiveness of additional radon in carbon dioxide baths, we found no statistically significant differences between groups for all outcomes at three-month follow-up (2 studies; N.=194; low to moderate level of evidence). We noted some benefit of additional radon at six months in pain (moderate level of evidence). One study (N.=148) compared balneotherapy (seated immersion) versus hydrotherapy (exercises in water), land exercises or relaxation therapy. We found no statistically significant differences in pain or in physical disability (very low level of evidence) between groups. We found no statistically significant differences in pain intensity at eight weeks, but some benefit of mineral baths in overall improvement at eight weeks compared to Cyclosporin A (1 study; N.=57; low level of evidence). CONCLUSION: Overall evidence is insufficient to show that balneotherapy is more effective than no treatment; that one type of bath is more effective than another or that one type of bath is more effective than exercise or relaxation therapy. CLINICAL REHABILITATION IMPACT: We were not able to assess any clinical relevant impact of balneotherapy over placebo, no treatment or other treatments.
27117700 Autologous tolerogenic dendritic cells for rheumatoid and inflammatory arthritis. 2017 Jan OBJECTIVES: To assess the safety of intra-articular (IA) autologous tolerogenic dendritic cells (tolDC) in patients with inflammatory arthritis and an inflamed knee; to assess the feasibility and acceptability of the approach and to assess potential effects on local and systemic disease activities. METHODS: An unblinded, randomised, controlled, dose escalation Phase I trial. TolDC were differentiated from CD14+ monocytes and loaded with autologous synovial fluid as a source of autoantigens. Cohorts of three participants received 1×10(6), 3×10(6) or 10×10(6) tolDC arthroscopically following saline irrigation of an inflamed (target) knee. Control participants received saline irrigation only. Primary outcome was flare of disease in the target knee within 5 days of treatment. Feasibility was assessed by successful tolDC manufacture and acceptability via patient questionnaire. Potential effects on disease activity were assessed by arthroscopic synovitis score, disease activity score (DAS)28 and Health Assessment Questionnaire (HAQ). Immunomodulatory effects were sought in peripheral blood. RESULTS: There were no target knee flares within 5 days of treatment. At day 14, arthroscopic synovitis was present in all participants except for one who received 10×10(6) tolDC; a further participant in this cohort declined day 14 arthroscopy because symptoms had remitted; both remained stable throughout 91 days of observation. There were no trends in DAS28 or HAQ score or consistent immunomodulatory effects in peripheral blood. 9 of 10 manufactured products met quality control release criteria; acceptability of the protocol by participants was high. CONCLUSION: IA tolDC therapy appears safe, feasible and acceptable. Knee symptoms stabilised in two patients who received 10×10(6) tolDC but no systemic clinical or immunomodulatory effects were detectable. TRIAL REGISTRATION NUMBER: NCT01352858.
27883999 Low Prevalence of Nodules in Rheumatoid Arthritis Patients in Kuwait: A Description and a 2017 OBJECTIVES: To describe the prevalence of rheumatoid nodules (RN) in patients with rheumatoid arthritis (RA) and to compare their features with those of patients without RN. SUBJECTS AND METHODS: Adult RA patients (n = 952) in the Kuwait Registry for Rheumatic Diseases from February 2013 to December 2015 were evaluated for RN. Demographic and serological features and disease activity and severity were obtained from the registry. RESULTS: Of the 952 RA patients, 22 (2.3%) had RN and 930 (97.7%) did not. Age, sex, disease duration, smoking, and family history of an autoimmune rheumatic disease were similar. Obesity was more prevalent in the RN group, i.e. 11 (50%) vs. 326 (35.1%), p = 0.016. There was no difference in rheumatoid factor (RF) or anti-cyclic citrullinated peptide antibody positivity. Patients with RN had more sicca symptoms, i.e. 8 (36.4%) vs. 152 (16.3%), p = 0.025, a higher mean score on the visual analogue scale pain (3 ± 2.9 vs. 2 ± 2.7, p < 0.001), more tender joints (6.4 ± 8.8 vs. 4.2 ± 7.2, p = 0.001), a higher patient global assessment of disease activity (3.3 ± 2.7 vs. 2.3 ± 2.7, p < 0.001), and more deformities, i.e. 3 (13.6%) vs. 74 (8%), p = 0.034. The mean health assessment questionnaire score in RN patients was 1.1 versus 0.9 in patients without RN (p = 0.08). Patients with RN had a low disease activity (means: disease activity score [DAS-28], 3.02; clinical disease activity index, 7.7; and simple disease activity index, 10.4), similar to the other group. While the rates of methotrexate treatment were comparable, biologic therapy was administered more in patients with RN (i.e. 15 [68.2%] vs. 478 [51.4%], p < 0.001). CONCLUSION: In Kuwait, the prevalence of RN is low among RA patients. Patients with and without RN are similar in terms of demographics and serologic features, except for more obesity. However, patients with RN have more sicca symptoms, joint deformities, and painful and tender joints. Disease activity scores are low with more frequent biologic therapy.
25671614 A HPLC-SRM-MS based method for the detection and quantification of methotrexate in urine a 2015 Mar 21 Rheumatoid arthritis (RA) is a common autoimmune disease that causes significant disability and reduced life expectancy. The folate antagonist methotrexate (MTX) is first-line therapy for RA when used weekly at low doses (5-25 mg). However, the true rate of adherence to MTX is uncertain. This is in part due to the different methods of measurement of adherence employed with no biochemical test currently available to determine adherence to low dose MTX. Common methods of MTX measurement include immunoassays in patients with high dose therapy, but these assays cross-react with MTX metabolites and lack the sensitivity required to measure adherence to low dose MTX. HPLC-SRM-MS (selected reaction monitoring-mass spectrometry) has several theoretical advantages over immunoassays with improved specificity, minimal cross-reaction and higher sensitivity. The aim of this study was to develop an assay to measure MTX and its major metabolite 7-OH-MTX in urine as a tool to monitor adherence to low dose MTX in clinic. As a proof of concept, urine samples from 4 participants with RA were measured after directly observed therapy. The assay showed improved sensitivity compared to that reported by immunoassays, with low carryover and high within-run precision. In participant samples, MTX was measurable in the urine for up to 105 hours after administration and 7-OH-MTX was detectable up to 98 hours after administration, suggesting that this assay is suitable for the measurement of adherence to therapy. The assay requires minimal sample preparation and can be adopted by other laboratories with minimal study set up.
27312203 Optimal responses in disease activity scores to treatment in rheumatoid arthritis: Is a DA 2016 Jun 16 BACKGROUND: The overall benefit of intensive treatment strategies in rheumatoid arthritis (RA) remains uncertain. We explored how reductions in disability and improvements in quality of life scores are affected by alternative assessments of reductions in disease activity scores for 28 joints (DAS28) in two trials of intensive treatment strategies in active RA. METHODS: One trial (CARDERA) studied 467 patients with early active RA receiving 24 months of methotrexate monotherapy or steroid and disease-modifying anti-rheumatic drug (DMARD) combinations. The other trial (TACIT) studied 205 patients with established active RA; they received 12 months of treatment with DMARD combinations or biologic agents. We compared changes in the health assessment questionnaire (HAQ) and Euroqol-5D (EQ5D) at trial endpoints in European League Against Rheumatism (EULAR) good and moderate EULAR responders in patients in whom complete endpoint data were available. RESULTS: In the CARDERA trial 98 patients (26 %) were good EULAR responders and 160 (32 %) were EULAR moderate responders; comparable data in TACIT were 66 (35 %) and 86 (46 %) patients. The magnitude of change in the HAQ and EQ5D was greater in both trials in EULAR good responders than in EULAR moderate responders. HAQ scores had a difference in of -0.49 (95 % CI -0.66, -0.32) in the CARDERA and -0.31 (95 % CI -0.47, -0.13) in the TACIT trial. With the EQ5D comparable differences were 0.12 (95 % CI 0.04, 0.19) and 0.15 (95 % CI 0.05, 0.25). Both exceeded minimum clinically important differences in HAQ and EQ5D scores. CONCLUSIONS: We conclude that achieving a good EULAR response with DMARDs and biologic agents in active RA results in substantially improved mean HAQ and EQ5D scores. Patients who achieve such responses should continue on treatment. However, continuing such treatment strategies is more challenging when only a moderate EULAR response is achieved. In these patients evidence of additional clinically important benefits in measures such as the HAQ should also be sought.
27548651 Myopathy in scleroderma and in other connective tissue diseases. 2016 Nov PURPOSE OF REVIEW: This review discusses the most updated literature of myopathy in scleroderma and other connective tissue diseases. RECENT FINDINGS: In the past year, studies have demonstrated that myopathy in scleroderma is associated with poor outcomes such as disability and mortality. In addition, muscle histopathology in scleroderma continues to reveal that it is a heterogeneous entity, and that necrosis and acute neurogenic atrophy may be a more prevalent histopathologic feature in muscle biopsies than previously reported. In other connective tissue diseases such as SLE, the onset of overlap myositis typically does not occur simultaneously as it does in scleroderma or rheumatoid arthritis. SUMMARY: Myopathy in scleroderma is heterogeneous and given that it is associated with poor outcomes, it is imperative that optimal diagnostic strategies and therapies including a classification criterion be developed. In other connective tissue diseases, such as rheumatoid arthritis and systemic lupus erythematosus, myopathy is even more poorly defined and requires more robust studies to clarify both the clinical features and muscle histopathology in this group.
24928343 Disease-modifying anti-rheumatic drugs improve autonomic neuropathy in arthritis: DIANA st 2015 Jul Autonomic neuropathy (AN) is a risk predictor for sudden cardiac death in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). However, the impact of most commonly employed disease-modifying anti-rheumatic drug (DMARD) therapy on autonomic neuropathy in rheumatic diseases is not known. Hence, we investigated the efficacy of DMARDs on autonomic neuropathy in RA and AS. We performed autonomic function assessment in 60 patients in this open-label, 12-week pilot study including 42 patients with RA, 18 with AS, and 30 aged-matched healthy subjects. The methodology included assessment of cardiovascular autonomic reflex tests according to Ewing. Parasympathetic dysfunction was established by performing three tests: heart rate response to deep breathing, standing, and Valsalva tests. Sympathetic dysfunction was examined by applying two tests: blood pressure response to standing and handgrip tests. Sudomotor function was assessed by Sudoscan. Cardiovascular reflex tests were impaired significantly among the patients as compared to healthy subjects (p < 0.05). Autonomic neuropathy was more pronounced in biologic-naive RA and AS patients. After treatment with combination synthetic DMARDs, parasympathetic, and sudomotor dysfunction significantly (p < 0.05) improved in RA and AS. Biologic DMARDs significantly improved parasympathetic, sympathetic and peripheral sympathetic autonomic neuropathy (p < 0.05) in biologic-naive RA and AS patients. In conclusion, synthetic DMARDs improved parasympathetic and sudomotor dysfunction in both DMARD-naive RA and AS patients. However, biologic DMARDs improved parasympathetic, sympathetic and sudomotor dysfunction to a greater extent than synthetic DMARDs in both RA and AS patients.
25561360 Evaluating relationships between symptom duration and persistence of rheumatoid arthritis: 2015 May BACKGROUND: A prolonged symptom or disease duration at treatment initiation is associated with unfavourable outcomes in rheumatoid arthritis (RA). It is unknown whether this relation is linear, referring to a common 'the-earlier-the-better principle', or whether a transient time frame in which the disease is more susceptible to treatment exists, referring to a 'window of opportunity'. To elucidate this, we evaluated the shape of the associations of symptom duration with persistence of RA. METHODS: Patients with 1987 RA treated with disease modifying antirheumatic drugs (DMARDs) in the Leiden Early Arthritis Clinic (EAC, n=738) and Evaluation et Suivi de POlyarthrites Indifférenciées Récentes (ESPOIR) (n=533) were studied. Cox proportional hazards regression models using natural cubic splines were performed; the log-HR on DMARD-free sustained remission (the opposite of RA persistence) during 5-year follow-up was plotted against symptom duration. Discrimination was measured using time-dependent receiver operator characteristic curves. Subanalyses were performed stratified for the DMARDs used (methotrexate or other conventional DMARDs) and for anticitrullinated peptide antibody (ACPA). RESULTS: 11.5% (85/738) and 5.4% (29/533) of EAC and ESPOIR RA patients achieved DMARD-free sustained remission. In both cohorts and all analyses, the curves depicting the log-HRs on remission in relation to symptom duration were not linear. The symptom duration with optimal discriminative ability was 14.9 weeks (95% CI 12.3 to 16.0; area under the curve (AUC) 0.61) in the EAC and 19.1 weeks (95% CI 12.3 to 28.0; AUC 0.59) in ESPOIR. For ACPA-positive RA, this was 11.4 weeks (95% CI 7.7 to 79.0; AUC 0.56) and for ACPA-negative RA 15.0 weeks (95% CI 9.7 to 48.7; AUC 0.56). CONCLUSIONS: The association between symptom duration and RA persistence is not linear, suggesting the presence of a confined period in which RA is more susceptible to treatment.
26712373 Ultrasound-detected activity in rheumatoid arthritis on methotrexate therapy: Which joints 2016 Mar The aim of the study was to investigate the predictive value of different reduced joint ultrasound (US) assessments of synovitis and tenosynovitis in relation to unstable remission in a cohort of rheumatoid arthritis (RA) patients on methotrexate therapy. Forty-seven RA patients (38 women, 9 men), being treated with methotrexate (MTX), in clinical remission as judged by their consultant rheumatologist were evaluated for disease activity according to the Disease Activity Score (DAS) 28 at baseline and 6 months. Sustained remission and unstable remission were defined according to the baseline and 6-month DAS28 and changes in RA therapy during the follow-up. Each patient underwent at baseline a B-mode and power Doppler (PD) assessment of 44 joints and 20 tendons/tendon compartments by a rheumatologist blinded to the clinical and laboratory data. B-mode synovial hypertrophy (SH), synovial PD signal, B-mode tenosynovitis, and Doppler tenosynovitis were scored 0-3. The presence and index of synovial PD signal in 44 joints [odds ratio (OR) 8.21 (p = 0.016) and OR 2.20 (p = 0.049), respectively] and in 12 joints [OR 5.82 (p = 0.041) and OR 4.19 (p = 0.020), respectively], the presence of SH in wrist and MCP joints [OR 4.79 (p = 0.045)], and the presence of synovial PD signal in wrist-MCP-ankle-MTP joints [OR 4.62 (p = 0.046)] were predictors of unstable remission. The 12-joint or wrist-hand-ankle-MTP US assessments can predict unstable remission in RA patients in apparent clinical remission being treated with MTX.
26915265 [Misfolded proteins complexed with HLA class II molecules are involved in autoimmune disea 2016 Feb HLA class II molecules play an important role in immune response by presenting peptide antigens to T cells. However, when misfolded proteins in endoplasmic reticulum, which are generally degraded in the cells, are associated with MHC class II molecules instead of invariant chain, the misfolded proteins are transported to the cell surface without processing to peptides. Furthermore, misfolded proteins associated with MHC class II molecules are recognized by autoantibodies produced in autoimmune diseases such as rheumatoid arthritis and antiphospholipid syndrome. More importantly, autoantibody binding to misfolded protein/MHC class II complex is associated with susceptibility to rheumatoid arthritis conferred by each MHC class II allele. Therefore, cellular misfolded proteins rescued from degradation by MHC class II molecules seem to be involved in autoimmune diseases as a target for autoantibodies.
25660991 Relapse rates in patients with rheumatoid arthritis in stable remission tapering or stoppi 2016 Jan OBJECTIVE: To prospectively analyse the risk for disease relapses in patients with rheumatoid arthritis (RA) in sustained remission, either continuing, tapering or stopping disease-modifying antirheumatic drugs (DMARDs) in a prospective randomised controlled trial. METHODS: Reduction of Therapy in patients with Rheumatoid arthritis in Ongoing remission is a multicentre, randomised controlled, parallel-group phase 3 trial evaluating the effects of tapering and stopping all conventional and/or biological DMARDs in patients with RA in stable remission. Patients (disease activity score 28 (DAS28)<2.6 for least 6 months) were randomised into three arms, either continuing DMARDs (arm 1), tapering DMARDs by 50% (arm 2) or stopping DMARDs after 6 months tapering (arm 3). The primary endpoint was sustained remission during 12 months. RESULTS: In this interim analysis, the first 101 patients who completed the study were analysed. At baseline, all patients fulfilled DAS28 remission and 70% also American College of Rheumatology- European League Against Rheumatism Boolean remission. 82.2% of the patients received methotrexate, 40.6% biological DMARDs and 9.9% other DMARDs. Overall, 67 patients (66.3%) remained in remission for 12 months, whereas 34 patients (33.7%) relapsed. The incidence of relapses was related to study arms (p=0.007; arm 1: 15.8%; arm 2: 38.9%; arm 3: 51.9%). Multivariate logistic regression identified anticitrullinated protein antibodies (ACPA) positivity (p=0.038) and treatment reduction (in comparison to continuation) as predictors for relapse (arm 2: p=0.012; arm 3: p=0.003). CONCLUSIONS: This randomised controlled study testing three different treatment strategies in patients with RA in sustained remission demonstrated that more than half of the patients maintain in remission after tapering or stopping conventional and biological DMARD treatment. Relapses occurred particularly in the first 6 months after treatment reduction and were associated with the presence of ACPA. TRIAL REGISTRATION NUMBER: 2009-015740-42.
25300699 Tocilizumab in rheumatoid arthritis: a case study of safety evaluations of a large postmar 2015 Feb OBJECTIVES: To evaluate the magnitude of serious adverse events (SAEs) observed in postmarketing reports of tocilizumab (TCZ) for rheumatoid arthritis (RA) in relation to SAEs observed in TCZ clinical trials and external epidemiology data. METHODS: A total of 64,000 patient-years (PY) of TCZ exposure was needed to determine, with 90% power, whether rates of SAEs of interest (eg, death, hepatic, gastrointestinal, and cardiovascular) were ≥50% higher (agreed with the Food and Drug Administration) than expected. Reporting rates were calculated for spontaneously reported SAEs, open-label or unblinded postmarketing clinical trials (phase 3b/4), and a Japanese postmarketing surveillance program in the global postmarketing safety database. Event rates were calculated for the registrational placebo-controlled trials and long-term extension data. External comparators for anti-tumor necrosis factor (aTNF)-treated RA patients were derived from a US-based health care insurance claims database or published literature. RESULTS: The global postmarketing safety database provided 65,099 PY of TCZ exposure; the aTNF external comparator population provided 53,360 PY. Spontaneous reporting rates per 100 PY (95% confidence interval) were 8.3 (8.1, 8.5) SAEs, 0.39 (0.34, 0.44) deaths, 0.06 (0.04, 0.08) serious hepatic events, 0.15 (0.12, 0.18) serious gastrointestinal events, 0.09 (0.07, 0.12) serious myocardial infarctions, 0.15 (0.12, 0.18) serious strokes, and 0.07 (0.05, 0.09) cardiac deaths in the global postmarketing safety database. These were of similar magnitude to corresponding rates from registrational clinical trials, the aTNF external comparator population, and published literature. CONCLUSIONS: SAE rates observed among postmarketing TCZ users were similar to those of various comparison populations. Predetermined design of studies to compare postmarketing AEs using multiple data sources is a useful strategy that can be applied to other medications.
25073584 "Better but not best": a qualitative exploration of the experiences of occupational gain f 2015 OBJECTIVES: To investigate whether patients with improved clinical markers during their anti-TNFα treatment experience improvements in their functional and psychological ability to undertake activities. METHODS: Patients receiving anti-TNFα treatment for rheumatoid arthritis (RA) or ankylosing spondylitis (AS) were recruited from outpatient clinics in East Anglia and North West England. Purposive sampling recruited variety in demographic and treatment experiences. Data were collected through in-depth qualitative interviews and analysed using an interpretive phenomenological framework. Twenty-seven patients were recruited; 19 with RA, eight with AS, and aged from 21 to 73 years. RESULTS: While people generally experienced an improvement in their functional ability, known as occupational gain, they continued to experience difficulties through previous biomechanical damage, continuing symptoms of inflammatory arthritis, or concerns about anti-TNFα treatment. These disruptions affected how participants retained or regained employment. Lack of healthcare support, including an absence of occupational therapy intervention, resulted in people testing new boundaries through a process of unsupported trial and error. CONCLUSION: Occupational gain was not maximised for people on anti-TNFα treatment. Improved referral pathways to occupational therapy could facilitate the management of continuing functional difficulties, thereby maximising the benefit of treatment to people with inflammatory arthritis.
27115106 Sonographic Measurements Can Be Misleading for Diagnosing Carpal Tunnel Syndrome in Patien 2016 Jan OBJECTIVES: To compare the nerve cross sectional areas (CSA) of patients with RA without any sign of peripheral neuropathy to healthy controls. METHODS: Clinical, electrophysiological and sonographic assessments were done by three blinded researchers. The patients who had an electrodiagnostic or clinical of peripheral neuropathy were excluded from the study. Nerve CSA were measured in various levels; hamatum hook, pisiform bone, radio-ulnar joint, distal 1/3 of forearm, and elbow for median nerve; radio-ulnar joint, pisiform bone, distal 1/3 of forearm, and medial epicondyle for ulnar nerve. RESULTS: The study was completed with 30 women with RA and 30 healthy women. Despite both groups had neither clinical nor electrophysiological neuropathy, the sonographic measurements showed that median nerve CSA at radioulnar joint, pisiform and hamatum levels of patients with RA were larger in rheumatoid arthritis patients than healthy controls. Ulnar nerve CSA at radioulnar joint, pisiform and distal 1/3 forearm and medial epicondyle levels of patients with RA were also increased (p<0.05). If the pisiform level median nerve CSA>10 mm2 was used as sonographic carpal tunnel syndrome (CTS) criterion, 23/60 hands of 30 patients with RA and 5/60 hands of 30 healthy controls could be diagnosed as CTS. CONCLUSION: Median and ulnar nerve CSA were larger than healthy control in patients with rheumatoid arthritis without clinical and electrophysiological peripheral neuropathy. The rheumatologists should be careful to diagnose CTS in patients with RA while using US.
26139357 The moral experience of illness and its impact on normalisation: Examples from narratives 2015 Nov The moral component of living with illness has been neglected in analyses of long-term illness experiences. This article attempts to fill this gap by exploring the role of the moral experience of illness in mediating the ability of those living with a long-term condition (LTC) to normalise. This is explored through an empirical study of women of Punjabi origin living with rheumatoid arthritis (RA) in the UK. Sixteen informants were recruited through three hospitals in UK cities and interviews conducted and analysed using a grounded theory approach. The intersection between moral experience and normalisation, within the broader context of ethnic, gender and socioeconomic influences, was evident in the following: disruption of a core lived value (the centrality of family duty), beliefs about illness causation affecting informants' 'moral career', and perceived discrimination in the workplace. The data illustrate the importance of considering an ethnic community's specific values and beliefs when understanding differences in adapting to LTCs and changing identities.
27384923 Expression of ERAP2 and LST1 is increased before start of therapy in rheumatoid arthritis 2016 Jul OBJECTIVES: Glucocorticoids (GC) remain a cornerstone of rheumatoid arthritis (RA) therapy, although a third of patients do not respond adequately. In order to find potential predictors for clinical response, the gene expression profile of CD4+T-cells as important players in the pathogenesis of RA was analysed before pulse therapy with 1000 mg methylprednisolone. METHODS: Patients were treated with 3x1000 mg methylprednisolone in 5 days; hereafter response was determined by the European League Against Rheumatism (EULAR) response criteria. Before start of treatment, CD4+T-cells (and CD14+monocytes) were separated by MACS sorting. Labelled cRNA from CD4+T-cells from 5 responders and 5 non-responders was hybridised to Agilent 4x44K microarray chips and differentially expressed genes were identified via mixed-model analysis of variance based on permutation-based false discovery rates. Selected genes were validated by quantitative real-time PCR (qPCR). RESULTS: Four genes were significantly increased in CD4+T-cells of GC-responders; expression of ERAP2 (endoplasmic reticulum aminopeptidase 2), LST1 (leucocyte-specific transcript 1) and FAM26F (Family With Sequence Similarity 26, Member F) was confirmed by quantitative PCR (qPCR); their expression was inversely correlated with DAS28 at day 5 (LST1 and FAM26F p<0.05; ERAP2: p=0.07). Elevated expression of ERAP2 was also detected by qPCR in CD14+monocytes and after 24 hours in both cell types (all p<0.02). CONCLUSIONS: The increased expression of ERAP2, LST1 and FAM26F in GC-responders before therapy warrants further investigation into their role as potential predictors for the response to GC, and in the inflammatory process of RA.
25641888 Characterization of cumulative joint damage patterns in patients with rheumatoid arthritis 2015 Mar OBJECTIVE: To characterize cumulative joint damage (CJD) patterns in rheumatoid arthritis (RA) and determine their associations with demographic/clinical features and HLA-DRB1 gene polymorphism. METHODS: Hand and foot radiographs were obtained from 404 patients with RA. CJD patterns were determined by 3 derivations from Sharp/van der Heijde scores, obtained by the mathematical division of scores for hands/feet (Sharp-h/f score), fingers/wrists (Sharp-f/w score), and erosion/space narrowing (Sharp-e/sn score), respectively. DNA and serum were obtained for determination of HLA-DRB1 polymorphism, rheumatoid factor (RF), and anticitrullinated protein antibodies (ACPA). RESULTS: Patients with wrist-dominant CJD pattern were more likely to have severe RA than those with finger-dominant pattern (68.4% vs 46.0%; p = 0.036) as were those with foot-dominant vs hand-dominant CJD pattern (76.5% vs 56.4%; p = 0.044). HLA-DRB1 shared epitope (SE) alleles were associated with erosion-dominant CJD pattern (p = 0.021). Patients with erosion-dominant CJD pattern had higher levels of RF and ACPA than those with space-narrowing-dominant CJD pattern (median RF 71.35 U/ml vs 22.05 U/ml, respectively; p = 0.003; median ACPA 187.9 U/ml vs 143.2 U/ml, respectively; p < 0.001). The majority of triple-positive patients (SE+, RF+, ACPA+) had erosion-dominant CJD pattern (62.3%) while the majority of triple-negative patients (SE-, FR-, ACPA-) had space narrowing-dominant CJD pattern (75%; p = 0.017). ACPA was associated with HLA-DRB1 SE alleles (p < 0.05). Patients with foot-dominant CJD pattern were taller than those with hand-dominant CJD pattern (p = 0.002); those with erosion-dominant CJD pattern had higher weight and body mass index than those with space narrowing-dominant CJD pattern (p = 0.014, p = 0.001). CONCLUSION: CJD patterns were associated with disease severity, HLA-DRB1 SE status, presence and titer of ACPA and RF, and morphometric features.
27613285 Infections With Biologics in Rheumatoid Arthritis and Related Conditions: a Scoping Review 2016 Oct Biologic use is a major advance in the treatment of several autoimmune conditions, including rheumatoid arthritis. In this review, we summarize key studies of serious/hospitalized infections in rheumatoid arthritis (RA). RA is a risk factor for infections. High RA disease activity is associated with higher risk of serious infection. The risk of serious infections with tumor necrosis factor inhibitor (TNFi) biologics is increased in the first 6 months of initiating therapy, and this risk was higher compared to the use of traditional disease-modifying anti-rheumatic drugs (DMARDs). Emerging data also suggest that biologics may differ from each other regarding the risk of serious or hospitalized infections. Past history of serious infections, glucocorticoid dose, and older age were other important predictors of risk of serious infections in patients treated with biologics.
26558294 A case of rheumatoid arthritis with methotrexate related lymphoproliferative diseases of t 2018 May Methotrexate (MTX) is the first choice disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis (RA) and is referred to as an "anchor drug"; its use has been steadily increasing annually. However, MTX-related lymphoproliferative diseases (MTX-LPDs) have emerged as important complications in the patients with RA. There have been no reports of intra-articular MTX-LPDs of the patients with RA. Atypical cells were found in the patient's joint fluid by cytological examinations, and MTX-LPDs were suspected. The patient discontinued MTX and open synovectomy was performed. The histological findings and immunohistochemical staining of the specimens confirmed the diagnosis of diffuse large B-cell lymphoma (DLBCL) of MTX-LPDs. After the operation of the patient's left knee joint, pains and swollen joint disappeared with no relapse. The cytological examinations of the synovial fluid followed by knee operation were effective for early diagnosis of MTX-LPD. MTX discontinuation with no chemotherapy followed up with a knee operation improved the recovery of the MTX-LPD.