To investigate the association between insulin resistance (IR) and all-cause mortality among adults with rheumatoid arthritis (RA). In this cohort study, we included 1,427 adults with self-reported RA from the National Health and Nutrition Examination Survey (NHANES) 1999–2010 and 2015–2018. IR was assessed using the homeostatic model assessment of insulin resistance (HOMA-IR). Survey-weighted multivariable Cox proportional hazards models were used to evaluate the association between HOMA-IR and all-cause mortality. During a mean follow-up of 9.7 years, 491 deaths occurred. Compared with participants in the lowest tertile of HOMA-IR, the multivariable-adjusted hazard ratios (HRs) and 95
Rheumatoid arthritis (RA) and multiple myeloma (MM) are rare coexisting conditions that present diagnostic and therapeutic challenges, and while autologous hematopoietic stem cell transplantation (auto-HSCT) is standard for MM, its effect on concomitant RA remains unclear. We report a 50-year-old woman with a 10-year history of RA who developed IgG-κ MM and underwent auto-HSCT following VRD induction and high-dose melphalan conditioning. Serial assessments showed that MM response deepened from partial remission to very good partial remission, with M protein declining and the free light chain ratio normalizing, while RA activity markedly improved—rheumatoid factor decreased from 67.8 to 5.5 IU/mL and DAS28-ESR dropped from 4.33 to 2.25, with complete resolution of joint symptoms and no severe transplant-related complications. A review of the relevant literature supports these findings, suggesting that auto-HSCT may be a safe and effective strategy for simultaneously managing both diseases, although long-term follow-up is necessary to confirm the durability of remission.
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and progressive joint destruction. Although current therapies can control symptoms, many patients still have limited responses or safety concerns. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have shown therapeutic potential in autoimmune diseases, but their effects on joint-associated pathways and systemic metabolism in RA remain unclear. hUC-MSCs were commercially obtained, expanded, and characterized. A collagen-induced arthritis (CIA) mouse model was established to evaluate therapeutic efficacy. Disease severity was assessed by arthritis scoring, gross observation, and histopathology. Flow cytometry and ELISA were used to analyze Th17/Treg balance and circulating cytokines. NF-κB- and Wnt/β-catenin-related molecules, together with components of the RANKL/OPG axis, were examined by Western blotting and RT-qPCR. Untargeted plasma metabolomics was performed to assess systemic metabolic changes. hUC-MSC treatment reduced arthritis scores and joint swelling in CIA mice. Histological analysis showed reduced synovial hyperplasia and less cartilage and bone damage. hUC-MSCs shifted the immune profile toward an anti-inflammatory state, with decreased Th17 cells, increased Treg cells, and lower serum TNF-α, IL-6, IL-1β, and IL-17 levels. In synovial tissue, hUC-MSC treatment was associated with lower expression of NF-κB p65, Wnt-4, and β-catenin, as well as a decreased RANKL/OPG ratio. Exploratory untargeted metabolomics further suggested treatment-associated changes in the systemic metabolic profile. hUC-MSCs alleviated arthritis in CIA mice and were associated with immune rebalancing, lower expression of inflammation-related molecular markers, and systemic metabolic changes.
Anti-Ro52/TRIM21 antibodies have been linked to interstitial lung disease (ILD) severity in anti-synthetase syndrome (ASS), but their broader clinical relevance remains uncertain. We compared clinical, pulmonary, treatment, and outcome characteristics according to Anti-Ro52/TRIM21 status in a Swiss single-center cohort. This retrospective cohort included patients diagnosed with ASS followed at Geneva University Hospitals from 2010 to 2024 who met the Connors criteria and had available anti-Ro52 kDa antibody testing. Group comparisons used two-sided Wilcoxon rank-sum or Fisher’s exact tests, and exploratory associations were assessed using univariate Firth logistic regression. Among 295 screened records, 38 patients were included (16 anti-Ro52/TRIM21-positive patients and 22 anti-Ro52/TRIM21-negative); mean follow-up was 6.63 ± 5.34 years. Pulmonary involvement was numerically more frequent in anti-Ro52/TRIM21-positive patients (15/16 [93.8
Osteoarthritis (OA) is common in rheumatoid arthritis (RA), but its radiographic distribution and functional impact in elderly patients remain poorly characterized. We aimed to determine the prevalence of radiographic and symptomatic lower extremity OA, characterize radiographic-clinical discordance, identify factors associated with knee OA, and assess its functional impact in elderly patients with RA. In this single-center cross-sectional study, 230 patients with RA aged ≥ 60 years underwent standing full-length lower extremity radiography, joint-based clinical assessment by an orthopedist, and Lower Extremity Functional Scale (LEFS) evaluation. Radiographic OA was defined as Kellgren-Lawrence grade ≥ 2, and symptomatic OA as radiographic OA with corresponding clinical findings. Multivariable logistic and linear regression analyses were performed. Radiographic OA was present in 62.2
To estimate time to first recurrent thrombosis and to explore the association between recurrent thrombosis and clinical, laboratory/immunological, and treatment-related factors among Colombian adults with thrombotic antiphospholipid syndrome (APS) enrolled in the ARTMEDICA autoimmune diseases program (2013–2024). We conducted a registry-based retrospective follow-up study of patients with thrombotic APS. Patients were followed from the index thrombotic event to the first recurrent arterial or venous thrombosis. Time-to-event analyses used interval-censored parametric survival regression with a log-logistic distribution. To explore factors associated with recurrence, we also applied a matched nested case–control design using conditional logistic regression. We included 355 patients (mean follow-up 6.6 years), 71.0
Interstitial lung disease (ILD) is a major extra-articular manifestation of rheumatoid arthritis (RA), but the significance of pulmonary manifestations preceding or coinciding with articular disease remains unclear. This study aimed to compare the clinical and prognostic characteristics of RA-associated ILD (RA-ILD) stratified by lung-onset status. In this single-center retrospective cohort study, 1,344 hospitalized patients with confirmed RA between 2008 and 2020 were screened and 192 RA-ILD patients with complete pulmonary function, HRCT, and follow-up data were included. Patients were classified into lung-onset and non-lung-onset groups based on the temporal relationship between ILD recognition and RA diagnosis. Clinical, pulmonary function, and HRCT characteristics were compared. Pulmonary-cause mortality was analyzed using Fine–Gray competing-risk regression, with cause-specific Cox regression as a complementary analysis. Among the 192 patients, 51 (26.6
To identify the specific gastrointestinal (GI) symptoms associated with clinically relevant fatigue in systemic sclerosis (SSc), beyond the established association between overall GI involvement and fatigue. We conducted a cross-sectional study including consecutive patients with SSc fulfilling the 2013 ACR/EULAR classification criteria. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-Fatigue) scale, with clinically relevant fatigue defined as a score ≤ 30. Demographic, clinical, laboratory, and organ involvement data were collected. Individual GI symptom domains (GERD, dysphagia, bloating, diarrhea and constipation), together with the Medsger GI severity score, were analyzed. Bivariate analyses and multivariable logistic regression analyses were performed to evaluate symptom-specific associations with clinically relevant fatigue. Among 115 patients, clinically relevant fatigue was observed in 42 (36.5
Telitacicept and belimumab are two biological agents approved for treating systemic lupus erythematosus (SLE) in China. This study mainly discusses the therapeutic efficacy of these two biological agents in SLE. SLE patients who received telitacicept or belimumab at Nanjing Drum Tower Hospital from March 2021 to March 2023 were included. Clinical characteristics were compared, and 1:1 propensity score matching (PSM) was performed. Statistical analyses included normality tests, t tests, Mann‒Whitney U tests, and chi‒square tests. Both telitacicept and belimumab demonstrated robust clinical efficacy. Pre-matching, SLE responder index-4 (SRI-4) response rates were 42.4
Idiopathic granulomatous mastitis (IGM) is a rare, chronic inflammatory breast disease that mimics infection and malignancy, with no standardized treatment approach. We conducted a single center retrospective case series of 25 women with histopathologically confirmed IGM managed at a tertiary center in Dubai, UAE (June 2022–June 2025). Demographic, clinical, imaging, histopathological, treatment, and outcome data were analyzed. Remission was defined as complete clinical and radiological resolution sustained for at least 6 months after cessation of therapy. The median follow-up duration was 20 months. The median age was 38 years; all patients were pre-or perimenopausal, and 92
Sjögren’s disease (SjD) is a heterogeneous systemic autoimmune disorder with diverse clinical presentations. While sicca symptoms are considered hallmark features, a substantial proportion of patients present with non-sicca manifestations. Although major salivary gland swelling is a recognized feature, its potential implications for baseline evaluation and clinical characterization at diagnosis remain incompletely understood. We aimed to classify SjD patients according to presenting symptoms at diagnosis and to characterize the clinical features of patients presenting with major salivary gland swelling. We conducted a retrospective observational study of patients with SjD who were enrolled at a tertiary referral center between June 2020 and March 2025. Patients were categorized by the predominant presenting symptom documented at diagnosis. Baseline clinical indices, imaging, laboratory findings, and treatment status were assessed at cohort enrollment. Clinical features were compared between patients presenting with major salivary gland swelling and those with other presenting symptoms. Among 731 patients with SjD, major salivary gland swelling was the presenting symptom at diagnosis in 48 (6.6
Relapse is a frequent challenge in idiopathic inflammatory myopathies (IIM); however, predictors in adults remain insufficiently defined. This study aimed to determine the relapse frequency and risk factors, with an emphasis on myositis-specific autoantibodies (MSAs), in a Turkish IIM cohort. Patients diagnosed with IIM according to established classification criteria between 2017 and 2024 at Hacettepe University Hospital, a referral center were retrospectively analyzed in a single-center cohort. Relapse was defined as a ≥ twofold increase in creatine kinase and/or escalation of immunosuppressive therapy for active muscle or extramuscular disease. Predictors were identified using logistic regression analysis. A total of 136 patients were included (66.2
Reactive arthritis (ReA) is characterized by substantial clinical heterogeneity and lacks universally accepted diagnostic criteria. The scarce evidence-based treatment guidelines highlight the urgent need for regionally relevant consensus recommendations. To develop recommendations based on evidence and clinical experience to establish definitions, accurate diagnosis, and therapeutic management of patients with ReA. A methodological team and a multidisciplinary group of experts were established. MEDLINE, LILACS, Cochrane, and gray literature from conferences (EULAR, ACR, PANLAR, SAR) were analyzed in a systematic literature review (PRISMA). Based on the PICO format and GRADE methodology, treatment recommendations were made. For the development of definitions, a Delphi process was performed until consensus was reached. Consensus for recommendations required at least 70
Rheumatoid arthritis (RA) and depressive disorders (DEP) frequently co-occur in clinical populations, but their population-level temporal patterns and variation across developmental contexts remain insufficiently characterized. Using Global Burden of Disease (GBD) 2021 data, this study assessed population-level spatial concurrence, temporal predictability, and projected combined estimated incident cases of RA and DEP across 204 countries and territories, with particular attention to the role of the Sociodemographic Index (SDI). Countries were grouped by SDI quintile. Annual age-standardized incidence rates (ASIRs) for RA and DEP from 1992 to 2021 were analyzed. ARIMAX models were used to describe single-disease trends, whereas VARX models jointly modelled RA and DEP while adjusting for SDI. Granger causality tests assessed whether the past burden of one condition improved prediction of the other, and impulse response functions (IRFs) summarized model-estimated responses over subsequent years. Projections to 2030 were interpreted as conditional model-based estimates. RA and DEP incidence rates were positively correlated globally. After SDI adjustment, the number of countries showing bidirectional temporal predictability increased from 67 to 104. IRF analyses indicated larger and more heterogeneous model-estimated RA-to-DEP responses than DEP-to-RA responses, while supporting bidirectional temporal associations. Conditional projections suggested that some middle-SDI countries may experience changes in population-scaled combined estimated incident cases by 2030, whereas several higher-SDI settings showed stable or declining projected rankings under the model assumptions. Developmental context shaped the detectability and magnitude of country-level RA–DEP temporal associations. These findings provide population-level context for interpreting RA and DEP patterns across settings; clinical screening and treatment decisions require evidence from individual-level studies and guidelines.
To compare chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy prevalence, risk factors, severity, and patterns in a cohort of Hispanic patients with rheumatic diseases in Mexico. Retrospective, cross-sectional study of patients with rheumatic diseases treated with CQ/HCQ who underwent retinopathy screening (from 2014 to 2019) with macular spectral domain optical coherence tomography and automated visual field tests. The most recent screening report was included to define the presence or absence of retinopathy. A total of 571 patients were recruited; 27 were excluded due to missing reports. A total of 544 patients were analyzed, 26
This study aimed to evaluate the therapeutic efficacy of Compound Nanxing Zhitong Plaster (CNZP) against rheumatoid arthritis (RA) and to investigate its underlying mechanism through an integrated approach combining network pharmacology and metabolomics. A collagen-induced arthritis (CIA) rat model was established to assess the anti-RA effects of CNZP. A comprehensive strategy, incorporating network pharmacology (based on previously reported chemical constituents), molecular docking, serum biochemical assays, histopathological examination, immunohistochemistry, and Western blotting, was employed to elucidate its therapeutic actions, associated pathways, and molecular targets. Network pharmacology identified 53 common targets between CNZP and RA, with IL1β, TLR4, and STAT3 as the top three hub genes. GO and KEGG enrichment analyses revealed that the therapeutic effects of CNZP are primarily mediated through inflammatory response, endopeptidase activity, and signaling pathways such as TNF, IL-17, and Toll-like receptor signaling. Quercetin, imperatorin, and isoimperatorin were identified as the core components. Molecular docking confirmed favorable binding affinities of these three components to IL1β, TLR4, and STAT3. Metabolomics analysis revealed eight potential biomarkers, among which six were significantly modulated by CNZP. These metabolites were primarily involved in arginine and proline metabolism, histidine metabolism, and glycerophospholipid metabolism pathways. Integrated analysis of metabolomics and network pharmacology highlighted the arginine and proline metabolism and arginine biosynthesis pathways as the common mechanisms. l-Arginine was pinpointed as the key differential metabolite, with nitric oxide synthase 1 (NOS1) as its associated regulatory enzyme. CNZP treatment is associated with reduced activation of the JAK1/STAT1 pathway and downregulation of NOS1, suggesting a potential involvement of this axis in the therapeutic effect of CNZP against RA. CNZP exhibits significant therapeutic effects on RA, potentially by downregulating NOS1 expression and subsequently correcting the metabolic imbalance of l-arginine.
To explore how neutrophil extracellular traps (NETs) mediate neuropathic pain in primary Sjögren's syndrome-associated peripheral neuropathy (pSS-PN). We analyzed clinical features in pSS-PN (n = 6) by DN4 Questions, Electromyography examination and sural nerve biopsies from six pSS-PN patients and six traumatic amputees using histology, immunohistochemistry (IHC), transmission electron microscopy (TEM), and immunofluorescence (IF) for NETs markers (cit-H3/MPO). And we created a model of pSS-PN. Pain behaviors were assessed, plasma cit-H3 was measured by ELISA, and hindlimb perfusion was quantified via laser speckle imaging. To inhibit NETosis, DNase I was administered intravenously. PSS-PN patients exhibited neuropathic pain, nerve conduction deficits, reduced nerve fiber density, and inflammatory vasa nervorum injury with significant cit-H3/MPO accumulation. NOD. Aire⁻/⁻ mice developed mechanical allodynia (1.885 vs. 2.497, P < 0.001 vs. C57BL/6 J; 1.885 vs. 2.367 P < 0.01 vs. NOD WT) and thermal hyperalgesia (6.993 vs. 8.585, P < 0.05 vs. C57BL/6 J; 6.93 vs. 8.815 P < 0.05 vs. NOD WT), accompanied by elevated plasma cit-H3 (44.61 vs. 27.49, P < 0.0001 vs. C57BL/6 J; 44.61 vs. 30.96 P < 0.0001 vs. NOD WT), sciatic nerve NETs deposition (44.61 vs. 35.60, P < 0.0001 24 vs. 18 weeks, NOD. Aire⁻/⁻), and increased hindlimb perfusion. DNase I treatment effectively reduced plasma cit-H3, alleviated pain behaviors, mitigated microvascular damage, and normalized perfusion. NETs drive peripheral neuropathy in pSS by inducing vasa nervorum inflammation and microcirculatory dysfunction, leading to neuropathic pain. These findings identify NETs as a key mechanistic link, biomarker, and promising therapeutic target in pSS-PN.
The objective of this study is to systematically evaluate the organ-specific efficacy and safety of six BAFF/APRIL-targeted therapies in Systemic Lupus Erythematosus (SLE) and Lupus Nephritis (LN), and to construct the first organ-specific evidence map identifying research gaps across six clinical domains. PubMed, Cochrane CENTRAL, Embase, Web of Science, registries and Chinese databases were searched through June 2026 for adult Phase II/III RCTs. Primary quantitative outcomes were SRI-4 response and complete renal response. Random-effects models calculated risk ratios (RRs). Primary syntheses used verifiable full-text data; limited-source datasets were retained only for qualitative or sensitivity analyses. RoB 2 and GRADE were applied, and an evidence map visualized gaps. Eighteen independent RCTs were included; 13 contributed quantitative data, and five were retained for qualitative synthesis only. For SRI-4 response, belimumab showed RR 1.29 (95
