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ID PMID Title PublicationDate abstract
28884308 Spa therapy adjunct to pharmacotherapy is beneficial in rheumatoid arthritis: a crossover 2018 Feb This study aims to investigate whether 2-week spa therapy, as an adjunct to usual pharmacological therapy, has any beneficial effect in patients with rheumatoid arthritis (RA). In this single-blind crossover study, 50 patients were randomly assigned in a 1:1 manner to receive usual pharmacological therapy plus 2-week spa therapy or usual pharmacological therapy alone (period 1.6 months); after a 9-month washout, patients were crossed over to the opposite assignment (period 2.6 months). Spa therapy program included a daily saline balneotherapy session at 36-37 °C for 20 min except Sundays. The clinical outcomes were evaluated at baseline, after spa therapy (2 weeks) and 3 and 6 months after the spa therapy in both period and were pain (Visual Analogue Scale (VAS)), patient and physician global assessments (VAS), Health Assessment Questionnaire (HAQ), and Disease Activity Score (DAS28). Spa therapy was superior to control therapy in improving all the assessed clinical outcomes at the end of the spa therapy. This superiority persisted significantly in physician global assessment (p = 0.010) and with a trend in favor of spa group in patient global assessment (p = 0.058), function (p = 0.092), and disease activity (p = 0.098) at 3 months. Statistically significant improvements were found in spa therapy compared to control in disease activity (p = 0.006) and patient (p = 0.020) and physician global (p = 0.011) assessments, and a trend toward improvements in pain (p = 0.069) and swollen joints (p = 0.070) at 6 months. A 2-week spa therapy adjunct to usual pharmacological therapy provided beneficial clinical effects compared to usual pharmacological therapy alone, in RA patients treated with traditional disease-modifying antirheumatic drugs. These beneficial effects may last for 6 months.
29235264 Reconceptualizing motivation for smoking cessation among people with rheumatoid arthritis 2018 Mar OBJECTIVES: Smokers with rheumatoid arthritis (RA) may have different motivations for, and barriers to, quitting. Understanding the motivations of smokers and ex-smokers with RA will help in the design and implementation of targeted smoking cessation interventions for people with RA that are not based solely on extrapolation from the general population or populations with other chronic illnesses. METHODS: Twenty-nine smokers and 10 recent ex-smokers with RA participated in semi-structured interviews via telephone 18 months after being offered a smoking cessation intervention in Aotearoa/New Zealand. The sample consisted of 27 women and 12 men (age range 32-78 years), of whom 14 had received the intervention, 14 had been in the control group and 11 had declined participation in the trial. RESULTS: Thematic analysis led to the formulation of four "incentives" to quit and five "facilitators" of quitting for people with RA. Desiring improvements to health (overall and specific to arthritis), social relationships and avoiding costs were incentives to quit. Coping with stress without smoking, commitment, mental preparedness, willpower and interventions were facilitators of quitting. CONCLUSIONS: Becoming aware of the effects of smoking on arthritis provides an important motivation to quit smoking that may counter RA-specific barriers to smoking cessation. Further research is needed to test whether similar incentives and facilitators of smoking cessation exist in other chronic illnesses, and how to develop interventions to address these motivational processes.
30341453 On-drug and drug-free remission by baseline symptom duration: abatacept with methotrexate 2018 Dec Clinical outcomes in patients with early rheumatoid arthritis (RA) were assessed by baseline symptom duration in the Assessing Very Early Rheumatoid arthritis Treatment trial (ClinicalTrials.gov; NCT01142726). Patients with early, active RA were randomized to subcutaneous (SC) abatacept 125 mg/week plus methotrexate (MTX), SC abatacept alone, or MTX monotherapy for 12 months. All RA treatments were withdrawn after 12 months in patients with Disease Activity Score in 28 joints (C-reactive protein; DAS28-CRP) < 3.2. In this post hoc analysis, the proportion of patients achieving protocol-defined remission (DAS28-CRP < 2.6) or improvement in physical function at 12 and at both 12 and 18 months was assessed according to symptom duration (≤ 3 months, > 3 to ≤ 6 months, or > 6 months) and treatment group. No clinically significant differences were seen in baseline demographics or characteristics across symptom duration groups. Irrespective of baseline symptom duration, a numerically higher proportion of abatacept plus MTX-treated patients achieved DAS-defined remission at month 12 and sustained remission at month 18 compared with MTX monotherapy. A numerically higher proportion of abatacept plus MTX-treated patients with symptom duration ≤ 3 months maintained DAS-defined remission after complete treatment withdrawal from 12 to 18 months compared with longer symptom duration groups. This subgroup also had the fastest onset of clinical response (DAS28-CRP < 2.6) after initiation of treatment. Health Assessment Questionnaire-Disability Index response was similar regardless of baseline symptom duration. Overall, symptom duration of ≤ 3 months was associated with a faster onset of clinical response and higher rates of drug-free remission following treatment with abatacept plus MTX.
29323343 Targeting lymphatic function as a novel therapeutic intervention for rheumatoid arthritis. 2018 Feb Although clinical outcomes for patients with rheumatoid arthritis (RA) have greatly improved with the use of biologic and conventional DMARDs, approximately 40% of patients do not achieve primary clinical outcomes in randomized trials, and only a small proportion achieve lasting remission. Over the past decade, studies in murine models point to the critical role of the lymphatic system in the pathogenesis and therapy of inflammatory-erosive arthritis, presumably by the removal of catabolic factors, cytokines and inflammatory cells from the inflamed synovium. Murine studies demonstrate that lymphatic drainage increases at the onset of inflammatory-erosive arthritis but, as inflammation progresses to a more chronic phase, lymphatic clearance declines and both structural and cellular changes are observed in the draining lymph node. Specifically, chronic damage to the lymphatic vessel from persistent inflammation results in loss of lymphatic vessel contraction followed by lymph node collapse, reduced lymphatic drainage, and ultimately severe synovitis and joint erosion. Notably, clinical pilot studies in patients with RA report lymph node changes following treatment, and thus draining lymphatic vessels and nodes could represent a potential biomarker of arthritis activity and response to therapy. Most importantly, targeting lymphatics represents an innovative strategy for therapeutic intervention for RA.
29747994 A systematic review of viral exposures as a risk for rheumatoid arthritis. 2019 Feb OBJECTIVE: Different viral exposures have been implicated in the etiology of rheumatoid arthritis (RA). Evidence relating to the association between putative viral exposures and the development of RA was reviewed. METHODS: A systematic literature search was conducted using MEDLINE-OVID, EMBASE-OVID, PUBMED and Cochrane library databases. Articles were included if they were case-controls, cross-sectional or cohort studies and were published in English. Case-series were included if there was a lack of other study designs. RESULTS: Of 6724 citations, 48 were included in meta-analysis. Studies had poor quality. PBV19 infection was increased in RA compared to controls [N = 12, odds ratio (OR) 1.77 (95% CI: 1.11; 2.80) p = 0.02 for PVB19 IgG]. IgG anti-EBNA antibodies were not increased in RA (N = 17, p = 0.75), but anti-VCA [N = 18, OR 1.5 (95% CI: 1.07; 2.10), p = 0.02] and anti-EA antibodies [N = 11, OR 2.74 (95% CI: 1.27; 5.94), p = 0.01] were increased in RA. CMV was not associated with RA (N = 13, p = 0.42), nor was HBV (N = 5, p = 0.09). HCV was associated with RA in 7 case-control studies [OR 2.82 (95% CI: 1.35; 5.90), p = 0.006] and one cohort study [hazard ratio (HR) 2.03 (95% CI: 1.27, 3.22), p < 0.01]. Persistent arthritis was increased after Chikungunya fever [N = 2, OR 90 (95% CI: 15.2, 134.3), p = 0.047]. CONCLUSIONS: Studies of RA after viral exposures have poor quality. There is a risk of RA after Parvo B19, HCV and possibly EBV infection. CMV and HBV infections are not associated with RA. CHIKV is associated with the persistent inflammatory arthritis.
29745884 Type IV collagen metabolism is associated with disease activity, radiographic progression 2018 Sep OBJECTIVES: The expanding spectrum of targeted therapies for rheumatoid arthritis (RA) implies a need for development of precision tools for disease assessment reflecting pathobiologic processes. Type IV collagen is an abundant protein of basement membranes, but is also present in the intercellular matrix of the synovial lining layer. We aimed to investigate the association of type IV collagen turnover with RA disease activity, response to IL-6 inhibition and radiographic progression. METHODS: C4M, a serologic marker of type IV collagen metabolism, was measured at baseline and at follow-up in serum samples of RA patients participating in the phase III studies LITHE (n=687) and RADIATE (n=217). Both were double-blinded, placebo-controlled clinical trials testing the safety and efficacy of 4 and 8 mg/kg tocilizumab (TCZ) in combination with methotrexate (MTX) vs. MTX plus placebo. Associations with disease activity, radiographic severity and ACR response were investigated. RESULTS: Baseline C4M correlated significantly with clinical disease parameters in both study populations, including DAS28, HAQ score and VASpain (all p<0.00001). C4M at baseline correlated significantly with change in JSN (p=0.001) and Sharp score (p=0.00002) at 52 weeks. TCZ lowered C4M by 11-40% in a dose dependent manner. The likelihood of achieving an ACR20 response by week 16 was associated with C4M suppression exceeding the median decrease at week 4 (p<0.0001). CONCLUSIONS: Type IV collagen remodelling was associated with disease activity and radiographic progression in RA and was persistently and dose-dependently suppressed by TCZ. These findings indicate that C4M may serve as a plausible biologic marker of destructive synovitis growth in RA.
29556750 The effect of interactive digital interventions on physical activity in people with inflam 2018 Sep The aim of this systematic review was to evaluate the evidence from randomised controlled trials (RCTs) evaluating the effectiveness of interactive digital interventions (IDIs) for physical activity (PA) and health related quality of life (HRQoL) in people with Inflammatory Arthritis [rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA) axial Spondyloarthritis (AS) and psoriatic arthritis (PsA)]. Seven electronic databases identified published and unpublished studies. Two reviewers conducted independent data extraction and quality assessment using the Cochrane risk of bias tool (RoB). The primary outcome was change in objective PA after the intervention; secondary outcomes included self-reported PA and HRQoL after the intervention and objective or self-reported PA at least 1 year later. Five manuscripts, reporting four RCTs (three high and one low RoB) representing 492 (459 RA, 33 JIA) participants were included. No trials studying PsA or AS met the inclusion criteria. Interventions ranged from 6 to 52 weeks and included 3-18 Behaviour Change Techniques. Due to heterogeneity of outcomes, a narrative synthesis was conducted. No trials reported any significant between group differences in objective PA at end of intervention. Only one low RoB trial found a significant between group difference in self-reported vigorous [MD Δ 0.9 days (95% CI 0.3, 1.5); p = 0.004], but not moderate, PA in people with RA but not JIA. There were no between group differences in any other secondary outcomes. There is very limited evidence for the effectiveness of IDIs on PA and HRQoL in RA and JIA and no evidence for their effectiveness in PsA or AS.
29532212 Predicting methotrexate resistance in rheumatoid arthritis patients. 2018 Jun Rheumatoid arthritis (RA) is an incurable, systemic autoimmune disease that decreases quality of life and can lead to severe disability. While there are many medications available to treat RA, the first-line of therapy is low-dose methotrexate (MTX), a small molecule disease-modifying anti-rheumatic drug (DMARD). MTX is the recommended therapy due to its affordability and efficacy in reducing symptoms in most RA patients. Unfortunately, there is great person-to-person variability in the physiological response to MTX, with up to 50% of patients showing little response to the medication. Thus, many RA patients initially placed on MTX do not experience an adequate reduction of symptoms, and could have benefited more in both the short and long terms if initially prescribed a different drug that was more effective for them. To combat this problem and better guide treatment decisions, many research groups have attempted to develop predictive tools for MTX response. Currently, there is no reliable, clinical-grade method to predict an individual's response to MTX treatment. In this review, we describe progress made in the area of MTX non-response/resistance in RA patients. We specifically focus on application of the following elements as predictive markers: proteins related to MTX transport and function, intracellular MTX concentration, immune cell frequencies, cytokines, and clinical factors.
29920067 Anti-Inflammation and Joint Lubrication Dual Effects of a Novel Hyaluronic Acid/Curcumin N 2018 Jul 18 Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, which can cause endless suffering to the patients and severely impact their normal lives. To treat RA, the drugs in use have many serious side effects, high cost, or only focus on their anti-inflammatory mechanisms without taking joint lubrication into consideration. Therefore, in this study, we aim to construct a novel anti-RA drug composed of hyaluronic acid/curcumin (HA/Cur) nanomicelle to resolve these problems. Characterizations show that Cur is bound to HA by ester linkages and self-assembles to form a spherical nanomicelle with a diameter of around 164 nm under the main driving of the hydrophilic and hydrophobic forces. The nanomicelle enjoys excellent biocompatibility that effectively promotes the proliferation of chondrocytes. When injected to the RA rats, the nanomicelle significantly lowers the edema degree of the arthritic rats compared to other groups; more critically, a dramatic decrease in friction between the surfaces of cartilage around the joints has been found, which protects the cartilage from the RA-induced damage. Additionally, systematic mechanism investigation indicates that the nanomicelle diminishes the expression of related cytokines and vascular endothelial growth factor, finally leading to the excellent performance. The newfound nanomicelle has a potential for clinical practice of RA therapy, which will contribute significantly to alleviating the pain of patients and improving the quality of life for them.
28927869 What have we learned from BeSt? 2018 Jan BACKGROUND: How have the long term outcomes of RA improved in the last decade? METHODS: Patients with DMARD naïve RA were randomized to 4 treatment strategies: 1. sequential DMARD monotherapy, 2. step-up combination therapy, 3. initial combination therapy including prednisone or 4. including infliximab. Treatment-to-target was aimed at DAS≤2.4 (three-monthly calculations). Functional ability (HAQ), radiologic damage progression (Sharp/vanderHeijde Score) and overall survival were reported. RESULTS: Patients in arms 3 and 4 showed earlier clinical improvement. Up to 50% achieved DAS-remission (<1.6), up to 29% achieved drug free remission. Damage progression was well suppressed (median after 10years in completers 2 SHS points), functional ability approached normality (mean HAQ 0.6). There was no increased mortality (Standardized Mortality Ratio 1.16, 95% CI 0.92-1.46). CONCLUSIONS: Early treatment determines early clinical improvement, treatment-to-target determines long term outcomes. Prevention of relevant radiologic damage progression and disability, drug free remission and normalized survival are realistic goals.
29447376 The relationship between depression and biologic treatment response in rheumatoid arthriti 2018 May 1 OBJECTIVE: To investigate the relationship between depressive symptoms and treatment response and disease activity in RA over a 1-year follow-up. METHODS: Data from the British Society for Rheumatology Biologics Register were used, representing 18 421 RA patients receiving biologic treatment. Depressive symptoms were identified through one of three assessments: reporting a history of depression, the Medical Outcomes Survey 36-item Short Form or the EuroQol five-dimension scale. Logistic regression analyses examined the relationship between baseline depressive symptoms and odds of good treatment response by 1 year. Multilevel models addressed the association between baseline depressive symptoms and disease activity outcomes over 1-year follow-up, adjusting for age, gender, disease duration, comorbidities and baseline disease activity and physical disability. RESULTS: Depression symptoms at biologic treatment initiation were associated with 20-40% reduced odds of achieving a good treatment response at 1 year. Depressive symptoms at baseline also associated with reduced improvement in disease activity over the course of follow-up. Patients with a history of depression or reporting symptoms of depression according to the EuroQol five-dimension scale showed reduced improvement in tender and swollen joints, patient global assessment and ESR over 1-year follow-up. Patients with depression symptoms according to the 36-item Short Form showed reduced improvement in tender and swollen joints, but not ESR or patient global assessment. CONCLUSION: Experiencing symptoms of depression at the start of biologics treatment may reduce the odds of achieving a good treatment response, and reduce improvement in disease activity over time. Depression should be managed as part of routine clinical care to optimize treatment outcomes.
29911396 Epidemiology of Swallowing Disorders in Rheumatoid Arthritis: Prevalence, Risk Factors, an 2018 Sep OBJECTIVE: This investigation examined the prevalence, symptoms, risk factors, and quality-of-life burden of swallowing disorders in rheumatoid arthritis (RA), a chronic, progressive autoimmune inflammatory disease. METHODS: One hundred individuals with RA (84 women, 16 men; mean age = 61.1 years, SD = 13.1) were interviewed regarding the presence, nature, and impact of swallowing symptoms and disorders. Associations between swallowing disorders, medical factors, RA disease severity, and quality of life were examined. RESULTS: Forty-one percent of participants reported a current swallowing disorder that began gradually and was longstanding (most experiencing symptoms on a daily basis for at least 4 years). Symptoms compatible with solid food dysphagia contributed disproportionately to reporting a current swallowing disorder. Risk factors for dysphagia included a self-reported voice disorder, thyroid problems, esophageal reflux, and being physically inactive. Swallowing disorders increased with self-reported RA disease severity and contributed to a significantly greater burden on overall quality of life. CONCLUSION: Chronic, longstanding swallowing disorders are common in individuals with RA and appear to increase with disease severity. Those individuals with dysphagia reported greater reductions in quality of life as compared to those without, highlighting the need for improved awareness, exploration, and management of swallowing disorders in this population.
29970432 Red Blood Cell Distribution Width in Rheumatoid Arthritis, Ankylosing Spondylitis and Oste 2018 May OBJECTIVE: To date, there have been no studies systematically comparing red blood cell distribution width (RDW) among rheumatoid arthritis (RA), ankylosing spondylitis (AS) and osteoarthritis (OA). Therefore, this study aimed to make comparisons and to explore whether erythrocytopenia and hemoglobin (Hb) reduction could influence RDW level and its association with conventional inflammatory or immune markers in RA, AS and OA. METHODS: A total of 222 patients with RA, 150 with AS, 78 with OA and 126 healthy controls (HC) were enrolled. Clinical and laboratory data of all subjects were extracted from electronically stored medical records. RESULTS: Increased RDW level was found only in RA patients and showed significant diagnostic value for RA. It was much higher in those with erythrocytopenia and Hb reduction. However, those without Hb reduction did not show significant difference of RDW from HC. RDW positively correlated with CRP and ESR respectively in RA and OA patients. However, when the patients were divided into Hb reduction and non-Hb reduction groups, the correlations became insignificant. CONCLUSIONS: RDW level is increased only in RA patients, but not in those with AS and OA. However, increased RDW and its association with CRP may be mainly due to Hb reduction. Therefore, whether RDW could be used as useful inflammatory index for RA, AS and OA remains to be evaluated.
29063462 The role of microalbuminuria as a predictor of subclinical cardiovascular events in rheuma 2018 Mar Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that affects many body tissues and leads to major morbidity and mortality. Renal disease in RA is clinically important because it restricts the management of primary disease and increases mortality. The objectives of this study are to (1) investigate the difference between RA patients with and without microalbuminuria (MAU) and (2) find out the relation between MAU and disease activity as well as subclinical cardiovascular effects. Ninety RA patients were divided into two groups according to the presence of MAU, in addition to 30 healthy volunteers. ESR, hs-CRP, RF, lipid profile, urinary microalbumin, GFR, renal function tests, carotid intima media thickness (cIMT), flow-mediated dilatation of the brachial artery (FMD), ECG, and echocardiographic examination were performed for patients and controls. MAU positive RA patients revealed significantly higher lipid profile, ESR, hs-CRP, DAS 28, cIMT, and lower FMD as well as ECG and echocardiographic abnormalities compared to MAU negative RA patients. Moreover, there was significant positive correlation between MAU and DAS28, hs-CRP, LDL, cIMT as well as negative correlation with FMD%. In our study, all RA patients with MAU had a normal serum creatinine concentration and gave a negative result with Albustix. MAU is significantly correlated with ESR, hs-CRP, lipid profile, cIMT, and FMD% in RA patients; therefore, it can be used as an index to measure disease activity as well as subclinical cardiovascular affection in RA patients.
29102157 The UltraSound-CLinical ARthritis Activity (US-CLARA) index: Properties of a new composite 2018 Apr OBJECTIVE: To assess validity, responsiveness and interpretability of the UltraSound-CLinical ARthritis Activity (US-CLARA) index in patients with rheumatoid arthritis (RA). METHODS: In this longitudinal study were involved RA patients starting treatment with abatacept. Subjects were followed along three visits in the first 6 months of therapy and underwent a comprehensive clinimetric evaluation. Validity was explored correlating the baseline scores and the cumulative inflammatory burden of the US-CLARA with the other composite indices applied. Sensitivity to change was assessed after 6 months of treatment in terms of internal and external responsiveness. Interpretability was defined in terms of determination of cutoffs against external criteria for remission (REM), low disease activity (LDA), moderate disease activity (MDA), and high disease activity (HDA) of SDAI. RESULTS: One-hundred and thirty patients completed the study. VALIDITY: moderate correlations were observed between US-CLARA and both DAS28-CRP and DAS28-ESR. Higher correlations were also found between US-CLARA and both SDAI and CDAI scores. Responsiveness: internal responsiveness was wide, with SRM and ES ranging from 0.91 to 1.51. US-CLARA responsiveness was similar to that of DAS28, SDAI, or CDAI. Similarly, the area under ROC curve (AUC-ROC) of US-CLARA gives identical results. The AUC of cumulative inflammatory burden, calculated during the 6-months follow-up of all combinations were highly correlated (p < 0.0001). Interpretability: cutoff values for REM, US-CLARA <2.0; for LDA, 2.0 ≤US-CLARA <3; for MDA, 3 ≤US-CLARA ≤4.8; for HDA, US-CLARA >4.8. CONCLUSION: The US-CLARA is valid and sensitive tool to assess disease activity in RA.
29584788 IL-17A, IL-17RC polymorphisms and IL17 plasma levels in Tunisian patients with rheumatoid 2018 BACKGROUND: Interleukin-17 (IL-17), a cytokine mainly secreted by Th17 cells, seems to play a significant role in the pathogenesis of rheumatoid arthritis (RA). Functional genetic polymorphisms in IL-17 and its receptor genes can influence either qualitatively or quantitatively their functions. Therefore, we aimed to study the impact of IL17-A and IL17RC polymorphisms on plasma level of IL-17 and RA susceptibility and severity. METHODS: In this context, IL-17A*rs2275913 and IL-17RC*rs708567 polymorphisms were investigated together with the quantification of IL17 plasma level in 115 RA patients and 91 healthy control subjects matched in age, sex and ethnic origin. RESULTS: There were no statistically significant associations between IL-17A and IL-17RC studied polymorphisms and RA susceptibility. In contrast, IL-17A plasma levels were significantly higher in patients (55.07 pg/ml) comparatively to controls (4.75 pg/ml), p<10E-12. A ROC curve was used to evaluate the performance of plasma IL-17 in detecting RA. Given 100% specificity, the highest sensitivity of plasma IL-17A was 61.7% at a cut-off value of 18.25 pg/ml; p < 10E-21, CI = [0.849-0.939]. Analytic results showed that the IgM-rheumatoid factor and anti-CCP antibodies were significantly less frequent in patients with the IL-17RC*A/A genotype than those carrying *G/G and *G/A genotypes; p = 0.013 and p = 0.015, respectively. Otherwise, IL-17 plasma levels' analysis showed a significant association with the activity of RA (DAS28≥5.1 = 74.71 pg/ml vs. DAS28<5.1 = 11.96 pg/ml), p<10E-6. CONCLUSION: IL-17A*rs2275913 (G/A) and IL-17RC*rs708567 (G/A) polymorphisms did not seem to influence RA susceptibility in Tunisian population. This result agrees with those reported previously. Plasma IL-17A level seems to be predictive of severe RA occurrence.
29516758 Targeted delivery of hyaluronic acid-coated solid lipid nanoparticles for rheumatoid arthr 2018 Nov Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease. Long-term, high-dose glucocorticoid therapy can be used to treat the disease, but the fact that the drug distributes systemically can give rise to severe adverse effects. Here we develop a targeted system for treating RA in which the glucocorticoid prednisolone (PD) is encapsulated within solid lipid nanoparticles (SLNs) coated with hyaluronic acid (HA), giving rise to HA-SLNs/PD. HA binds to hyaluronic receptor CD44, which is over-expressed on the surface of synovial lymphocytes, macrophages and fibroblasts in inflamed joints in RA. As predicted, HA-SLNs/PD particles accumulated in affected joint tissue after intravenous injection into mice with collagen-induced arthritis (CIA), and HA-SLNs/PD persisted longer in circulation and preserved bone and cartilage better than free drug or drug encapsulated in SLNs without HA. HA-SLNs/PD reduced joint swelling, bone erosion and levels of inflammatory cytokines in serum. These results suggest that encapsulating glucocorticoids such as PD in HA-coated SLNs may render them safe and effective for treating inflammatory disorders.
30142184 Non-alcoholic steatohepatitis-like pattern in liver biopsy of rheumatoid arthritis patient 2018 OBJECTIVE: The mechanism of liver injury with low-dose methotrexate (MTX) is incompletely understood. This study was designed to evaluate the association between non-alcoholic fatty liver disease (NAFLD) and liver injury during MTX treatment for rheumatoid arthritis (RA). METHODS: Between October 2014 and May 2015, we enrolled all MTX users for RA and monitored participant serum hepatic transaminase levels for 1 year. All patients had normal transaminase levels before the first MTX prescription. Using diagnostic criteria for non-alcoholic steatohepatitis (NASH), we performed histological analyses for patients presenting persistent transaminitis, defined as elevations of hepatic transaminases in four of six determinations during the follow-up period. Possible risk factors for persistent transaminitis were also examined. RESULTS: We followed 846 RA patients with a mean cumulative MTX dose of 2.48 g and identified 51 patients presenting persistent transaminitis. According to multivariate logistic regression analysis, obesity (odds ratio [OR] 3.23, p < 0.001), type 2 diabetes (OR 3.52, p = 0.001), hypercholesterolemia (OR 2.56, p = 0.004), and hyperuricemia (OR 3.52, p = 0.019), which are recognized as risk factors for NAFLD, were independently associated with a risk of persistent transaminitis. Among patients with persistent transaminitis, 42 showed fatty liver at ultrasonography. These patients had no evidence of alcoholic fatty liver, chronic viral hepatitis, autoimmune liver diseases, or hereditary liver diseases. Biopsy specimens were obtained from 32 patients, and we found that a NASH-like pattern was the most prevalent histological abnormality. There was no significant impact of MTX dose and duration on the histological severity. CONCLUSION: Risk factors and histological findings are similar between NAFLD/NASH and liver injury during low-dose MTX treatment for RA, which suggests a strong association between both entities. NAFLD/NASH may be an underlying condition causing persistent transaminitis in MTX-treated RA patients. The results of this study illustrate the need for monitoring liver injury in RA patients with NAFLD risk factors during MTX treatment.
30345642 Association between rheumatoid arthritis and genetic variants of natural resistance-associ 2018 Sep AIM: To evaluate the association between natural resistance-associated macrophage protein 1 (NRAMP1) polymorphisms and rheumatoid arthritis (RA). METHOD: All related studies were retrieved and screened from PubMed, CNKI and Web of Science. Pooled odds ratios (ORs) and 95% CIs were assessed for the strength of association between NRAMP1 and RA. Publication bias was measured by Begg's funnel plot and Egger's regression test. The robustness of this meta-analysis was detected by sensitivity analysis. RESULTS: A total of five eligible publications were included in the present meta-analysis. The polled data showed no association between RA and NRAMP1 D543N and 1729 + 55del4 in the allele model. However, the relationship between RA and NRAMP1 INT4 was statistically significant (OR 1.65, 95% CI 1.14-2.38). Genotypic analysis demonstrated that there were no associations between RA and NRAMP1 D543N, 1729 + 55del4 and INT4 in homozygous comparison (D543N: OR 0.97, 95% CI 0.15-6.09; 1729 + 55del4: OR 1.19, 95% CI 0.29-24.88; INT4: OR 3.18, 95% CI 0.62-16.26), dominant model (D543N: OR 1.04, 95% CI 0.61-61.78; 1729 + 55del4: OR 1.41, 95% CI 0.81-2.47; INT4: OR 1.22, 95% CI 0.72-2.06) and recessive model (D543N: OR 0.93, 95% CI 0.15-5.91; 1729 + 55del4: OR 0.99, 95% CI 0.26-3.86; INT4: OR 2.95, 95% CI 0.61-14.16). In heterozygous comparison, it no association was shown between RA and NRAMP1 D543N and INT4, excepting NRAMP1 1729 + 55del4 (OR 1.73, 95% CI 1.17-2.56). Further subgroup analysis indicated that NRAMP1 1729 + 55del4 and INT4 were related to RA in Asia and in the Hardy-Weinberg equilibrium group. There exists no publication bias in this meta-analysis. CONCLUSION: This meta-analysis indicated that NRAMP1 1729 + 55del4 and INT4 confer susceptibility to RA.
28735350 Inflammatory Joint Disorders and Neutrophilic Dermatoses: a Comprehensive Review. 2018 Apr Rheumatoid arthritis and spondyloarthritis are inflammatory joint disorders with an autoimmune pathogenesis and systemic involvement. The skin is one of the most frequently affected extraarticular sites with a number of manifestations or distinct diseases, including common conditions, such as rheumatoid nodules and psoriasis, and rare diseases like neutrophilic dermatoses. The latter are clinically characterised by polymorphic lesions, including pustules, bullae, abscesses, papules, nodules, plaques and ulcers, and histologically by neutrophil-rich inflammatory infiltrates. Inflammatory joint disorders and neutrophilic dermatoses share a number of pathophysiological features related to their cytokine overexpression profile. Moreover, any organ system can be potentially involved in neutrophilic dermatoses, giving rise to the concept of neutrophilic disease. Among the extracutaneous manifestations of neutrophilic disease, joint involvement is regarded as the most common. It is not associated with erosions and disability and usually responds to treatment for skin involvement, consisting of systemic corticosteroids and, in refractory cases, immunosuppressants or biologics. Arthritis may also be the initial manifestation of rheumatoid arthritis or spondyloarthritis, which has a chronic or recurrent course and requires a continuous treatment with synthetic or biologic disease-modifying anti-rheumatic drugs. If not properly treated, they may be associated with disability and reduced quality of life. Skin lesions occurring during the course of rheumatoid arthritis and spondyloarthritis require a multidisciplinary approach envisaging the collaboration of dermatologists and rheumatologists in order to achieve early diagnosis and treatment. Several biomarkers may help the clinician in the differential diagnosis of arthritis while histology is pivotal for the correct classification of the skin disease. However, in some cases, only regular follow-up allows a definite diagnosis. In this review article, we focus on the prototypic neutrophilic dermatoses like pyoderma gangrenosum, Sweet's syndrome, hidradenitis suppurativa and their syndromic forms as well as on their articular involvement, providing a simple approach for their diagnosis and therapy.