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ID PMID Title PublicationDate abstract
25216947 The incidence and risk factors for falls in adults with rheumatoid arthritis: a systematic 2015 Feb OBJECTIVE: To conduct a systematic review of the incidence and risk factors for falls in people with rheumatoid arthritis (RA). METHODS: A search was conducted of the electronic databases AMED, CINAHL, MEDLINE, Scopus and The Cochrane Library. Study participants were adults with RA. Outcome measures were falls experienced in the preceding 6-12 months or prospective falls over a 12-month period. Articles were scored for quality using a modified version of the Downs and Black Quality Index Tool. RESULTS: Nine articles were included with mean (range) quality scores 72% (43-93%). The quality assessment revealed inconsistency in falls data attainment. Falls incidence ranged from 10% to 50% and was independent of age, gender or RA disease duration. History of a prior fall (odds ratio (OR) = 3.6 and 9.8) and increasing number of medications (OR = 1.4 and 2.1) were consistently associated with falls in RA. Number of co-morbid conditions, swollen and tender lower extremity joints, anti-depressants, anti-hypertensives, psychotropics, pain intensity and static balance were also identified as significant fall risk factors in at least one study. However, the evidence was limited to a single study or conflicted with other studies. CONCLUSION: In studies of falls in people with RA, there is a wide range in reported falls incidence, which may be due to inconsistency in falls data attainment. Numerous potential fall risk factors have been evaluated, producing limited or conflicting evidence. It is recommended that future studies follow previous consensus guidelines for collecting and reporting falls data.
25844967 Depressive symptoms are independently associated with pain perception in Colombians with r 2015 Jan AIMS: To examine the relationships between psychosocial factors and reported pain in Colombians with Rheumatoid Arthritis (RA). METHODS: One hundred and three RA patients [85% from the lowest socio-economic strata (SES) in the country] recruited from outpatient centers in Neiva, Colombia were administered the Disease Activity Scale (DAS) , which included a Visual Analog Scale (VAS) arthritis pain/activity rating, Zung Depression Scale, State-Trait Anxiety Inventory (STAI), Interpersonal Support Evaluation List-12 (ISEL-12), and Symptom Checklist-90 Revised (SCL-90R). MAJOR RESULTS: VAS pain was not associated with socio-demographic or medical factors, but was negatively associated with ISEL tangible subscale (r=-0.22, p< 0.01; r=0.28, p<0.01). VAS pain was positively associated with Zung Depression Scale score (r=0.38, p<0.001), STAI-State and STAI-Trait Anxiety (r=0.23 and r=0.25 respectively, p's<0.01), SCL-90R Global Severity Index (GSI) and Positive Symptom Total (PST) (r=0.23, p<0.05 and r=0.29, p<0.01 respectively), and SCL-90R Somatization, Depression, and Anxiety subscales (r=0.30, p< 0.01; r=0.28, p<0.01; and r=0.20, p<0.05 respectively). A linear regression model showed that socio-demographic characteristics theoretically associated with pain perception (gender, age, and SES) explained only 2.4% of the variance of VAS scores (R(2)=0.02, p=0.49). The full model, including psychosocial factors significantly associated with VAS scores explained 18.9% of the variance in VAS pain perception scores (R(2)=0.19, p=0.02). The Zung Depression Scale score was the only factor independently associated with VAS pain, such that higher depression scores were associated with higher VAS ratings (β =0.13, p<0.01), controlling for gender, age, SES, STAI-State, STAI-Trait, ISEL tangible, SCL-90R GSI, and SCL-90R PST. CONCLUSIONS: Depressive symptoms, anxiety, social support, and psychopathological symptom distress were associated with pain ratings, but only depressive symptoms were found to be uniquely associated with higher pain perception, taking into account socio-demographic characteristics and other psychosocial factors. Findings provide evidence for the need to assess and treat pain in RA in Colombia from a bio-psycho-social perspective. Future research is needed to determine effective depression screening and evidence-based interventions for depressive symptoms in RA patients in this socio-cultural context, as intervening in depression may decrease pain perception.
27556964 Treatment persistence in patients with rheumatoid arthritis and ankylosing spondylitis. 2016 Aug 22 OBJECTIVE: To evaluate treatment persistence in patients with rheumatoid arthritis and ankylosing spondylitis who started therapies with disease-modifying antirheumatic drugs (DMARD) and tumor necrosis factor blockers (anti-TNF drugs). METHODS: This retrospective cohort study from July 2008 to September 2013 evaluated therapy persistence, which is defined as the period between the start of treatment until it is discontinued, allowing for an interval of up to 30 days between the prescription end and the start of the next prescription. Odds ratio (OR) with 95% confidence intervals (95%CI) were calculated by logistic regression models to estimate the patients' chances of persisting in their therapies after the first and after the two first years of follow-up. RESULTS: The study included 11,642 patients with rheumatoid arthritis - 2,241 of these started on anti-TNF drugs (+/-DMARD) and 9,401 patients started on DMARD - and 1,251 patients with ankylosing spondylitis - 976 of them were started on anti-TNF drugs (+/-DMARD) and 275 were started on DMARD. In the first year of follow-up, 63.5% of the patients persisted in their therapies with anti-TNF drugs (+/-DMARD) and 54.1% remained using DMARD in the group with rheumatoid arthritis. In regards to ankylosing spondylitis, 79.0% of the subjects in anti-TNF (+/-DMARD) group and 41.1% of the subjects in the DMARD group persisted with their treatments. The OR (95%CI) for therapy persistence was 1.50 (1.34-1.67) for the anti-TNF (+/-DMARD) group as compared with the DMARD group in the first year for the patients with rheumatoid arthritis, and 2.33 (1.74-3.11) for the patients with ankylosing spondylitis. A similar trend was observed at the end of the second year. CONCLUSIONS: A general trend of higher rates of therapy persistence with anti-TNF drugs (+/-DMARD) was observed as compared to DMARD in the study period. We observed higher persistence rates for anti-TNF drugs (+/-DMARD) in patients with ankylosing spondylitis as compared to rheumatoid arthritis; and a higher persistence for DMARD in patients with rheumatoid arthritis as compared to ankylosing spondylitis. OBJETIVO: Avaliar a persistência do tratamento em pacientes com artrite reumatoide e espondilite anquilosante que iniciaram terapia com medicamentos modificadores do curso da doença (MMCD) e agentes bloqueadores do fator de necrose tumoral (anti-TNF). MÉTODOS: Este estudo de coorte retrospectiva de julho de 2008 a setembro de 2013 avaliou a persistência na terapia, definida como o tempo do início até a descontinuação, permitindo-se um intervalo de até 30 dias entre o fim da prescrição e o início da prescrição seguinte. Odds ratio (OR) com intervalos de confiança de 95% (IC95%) foram calculados por meio de modelos de regressão logística para estimar a chance de apresentar persistência na terapia após o primeiro e os dois primeiros anos de seguimento. RESULTADOS: Foram incluídos 11.642 pacientes com artrite reumatoide - 2.241 iniciaram uso de agentes anti-TNF (+/-MMCD) e 9.401 iniciaram MMCD - e 1.251 pacientes com espondilite anquilosante - 976 iniciaram uso de agentes anti-TNF (+/-MMCD) e 275 iniciaram MMCD. No primeiro ano de acompanhamento, 63,5% persistiram em terapia com anti-TNF (+/-MMCD) e 54,1% em uso de MMCD do grupo com artrite reumatoide. Em relação à espondilite anquilosante, 79,0% do grupo anti-TNF (+/-MMCD) e 41,1% do grupo MMCD persistiram no tratamento. O OR (IC95%) para persistência na terapia foi de 1,50 (1,34-1,67) para o grupo anti-TNF (+/-MMCD) comparado com MMCD no primeiro ano em pacientes com artrite reumatoide, e de 2,33 (1,74-3,11) em pacientes com espondilite anquilosante. Foi observada tendência semelhante ao final do segundo ano. CONCLUSÕES: Observou-se uma tendência geral de taxas mais elevadas de persistência na terapia com anti-TNF (+/-MMCD) em relação a MMCD no período estudado. Foram observadas taxas de persistência mais elevadas para os usuários de anti-TNF (+/-MMCD) em pacientes com espondilite anquilosante em relação a artrite reumatoide, e maior persistência para MMCD em pacientes com artrite reumatoide em relação à espondilite anquilosante.
26666486 Fragmented gelsolins are increased in rheumatoid arthritis-associated interstitial lung di 2016 Jan BACKGROUND: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) occurs in 10%-30% of patients with RA, and interstitial lung disease (ILD) is associated with increased mortality in up to 10% of patients with RA. The pathogenesis of RA-ILD is virtually unknown. The aim of this study is to investigate the proteins related to UIP pattern by comparing to OP pattern in RA-ILD using proteome analysis of bronchoalveolar lavage fluid (BALF). METHODS: Proteomic differences in BALF were compared between the UIP pattern and OP pattern by examining BALF from 5 patients with the UIP pattern and 7 patients with the OP pattern by two-dimensional gel electrophoresis and mass spectrometry. RESULTS: In individual comparisons of BALF samples, the levels of the protein gelsolin and Ig kappa chain C region were significantly higher in the UIP pattern than in the OP pattern. In contrast, the levels of α-1 antitrypsin, CRP, haptoglobin β, and surfactant protein A (isoform number 5) were all significantly higher in the OP pattern than in the UIP pattern. Gelsolin was cleaved into two fragments, a C-terminal half and N-terminal half, and the levels of both were significantly higher in the UIP pattern than in the OP pattern. CONCLUSIONS: Fragmented gelsolins may be associated with the pathogenesis of fibrosis in RA-ILD.
26225917 Expression of Prostaglandin E2 Enzymes in the Synovium of Arthralgia Patients at Risk of D 2015 OBJECTIVE: Arthralgia may precede the development of synovial inflammation in autoantibody-positive individuals at risk of developing rheumatoid arthritis (RA). A major pathway involved in pain is the prostaglandin (PG) E2 pathway. We investigated this pathway in the synovium of individuals with RA-specific autoantibodies and in early arthritis patients. METHODS: Nineteen autoantibody-positive individuals (IgM-rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies) with arthralgia (n=15) and/or a positive family history of RA (n=8), who had been prospectively followed for at least 2 years, were included. In addition, we included early arthritis patients (disease-modifying antirheumatic drug naïve) who after 2 years follow up fulfilled classification criteria for RA (n=63), spondyloarthritis (SpA; n=14), or had unclassified arthritis (UA; n=27). In all subjects we assessed pain and performed synovial biopsy sampling by mini-arthroscopy at baseline. Tissue sections were examined by immunohistochemistry to detect and quantify PGE2 pathway enzymes expression levels (mPGES-1; COX-1 and -2; 15-PGDH). RESULTS: In both study groups synovial expression of PGE2 enzymes was not clearly related to pain sensation. Expression levels at baseline were not associated with the development of arthritis after follow up (6 out of 19 autoantibody-positive individuals). However, in early SpA patients the expression levels of mPGES-1 and COX-1 were significantly increased compared to RA and UA patients. CONCLUSION: Pain in autoantibody-positive individuals without synovial inflammation who are at risk of developing RA and in early arthritis patients may be regulated by pathways other than the PGE2 pathway or originate at sites other than the synovium. In contrast, in SpA, the PGE2 pathway may be inherently linked to the pathophysiology/etiology of the disease.
25766640 Anti-tumour necrosis factor treatment increases circulating T helper type 17 cells similar 2015 Sep We investigated changes in circulating T helper type 17 (Th17) cells following anti-tumour necrosis factor (TNF) in rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) patients. Peripheral blood mononuclear cells (PBMC) were isolated from 25 RA, 15 AS and eight PsA patients at baseline 4 and 12 weeks after treatment, and Th17 cell frequencies were analysed using interleukin (IL)-17 enzyme-linked immunospot (ELISPOT) and flow cytometry. A significant increase in IL-17-producing cells was observed by ELISPOT in RA and AS patients at 12 weeks. Flow cytometry confirmed significant increases in CD4(+) IL-17(+) cells at 12 weeks in RA and AS and 4 weeks in PsA patients. Anti-TNF treatment increases circulating Th17 cells in three different diseases.
27565176 Detection of anti-drug antibodies using a bridging ELISA compared with radioimmunoassay in 2016 Nov OBJECTIVE: To determine the concordance between RIA and bridging ELISA at detecting anti-drug antibodies (ADAbs) in the context of random adalimumab levels and investigate the additional clinical utility of detecting ADAbs in RA patients who test ADAb positive by RIA and negative by ELISA. METHODS: ADAb levels were determined using RIA and bridging ELISA in 63 adalimumab-treated RA patients (159 samples). Immunogenicity concordance was determined using receiver operating characteristic curves. To determine the additional clinical value provided by a positive RIA in the presence of negative ELISA, association between treatment response (ΔDAS28), adalimumab drug levels and ADAbs was evaluated longitudinally using generalized estimating equation. RESULTS: Of the 60 RIA(+) samples (n = 31 patients), 19 (n = 10 patients) were also ELISA(+), corresponding to 31.7% of samples. Area under the curve for detecting ADAbs using ELISA (compared with RIA) using receiver operating characteristic curves was 0.65 (95% CI: 0.59, 0.71); this increased to 0.91 (95% CI: 0.81, 0.99) if ADAbs were ⩾100 AU/ml using RIA. In RIA(+)/ELISA(-) patients, adalimumab levels were associated with ΔDAS28 over 12 months [regression coefficient: 0.098 (95% CI: 0.043, 0.15), P < 0.0001] and while ADAbs were significantly associated with drug level, they were not directly associated with ΔDAS28 over 12 months [β coefficient: 0.00083 (95% CI: -0.0038 to 0.0054), P = 0.72]. CONCLUSION: ADAbs were detected using ELISA more frequently when present in high titres as measured by RIA. In RIA(+)/ELISA(-) patients, only drug levels were significantly associated with treatment response. Although ADAbs were not independently associated with treatment response, they may be helpful in determining the aetiology of low drug levels.
27181685 Efficacy of Combined Ultrasound-and-Microbubbles-Mediated Diclofenac Gel Delivery to Enhan 2016 Aug A previous study that investigated the effect of ultrasound (US) on the transdermal permeation of the non-steroidal anti-inflammatory drug diclofenac found that therapeutic US can increase circulation in an inflamed joint and decrease arthritic pain. Transdermal drug delivery has recently been demonstrated by US combined with microbubbles (MB) contrast agent (henceforth referred to as "US-MB"). The present study evaluated the efficacy of US-MB-mediated diclofenac delivery for treating adjuvant-induced rheumatoid arthritis (RA) in rats. RA was induced by injecting 100 μL of complete Freund's adjuvant into the ankle joint of male Sprague-Dawley rats (250-300 g) that were randomly divided into five treatment groups: (i) carbopol gel alone (the control [group C]), (ii) diclofenac-carbopol gel (group D), (iii) US plus carbopol gel (group U), (iv) US plus diclofenac-carbopol gel (group DU) and (v) US-MB plus diclofenac-carbopol gel (group DUB). The ankle width was measured over 10 d using high-frequency (40-MHz) US B-mode and color Doppler-mode imaging, covering the period before and after treatment. Longitudinal US images of the induced RA showed synovitis and neovascularity. Only a small amount of neovascularity was observed after treatment. The recovery rate on day 10 was significantly higher in group DUB (97.7% ± 2.7%, mean ± standard deviation [SD]) than in groups C (1.0% ± 2.7%), D (37.5% ± 4.6%), U (75.5% ± 4.2%) and DU (87.3% ± 5.2%) (p < 0.05). The results obtained indicate that combining US and MB can increase the skin permeability and thereby enhance the delivery of diclofenac sodium gel and thereby inhibit inflammation of the tissues surrounding the arthritic ankle. Color Doppler-mode imaging revealed that US-MB treatment induced a rapid reduction in synovial neoangiogenesis in the arthritic area.
26313435 An update of neurological manifestations of vasculitides and connective tissue diseases: a 2015 Oct Vasculitides comprise a heterogeneous group of autoimmune disorders, occurring as primary or secondary to a broad variety of systemic infectious, malignant or connective tissue diseases. The latter occur more often but their pathogenic mechanisms have not been fully established. Frequent and varied central and peripheral nervous system complications occur in vasculitides and connective tissue diseases. In many cases, the neurological disorders have an atypical clinical course or even an early onset, and the healthcare professionals should be aware of them. The purpose of this brief review was to give an update of the main neurological disorders of common vasculitis and connective tissue diseases, aiming at accurate diagnosis and management, with an emphasis on pathophysiologic mechanisms.
25974992 Neutrophil- and platelet-to-lymphocyte ratios are correlated with disease activity in rheu 2015 BACKGROUND: Both neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are reported to be increased in various inflammation-related diseases, but their clinical significance in rheumatoid arthritis (RA) remains unclear. The aim of the present study was to explore whether NLR and PLR were candidate indices for RA disease-activity assessment. METHODS: The medical records of 128 RA patients and 78 healthy individuals were retrospectively reviewed. Correlations of NLR and PLR with the disease activity of RA were evaluated. RESULTS: NLR and PLR were increased significantly in RA patients. NLR was significantly positively correlated with C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and Disease-Activity Score including 28 joints (DAS28) in RA patients, while PLR was positively correlated with CRP and DAS28, but not with ESR. CONCLUSIONS: Both NLR and PLR values may prove to be potential indices for RA disease-activity assessment.
26386566 Evaluation of the Safety and Effectiveness of Add-On Tacrolimus in Patients with Rheumatoi 2015 Dec BACKGROUND: Tacrolimus (TAC) is an immunosuppressive macrolide that blocks T-cell activation by specifically inhibiting calcineurin. TAC was approved in Japan for the treatment of rheumatoid arthritis (RA) in 2005. However, the safety and effectiveness of TAC adding on to biological disease-modifying anti-rheumatic drugs (DMARDs) in the real clinical setting may not be clear enough. OBJECTIVES: We report here the interim results of post marketing surveillance (PMS) of TAC adding on to biological DMARDs in RA patients who failed to show an adequate response to biological DMARDs. METHODS: Patients who had an inadequate response to biological DMARDs were enrolled. An inadequate response to biological DMARDs was defined as that all of the following conditions were met: a Simplified Disease Activity Index (SDAI) score of >3.3 when TAC was started; both the tender joint count and swollen joint count were the same or increased compared with those at 4-8 weeks prior to TAC; and biological DMARDs were used for at least 8 weeks prior to TAC. This study was conducted in compliance with the ministerial ordinance on "Good Post-Marketing Study Practice" (GPSP). RESULTS: The safety data collection and evaluation for 172 patients and effectiveness data collection and evaluation for 165 patients were reported. The mean age was 61.9 years. Adverse drug reactions occurred in 18 patients. The mean SDAI decreased from 20.1 at baseline to 11.7 at week 24. CONCLUSIONS: TAC is well tolerated and effective when added on to biological DMARDs in RA patients who failed to achieve an adequate response to biological DMARDs.
25857722 Within-day variation and influence of physical exercise on circulating Galectin-3 in patie 2015 Jul Galectin-3 has been suggested as a pro-inflammatory mediator in rheumatoid arthritis (RA). Previous studies have reported overexpression of Galectin-3 in RA synovitis and increased levels in synovial fluid and serum in long-standing RA compared with osteoarthritis and healthy controls. Our objectives were to study whether serum Galectin-3 (1) exhibits circadian variation and/or (2) responds to exercise in RA and controls. The study on circadian patterns (1) comprised eleven patients with newly diagnosed RA, disease duration less than 6 months (ERA), 10 patients with long-standing RA [5-15 years (LRA)] and 16 self-reportedly healthy control subjects. During 24 h, 7 blood samples were drawn at 3-h intervals starting at 10 a.m. through 10 p.m. and at 7 and 10 a.m. on the following day. The study on the effect of physical activity (2) included 10 patients with ERA, 10 with LRA and 14 controls. The participants underwent a standardized exercise programme and four blood samples were drawn before, during and after exercise. Serum Galectin-3 was quantified by ELISA (R&D systems). (1) Galectin-3 was increased at baseline in both RA subsets (P = 0.08). There were no diurnal oscillations (P = 0.85). Day-to-day variation amounted to 3%. (2) Baseline Galectin-3 was increased in LRA versus controls and ERA (P < 0.01 and 0.05). Physical exercise induced 10-15% Galectin-3 increments in RA and controls (P < 0.001) peaking after 1-3 h. To conclude, Galectin-3 did not exhibit circadian variation. Day-to-day variation was 3%. Exercise elicited comparable increments in patients with RA of short and long duration and controls, approaching normal after 1-3 h.
24911431 Role of Endocannabinoid Activation of Peripheral CB1 Receptors in the Regulation of Autoim 2015 The impact of the endogenous cannabinoids (AEA, 2-AG, PEA, and virodamine) on the immune cell expressed cannabinoid receptors (CB1, CB2, TRPV-1, and GPR55) and consequent regulation of immune function is an exciting area of research with potential implications in the prevention and treatment of inflammatory and autoimmune diseases. Despite significant advances in understanding the mechanisms through which cannabinoids regulate immune functions, not much is known about the role of endocannabinoids in the pathogenesis or prevention of autoimmune diseases. Inasmuch as CB2 expression on immune cells and its role has been widely reported, the importance of CB1 in immunological disorders has often been overlooked especially because it is not highly expressed on naive immune cells. Therefore, the current review aims at delineating the effect of endocannabinoids on CB1 receptors in T cell driven autoimmune diseases. This review will also highlight some autoimmune diseases in which there is evidence indicating a role for endocannabinoids in the regulation of autoimmune pathogenesis. Overall, based on the evidence presented using the endocannabinoids, specifically AEA, we propose that the peripheral CB1 receptor is involved in the regulation and amelioration of inflammation associated with autoimmune diseases.
27432356 Effectiveness of methotrexate with step-down glucocorticoid remission induction (COBRA Sli 2017 Mar OBJECTIVES: Combining disease-modifying antirheumatic drugs (DMARDs) with glucocorticoids (GCs) is an effective treatment strategy for early rheumatoid arthritis (ERA), yet the ideal schedule and feasibility in daily practice are debated. We evaluated different DMARD combinations and GC remission induction schemes in poor prognosis patients; and methotrexate (MTX) with or without GC remission induction in good prognosis patients, during the first treatment year. METHODS: The Care in ERA (CareRA) trial is a 2-year investigator-initiated randomised pragmatic open-label superiority trial comparing remission induction regimens in a treat-to-target approach. DMARD-inexperienced patients with ERA were stratified into a high-risk or low-risk group based upon presence of erosions, disease activity, rheumatoid factor and anticitrullinated protein antibodies. High-risk patients were randomised to a COBRA Classic (MTX + sulfasalazine + prednisone step-down from 60 mg), COBRA Slim (MTX + prednisone step-down from 30 mg) or COBRA Avant Garde (MTX + leflunomide + prednisone step-down from 30 mg) scheme. Low-risk patients were randomised to MTX tight step-up (MTX-TSU) or COBRA Slim. Primary outcome was the proportion of patients in 28 joint disease activity score calculated with C-reactive protein remission at week 52 in an intention-to-treat analysis. Secondary outcomes were safety and effectiveness (ClinicalTrial.gov identifier NCT01172639). RESULTS: 98 COBRA Classic, 98 COBRA Slim (high risk), 93 COBRA Avant Garde, 47 MTX-TSU and 43 COBRA Slim (low risk) patients were evaluated. Remission was achieved in 64.3% (63/98) COBRA Classic, 60.2% (59/98) COBRA Slim (high risk) and 62.4% (58/93) COBRA Avant Garde patients at W52 (p=0.840); and in 57.4% (27/47) MTX-TSU and 67.4% (29/43) COBRA Slim (low risk) patients (p=0.329). Less adverse events occurred per patient with COBRA Slim (high risk) compared with COBRA Classic or COBRA Avant Garde (p=0.038). Adverse events were similar in MTX-TSU and COBRA Slim (low risk) patients (p=0.871). At W52, 76.0% patients were on DMARD monotherapy, 5.2% used GCs and 7.5% biologicals. CONCLUSIONS: MTX with a moderate-dose GC remission induction scheme (COBRA Slim) seems an effective, safe, low-cost and feasible initial treatment strategy for patients with ERA regardless of their prognostic profile, provided a treat-to-target approach is followed. TRIAL REGISTRATION NUMBERS: EudraCT-number 2008-007225-39 and NCT01172639; Results.
27321430 Intensive immunosuppressive therapy for endogenous lipoid pneumonia associated with rheuma 2018 Nov Endogenous lipoid pneumonia is an uncommon inflammatory pulmonary disease that is caused by lipids from an endogenous source, the treatment for which has not been established. We report the first case of endogenous lipoid pneumonia presenting as lung consolidation and which was associated with rheumatoid arthritis. Treatment was successful with intensive immunosuppressive therapy. When a physician finds lung consolidation in a patient with active rheumatic disease, lipoid pneumonia should be considered.
26584911 Inhibition of each module of connective tissue growth factor as a potential therapeutic ta 2016 We previously reported the importance of connective tissue growth factor (CTGF) in rheumatoid arthritis (RA). CTGF contains four distinct modules connected in tandem, namely insulin-like growth factor-binding protein (IGFBP)-like, von Willebrand factor (vWF) type C repeat, thrombospondin type 1 (TSP-1) repeat, and carboxyl-terminal (CT) modules. The relationships between each of these modules of CTGF and RA remain unknown. Here, we analyzed how inhibition of each CTGF module affects the pathophysiology of RA. We conducted stimulation and suppression experiments on synovial cells (MH7A) obtained from patients with RA. Moreover, we examined angiogenesis by means of a tube-formation assay performed using human umbilical vein endothelial cells (HUVECs), and we used tartrate-resistant acid phosphatase (TRAP) staining to analyze osteoclastogenesis. Our results showed that M-CSF/RANKL-mediated osteoclastogenesis was enhanced when CTGF was added, but the effect of CTGF was neutralized by mAbs against CTGF modules 1-4. Furthermore, CTGF treatment of HUVECs induced formation of tubular networks, which resulted in acceleration of the angiogenesis of RA synoviocytes, and quantification showed that this tubular-network formation was also disrupted by anti-CTGF module 1-4 mAbs. Lastly, TNF-α enhanced the expression of CTGF and matrix metalloproteinase-3 (MMP3) in MH7A cells, and this enhancement was potently neutralized by mAbs against CTGF modules 1, 3 and 4. Thus, our results indicate that not only a mAb against CTGF but also mAbs against each specific module of CTGF might serve as potential therapeutic agents in the treatment of RA.
25623141 Trends in Excess Mortality Among Patients With Rheumatoid Arthritis in Ontario, Canada. 2015 Aug OBJECTIVE: To evaluate excess mortality over time, comparing rheumatoid arthritis (RA) patients with the general population. METHODS: We computed all-cause mortality rates among Ontario residents age ≥15 years with RA versus without RA from 1996 to 2009. Age- and sex-standardized mortality rates were expressed as the number of deaths per 1,000 population. Excess mortality rates were calculated as the difference between death rates among RA patients and those in the general population. We estimated standardized mortality ratios (SMRs) and mortality rate ratios (MRRs) to assess relative excess mortality over time. RESULTS: From 1996 to 2009, SMRs in RA ranged from 13.0 (95% confidence interval [95% CI] 12.2, 13.9) to 9.2 deaths per 1,000 RA patients (95% CI 8.4, 10.0); and for those without RA from 8.7 (95% CI 8.6, 8.7) to 6.0 deaths (95% CI 5.9, 6.0) per 1,000 general population. Over the study period, the excess mortality rate among RA patients was approximately 3 excess deaths per 1,000 population. Relative reductions in standardized mortality rates occurred over time for those with and without RA (-21.4% versus -13.4%). The SMRs for RA patients in 1996-1997, 2000-2001, 2004-2005, and 2008-2009 were 1.51 (95% CI 1.43, 1.59), 1.50 (95% CI 1.43, 1.57), 1.43 (95% CI 1.37, 1.50), and 1.41 (95% CI 1.35, 1.47), respectively. We did not find a significant change in the MRR by calendar time. CONCLUSION: Mortality for RA patients has decreased over time but remains elevated compared to the general population, with 40-50% more deaths among RA patients. The relative excess mortality over time (mortality gap) remains unchanged in our sample.
27180974 Pneumocystis jirovecii pneumonia developed in a patient with rheumatoid arthritis after 14 2018 Nov A 66-year-old woman who had rheumatoid arthritis and underwent a long-term treatment with methotrexate and etanercept developed Pneumocystis jirovecii pneumonia (PCP) 3 months after iguratimod add-on. Although most rheumatologists might have the impression that iguratimod has less toxicity and immunosuppressive effect compared with methotrexate and biologic disease-modifying antirheumatic drugs, this case suggests that iguratimod may increase the risk of PCP, especially in combination with other drugs.
27015729 Prospective outcome analysis of total replacement of the temporomandibular joint with the 2016 Jul We report the outcomes of patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis, who had total replacement of the temporomandibular joint (TMJ) using the TMJ Concepts system between 2005 and 2014. We prospectively measured mouth opening (mm), and pain and dietary function (visual analogue scale (VAS), 1 - 100) before operation, and at 6 weeks, 6 months, one year, and beyond. Forty-six joints were replaced in 26 patients (mean age 40, range 16 - 71), 22 of whom were female. Most had rheumatoid (n=17) or psoriatic arthritis (n=7). At one year the mean (SD) pain scores had fallen from 55 (36) to 2 (7) on the left, and from 62 (31) to 2 (5) on the right (p<0.001). Mean (SD) scores for dietary function had increased from 48(25) to 95(9) (p<0.001), and mouth opening had increased from a mean (SD) of 23(10) mm to 35(5) mm (p<0.001). The joints dislocated during the operation in 5 patients, and 4 had temporary weakness of the facial nerve. Outcomes after replacement of the TMJ with the TMJ Concepts system were good in patients with inflammatory arthritis, which further validates the procedure, as damage to the joint is severe in this group.
26474614 [Relationship between wrist bone mineral density and synovitis, erosion by ultrasonography 2015 Oct 18 OBJECTIVE: To find the correlation of wrist bone mineral density (BMD) to wrist synovitis and erosion, by comparing wrist BMD and ultrasonography. METHODS: A number of 80 female RA patients were examined by BMD measurement of the femoral neck, spine and non-dominant wrist using dual-energy X-ray absorptiometry (DXA). Synovitis of the wrist was examined by ultrasonography. The wrist joint (radiocarpal joint, dorsal midline, and carpoulnar joint) was assessed in the same side of DXA, with transverse and longitudinal scans for USGS synovial hypertrophy and proliferation, tenosynovitis,tendinitis and bone erosion. Colour and power doppler ultrasonography (PDUS) were used to sum the synovitis score. RESULTS: We found: (1) In the study, 80 female RA patients were enrolled, the mean age was 54.6±13.3 (27.0-80.0) years, the disease duration was 48 (12-116) months, and the body Mass Index was 23.0±4.0 (14.8-31.2) kg/m2. The Wrist BMD (g/cm2) in RA significantly reduced, compared with normal controls(0.297±0.121 vs. 0.420±0.180,P<0.01). (2) The Wrist BMD (g/cm2) exceeded in early RA compared with the established RA (0.326±0.103 vs. 0.285±0.132,P<0.01); the positive rate of severe osteoporosis in wrist was lower in early RA compared with the established RA (47.8% vs. 64.9%, P<0.05); the positive rate of bone erosion in wrist by ultrasound was lower in early RA compared with the established RA (39.1% vs. 56.1%, P<0.01). (3) The wrist BMD (g/cm2) in RA with high disease activity reduced compared with moderate and low disease activity (0.267±0.140 vs. 0.280±0.126) and (0.267±0.140 vs. 0.320±0.103) respectively, P<0.05). The percentages of positive ACPA in the high and moderate disease activity groups were significantly higher than those in the remission group (85% vs. 81.8% and 92.6% vs. 81.8%, respectively). DAS28ESR was correlated with wrist BMD (r=-0.288, P<0.01). (4) A significant positive correlation was found between wrist and spine/femur BMD (r=0.634, P<0.01, r=0.795, P<0.01), and a negative correlation between wrist and disease duration and DAS28ESR (r=-0.286, r=-0.301, P<0.01). There was a highly significant positive correlation between wrist BMD and femur BMD (r=0.95, P<0.05). (5) RA patients in wrist osteoporosis group had higher RF positive rate and ACPA rate than wrist osteopenia group (75.5% vs. 55.6%, P<0.05,100% vs. 83.3%, P<0.05). The patients of BMD osteoporosis group had higher DAS28ESR compared with osteopenia group (5.3±1.8 vs. 3.7±1.5, P<0.01). The percentages of synovitis (61.5% vs. 51.7%, P<0.05), tendenitis (14.3% vs. 10.0%, P<0.05) and bone erosion (54.2% vs. 46.2%, P<0.05) in wrist by ultrasonography in osteoporosis group were higher than those of osteopenia group. (6) The wrist BMD in negative bone erosion group by ultrasonography was lower than that in positive bone erosion group [(0.333±0.107) g/cm2 vs. (0.264±0.125) g/cm2, P<0.01], also the PDUS score was higher than positive bone erosion group (4.53±1.40 vs. 2.55±2.66, P<0.01). Compared with negative bone erosion group, the patients in positive bone erosion group had longer disease duration (96.0±104.7) months vs. (66.2±78.0) months, P<0.05), higher percentage of RF (81.0% vs. 53.8%, P<0.01), ACPA (92.7% vs. 79.5%, P<0.05). and higher DAS28ESR (5.4±1.8 vs. 4.2±2.0, P<0.05). The percentage of wrist synovitis in positive bone erosion group was higher (75.6% vs. 30.8%, P<0.01) than that of negative bone erosion group, and moreover, the percentage of severe osteoporosis in the wrist was significantly higher (75.0% vs. 46.4%, P<0.01). (7) A stepwise multivariate linear regression model was constructed to explore the relationship between the different clinical factors studied and a low wrist BMD. Statistically significant variables were age (P=0.001), disease duration (P=0.017), DAS28ESR (P=0.021), and ACPA (P=0.05). CONCLUSION: This study shows a highly significant correlation between hand BMD with disease duration and disease activity, and female RA patients with high titer of ACPA have lower wrist BMD.