Clinical Rheumatology最新文献

{"title":"Characteristic clinical and immunologic features of Sjögren's disease patients presenting with major salivary gland swelling at diagnosis.","authors":"Youngjae Park, Jiwon Yang, Jennifer Jooha Lee, Seung-Ki Kwok","doi":"10.1007/s10067-026-08239-z","DOIUrl":"https://doi.org/10.1007/s10067-026-08239-z","url":null,"abstract":"<p><strong>Introduction/objectives: </strong>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.</p><p><strong>Method: </strong>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.</p><p><strong>Results: </strong>Among 731 patients with SjD, major salivary gland swelling was the presenting symptom at diagnosis in 48 (6.6%). These patients were significantly younger at diagnosis and had higher objective disease activity despite comparable patient-reported symptom burden. Salivary gland ultrasonography demonstrated more severe abnormalities. Lymphadenopathy, hypergammaglobulinemia, and low C3 levels were more frequent. In multivariable analysis, younger age and low C3 remained independently associated with major salivary gland swelling presentation.</p><p><strong>Conclusions: </strong>Major salivary gland swelling as a presenting symptom at diagnosis was associated with a distinct SjD phenotype. Recognition of this presentation may support a more comprehensive baseline clinical and immunologic evaluation. Key Points • Major salivary gland swelling as a presenting symptom represents a clinically meaningful phenotype of Sjögren's disease. • This phenotype is characterized by younger age, higher systemic disease activity, and more severe ultrasonographic glandular involvement. • Recognition of this presentation may support a more comprehensive baseline clinical and immunologic evaluation.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ibero-American consensus on reactive arthritis: definition, diagnosis, and management.","authors":"M Benegas, N Zamora, M V Martire, D C Fernández-Ávila, C Airoldi, G Citera, E E Schneeberger, E R Soriano, C López Medina, E Buschiazzo, V Navarro-Compán, S Ibáñez, C Vera, C Macía-Villa, W Bautista-Molano, E Collantes-Estévez","doi":"10.1007/s10067-026-08400-8","DOIUrl":"https://doi.org/10.1007/s10067-026-08400-8","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Objective: </strong>To develop recommendations based on evidence and clinical experience to establish definitions, accurate diagnosis, and therapeutic management of patients with ReA.</p><p><strong>Methods: </strong>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% agreement.</p><p><strong>Results: </strong>A total of 13 overarching principles and 54 recommendations were formulated, arranged into concepts, definitions, and treatment guidelines. Seventeen specific recommendations regarding the diagnostic process were included. A therapeutic approach was established using an algorithm based on whether the involvement was peripheral, predominantly axial, or entheseal. Treatment was also specified according to extra-musculoskeletal manifestations.</p><p><strong>Conclusions: </strong>For the first time, this agreement allows for the establishment of uniform therapeutic algorithms and classification criteria across the region. The document represents an essential tool for standardizing healthcare and raising the level of care for patients with ReA. Keypoints • Establishes the first regional consensus providing standardized definitions, diagnostic criteria, and uniform therapeutic algorithms for ReA. • Employs a Delphi process, GRADE methodology, and a rigorous systematic review to develop 54 recommendations and 13 overarching principles. • Despite the limited evidence available for ReA, several treatment recommendations achieved moderate certainty of evidence and strong recommendations, with high expert agreement, including the use of csDMARDs after failure of NSAIDs and/or corticosteroids (100%) and sulfasalazine as the preferred csDMARD (91%).</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chloroquine and hydroxychloroquine retinopathy in a cohort with rheumatic diseases in Mexico: prevalence, risk factors, and retinopathy patterns.","authors":"Karim Mohamed-Noriega, Janett L Riega-Torres, Eduardo Alejandro Treviño-Fernández, Karina Palomo-Arnaud, Jesus Hernán González-Cortés, Abraham Olvera-Barrios, Jibran Mohamed-Noriega, Sergio Ayala-de la Cruz, Jorge A Esquivel-Valerio, Fernando Morales-Wong, Dionicio Ángel Galarza-Delgado, Jesus Mohamed-Hamsho","doi":"10.1007/s10067-026-08375-6","DOIUrl":"https://doi.org/10.1007/s10067-026-08375-6","url":null,"abstract":"<p><strong>Introduction/objectives: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>A total of 571 patients were recruited; 27 were excluded due to missing reports. A total of 544 patients were analyzed, 26% (140/544) used CQ, and 74% (404/544) HCQ. Mean age at treatment initiation was 44.9 ± 15.8 years; 95% were female. Retinopathy prevalence was higher with CQ (19%) than HCQ (2%) (P < 0.001). This was consistent in those using antimalarials < 5 years (CQ: 8.5% vs. HCQ: 1.8%; P < 0.007) and those using antimalarials ≥ 5 years (CQ: 33% vs. HCQ: 2.4%; P < 0.001). CQ patients had more years of use at retinopathy diagnosis than HCQ patients (9.0 ± 4.3 vs. 5.1 ± 3.3, P < 0.023). Parafoveal retinopathy pattern was most frequent in patients using CQ (81%) and HCQ (100%), with no isolated perifoveal pattern. Most patients with retinopathy (59%) had a severe grade. In multivariable regression model, CQ was associated with higher odds of retinopathy compared with HCQ (OR, 12.03; 95% CI 4.41-35.74; P < 0.001). Observed independent risk factors for retinopathy were older age at treatment initiation (OR, 1.04; 95% CI 1.00-1.08; P = 0.029) and years of antimalarial use (OR, 1.18; 95% CI 1.09-1.28; P < 0.001).</p><p><strong>Conclusion: </strong>CQ poses a higher risk of antimalarial retinopathy than HCQ. Older age at treatment initiation and duration of use were independent risk factors. Parafoveal was the most frequent retinopathy pattern. Key Points • Antimalarial retinopathy prevalence is significantly higher with chloroquine (19%) than with hydroxychloroquine (2%). • Chloroquine use is associated with significantly higher odds of retinopathy compared with hydroxychloroquine (OR, 12.03; 95% CI 4.41-35.74; P < 0.001). • An older age at treatment initiation (OR, 1.04; 95% CI 1.00-1.08; P = 0.029) and years of antimalarial use (OR, 1.18; 95% CI 1.09-1.28; P < 0.001) are independent risk factors for chloroquine/hydroxychloroquine retinopathy. • The most frequently observed antimalarial retinopathy pattern in this cohort of rheumatic patients in Mexico was the parafoveal (85%), with no cases of perifoveal pattern.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global population-level concurrence and directional associations between rheumatoid arthritis and depressive disorders: an SDI-stratified time-series analysis using GBD 2021.","authors":"Yukang Lin, Yue Qu, Xuantong Qiu, Qiuchan Huan, Jiajia Wang, Tingting Fang, Zhengqi Qiu, Ying Xie","doi":"10.1007/s10067-026-08358-7","DOIUrl":"https://doi.org/10.1007/s10067-026-08358-7","url":null,"abstract":"<p><strong>Aims: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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. Key Points • SDI adjustment increased the number of countries with detectable bidirectional temporal predictability between rheumatoid arthritis (RA) and depressive disorders (DEP) from 67 to 104. • Granger analyses of both-sex country-level annual ASIR series indicated bidirectional temporal predictability, while impulse response analyses showed larger and more heterogeneous model-estimated RA-to-DEP responses than DEP-to-RA responses. • Conditional time-series projections suggested that some middle-SDI settings may experience changes in population-scaled combined estimated incident cases by 2030 under historical-trend and model assumptions. • The findings provide population-level context for interpreting RA and DEP patterns across settings.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relapse in adult idiopathic inflammatory myopathies: clinical predictors and the potential role of anti-NXP2 in a single-center retrospective cohort study.","authors":"Mustafa Ekici, İrem Yıldız İçli, Gözde Kübra Yardımcı, Zehra Özsoy, Erdinç Ünaldı, Büşra Fırlatan, Gözde Sevgi Kart Bayram, Buğu Bulat, Levent Kılıç, Umut Kalyoncu, Ömer Karadağ, Şule Apraş Bilgen, Ali İhsan Ertenli, Sedat Kiraz, Ali Akdoğan","doi":"10.1007/s10067-026-08374-7","DOIUrl":"https://doi.org/10.1007/s10067-026-08374-7","url":null,"abstract":"<p><strong>Introduction/objectives: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>A total of 136 patients were included (66.2% female; mean age, 47.6 ± 17.5 years). The mean follow-up period was 5.3 ± 5.9 years. During this period, 46 patients (33.8%) relapsed, with a median time to relapse of 2.86 years (95% CI: 0.73-4.99). In the multivariate analysis, younger age at diagnosis (OR 0.97, 95% CI 0.95-0.99, P = 0.009), anti-NXP2 positivity (OR 5.31, 95% CI 1.24-22.58, P = 0.02), and intravenous immunoglobulin use during induction (OR 2.69, 95% CI 1.16-6.26, P = 0.02) independently predicted relapse. Maintenance immunosuppressive therapy for ≥ 5 years was associated with a significantly delayed relapse (log-rank P = 0.01).</p><p><strong>Conclusions: </strong>Relapse occurred in one-third of adult patients with IIM. Younger age, anti-NXP2 positivity, and IVIG use independently increased relapse risk, whereas long-term maintenance therapy substantially delayed relapse. These findings highlight the need for long-term immunosuppression and close monitoring of high-risk subgroups.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NETs mediate neuropathic pain in PSS-PN by participating in inflammatory injury to the vasa nervorum.","authors":"Liying Xu, Jiying Wei, Donghua Chen, Bihua Xu, Yuxin Liu, Xiangmingyang Fu, Jiaman Zheng, Ling Tang, Junhao Lin, Yi Yang, Wei Li, Chao Yuan","doi":"10.1007/s10067-026-08384-5","DOIUrl":"https://doi.org/10.1007/s10067-026-08384-5","url":null,"abstract":"<p><strong>Objectives: </strong>To explore how neutrophil extracellular traps (NETs) mediate neuropathic pain in primary Sjögren's syndrome-associated peripheral neuropathy (pSS-PN).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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. Highlights • Higher consumption of ultra-processed foods is associated with increased disease activity in patients with ankylosing spondylitis • A novel murine model (NOD. Aire⁻/⁻) recapitulates human pSS-PN, exhibiting spontaneous neuropathic pain, peripheral nerve inflammation, elevated NETs, and microcirculatory dysfunction; • DNase1-mediated NETs degradation alleviates neuropathic pain and normalizes hindlimb perfusion, supporting NETs as a promising therapeutic target in pSS-PN.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation between perivascular spaces and clinical features in patients with rheumatoid arthritis.","authors":"Lan-Qi Jiao, Yi Bian, Chao Yang, Sha Ni, Fei Han, Peng-Fei Qiao, Xue-Ying Ma","doi":"10.1007/s10067-026-08383-6","DOIUrl":"https://doi.org/10.1007/s10067-026-08383-6","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aims to compare perivascular space (PVS) parameters across different rheumatoid factor (RF) titer subgroups within a rheumatoid arthritis (RA) cohort, and to explore their correlations with serological markers.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this cross-sectional study, 160 RA patients were enrolled and categorized into three groups based on RF titer: the negative group (n = 35), the low-titer group (n = 26), and the high-titer group (n = 99). Demographic, clinical, and laboratory data were systematically collected. PVS parameters across various brain regions were quantitatively assessed using 3.0 T magnetic resonance imaging (MRI). Spearman correlation analysis was employed to explore associations, and multiple linear regression was conducted for multivariate analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Statistically significant differences were identified among the three groups concerning the number of PVS in the right frontal lobe (p = 0.022), the number of PVS in the right parietal lobe (p = 0.032), the volume of PVS in the right parietal lobe (p = 0.004), and the number of PVS in the pons (p = 0.006). The high-titer group exhibited significantly elevated values of the frontal and parietal PVS parameters compared to the negative group (all p &lt; 0.05). Correlation analysis demonstrated that RF-IgA showed weak-to-moderate but statistically significant positive correlations with the number of PVS in the right frontal lobe (R = 0.181), the number of PVS in the right parietal lobe (R = 0.193), and the volume of PVS in the right parietal lobe (R = 0.162) (all p &lt; 0.05). Additionally, the anti-cyclic citrullinated peptide III antibody (Anti-CCPIII) was positively correlated with the number of PVS in the right parietal lobe (R = 0.196), while the anti-mutated citrullinated vimentin antibody (MCV) was positively correlated with the number of PVS in the pons (R = 0.168) (all p &lt; 0.05). Multiple regression analysis revealed that the erythrocyte sedimentation rate (ESR) was independently negatively associated with the number of PVS in the right frontal lobe (β = - 0.142, p = 0.022). In conclusion, autoantibody titers and inflammatory levels in RA patients are linked to PVS enlargement in specific brain regions. These intra-group differences suggest that PVS burden varies with autoimmune load in RA patients, highlighting its potential as a surrogate imaging marker for immune-mediated cerebral microvascular involvement within the RA population.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study demonstrates that distinct autoantibody profiles in RA correlate with region-specific enlargement of PVS. Perivascular space abnormalities may potentially serve as a non-invasive imaging marker to reflect immune-mediated cerebral small vessel injury. Longitudinal multicenter trials with cognitive assessments are required to further validate the association and explore the therapeutic effects of immune regulation on brain microvasc","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated network pharmacology and metabolomics reveal the mechanisms of Compound Nanxing Zhitong Plaster in anti-rheumatoid arthritis.","authors":"Zhiqiang Li, Liang Cao, Jiajia Wang, Xia Gao, Fengtai Suo, Fengshou Luo, Wentao Xu, Zhenzhong Wang, Xinzhuang Zhang, Wei Xiao","doi":"10.1007/s10067-026-08385-4","DOIUrl":"https://doi.org/10.1007/s10067-026-08385-4","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;CNZP exhibits significant therapeutic effects on RA, potentially by downregulating NOS1 expression and subsequently correcting the metabolic imbalance of L-arginine. Key Points • CNZP demonstrated significant therapeutic efficacy in a CIA rat model; serum metabolomics revealed the associated differential metabolites and key metabolic pathways involved in its action. • Network pharmacology and molecular docking revealed that CNZP exerts multi-target effects on RA by modulating TNF, IL-17, and Toll-like receptor signaling pathways via its core components quercetin, imperatorin, and isoimperatorin. • Integrated analysis suggests that CNZP treatment is associated with downregulation of NOS1 and correction of l-arginine metabolic imbalance, implicating the JAK1/STAT1 pathway in its anti-RA effect. • This preclinical study provides mechanistic evidence for the ant","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The incidence of clinically diagnosed chronic obstructive pulmonary disease in patients with spondyloarthritis compared to matched population-based references: a register-based study.","authors":"Sofia Exarchou, Ankita Sharma, Petros Zamout, Carl Turesson","doi":"10.1007/s10067-026-08382-7","DOIUrl":"https://doi.org/10.1007/s10067-026-08382-7","url":null,"abstract":"<p><strong>Introduction/objective: </strong>To estimate and compare the incidence of chronic obstructive pulmonary disease (COPD) in patients with spondyloarthritis (SpA) to matched population-based references.</p><p><strong>Methods: </strong>Patients with ≥ 1 SpA-diagnosis from an outpatient department of rheumatology/internal medicine (≥ 17 years at diagnosis) between January 1, 2000, and June 30, 2005, were identified in a regional healthcare register. From the same register, five controls without SpA-diagnosis were matched to each SpA-case on age at the first ever SpA-diagnosis for the case, municipality of residence at this time, and sex. SpA-cases and controls were followed from Jan 1, 2006, until first occurrence of either COPD (diagnosed in primary or secondary inpatient/outpatient care), rheumatoid arthritis diagnosis, moving from the region, death, or Dec 31, 2018. The incidence rates of COPD in SpA-cases and controls, overall and by age-groups and sex, and the corresponding incidence rate ratios, were estimated.</p><p><strong>Results: </strong>A total of 1083/4950 SpA-cases and controls were followed in the present study for 11,790.9/58,876.4 person-years, with 38/220 incident COPD-cases respectively. The estimated incidence of COPD in SpA-cases was 3.22 (95% CI 2.28-4.42) per 1000 person-years, with an incidence rate ratio compared to controls of 0.86 (95% CI 0.59-1.22). Similarly, there were no significant differences in the incidence of COPD in patients with SpA compared to controls in any age group and in both sexes.</p><p><strong>Conclusions: </strong>In this register-based cohort study the incidence of COPD in patients with SpA was similar to that in matched population-based references, overall and after stratification for sex and age-groups. Key Points • Spondyloarthritis (SpA) has been associated with comorbidities, e.g. cardiovascular disease. However, evidence regarding the relation between SpA and chronic obstructive pulmonary disease (COPD) is limited. • To our knowledge, this is the first study to investigate the incidence of COPD in a population-based cohort of patients with SpA in general and compare it to the background population. • Using a regional register of primary and specialized care, we found no difference in COPD incidence between those diagnosed with SpA and matched population-based references, overall and after stratification for sex and age group. • The results of the present study suggest that there may not be an association between SpA and COPD. However, further studies in other countries and settings are needed.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness and safety of Janus Kinase inhibitors in patients with rheumatoid arthritis, results from a multicenter observational \"real-life\" GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) study.","authors":"Daniela Iacono, Maura Raimondi, Valentina Marino, Flavia Riccio, Maria Laura Marchesano, Alessandra Milone, Addolorata Corrado, Cinzia Rotondo, Ilaria Firenze, Lidia La Barbera, Chiara Rizzo, Simona Montalbano, Luca Navarini, Alberto Lo Gullo, Marianna Oliva, Elvira Favoino, Ida Orlando, Francesco Paolo Cantatore, Paola Cipriani, Enrico Tirri, Roberto Giacomelli, Federico Perosa, Giuliana Guggino, Piero Ruscitti, Francesco Ciccia","doi":"10.1007/s10067-026-08373-8","DOIUrl":"https://doi.org/10.1007/s10067-026-08373-8","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the \"real-life\" effectiveness and safety of Janus kinase inhibitors (JAKis) in patients with rheumatoid arthritis (RA) and to analyze the impact of cardiometabolic comorbidities on these outcomes.</p><p><strong>Methods: </strong>Patients with RA treated with JAKis were evaluated for disease activity scores, patient-reported outcomes (PROs), and safety in a 12‑month multicenter observational study conducted within the GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale). Patients were grouped and compared according to the presence of type 2 diabetes (T2D), cardiometabolic multimorbidity (defined as the simultaneous presence of two or more among high blood pressure, T2D, and/or dyslipidaemia), and age ≥ 65 years.</p><p><strong>Results: </strong>440 patients treated with JAKis were included (82.9% female; mean age 61.0 ± 11.0 years); 41.4% had high blood pressure, 39.0% obesity, 28.4% dyslipidaemia, 14.3% T2D, and 3.2% a history of cardiovascular events. A statistically significant improvement was observed in all disease activity measures and PROs over the follow-up period. These improvements seemed to be not influenced by the presence of T2D, cardiometabolic multimorbidity, or age ≥ 65 years. During follow-up, a cumulative adverse events incidence of 18.9% was reported; these were mostly mild and reversible, with no life-threatening events. Drug discontinuation due to adverse events occurred in 7.7% of assessed patients (34 discontinuations due to adverse events). Safety outcomes appeared to be not significantly affected by T2D, cardiometabolic multimorbidity, or age ≥ 65 years.</p><p><strong>Conclusions: </strong>In our \"real-life\" multicenter cohort in patients with RA, JAKis demonstrated effectiveness with an acceptable safety profile despite the relatively short follow-up and the lack of power to assess clinically relevant differences for rare events. The safety profile should therefore be interpreted with appropriate caution. The presence of T2D, cardiometabolic multimorbidity, and age ≥ 65 years did not appear to adversely influence treatment response or safety. Key Points • TJAK inhibitors were effective in reducing disease activity and improving patient-reported outcomes in real-life patients with RA. • Type 2 diabetes, cardiometabolic multimorbidity, and older age did not appear to impair treatment effectiveness of JAK inhibitors in patients with RA. • Most adverse events of JAK inhibitors were mild, reversible, and infrequently led to treatment discontinuation. • These findings may support the use of JAK inhibitors in clinically complex real-life RA populations encountered in daily practice.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}