Brazilian Registry of Sjögren’s Disease (BRAS): a full picture of Sjögren’s disease

Brazilian Registry of Sjögren’s Disease (BRAS): a full picture of Sjögren’s disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Brazilian Registry of Sjögren’s Disease (BRAS): a full picture of Sjögren’s disease Valéria Valim, Samira Tatiyama Miyamoto, Fabiola Reis de Oliveira, and 24 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4960285/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The Brazilian Registry on Sjögren's Disease (BRAS) is a prospective, national cohort registry. To date, 16 centers from all Brazilian regions are engaged in collaborative research, with the potential for additional centers to be included over time. The BRAS project started in 2021 and has the support of the Brazilian Society of Rheumatology (SBR). The primary objective of BRAS is to generate a set of Brazilian epidemiological data on patients with SjD who meet the 2002 AECG and/or 2016 ACR-EULAR classification criteria, and to promote high-quality clinical research. The Research Electronic Data Capture (REDCap) platform is being used for the entry of clinical data. In addition to demographic and laboratory data, clinical data are being collected, including disease activity (EULAR Sjögren's Syndrome Disease Activity Index - ESSDAI), disease damage (Sjögren's Syndrome Disease Damage Index-SSDDI), comorbidities, cardiovascular risk (Framingham), labial salivary gland biopsy, salivary gland ultrasound, and pharmacological and non-pharmacological treatment. Additionally, patient-reported outcome measures (PROMs) are being incorporated, including the EULAR Sjögren's Syndrome Patient-Reported Index (ESSPRI), Profile of Fatigue and Discomfort (PROFAD), Hospital Anxiety and Depression Scale (HADS), Epworth sleepiness scale (ESE), International Physical Activity Questionnaire-short form (IPAQ-SF), and EuroQol-5 Domain (EQ-5D). The study is currently enrolling 1,010 patients. The mean age of the 1,010 SjD patients is 55.6 ± 13.6 years, with 96.5% of women. Ninety-three percent of patients present with xerostomia, 93.7% xerophthalmia, 78.9% anti-Ro/SSA, and 41.8% anti-La/SSB. Ninety-four percent and 90% of patients have met the 2002 AECG and 2016 ACR-EULAR classification criteria, respectively. There is a potential for future studies to investigate the clinical and laboratory profile, predictors of systemic involvement and cardiovascular risk; prevalence of anxiety and depression and associations, level of physical activity and associations, comorbidities and polypharmacy; in addition, treatment response, follow-up of disease activity and mortality. The next step is to create a biorepository for biological specimens. Sjögren's disease registry epidemiology cohort prevalence Figures Figure 1 Figure 2 Background Sjögren's disease (SjD) is a chronic, immune-mediated, systemic inflammatory disease. It is characterized by the presence of lymphocytic infiltrate in the salivary and lacrimal glands, autoantibodies, and glandular disorders that are clinically expressed by xerostomia and xerophthalmia. Systemic manifestations occur in approximately 50% of patients and can be severe, with an association between these manifestations and the prognosis and development of lymphoma [ 1 , 2 ]. SjD without overlap with other autoimmune rheumatic diseases affects 43.03 (25.74 to 60.31) individuals per 100,000 inhabitants, with a female-to-male ratio of 9–14 to 1 [ 3 ]. In Brazil, the prevalence of SjD in the general population was found to be 0.17% [ 4 ]. However, the clinical spectrum of SjD differs between countries and continents due to the influence of genetic and environmental factors [ 5 , 6 ]. While treatments may improve symptoms and prevent complications, there is currently no approved option that can alter the natural history of the disease. The most prevalent benign symptoms, such as dryness, fatigue, and pain, continue to present a challenge to health professionals in their management and biomedical researchers in the delineation of the intricate pathophysiological pathways. Systemic manifestations can present diagnostic and management challenges, particularly when there is overlap with other autoimmune diseases. The ongoing treatment strategies are empirical and rely on symptomatic management. There is currently no biological or synthetic disease-modifying antirheumatic drug (DMARD) that has been proven to alter the progression of the disease [ 7 , 8 ]. The health-related quality of life (HRQoL) of individuals with SjD has been shown to be markedly reduced in numerous cross-sectional studies conducted in various countries when compared with that of healthy controls. This reduction in HRQoL has been associated not only with the primary symptoms experienced by these individuals, such as dryness, pain, and fatigue, but also with dysautonomia, low physical function and activity level, pruritus, and a range of additional disorders, including psychological, oral, ocular, sexual, and sleep-related disorders. However, some studies have indicated that pain and fatigue are predictors of poor HRQoL, while symptoms are not associated with systemic disease activity [ 9 ]. As HRQoL plays an increasingly pivotal role in medical decision-making, it is imperative to conduct long-term follow-up of individuals to ascertain the predictors of worsening HRQoL in accordance with disease fluctuations and multidisciplinary clinical management. Significant advances have been made in the field of SjD research since the development and validation of the evaluation tools by the EULAR Sjögren's Task Force. These include the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) for patients' symptoms and the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) for systemic features [ 10 ]. Furthermore, the 2016 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for SjD [ 11 ] have enabled the establishment of international consensus for the classification of the disease, thereby facilitating cohort studies that are more comparable and enabling the compilation of more detailed information to better understand the course of the disease. Large cohort studies are a valuable tool for understanding the chronic pathological mechanisms of SjD due to the slow and progressive nature of the disease, coupled with significant heterogeneity among patient populations regarding their geographical, environmental, and genetic diversity, as well as their phenotypic and endotype manifestations of the disease. To illustrate, the "Big Data Sjögren Project" yielded initial evidence indicating that geographic location and ethnicity have a pronounced influence on the clinical manifestation of SjD at the time of diagnosis [ 5 ]. Moreover, it has the potential to elucidate whether environmental factors such as pollution may contribute to the disease's risk and progression [ 12 ]. The Big Data Sjögren's Project Consortium, an international multicenter registry initiated in 2014, aggregated the extant clinical databases from leading centers in clinical research across the five continents for the purpose of analyzing the clinical and geoepidemiological characterization of SjD [ 13 ]. By January 2023, the number of patients enrolled at the participating centers had reached 16,679, with contributions from 27 countries [ 14 ]. Prior to the beginning of the Big Data Sjögren Project, another initiative aimed at the collection of longitudinal data from patients diagnosed with Sjogren's disease (SjD) from a range of geographical locations was the Sjögren's International Collaborative Clinical Alliance (SICCA). This was a project funded by the United States National Institutes of Health (NIH) from 2003 onwards. Enrollment started in the fall of 2004 at six international SICCA research groups (Argentina, China, Denmark, Japan, the United Kingdom, and the United States) [ 15 ]. At present, there are nine international research sites with a total of 3,514 participants [ 16 ]. To successfully harmonize the maximum possible data from all the involved clinical partners and offer new tools for large data analysis, the European Commission funded the HarmonicSS project. This project was designed to collect important clinical and research centers of SjD in Europe with the goal of improving stratification, treatment, and health policy making. Additionally, highly experienced engineers and bio-informaticians were included in the project team. The users of the platform have successfully interlinked, curated, and harmonized 21 regional, national, and international European cohorts of 7,551 SjD patients in terms of ethical and legal issues for data sharing. This has led to improvements in stratification, treatment, and the development of health policies [ 17 ]. The organization of local national data can facilitate collaboration on international projects [ 18 ]. National cohorts, such as the UK Primary Sjögren's Syndrome Registry (UKPSSR), which is funded by the Medical Research Council [ 19 ], comprise over 900 participants from 32 centers across the UK [ 20 ]. Another example is the Assessment of Systemic Signs and Evolution in Sjögren's Syndrome (ASSESS), which was established in 2006 with a grant from the French Ministry of Health. It includes SjD patients from 15 tertiary French centers between 2006 and 2009 [ 21 ]. The SJOGREN-SER is a collaborative project supported by the Sociedad Española de Reumatología and comprises 437 SjD patients from 33 Spanish centers [ 22 ]. Additionally, the Portuguese Registry of Sjögren's Syndrome (PORTRESS) is a notable example of an international collaboration in this field. In alignment with this approach, the Brazilian Committee on Sjögren's Disease of the Brazilian Society of Rheumatology (SBR) devised the prospective national cohort known as the Brazilian Registry of Sjögren's Disease (BRAS). The epidemiological and clinical profile of the BRAS study is prompting questions from real-life and driving the publication on disease management [ 23 – 26 ]. The objective of this manuscript is to introduce the BRAS registry, delineate its objectives and methods, and present preliminary descriptive data. Methods The BRAS cohort is a prospective national registry. To date, 16 centers from all Brazilian regions are engaged in the collaborative endeavor, with the potential for additional centers to join over time until 2026 (Fig. 1 ). Patients enrolled in the registry will be monitored for a period of ten years (Fig. 2 ). The study includes patients diagnosed with SjD who meet the classification criteria set forth by the American-European Consensus Group (AECG) of 2002 and/or 2016 ACR/EULAR [ 11 ]. Individuals with a prior diagnosis of other conditions that manifest with xerophthalmia and xerostomia are excluded from participation. These conditions include, but are not limited to, hepatitis C, acquired immunodeficiency syndrome (AIDS), head and neck radiotherapy in the past, graft versus host disease, sarcoidosis, and hyperIgG4-related disease, as well as SjD associated with other connective tissue diseases. The overall aim of BRAS is to generate a set of Brazilian clinical epidemiological data on patients with SjD who fulfill the 2002 AECG and/or 2016 ACR-EULAR classification criteria, and to promote high-quality clinical research. The BRAS has the following specific objectives: 1. To characterize the cluster and endotypes of the disease; 2. To assess the frequency of patients meeting the 2016 ACR-EULAR classification criteria for SjD; 3. To describe the disease activity index, symptom, severity and damage index. 4; To study the clinical correlation with histological and immunological data; 5. To describe salivary gland ultrasound findings and correlate them with disease activity, severity of symptoms and damage, as well as histological and immunological data 6; To compare the clinical profile of patients from different Brazilian geographic regions and ethnicities with those from other countries; 7. To assess the relationship between symptoms (fatigue, pain, dryness, anxiety, depression, and sleepiness), disease activity, and physical activity level; 8. To assess cardiovascular risk; 9. To assess the prevalence of comorbidities and polypharmacy; 10. To study the mortality of SjD. The registry is currently collecting data pertaining to demographics, clinical characteristics, laboratory results, and imaging findings. The Research Electronic Data Capture (REDCap) platform, which is an integrated web-based system, is being employed for the purposes of data entry. All research centers must be approved by the local Ethics Committee (coordinating center approval CAAE: 99071018.3.1001.5071) and patients must provide informed consent to participate in the study. The current analysis encompasses 1,010 patients from 16 clinical centers. Descriptive analyses were conducted to characterize the demographic and clinical data. RESULTS The mean age of the 1,010 SjD patients was 55.6 ± 13.6 years, with 96.5% of the cohort comprising women. The majority of patients were identified as white (52%), employed (37.6%), and married (56.1%) (Table 1 ). Ninety-three percent of patients presented with xerostomia, 93.7% with xerophthalmia, 78.9% with anti-Ro/SSA, and 41.8% with anti-La/SSB. Of the 70.5% of patients who underwent labial biopsy, 86.3% tested positive (Table 2 ). Additionally, 94% and 90% met the 2002 AECG and 2016 ACR-EULAR classification criteria, respectively. The mean time from the initial symptom was 11.9 ± 0.5 years, and from the diagnosis, 8.0 ± 0.4 years, which means 3–4 years delay in diagnosis. Table 1 Demographic data from the first 1,010 patients of BRAS. n (%) Self-reported race White 523 (52.0) Mixed 308 (30.6) Black 77 (7.7) Asian 10 (1.0) Indigenous 2 (0.2) NR 86 (8.5) Gender Female 975 (96.5) Male 35 (3.5) Marital status Married 489 (56.1) Separated or divorced 189 (21.7) Single 164 (18.8) NR 29 (3.3) Employment status Employed 322 (37.6) Retired 267 (31.2) Housework 208 (24.3) Unemployed 49 (5.7) Study 11 (1.3) Age group, years ≤ 55 481 (47.6) > 55 529 (52.4) NR: not reported Table 2 Criteria for Sjögren's disease classification according to American-European consensus group 2022 or ACR-Eular 2016 from 1,010 patients of BRAS. Yes No Not performed n (%) n (%) n (%) Ocular symptoms 940 (93.1) 70 (6.9) 0 Oral symptoms 946 (93.7) 64 (6.3) 0 Ocular signs 740 (73.3) 249 (24.6) 21 (2.1) Schirmer’s I test 662 (65.5) 264 (26.1) 84 (8.4) Rose bengal score or other ocular dye score 277 (27.4) 142 (14.0) 591 (58.6) Focal lymphocytic sialadenitis 614 (60.8) 98 (9.7) 298 (29.5) Unstimulated whole salivary flow 471 (46.7) 128 (12.7) 411 (40.7) Parotid sialography 12 (1.2) 14 (1.4) 984 (97.4) Salivary scintigraphy 247 (24.5) 27 (2.7) 735 (72.8) Anti-Ro/SSA 797 (78.9) 205 (20.3) 8 (0.8) Anti-La/SSB 422 (41.8) 529 (52.3) 59 (5.8) Discussion The BRAS registry represents a well-characterized cohort, with an anti-Ro/SSA frequency of 79% and anti-La/SSB of 42%. These values align with those observed in other cohorts [ 5 , 19 , 21 ]. The average diagnosis occurred after eight years of symptom onset, with the illness persisting for approximately 12 years. The use of registries and consortia studies is particularly pertinent in the context of rare diseases, where phenotypic manifestations can vary significantly. The initial national registries to study SjD emerged over a decade ago [ 19 , 21 , 22 ] and has been important to recruit patients for clinical trials and for the development of disease activity and symptom assessment tools. The current decade has seen the establishment of numerous international registries, which have led to the creation of sizable banks such as BigData [ 5 , 13 ] as well as biobanks [ 17 ]. Brazil is a continental country with huge potential for including patients in collaborative studies. Furthermore, given the cultural and ethnic diversity of the Brazilian population, it is imperative that studies are validated within this population. The BRAS cohort is highly characterized and comprises a substantial number of individuals, which can facilitate the identification of potential participants for clinical trials, the evaluation of novel tools and classification criteria, the testing of artificial intelligence, and collaboration in international initiatives. The BRAS was designed to characterize a representative cohort of Brazilian patients with SjD in real-life clinical practice. Its objectives included the analysis of the clinical and laboratory profile, predictors of systemic involvement and cardiovascular risk, prevalence of anxiety and depression and associations, physical activity level and associations, comorbidities and polypharmacy, response to treatment, monitoring of disease activity and mortality. Furthermore, the study offers insights from a patient perspective, employing patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs). This study presents the design of this longitudinal cohort and provides a characterization of the population of the first 1,010 participants. As with other studies in this field, the epidemiological data show a predominance of women in the sixth decade of life, with a ratio of approximately 15:1. The Brazilian population is a mosaic of diverse ethnicities. The classification of ethnicities in Brazil differs from that in Europe and the USA. In Brazil, ethnic groups are distinguished by color: Black (Afro-Brazilian), Brown (mixed), White (White European), Indigenous (Native Indian), and Yellow (from Asia). Most of the white population (50%) can be predominantly of Portuguese, Italian, German, Spanish, Dutch or French descent. The indigenous population is indigenous to the Amazon and South America. Black people are of African descent. The term "Hispanic" is not an accurate description of the Brazilian population. It is notable that only 41.4% of the participants had undergone an ophthalmological examination that included a staining test of the ocular surface with lysamine green and fluorescein. Nevertheless, the Schirmer I test was readily available in 91.6% of cases, primarily conducted by rheumatologists or nurses in SjD referral centers. This indicates that the test remains a valuable tool for screening and confirming dry eye, while also highlighting the difficulty in accessing ophthalmological expertise. A significant proportion of patients do not undergo standardized testing for the diagnosis and monitoring of SjD. Similarly, unstimulated salivary flow has been conducted in referral centers, with a 60% success rate. Sialography was conducted in only 2.6% of cases, indicating that it is a proscribed examination. Additionally, although salivary gland scintigraphy remains a valuable diagnostic tool, it was performed in only 27.2% of cases, primarily in a few centers with access to the examination through the Public Health System. It is also possible that the modification of the classification criteria may be contributing to the observed reduction in the number of indications for these tests. Despite its invasive nature, labial salivary gland biopsy was performed in 70% of participants. Conclusion BRAS can provide valuable insights into patient journeys within the healthcare system. Data pertaining to cancer prevalence, disease activity, symptoms, medications, and comorbidities are currently being analyzed for future publication. The subsequent phase will entail integrating the BRAS data set with those from other consortia and obtaining biological specimens with a view to establishing a research biobank. Abbreviations ACR/EULAR: American College of Rheumatology/European League Against Rheumatism AECG: American-European Consensus Group ASSESS: Assessment of Systemic Signs and Evolution in Sjögren's Syndrome BRAS: Brazilian Registry of Sjögren's Disease DMARD: disease-modifying antirheumatic drug ESSDAI: EULAR Sjögren's Syndrome Disease Activity Index ESSPRI: EULAR Sjögren's Syndrome Patient Reported Index HRQoL: health-related quality of life PORTRESS: Portuguese Registry of Sjögren's Disease PREMs: patient-reported experience measures PROMs: patient-reported outcome measures REDCap: Research Electronic Data Capture SBR: Brazilian Society of Rheumatology SICCA: Sjögren's International Collaborative Clinical Alliance SjD: Sjögren's disease UKPSSR: UK Primary Sjögren's Syndrome Registry Declarations Ethics approval and consent to participate: The study was approved by the institutional ethics committee under the number 2.930.715 (CAAE 99071018.3.1001.5071), on October 01, 2018, and all patients provided written consent for participation. Consent for publication: Not applicable. Availability of data and materials: The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. Competing interests: The authors declare that they have no competing interests. Funding: Brazilian Society of Rheumatology. Authors' contributions: VV, FRO, VFMT designed the research, interpreted the data and wrote the manuscript; STM analyzed and interpreted the data and wrote the manuscript; LC, RPA, SA, JM, LAT, MLLP, RC, ACP, VH, AZF, SLER, LGC, GSP, AP, MCZ, KLLM, EVS, PRT, NCS, ANMSM, DUC, VSB, RMX collected the data; all the authors have read, revised the manuscript and approved the final manuscript. Acknowledgements: BRAS Task Force - Ana Carolina Fragoso Motta, Adriana Machado, Eduardo Melani Rocha, Fernanda Lourenço Macagnan, Regis Sewa Marques, Luciana Dardin, Eduardo Rosa, Maria Carmen Lopes Ferreira Silva Santos, Mateus Maia Marzola. References Mariette X, Criswell LA. 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Griffiths B; UKPSSR study group. United Kingdom Primary Sjogren's Syndrome Registry--a united effort to tackle an orphan rheumatic disease. Rheumatology (Oxford). 2011 Jan;50(1):32-9. doi: 10.1093/rheumatology/keq240. Tarn J. Lendrem D. Barnes M. Casement J. Ng WF. Comorbidities in the UK Primary Sjögren's Syndrome Registry. Front Immunol. 2022 Apr 22;13:864448. doi: 10.3389/fimmu.2022.864448. Gottenberg JE. Seror R. Miceli-Richard C. Benessiano J. Devauchelle-Pensec V. Dieude P. Dubost JJ. Fauchais AL. Goeb V. Hachulla E. Hatron PY. Larroche C. Le Guern V. Morel J. Perdriger A. Puéchal X. Rist S. Saraux A. Sene D. Sibilia J. Vittecoq O. Nocturne G. Ravaud P. Mariette X. Serum levels of beta2-microglobulin and free light chains of immunoglobulins are associated with systemic disease activity in primary Sjögren's syndrome. Data at enrollment in the prospective ASSESS cohort. PLoS One. 2013 May 24;8(5):e59868. doi: 10.1371/journal.pone.0059868. Fernández Castro M. Andreu JL. Sánchez-Piedra C. Martínez Taboada V. Olivé A. Rosas J. Sánchez-Alonso F; en representación del Grupo de trabajo en Enfermedades Autoinmunes Sistémicas de la Sociedad Española de Reumatología (EAS-SER) y de la Unidad de Investigación de la Sociedad Española de Reumatología (UI-SER). Sjögren SER: National registry of the Spanish Society of Rheumatology of patients with primary Sjögren syndrome: Objectives and methodology. Reumatol Clin. 2016 Jul-Aug;12(4):184-9. doi: 10.1016/j.reuma.2015.09.002. 23. Trevisani VFM. Pasoto SG. Fernandes MLMS. Lopes MLL. de Magalhães Souza Fialho SC. Pinheiro AC. Dos Santos LC. Appenzeller S. Fidelix T. Ribeiro SLE. de Brito DCSE. Libório T. Santos MCLFS. Tanure L. Gennari JDA. Civile VT. Pinto ACPN. Oliveira FR. de Sousa JM. Miyamoto ST. Valim V. Recommendations from the Brazilian society of rheumatology for the diagnosis of Sjögren's syndrome (Part I): glandular manifestations (systematic review). Adv Rheumatol. 2019 Dec 18;59(1):58. doi: 10.1186/s42358-019-0102-8. Oliveira FR, Valim V, Pasoto SG, Fernandes MLMS, Lopes MLL, de Magalhães Souza Fialho SC, Pinheiro AC, Dos Santos LC, Appenzeller S, Fidelix T, Ribeiro SLE, de Brito DCSE, Libório T, Santos MCLFS, Tanure L, Gennari JD, Civile VT, Pinto ACPN, Rocha-Filho CR, Miyamoto ST, Guedes LKN, Pugliesi A, Trevisani VFM. 2021 recommendations of the Brazilian Society of Rheumatology for the gynecological and obstetric care of patients with Sjogren's syndrome. Adv Rheumatol. 2021 Sep 3;61(1):54. doi: 10.1186/s42358-021-00208-1. Erratum in: Adv Rheumatol. 2022 Mar 20;62(1):8. doi: 10.1186/s42358-022-00242-7. Trevisani VFM. Pinheiro AC. de Magalhães Souza Fialho SC. Fernandes MLMS. Pugliesi A. Pasoto SG. Lopes MLL. Guedes LKN. Miyamoto ST. Dos Santos LC. Appenzeller S. Fidelix T. Ribeiro SLE. de Brito DCSE. Libório-Kimura TN. Santos MCLFS. Cantali DU. Gennari JD'. Capobianco KG. Civile VT. Pinto ACPN. da Rocha AP. Rocha-Filho CR. Oliveira FR. Valim V. Recommendations for evaluation and diagnosis of extra-glandular manifestations of primary Sjögren syndrome: results of an epidemiologic systematic review/meta-analysis and a consensus guideline from the Brazilian society of rheumatology (hepatic. gastrointestinal and pancreatic). Adv Rheumatol. 2022 Oct 10;62(1):35. doi: 10.1186/s42358-022-00267-y. Trevisani VFM. Pugliesi A. Pasoto SG. Lopes MLL. Guedes LKN. Miyamoto ST. Fernandes MLMS. Fialho SCMS. Pinheiro AC. Dos Santos LC. Appenzeller S. Fidelix T. Ribeiro SLE. de Brito DCSE. Nayara Libório-Kimura T. Santos MCLFS. Cantali DU. Gennari JD. Civile VT. Pinto ACPN. Rocha-Filho CR. Oliveira FR. da Rocha AP. Valim V. Recommendations for evaluation and diagnosis of extra-glandular manifestations of primary sjogren syndrome: results of an epidemiologic systematic review/meta-analysis and a consensus guideline from the Brazilian Society of Rheumatology (articular. pulmonary and renal). Adv Rheumatol. 2022 Jun 1;62(1):18. doi: 10.1186/s42358-022-00248-1. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4960285","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":349165441,"identity":"2691ba60-1610-46de-98f3-7f5dcc8ad79c","order_by":0,"name":"Valéria 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Federal de São Paulo","correspondingAuthor":false,"prefix":"","firstName":"Virgínia","middleName":"Fernandes Moça","lastName":"Trevisani","suffix":""}],"badges":[],"createdAt":"2024-08-22 21:07:56","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4960285/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4960285/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":66741706,"identity":"04a7bae3-aff5-4983-a38a-df7eb96ec887","added_by":"auto","created_at":"2024-10-16 05:56:29","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":843199,"visible":true,"origin":"","legend":"\u003cp\u003eBRAS centers in all regions of Brazil.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4960285/v1/fc226365b6f81134ffc8f466.png"},{"id":66741705,"identity":"63052cb8-0304-4e7f-b6bd-2911ae7e5513","added_by":"auto","created_at":"2024-10-16 05:56:29","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":173599,"visible":true,"origin":"","legend":"\u003cp\u003eOutcomes evaluated in the Brazilian Registry on Sjögren’s Disease (BRAS) over 10-years of follow-up.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4960285/v1/c6fb5a572b54cdd35c6eb9f3.png"},{"id":76055798,"identity":"67d3b861-c748-429b-9457-5d50fa18d4f5","added_by":"auto","created_at":"2025-02-11 23:46:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1788320,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4960285/v1/1abd7b83-f33e-4be4-9dea-0b35a992cf8a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Brazilian Registry of Sjögren’s Disease (BRAS): a full picture of Sjögren’s disease","fulltext":[{"header":"Background","content":"\u003cp\u003eSj\u0026ouml;gren's disease (SjD) is a chronic, immune-mediated, systemic inflammatory disease. It is characterized by the presence of lymphocytic infiltrate in the salivary and lacrimal glands, autoantibodies, and glandular disorders that are clinically expressed by xerostomia and xerophthalmia. Systemic manifestations occur in approximately 50% of patients and can be severe, with an association between these manifestations and the prognosis and development of lymphoma [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. SjD without overlap with other autoimmune rheumatic diseases affects 43.03 (25.74 to 60.31) individuals per 100,000 inhabitants, with a female-to-male ratio of 9\u0026ndash;14 to 1 [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In Brazil, the prevalence of SjD in the general population was found to be 0.17% [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, the clinical spectrum of SjD differs between countries and continents due to the influence of genetic and environmental factors [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhile treatments may improve symptoms and prevent complications, there is currently no approved option that can alter the natural history of the disease. The most prevalent benign symptoms, such as dryness, fatigue, and pain, continue to present a challenge to health professionals in their management and biomedical researchers in the delineation of the intricate pathophysiological pathways. Systemic manifestations can present diagnostic and management challenges, particularly when there is overlap with other autoimmune diseases. The ongoing treatment strategies are empirical and rely on symptomatic management. There is currently no biological or synthetic disease-modifying antirheumatic drug (DMARD) that has been proven to alter the progression of the disease [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe health-related quality of life (HRQoL) of individuals with SjD has been shown to be markedly reduced in numerous cross-sectional studies conducted in various countries when compared with that of healthy controls. This reduction in HRQoL has been associated not only with the primary symptoms experienced by these individuals, such as dryness, pain, and fatigue, but also with dysautonomia, low physical function and activity level, pruritus, and a range of additional disorders, including psychological, oral, ocular, sexual, and sleep-related disorders. However, some studies have indicated that pain and fatigue are predictors of poor HRQoL, while symptoms are not associated with systemic disease activity [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. As HRQoL plays an increasingly pivotal role in medical decision-making, it is imperative to conduct long-term follow-up of individuals to ascertain the predictors of worsening HRQoL in accordance with disease fluctuations and multidisciplinary clinical management.\u003c/p\u003e \u003cp\u003eSignificant advances have been made in the field of SjD research since the development and validation of the evaluation tools by the EULAR Sj\u0026ouml;gren's Task Force. These include the EULAR Sj\u0026ouml;gren's Syndrome Patient Reported Index (ESSPRI) for patients' symptoms and the EULAR Sj\u0026ouml;gren's Syndrome Disease Activity Index (ESSDAI) for systemic features [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Furthermore, the 2016 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for SjD [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] have enabled the establishment of international consensus for the classification of the disease, thereby facilitating cohort studies that are more comparable and enabling the compilation of more detailed information to better understand the course of the disease.\u003c/p\u003e \u003cp\u003eLarge cohort studies are a valuable tool for understanding the chronic pathological mechanisms of SjD due to the slow and progressive nature of the disease, coupled with significant heterogeneity among patient populations regarding their geographical, environmental, and genetic diversity, as well as their phenotypic and endotype manifestations of the disease. To illustrate, the \"Big Data Sj\u0026ouml;gren Project\" yielded initial evidence indicating that geographic location and ethnicity have a pronounced influence on the clinical manifestation of SjD at the time of diagnosis [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Moreover, it has the potential to elucidate whether environmental factors such as pollution may contribute to the disease's risk and progression [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe Big Data Sj\u0026ouml;gren's Project Consortium, an international multicenter registry initiated in 2014, aggregated the extant clinical databases from leading centers in clinical research across the five continents for the purpose of analyzing the clinical and geoepidemiological characterization of SjD [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. By January 2023, the number of patients enrolled at the participating centers had reached 16,679, with contributions from 27 countries [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePrior to the beginning of the Big Data Sj\u0026ouml;gren Project, another initiative aimed at the collection of longitudinal data from patients diagnosed with Sjogren's disease (SjD) from a range of geographical locations was the Sj\u0026ouml;gren's International Collaborative Clinical Alliance (SICCA). This was a project funded by the United States National Institutes of Health (NIH) from 2003 onwards. Enrollment started in the fall of 2004 at six international SICCA research groups (Argentina, China, Denmark, Japan, the United Kingdom, and the United States) [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. At present, there are nine international research sites with a total of 3,514 participants [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTo successfully harmonize the maximum possible data from all the involved clinical partners and offer new tools for large data analysis, the European Commission funded the HarmonicSS project. This project was designed to collect important clinical and research centers of SjD in Europe with the goal of improving stratification, treatment, and health policy making. Additionally, highly experienced engineers and bio-informaticians were included in the project team. The users of the platform have successfully interlinked, curated, and harmonized 21 regional, national, and international European cohorts of 7,551 SjD patients in terms of ethical and legal issues for data sharing. This has led to improvements in stratification, treatment, and the development of health policies [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe organization of local national data can facilitate collaboration on international projects [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. National cohorts, such as the UK Primary Sj\u0026ouml;gren's Syndrome Registry (UKPSSR), which is funded by the Medical Research Council [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], comprise over 900 participants from 32 centers across the UK [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Another example is the Assessment of Systemic Signs and Evolution in Sj\u0026ouml;gren's Syndrome (ASSESS), which was established in 2006 with a grant from the French Ministry of Health. It includes SjD patients from 15 tertiary French centers between 2006 and 2009 [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The SJOGREN-SER is a collaborative project supported by the Sociedad Espa\u0026ntilde;ola de Reumatolog\u0026iacute;a and comprises 437 SjD patients from 33 Spanish centers [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Additionally, the Portuguese Registry of Sj\u0026ouml;gren's Syndrome (PORTRESS) is a notable example of an international collaboration in this field.\u003c/p\u003e \u003cp\u003e In alignment with this approach, the Brazilian Committee on Sj\u0026ouml;gren's Disease of the Brazilian Society of Rheumatology (SBR) devised the prospective national cohort known as the Brazilian Registry of Sj\u0026ouml;gren's Disease (BRAS). The epidemiological and clinical profile of the BRAS study is prompting questions from real-life and driving the publication on disease management [\u003cspan additionalcitationids=\"CR24 CR25\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe objective of this manuscript is to introduce the BRAS registry, delineate its objectives and methods, and present preliminary descriptive data.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe BRAS cohort is a prospective national registry. To date, 16 centers from all Brazilian regions are engaged in the collaborative endeavor, with the potential for additional centers to join over time until 2026 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Patients enrolled in the registry will be monitored for a period of ten years (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe study includes patients diagnosed with SjD who meet the classification criteria set forth by the American-European Consensus Group (AECG) of 2002 and/or 2016 ACR/EULAR [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Individuals with a prior diagnosis of other conditions that manifest with xerophthalmia and xerostomia are excluded from participation. These conditions include, but are not limited to, hepatitis C, acquired immunodeficiency syndrome (AIDS), head and neck radiotherapy in the past, graft versus host disease, sarcoidosis, and hyperIgG4-related disease, as well as SjD associated with other connective tissue diseases.\u003c/p\u003e \u003cp\u003eThe overall aim of BRAS is to generate a set of Brazilian clinical epidemiological data on patients with SjD who fulfill the 2002 AECG and/or 2016 ACR-EULAR classification criteria, and to promote high-quality clinical research. The BRAS has the following specific objectives: 1. To characterize the cluster and endotypes of the disease; 2. To assess the frequency of patients meeting the 2016 ACR-EULAR classification criteria for SjD; 3. To describe the disease activity index, symptom, severity and damage index. 4; To study the clinical correlation with histological and immunological data; 5. To describe salivary gland ultrasound findings and correlate them with disease activity, severity of symptoms and damage, as well as histological and immunological data 6; To compare the clinical profile of patients from different Brazilian geographic regions and ethnicities with those from other countries; 7. To assess the relationship between symptoms (fatigue, pain, dryness, anxiety, depression, and sleepiness), disease activity, and physical activity level; 8. To assess cardiovascular risk; 9. To assess the prevalence of comorbidities and polypharmacy; 10. To study the mortality of SjD.\u003c/p\u003e \u003cp\u003eThe registry is currently collecting data pertaining to demographics, clinical characteristics, laboratory results, and imaging findings. The Research Electronic Data Capture (REDCap) platform, which is an integrated web-based system, is being employed for the purposes of data entry.\u003c/p\u003e \u003cp\u003eAll research centers must be approved by the local Ethics Committee (coordinating center approval CAAE: 99071018.3.1001.5071) and patients must provide informed consent to participate in the study.\u003c/p\u003e \u003cp\u003eThe current analysis encompasses 1,010 patients from 16 clinical centers. Descriptive analyses were conducted to characterize the demographic and clinical data.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eThe mean age of the 1,010 SjD patients was 55.6\u0026thinsp;\u0026plusmn;\u0026thinsp;13.6 years, with 96.5% of the cohort comprising women. The majority of patients were identified as white (52%), employed (37.6%), and married (56.1%) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Ninety-three percent of patients presented with xerostomia, 93.7% with xerophthalmia, 78.9% with anti-Ro/SSA, and 41.8% with anti-La/SSB. Of the 70.5% of patients who underwent labial biopsy, 86.3% tested positive (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Additionally, 94% and 90% met the 2002 AECG and 2016 ACR-EULAR classification criteria, respectively. The mean time from the initial symptom was 11.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5 years, and from the diagnosis, 8.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4 years, which means 3\u0026ndash;4 years delay in diagnosis.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic data from the first 1,010 patients of BRAS.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003eSelf-reported race\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWhite\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e523 (52.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMixed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e308 (30.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBlack\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e77 (7.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAsian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (1.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIndigenous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (0.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e86 (8.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e975 (96.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e35 (3.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eMarital status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMarried\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e489 (56.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSeparated or divorced\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e189 (21.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e164 (18.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29 (3.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003eEmployment status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEmployed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e322 (37.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRetired\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e267 (31.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHousework\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e208 (24.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnemployed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e49 (5.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStudy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11 (1.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAge group, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e481 (47.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e529 (52.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eNR: not reported\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCriteria for Sj\u0026ouml;gren's disease classification according to American-European consensus group 2022 or ACR-Eular 2016 from 1,010 patients of BRAS.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNot performed\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003en (%)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003en (%)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003en (%)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOcular symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e940 (93.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e70 (6.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e946 (93.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e64 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOcular signs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e740 (73.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e249 (24.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21 (2.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSchirmer\u0026rsquo;s I test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e662 (65.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e264 (26.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e84 (8.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRose bengal score or other ocular dye score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e277 (27.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e142 (14.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e591 (58.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFocal lymphocytic sialadenitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e614 (60.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e98 (9.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e298 (29.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnstimulated whole salivary flow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e471 (46.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e128 (12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e411 (40.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParotid sialography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e984 (97.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSalivary scintigraphy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e247 (24.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e27 (2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e735 (72.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-Ro/SSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e797 (78.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e205 (20.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (0.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-La/SSB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e422 (41.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e529 (52.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e59 (5.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe BRAS registry represents a well-characterized cohort, with an anti-Ro/SSA frequency of 79% and anti-La/SSB of 42%. These values align with those observed in other cohorts [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The average diagnosis occurred after eight years of symptom onset, with the illness persisting for approximately 12 years.\u003c/p\u003e \u003cp\u003eThe use of registries and consortia studies is particularly pertinent in the context of rare diseases, where phenotypic manifestations can vary significantly. The initial national registries to study SjD emerged over a decade ago [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] and has been important to recruit patients for clinical trials and for the development of disease activity and symptom assessment tools.\u003c/p\u003e \u003cp\u003eThe current decade has seen the establishment of numerous international registries, which have led to the creation of sizable banks such as BigData [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] as well as biobanks [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Brazil is a continental country with huge potential for including patients in collaborative studies. Furthermore, given the cultural and ethnic diversity of the Brazilian population, it is imperative that studies are validated within this population. The BRAS cohort is highly characterized and comprises a substantial number of individuals, which can facilitate the identification of potential participants for clinical trials, the evaluation of novel tools and classification criteria, the testing of artificial intelligence, and collaboration in international initiatives.\u003c/p\u003e \u003cp\u003eThe BRAS was designed to characterize a representative cohort of Brazilian patients with SjD in real-life clinical practice. Its objectives included the analysis of the clinical and laboratory profile, predictors of systemic involvement and cardiovascular risk, prevalence of anxiety and depression and associations, physical activity level and associations, comorbidities and polypharmacy, response to treatment, monitoring of disease activity and mortality. Furthermore, the study offers insights from a patient perspective, employing patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs).\u003c/p\u003e \u003cp\u003eThis study presents the design of this longitudinal cohort and provides a characterization of the population of the first 1,010 participants. As with other studies in this field, the epidemiological data show a predominance of women in the sixth decade of life, with a ratio of approximately 15:1.\u003c/p\u003e \u003cp\u003eThe Brazilian population is a mosaic of diverse ethnicities. The classification of ethnicities in Brazil differs from that in Europe and the USA. In Brazil, ethnic groups are distinguished by color: Black (Afro-Brazilian), Brown (mixed), White (White European), Indigenous (Native Indian), and Yellow (from Asia). Most of the white population (50%) can be predominantly of Portuguese, Italian, German, Spanish, Dutch or French descent. The indigenous population is indigenous to the Amazon and South America. Black people are of African descent. The term \"Hispanic\" is not an accurate description of the Brazilian population.\u003c/p\u003e \u003cp\u003eIt is notable that only 41.4% of the participants had undergone an ophthalmological examination that included a staining test of the ocular surface with lysamine green and fluorescein. Nevertheless, the Schirmer I test was readily available in 91.6% of cases, primarily conducted by rheumatologists or nurses in SjD referral centers. This indicates that the test remains a valuable tool for screening and confirming dry eye, while also highlighting the difficulty in accessing ophthalmological expertise. A significant proportion of patients do not undergo standardized testing for the diagnosis and monitoring of SjD.\u003c/p\u003e \u003cp\u003eSimilarly, unstimulated salivary flow has been conducted in referral centers, with a 60% success rate. Sialography was conducted in only 2.6% of cases, indicating that it is a proscribed examination. Additionally, although salivary gland scintigraphy remains a valuable diagnostic tool, it was performed in only 27.2% of cases, primarily in a few centers with access to the examination through the Public Health System. It is also possible that the modification of the classification criteria may be contributing to the observed reduction in the number of indications for these tests. Despite its invasive nature, labial salivary gland biopsy was performed in 70% of participants.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eBRAS can provide valuable insights into patient journeys within the healthcare system. Data pertaining to cancer prevalence, disease activity, symptoms, medications, and comorbidities are currently being analyzed for future publication.\u003c/p\u003e \u003cp\u003eThe subsequent phase will entail integrating the BRAS data set with those from other consortia and obtaining biological specimens with a view to establishing a research biobank.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eACR/EULAR: American College of Rheumatology/European League Against Rheumatism \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAECG: American-European Consensus\u0026nbsp;Group\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eASSESS: Assessment of Systemic Signs and Evolution in Sj\u0026ouml;gren\u0026apos;s Syndrome\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBRAS: Brazilian Registry of Sj\u0026ouml;gren\u0026apos;s Disease\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDMARD: disease-modifying antirheumatic drug\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eESSDAI: EULAR Sj\u0026ouml;gren\u0026apos;s Syndrome Disease Activity Index\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eESSPRI: EULAR Sj\u0026ouml;gren\u0026apos;s Syndrome Patient Reported Index\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHRQoL: health-related quality of life\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePORTRESS: Portuguese Registry of Sj\u0026ouml;gren\u0026apos;s Disease\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePREMs: patient-reported experience measures\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePROMs: patient-reported outcome measures\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eREDCap:\u0026nbsp;Research Electronic Data Capture\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSBR: Brazilian Society of Rheumatology\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSICCA: Sj\u0026ouml;gren\u0026apos;s International Collaborative Clinical Alliance\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSjD: Sj\u0026ouml;gren\u0026apos;s disease\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eUKPSSR: UK Primary Sj\u0026ouml;gren\u0026apos;s Syndrome Registry\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cul\u003e\n \u003cli\u003eEthics approval and consent to participate: The study was approved by the institutional ethics committee under the number 2.930.715 (CAAE 99071018.3.1001.5071), on October 01, 2018, and all patients provided written consent for participation. \u0026nbsp;\u003c/li\u003e\n \u003cli\u003eConsent for publication: Not applicable.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAvailability of data and materials: The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eCompeting interests: The authors declare that they have no competing interests.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eFunding: Brazilian Society of Rheumatology.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAuthors\u0026apos; contributions: VV, FRO, VFMT designed the research, interpreted the data and wrote the manuscript; STM analyzed and interpreted the data and wrote the manuscript; \u0026nbsp;LC, RPA, SA, JM, LAT, MLLP, RC, ACP, VH, AZF, SLER, LGC, GSP, AP, MCZ, KLLM, EVS, PRT, NCS, ANMSM, DUC, VSB, RMX collected the data; all the authors have read, revised the manuscript and approved the final manuscript.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAcknowledgements: BRAS Task Force - \u0026nbsp;Ana Carolina Fragoso Motta, Adriana Machado, Eduardo Melani Rocha, Fernanda Lourenço Macagnan, Regis Sewa Marques, Luciana Dardin, Eduardo Rosa, Maria Carmen Lopes Ferreira Silva Santos, Mateus Maia Marzola.\u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMariette X, Criswell LA. 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Kalatzis F. Chatzis L. Kourou KD. Venetsanopoulou A. Exarchos TP. Gandolfo S. Votis K. Zampeli E. Burmeister J. May T. Marcelino P\u0026eacute;rez M. Lishchuk I. Chondrogiannis T. Andronikou V. Varvarigou T. Filipovic N. Tsiknakis M. Baldini C. Bombardieri M. Bootsma H. Bowman SJ. Soyfoo MS. Parisis D. Delporte C. Devauchelle-Pensec V. Pers JO. D\u0026ouml;rner T. Bartoloni E. Gerli R. Giacomelli R. Jonsson R. Ng WF. Priori R. Ramos-Casals M. Sivils K. Skopouli F. Torsten W. A G van Roon J. Xavier M. De Vita S. Tzioufas AG. Fotiadis DI. Addressing the clinical unmet needs in primary Sj\u0026ouml;gren\u0026apos;s Syndrome through the sharing. harmonization and federated analysis of 21 European cohorts. Comput Struct Biotechnol J. 2022 Jan 7;20:471-484. doi: 10.1016/j.csbj.2022.01.002. \u003c/li\u003e\n\u003cli\u003eGoules AV. Exarchos TP. Pezoulas VC. Kourou KD. Venetsanopoulou AI. De Vita S. Fotiadis DI. Tzioufas AG. Sj\u0026ouml;gren\u0026apos;s syndrome towards precision medicine: the challenge of harmonisation and integration of cohorts. Clin Exp Rheumatol. 2019 May-Jun;37 Suppl 118(3):175-184. \u003c/li\u003e\n\u003cli\u003eNg WF. Bowman SJ. Griffiths B; UKPSSR study group. United Kingdom Primary Sjogren\u0026apos;s Syndrome Registry--a united effort to tackle an orphan rheumatic disease. Rheumatology (Oxford). 2011 Jan;50(1):32-9. doi: 10.1093/rheumatology/keq240. \u003c/li\u003e\n\u003cli\u003eTarn J. Lendrem D. Barnes M. Casement J. Ng WF. Comorbidities in the UK Primary Sj\u0026ouml;gren\u0026apos;s Syndrome Registry. Front Immunol. 2022 Apr 22;13:864448. doi: 10.3389/fimmu.2022.864448. \u003c/li\u003e\n\u003cli\u003eGottenberg JE. Seror R. Miceli-Richard C. Benessiano J. Devauchelle-Pensec V. Dieude P. Dubost JJ. Fauchais AL. Goeb V. Hachulla E. Hatron PY. Larroche C. Le Guern V. Morel J. Perdriger A. Pu\u0026eacute;chal X. Rist S. Saraux A. Sene D. Sibilia J. Vittecoq O. Nocturne G. Ravaud P. Mariette X. Serum levels of beta2-microglobulin and free light chains of immunoglobulins are associated with systemic disease activity in primary Sj\u0026ouml;gren\u0026apos;s syndrome. Data at enrollment in the prospective ASSESS cohort. PLoS One. 2013 May 24;8(5):e59868. doi: 10.1371/journal.pone.0059868. \u003c/li\u003e\n\u003cli\u003eFern\u0026aacute;ndez Castro M. Andreu JL. S\u0026aacute;nchez-Piedra C. Mart\u0026iacute;nez Taboada V. Oliv\u0026eacute; A. Rosas J. S\u0026aacute;nchez-Alonso F; en representaci\u0026oacute;n del Grupo de trabajo en Enfermedades Autoinmunes Sist\u0026eacute;micas de la Sociedad Espa\u0026ntilde;ola de Reumatolog\u0026iacute;a (EAS-SER) y de la Unidad de Investigaci\u0026oacute;n de la Sociedad Espa\u0026ntilde;ola de Reumatolog\u0026iacute;a (UI-SER). Sj\u0026ouml;gren SER: National registry of the Spanish Society of Rheumatology of patients with primary Sj\u0026ouml;gren syndrome: Objectives and methodology. 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Adv Rheumatol. 2019 Dec 18;59(1):58. doi: 10.1186/s42358-019-0102-8. \u003c/li\u003e\n\u003cli\u003eOliveira FR, Valim V, Pasoto SG, Fernandes MLMS, Lopes MLL, de Magalh\u0026atilde;es Souza Fialho SC, Pinheiro AC, Dos Santos LC, Appenzeller S, Fidelix T, Ribeiro SLE, de Brito DCSE, Lib\u0026oacute;rio T, Santos MCLFS, Tanure L, Gennari JD, Civile VT, Pinto ACPN, Rocha-Filho CR, Miyamoto ST, Guedes LKN, Pugliesi A, Trevisani VFM. 2021 recommendations of the Brazilian Society of Rheumatology for the gynecological and obstetric care of patients with Sjogren\u0026apos;s syndrome. Adv Rheumatol. 2021 Sep 3;61(1):54. doi: 10.1186/s42358-021-00208-1. Erratum in: Adv Rheumatol. 2022 Mar 20;62(1):8. doi: 10.1186/s42358-022-00242-7. \u003c/li\u003e\n\u003cli\u003eTrevisani VFM. Pinheiro AC. de Magalh\u0026atilde;es Souza Fialho SC. Fernandes MLMS. Pugliesi A. Pasoto SG. Lopes MLL. Guedes LKN. Miyamoto ST. Dos Santos LC. Appenzeller S. Fidelix T. Ribeiro SLE. de Brito DCSE. Lib\u0026oacute;rio-Kimura TN. Santos MCLFS. Cantali DU. Gennari JD\u0026apos;. Capobianco KG. Civile VT. Pinto ACPN. da Rocha AP. Rocha-Filho CR. Oliveira FR. Valim V. Recommendations for evaluation and diagnosis of extra-glandular manifestations of primary Sj\u0026ouml;gren syndrome: results of an epidemiologic systematic review/meta-analysis and a consensus guideline from the Brazilian society of rheumatology (hepatic. gastrointestinal and pancreatic). Adv Rheumatol. 2022 Oct 10;62(1):35. doi: 10.1186/s42358-022-00267-y. \u003c/li\u003e\n\u003cli\u003eTrevisani VFM. Pugliesi A. Pasoto SG. Lopes MLL. Guedes LKN. Miyamoto ST. Fernandes MLMS. Fialho SCMS. Pinheiro AC. Dos Santos LC. Appenzeller S. Fidelix T. Ribeiro SLE. de Brito DCSE. Nayara Lib\u0026oacute;rio-Kimura T. Santos MCLFS. Cantali DU. Gennari JD. Civile VT. Pinto ACPN. Rocha-Filho CR. Oliveira FR. da Rocha AP. Valim V. Recommendations for evaluation and diagnosis of extra-glandular manifestations of primary sjogren syndrome: results of an epidemiologic systematic review/meta-analysis and a consensus guideline from the Brazilian Society of Rheumatology (articular. pulmonary and renal). Adv Rheumatol. 2022 Jun 1;62(1):18. doi: 10.1186/s42358-022-00248-1. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Sjögren's disease, registry, epidemiology, cohort, prevalence","lastPublishedDoi":"10.21203/rs.3.rs-4960285/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4960285/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe Brazilian Registry on Sj\u0026ouml;gren's Disease (BRAS) is a prospective, national cohort registry. To date, 16 centers from all Brazilian regions are engaged in collaborative research, with the potential for additional centers to be included over time. The BRAS project started in 2021 and has the support of the Brazilian Society of Rheumatology (SBR). The primary objective of BRAS is to generate a set of Brazilian epidemiological data on patients with SjD who meet the 2002 AECG and/or 2016 ACR-EULAR classification criteria, and to promote high-quality clinical research. The Research Electronic Data Capture (REDCap) platform is being used for the entry of clinical data. In addition to demographic and laboratory data, clinical data are being collected, including disease activity (EULAR Sj\u0026ouml;gren's Syndrome Disease Activity Index - ESSDAI), disease damage (Sj\u0026ouml;gren's Syndrome Disease Damage Index-SSDDI), comorbidities, cardiovascular risk (Framingham), labial salivary gland biopsy, salivary gland ultrasound, and pharmacological and non-pharmacological treatment. Additionally, patient-reported outcome measures (PROMs) are being incorporated, including the EULAR Sj\u0026ouml;gren's Syndrome Patient-Reported Index (ESSPRI), Profile of Fatigue and Discomfort (PROFAD), Hospital Anxiety and Depression Scale (HADS), Epworth sleepiness scale (ESE), International Physical Activity Questionnaire-short form (IPAQ-SF), and EuroQol-5 Domain (EQ-5D). The study is currently enrolling 1,010 patients. The mean age of the 1,010 SjD patients is 55.6\u0026thinsp;\u0026plusmn;\u0026thinsp;13.6 years, with 96.5% of women. Ninety-three percent of patients present with xerostomia, 93.7% xerophthalmia, 78.9% anti-Ro/SSA, and 41.8% anti-La/SSB. Ninety-four percent and 90% of patients have met the 2002 AECG and 2016 ACR-EULAR classification criteria, respectively. There is a potential for future studies to investigate the clinical and laboratory profile, predictors of systemic involvement and cardiovascular risk; prevalence of anxiety and depression and associations, level of physical activity and associations, comorbidities and polypharmacy; in addition, treatment response, follow-up of disease activity and mortality. The next step is to create a biorepository for biological specimens.\u003c/p\u003e","manuscriptTitle":"Brazilian Registry of Sjögren’s Disease (BRAS): a full picture of Sjögren’s disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-16 05:56:24","doi":"10.21203/rs.3.rs-4960285/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8449d515-213d-4751-8ac0-adfe0ab6404c","owner":[],"postedDate":"October 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-02-11T23:38:17+00:00","versionOfRecord":[],"versionCreatedAt":"2024-10-16 05:56:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4960285","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4960285","identity":"rs-4960285","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}