Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
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| 34803427 | Gintonin regulates inflammation in human IL-1β-stimulated fibroblast-like synoviocytes an | 2021 Sep | BACKGROUND: In ginseng, there exists a glycolipoprotein complex with a special form of lipid LPAs called Gintonin. The purpose of this study is to show that Gintonin has a therapeutic effect on rheumatoid arthritis through LPA2 receptors. METHODS: Fibroblast-like synoviocytes (FLS) were treated with Gintonin and stimulated with interleukin (IL)-1β. The antioxidant effect of Gintonin was measured using MitoSOX and H(2)DCFDA experiments. The anti-arthritic efficacy of Gintonin was examined by analyzing the expression levels of inflammatory mediators, phosphorylation of mitogen-activated protein kinase (MAPK) pathways, and translocation of nuclear factor kappa B (NF-κB)/p65 into the nucleus through western blot. Next, after treatment with LPAR2 antagonist, western blot analysis was performed to measure inflammatory mediator expression levels, and NF-κB signaling pathway. Carrageenan/kaolin-induced arthritis rat model was used. Rats were orally administered with Gintonin (25, 50, and 100 mg/kg) every day for 6 days. The knee joint thickness, squeaking score, and weight distribution ratio (WDR) were measured as the behavioral parameters. After sacrifice, H&E staining was performed for histological analysis. RESULTS: Gintonin significantly inhibited the expression of iNOS, TNF-α, IL-6 and COX-2. Gintonin prevented NF-κB/p65 from moving into the nucleus through the JNK and ERK MAPK phosphorylation in FLS cells. However, pretreatment with an LPA2 antagonist significantly reversed these effects of Gintonin. In the arthritis rat model, Gintonin suppressed all parameters that were measured. CONCLUSION: This study suggests that LPA2 receptor plays a key role in mediating the anti-arthritic effects of Gintonin by modulating inflammatory mediators, the MAPK and NF-κB signaling pathways. | |
| 34060254 | Exploring the Role of Antinuclear Antibody Positivity in the Diagnosis, Treatment, and Hea | 2021 Jun | OBJECTIVE: The objective of this study was to describe differences in the clinical course of patients with rheumatoid arthritis (RA) who are antinuclear antibody (ANA)-positive compared with those who are ANA-negative. METHODS: This was a retrospective population-based cohort study of residents in Olmsted County, Minnesota, who first fulfilled 1987 American College of Rheumatology criteria for RA in 2009-2014. Data were collected on first documentation of joint swelling. Data on rheumatoid factor or anti-cyclic citrullinated peptide antibody testing and the ANA level were also collected. Comparisons between groups were performed by using χ(2) and rank sum tests. RESULTS: In this cohort, 64% of patients were tested for ANA within ±90 days of RA criteria fulfillment. In the161 patients with ANA testing, 25% were ANA-positive. Patients who were ANA-positive were younger, female, and less likely to be current smokers. ANA positivity did not differ between patients with RA who were seropositive and seronegative. In seropositive patients who were ANA-positive, there was an increased time to fulfillment of RA criteria, increased time to treatment with disease-modifying antirheumatic drugs (DMARDs), and increased likelihood of being treated with hydroxychloroquine as opposed to methotrexate. Other outcomes, including disease activity and mortality, did not differ significantly between groups. CONCLUSION: In patients with RA, important differences exist between those who are ANA-positive and ANA-negative in terms of time to fulfillment of RA criteria and time to DMARD initiation as well as choice of initial pharmacotherapy. These findings could indicate a difference in clinical presentation or perception of patients with RA who are ANA-positive. Further research is needed to study the long-term outcomes of patients with RA who are ANA-positive. | |
| 34168653 | The Multiple Roles of B Cells in the Pathogenesis of Sjögren's Syndrome. | 2021 | Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease characterized by lymphocytic infiltration and tissue destruction of exocrine glands such as salivary glands. Although the formation of ectopic lymphoid tissue in exocrine glands and overproduction of autoantibodies by autoreactive B cells highlight the critical involvement of B cells in disease development, the precise roles of various B cell subsets in pSS pathogenesis remain partially understood. Current studies have identified several novel B cell subsets with multiple functions in pSS, among which autoreactive age-associated B cells, and plasma cells with augmented autoantibody production contribute to the disease progression. In addition, tissue-resident Fc Receptor-Like 4 (FcRL4)(+) B cell subset with enhanced pro-inflammatory cytokine production serves as a key driver in pSS patients with mucosa-associated lymphoid tissue (MALT)-lymphomas. Recently, regulatory B (Breg) cells with impaired immunosuppressive functions are found negatively correlated with T follicular helper (Tfh) cells in pSS patients. Further studies have revealed a pivotal role of Breg cells in constraining Tfh response in autoimmune pathogenesis. This review provides an overview of recent advances in the identification of pathogenic B cell subsets and Breg cells, as well as new development of B-cell targeted therapies in pSS patients. | |
| 33633444 | Treatment Satisfaction, Patient Preferences, and the Impact of Suboptimal Disease Control | 2021 | BACKGROUND: Patients' needs and perspectives are important determinants of treatment success in rheumatoid arthritis (RA). Assessing patients' perspectives can help identify unmet needs and enhance the understanding of treatment benefits. OBJECTIVE: The SENSE study assessed the impact of inadequate response to disease-modifying antirheumatic drugs (DMARDs) on treatment satisfaction, disease outcomes, and patient perspectives related to RA disease management. METHODS: SENSE was a noninterventional, cross-sectional study conducted in 18 countries across Europe, Asia, and South America. Adult patients with poorly controlled RA of moderate/high disease activity were eligible. Patient satisfaction was assessed by the Treatment Satisfaction Questionnaire for Medication (TSQM v1.4). Treatment adherence, healthcare resource utilization (HRU), quality of life (QoL), work ability, digital health literacy (DHL), patient preference information, and treatment strategy were also assessed. RESULTS: A total of 1624 patients were included in the study: most were female (84.2%) and middle-aged, and mean disease duration was 10.5 years. Mean TSQM global satisfaction subscore was 60.9, with only 13.5% of patients reporting good treatment satisfaction (TSQM global ≥80). The strongest predictor of good treatment satisfaction was treatment with advanced therapies. Most patients (87.4%) reported good treatment adherence. In general, patients had impaired QoL and work ability, high HRU, and 67.4% had poor DHL. Leading treatment expectations were "general improvement of arthritis" and "less joint pain". Most patients preferred oral RA medications (60.7%) and rapid (≤1 week) onset of action (71.1%). "Increased risk for malignancies" and "increased risk for cardiovascular disease" were the least acceptable side effects. Despite suboptimal control, advanced therapies were only used in a minority of patients, and DMARD switches were planned for only half of the patients. CONCLUSION: Suboptimal disease control negatively impacts treatment satisfaction, work ability, QoL, and HRU. Data collected on patient perspectives may inform shared decision-making and optimize treat-to-target strategies for improving patient outcomes in RA. | |
| 34305928 | Deregulation of the Kallikrein Protease Family in the Salivary Glands of the Sjögren's Sy | 2021 | INTRODUCTION: The purpose of this study was to identify differentially expressed proteins in salivary glands of the ERdj5 knockout mouse model for Sjögren's syndrome and to elucidate possible mechanisms for the morbid phenotype development. At the same time, we describe for the first time the sexual dimorphism of the murine submandibular salivary gland at the proteome level. METHODS: We performed Liquid Chromatography/Mass Spectrometry in salivary gland tissues from both sexes of ERdj5 knockout and 129SV wildtype mice. The resulting list of proteins was evaluated with bioinformatic analysis and selected proteins were validated by western blot and immunohistochemistry and further analyzed at the transcription level by qRT-PCR. RESULTS: We identified 88 deregulated proteins in females, and 55 in males in wildtype vs knockout comparisons. In both sexes, Kallikrein 1b22 was highly upregulated (fold change>25, ANOVA p<0.0001), while all other proteases of this family were either downregulated or not significantly affected by the genotype. Bioinformatic analysis revealed a possible connection with the downregulated NGF that was further validated by independent methods. Concurrently, we identified 416 proteins that were significantly different in the salivary gland proteome of wildtype female vs male mice and highlighted pathways that could be driving the strong female bias of the pathology. CONCLUSION: Our research provides a list of novel targets and supports the involvement of an NGF-mediating proteolytic deregulation pathway as a focus point towards the better understanding of the underlying mechanism of Sjögren's syndrome. | |
| 33986742 | Protein-Based Immunome Wide Association Studies (PIWAS) for the Discovery of Significant D | 2021 | Identification of the antigens associated with antibodies is vital to understanding immune responses in the context of infection, autoimmunity, and cancer. Discovering antigens at a proteome scale could enable broader identification of antigens that are responsible for generating an immune response or driving a disease state. Although targeted tests for known antigens can be straightforward, discovering antigens at a proteome scale using protein and peptide arrays is time consuming and expensive. We leverage Serum Epitope Repertoire Analysis (SERA), an assay based on a random bacterial display peptide library coupled with next generation sequencing (NGS), to power the development of Protein-based Immunome Wide Association Study (PIWAS). PIWAS uses proteome-based signals to discover candidate antibody-antigen epitopes that are significantly elevated in a subset of cases compared to controls. After demonstrating statistical power relative to the magnitude and prevalence of effect in synthetic data, we apply PIWAS to systemic lupus erythematosus (SLE, n=31) and observe known autoantigens, Smith and Ribosomal protein P, within the 22 highest scoring candidate protein antigens across the entire human proteome. We validate the magnitude and location of the SLE specific signal against the Smith family of proteins using a cohort of patients who are positive by predicate anti-Sm tests. To test the generalizability of the method in an additional autoimmune disease, we identified and validated autoantigenic signals to SSB, CENPA, and keratin proteins in a cohort of individuals with Sjogren's syndrome (n=91). Collectively, these results suggest that PIWAS provides a powerful new tool to discover disease-associated serological antigens within any known proteome. | |
| 33825332 | Lycium barbarum Polysaccharide Ameliorates Sjögren's Syndrome in a Murine Model. | 2021 Jun | SCOPE: This study aims to evaluate the therapeutic efficacy and mechanisms of Lycium barbarum polysaccharide (LBP) in primary Sjögren's syndrome (pSS). METHODS AND RESULTS: Non-obese diabetic mice (the pSS model) are randomly divided into four groups: Low dose LBP (LBP.L, 5 mg kg(-1)  d(-1) ), high dose LBP (10 mg kg(-1)  d(-1) ), low dose interleukin (IL)-2 (25 000 IU/d), and control (saline water). Drugs were treated for 12 weeks. LBP.L significantly reduces the salivary gland inflammation compared with the control group (histological score p (LBP.L) vs (Control)  = 0.019; foci number: p (LBP.L) vs (Control)  = 0.038). LBP.L also remarkably reduces the effector follicular helper T (Tfh) cells and the CD4(+) IL-17A(+) helper T (Th17) cells in both spleen and cervical lymph node (cLN) cells. Additionally, the ratios of regulatory T cell (Treg)/Tfh cells and Treg/Th17 cells are substantially increased in mice treated with LBP.L in both spleen and cLNs. LBP also inhibits Th17 and Tfh cells and markedly increases the Treg/Tfh ratio in human peripheral blood mononuclear cells. CONCLUSION: LBP.L inhibits the progression of pSS in mice, associated with modulation of T cell differentiation. | |
| 34691064 | Usefulness of Interleukin-18 as a Diagnostic Biomarker to Differentiate Adult-Onset Still' | 2021 | BACKGROUND: Interleukin (IL)-18 is markedly elevated in systemic inflammatory diseases that cause the 'cytokine storm' such as adult-onset Still's disease (AOSD) and hemophagocytic lymphohistiocytosis (HLH). The differences in IL-18 between AOSD and HLH, especially in adults, is uncertain. Macrophage activation syndrome (MAS), a form of secondary HLH, is often difficult to differentiate cases of AOSD that include MAS from other secondary HLH. In this case-control study, we investigated whether serum IL-18 levels could be a useful biomarker for the differential diagnosis of AOSD with or without MAS (AOSD group) and other secondary HLH in adults (adult HLH group). PATIENTS AND METHODS: We enrolled 46 patients diagnosed with AOSD including 9 patients with MAS and 31 patients in the adult HLH group, which excluded AOSD-associated MAS. The clinical features and laboratory data were compared between the AOSD and adult HLH groups. In addition, we subdivided the AOSD group (with or without MAS) and the adult HLH group (whether lymphoma-associated or not) and compared the four groups. A logistic regression analysis was used to identify factors with high efficacy in differentiating the two groups, followed by a receiver operating characteristic (ROC) curve analysis to evaluate the differential diagnostic ability of IL-18. We analyzed the correlation between IL-18 and various laboratory parameters in the AOSD group. RESULTS: Serum IL-18 levels of patients in the AOSD groups were significantly higher than those of the adult HLH groups, and were closely correlated with ferritin, soluble interleukin-2 receptor (sIL-2R), and other laboratory data. Univariate and multivariate logistic regression analyses revealed that IL-18, sIL-2R, and 'arthralgia or arthritis' are independent factors useful in the differential diagnosis of AOSD from adult HLH. In the differential diagnosis of both groups, the area under the curve obtained from the ROC curve of IL-18 with a cutoff value of 18,550 pg/mL was 0.91 (95% confidence interval 0.83-1.00; sensitivity 90.3%, specificity 93.5%), and the differential diagnosis ability of IL-18 was superior to that of other laboratory data. CONCLUSIONS: IL-18 could be a useful biomarker for the differential diagnosis of AOSD and adult HLH. | |
| 33763056 | Proteinase-Mediated Macrophage Signaling in Psoriatic Arthritis. | 2020 | OBJECTIVE: Multiple proteinases are present in the synovial fluid (SF) of an arthritic joint. We aimed to identify inflammatory cell populations present in psoriatic arthritis (PsA) SF compared to osteoarthritis (OA) and rheumatoid arthritis (RA), identify their proteinase-activated receptor 2 (PAR2) signaling function and characterize potentially active SF serine proteinases that may be PAR2 activators. METHODS: Flow cytometry was used to characterize SF cells from PsA, RA, OA patients; PsA SF cells were further characterized by single cell 3'-RNA-sequencing. Active serine proteinases were identified through cleavage of fluorogenic trypsin- and chymotrypsin-like substrates, activity-based probe analysis and proteomics. Fluo-4 AM was used to monitor intracellular calcium cell signaling. Cytokine expression was evaluated using a multiplex Luminex panel. RESULTS: PsA SF cells were dominated by monocytes/macrophages, which consisted of three populations representing classical, non-classical and intermediate cells. The classical monocytes/macrophages were reduced in PsA compared to OA/RA, whilst the intermediate population was increased. PAR2 was elevated in OA vs. PsA/RA SF monocytes/macrophages, particularly in the intermediate population. PAR2 expression and signaling in primary PsA monocytes/macrophages significantly impacted the production of monocyte chemoattractant protein-1 (MCP-1). Trypsin-like serine proteinase activity was elevated in PsA and RA SF compared to OA, while chymotrypsin-like activity was elevated in RA compared to PsA. Tryptase-6 was identified as an active serine proteinase in SF that could trigger calcium signaling partially via PAR2. CONCLUSION: PAR2 and its activating proteinases, including tryptase-6, can be important mediators of inflammation in PsA. Components within this proteinase-receptor axis may represent novel therapeutic targets. | |
| 35005594 | Regulatory T cell function in autoimmune disease. | 2021 | Autoimmune diseases are characterized by a failure of tolerance to own body components resulting in tissue damage. Regulatory T cells are gatekeepers of tolerance. This review focusses on the function and pathophysiology of regulatory T cells in the context of autoimmune diseases including rheumatoid and juvenile idiopathic arthritis as well as systemic lupus erythematosus with an overview over current and future therapeutic options to boost Treg function. | |
| 34880054 | Whole gut virome analysis of 476 Japanese revealed a link between phage and autoimmune dis | 2022 Feb | OBJECTIVE: The relationship between autoimmune diseases and the gut microbiome has been intensively studied, and several autoimmunity-associated bacterial taxa have been identified. However, much less is known about the roles of the gut virome in autoimmune diseases. METHODS: Here, we performed a whole gut virome analysis based on the shotgun sequencing of 476 Japanese which included patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis and healthy control subjects. RESULTS: Our case-control comparison of the viral abundance revealed that crAss-like phages, which are one of the main components of a healthy gut virome, significantly decreased in the gut of the patients with autoimmune disease, specifically the patients with RA and SLE. In addition, Podoviridae significantly decreased in the gut of the patients with SLE. To understand how these viruses affected the bacteriome, we performed a quantitative virus-bacterium association analysis and clustered regularly interspaced short palindromic repeat-based virus-bacterium interaction analysis. We identified a symbiosis between Podoviridae and Faecalibacterium. In addition, multiple bacterial targets of crAss-like phages were identified (eg, Ruminococcus spp). CONCLUSION: Our data suggest that the gut virome can affect our body either directly or via bacteria. Our analyses have elucidated a previously missing part of the autoimmunity-associated gut microbiome and presented new candidates that contribute to the development of autoimmune diseases. | |
| 33785415 | Systemic Conditions Associated with Severity of Dry Eye Signs and Symptoms in the Dry Eye | 2021 Oct | PURPOSE: Certain systemic conditions are reported to be risk factors for dry eye disease (DED), but their associations with DED severity are not well studied. We evaluated whether systemic conditions reported to be DED risk factors are associated with severity of DED signs and symptoms. DESIGN: Secondary analysis of data from the Dry Eye Assessment and Management Study, a large-scale multicenter randomized clinical trial of patients with moderate to severe DED. PARTICIPANTS: Five hundred thirty-five adult patients with moderate to severe DED from 27 United States centers. METHODS: Patients reported their medical history at baseline. They underwent ocular surface examinations and symptom evaluation using standardized protocols at baseline, 6 months, and 12 months. We analyzed the associations of systemic conditions (a systemic disease or smoking history) reported as potential DED risk factors with the severity of DED signs and symptoms using generalized linear regression models adjusted by age, gender, race, and visit. MAIN OUTCOME MEASURES: Dry eye disease symptoms assessed using the Ocular Surface Disease Index (OSDI), 6 DED signs (tear film break-up time, anesthetized Schirmer testing, corneal fluorescein staining, conjunctival lissamine green staining, tear osmolarity, and meibomian gland dysfunction), and a composite signs severity score from 0 to 1 (1 = most severe). RESULTS: The mean age was 58 years; 81% were women. More severe DED signs were associated significantly with Sjögren syndrome (mean composite signs severity score 0.52 with disease vs. 0.43 without disease; P < 0.001), facial rosacea (0.47 vs. 0.43; P = 0.002), rheumatoid arthritis (0.47 vs. 0.42; P = 0.002), peripheral artery disease (0.50 vs. 0.43; P < 0.001), and daily smoking history (0.45 vs. 0.43; P = 0.047). Thyroid dysfunction, osteoarthritis, diabetes, irritable bowel syndrome, hypercholesterolemia, hypertension, and hypertriglyceridemia were not associated significantly with DED signs. No conditions were associated significantly with OSDI. CONCLUSIONS: In this large, well-characterized cohort of patients with DED assessed under standardized procedures, patients with certain systemic diseases and smoking history showed more severe DED signs compared with patients without the conditions. The profile of significant DED signs varied by systemic condition, reflecting different DED causes. Understanding the systemic conditions and underlying causes that predispose some patients to severe DED can improve management. | |
| 33364263 | Connective tissue disease-related interstitial lung disease (CTD-ILD) and interstitial lun | 2021 | The connective tissue diseases (CTDs) demonstrating features of interstitial lung disease (ILD) include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), progressive systemic sclerosis (PSS), dermatomyositis (DM) and polymyositis (PM), ankylosing spondylitis (AS), Sjogren's syndrome (SS), and mixed connective tissue disease (MCTD). In RA patients in particular, interstitial lung abnormality (ILA) (of varying degrees; severe vs. mild) is reported to occur in approximately 20-60 % of individuals and CT disease progression occurs in approximately 35-45 % of them. The ILAs have been associated with a spectrum of functional and physiologic decrement. The identification of progressive ILA may enable appropriate surveillance and the commencement of treatment with the goal of improving morbidity and mortality rates of established RA-ILD. Subpleural distribution and higher baseline ILA/ILD extent were risk factors associated with disease progression. At histopathologic analysis, connective tissue disease-related interstitial lung diseases (CTD-ILDs) are diverse and include nonspecific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), organizing pneumonia (OP), apical fibrosis, diffuse alveolar damage (DAD), and lymphoid interstitial pneumonia (LIP). Even though proportions of ILDs vary, NSIP pattern accounts for a large proportion, especially in PSS, DM/PM and MCTD, followed by UIP pattern. Evidence has been published that treatment of subclinical CT lung abnormalities showing a tendency to progress to ILD may stabilize the CT alterations. The identification of subclinical lung abnormalities can be appropriate in the management of the disease and CT appears to be the gold standard for the evaluation of lung parenchyma. | |
| 34766910 | The Relationship Between Electronic Health Record System and Performance on Quality Measur | 2021 Nov 12 | BACKGROUND: Routine collection of disease activity (DA) and patient-reported outcomes (PROs) in rheumatoid arthritis (RA) are nationally endorsed quality measures and critical components of a treat-to-target approach. However, little is known about the role electronic health record (EHR) systems play in facilitating performance on these measures. OBJECTIVE: Using the American College Rheumatology's (ACR's) RISE registry, we analyzed the relationship between EHR system and performance on DA and functional status (FS) quality measures. METHODS: We analyzed data collected in 2018 from practices enrolled in RISE. We assessed practice-level performance on quality measures that require DA and FS documentation. Multivariable linear regression and zero-inflated negative binomial models were used to examine the independent effect of EHR system on practice-level quality measure performance, adjusting for practice characteristics and patient case-mix. RESULTS: In total, 220 included practices cared for 314,793 patients with RA. NextGen was the most commonly used EHR system (34.1%). We found wide variation in performance on DA and FS quality measures by EHR system (median 30.1, IQR 0-74.8, and median 9.0, IQR 0-74.2), respectively). Even after adjustment, NextGen practices performed significantly better than Allscripts on the DA measure (51.4% vs 5.0%; P<.05) and significantly better than eClinicalWorks and eMDs on the FS measure (49.3% vs 29.0% and 10.9%; P<.05). CONCLUSIONS: Performance on national RA quality measures was associated with the EHR system, even after adjusting for practice and patient characteristics. These findings suggest that future efforts to improve quality of care in RA should focus not only on provider performance reporting but also on developing and implementing rheumatology-specific standards across EHRs. | |
| 33427541 | Inflammatory rheumatic diseases in patients with ochronotic arthropathy. | 2021 Sep | BACKGROUND: Ochronotic arthropathy (OcA) refers to excessive homogentisic acid (HGA) deposition in the musculoskeletal system. Our current understanding of OcA is limited, as there are less than a thousand alkaptonuria (AKU) cases reported in the literature. Herein, we investigated the rheumatological manifestations of OcA in a group of adult AKU patients. METHODS: Adult AKU patients with symptoms suggestive of OcA were included. Patients underwent a detailed rheumatological assessment. Laboratory testing, including autoantibodies and radiological investigations such as conventional X-rays, and magnetic resonance imaging (MRI) were performed. RESULTS: Eight out of 12 (66%) patients had symptoms consistent with OcA. The median age at OcA symptoms was 36 (27-48) years, and the presenting symptom was back pain in 87.5% of the patients. All patients had chronic back pain, and three (37.5%) had an inflammatory type of pain character. Radiographic sacroiliitis based on X-rays was present in 2 (25%) cases. MRI of the sacroiliac joints documented bone marrow edema in five (62.5%), and spinal MRI identified corner inflammatory lesions in three patients (37.5%). One patient (12.5%) had rheumatoid arthritis. Extra-articular involvement, including enthesitis (n = 1; 12.5%), interstitial lung disease (n = 1; 12.5%), and scleritis (n = 1; 12.5%), was also noted. CONCLUSION: The frequent occurrence of OcA-related inflammatory manifestations in our patients contradicts the conventional concept of OcA as a non-inflammatory disorder. The activation of inflammatory pathways, possibly by the HGA products, may responsible for this condition.Significance and innovationsAbout three-fourths of adult ochronotic arthropathy (OcA) patients in our group had associated inflammatory disease.OcA associated inflammatory diseases were showing a severe phenotypeNearly half of the OcA patients required early prosthesis operations compared to their healthy counterparts. | |
| 33934270 | Healthcare utilization and costs among patients with psoriasis and psoriatic arthritis in | 2021 Oct | OBJECTIVES: To compare healthcare resource utilization and costs among patients with psoriasis, psoriatic arthritis (PsA), and a control group of patients without psoriasis and PsA in the USA. METHODS: The IBM® MarketScan® Commercial Database was used to identify three adult patient groups from 1/1/2009 through 4/30/2020: (1) Psoriasis: ≥ 2 diagnoses ≥ 30 days apart for psoriasis (no PsA diagnoses); (2) PsA: ≥ 2 diagnoses for PsA; (3) Control: no psoriasis or PsA diagnoses in their entire claims records. Patients with comorbid rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, or ulcerative colitis were excluded from the analyses. Controls were matched 1:1 to psoriasis and PsA patients based on age, gender, index year, and number of non-rheumatological comorbidities. Healthcare resource utilization and costs (in 2019 USD) were evaluated descriptively and through mixed models for five years of follow-up. RESULTS: A total of 142,531 psoriasis and 21,428 PsA patients were matched to the control group (N = 163,959). Annual all-cause healthcare costs per patient were $7,470, $11,062, and $29,742 for the control, psoriasis, and PsA groups, respectively. All-cause healthcare costs increased over time and were significantly greater among PsA vs. psoriasis (p < 0.0001) and the control groups (p < 0.0001). Across all categories of healthcare resources, utilization was greatest among patients with PsA and lowest in the control group. CONCLUSION: Annual healthcare costs and resource utilization were significantly higher with PsA compared with psoriasis and the control group, confirming the substantial economic burden of PsA. The cost disparity between these patient groups highlights a continued unmet medical need. Key Points • Patients with PsA incurred significantly greater healthcare resource utilization and costs than patients with psoriasis and patients without psoriasis and PsA. • Significantly greater costs and healthcare resource utilization were also observed among patients with psoriasis compared with patients without psoriasis and PsA. | |
| 34184820 | Familial aggregation of juvenile idiopathic arthritis with other autoimmune diseases: Impa | 2021 Aug | OBJECTIVES: To evaluate the impact of family history of autoimmune diseases (FHADs) on the clinical characteristics and outcome of juvenile idiopathic arthritis (JIA). METHODS: We retrospectively reviewed children with JIA seen in 7 pediatric rheumatology clinics from 6 Arab countries. All included patients met the International League of Associations for Rheumatology classification criteria for JIA and had a disease duration greater than 1 year. Data were collected at the last follow-up visit and comprised clinical findings, including FHADs. Disease activity and disease damage were assessed by Juvenile Arthritis Multidimensional Assessment Report, and juvenile arthritis damage index (JADI) respectively. Disease activity was categorized as remission off treatment, remission on treatment, or active disease. RESULTS: A total of 349 (224 females) JIA patients with a disease duration of 5 (interquartile range 2.9-7.5) years were included. The most frequent JIA categories were polyarticular JIA and oligoarticular JIA, followed by systemic JIA. There were 189 patients with FHADs and 160 patients without FHADs. The most frequent FHADs were diabetes mellitus (21.2%), JIA (18.5%), rheumatoid arthritis (12.7%). Among patients with FHADs, 140/189 (74.1%) achieved clinical remission, while 131/160 (81.9%) patients without FHDs had clinical remission (odds ratio [OR]Â =Â 1.2, 95% CI 0.97-1.5). Rate of consanguinity, enthesitis-related arthritis (ERA) and psoriatic arthritis were higher in patients with FHADs (ORÂ =Â 0.6, 95% CI 0.4-0.9 and ORÂ =Â 1.2, 95% CI 1.1-1.4). Also, articular JADI correlated significantly with presence of FHADs (ORÂ =Â 1.1, 95% CI 1.0-1.1). CONCLUSION: This study shows that autoimmune diseases cluster within families of patients with JIA with a high proportion of ERA and psoriatic arthritis. JIA patients with FHADs are likely to have more disease damage. | |
| 33499113 | A New Peracetylated Oleuropein Derivative Ameliorates Joint Inflammation and Destruction i | 2021 Jan 22 | : Oleuropein (OL), an olive tree secoiridoid and its peracetylated derivate (Per-OL) have exhibited several beneficial effects on LPS-stimulated macrophages and murine experimental systemic lupus erythematosus (SLE). This study was designed to evaluate dietary Per-OL in comparison with OL supplementation effects on collagen-induced arthritis (CIA) murine model. Three-weeks-old DBA-1/J male mice were fed from weaning with a standard commercial diet or experimental enriched-diets in 0.05 % (w/w) OL, 0.05% and 0.025% Per-OL. After six weeks of pre-treatment, arthritis was induced by bovine collagen type II by tail base injection (day 0) and on day 21, mice received a booster injection. Mice were sacrificed 42 days after the first immunization. Both Per-OL and OL diets significantly prevented histological damage and arthritic score development, although no statistically significant differences were observed between both compounds. Also, serum collagen oligomeric matrix protein (COMP), metalloprotease (MMP)-3 and pro-inflammatory cytokines levels were ameliorated in paws from secoiridoids fed animals. Mitogen-activated protein kinases (MAPK)s and nuclear transcription factor-kappa-B (NF-κB) activations were drastically down-regulated whereas nuclear factor E2-related factor 2 (Nrf2) and heme-oxygenase-1 (HO-1) protein expressions were up-regulated in those mice fed with OL and Per-OL diets. We conclude that both Per-OL and its parent compound, OL, supplements might provide a basis for developing a new dietary strategy for the prevention of rheumatoid arthritis. | |
| 33737966 | Psoriatic arthritis and the association with cardiometabolic disease: a narrative review. | 2021 | Psoriatic arthritis (PsA) is associated with a higher burden of cardiometabolic disorders, such as hypertension, dyslipidemia, diabetes, obesity, and cardiovascular disease (CVD), compared with the general population. These comorbidities are associated with the severity of disease, and adversely affect treatment outcomes in PsA. Comorbidities lead to increased physician visits and medications for patients and make the selection and maintenance of therapies challenging for physicians. Moreover, CVD is a leading cause of mortality in PsA. Therefore, optimal management of PsA should include not only treating the skin and joint disease, but also identifying comorbidities early, and managing them to improve long-term outcomes. Further studies are needed to understand the complex mechanisms, interactions, and trajectories of cardiometabolic comorbidities in psoriatic disease. PLAIN LANGUAGE SUMMARY: Psoriatic arthritis and the association with cardiometabolic disease Psoriatic arthritis (PsA) is associated with a higher incidence and prevalence of cardiometabolic comorbidities compared with the general population, and higher than psoriasis and other inflammatory arthritides, such as rheumatoid arthritis and other spondyloarthritides.Obesity and hyperlipidemia are associated with an increased risk of developing PsA.Cardiometabolic comorbidities in PsA are associated with more severe disease and a lower likelihood of response to therapy.Suggested approaches to improve screening and management of CVD in PsA include education of family physicians and relevant specialists, development of mechanisms to improve communication between the rheumatologists and primary care providers, and novel models of care, including interdisciplinary cardio-rheumatology clinics. | |
| 34354936 | Arthrodesis of the first metatarsophalangeal joint: The "when and how". | 2021 Jul 18 | Arthrodesis of the first metatarsophalangeal (MTP) joint has been established as the "gold standard" for the treatment of several first ray disorders, due to its perceived efficacy and the consistently reported good results in the literature. Arthrodesis is a commonly performed procedure for the treatment of end stage arthritis, rheumatoid arthritis with severe deformity, selected cases of severe hallux valgus (with or without signs of degenerative joint disease), as well as a salvage procedure after failed previous operation of the first ray. The goals of a successful 1(st) MTP arthrodesis are pain alleviation and deformity correction in order to restore a comfortable gait pattern and to improve shoe wear. Several techniques have been reported with several proposals regarding the preparation of the articular surfaces and the method of definitive fixation. As with any given surgical procedure, various complications may occur after arthrodesis of the 1(st) MTP joint, namely delayed union, nonunion, malunion, irritating hardware, etc. |