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Microscopic bowel inflammation is present in up to 60% of all patients with spondyloarthritis (SpA) and appears to be associated with more severe joint disease and a higher risk of developing inflammatory bowel disease (IBD). This study aimed to determine the utility of fecal calprotectin (fCAL) in evaluating endoscopic and histological bowel inflammation in SpA patients.Ileocolonoscopies with biopsies and fCAL measurements were performed in 65 patients with SpA.In 47 (72.3%) patients, the fCAL levels were higher than 50 μg/g, whereas in 20 (30.7%), these levels were greater than 250 μg/g. A total of 38 (58.5%) patients presented with microscopic bowel inflammation, and 13 (20%) presented with signs of endoscopic inflammation. fCAL levels were significantly higher in patients with microscopic bowel inflammation than in those without inflammatory findings (P .001); additionally, these levels were slightly higher in patients with endoscopic signs of bowel inflammation (P = .053). A fCAL cutoff value of 96 μg/g predicted histological bowel inflammation with 73% sensitivity and 67% specificity. No statistically significant difference was observed in the fCAL levels between patients who had been treated or not treated with nonsteroidal anti-inflammatory drugs (NSAIDs).Our findings confirm a high prevalence of microscopic bowel inflammation in SpA patients, regardless of the use of NSAIDs. The evaluation of fCAL levels proved to be useful in the identification of microscopic inflammation and could help in the more judicious indication of ileocolonoscopy. These results support the use of fCAL for the evaluation of microscopic bowel inflammation in SpA patients.

Background Some studies have suggested the HLA-B27 gene may protect against some infections, as well as it could play a benefit role on the viral clearance, including hepatitis C and HIV. However, there is lack of SARS-CoV-2 pandemic data in spondyloarthritis (SpA) patients. Aim To evaluate the impact of HLA-B27 gene positivity on the susceptibility and severity of COVID-19 and disease activity in axial SpA patients. Methods The ReumaCoV-Brasil is a multicenter, observational, prospective cohort designed to monitor immune-mediated rheumatic diseases patients during SARS-CoV-2 pandemic in Brazil. Axial SpA patients, according to the ASAS classification criteria (2009), with (cases) and without (control group) COVID-19 diagnosis, were paired to sex and age. Other immunodeficiency diseases, past organ or bone marrow transplantation, neoplasms and current chemotherapy were excluded. Demographic data, managing of COVID-19 (diagnosis, treatment, and outcomes, including hospitalization, mechanic ventilation and death), comorbidities, clinical details (disease activity and concomitant medication) were collected using the Research Electronic Data Capture (REDCap) database. Data are presented as descriptive analysis and multiple regression models, using SPSS program, version 20. P level was set as 5%. Results From May 24th, 2020 to Jan 24th, 2021, a total of 269 axial SpA patients were included, of whom 165 (61.3%) with COVID-19 and 104 (38.7%) without COVID-19. Most of them were men (N = 153; 56.9%) with mean age of 46.3 ± 13.8 years and long-term disease (13.1 ± 9.9 years). There were no significant statistically differences concerning social distancing, smoking, BMI, waist circumference and comorbidities. Regarding b-DMARDs, 134 (75.3%) were on TNF inhibitors and 17 (9.6%) on IL-17 antagonists. Comparing those patients with and without COVID-19, the HLA-B27 positivity was not different between groups (n = 45, 73.8% vs. n = 38, 73.1%, respectively; p = 0.93). In addition, disease activity was similar before and after the infection. On the other hand, the control group had significantly higher disease activity score, according to ASDAS-CRP (2.8 ± 1.8 vs. 1.8 ± 1.2, p = 0.03). Interestingly, no new episodes of arthritis, enthesitis or extra-musculoskeletal manifestations were reported after the COVID-19. The mean time from the first symptoms to hospitalization was 7.2 ± 3.6 days, with length of hospitalization quite similar between patients who died and those discharged (12.6 ± 7 and 13.9 ± 11.7, respectively). The global death estimation for COVID-19 was 1.9 (95%CI 0.6–4.3), regardless HLA-B27 status. No significant difference was found regarding concomitant medications, including conventional or biologic DMARDs between the groups. Conclusions No significant difference of COVID-19 frequency rate was observed in patients with axial SpA regarding the HLA-B27 positivity, suggesting a lack of protective effect with SARS-CoV-2 infection. In addition, the disease activity was similar before and after the infection. Trial registration: This study was approved by the Brazilian Committee of Ethics in Human Research (CONEP), CAAE 30186820.2.1001.8807, and was registered at the Brazilian Registry of Clinical Trials – REBEC, RBR-33YTQC. All patients read and signed the informed consent form before inclusion.

Psoriatic arthritis (PsA) is a chronic and systemic immune disease characterized by inflammation of peripheral and/or axial joints and entheses in patients with psoriasis (PsO). Extra-articular and extracutaneous manifestations and numerous comorbidities can also be present. These recommendations replace the previous version published in May 2013. A systematic review of the literature retrieved 191 articles that were used to formulate 12 recommendations in response to 12 clinical questions, divided into 4 sections: diagnosis, non-pharmacological treatment, conventional drug therapy and biologic therapy. These guidelines provide evidence-based information on the clinical management for PsA patients. For each recommendation, the level of evidence (highest available), degree of strength (Oxford) and degree of expert agreement (interrater reliability) are reported.

Background Fibroblast-like synoviocytes (FLS) play a prominent role in rheumatoid synovitis and degradation of the extracellular matrix through the production of inflammatory cytokines and metalloproteinases (MMPs). Since animal models are frequently used for elucidating the disease mechanism and therapeutic development, it is relevant to study the ultrastructural characteristics and functional responses in human and mouse FLS. The objective of the study was to analyze ultrastructural characteristics, Interleukin-6 (IL-6) and Metalloproteinase-3 (MMP-3) production and the activation of intracellular pathways in Fibroblast like synoviocytes (FLS) cultures obtained from patients with rheumatoid arthritis (RA) and from mice with collagen-induced arthritis (CIA). Methods FLSs were obtained from RA patients (RA-FLSs) (n = 8) and mice with CIA (CIA-FLSs) (n = 4). Morphology was assessed by transmission and scanning electron microscopy. IL-6 and MMP-3 production was measured by ELISA, and activation of intracellular signaling pathways (NF-κB and MAPK: p-ERK1/2, p-P38 and p-JNK) was measured by Western blotting in cultures of RA-FLSs and CIA-FLSs stimulated with tumor necrosis factor-alpha (TNF-α) and IL-1β. Results RA-FLS and CIA-FLS cultures exhibited rich cytoplasm, rough endoplasmic reticula and prominent and well-developed Golgi complexes. Transmission electron microscopy demonstrated the presence of lamellar bodies, which are cytoplasmic structures related to surfactant production, in FLSs from both sources. Increased levels of pinocytosis and numbers of pinocytotic vesicles were observed in RA-FLSs (p Conclusion This study provides a comprehensive understanding of the biology of RA-FLS and CIA-FLS. The differences and similarities in ultrastructural morphology and important inflammatory cytokines shown, contribute to future in vitro studies using RA-FLS and CIA-FLS, in addition, they indicate that the adoption of CIA-FLS for studies should take careful and be well designed, since they do not completely resemble human diseases.

Background:Rheumatoid arthritis (RA) is associated with high frequency of comorbidities and increased risk of polypharmacy. Although there is a great potential for complications, there is a gap in literature on polypharmacy in patients with rheumatic arthritis.Objective:To evaluate the prevalence and factors associated with polypharmacy in a population in a real-life setting.Methods:A cross-sectional multicenter study was conducted in Brazil. Patients underwent clinical evaluation and medical records analysis. Polypharmacy was considered as a dependent variable. To test independent variables, we used Poisson regression.Results:We evaluated 792 patients (89% female, median age 56.6 years). Median duration of disease was 12.7 years, 78.73% had a positive rheumatoid factor. The median of disease activity score-28 was 3.5 (disease with mild activity), median of the clinical disease activity index score was 9, and median of health assessment questionnaire-disability index was 0.875; 47% used corticosteroids, 9.1% used nonsteroidal anti-inflammatory drugs, 90.9% used synthetic disease-modifying antirheumatic drugs, 35.7% used biologic disease-modifying antirheumatic drugs (DMARDs). In total, 537 (67.9%) patients used 5 or more drugs. Polypharmacy showed a relationship with a number of comorbidities and use of specific drugs (corticosteroids, methotrexate, and biological DMARDs).Conclusion:We found a high prevalence of polypharmacy (67.9%) in RA. Solutions to management this problem should be stimulated.

BackgroundPatients with severe COVID-19 seem to have a compromised antiviral response and hyperinflammation. Neutrophils are critical players in COVID-19 pathogenesis. IL-17A plays a major role in protection against extracellular pathogens and neutrophil attraction and activation. We hypothesized that secukinumab, an anti-IL17A monoclonal antibody, could mitigate the deleterious hyperinflammation in COVID-19.MethodsBISHOP was an open-label, single-center, phase-II controlled trial. Fifty adults hospitalized Covid-19 patients, confirmed by a positive SARS-CoV-2 RT-PCR, were randomized 1:1 to receive 300mg of secukinumab subcutaneously at day-0 (group A) plus standard of care (SoC: antiviral drugs, antimicrobials, corticosteroids, and/or anticoagulants) or SoC alone (group B). A second dose of 300mg of secukinumab could be administered on day-7, according to staff judgment. The primary endpoint was ventilator-free days at day-28 (VFD-28). Secondary efficacy and safety outcomes were also explored.FindingsAn intention-to-treat analysis showed no difference in VFD-28: 23.7 (95%CI 19.6-27.8) in group A vs. 23.8 (19.9-27.6) in group B, p=0.62; There was also no difference in hospitalization time, intensive care unit demand, the incidence of circulatory shock, acute kidney injury, fungal or bacterial co-infections, and severe adverse events. Pulmonary thromboembolism was less frequent in group A (4.2% vs. 26.2% p=0.04). There was one death in each group. Viral clearance, defined by the viral load fold change (2-ΔΔCT) in upper airways, between day-0 and day-7, was also similar: 0.17 (0.05-0.56) in group A vs. 0.24 (0.10-0.57) in group B.InterpretationThe efficacy of secukinumab in the treatment of Covid19 was not demonstrated. No difference between groups in adverse events and no unexpected events were observed.FundingNovartis Brazil supported this research providing expert input in the development of the project, drug supply, data management, and monitoring.

BackgroundFibroblast-like synoviocytes (FLS) play a prominent role in rheumatoid synovitis and degradation of the extracellular matrix through the production of inflammatory cytokines and metalloproteinases (MMPs). Since animal models are frequently used for elucidating the disease mechanism and therapeutic development, it is relevant to compare ultrastructural characteristics and functional responses by human and mouse FLS. The objective of this study is to compare ultrastructural characteristics, IL-6 and MMP-3 production, and the activation of intracellular pathways in FLS from patients with RA (RA-FLS) and mice with collagen-induced arthritis (CIA-FLS). The objective of the study was to compare ultrastructural characteristics, Interleukin-6 (IL-6) and Metalloproteinase-3 (MMP-3) production and the activation of intracellular pathways in Fibroblast like synoviocytes (FLS) cultures obtained from patients with Rheumatoid Arthritis (RA) and from mice with collagen-induced arthritis.MethodsFLSs were obtained from RA patients (RA-FLSs) (n = 8) and mice with collagen-induced arthritis (CIA-FLSs) (n = 4). Morphology was assessed by transmission and scanning electron microscopy. IL-6 and MMP-3 production was measured by ELISA, and activation of intracellular signaling pathways (NF-κB and MAPK: p-ERK1/2, p-P38 and p-JNK) was measured by Western blotting in cultures of RA-FLSs and CIA-FLSs stimulated with tumor necrosis factor - alpha (TNF-α) and IL-1β.ResultsRA-FLS and CIA-FLS cultures exhibited rich cytoplasm, rough endoplasmic reticula and prominent and well-developed Golgi complexes. Transmission electron microscopy demonstrated the presence of lamellar bodies, which are cytoplasmic structures related to surfactant production, in FLSs from both sources. Increased levels of pinocytosis and numbers of pinocytotic vesicles were observed in RA-FLSs (p in vitro studies of RA etiopathogenesis and new therapeutic targets.

Rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) are inflammatory diseases with different bone remodeling patterns. Fibroblast-like synoviocytes (FLS) are cells involved in the transition from an acute and reparable phase to a chronic and persistent stage in these diseases. The distinction of joint phenotypes involves inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-17, and IL-22 directly or through key signaling pathways such as Wnt. To evaluate the role of FLS as the source of Wnt antagonists (sFRP3/FRZB and Dkk1) in the synovia, levels of TNF- α, IL-17, IL-22, Dkk1, and sFRP3 were measured by ELISA directly in the synovial fluid of patients with RA, PsA, or AS. Dkk1 and sFRP3 were also measured in the FLS culture supernatants after different inflammatory stimulus. sFRP3 and Dkk1 are constitutively expressed by FLS. IL-22 and sFRP3 were positively correlated (r=0.76; P

Background Discordance between patient’s global assessment (PtGA) and physician’s global assessment (PhGA) has been described in rheumatoid arthritis (RA). Understanding the reasons for this discrepancy is important in the context of treat-to-target treatment strategy. Objective To assess the determinants of PtGA and PhGA and factors associated with discordance between them. Methods The REAL study included RA patients from Brazilian public health centers. Clinical, laboratory and outcomes measures were collected. PtGA and the PhGA were rated on a visual analog scale and analyzed. Three groups were defined: no discordance (difference between PtGA and PhGA within 3 cm), positive discordance (PtGA exceeding PhGA by >3 cm), and negative discordance (PtGA less than PhGA by >3 cm). Multivariate regression analysis was used to identify determinants of PtGA and PhGA and their discordance. Results 1115 patients (89,4% female, mean age 56.7y and median disease duration of 12.7y) were enrolled. Two factors were associated with PtGA in the final multivariate model: one point increase in the pain scale leads to an increase of 0.62 in PtGA; one point increase in HAQ increases by 9,25 points the PtGA. The factors associated with PhGA were pain scale, number of tender and swollen joints (NTJ and NSJ), positive RF, ESR, HAQ-DI and use of corticosteroids. Discordance between patient and physician was found in 30.52%: positive discordance in 24.6% and negative discordance in 5.92%. An increase of one point in the NSJ was associated with a 12% increase in the chance of negative discordance. The chance of positive discordance increased by 90% and 2% for each unit increased in HAQ-DI and pain scale respectively. Finally, the chance of positive discordance decreased by 3% for each point increased in NTJ and by 15% for each point increased in NSJ. Conclusion In one-third of the assessments, there was disagreement between PtGA and PhGA (a positive discordance was found in 80% of them). Pain and function were determinants for patients to estimate disease activity, while swollen joints was the main factor related to a worse physician’s evaluation. These data show how different can be the perspectives of patients and assistants.

Background Discordance between the patient‘s global assessment of disease activity (PGA) and examiner’s global assessment (EGA) has been described in rheumatoid arthritis (RA) (1,2). Understanding the reasons for this discrepancy is essential in the context of treat-to-target treatment strategy. Objectives To assess the determinants of PGA and EGA and factors associated with discordance between them. Methods The REAL study included RA patients from Brazilian public health centers. Clinical, laboratory and outcomes measures were collected. PGA and EGA were rated on a visual analog scale and analyzed. Three groups were defined: no discordance (a difference between PGA and EGA within 3 cm), positive discordance (PGA exceeding EGA by >3 cm), and negative discordance (PGA less than EGA by >3 cm). Multivariate regression analysis was used to identify determinants of PGA and EGA and their discordance. Results 1115 patients (89,4% female, mean age 56.7y and median disease duration of 12.7y) were enrolled. Two factors were associated with PGA in the final multivariate model: one point increase in the pain scale (PS) leads to an increase of 0.62 in PGA; one point increase in HAQ increases by 9,25 points the PGA. The factors associated with EGA were: PS, number of tender and swollen joints (NTJ and NSJ), RF, ESR, HAQ and use of corticosteroids. Discordance between patient and physician was found in 30.52%: positive discordance (PD) in 24.6% and negative discordance (ND) in 5.92%. An increase of one point in the NSJ was associated with a 12% increase in the chance of ND. The chance of PD increased by 90% and 2% for each unit increased in HAQ and PS respectively. Finally, the chance of PD decreased by 3% for each point increased in NTJ and by 15% for each point increased in NSJ. Conclusion In one-third of the assessments, there was disagreement between PGA and EGA (a PD in 80% of them). Pain and function were determinants for patients to estimate disease activity, while swollen joints were the main factor related to a worse examiner’s evaluation. These data show how different can be the perspectives of patients and assistants. References [1] Smolen JS, Strand V, Koenig AS, Szumski A, Kotak S, Jones TV. Discordance between patient and physician assessments of global disease activity in rheumatoid arthritis and association with work productivity. Arthritis Res Ther. 2016; 18:114. [2] Desthieux C, Hermet A, Granger B, Fautrel B, Gossec L. Patient-physician discordance in global assessment in rheumatoid arthritis: a systematic literature review with meta-analysis. Arthritis Care Res (Hoboken). 2016; 68:1767. Disclosure of Interests Maria Fernanda Guimaraes: None declared, Maria Raquel Pinto: None declared, Gustavo Resende Grant/research support from: ABBVIE, PFIZER, Consultant for: ABBVIE, JANSSEN, NOVARTIS, Paid instructor for: Novartis, Janssen, Speakers bureau: ABBVIE, JANSSEN, NOVARTIS, PFIZER, UCB, Carla Machado: None declared, Ana Beatriz Vargas-Santos Grant/research support from: Has received personal fees and/or non-financial support from Pfizer, AbbVie, AstraZeneca, Janssen, Bristol-Myers Squibb, Roche, Novartis and UCB, Cleandro Albuquerque Shareholder of: Has received personal fees and/or non-financial support from Pfizer, AbbVie, AstraZeneca, Janssen, Bristol-Myers Squibb, Roche, Novartis and UCB, Grant/research support from: Has received personal fees and/or non-financial support from Pfizer, AbbVie, AstraZeneca, Janssen, Bristol-Myers Squibb, Roche, Novartis and UCB, Consultant for: Has received personal fees and/or non-financial support from Pfizer, AbbVie, AstraZeneca, Janssen, Bristol-Myers Squibb, Roche, Novartis and UCB, Paid instructor for: Has received personal fees and/or non-financial support from Pfizer, AbbVie, AstraZeneca, Janssen, Bristol-Myers Squibb, Roche, Novartis and UCB, Speakers bureau: Has received personal fees and/or non-financial support from Pfizer, AbbVie, AstraZeneca, Janssen, Bristol-Myers Squibb, Roche, Novartis and UCB, Manoel Bertolo Speakers bureau: Has delivered speeches at events sponsored by AbbVie and Pfizer, Paulo Louzada Jr Consultant for: Has received consulting fees from Pfizer, Rina Giorgi Consultant for: Has received consulting fees from Roche, Pfizer, Bristol-Myers Squibb, UCB, Eli-Lilly, AbbVie, Abbott and EMS, Speakers bureau: Has received speaking fees from Roche, Pfizer, Bristol-Myers Squibb, UCB, Eli-Lilly, AbbVie, Abbott and EMS, Sebastiao Radominski Consultant for: Abbvie, Celgene, Genentech/Roche, Janssen, Pfizer, UCB, Speakers bureau: Abbvie, Celgene, Genentech/Roche, Janssen, Pfizer, UCB, Karina Bonfiglioli Speakers bureau: Has received speaking fees from Roche, Pfizer, Bristol-Myers Squibb, Abbvie and Janssen., Maria de Fatima Sauma: None declared, Ivanio Pereira Consultant for: Has received consulting fees from Roche, Pfizer, UCB Pharma, Eli-Lilly, Abbvie and Janssen, Speakers bureau: Has received speaking fees Roche, Pfizer, UCB Pharma, Eli-Lilly, Abbvie and Janssen, Claiton Brenol Shareholder of: Has participated in clinical and/or experimental studies related to this work and sponsored by AbbVie, BMS, Janssen, Pfizer and Roche; has received personal or institutional support from AbbVie, BMS, Janssen, Pfizer and Roche; has delivered speeches at events related to this work and sponsored by AbbVie, Janssen, Pfizer and Roche, Grant/research support from: Has participated in clinical and/or experimental studies related to this work and sponsored by AbbVie, BMS, Janssen, Pfizer and Roche; has received personal or institutional support from AbbVie, BMS, Janssen, Pfizer and Roche; has delivered speeches at events related to this work and sponsored by AbbVie, Janssen, Pfizer and Roche, Consultant for: Has participated in clinical and/or experimental studies related to this work and sponsored by AbbVie, BMS, Janssen, Pfizer and Roche; has received personal or institutional support from AbbVie, BMS, Janssen, Pfizer and Roche; has delivered speeches at events related to this work and sponsored by AbbVie, Janssen, Pfizer and Roche, Paid instructor for: Has participated in clinical and/or experimental studies related to this work and sponsored by AbbVie, BMS, Janssen, Pfizer and Roche; has received personal or institutional support from AbbVie, BMS, Janssen, Pfizer and Roche; has delivered speeches at events related to this work and sponsored by AbbVie, Janssen, Pfizer and Roche, Speakers bureau: Has delivered speeches at events sponsored by AbbVie, Janssen, Pfizer and Roche, Licia Mota Speakers bureau: Has delivered speeches at events sponsored by AbbVie, Janssen, Pfizer, Roche and UCB., Geraldo Castelar-Pinheiro Consultant for: Has received consulting fees from AbbVie, Bristol-Myers Squibb, Eli Lilly, Glaxosmithkline, Janssen, Pfizer, Sanofi Genzyme and Roche

WhatsApp has revolutionized the way people communicate and interact. It is not only cheaper than the traditional Short Message Service (SMS) communication but it also brings a new form of mobile communication: the group chats. Such groups are great forums for collective discussions on a variety of topics. In particular, in events of great social mobilization, such as strikes and electoral campaigns, WhatsApp group chats are very attractive as they facilitate information exchange among interested people. Yet, recent events have raised concerns about the spreading of misinformation in WhatsApp. In this work, we analyze information dissemination within WhatsApp, focusing on publicly accessible political-oriented groups, collecting all shared messages during major social events in Brazil: a national truck drivers' strike and the Brazilian presidential campaign. We analyze the types of content shared within such groups as well as the network structures that emerge from user interactions within and cross-groups. We then deepen our analysis by identifying the presence of misinformation among the shared images using labels provided by journalists and by a proposed automatic procedure based on Google searches. We identify the most important sources of the fake images and analyze how they propagate across WhatsApp groups and from/to other Web platforms.

Microbiota is the name given to the set of microorganisms that cohabit a multicellular organism. In the human microbiota, the number of bacteria exceeds that of eukaryotes and archaea by 2–3 orders of magnitude, and therefore, it has been estimated that in an adult human body there would be 10 times more cells of microorganisms than human cells. Dysbiosis is any loss of the microbial state of equilibrium in a given ecosystem. Considering the relationship between microbiota and the bidirectional immune system, the problem that dysbiosis may not be a cause but a consequence of these diseases (its microbial phenotype) still persists without definitive solution. Given the large amount of evidence of microbioma participation in various clinical conditions, the manipulation of this ecosystem in favor of the rescue of beneficial functions or the suppression of harmful activities presents itself as an attractive therapeutic alternative. The stimulus to rebalance of the microbiome could be tried through nutritional therapy, the use of probiotics (live microorganisms administered in sufficient amounts to bring health benefits), prebiotics (food compounds not digestible by the host, but with a capacity of stimulate the growth of specific members of the microbiota), or symbiotic (probiotics and prebiotics administered simultaneously). Finally, another way to permanently change the diseased microbiota is fecal microbiota transplantation from healthy donors.

In Brazil, 48% of the population use WhatsApp to share and discuss news. Currently, there are serious concerns that this platform can become a fertile ground for groups interested in disseminating misinformation, especially as part of articulated political campaigns. Particularly, WhatsApp provides an important space for users to engage in public conversations that worth attention, the public groups. These groups are suitable for political activism and social movement organization. Additionally, it is reasonable to assume that a malicious misinformation campaign might attempt to maximize the audience of a fake story by sharing it in existing public groups. In this paper, we present a system for gathering, analyzing and visualize public groups in WhatsApp. In addition to describe our methodology, we also provide a brief characterization of the content shared in 127 Brazilian groups. We hope our system can help journalists and researchers to understand the repercussion of events related to the Brazilian elections within these groups.

ResumoObjetivoAvaliar os resultados da aplicação do Índice de Atividade de Doença da Espondilite Anquilosante de Bath (BASDAI) numa série de pacientes brasileiros com EpA e estabelecer suas correlações com as variáveis específicas do grupo.MétodosUm protocolo comum de investigação foi prospectivamente aplicado em 1.492 pacientes brasileiros classificados como EpA pelos critérios do Grupo Europeu de Estudo das Espondiloartropatias (ESSG), acompanhados em 29 centros de referência em reumatologia no Brasil. Variáveis clínicas, demográficas e índices de doença foram colhidos. Os valores totais do BASDAI foram comparados com a presença das diferentes variáveis.ResultadosO valor médio do BASDAI foi de 4,20 ± 2,38. Os escores médios do BASDAI foram mais elevados nos pacientes com forma clínica combinada, comparado às formas axiais e periféricas isoladas, nos pacientes do sexo feminino e nos sedentários. Com relação ao componente axial, valores mais altos do BASDAI estiveram significativamente associados à lombalgia inflamatória, à dor alternante em nádegas, à dor cervical e ao acometimento de coxofemorais. Houve associação estatística entre os valores do BASDAI e o comprometimento periférico, relacionado ao número de articulações inflamadas, tanto dos membros inferiores quanto dos membros superiores, e às entesites. A positividade do HLA‐B27 e a presença de manifestações extra‐articulares não estiveram correlacionadas com os valores médios do BASDAI. Valores mais baixos do BASDAI estiveram associados ao uso de agentes biológicos (p

Background Rheumatoid arthritis (RA) and osteoarthritis (OA) are chronic joint diseases in which fibroblast-like synoviocytes (FLS) actively participate in the synovitis- damage cycle, trough production of cytokines such as IL-6 and metalloproteinases (MMPs)(1). It has already been showed that serum IL-33 levels correlated with disease activity in RA(2). IL-33 is capable to enhance TNF-α effects in FLS(3). In the collagen-induced arthritis (CIA) model, the injection of IL-33 exacerbated the disease(4). Since ST2 receptor is expressed in FLS, it is hypothesized that IL-33 could activate FLS and increase downstream production of inflammatory cytokines. Objectives To evaluate the production of IL-6, MMP-1, and MMP-3 by FLS stimulated with IL-33, TNF-α, and IL-1β. Methods FLS were cultured from samples of synovial fluid and tissue of OA patients (OAFLS n=8), RA patients (RAFLS n=3), and patients without rheumatic disease (health) (HFLS n=4). FLS were stimulate with TNF-α at concentrations of 1; 5; 10 and 50 ng/ml, IL-1β at concentrations of 0.1; 0.2; 0.3; 0.5 and 1 ng/ml and IL-33 at concentrations of 1; 3; 10; 30; 100 ng/ml, soon after, IL-6, MMP-1, and MMP-3 levels were evaluated by ELISA, in the cell supernatant. Results MMP-1, MMP-3 and IL-6 were constitutively expressed by FLS at baseline in all groups. Both TNF-α and IL-1β stimulated the production of IL-6 and MMP-1 with statistical significance in a dose-dependent manner in all three groups. Only IL-1β increased the production of MMP-3. TNF-α stimulated the production of MMP-3 only on HFLS. There was no difference between the concentration of MMP-1, MMP-3 and IL6 in the supernatant of OAFLS, ARFLS and HFLS when IL-33 stimulated and non-stimulated were compared. Conclusions This study demonstrated that IL-33 failed to induce the production of IL-6, MMP-1 and MMP-3 by FLS of different diseases sources, suggesting that must be another cell type that plays the role of target to IL-33 in physiopathology of joint inflammation. The absence MMP-3 in response to TNF-α stimulus in RAFLS and OAFLS could be explain by saturation of this cytokine in synovial cells from these diseases. References Bartok B, Firestein GS. Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. Immunological reviews. 2010;233(1):233–55. Matsuyama Y, Okazaki H, Tamemoto H, Kimura H, Kamata Y, Nagatani K, et al. Increased levels of interleukin 33 in sera and synovial fluid from patients with active rheumatoid arthritis. The Journal of rheumatology. 2010;37(1):18–25. Kunisch E, Chakilam S, Gandesiri M, Kinne RW. IL-33 regulates TNF-alpha dependent effects in synovial fibroblasts. International journal of molecular medicine. 2012;29(4):530–40. Xu D, Jiang HR, Kewin P, Li Y, Mu R, Fraser AR, et al. IL-33 exacerbates antigen-induced arthritis by activating mast cells. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(31):10913–8. Acknowledgements Capes, Fapemig and Fundo de Apoio a Pesquisa e Ensino da Sociedade Brasileira de Reumatologia - FAPE-SBR. Disclosure of Interest None declared

The aim of the present study was to analyze the score of fatigue in a large cohort of Brazilian patients with SpA, comparing different disease patterns and its association with demographic and disease-specific variables.A common protocol of investigation was prospectively applied to 1492 Brazilian patients classified as SpA according to the European Spondyloarthropathies Study Group (ESSG) criteria, attended at 29 reference centers. Clinical and demographic variables were recorded. Fatigue was evaluated using the first item of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questionnaire.The mean BASDAI fatigue score was 4.20 ± 2.99. There was no significant difference in the fatigue score between the different SpA. Fatigue was higher in female patients (p0.001), with mixed (axial + peripheral) involvement (p0.001) and in those who did not practice exercises (p0.001). Higher scores of fatigue were significantly associated with inflammatory low back pain (p = 0.013), alternating buttock pain (p = 0.001), cervical pain (p = 0.001), and hip involvement (p = 0.005). Fatigue presented a moderate positive statistical correlation with Bath Ankylosing Spondylitis Functional Index (BASFI) (0.469; p0.001) and Ankylosing Spondylitis Quality of Life (0.462; p0.001).In this large series of Brazilian SpA patients, higher fatigue scores were associated with female gender, sedentary, worse functionality, and quality of life.

Introdução: Poucos estudos avaliaram o perfil do uso de drogas modificadoras de doença (DMD) em pacientes brasileiros com diagnóstico de espondiloartrite (EpA). Métodos: Um protocolo comum de investigação foi prospectivamente aplicado em 1505 pacientes classificados como EpA pelos critérios do Grupo Europeu de Estudo das Espondiloartrites (ESSG), acompanhados em 29 centros de referência em Reumatologia no Brasil. Variáveis clínicas e demográficas foram obtidas e avaliadas, analisando-se suas correlações com o uso das DMD metotrexato (MTX) e sulfasalazina (SSZ). Resultados: Pelo menos uma DMD foi utilizada por 73,6% dos pacientes, sendo MTX por 29,2% e SSZ por 21,7%, enquanto 22,7% utilizaram ambas as drogas. O uso do MTX foi significativamente associado ao acometimento periférico, e a SSZ foi associada ao comprometimento axial, sendo que as duas drogas foram mais utilizadas, isoladas ou combinadas, no comprometimento misto (p < 0,001). O uso de uma DMD esteve significativamente associado à etnia branca (MTX; p = 0,014), lombalgia inflamatória (SSZ; p = 0,002), dor em nádegas (SSZ; p = 0,030), cervicalgia (MTX; p = 0,042), artrite de membros inferiores (MTX; p < 0,001), artrite de membros superiores (MTX; p < 0,001), entesite (p = 0,007), dactilite (MTX; p < 0,001), doença inflamatória intestinal (SSZ; p < 0,001) e acometimento ungueal (MTX; p < 0,001). Conclusão: O uso de pelo menos uma DMD foi referido por mais de 70% dos pacientes numa grande coorte brasileira de pacientes com EpA, sendo o uso do MTX mais associado ao acometimento periférico e o uso da SSZ mais associado ao acometimento axial. Introduction: Few studies have evaluated the profile of use of disease modifying drugs (DMD) in Brazilian patients with spondyloarthritis (SpA). Methods: A common research protocol was applied prospectively in 1505 patients classified as SpA by criteria of the European Spondyloarthropathies Study Group (ESSG), followed at 29 referral centers in Rheumatology in Brazil. Demographic and clinical variables were obtained and evaluated, by analyzing their correlation with the use of DMDs methotrexate (MTX) and sulfasalazine (SSZ). Results: At least one DMD was used by 73.6 % of patients: MTX by 29.2 % and SSZ by 21.7%, while 22.7 % used both drugs. The use of MTX was significantly associated with peripheral involvement, and SSZ was associated with axial involvement, and the two drugs were more administered, separately or in combination, in the mixed involvement (p < 0.001). The use of a DMD was significantly associated with Caucasian ethnicity (MTX , p = 0.014), inflammatory back pain (SSZ, p = 0.002) , buttock pain (SSZ, p = 0.030), neck pain (MTX, p = 0.042), arthritis of the lower limbs (MTX, p < 0.001), arthritis of the upper limbs (MTX, p < 0.001), enthesitis (p = 0.007), dactylitis (MTX, p < 0.001), inflammatory bowel disease (SSZ, p < 0.001) and nail involvement (MTX, p < 0.001). Conclusion: The use of at least one DMD was reported by more than 70% of patients in a large cohort of Brazilian patients with SpA, with MTX use more associated with peripheral involvement and the use of SSZ more associated with axial involvement.

Objective.To analyze the clinical effect of enthesitis in a large Brazilian cohort of patients with spondyloarthritis (SpA).Methods.A common protocol of investigation was prospectively applied to 1505 patients with SpA in 29 centers in Brazil. Clinical and demographic variables and disease indexes were investigated. The Maastricht Ankylosing Spondylitis Enthesitis Score was used to investigate the enthesitis component. Ankylosing spondylitis was the most frequent disease in the group (65.4%). Others were psoriatic arthritis (18.4%), undifferentiated SpA (6.7%), reactive arthritis (3.3%), and enteropathic arthritis (3.2%).Results.At least 1 affected enthesis was observed in 54% of the patients with SpA, with a mean of 2.12 ± 2.98 entheses affected. According to the clinical presentation, enthesitis was significantly more frequent in patients with axial + peripheral joint involvement compared to isolated axial or peripheral involvement (p < 0.001). There was a statistical association between the presence of enthesites and axial symptoms (buttock pain, cervical pain, and hip pain), and peripheral symptoms (lower limb arthritis, number of painful and swollen joints; p < 0.05). Patients with enthesitis also presented higher mean scores of Bath Ankylosing Spondylitis Functional Index (BASFI; p < 0.001), Bath Ankylosing Spondylitis Disease Activity Index (p < 0.001), and Ankylosing Spondylitis Quality of Life (ASQoL; p < 0.001). Multivariate logistic regression showed that BASFI (p < 0.0001; OR 74.839), ASQoL (p = 0.0001; OR 14.645), and Achilles tendonitis (p = 0.0059; OR 7.593) were associated with work incapacity.Conclusion.The clinical presence of enthesitis in this large cohort of patients with SpA was frequent and was associated with a significant increase in disease activity and decline in functional capacity and quality of life.

Introdução A artrite reumatoide (AR), a artrite psoriásica (AP) e a espondilite anquilosante (EA) são exemplos de doenças articulares inflamatórias (DAI) com diferentes padrões de remodelação articular. Os FLS estão envolvidos na transição de uma fase aguda e reparável, para um estágio crônico e persistente, nestas enfermidades. A distinção dos fenótipos articulares envolve citocinas inflamatórias como TNFa, IL17 e IL22, de maneira direta, ou através de vias de sinalização como a Wnt. Objetivos Avaliar a expressão de dois moduladores extracelulares (sFRP3/Frzb e Dkk1) da via Wnt por FLS de pacientes com diferentes DAI, em resposta a IL17, IL22 ou TNFa. Métodos FLS foram cultivados a partir do líquido sinovial de pacientes com DAI. Os níveis de Dkk1 e sFRP3/Frzb foram medidos por ELISA, nos sobrenadantes das culturas, após diferentes estímulos com IL17, IL22 ou TNFa. As concentrações de Dkk1, sFRP3/Frzb, TNFa, IL17 e IL22 também foram mensuradas no líquido sinovial por ELISA. Resultados sFRP3/Frzb e Dkk1 são expressos de forma constitutiva pelos FLS. IL22 se correlacionou positivamente com sFRP3/Frzb (r = 0,76; p

Objective.Spondyloarthritides (SpA) can present different disease spectra according to ethnic background. The Brazilian Registry of Spondyloarthritis (RBE) is a nationwide registry that comprises a large databank on clinical, functional, and treatment data on Brazilian patients with SpA. The aim of our study was to analyze the influence of ethnic background in SpA disease patterns in a large series of Brazilian patients.Methods.A common protocol of investigation was prospectively applied to 1318 SpA patients in 29 centers distributed through the main geographical regions in Brazil. The group comprised whites (65%), African Brazilians (31.3%), and people of mixed origins (3.7%). Clinical and demographic variables and various disease index scores were compiled. Ankylosing spondylitis (AS) was the most frequent disease in the group (65.1%); others were psoriatic arthritis (18.3%), undifferentiated SpA (6.8%), enteropathic arthritis (3.7%), and reactive arthritis (3.4%).Results.White patients were significantly associated with psoriasis (p = 0.002), positive HLA-B27 (p = 0.014), and use of corticosteroids (p < 0.0001). Hip involvement (p = 0.02), axial inflammatory pain (p = 0.04), and radiographic sacroiliitis (p = 0.025) were associated with African Brazilian descent. Sex distribution, family history, and presence of peripheral arthritis, uveitis, dactylitis, urethritis, and inflammatory bowel disease were similar in the 3 groups, as well as age at disease onset, time from first symptom until diagnosis, and use of anti-tumor necrosis factor-α agents (p > 0.05). Schober test and thoracic expansion were similar in the 3 groups, whereas African Brazilians had higher Maastricht Ankylosing Spondylitis Enthesitis Scores (p = 0.005) and decreased lateral lumbar flexion (p = 0.003), while whites had a higher occiput-to-wall distance (p = 0.02). African Brazilians reported a worse patient global assessment of disease (p = 0.011). Other index scores and prevalence of work incapacity were similar in the 3 groups, although African Brazilians had worse performance in the Ankylosing Spondylitis Quality of Life questionnaire (p < 0.001).Conclusion.Ethnic background is associated with distinct clinical aspects of SpA in Brazilian patients. African Brazilian patients with SpA have a poorer quality of life and report worse disease compared to whites.

Gustavo G. Resende a,*, Cristina C. D. Lannaa, Adriana B. Bortoluzzob, Celio R. Goncalvesc, Percival D. Sampaio -Barrosc, Jose Antonio Braga da Silvad, Antonio Carlos Ximenese, Manoel B. Bertolo f, Sandra L.E. Ribeiro g, Mauro Keisermanh, Rita Menini, Thelma L. Skare j, Sueli Carneirok, Valderilio F. Azevedol, Walber P. Vieiram, Elisa N. Albuquerquen, Washington A. Bianchio, Rubens Bonfiglioli p, Cristiano Campanholoq, Hellen M. S. Carvalhor, Izaias P. Costas, Angela P. Duartet, Charles L. Kohemu, Nocy Leitev, Sonia A. L. Limaw, Eduardo S. Meirelles x, Ivânio A. Pereiray, Marcelo M. Pinheiro z, Elizandra Polito A, Francisco Airton C. RochaB, Mittermayer B. SantiagoC, Maria de Fatima L. C. SaumaD, Valeria ValimE

Objective: To analyze quality of life and demographic and clinical variables associated to its impairment in a large Brazilian cohort of patients with spondyloarthritis (SpA). Methods: A common protocol of investigation was applied to 1465 Brazilian patients classified as SpA according to the European Spondyloarthropaties Study Group (ESSG) criteria, attended at 29 reference centers for Rheumatology in Brazil. Clinical and demographic variables were recorded. Quality of life was analyzed through the Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire. Results: The mean ASQoL score was 7.74 (+/- 5.39). When analyzing the specific diseases in the SpA group, the ASQoL scores did not present statistical significance. Demographic data showed worse scores of ASQoL associated with female gender (p = 0.014) and African Brazilian ethnicity (p

Objetivo Analisar as características clínicas e epidemiológicas das espondiloartrites (EpA) de início juvenil (< 16 anos) e compará-las com um grupo de pacientes com EspA de início na vida adulta (≥ 16 anos). Pacientes e métodos Coorte prospectiva, observacional e multicêntrica com 1.424 pacientes com diagnóstico de EspA de acordo com o European Spondyloarthropathy Study Group (ESSG) submetidos a um protocolo comum de investigação e recrutados em 29 centros de referência participantes do Registro Brasileiro de Espondiloartrites (RBE). Os pacientes foram divididos em dois grupos: idade no início