Para médicos · reumatologia
Resumos de artigos, podcasts e newsletters sobre Lúpus Eritematoso Sistêmico, para atualização médica.
A newsletter destaca a revisão do índice de dano (SDI) no Lúpus Eritematoso Sistêmico, que busca maior precisão clínica ao remover itens de atividade inflamatória e incluir critérios de gravidade. Além disso, apresenta novos guidelines da EULAR para vasculites e polimialgia reumática, e discute evidências recentes sobre terapias biológicas e inibidores de fosfodiesterase em doenças autoimunes.
A newsletter analisa um estudo populacional que revela alta prevalência de edema ósseo sacroilíaco em indivíduos saudáveis, alertando para a necessidade de contexto clínico no diagnóstico de espondiloartrites. Além disso, discute as divergências entre diretrizes globais para esclerose sistêmica e apresenta avanços em novas terapias biológicas para o lúpus.
A newsletter discute as novas diretrizes do ACR 2025 para o lúpus eritematoso sistêmico, enfatizando a importância da ultrassonografia para identificar sinovites frequentemente subestimadas no exame clínico. O conteúdo detalha o desempenho de terapias como anifrolumabe e belimumabe em diferentes perfis de pacientes, além de abordar a aprovação do anacinra e casos de fraturas por insuficiência na artrite reumatoide.
A newsletter discute a descoberta de que a assinatura do interferon tipo 1 pode preceder o diagnóstico da Síndrome de Sjögren em até 14 anos, definindo um endotipo biológico específico. Além disso, aborda o aumento da detecção de miopatias necrosantes por estatinas e a integração de mecanismos inflamatórios na perda de massa óssea e muscular em pacientes obesos.
PURPOSE OF REVIEW: Genetic autoinflammatory conditions constitute an increasing field. Among them, type I interferonopathies (IFNp-I) were conceptualized 15 years ago as inborn errors of immunity due to chronic activation of the type I interferon (IFN-I) signalling pathway. Here, we provide recent insights in genetic mechanisms, clinical phenotypes and therapeutic options for these severe and rare disorders. RECENT FINDINGS: We will cover the novel findings into disease mechanisms, particularly the role of PTP1B in STING and IFNAR signalling, as well as the contribution of endosomal TLR pathways. We will also discuss the expanding phenotypic spectrum highlighted by recent case reports and cohort studies, together with the topic of clinical expressivity, including clinical non-penetrance, and possible mechanistic explanations such as monoallelic expression, the STING HAQ haplotype, and innovative approaches to characterise disease variability. Finally, we discuss current targeted therapeutic approaches for these disabling conditions, as well as potential new treatments for the future. SUMMARY: Overall, these findings highlight the need to consider these rare diseases across a wide range of clinical phenotypes. Advances in next-generation sequencing have enabled a genetic diagnosis in suspected cases and the implementation of targeted treatments, thereby reducing diagnostic uncertainty and providing the possibility of genetic counselling.
OBJECTIVE: To characterize the long-term clinical course of children with hematologic non-criteria manifestations and persistent antiphospholipid antibodies (aPL), and to identify predictors of progression to antiphospholipid syndrome (APS) and/or systemic lupus erythematosus (SLE). METHODS: We conducted a prospective cohort study of children (<18 years) with persistent aPL positivity and hematologic involvement (thrombocytopenia, autoimmune hemolytic anemia [AIHA], or Evans syndrome) followed at a tertiary pediatric rheumatology center between 1995 and 2024, with follow-up extending into adulthood. Progression to clinically classifiable APS and/or SLE was the primary endpoint. Kaplan-Meier and Cox proportional hazards models evaluated predictors at presentation and in complementary time-dependent analyses. RESULTS: Among 42 enrolled children, 40 were evaluable, of whom 11 (27.5%) progressed to APS and/or SLE. Evans syndrome at presentation was associated with the highest hazard of progression compared with isolated thrombocytopenia (HR 6.21, 95% CI 1.46-26.41). In time-dependent analyses, Evans syndrome emerging during follow-up remained associated with progression. Isolated thrombocytopenia showed the lowest risk, whereas AIHA represented an intermediate state that did not independently predict progression. Lupus anticoagulant was nearly universal, and broader high-risk aPL profiles were more common among progressors but were not statistically significant. CONCLUSION: In children with persistent aPL positivity, Evans syndrome was the hematologic phenotype most strongly associated with progression to APS and/or SLE, whereas isolated thrombocytopenia followed a largely indolent course. Evolving hematologic phenotypes may improve risk stratification and inform long-term monitoring strategies within the APS-SLE spectrum.
A newsletter discute a alta prevalência de manifestações cardíacas na Síndrome de Behçet, frequentemente subestimada e associada à atividade sistêmica da doença. O conteúdo também aborda a importância do rastreio de HPV em pacientes imunossuprimidos e apresenta a LBFSS, a primeira escala específica para mensurar a disfunção cognitiva no Lúpus.
To co-develop disease-specific patient questions for connective tissue diseases (CTDs), compare patient/rheumatologist ratings of answers from language models (LLMs) versus Google Search, and quantify EULAR coverage of these patient-prioritized questions. In this prospective single-center observational study, reported in accordance with STROBE, patient advocacy groups curated 20 frequently asked questions (FAQs) for each CTD (systemic lupus erythematosus, idiopathic inflammatory myopathy, Sjögren disease, systemic sclerosis). Questions were submitted to Claude 4.0 Sonnet, ChatGPT-5, Gemini 2.5 Pro, and Google Search. Five patients per disease and five rheumatologists rated blinded outputs using forced-rank preference and 5-point Likert scales (patients: empathy, trustworthiness, comprehensibility; physicians: medical correctness, empathy, comprehensibility). Guideline mapping assessed whether EULAR recommendations addressed each question. All three LLMs answered 100% of questions (80/80), whereas Google Search answered 90% (72/80). Across CTDs, patients rated LLM outputs favorably for empathy (mean 1.40-2.77), trustworthiness (1.47-2.6), and comprehensibility (1.33-2.27), and rheumatologists for medical correctness (1.23-1.98). Patients and physicians most often ranked Gemini 2.5 Pro best overall (rank 1: 59% and 63%), and Google Search most often worst (rank 4: 55% and 57%). Cluster analyses showed no consistent differences across five clusters. Guideline mapping revealed substantial gaps: 40-55% of prioritized FAQs were not addressed by EULAR recommendations, with largest gaps in cluster E, life impact, psychosocial aspects and family planning (75-100% not addressed; 0% fully addressed). In this blinded evaluation, LLMs produced CTD FAQs responses patients perceived as empathic, trustworthy and rheumatologists rated medically correct, with Gemini 2.5 Pro most consistently preferred overall. However, the mismatch between prioritized questions and guideline coverage underscores the need for patient-centered, evidence-grounded information resources.
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.
Background Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease that may damage multiple organs. About one-third of SLE patients have ocular manifestations. SLE as a potential risk factor for glaucoma has attracted attention, but existing study conclusions remain controversial. This meta-analysis aimed to evaluate the risk association between SLE and glaucoma and provide supportive evidence for the comorbidity follow-up of SLE patients. Methods The PubMed, EMBASE and Web of Science databases from the establishment of the database to November 2025 were retrieved, and studies measuring the association between SLE and glaucoma risk by hazard ratio (HR), odds ratio (OR), relative risk (RR), incidence rate ratio (IRR) and 95% confidence interval (CI) were included. Two researchers independently screened the literature, extracted the data and evaluated the risk of bias in the included studies. Meta-analysis was conducted using RevMan 5.3 software. Results Five cohort studies were included, involving 5516709 participants. Meta-analysis showed that SLE was associated with an increased risk of glaucoma (OR = 2.85, 95% CI: 1.26–6.47, P = 0.01). Subgroup analyses showed stronger associations in studies with fewer covariate adjustments and in those that did not adjust for corticosteroid use. Conclusions Existing evidence suggests that SLE may be associated with an increased risk of glaucoma. Given the limitations of this study, more prospective studies with rigorous design and full control of confounding factors are needed for further verification. Systematic review registration https://www.crd.york.ac.uk/prospero , identifier CRD420261303001.
Background Leprosy can mimic systemic lupus erythematosus (SLE) due to overlapping clinical, laboratory, and immunological features, frequently resulting in misdiagnosis and inappropriate immunosuppressive treatment. We report a case of leprosy initially misdiagnosed as SLE and systematically review the literature on leprosy cases mimicking SLE, emphasizing clinical, laboratory, therapeutic, and outcome characteristics, evaluated in light of the 2019 ACR/EULAR classification criteria for SLE. Methods A systematic review was conducted according to PRISMA guidelines. PubMed, SciELO, and Google Scholar were searched for articles published up to August 2025. Case reports and case series describing leprosy previously diagnosed as SLE were included. The protocol was prospectively registered in PROSPERO (CRD420261283210). Results Twenty-three patients, including the index case, were analyzed. Most were female (78.2%), with a median age of 35 years (interquartile range [IQR] 30–47.5). Cutaneous manifestations were present in all patients, particularly malar rash (43.4%), photosensitivity (34.7%), and cutaneous nodules (30.4%). Osteoarticular involvement occurred in 78.2% and neurological manifestations in 43.4%. Antinuclear antibodies were positive in 74% of cases, frequently at low to moderate titers. Lepromatous leprosy was the most frequent form (69.5%). Prior to the correct diagnosis, 65.2% of patients fulfilled the EULAR/ACR classification criteria for SLE, 87% received corticosteroids and 69.5% antimalarials. Diagnostic delay exceeded one year in nearly half of cases. After initiation of multidrug therapy, 47% of patients showed clinical improvement, although leprosy reactions and residual symptoms remained common (35.3%). Conclusion Leprosy should be considered in the differential diagnosis of SLE, particularly in patients presenting with cutaneous and articular manifestations accompanied by peripheral neuropathy and poor response to immunosuppressive therapy. By delineating recurring clinical patterns and diagnostic pitfalls, our findings provide practical clues for earlier recognition, helping to prevent
Systemic lupus erythematosus (SLE) is a disease with considerable unmet treatment needs. Endosomal nucleic acid sensing by Toll-like receptor 7 (TLR7) is emerging as a key pathogenic pathway. Gain-of-function mutations in the genes encoding TLR7 and its chaperone UNC93B1 can cause monogenic childhood-onset SLE; rare variants in proteins that regulate ligand availability or downstream signalling proteins also contribute to disease. TLR7 variants can increase the affinity of this receptor for its ligands and can alter binding to endogenous antagonists. Both self RNA–protein complexes and viruses have been implicated in TLR7 activation. Key pathogenic mechanisms include breakdown in B cell tolerance and autoantibody production and type I interferon secretion. Although current therapies such as B cell-depleting chimeric antigen receptor (CAR) T cells and anifrolumab (anti-type I interferon receptor) offer benefit, they are limited by high costs and lack of oral options. In this context, TLR7 has emerged as a promising therapeutic target. Phase II trials of an oral dual TLR7–TLR8 antagonist show durable suppression of the interferon signature in all patients, indicating that TLR7 and TLR8 drive this signature in SLE. This treatment has shown clinical benefit for SLE and cutaneous lupus erythematosus, although the primary endpoint (a dose–response effect) was only met in cutaneous lupus erythematosus. Thus, TLR7–TLR8 antagonists might reshape SLE treatment, alone or in combination with other drugs.
A newsletter apresenta os destaques do EULAR 2026, com foco na superioridade articular do bimequizumabe frente ao risanquizumabe na artrite psoriásica e o uso inovador de CAR-T in vivo para o lúpus. Também discute um grande estudo sobre as lesões cutâneas atípicas na Doença de Still e a rápida resposta dermatológica do brepocitinibe na dermatomiosite.
Janus kinase (JAK) inhibitors have emerged as a transformative therapeutic class across autoimmune diseases by targeting multiple cytokine networks implicated in inflammation and fibrosis. Beyond inflammatory arthritis, increasing evidence supports their potential efficacy in connective tissue diseases such as idiopathic inflammatory myopathies, systemic sclerosis, primary Sjögren's disease, and systemic lupus erythematosus. Through modulation of type I/II interferon and interleukin signaling, JAK inhibition exerts broad anti-inflammatory and antifibrotic effects, translating into clinical improvements in cutaneous, articular, and pulmonary domains. Early clinical trials and real-world data confirm meaningful responses in refractory disease, though randomized evidence remains limited. Overall, JAK inhibitors represent a promising, mechanistically grounded option for systemic autoimmune diseases, with ongoing studies expected to refine selectivity, indications, and long-term safety profiles.
Incomplete lupus erythematosus (ILE) and non-Sjögren’s disease sicca (nSjD-sicca) are clinically heterogeneous, incompletely classified autoimmune conditions that share features with systemic lupus erythematosus (SLE) and Sjögren’s disease (SjD), respectively. Although some patients progress to classified disease, many remain stable. The immunologic features distinguishing incomplete from established autoimmune disease remain poorly defined. We sought to characterize and compare autoantibody immune signatures across ILE, SLE, nSjD-sicca, and SjD using expanded autoantibody profiling. Serum samples were obtained from patients with ILE (n=80), SLE (n=80), nSjD-sicca (n=52), SjD (n=60), and matched healthy controls (n=79). Initial screening was performed using the Bio-Rad BioPlex 2200. Expanded profiling utilized the GeneCopoeia Human Autoimmune Array (120 autoantigens) with parallel IgM and IgG detection. Traditional screening demonstrated expected patterns: ILE (anti-nRNP 26.3%; anti-chromatin 25.0%), SLE (anti-SmRNP 40.0%; anti-dsDNA 31.3%), nSjD-sicca (anti-La 9.6%), and SjD (anti-Ro/SSA 53.3%). Expanded analysis revealed significantly increased IgM autoreactivity in ILE compared with SLE (BH-FDR-adjusted p&lt;0.05), targeting nuclear (KU, Nup62, CENP-A/B), cytokine (IFN-α1, IFN-ϵ, IL-15, GM-CSF), mitochondrial (M2), extracellular matrix (collagen IV, fibrinogen), vascular (β2-glycoprotein I, AGTR), and gut-associated antigens (tissue transglutaminase, intrinsic factor). In contrast, SLE demonstrated enriched IgG responses to canonical nuclear antigens, including core histone and dsDNA. Within the sicca spectrum, Ro52 (TRIM21) IgG autoantibodies were significantly increased in SjD compared to nSjD-sicca. These findings indicate that incomplete autoimmune disease states exhibit distinct IgM-dominant autoantibody profiles rather than simply attenuated versions of the IgG dominant responses in classified disease, highlighting the potential value of isotype-specific profiling for disease classification.
Background Patients with systemic lupus erythematosus (SLE) often develop age-related adverse outcomes at a young age, raising the possibility that immune-aging processes may interact with chronic immune activation, treatment exposure, and accumulated damage in shaping long-term disease burden. Although immune-age acceleration has also been reported in rheumatoid arthritis and chronic viral infections (e.g., HIV/CMV), SLE is particularly well suited as a human model of inflammation-driven immune aging because of its typical onset in young women and the convergence of aging signatures across clinical, cellular, and molecular levels. Main body This review synthesizes evidence for accelerated immunosenescence in SLE across systemic manifestations, immune cell remodeling, and molecular senescence markers. Clinically, SLE is linked to premature cardiovascular disease, frailty, cognitive impairment, severe infections, and reduced vaccine responsiveness. Immunologically, senescent-like immune subsets (including terminally differentiated T cells, age-associated/double-negative B cells, dysfunctional NK cells, and senescence-like myeloid cells) expand prematurely. Molecular features include inflammaging-like cytokine patterns, telomere attrition, and epigenetic age acceleration. We also discuss a translational framework for quantifying immunosenescence using immunophenotyping, telomere/epigenetic clocks, and composite immune clocks, with potential applications in risk stratification, treatment decisions, and monitoring immune-reprogramming strategies. Conclusions Accelerated immunosenescence provides a biologically plausible and clinically relevant framework for understanding SLE heterogeneity across systemic, cellular, and molecular levels. However, immune-aging measures should currently be regarded as candidate research biomarkers rather than validated clinical decision tools. Prospective SLE-specific studies are needed to establish their predictive value, disease specificity, and clinical utility.
Background The expanding use of biologic and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) has substantially improved outcomes in autoimmune diseases but is accompanied by complex safety concerns. Risk management plans (RMPs) have been introduced to mitigate treatment-related risks; however, real-world adherence to these strategies and their broader clinical impact remain incompletely characterized. Methods We conducted a retrospective observational cohort study of adult patients with autoimmune diseases who received bDMARDs, tsDMARDs, or biosimilars at a tertiary medical center in southern Taiwan between October 2014 and December 2023. Patients were classified into RMP and non-RMP groups based on completion of predefined pre-treatment safety assessments within 6 months prior to therapy initiation, including pulmonary and tuberculosis evaluation, viral hepatitis screening, and documentation of cardiovascular and malignancy risk factors. Clinical outcomes included Pneumocystis jirovecii pneumonia (PJP), major adverse cardiovascular events (MACE), treatment-related respiratory adverse events, and all-cause mortality. Multivariable logistic regression and time-to-event analyses were performed to evaluate associations between RMP implementation and clinical outcomes. Results Among 1,078 patients included, only 348 (32.3%) fulfilled the predefined RMP criteria prior to treatment initiation. Compared with the RMP group, patients without RMP exhibited significantly higher incidences of PJP (11.9% vs. 2.3%), MACE (8.5% vs. 2.6%), treatment-related respiratory adverse events (50.4% vs. 42.8%), and all-cause mortality (7.3% vs. 1.7%) (all p < 0.05). After multivariable adjustment, RMP implementation remained independently associated with lower risks of PJP (adjusted odds ratio [aOR] 0.18, 95% CI 0.15–0.84), MACE (aOR 0.30, 95% CI 0.13–0.71), and all-cause mortality (aOR 0.21, 95% CI 0.07–0.61). Subgroup and time-to-event analyses demonstrated that anti-CD20 therapy was associated with the highest risk of early-onset PJP, MACE, and mortality, with most events occurring within the first three
BackgroundShrinking lung syndrome (SLS) is a rare manifestation of systemic lupus erythematosus (SLE) lacking standardized management. This systematic review summarizes the current evidence on therapeutic interventions and clinical outcomes.MethodsFollowing PRISMA guidelines, we searched six databases (e.g., PubMed, Scopus, and Web of Science) for studies on adult SLS patients published up to January 2026. Methodological quality was assessed using JBI tools.ResultsForty studies (111 patients) were included (30 case reports and 10 case series); 87.5% presented a low risk of bias. There was a marked female predominance (91%), with a mean age of 33.5 ± 9.8 years. All patients showed a restrictive pattern (forced vital capacity: 47-52%). Glucocorticoids were the mainstay of therapy (95-96%). Rituximab emerged as an effective primary biologic for refractory cases. Non-pharmacological interventions, such as inspiratory muscle training and non-invasive ventilation, improved diaphragmatic strength. Although symptomatic resolution occurred in 75-95% of patients, complete functional recovery (normalization of pulmonary function tests) was achieved in only 20-23% of patients. Mortality directly attributed to SLS was low (2-5.5%).ConclusionsEarly glucocorticoid therapy remains essential, but complete functional recovery is rare, with 80% of patients maintaining chronic restriction. For refractory cases, multidisciplinary care integrating rituximab and respiratory rehabilitation should be considered to optimize functional outcomes.
OBJECTIVES: Systemic lupus erythematosus (SLE) is strongly associated with lupus nephritis (LN), a major cause of chronic kidney disease (CKD). However, long-term renal and cardiovascular outcomes in patients with SLE who have preserved kidney function and do not develop LN remain poorly characterized. We sought to investigate the development of CKD among newly diagnosed patients with SLE who had preserved kidney function and no evidence of concomitant LN at baseline, compared with matched control individuals. METHODS: A national database study of newly diagnosed patients with SLE between 2015 and 2023. Patients with estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2 at diagnosis were matched to non-SLE controls by age, sex, and ethnicity. Patients with LN were excluded. The primary outcome was incident CKD, defined as eGFR ≤60 mL/min/1.73 m2 after diagnosis. Secondary outcomes included end-stage kidney disease (ESKD), major adverse cardiovascular events (MACE), and all-cause mortality. RESULTS: We identified 1,145 patients with SLE and 91,681 matched controls, with a median follow-up of 5.77 years and similar baseline eGFR (103 vs 104 mL/min/1.73 m2). SLE was associated with a higher risk of CKD (5.2% vs 2.7%; HR 1.96, 95% CI 1.50-2.54), ESKD (HR 3.13, 95% CI 1.38-7.08), MACE (HR 1.63, 95% CI 1.31-2.04), and all-cause mortality (HR 4.52, 95% CI 3.71-5.50). Mean eGFR trajectories were similar between groups. Diabetes (HR 1.51, 95% CI 1.39-1.64) and hypertension (HR 2.72, 95% CI 2.42-3.07) were the strongest risk factors for CKD and ESKD. CONCLUSION: Patients with SLE and preserved kidney function at diagnosis, without LN, are at increased risk of adverse renal outcomes, cardiovascular events, and mortality, highlighting the importance of long-term monitoring and optimization of modifiable CKD risk factors.
A newsletter apresenta os principais destaques do congresso EULAR 2026, abordando desde a eficácia da manutenção do alopurinol na gota até novos alvos terapêuticos para a Síndrome de Sjögren. Além das atualizações clínicas, explora como fatores psicossociais e a satisfação conjugal influenciam diretamente o prognóstico e a saúde mental de pacientes com doenças reumáticas crônicas.
ObjectiveTo compare the performance of five lupus disease-activity indices measured at a single retrospective pregnancy timepoint for discriminating a composite adverse obstetric outcome (AO), and to perform exploratory clinically interpretable categorical and renal-item analyses across indices.MethodsRetrospective cohort at a tertiary center in Bogotá, Colombia (2012-2024). For each pregnancy, one retrospective assessment with complete clinical and laboratory information required to compute all indices was selected. AO was defined as any of: preterm birth, miscarriage, stillbirth/early fetal death, preeclampsia/eclampsia, premature rupture of membranes, postpartum hemorrhage, thromboembolism, placental abruption, or maternal death. We calculated SLEPDAI, Lupus Activity Index in Pregnancy (LAI-P), modified SLAM (m-SLAM), SLE Disease Activity Score (SLE-DAS), and BILAG2004-P. Because the dataset was retrospective and selected on complete data, we treated categorical and renal-item analyses as exploratory.ResultsTwenty-nine pregnancies (28 women) were included; AO occurred in 18/29 (62.1%). The original continuous-score analyses showed overlapping confidence intervals across indices. Exploratory clinically interpretable analyses showed AO in 15/18 (83.3%) pregnancies with any BILAG2004-P A/B domain, 16/20 (80.0%) with SLEPDAI ≥3, and 13/14 (92.9%) with SLE-DAS >7.64. Exploratory renal analyses showed the clearest signals for BILAG2004-P renal A/B (13/14 vs 5/15; OR 26.0, 95% CI 2.61-259.31), SLEPDAI renal-item score >0 (13/13 vs 5/16; OR 56.45, 95% CI 2.81-1133.97), and the LAI-P renal item >0 (12/13 vs 6/16; OR 20.00, 95% CI 2.05-195.01).ConclusionIn this small single-center cohort, active lupus was associated with adverse obstetric outcomes across disease-activity instruments. However, the study is underpowered to detect meaningful differences in discrimination between indices. Renal activity remained the most clinically relevant organ-specific signal in exploratory analyses, but these findings should be interpreted cautiously and confirmed in larger longitudinal cohorts.
Patients with systemic lupus erythematosus (SLE) are at markedly increased risk of premature atherosclerosis (AS) and atherosclerotic cardiovascular disease (ASCVD), and this excess risk is not fully explained by traditional Framingham factors. Increasing evidence suggests that SLE does not merely coexist with AS; rather, persistent immune activation and immunometabolic dysregulation reshape the vascular microenvironment toward endothelial dysfunction, lipoprotein impairment, maladaptive myeloid activation, and immunothrombosis. This review synthesizes current epidemiologic, mechanistic, and translational evidence supporting an immune–metabolic–vascular framework for SLE-accelerated AS. We focus on four interconnected processes: (1) type I interferon (IFN-I)-associated endothelial injury and defective vascular repair; (2) neutrophil extracellular traps (NETs) and oxidative modification of high-density lipoprotein, contributing to dysfunctional or pro-inflammatory HDL; (3) monocyte/macrophage immunometabolic reprogramming, which favors foam-cell formation and inflammasome activation; and (4) T- and B-cell metabolic disequilibrium, which sustains vascular inflammation and autoantibody-driven immune injury. Across these pathways, metabolic rewiring appears to function not merely as a parallel phenomenon, but as a shared amplifier linking systemic autoimmunity to lesion-level vascular progression. Recognizing these shared checkpoints has therapeutic implications. These observations suggest that future strategies may need to integrate upstream metabolic resetting, midstream immune-specific blockade, and downstream lipid or vascular-wall protection, rather than relying solely on lipid lowering or broad immunosuppression. However, most available evidence remains confined to mechanistic studies, biomarker readouts, or surrogate vascular endpoints, and dedicated trials with plaque or cardiovascular event outcomes are still needed.
Advances in high-throughput sequencing and genotype-first approaches have revealed a growing number of monogenic autoimmune and autoinflammatory conditions that present in late adolescence or adulthood and sometimes mimic more common rheumatologic diseases. These disorders arise from both germline and somatic mutations and span a broad spectrum of immune dysregulation, including autoinflammation, autoimmunity, immunodeficiency, allergic disease, and hematological disorders. Importantly, many affected individuals do not exhibit classical Mendelian inheritance or early-onset disease, instead presenting with incomplete penetrance, variable expressivity, or atypical phenotypes that fulfill established classification criteria for diseases such as systemic lupus erythematosus and vasculitides. In this review, we highlight recently described monogenic immune disorders with relevance to adult rheumatology practice, including germline inborn errors of immunity and somatic mutation-driven conditions. We discuss emerging mechanisms that link innate and adaptive immune dysregulation, clinical features that should prompt genetic evaluation, and practical considerations for genetic testing in adult patients. Finally, we examine current challenges and future opportunities in integrating molecular diagnostics into rheumatology care, emphasizing the potential for genetic diagnoses to refine disease classification and inform targeted, mechanism-based therapeutic approaches.
Objective Individuals with systemic autoimmune rheumatic diseases (SARDs) are at risk for worse acute and post–acute COVID‐19 outcomes, though whether individuals with SARDs have longer persistence of viral antigens after COVID‐19 has not been studied. Methods This retrospective cohort study evaluated post–COVID‐19 differences in SARS‐CoV‐2 antigen (spike, spike protein that contains the receptor‐binding domain, and nucleocapsid) positivity between individuals with SARDs (COVID‐19 and Rheumatic Diseases [RheumCARD]) and without SARDs (Researching COVID to Enhance Recovery [RECOVER]–Adult). SARS‐CoV‐2 antigens were measured in collected samples using a validated ultrasensitive single molecule array. This digital enzyme‐linked immunosorbent assay used antibody‐coated magnetic beads to capture antigen molecules, which were loaded into microwell arrays and detected through enzymatic cleavage of a fluorescent substrate. We used logistic regression to estimate unadjusted and adjusted (for age, sex, infection year, vaccination status, and COVID‐19 treatment) odds ratios for SARS‐CoV‐2 antigen positivity at months 3 and 6 following COVID‐19. Results Among 210 individuals with SARDs in RheumCARD and 348 individuals without SARDs in RECOVER‐Adult, any SARS‐CoV‐2 antigen positivity was more common in those with SARDs (36.7% in RheumCARD vs 18.9% in RECOVER‐Adult; P < 0.001). Those with SARDs had higher odds of nucleocapsid antigen positivity (adjusted odds ratio [aOR] 3.73, 95% confidence interval [CI] 1.28–10.85) or any antigen positivity (aOR 2.89, 95% CI 1.43–5.85) three months after COVID‐19 infection and higher odds of nucleocapsid antigen positivity (aOR 6.62, 95% CI 1.09–40.30) six months after COVID‐19 infection. Conclusion Individuals with SARDs were more likely to have SARS‐CoV‐2 antigen positivity at months 3 and 6 following COVID‐19 infection compared with individuals without SARDs, not explained by demographics, variant, vaccination, or treatment.
Objective Hydroxychloroquine (HCQ) nonadherence in systemic lupus erythematosus (SLE) stemming from decision complexities can be improved with shared decision‐making (SDM) tools clarifying benefits and harms. This study aimed to develop and evaluate HCQ‐SAFE, a pictogram‐based SDM tool during SLE visits. Methods HCQ‐SAFE was developed in English and Spanish using an iterative process with 30 patient and clinician advisers. We recruited 200 adults with SLE on HCQ across eight clinics in two health systems. Implementation outcome metrics, including mean feasibility ratings and time to complete intervention, were collected. We examined the mean change in adherence using proportion of days covered (PDC) data and Decisional Conflict Scale (DCS) scores post–HCQ‐SAFE intervention compared with baseline using paired t ‐test and adjusted linear regression. Results Among 200 participants, 90% were female, 51% were White, 8% spoke Spanish, and 50% reported high school education or less. At baseline, 62% were adherent to HCQ (PDC ≥80%), and 43% reported residual decisional conflicts (DCS ≥25). Nurses (21%), pharmacists (29%), and physicians (50%) reported high feasibility (mean = 8.5) and required five minutes (interquartile range [IQR] 5–7) to complete the intervention during a visit. Among HCQ nonadherers, adjusted HCQ adherence improved by 47% (95% confidence interval [CI] 38–57). Post‐intervention, only 1% of patients reported residual decisional conflicts, and mean change in DCS scores was 35 points (95% CI −30 to −39) after intervention. Findings were significant across language, education level, and clinician role ( P < 0.0001). Conclusion HCQ‐SAFE is a feasible SDM intervention with the potential to improve adherence and reduce decisional conflicts.
Objective We aimed to characterize CD4 + T cell plasticity in human systemic lupus erythematosus (SLE) by leveraging T cell receptor (TCR) repertoire features as markers of prior lineage states, integrating TCR and transcriptomic profiling to delineate plasticity patterns and evaluate their association with clinical disease activity. Methods We used TCR repertoire data as molecular signatures alongside a transcriptomic data set. Using a large‐scale ImmuNexUT database of patients with autoimmune disease, including 117 with SLE, we quantified T cell plasticity across 13 fine‐grained T cell types. We analyzed 6,392 samples in total. We defined “cell type” and “disease” signatures and evaluated plasticity by correlations between these signatures and by within‐donor TCR clonotype overlap. Replication was performed in independent bulk and single‐cell cohorts. Results We identified two orthogonal signatures of the repertoire and transcriptome, the cell type and disease signatures, allowing us to investigate CD4 + T cell plasticity comprehensively. Among all possible patterns, the strongest signal was observed between effector Treg cells (eTreg cells) and Th1 cells, and this was replicated in an independent cohort. SLE Th1 cells exhibited Treg‐like TCR features and transcriptomic profiles, and eTreg cells showed increased clonotype sharing with Th1 cells compared with healthy controls. The Th1 “Tregness” score positively correlated with SLE disease activity. Conclusion Our study identifies a Treg‐associated Th1 state in human SLE, consistent with Treg cell to Th1 cell plasticity. image
Objective Systemic lupus erythematosus (SLE) is a complex autoimmune disease driven by neutrophil dysregulation and neutrophil extracellular trap (NET) formation, with unmet therapeutic needs. This study aimed to investigate the therapeutic potential of protein kinase CK2 inhibitor CX‐4945 in SLE as well as to elucidate the underlying mechanisms. Methods CX‐4945 was administered to multiple murine models, including MRL/lpr mice, imiquimod (IMQ)‐induced lupus model, IMQ‐induced psoriasis model, and cecal ligation and puncture–induced sepsis model. Renal function, histopathological changes, immune complex deposition, NET formation, and inflammatory cytokine levels were evaluated. Results CX‐4945 significantly ameliorated renal damage in MRL/lpr and IMQ‐induced lupus models, as evidenced by reduced urinary albumin‐to‐creatinine ratio, glomerular abnormalities, immune complex/complement C3 deposition, and neutrophil infiltration. The neutrophils from patients with SLE exhibited elevated CK2α expression and enzyme activity. Mechanistically, CX‐4945 suppressed interferon‐stimulated genes and reactive oxygen species–related pathways, induced mitochondrial metabolic rewiring, inhibited JNK/p38 MAPK phosphorylation, and modified NET protein composition to abrogate macrophage proinflammatory responses. Conclusion CK2α is aberrantly up‐regulated in SLE neutrophils, and targeting CK2 with CX‐4945 exerts therapeutic effects in SLE. These findings identify CK2 as a novel therapeutic target for SLE and support the repurposing of CX‐4945 for treating neutrophil‐driven inflammatory and autoimmune diseases. image
Background Cardiopulmonary involvement in systemic lupus erythematosus (SLE) refers to a group of serious manifestations, with a high prevalence for some, such as pericarditis and pleuritis, and high mortality in others, such as lupus myocarditis (LM) and diffuse alveolar haemorrhage (DAH). There is a paucity of systematic literature reviews on the management of inflammatory cardiopulmonary manifestations in SLE. We aimed to assess the available evidence in this area. Methods A systematic literature search was conducted from January 1990 to June 2025 using keywords related to the cardiac and pulmonary systems, SLE, and treatments. Manifestations related to atherosclerosis or anti-phospholipid syndrome were excluded. Results A total of 67 studies, covering pericarditis, LM, pulmonary arterial hypertension (PAH), pleuritis, acute lupus pneumonitis (ALP), DAH, interstitial lung disease, and shrinking lung syndrome (SLS) were included. Glucocorticoids (GCs) were utilized as first-line treatment for all these conditions, and GC pulse was commonly administered in serious manifestations such as pericardial tamponade, LM, ALP, and DAH. Cyclophosphamide was the most used immunosuppressant, with low-to-moderate evidence indicating its effectiveness. Low-to-moderate evidence supported rituximab as a second-line therapy for LM, DAH, and SLS, and plasma exchange was commonly used in DAH. For PAH, high-quality evidence from RCTs supported the use of PAH-targeted therapies, and initial PAH-targeted combination therapy showed more benefits than monotherapy. In addition, immunosuppressive therapy may be beneficial for SLE-PAH patients, especially those with early, mild PAH. Anti-fibrotic therapy, such as nintedanib and pirfenidone, had no evidence of effectiveness in SLE-ILD. Evidence for the benefit of belimumab and anifrolumab for cardiopulmonary manifestations was also minimal. Patients with some conditions, such as LM, ALP, and DAH, had poor prognoses under current therapies, with reported short-term mortalities of up
A newsletter destaca os resultados do estudo de fase 3 VALOR, que comprovou a eficácia do brepocitinibe na melhora cutânea e muscular da dermatomiosite, permitindo o desmame de corticoides. São discutidas também inovações como o uso de blinatumomabe para restaurar a responsividade terapêutica na artrite reumatoide e a aplicação de células CAR-T em casos refratários, além de novos escores para estratificação de risco gestacional.
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.
Background Systemic lupus erythematosus (SLE) is characterized by the immune system producing autoantibodies that target the body’s own cells and tissues, leading to inflammation and tissue damage. Sphingosine-1-phosphate receptor 1 (S1PR1) plays a crucial role in regulating immune cell trafficking, and its function relies on a gradient of sphingosine-1-phosphate (S1P). During inflammatory immune responses, the S1P gradient is altered, promoting lymphocyte migration to inflammatory sites. Consequently, S1PR1 has become a therapeutic target for inhibiting lymphocyte egress from lymphoid tissues in autoimmune and inflammatory diseases. However, knowledge of S1PR1 expression and function in B cell subsets and antibody-secreting cells (ASCs) in SLE remains limited. Methods Peripheral blood mononuclear cells (PBMCs) from forty-nine patients with SLE were enrolled to assess S1PR1 expression in B cell subsets and plasma cells. Significant differences in surface S1PR1 expression on activated naive (aNAV), Double Negative 2 (DN2) B cells and ASCs were further analyzed for correlations with disease activity, Lupus Nephritis (LN) involvement, inflammatory markers, S1P levels, and chemokine receptor expression. Results Intracellular S1PR1 expression was significantly increased across all B cell subsets, including naive (rNAV and aNAV), memory (SWM, USM, DN1, DN2), and ASCs. In contrast, surface S1PR1 expression differed markedly among subsets, with downregulation observed in aNAV and DN2 B cells and upregulation in ASCs. Further analysis revealed that surface S1PR1 downregulation on aNAV B cells was significantly associated with active disease status, SLEDAI-2 K scores, and LN involvement. Inflammatory markers (IL-6, IL-8, and C3c levels) showed no correlation with surface S1PR1 expression, whereas erythrocyte sedimentation rate (ESR) demonstrated a significant negative correlation. In addition, lupus aNAV and DN2 B cells exhibited reduced surface CXCR3 expression without correlation to S1PR1 expression, whereas other B cell
Sex and gender shape disease presentation, diagnostic accuracy, treatment response and clinical outcomes in rheumatology, yet these dimensions remain insufficiently embedded in clinical practice. Owing to the markedly unbalanced sex prevalence ratios across many rheumatic diseases, the ‘minority’ sex is consistently under-represented in clinical studies, limiting the interpretation of long-term outcomes and treatment effectiveness. Sex-related differences in pain perception, inflammatory biomarkers and imaging patterns further complicate disease assessment, and treatment allocation and drug persistence also differ between women and men. Gender-related factors — including disparities in care-seeking behaviours, social roles and lifestyle factors — additionally modulate symptom burden and disease trajectories. Evidence remains particularly scarce for transgender, gender-diverse and intersex individuals, who are rarely captured in clinical cohorts, restricting the development of inclusive and generalizable evidence. Embedding sex-aware and gender-aware approaches into diagnostic reasoning, risk assessment and therapeutic decision-making is therefore essential for advancing precision, equity and truly personalized rheumatological care. Such integration enables clinicians to interpret disease signals more accurately, anticipate divergent multimorbidity trajectories and tailor treatment strategies to the biological and sociocultural contexts of each patient.
A newsletter destaca o benefício clínico do TENS na fibromialgia e a utilidade do ultrassom pulmonar como ferramenta portátil para monitorar a progressão da doença intersticial na artrite reumatoide. Também são discutidos a correlação entre o local das crises de reumatismo palindrômico e a cronificação articular, além do papel da disbiose oral na Síndrome de Sjögren.
ObjectiveTo develop and validate a frailty assessment scale tailored for patients with systemic lupus erythematosus (SLE).MethodsBased on the theory of the frailty integration model, an initial draft of the frailty index questionnaire was developed through a comprehensive literature review and a two - round Delphi expert consultation. The final version of the scale was formed through a pre - survey and a formal survey. The validity of the questionnaire was tested using content validity, structural validity, and criterion - related validity. The reliability was evaluated using Cronbach's α coefficient, split - half reliability, and test - retest reliability.ResultsThe initial item pool of the scale contained 3 dimensions and 32 items. After two rounds of Delphi expert consultations, the draft scale was refined to 21 items across 3 dimensions. Pilot testing with 50 SLE patients further reduced it to 14 items. The formal content validity Cronbach's α coefficient was 0.809, the split - half reliability was 0.745, the KMO was 0.820, and the Bartlett's test value was 2915.855 ( p p < 0.001). The optimal cutoff value for the pre - frailty stage was 28.5, and that for the frailty stage was 40.5.ConclusionThe frailty index scale developed in this study is a valid and reliable tool for assessing frailty in SLE patients in China, with potential utility in clinical and research settings.
A newsletter aborda a importância da reabilitação imunológica pós-transplante renal em pacientes com doenças reumáticas, focando no equilíbrio entre evitar a rejeição e prevenir a recorrência da doença de base. Destaca o sucesso do brepocitinibe (inibidor de TYK2/JAK1) no tratamento da dermatomiosite refratária e discute o uso de terapias biológicas combinadas para artrite psoríasica. O conteúdo também revisa biomarcadores preditivos e estratégias de monitoramento personalizado para otimizar a sobrevida do enxerto e do paciente.
Lupus nephritis (LN) represents the most severe and frequent complication of systemic lupus erythematosus (SLE), yet its treatment remains a significant unmet clinical need. Recent advances in immunometabolism have revealed that glucose metabolic reprogramming—including shifts in glycolysis, the pentose phosphate pathway (PPP), and the tricarboxylic acid (TCA) cycle—plays a central role in driving pathogenic immune cell activation in SLE. However, a critical gap persists in understanding how these metabolic alterations specifically operate within the renal microenvironment to promote immune cell infiltration and intrinsic kidney cell injury in LN. This review synthesizes current evidence on the molecular mechanisms linking glucose metabolism to immune dysfunction in innate immune cells including monocytes/macrophages, neutrophils and DCs and adaptive immune cells including T cells, B cells and renal resident cells. We further discuss therapeutic strategies targeting metabolic pathways, including repurposed drugs (metformin, hydroxychloroquine, rapamycin), preclinical small molecules (PKM2, PFKFB3, LDHA, GLUT1 inhibitors), and combination therapies with biologics. Safety considerations, particularly the sensitivity of regulatory T cells (Tregs) to glycolysis inhibition, underscore the need for dose optimization. Finally, we highlight future directions, including real-time metabolic imaging, personalized glycolysis scoring, and spatiotemporal metabolic epigenetic models, which hold promise for advancing precision medicine in LN.
Cardiovascular disease (CVD) remains a leading cause of mortality in patients with systemic lupus erythematosus (SLE). Decades of data have established that patients with SLE experience myocardial infarctions and strokes at rates far exceeding those of the general population, often at strikingly young ages. 1
Objective Steroid‐induced osteonecrosis of the femoral head (SONFH) is a refractory skeletal disorder influenced by genetic and environmental factors. However, conclusive pathogenic genetic evidence remains elusive due to the limited exploration of rare damaging variants. In this study, we aimed to identify rare variants associated with SONFH. Methods We conducted whole‐exome sequencing (WES) in a SONFH case‐control study comprising 174 systemic lupus erythematosus (SLE) patients on steroids. Followed by comparing the cases with an ethnically matched healthy population and validation in an additional SONFH cohort of 246 patients without SLE. Rare damaging variants were identified via genetic burden analysis and confirmed by Sanger sequencing and pedigree studies. The functional assessments of the erythrocytes on target variants were performed. Results We identified 10 heterozygous ANK1 and EPB41 rare variants in 9 (10.8%) of 83 SONFH patients compared with 0 (0%) of the 91 non‐SONFH controls.The burden effect of them remained robust after adjusted analysis (aOR [Firth's logistic regression adjusted odds ratio] ANK1 11.3; aOR EPB41 32.3; both p<0.05). The variants were detected in 10 (4.1%) of the validated SONFH cohort with 246 non‐SLE conditions. Functional analyses revealed that the variants result in membrane dysfunctions in the patients’ erythrocytes, characterized by reduced ANK1 expression, abnormal morphology, and increased hypotonic hemolysis. Conclusion These findings suggest that the rare variants in ANK1 and EPB41 are novel SONFH disease risk factors which compromise erythrocyte membrane integrity, exacerbating microcirculatory damage in the presence of glucocorticoid as a second hit.
Our study found that organ damage accrual, specifically pulmonary fibrosis and neuropathy as measured by SLICC-ACR DI and high BMI, is associated with clinically significant fatigue in SLE. Furthermore, our results support previous findings that fatigue is independent of SLE disease activity. Findings of our study need to be replicated in independent SLE cohorts measuring fatigue at multiple time points. Mechanistic studies are needed to better understand pathogenesis of fatigue in SLE.
Isolated anti-SSB positivity is associated with a significantly lower likelihood of Sjögren disease, SLE, and RA. These findings suggest that isolated anti-SSB may lack diagnostic utility and could represent a clinically insignificant serologic finding in many patients.
BackgroundThere is limited qualitative research on the patient experience of cutaneous lupus erythematosus (CLE), and no fit-for-purpose patient-reported outcome (PRO) instruments are currently available in this population. This study aimed to better characterise the disease experience of CLE, focusing on the most prevalent subtypes, discoid lupus erythematosus (DLE) and sub-acute CLE (SCLE), and to develop a conceptual model depicting the core signs, symptoms, and impacts of the disease.MethodsSemi-structured, concept elicitation interviews were conducted in the United States among 25 patients with CLE ( n = 15 DLE; n = 10 SCLE) and three expert clinicians to explore the signs, symptoms, and impacts of CLE. Interviews were audio-recorded and verbatim transcripts were coded and thematically analysed. Concepts reported by ≥ 50% of patients with an average bothersome rating of ≥5/10 were considered salient.ResultsThe most frequently reported signs and symptoms included itch ( n = 25/25), skin lesions ( n = 24/25), skin sensitivity to light ( n = 23/25), skin redness ( n = 22/25), skin scaling ( n = 20/25), fatigue ( n = 21/25), skin crusting, skin pain, joint pain, headaches ( n = 19/25, each), and hair loss ( n = 18/25). The most frequently reported impacts included limited social functioning ( n = 22/25), body image concerns ( n = 21/25), affected family/partner relationships ( n = 19/25), recreational/leisure activities ( n = 18/25), and sleep ( n = 16/25). Key signs, symptoms, and impacts reported were generally consistent across SCLE and DLE subtypes, although patients with DLE reported greater scalp involvement and hair loss. The conceptual model summarises the core signs, symptoms, and impacts of CLE, while also highlighting any subtype-specific differences.ConclusionsThis study provides robust patient
Objectives Erythrocyte sedimentation rate (ESR) is one of the most commonly used markers of inflammation in clinical practice. However, its value in predicting disease behavior in patients with systemic lupus erythematosus (SLE) remains controversial. The aim of this study was to determine the clinical significance of ESR in a large cohort of Chinese patients with SLE. Methods Data of 1,217 patients with documented ESR values were extracted from a lupus database collected by Jiangsu Lupus Collaborative Group. The associations of ESR with diverse manifestations, disease activity, damage accruement, and concurrent infection status were evaluated using logistic regression, and receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cutoffs for ESR and the C-reactive protein (CRP)/ESR ratio. The prognosis of patients with normal and high ESR was assessed using Kaplan–Meier analysis. Results Of the patients in this cohort, 81.0% had increased ESR values. ESR elevation was independently associated with fever (OR = 1.664, 95%CI = 1.072–2.583), serositis (OR = 2.005, 95%CI = 1.105–3.64), interstitial pneumonia (OR = 3.394, 95%CI = 1.176–9.796), hypoalbuminemia (OR = 1.536, 95%CI = 1.076–2.193), and anemia (OR = 3.102, 95%CI = 2.213–4.348). Compared with the damage accrual score [the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI)], there was a stronger correlation between the ESR value and the SLE Disease Activity Index (SLEDAI) score, and a value not less than 25 mm/h helped to define disease activity with high sensitivity. The increase of ESR was much slower than that of CRP at the time of infection, and a CRP/ESR ratio ≥0.5 had high specificity to depict the presence of infection. The 5- and 10-year survival rates of patients with elevated ESR
Diabetes mellitus (DM) is characterized by persistent hyperglycemia due to impaired insulin secretion, action, or both. Glucocorticoid-induced DM (GIDM) is a clinically significant subtype, especially in rheumatology, where glucocorticoids (GCs) are widely used for the management of autoimmune rheumatic diseases (ARDs). GCs increase gluconeogenesis, reduce insulin sensitivity, impair β-cell function, and alter adipokines and hypothalamic signaling, promoting hyperglycemia. Oral GCs carry the greatest risk, though intra-articular and intramuscular injections can also cause dysglycemia. Risk factors include older age, higher body mass index (BMI) and central adiposity, hypertriglyceridemia, family history of DM, higher GC dose and treatment duration, and disease activity. In non-ARD populations, GIDM occurs in 15–52% of GC-treated individuals, while in ARDs, rates vary by disease. In Systemic lupus erythematosus, occurrence ranges from 10–26% and, beyond classic metabolic risk factors, higher disease activity and damage scores, higher GC doses, and mycophenolate mofetil are associated with increased risk, whereas hydroxychloroquine seems to be protective. In Rheumatoid arthritis, true incidence remains uncertain, though GC dose, especially > 10 mg/day, and prolonged duration correlate with increased risk. In Polymyalgia rheumatica and Giant cell arteritis, GIDM increases dose-dependently, with an occurrence of 6% and 13%, respectively. Evidence for other ARDs is limited. Management of GIDM should be guided by a multidisciplinary approach, aiming for a personalized therapeutic strategy. This review summarizes current knowledge on the mechanisms, epidemiology, and risk factors of GIDM in ARDs, aiming to raise awareness within the rheumatology community, highlight key gaps in the literature, and outline implications for future research.
Objectives Proteome‐wide risk models for lupus remain underexplored. We developed classification models to identify lupus from serum proteomic profiles. Methods Lupus patients and individuals with other autoimmune diseases in the UK Biobank were included. Differential proteomic expressions were characterized and followed by hierarchical clustering analysis. Proteomic linear and machine learning models were developed for established disease classification and future lupus prediction, and compared to polygenic risk scores (PRS). Two additional independent lupus cohorts from Sweden, as part of the Human Protein Atlas (HPA), and from China were used for replication. Results 44,173 participants with proteomic data including 2,063 individuals with at least one autoimmune disease at enrollment were studied in the UK Biobank. This included 383 lupus patients with a mean age of 43.6 ± 11.7 at disease onset. Lupus showed the largest number of dysregulated proteins among autoimmune diseases and clustered with rheumatoid arthritis. Comparison with HPA showed that ~70% of lupus proteomic associations could be replicated with moderate correlation in effect sizes. The machine learning model outperformed the linear model in identifying preexisting lupus and generalized well to future lupus prediction. Among lupus patients on immunomodulatory medications, the model reached ~90% sensitivity at 95% specificity, which was replicated in an independent cohort. Model interpretation highlighted SCARB2, SOD2, CD302, Galectin‐9, and GGT5 proteins with substantial effects on lupus identification. Conclusions Proteomic machine learning models show excellent performance for identifying preexisting lupus and generalizes well for predicting lupus before clinical diagnosis. Model interpretation identified novel candidate biomarkers for lupus. image
Heart failure (HF) is an increasingly important cause of morbidity and mortality in patients with autoimmune rheumatic diseases. Despite advances in cardiovascular prevention and treatment, HF incidence continues to rise in this population, driven by chronic systemic inflammation, immune-mediated myocardial injury, microvascular dysfunction, fibrosis, and treatment-related cardiotoxicity. Epidemiological studies consistently demonstrate a markedly increased HF risk across a broad spectrum of rheumatic diseases—including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, idiopathic inflammatory myopathies, ankylosing spondylitis, and primary Sjögren syndrome—often manifesting at younger age and independently of traditional cardiovascular risk factors. Subclinical myocardial involvement is frequent and commonly precedes overt HF, with preserved ejection fraction representing the dominant phenotype, particularly in inflammatory arthritis and systemic sclerosis. Advances in speckle-tracking echocardiography, cardiac magnetic resonance, and circulating biomarkers such as natriuretic peptides and cardiac troponins have enabled earlier detection and refined risk stratification. Although anti-inflammatory therapies, including conventional and biologic disease-modifying antirheumatic drugs, may mitigate HF risk, optimal control of traditional cardiovascular risk factors and cautious use of cardiotoxic agents remain essential.
Objective Baricitinib is a JAK1 inhibitor that showed efficacy in patients with systemic lupus erythematosus (SLE) in a phase 2 study but failed to meet the primary endpoint in phase 3 trials. To understand this discrepancy and identify patients with SLE who are responsive to baricitinib, we conducted baseline and longitudinal transcriptomic analysis in patients enrolled in the phase 2 trial. Methods Whole‐blood samples from 272 patients with SLE were analyzed. Clinical response was assessed using SLE Responder Index‐4 after 24 weeks of placebo or baricitinib (2 or 4 mg daily). Gene expression profiling was conducted using Gene Set Variation Analysis (GSVA) of 32 immune‐related gene modules. Results Eight distinct molecular endotypes (A–H) were identified from baseline GSVA scores, with progressively increasing immune disturbances. Baseline demographics were similar across endotypes, with modest but significant differences in anti–double‐stranded DNA and complement levels but no SLE Disease Activity Index differences. Significant clinical responses to baricitinib were confined to endotypes D and G ( P = 0.004 and 0.048 vs placebo, with effect sizes of 41.54% and 31.89%, respectively). Importantly, patient clustering based on clinical features failed to identify treatment‐responsive subsets. Endotype G demonstrated the most pronounced treatment‐related transcriptional modulation, with dose‐dependent suppression of interferon, JAK1/JAK2/TYK2 signaling, immunoproteasome, and inflammatory pathways evident as early as week 2 and sustained through week 24. Transcriptional changes in response to baricitinib were largely confined to clinical responders in endotype G. Feature importance analysis identified the interferon and Treg cell signatures as major predictors of response. Conclusion Transcriptomic analysis identified subsets of patients with SLE responsive to baricitinib. image
Telemedicine is a promising solution for addressing regional disparities and improving access to specialized care for patients with rheumatic diseases in Japan. This review provides a comprehensive overview of the current challenges, proposed clinical models, and future directions for implementing telemedicine for these conditions. Drawing from the European Alliance of Associations for Rheumatology (EULAR) points to consider and national surveys, we highlight the potential of hybrid care models, the importance of digital literacy, and the need for interdisciplinary collaboration in this field. We introduce innovative remote care systems currently being piloted in island regions to deliver high-quality care in underserved settings. Additionally, we discuss the outcomes of a health economic simulation, revealing the benefits and financial concerns regarding the current reimbursement structures. Key barriers-technical, clinical, patient-related, organizational, and legal-are analysed alongside proposed countermeasures. Finally, we outline a research agenda to evaluate the effectiveness, safety, and sustainability of telemedicine. With appropriate policy support and system development, telemedicine could play a pivotal role in enhancing the quality and equity of rheumatologic care in Japan.
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Introduction : Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder influenced both intrinsically by immune cell alterations, genetic factors, and the microbiome, as well as extrinsically by environmental factors. Methods : In this pilot study, we investigated the role of various peripheral immune cells (CD3 + , CD4 + , CD8 + , CD4 + /CD8 + , CD4-/CD8-, NK cells (CD16 + CD56 + ), and CD19 + ) and the gut and salivary microbiota in patients with SLE, comparing these factors to healthy controls. Results and Discussion : Results showed significant alterations in the proportions of CD4 + and CD8 + T cells in SLE patients, with an inverse correlation between these subsets. Additionally, the CD4 + ratio was found to be elevated in SLE. CD4 + T cells were strongly correlated with double-negative T cells, while CD8 + T cells correlated with NK cells. Metagenomic shotgun sequencing of fecal and salivary samples revealed a disruption in the microbiome, particularly the taxa Pasteurellaceae and Veillonella , which were altered in both the gut and oral microbiomes of SLE patients. These changes suggest that there may be overlap in the composition and function of these microbial populations across different body sites. Dysbiosis was observed in both the gut and oral microbiomes of individuals with SLE, distinguishing them from healthy controls. Conclusion : Our findings highlight specific microbiome alterations in SLE patients and suggest that microbiome composition could serve as a potential exploratory tool for diagnosing and prognosticating the disease in larger, adequately powered cohorts.
A newsletter destaca que a infecção por SARS-CoV-2 aumenta a positividade de anticorpos antifosfolípides em gestantes com SAF, especialmente no terceiro trimestre, embora o manejo padrão pareça mitigar desfechos adversos graves. Paralelamente, apresenta dados robustos de fase 3 que posicionam o obinutuzumabe como uma terapia eficaz para o LES sistêmico, alcançando altas taxas de resposta clínica e redução sustentada do uso de corticoides. O informativo também revisa casos de hipermobilidade articular e novas diretrizes internacionais para o manejo de doenças reumáticas.
Arthritis &amp;Rheumatology, Volume 78, Issue 3, Page 548-557, March 2026.
Arthritis &amp;Rheumatology, Volume 78, Issue 3, Page 665-671, March 2026.
Arthritis &amp;Rheumatology, Volume 78, Issue 3, Page 684-694, March 2026.
Arthritis &amp;Rheumatology, Volume 78, Issue 3, Page 558-565, March 2026.
Objective To analyze unselected routine care patients with all rheumatic diagnoses for positive anxiety, depression, and/or fibromyalgia screening within a single MDHAQ (multidimensional health assessment questionnaire), and for pain and RAPID3 (routine assessment of patient index data) in patients with positive vs negative screens. Methods Each rheumatology patient with any diagnosis at Rush University is given an MDHAQ at each encounter to provide comprehensive medical history information, completed by most patients in 5-10 minutes and scored by a professional in <30 seconds. Frequencies of positive MDHAQ anxiety, depression, and fibromyalgia screening indices were computed in patients with 15 rheumatic diagnoses in 5 categories: inflammatory, connective tissue, non-inflammatory, bone mineral disorders, and primary fibromyalgia. Median pain 0-10 visual numeric scale (VNS) and 0-30 RAPID3 scores were compared in patients with positive vs negative screens. Results In 1,337 study patients (excluding primary fibromyalgia), 30% had positive screens for anxiety, 24% for depression, and 25% for (non-primary) fibromyalgia, and 44% any of these 3 multimorbidity screens. Positive screens in different rheumatic diagnosis categories ranged from 17%-39% for anxiety, 9%-33% for depression, 7%-31% for (non-primary) fibromyalgia, and 30%-52% for any multimorbidity screen. Median pain was 7.0/10 vs 4.0/10 and median (RAPID3) 17.0/30 vs 8.2/30 in patients with any of 3 positive vs all negative screens (p< 0.001). Conclusion Positive anxiety, depression, and/or fibromyalgia screens in 44% of routine care patients who have significantly higher pain scores agree with extensive research findings, suggesting inclusion of pragmatic screening for clinical decisions at all routine encounters.
Introduction To quantify ocular microcirculation by optical coherence tomography angiography (OCTA) and peripheral microcirculation by nailfold videocapillaroscopy (NVC) in systemic lupus erythematosus (SLE), to compare OCTA/optical coherence tomography (OCT) metrics with healthy controls, and to explore NVC–ocular relationships. Methods In this single-center, cross-sectional case–control study, 32 SLE patients and 34 controls were evaluated at one visit. NVC was scored semi-quantitatively (EULAR-standardized) in SLE. OCTA provided macular superficial/deep plexus and optic nerve head/peripapillary radial peripapillary capillary (RPC) vessel density metrics; structural OCT measured peripapillary retinal nerve fiber layer (RNFL) thickness. Multiple testing was controlled with Benjamini–Hochberg false discovery rate (FDR). Exploratory ROC analysis and age/BMI-adjusted logistic regression were performed for inside-disc RPC vessel density (RPCID). Results RPCID was lower in SLE than controls (50.6 [43.4–55.7] vs 55.3 [44.3–59.7]; FDR-adjusted p < 0.001) and showed good in-sample discrimination (AUC = 0.804). Higher RPCID was associated with lower odds of SLE after adjustment (OR = 0.737; 95% CI 0.625–0.869; p < 0.001). Within SLE, higher NVC dilation scores correlated with lower macular vessel density (deep superior sector: r = − 0.384; FDR p = 0.041), and higher composite NVC morphology correlated with greater mean RNFL thickness (r = 0.505; FDR p < 0.05). Conclusions Optic nerve head/peripapillary microcirculation is reduced in SLE, and RPCID showed the largest between-group difference and promising in-sample discrimination of case–control status. NVC–ocular associations are exploratory and warrant longitudinal, multicenter validation. Key Points • Analysis of this cross-sectional case–control sample demonstrated that inside-disc RPC (RPCID) vessel density was significantly lower in SLE (50.6 [43.4–55.7] vs 55.3 [44.3–59.7]; FDR-adjusted p < 0.001), indicating reduced peripapillary microcirculation. • RPCID had the biggest difference between groups. Our analysis also showed good discrimination,
aPL showed an association with fetal loss in SLE, while anti-SSA/Ro antibodies did not. Anti-SSA/Ro may influence fetal development, necessitating further researches.
AimsShrinking lung syndrome (SLS) is a rare pulmonary manifestation of systemic lupus erythematosus (SLE) and affects approximately 0.5-1% of patients. This systematic review aimed to summarize the clinical features, imaging findings, therapeutic strategies, and outcomes of SLS in patients with SLE.MethodsThis systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies published between 2015 and 2025 were identified using the terms "shrinking lung syndrome" AND "systemic lupus erythematosus." Clinical characteristics, imaging findings, pulmonary function tests, treatments, and outcomes were analyzed.ResultsA total of 52 cases were included, comprising 44 cases from the literature and 8 from a single-center case series. The mean age was 31.5 ± 7.5 years in our cohort and 38.6 years in the literature, with a marked female predominance. All patients had a prior diagnosis of SLE. Dyspnea was present in all the patients, followed by pleuritic chest pain and dry cough. The most common imaging finding was reduced lung volume with elevated diaphragmatic domes, which was observed in all the patients in our cohort and in 77.2% of the reported cases, followed by basal atelectasis. Diaphragmatic ultrasonography, performed in half of our patients, demonstrated reduced diaphragmatic excursion. Pulmonary function tests consistently revealed a restrictive ventilatory pattern with reduced diffusing capacity for carbon monoxide (DLCO). Immunosuppressive therapy as a corticosteroid-sparing strategy was used in all patients from our cohort and was the most frequently reported treatment in the literature, with rituximab being the most commonly used agent. Improvement in pulmonary function occurred in 62.5% of our patients and 50% of the reported patients, whereas stabilization was observed in approximately one-quarter of the patients. Two cases of clinical worsening, including
Objective Analyze the clinical and laboratory characteristics of childhood-onset systemic lupus erythematosus (cSLE) complicated by macrophage activation syndrome (MAS), evaluate the applicability of the 2016 European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation classification criteria for sJIA-associated MAS (referred to as the 2016 sJIA-MAS classification criteria) in the context of different autoimmune diseases (cSLE-MAS), and propose new diagnostic predictive indicators to provide references for improving the early identification and diagnosis of patients with cSLE-MAS. Methods The clinical laboratory data of 32 children with cSLE-MAS admitted to the Department of Nephrology and Immunology in Children’s Hospital of Hebei Province from May 2015 to January 2025 were retrospectively analyzed. This data was compared with that of 32 children with cSLE, who had the same gender ratio and presented with fever but without MAS. Laboratory indicator cut-off values for cSLE combined with MAS were predicted from receiver operating characteristic (ROC) curves. Results Compared with cSLE, cSLE-MAS exhibited higher rates of lymphadenopathy, liver dysfunction, and hematologic abnormalities; higher levels of serum ferritin, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, hydroxybutyrate dehydrogenase, and triglycerides; lower levels of white blood cells, absolute neutrophil count, and fibrinogen; and longer durations of fever and hospitalization. The use of high-dose methylprednisolone sodium succinate pulse therapy and immunoglobulin was more frequent. All differences were statistically significant (P < 0.05). ROC curve analysis revealed that the following cutoff values provided optimal diagnostic differentiation for cSLE-MAS: ferritin ≥ 621.6 µg/L, aspartate aminotransferase ≥ 75.5 U/L, fibrinogen ≤ 1.96 g/L, triglycerides ≥ 2.31 mmol/L, and lactate dehydrogenase ≥ 382 U/L. The 2016 sJIA-MAS classification criteria demonstrated both sensitivity and specificity of 90.6% in the diagnosis of cSLE-MAS. The sensitivity and specificity were improved to
Background Severe lupus nephritis (LN) remains difficult to manage despite standard immunosuppressive therapy. Immunoadsorption (IA) has been increasingly used as an adjunctive treatment. However, comparative evidence across different IA columns is limited. Methods We conducted a systematic review and Bayesian network meta-analysis of randomized controlled trials evaluating six IA columns for severe LN. PubMed, Embase, Scopus, Web of Science, VIP, Wanfang, and CNKI were searched up to January 2025. Outcomes included disease activity (Systemic Lupus Erythematosus Disease Activity Index, SLEDAI), renal parameters, immunological markers, and adverse events. Risk of bias was assessed using the Cochrane risk-of-bias tool, and Bayesian network meta-analysis was performed in R (version 4.4.1). Results A total of 24 randomized controlled trials involving 1,442 patients were included. DNA280 plus conventional pharmacotherapy showed a favorable probability ranking for SLEDAI improvement. DNA280 plus plasma exchange (PE) plus conventional pharmacotherapy showed a statistically significant advantage versus conventional pharmacotherapy alone [mean difference (MD) = 1.8, 95% credible interval (95%CrI) = 0.05–3.5] for 24-h proteinuria and ranked favorably across several renal outcomes. PH-350 plus conventional pharmacotherapy showed a favorable probability ranking for serum creatinine improvement. Adverse events were reported in 17 studies; however, comparative safety analyses were not feasible due to inconsistent definitions and reporting. Conclusions IA strategies—in particular DNA280-based regimens—may offer relative advantages for severe LN. However, the evidence is limited by study quality, heterogeneity, sparse comparisons for some columns, and reliance on surrogate outcomes. The findings should be interpreted as hypothesis-generating, and higher-quality comparative trials with clinically meaningful endpoints are needed. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420251031348.