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ID PMID Title PublicationDate abstract
28970215 Metabolic and cardiovascular benefits of hydroxychloroquine in patients with rheumatoid ar 2018 Jan OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of mortality in patients with rheumatoid arthritis (RA). Hydroxychloroquine (HCQ) has been shown to improve survival rates in other inflammatory diseases. We aimed to assess the available literature on the cardiovascular impact of HCQ in patients with RA. METHODS: We systematically searched for studies evaluating the effects of HCQ on cardiovascular outcomes of known risk factors for CVD in patients with RA. Databases searched were MEDLINE (via PubMed), EMBase, Cochrane Library and the American College of Rheumatology and European League Against Rheumatism annual meetings. A meta-analysis was performed with a random-effects model, estimating mean differences (MDs), HRs and 95% CIs. Data were extracted by one investigator and independently checked by another. RESULTS: The literature search revealed 185 articles and abstracts of interest; further examination resulted in 16 studies fulfilling the criteria. The MDs between HCQ users and non-users in levels of total, low-density and high-density cholesterol and triglycerides were -9.8 (95% CI -14.0 to -5.6), -10.6 (95% CI -14.2 to -7.0), +4.1 (95% CI 2.2 to 6.0) and -19.2 (95% CI -27.2 to -11.1), respectively. Diabetes incidence was lower for HCQ ever users than never users (HR 0.59 (95% CI 0.49 to 0.70)). HCQ seemed to decrease insulin resistance and incidence of CVD, but data were too few for meta-analysis. CONCLUSION: Besides its limited efficacy for disease activity and progression, HCQ may benefit the metabolic profile and to a lesser extent cardiovascular events in patients with RA, which suggests its usefulness combined with other conventional synthetic disease-modifying antirheumatic drugs.
30328699 Effectiveness of Acupuncture on Pain, Functional Disability, and Quality of Life in Rheuma 2019 Jan BACKGROUND: Rheumatoid arthritis (RA) is characterized by pain, functional disability, poor quality of life (QoL), high socioeconomic impact, and annual costs of over $56 billion in the United States. Acupuncture (AC) is widely in use; however, studies show severe methodological shortcomings, did not consider the functional diagnosis for the allocation of acupoints and their results showed no differences between verum and control groups. OBJECTIVE: The authors aimed to objectively assess the safety and efficacy of AC treatments for RA. METHODS: 105 RA patients with a functional diagnosis of a "Pivot syndrome" or "Turning Point syndrome" were randomly assigned to (1) verum-AC (verum acupoints), (2) control-AC (sham acupoints-points outside of the conduits/meridians and of the extra-conduits), or (3) waiting list (each group n = 35). AC groups experienced the exact same number, depth, and stimulation of needles. Assessments took place before and 5 min after AC with follow-ups over 4 weeks. RESULTS: (1) Verum-AC significantly improved self-reported pain (Z = -5.099, p < 0.001) and pressure algometry (Z = -5.086, p < 0.001); hand grip strength (Z = -5.086, p < 0.001) and arm strength (Z = -5.086, p < 0.001); health status improved significantly (p < 0.001, Z = -4.895); QoL improved significantly in 7/8 survey domains; and number of swollen joints (Z = -2.862, p = 0.004) and tender joints (Z = -3.986, p < 0.001) significantly decreased. (2) Control-AC showed no significant changes, except in self-reported pain improvement. (3) Waiting list group showed an overall worsening. CONCLUSION: This is the first double-blind controlled study on AC in RA of the hand that objectively and specifically assesses positive effects supporting its integration in rheumatology. Acupoint allocation according to Chinese Medicine functional diagnoses is extremely relevant to assess AC effectiveness in a patient group primarily defined by a "western" medicine diagnosis. Based on clear allocation criteria for acupoints, the authors minimized the possible bias of unspecific and suggestive effects on the control group, showed the specific effects of the points chosen, improved efficacy, and identified an evidence base for AC.
29063463 Prevalence of depression and anxiety in rheumatoid arthritis patients and their associatio 2018 Jan Vitamin D deficiency may be associated with depression in the general population. This study aimed to describe the prevalence of depression and anxiety in rheumatoid arthritis (RA) patients from Northwestern China and identify associations of Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) scores with serum vitamin D level in these patients. We recruited 161 RA patients inform the First Affiliated Hospital of Xi'an Jiaotong University during Nov. 2016 to Feb. 2017. All patients completed a survey including HAMD and HAMA scales. RA activity (DAS28) was scored by a rheumatologist, and serum 25-OH-D3 levels were measured by electrochemiluminescence immunoassay. The data were analyzed using the SPSS16.0 based on "possible and probable" cut points for HAMD and HAMA. About 62 and 60% of patients had some degrees of depression and anxiety, respectively. The mean of serum 25-OH-D3 levels in RA patients with depression was 15.24 ± 8.78 ng/mL, which was significantly lower than those without depression (24.68 ± 10.98 ng/mL, p = 0.009). Despite negative correlations between serum 25-OH-D3 level and the score of HAMD (r = - 0.520, p < 0.001) or HAMA (r = - 0.469, p < 0.001), there was a positive correlations between DAS28and the score of HAMD (r = 0.459, p = 0.001) or HAMA (r = 0.486, p < 0.001). The multivariate logistic regression showed that disease duration, serum 25-OH-D3 level, and treatment of tumor necrosis factor inhibitor were associated with depression/anxiety in RA patients. Our study shows a high prevalence of depression and anxiety in RA patients from Northwestern China. Both disease activity of RA and low serum 25-OH-D3 level are associated with the severity of depression and anxiety. It is imperative for clinicians to screen hypovitaminosis of vitamin D and depression/anxiety in RA patients.
28198159 Meta-analysis of associations between XRCC1 gene polymorphisms and susceptibility to syste 2018 Jan OBJECTIVE: To determine whether X-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms confer susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). A meta-analysis was conducted to determine the associations between XRCC1 gene polymorphisms and susceptibility to SLE and RA. METHODS: A systematic literature search was conducted to identify all relevant studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of the association. RESULTS: A total of nine case-control articles, consisting of five SLE and four RA articles, involving 1138 patients and 1399 healthy controls, were included in the meta-analysis. This meta-analysis showed no significant association of the Arg399Gln and Arg194Trp polymorphisms with SLE were found in all models when all study subjects were considered together. Stratification by ethnicity indicated the variant Arg399 (A) allele carriers increased the risk of SLE in Asians (A vs. G: OR = 1.402, 95% CI = 1.139-1.726, P = 0.001) and decreased the risk of SLE in Caucasians (A vs. G: OR = 0.769, 95% CI = 0.630-0.937, P = 0.009; AA vs. AG+GG: OR = 0.727, 95% CI = 0.554-0.953, P = 0.021). However, we failed to reveal any association between XRCC1 gene polymorphisms (Arg399Gln, Arg280His and Arg194Trp) and RA risk under all analysis models. Similar results were obtained in the subgroup analysis based on ethnicity. CONCLUSIONS: The present study suggests that the XRCC1 Arg399Gln polymorphism might be associated with genetic susceptibility to SLE in Asians and Caucasians, and there is no significant association between XRCC1 gene polymorphisms (Arg399Gln, Arg280His and Arg194Trp) and RA risk.
30474480 Increased expression of the proprotein convertase enzyme FURIN in rheumatoid arthritis. 2019 May OBJECTIVE: FURIN is a proprotein convertase enzyme that inhibits the proinflammatory function of T cells and myeloid cells. Elevated FURIN expression levels have been reported in immune-mediated diseases, such as primary Sjögren's syndrome. Here, we investigated the levels of FURIN in peripheral blood (PB) and synovial fluid (SF) leucocytes from patients with rheumatoid arthritis (RA). METHOD: FURIN mRNA expression in PB and SF cells was determined by quantitative reverse transcription-polymerase chain reaction and FURIN plasma levels were measured using enzyme-linked immunosorbent assay. Associations between FURIN levels and demographic and clinical characteristics of the patients were determined. RESULTS: FURIN levels were significantly elevated in PB and SF mononuclear cells, T cells, and monocytes from RA patients compared to healthy controls. High FURIN levels were significantly associated with the prevailing prednisolone treatment, higher prednisolone doses, and increased C-reactive protein levels and Health Assessment Questionnaire values. CONCLUSION: FURIN is significantly upregulated in RA PB and SF leucocytes, suggesting that it may have a role in the pathogenesis of RA. In addition, our results suggest that elevated FURIN expression is associated with the indicators of more severe RA.
28722504 Role of tenascin-C in articular cartilage. 2018 Mar Tenascin-C (TN-C) is a glycoprotein component of the extracellular matrix (ECM). TN-C consists of four distinct domains, including the tenascin assembly domain, epidermal growth factor-like repeats, fibronectin type III-like repeats, and the fibrinogen-like globe (FBG) domain. This review summarizes the role of TN-C in articular cartilage. Expression of TN-C is associated with the development of articular cartilage but markedly decreases during maturation of chondrocytes and disappears almost completely in adult articular cartilage. Increased expression of TN-C has been found at diseased cartilage and synovial sites in osteoarthritis (OA) and rheumatoid arthritis (RA). TN-C is increased in the synovial fluid in patients with OA and RA. In addition, serum TN-C is elevated in RA patients. TN-C could be a useful biochemical marker for joint disease. The addition of TN-C results in different effects among TN-C domains. TN-C fragments might be endogenous inducers of cartilage matrix degradation; however, full-length TN-C could promote cartilage repair and prevent cartilage degeneration. The deficiency of TN-C enhanced cartilage degeneration in the spontaneous OA in aged joints and surgical OA model. The clinical significance of TN-C effects on cartilage is not straightforward.
29848348 The course of pain hypersensitivity according to painDETECT in patients with rheumatoid ar 2018 May 30 BACKGROUND: Evidence is emerging that pain in rheumatoid arthritis (RA) exists without underlying inflammation. Our objective was to evaluate the prognostic value of pain classification at treatment initiation using the painDETECT questionnaire (PDQ). Outcomes were change in DAS28-CRP and RAMRIS synovitis score. METHODS: RA patients initiating a disease-modifying anti-rheumatic drug (DMARD) or initiating/ switching a biological agent were included. Follow-up time was 4 months. Clinical examination, imaging (MRI, dynamic contrast-enhanced MRI (DCE-MRI)), and patient-reported outcomes were undertaken. The PDQ was used to differentiate pain mechanisms. Mean change (95% CI) was calculated using ANCOVA. Multivariable regression models were used to determine a prognostic value. RESULTS: A total of 102 patients were included; 75 were enrolled for MRI. Mean changes in baseline variables were greatest in the high PDQ classification group (> 18), while limited in the intermediate group (13-18). The 12 patients with high baseline PDQ score all changed pain classification group. No prognostic value of PDQ pain classification was found in relation to change of DAS28-CRP, RAMRIS score, or VAS pain. In the unadjusted model, RAMRIS score at baseline was associated with change in DAS28-CRP. The exploratory variables of DCE-MRI did not differ from other inflammatory variables. CONCLUSIONS: In RA patients a high PDQ score (non-nociceptive pain) at baseline was not associated with worse outcomes, in fact these patients had numerically greater improvement in DAS28-CRP. However, pain classification by PDQ was not independently associated with change in DAS28-CRP, RAMRIS score, or VAS pain in the prognostic models. Furthermore, patients classified with a high baseline PDQ score changed pain classification group. Patients with unclear pain mechanism had reduced numerically treatment response. TRIAL REGISTRATION: The study was approved by the Regional Ethics Committee of the Capital of Denmark April 18 2013; identification number H-3-2013-049 .
29779702 Vitamin D is not useful as a biomarker for disease activity in rheumatoid arthritis. 2020 Mar OBJECTIVE: To determine whether there is an association between serum vitamin D levels and the Disease Activity Index in patients with rheumatoid arthritis (RA). METHODOLOGY: An analytical, retrospective, cross-sectional study was performed at the Hospital Luis Vernaza and Center for Rheumatology and Rehabilitation. We included 18 to 75-year-old patients with a diagnosis of RA according to the 2010 classification criteria, and with a 25-hydroxyvitamin D (25 [OH] D) test within the last 3 months. The activity of the disease was assessed with the 28-joint Disease Activity Score (DAS28) and C-reactive protein (CRP) as an acute-phase reactant. Spearman's rank correlation coefficient was used to establish association between the variables. RESULTS: A total of 100 RA patients were studied. The mean vitamin D levels were 32.9 ± 11.5 ng/mL. In all, 45% showed insufficient 25 (OH) D and 55% had normal levels; no deficient vitamin D values were found. According to the DAS28-CRP, patients with low, moderate and high activity had an average vitamin D level of 30.4 ± 10.7, 31.9 ± 10.7, and 31.8 ± 12.1 ng/mL, respectively. There were no significant correlations between the disease activity and the serum vitamin D level (P=.60). CONCLUSION: In our group of RA patients, there was no statistically significant correlation between the levels of vitamin D and the activity of the disease, nor were other determining variables associated with vitamin D levels.
29411043 HIF-1A gene polymorphisms and its protein level in patients with rheumatoid arthritis: a c 2018 May OBJECTIVES: The aim of the study was to identify HIF-1A genetic variants and their possible association with HIF-1α, VEGF, KDR, RORc and Foxp3 protein levels, and susceptibility to and severity of RA. METHODS: The HIF-1A gene polymorphisms were genotyped for 587 RA patients and 341 healthy individuals. The HIF-1α, VEGF, KDR, RORc and Foxp3serum levels were evaluated. RESULTS: Under the codominant model, the frequency of the rs12434438 GG genotype was lower in RA patients than in controls (P = 0.02). Under the recessive model (AA + AG vs GG), the association was also significant (OR 3.32; CI 1.19-9.24; P = 0.02). Overall, rs12434438 A/G and rs1951795 A/C are in almost completed linkage disequilibrium with D' = 0.96 and r(2) = 0.85. The HIF-1A rs1951795 A allele was associated with rheumatoid factor (P = 0.02) and mean value of erythrocyte sedimentation rate (ESR) (P = 0.05). In RA patients with HIF-1A rs12434439 GG genotype, the parameters of disease activity such as DAS-28, VAS score, Larsen score or HAQ score were lower compared to RA patients with the HIF-1A rs12434439 AA genotype. Moreover, we also observed that Foxp3 serum levels were higher, and RORc2 serum levels were lower in RA patients with rs12434439 GG. CONCLUSION: The polymorphic HIF-1A rs12434439 GG genotype may play a protective role for RA development.
28912189 Associations between circulating macrophage migration inhibitory factor (MIF) levels and r 2018 Feb AIM: To systematically review evidence regarding the relationship between circulating macrophage migration inhibitory factor (MIF) levels and rheumatoid arthritis (RA), and the association between MIF gene polymorphisms and RA susceptibility. DESIGN: We performed a meta-analysis on data of serum/plasma MIF levels in patients with RA and in controls, and on associations between the MIF-173 C/G and -794CATT(5-8) polymorphisms and RA susceptibility. PATIENTS: Twelve studies, comprising a total of 362 RA cases and 531 controls evaluated for MIF levels, and 2367 RA cases and 2395 controls evaluated for MIF polymorphisms, were included. RESULTS: MIF levels were significantly higher in the RA group than in the control group (standardised mean difference (95% CI) 0.923 (0.766 to 1.080), p<0.001). Stratification by ethnicity revealed significantly higher MIF levels in the RA group in Caucasian, Asian and Latin American populations. MIF levels were significantly higher in patients with RA, regardless of adjustment, sample size or data type evaluated. RA was identified to be significantly associated with the MIF-173 C allele (OR (95% CI) 1.271 (1.141 to 1.416), p<0.001), as well as with the -794CATT(7) allele (OR (95% CI) 1.229 (1.084 to 1.415), p=0.002) and the -794CATT(7)-MIF-173C haplotype RA (OR (95% CI) 1.433 (1.138 to 1.805), p=0.002). CONCLUSIONS: Our meta-analyses revealed significantly higher circulating MIF levels in patients with RA, and found evidence of associations between the MIF-173 C/G and -794CATT(5-8) polymorphisms and RA susceptibility.
29475856 Biomechanical properties of bone are impaired in patients with ACPA-positive rheumatoid ar 2018 Jul OBJECTIVES: Bone loss is a well-established consequence of rheumatoid arthritis (RA). To date, bone disease in RA is exclusively characterised by bone density measurements, while the functional properties of bone in RA are undefined. This study aimed to define the impact of RA on the functional properties of bone, such as failure load and stiffness. METHODS: Micro-finite element analysis (µFEA) was carried out to measure failure load and stiffness of bone based on high-resolution peripheral quantitative CT data from the distal radius of anti-citrullinated protein antibody (ACPA)-positive RA (RA+), ACPA-negative RA (RA-) and healthy controls (HC). In addition, total, trabecular and cortical bone densities as well as microstructural parameters of bone were recorded. Correlations and multivariate models were used to determine the role of demographic, disease-specific and structural data of bone strength as well as its relation to prevalent fractures. RESULTS: 276 individuals were analysed. Failure load and stiffness (both P<0.001) of bone were decreased in RA+, but not RA-, compared with HC. Lower bone strength affected both female and male patients with RA+, was related to longer disease duration and significantly (stiffness P=0.020; failure load P=0.012) associated with the occurrence of osteoporotic fractures. Impaired bone strength was correlated with altered bone density and microstructural parameters, which were all decreased in RA+. Multivariate models showed that ACPA status (P=0.007) and sex (P<0.001) were independently associated with reduced biomechanical properties of bone in RA. CONCLUSION: In summary, µFEA showed that bone strength is significantly decreased in RA+ and associated with fractures.
30289535 20 years of experience with tumour necrosis factor inhibitors: what have we learned? 2018 Oct 1 TNF inhibitors are biologic DMARDs approved for the treatment of active RA in mid-1990s. They still represent a valuable therapeutic option to control the activity, disability and radiographic progression of the disease. In the context of TNF inhibitors, there are currently several molecules and different administration routes that provide optimal treatment personalization, allowing us to respond to a patient's needs in the best possible way. The increasing use of TNF inhibitors has not only improved the management of RA, but it has also helped in our understanding of the pathogenetic mechanisms of the disease. This review focuses on the basis of this targeted therapy and on the knowledge gained from their use about therapeutic effects and adverse events. Effectiveness analysed from drug registries and safety issues are presented together with recent data on infections (in particular, Mycobacterium tuberculosis and hepatitis B), cancer (lymphoma, skin cancers) and cardiovascular risk.
29409764 Unsaturated aldehyde, 4-hydroxynonenal (HNE) alters the structural integrity of HSA with c 2018 Jun Human serum albumin (HSA) - the most abundant plasma protein plays an important role in the transport of endogenous and exogenous molecules in the body. Its modifications have been implicated in a variety of pathological disorders. We have studied the interaction of HNE with HSA at a molecular level by docking experiment and the results suggest a strong interaction between HNE and HSA. Immunological studies revealed that the circulating auto-antibodies in rheumatoid arthritis (RA) patients have a stronger affinity towards HNE-modified HSA. The HSA isolated from RA patients (RA-HSA) exhibited HNE mediated damage in its secondary and tertiary structure when compared to HSA derived from healthy human subjects (NH-HSA). RA patients presented a significant rise in carbonyls and a considerable decline in free thiol content. Preferential binding of experimentally induced anti-HNE-HSA antibodies to RA-HSA over NH-HSA was observed by ELISA. The results suggest HNE induced structural perturbations in HSA with neoepitopes that generate anti-HNE-HSA antibodies in RA. Hence, HNE-HSA may provide lead towards the development of a biomarker for the disease.
30431436 Relationship of epigenetic variability of miR-124 to extracellular matrix remodelling and 2018 Sep The aim of study was to examine relation among miR-124 and serum levels of selected cytokines and chemokines, MMP-3, production of auto-antibodies, and factors describing clinical activity (DAS28) and radiographic progression in rheumatoid arthritis (RA). A total of 80 RA patients according to the ACR classification criteria, and 32 control subjects were recruited into study. The measurements of miR-124 and U-6 expression, CRP, anti-CCP, rheumatoid factors (RFs), radiographs of both hands with calculation of total sharp score (TSS), DAS28 and cytokines, chemokines and MMP levels in serum were obtained from all RA patients. miR-124 was down-regulated in RA patients compared to controls (7-fold decrease). The miR-124 expression correlated to MMP-3 levels (p < 0.001), which were in multivariate analysis associated to age of RA onset. Higher levels were detected in younger subjects. No relation of miR-124 expression to measures of RA activity (DAS28 score; TSS), auto-antibodies (anti-CCP, RF, RF IgG, RF IgA, RF IgM), acute inflammatory markers (CRP, IL-6), and other cytokine and chemokines (IL-13, IL-15, IL-8, TNF-α, MCP-1, RANTES) was observed. In conclusion, we present a down-regulation of miR-124 in RA patients and its correlation to MMP-3 levels, which associated to age of RA onset.
30007856 ACPA mediates the interplay between innate and adaptive immunity in rheumatoid arthritis. 2018 Sep The production of anti-citrullinated peptide antibodies (ACPAs) requires the participation of both innate immunity and adaptive immunity. On the one hand, activated innate immunity is able to produce citrullinated auto-antigens that fuel autoimmunity and provide an inflammatory environment that facilitates the breach of self-tolerance, proliferation of self-reactive T/B cells and the production of ACPAs. On the other hand, after their production by plasma B cells, ACPAs are also able to interact with innate immunity to exacerbate the manifestation and chronicity of rheumatoid arthritis (RA). This article discusses the roles of citrullinated peptides and ACPA played in innate immunity and autoimmunity. In addition, we emphasise the relationships between environmental factors and innate immunity, as well as the pathogenic function of ACPAs per se. In doing so, we hope to provide fundamental knowledge of RA pathogenesis and reveal potential therapeutic targets in RA treatment.
28826660 Anti -citrullinated peptide antibodies profiling in established rheumatoid arthritis. 2018 Jul OBJECTIVES: Anti-citrullinated protein/peptide antibodies (ACPA) represent an important tool for the diagnosis of rheumatoid arthritis (RA) and the presence of multiple ACPA specificities is highly correlated with the evolution towards RA. However, little is known about the association of single specificities with disease manifestations and response to therapy in established RA. The aim of this work is to evaluate in a retrospective study the clinico-serological association of ACPA detected using VCP1 and VCP2 (EBV-derived citrullinated peptides) and HCP1 and HCP2 (histone-H4-derived citrulinated peptides) in established RA. METHODS: In 413 RA patients, anti-VCP1, -VCP2, -HCP1, -HCP2 were measured by ELISA. Patients were evaluated for systemic involvement, disease activity/severity, ongoing and past therapies. Data were analyzed by cluster analysis (CA) and principal component analysis (PCA). RESULTS: Anti-VCP1 were detected in 44% of RA patients; anti-VCP2 in 52%; anti-HCP1 in 46% and anti-HCP2 in 63%. CA and PCA independently demonstrated that ACPA levels are associated with RF positivity, and lung involvement. Subdividing patients in 5 groups according to the number of anti-peptide antibodies, mean antibody level and RF positivity, as well as the frequency of lung involvement, progressively increase in parallel with the number of ACPA specificities. CONCLUSIONS: Higher number/levels of ACPA subtypes is associated with lung involvement but not with erosive disease. Moreover, a broader ACPA repertoire may identify patients treated with biological therapy, probably affected by a more severe disease. In conclusion, ACPA typing might be relevant for a better characterization of some disease features in established RA.
29341936 Rheumatic manifestations among cancer patients treated with immune checkpoint inhibitors. 2018 Mar BACKGROUND: The use of immune checkpoint inhibitors (ICI) has grown incessantly since they were first approved in 2014. These monoclonal antibodies inhibit T cell activation, yielding a dramatic tumor response with improved survival. However, immunotherapy is frequently hampered by immune adverse events (iAE) such as hypophysitis, colitis, hepatitis, pneumonitis and rash. Until recently, rheumatic side effects were only infrequently reported. AIM: To describe the rheumatic manifestations encountered among patients treated with ICIs in a large tertiary cancer center in Israel METHODS: The cancer center's patient registry was screened for patients who had ever been treated with ipilimumab, pembrolizumab and/or nivolumab with relevant data gathered from clinical charts. RESULTS: Rheumatic manifestations were encountered in 14 of 400 patients (3.5%) who had received immunotherapy between January 1st 2013 and April 30th, 2017. The most common rheumatic manifestation was inflammatory arthritis (85%) for which a third (4/11) had a clear cut predisposing factor such as a personal or family history of psoriasis, a prior episode of uveitis or ACPA positivity. Pulmonary sarcoidosis and biopsy-proven eosinophilic fasciitis were diagnosed in two additional patients. Treatment with NSAIDS was mostly unsuccessful while steroid therapy was beneficial in doses ≥20 mg/d. Methotrexate enabled steroid tapering without an excess of side effects or tumor progression in the short follow-up available. Overall, rheumatic manifestations tended to occur later in the course of immunotherapy as compared to other iAE. CONCLUSIONS: Our findings underscore that rheumatic iAE are part of the side effect profile of ICIs and require heightened awareness as these therapies are becoming the standard of care for various malignancies. We show that these appear later in the course of iAEs and respond preferentially to high dose steroids. MTX appears effective as a steroid sparing agent.
29034486 'Everyone assumes a man to be quite strong': Men, masculinity and rheumatoid arthritis: A 2018 Jan Current literature has overlooked the impact of chronic illness on masculine identity. We therefore aimed to investigate the impact of rheumatoid arthritis (a long term condition, affecting more women than men) on masculine identity. Six focus groups with 22 men with rheumatoid arthritis (RA) (data reported elsewhere) followed by five one-to-one interviews with men (English, mean age: 59 years) sampled to reflect a heterogeneous experience of life with RA based on knowledge gained from the focus groups. Transcripts were analysed using thematic analysis and are presented as individual case studies. Whilst the case studies provide five distinct experiences, common themes can be drawn across them, such as the importance of paid work. The men needed to renegotiate their masculine identity to deal with their RA. Two dealt with this by pushing through pain to retain masculine activities, two replaced masculine roles they could no longer do with other roles, and one rejected masculinity completely. Men with long term conditions may need to re-write their masculinity scripts to enable them to accept and adapt to their condition. However, some men struggle with this, which should be taken into consideration when designing self-management services for men with long term conditions.
29067846 Origins of fibroblasts in rheumatoid synovial tissues: Implications from organ fibrotic mo 2018 Jul Fibroblasts play crucial roles in the pathogenesis of rheumatoid arthritis (RA). Accumulation of fibroblasts in the synovial tissues characterizes the pathology of RA. Understanding how fibroblasts accumulate could lead to discovery of new therapeutic targets in RA treatment, while current antirheumatic therapies still have problems in efficacy and safety. In this regard, several studies have revealed cellular origins of fibroblasts in fibrotic tissues in murine models of organ fibrosis. Some studies employed lineage tracing, which bring generally convincing results, using transgenic mice. They demonstrated that resident fibroblasts, pericytes, mesenchymal stem cells, epithelial cells, endothelial cells and bone-marrow-derived and circulating cells can be cellular origins of fibroblasts in organ fibrotic tissues. In this review, we summarize and discuss available evidence for the origins of fibroblasts accumulating in the arthritic synovial tissues and organ fibrotic tissues.
28302039 Bone Degeneration, Inflammation and Secondary Complications of Arthritis: Potential Target 2018 Arthritis is marked by joint deterioration that affects articular cartilage and subchondral bone. Though cartilage degradation does the major damage during arthritis, subsequent bone degeneration cannot be neglected. Recent progress in arthritis research has identified the clinical importance of bone erosion in destructive arthritis. Studies have showed the key role played by osteoclasts and receptor activator of nuclear factor kappaB ligand (RANKL) signaling in bone erosion. Cathepsins and tartrate resistant acid phosphatase (TRAP) are considered key enzymatic factors contributing to bone erosion. Further, reactive oxygen species (ROS) formed at the ruffled border of osteoclasts also causes bone resorption and matrix degradation. Besides, severe inflammation during arthritis induces bone erosion by aiding in Ca2+ removal and activating osteoclastogenesis. The inflammatory cytokines and ROS influence osteoclast differentiation by regulating osteoclast-lineage cells or by acting on other cells to regulate the expression of RANKL and osteoprotegerin (OPG). The enhanced production of pro-inflammatory cytokines and ROS in arthritis stimulates tissue injury by means of oxidative damage leading to vital organ damage and synovial and circulatory cell apoptosis. Thus, blocking enzymatic and non-enzymatic factors responsible for bone erosion and inflammation is considered a prime strategy in the management of arthritis. In this review we provide an overview of the mechanisms of bone erosion, inflammation and associated oxidative stress/damage during arthritis perpetuation along with shedding light on potential targets. The article also describes the possible natural therapeutic agents that could prevent bone loss and inflammation, and related secondary complications of arthritis.