Para médicos · reumatologia
Resumos de artigos, podcasts e newsletters sobre Doença de Sjögren, para atualização médica.
A newsletter aborda inovações do EULAR 2026, destacando a embolização da artéria genicular como uma alternativa promissora e segura para o manejo da dor na osteoartrite de joelho refratária. O conteúdo também analisa a persistência da sarcopenia em pacientes com artrite reumatoide controlada e os desafios da inércia terapêutica no tratamento da hipertensão arterial pulmonar em pacientes com esclerose sistêmica.
A newsletter analisa a busca por biomarcadores para a nefrite lúpica, destacando que, apesar de candidatos promissores como a IL-16 e o CD163 urinários, a biópsia renal ainda é o padrão-ouro indispensável. O conteúdo também aborda benefícios da combinação leflunomida e hidroxicloroquina no tratamento de Sjögren e a confiabilidade do PHQ-8 no rastreio de depressão em pacientes com dor crônica, sem viés de sobreposição somática.
Objective To develop and validate a non-invasive predictive model for labial focus score (FS) ≥1 in patients suspected of having Sjögren's disease (SJD), by integrating salivary gland ultrasound (SGUS) findings with clinical parameters. Methods A novel semi-quantitative SGUS scoring system was applied to 449 patients prospectively recruited. Multivariable logistic regression analysis was conducted to identify independent predictors of FS ≥1, which were subsequently incorporated into a risk stratification matrices model. The model underwent both internal (n=139) and external validation (n=57). Results The derivation cohort included 449 patients (mean age 44.0 years, 94.7% female), with 284 (63.3%) showing labial FS≥1. Patients with FS≥1 were older and had higher total SGUS-scores and hyperglobulinemia. Multivariable logistic regression identified the SGUS-score (odds ratio [OR] 1.44), age (OR 1.51), and hyperglobulinemia (OR 1.91) as independent outcome predictors. This led to an age-stratified prediction model categorizing patients into high-, moderate-, and low-risk groups across three age brackets. This model showed strong predictive value for labial FS≥1 in both high-risk and low-risk populations (AUC: 0.91, 95%CI: 0.87-0.96, P<0.001), with specificity of 81%, sensitivity of 95%, positive predictive value (PPV) of 92%, and negative predictive value (NPV) of 87%. The model performed well in both internal validation (AUC: 0.90) and external validation (AUC: 0.83). Conclusion Our SGUS-based predictive model provides an exploratory, hypothesis-generating tool for guiding LSGB decisions in SJD by integrating imaging with clinical parameters, enabling personalized risk stratification. It effectively identifies high-risk patients needing biopsy and low-risk patients avoiding unnecessary procedures, offering a significant diagnostic advance.
Lung transplantation represents a potential life-extending therapy for patients with advanced CTD-ILD. This study aims to characterize lung transplant listing outcomes among CTD-ILD patients over a 20-year period using the Organ Procurement and Transplantation Network (OPTN) national database. Data analyzed from the OPTN between 2003-2023 included adults ≥18 years of age with CTD-ILD listed for lung transplantation. Patients were categorized into six diagnoses: scleroderma, lupus, rheumatoid arthritis (RA), myositis, Sjögren’s, and "Other" (including mixed connective tissue disease, CTD, etc.). Disease and patient specific data were obtained. Trends in listing and outcomes were analyzed in four time periods across the 20 years and among various diagnoses. We used descriptive summary statistics to characterize the sample, and univariate and multivariable logistic regression models to identify factors associated with undergoing lung transplantation. A total of 1,977 CTD-ILD patients were listed. Scleroderma constituted the majority (47%). Listings increased fourfold (185 to 744) from the first to last time periods. Listings for all diagnoses increased with time, with rising representation of non-White patients. Trend noted towards listing patients with more advanced lung disease with time. Transplant rates rose, while wait times, and waitlist mortality declined overtime. All diseases received transplants at comparable rates. Older age, lower lung allocation scores, and male sex were associated with higher odds of transplantation, female sex with lower odds. Over two decades, CTD-ILD transplant listings have increased in volume, matched with substantially improved outcomes. This reflects the evolution of listing practices and a growing confidence in lung transplantation as a viable option for CTD-ILD.
Objectives Fatigue is a disabling symptom in Sjögren’s disease (SjD); however, its severity and related factors in associated SjD remain unclear. We compared fatigue severity among patients with primary Sjögren’s disease (pSjD), associated SjD, and systemic autoimmune rheumatic diseases (SARDs) without SjD and identified fatigue-associated clinical and patient-reported factors in patients with pSjD and associated SjD. Methods This cross-sectional study included 115 patients with pSjD, 125 with associated SjD, and 52 with SARDs without SjD. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI). Clinical and laboratory parameters were analysed. Results Fatigue was significantly more severe in pSjD and associated SjD than in SARDs without SjD (FACIT-F total: 30 vs. 36 vs. 42, p < 0.001), with no significant difference between pSjD and associated SjD. Patients with pSjD reported greater subjective symptom burden, including higher ESSPRI fatigue (7.0 vs. 5.0, p = 0.011) and dryness (7.0 vs. 5.0, p = 0.012) scores. In multivariate analysis, pain (pSjD: β –2.12, p < 0.001; associated SjD: β –0.79, p = 0.019) and dryness (pSjD: β –1.26, p = 0.002; associated SjD: β –2.07, p < 0.001) were independently related with fatigue in both groups. Fibromyalgia (β –15.4, p < 0.001) and arthritis (β –7.7, p = 0.006) were related only in pSjD, and C-reactive protein (β –1.53, p = 0.029) only in associated SjD. Fatigue was not linked with systemic disease activity (ESSDAI) in pSjD. Conclusions Fatigue is a major burden across the SjD spectrum, with similar severity in pSjD and associated SjD but distinct contributing mechanisms. Key Points • Fatigue severity was comparable between pSjD and associated SjD; however, distinct factors
Autoimmune rheumatic diseases (ARDs) are a diverse group of chronic disorders characterized by immune dysregulation and multi-organ inflammation. B cell receptor (BCR) signaling emerges as a shared, yet heterogeneously regulated, pathogenic axis across these diseases. This dysregulation drives B cell activation, autoantibody production, and ultimately tissue damage. Recent research highlights its involvement in both common and disease-specific mechanisms, which helps explain the wide variation in clinical features and therapeutic responses across ARDs. This review summarizes current evidence establishing BCR signaling as a central regulatory and therapeutic target in rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, IgG4-related disease, and ANCA-associated vasculitis. It integrates mechanistic insights with recent clinical trial data on BCR signaling-targeted therapies, discussing factors that may contribute to variability in therapeutic responses and treatment limitations. Finally, we outline current challenges and future directions for precision medicine in ARDs, with a focus on biomarker-guided strategies and innovative combination therapies to improve patient outcomes.
A newsletter discute como o sequenciamento genômico pode revelar doenças raras monogênicas disfarçadas de condições comuns, explicando casos de refratariedade ao tratamento. Apresenta atualizações cruciais na Doença de Sjögren, destacando a estratificação por clusters de risco e a emergência de novas terapias como o dazodalibep. Além disso, alerta para a toxicidade renal por antimaláricos e o uso de proteômica urinária para monitorar a inflamação na nefrite lúpica.
Abstract Objectives Sjogren’s disease (SjD) shows a strong female predominance, but the contribution of age-related hormone changes to this sex bias remains uncertain. We investigated whether natural hormonal transitions across the lifespan align with variation in male and female prevalence of SjD. Methods Electronic health records from 101 856 SjD patients and 1.33 million controls were analyzed. Sex-specific prevalence was compared with serum testosterone, estradiol, and sex hormone-binding globulin (SHBG) levels. Population-level hormone distributions from the National Health and Nutrition Examination Survey (NHANES) were incorporated using imputation. Generalized linear models evaluated associations between hormone fluctuations and sex prevalence across age groups. Results Male prevalence among SjD patients peaked during early childhood (30.1% [95% CI: 26.2–34.1]), declining sharply in late puberty into adulthood (9.8% [95% CI: 9.5–10.2]), and rose again in older adults (13.5% [95% CI: 13.3–13.8]). These non-linear shifts paralleled age-dependent trajectories of testosterone and estradiol. Hormone concentrations did not differ significantly between SjD patients and controls, indicating that physiological transitions, rather than abnormal levels, align with disease risk. Conclusion Age-dependent hormonal changes correspond with evolving sex bias in SjD, challenging the static 9:1 female-to-male paradigm. These findings highlight the role of age-related hormonal dynamics in shaping autoimmune susceptibility.
Salivary gland ultrasonography (SGUS) is a promising, non-invasive tool in the diagnostic workup of suspected primary Sjögren’s disease (SjD). This study aimed to compare the diagnostic accuracy of two SGUS scoring methods - an ordinal score (0–6) and a sum score (0–12) - derived from the OMERACT 0–3 grading system, using labial salivary gland biopsy as the reference standard. Sixty consecutive patients with suspected primary SjD underwent SGUS of the four major salivary glands. Each gland was graded using the OMERACT 0–3 system. Two composite scores per patient were calculated: (1) ordinal score (maximum 6), considering the two most affected glands and (2) sum score (maximum 12), obtained by adding the scores of all four glands. Diagnostic accuracy was assessed using ROC curve analysis, with histopathology as reference. Labial biopsy was positive in 23 patients (38.3%). The ordinal score yielded an AUC of 0.687 (95% CI: 0.546–0.828), with 91.9% specificity (95% CI: 83.1–100%) at a threshold ≥ 4. The sum score showed an AUC of 0.683 (95% CI: 0.543–0.824), with 89.2% specificity (95% CI: 79.2–99.2%) at ≥ 5. SGUS scores ≥ 2 (ordinal) and ≥ 3 (sum) were significantly associated with anti-Ro52 antibody positivity (p = 0.017 and p = 0.007, respectively). At these high-specificity thresholds, labial biopsy could have potentially been deferred in 16.6% (ordinal ≥ 4) and 21.7% (sum score ≥ 5) of biopsy-positive cases, respectively. Although overall diagnostic performance was modest, SGUS scoring based on OMERACT definitions demonstrated high specificity at selected thresholds. These findings support its potential role as a biopsy-sparing tool in selected patients with high pre-test probability and compatible serological profiles. Prospective studies are needed to validate these results and optimize threshold selection. not
ABSTRACT Objectives Undifferentiated connective tissue disease (UCTD) represents a systemic autoimmune condition characterized by clinical and serological features suggestive of defined connective tissue diseases (CTDs), yet insufficient to fulfill existing classification criteria. Despite increasing interest, long-term outcomes—particularly progression to defined CTDs—remain incompletely understood. This study aimed to evaluate the clinical outcomes of a UCTD cohort followed for at least 5 years and to identify baseline clinical and serological factors associated with an increased risk of evolution to a defined CTD. Methods A total of 658 patients were screened for this retrospective cohort study. After applying predefined eligibility criteria, 504 patients who met established UCTD definitions were included. Baseline clinical, laboratory, and serological characteristics were analyzed. Two patient outcome groups were defined at 5-year follow-up: those who evolved to a defined CTD and those who remained stable. Given the limited number of cases evolving to defined CTDs, group comparisons were performed using Student’s t-test or Mann-Whitney U test rather than logistic regression. Autoantibodies were assessed using indirect immunofluorescence for ANA and validated immunoassays for anti-dsDNA, anti-Sm, anti-Ro/SS-A, anti-La/SS-B, anti-Scl-70, anti-centromere, anti-U1RNP, anti-Jo1, rheumatoid factor, anti-cyclic citrullinated peptide antibodies (ACPA), antiphospholipid antibodies (anti-β2 glycoprotein I IgM/IgG, anti-cardiolipin IgM/IgG), and lupus anticoagulant. Results After a mean follow-up of 82 months, 102 of the 504 UCTD patients (20.2%) developed a defined CTD (37 Sjögren’s disease (SjD), 35 systemic lupus erythematosus (SLE), 12 systemic sclerosis (SSc), 14 rheumatoid arthritis, and 4 mixed connective tissue disease) within a follow-up period of at least 5 years. The most common clinical manifestations of UCTD included arthralgias, sicca symptoms, photosensitivity, oral aphthae, and Raynaud’s phenomenon. Differentiation was significantly associated with features such as a Schirmer test <5 mm (p=0.007),
Introduction Chronic inflammation and immune cell communication underpin a wide range of chronic diseases, yet population-scale maps integrating systemic inflammatory, metabolic and proteomic signals across multiple disease states are scarce. Methods Using UK Biobank, we classified participants into six baseline groups—healthy controls, cancer, autoimmune, infectious, metabolic diseases, and multiple comorbidities. We profiled clinical and hematological indices, NMR-based metabolites and Olink proteomics, and trained four multi-class deep learning models (clinical/inflammatory only; +NMR; +Olink; three-tower multi-omics) with 10-fold cross-validation. Out-of-fold predicted probabilities were combined in a stacking meta-model to derive machine-learning risk scores for “any chronic disease.” Shapley value analyses were used to identify key features reflecting systemic immune and metabolic communication. Cause-specific cumulative incidence and Fine–Gray competing-risks models evaluated associations between these risk scores and cancer-related and non-cancer mortality, adjusting for conventional risk factors. To provide biological validation of model-prioritized immune mediators (BAFF [TNFSF13B], GDF15, IL-15 and CD276), we performed in vitro stimulation of healthy-donor PBMCs by ELISA, flow cytometry, and qPCR. Results We observed pronounced and pathway-specific heterogeneity of inflammatory markers, lipid-related metabolites and immune–inflammatory proteins across disease groups. Omics-augmented deep learning models outperformed the clinical-only model, and the stacking ensemble achieved the best accuracy, macro-F1 and multi-class AUC. Machine-learning–derived risk scores showed monotonic gradients in cancer and other-cause death and remained independently associated with several cause-specific outcomes. In vitro validation supported myeloid inflammatory inducibility of model-highlighted mediators. Conclusions By integrating multi-omics deep learning with competing-risks modelling, this study decodes population-level immune–metabolic communication patterns across chronic disease states, linking shared inflammatory and proteomic signatures to long-term mortality and providing a quantitative framework to support future, mechanism-focused and immunologically informed risk stratification.
A newsletter aborda as atualizações do ACR 2025 sobre a investigação de vasculites cutâneas, enfatizando a diferenciação entre quadros limitados à pele e manifestações sistêmicas. Destaca também que a doença pulmonar intersticial é uma complicação frequente e grave na esclerose sistêmica limitada, especialmente em pacientes com anticorpo anti-topoisomerase I positivo.
A newsletter destaca as principais atualizações do ACR 2025, focando na emergência dos T Cell Engagers (TCEs) como uma terapia celular mais acessível para o tratamento de doenças autoimunes graves. O conteúdo também revisa a falta de evidências robustas para terapias alternativas na osteoartrite de joelho e compila novos guidelines para o manejo de lúpus, gota e artrite idiopática juvenil.
A newsletter aborda o conceito de Gamopatia Monoclonal de Significado Reumatológico (GMSR), enfatizando sua relevância clínica na Crioglobulinemia e no risco de linfoma na Doença de Sjögren. Discute também os resultados de 17 anos do registro REGISPON-3, que revela a instabilidade fenotípica das espondiloartrites e o início tardio de terapias biológicas. Por fim, apresenta avanços no manejo remoto da osteoporose masculina e novos achados imunológicos na dermatomiosite anti-MDA5.
Ultrasound-guided core needle biopsy (CNB) of major salivary glands is a less invasive alternative to minor salivary gland biopsy for diagnosing Sjögren's disease (SjD), reducing risks of neurological deficits and pain. However, the optimal CNB specimen length for adequate glandular surface area remains uncertain. This study aimed to determine and validate the optimal CNB specimen length thresholds. This retrospective, dual-phase study included 119 consecutive patients undergoing submandibular gland CNB with an 18-gauge needle for suspicious chronic inflammatory sialadenitis. Specimen length, total surface area, and glandular surface area were recorded. A validation cohort (n=37) was analysed separately. Statistical analyses included correlation, regression, and ROC curve analysis. Specimen length correlated with glandular surface area (ρ=0.69, p<0.001). Multivariable analysis confirmed specimen length as a positive predictor (p<0.001) and fatty infiltration as a negative predictor (p=0.003) of glandular surface area. ROC analysis identified 7.6 mm as optimal for glandular surface area ≥4 mm², and 10.5 mm for ≥8 mm². Clinically significant haematomas occurred in 1.7% of cases. In the validation cohort, using the 7.6 mm threshold, PPV was 86.2%, and NPV 87.5% for glandular surface area ≥4 mm². For the 10.5 mm threshold, PPV was 76%, and NPV 100% for ≥8 mm². A CNB specimen length of ≥7.6 mm is sufficient for diagnosing SjD, while ≥10.5 mm may be required for clinical trials. These findings may support the integration of specimen length thresholds into CNB procedural guidelines.
International guidelines recommend having a positive anti-nuclear antibody (ANA) and clinical suspicion of systemic autoimmune rheumatic diseases (SARD) when requesting ANA subserologies. Compliance with these guidelines by physicians has been questioned in different parts of the world. To analyse the requesting pattern of ANA and anti-extractable nuclear antigens (ENA) simultaneously in the University of Malaya Medical Centre (UMMC). This is a retrospective descriptive study involving 1529 adult patients who had their ANA and ANA subserologies requested simultaneously by clinicians. The ANA, anti-ENA screening (ENASc) and anti-ENA specific (ENASp) results were retrieved. Their case records on their relevant diagnosis and follow-up tests were reviewed. Among the 1,529 samples, 536 (35%) patients were positive, and 993 (65%) patients were negative for ANA by indirect immunofluorescence assay (IIF). In the ANA positive group, 109 (20%) were positive and 46 (9%) were borderline for ENASc. Of those ENASc positive patients, only 47 patients were requested for ENASp. Forty-one (87.2%) were positive for ENASp, In the ANA negative group, 111 (11%) were positive and 66 (7%) were borderline for ENASc. The majority of the ENASc positive (86, 77%) or borderline (63, 95%) had not been requested for ENASp in this group. Of those who had ENASp tests done (28), 19 (76%) were positive and 3 were borderline positive for ENASp. A total of 223 patients were diagnosed with SARD, out of which 147 had SARD in the ANA positive group (66%), with systemic lupus erythematosus being identified as the commonest SARD. A total of 76 patients were diagnosed with SARD in the ANA negative group (34%), with rheumatoid arthritis being identified as the commonest SARD. A large number of ENASc negative results are obtained concurrently
To systematically review the prevalence, risk and associated factors of organ damage in Sjögren's disease (SjD) and to assess its impact on quality of life and long-term outcomes. A systematic search of PubMed (2005-2025) identified studies assessing damage accrual in SjD. Longitudinal and cross-sectional studies enrolling patients fulfilling the 2002 AECG and/or 2016 ACR/EULAR classification criteria were included. Damage was defined using validated indices, the Sjögren's Syndrome Damage Index (SSDI) or the Sjögren's Syndrome Disease Damage Index (SSDDI), or through conceptual definitions of irreversible disease attributable injury. The lymphoma domain was excluded. Study selection followed PRISMA guidelines, and predefined PICO frameworks guided data extraction. Twenty-three studies were included. Glandular damage was reported in 25-86% of patients, while systemic damage affected 9-73%. Older age, longer disease duration, higher baseline ESSDAI, hypergammaglobulinaemia, hypocomplementaemia, and absence of hydroxychloroquine therapy were the most consistent predictors of damage accrual. Pulmonary and renal involvement were associated with increased mortality and hospitalisation rates. Cumulative SSDDI scores correlated with reduced health-related quality of life (HRQoL). Organ damage in SjD is common nd progressive, reflecting sustained immunologic activity and agingrelated vulnerability. Damage burden predicts poorer outcomes and diminished HRQoL. Standardisation of damage definitions and assessment tools is essential to improve comparability across studies and to guide preventive therapeutic strategies.