Archives of rheumatology最新文献

Background/aims: Giant cell arteritis (GCA), a large-vessel vasculitis, is associated with increased risks of venous and arterial thrombotic events, such as visual ischemia, pulmonary embolism, and ischemic stroke. Traditional cardiovascular risk factors, such as diabetes mellitus, hypertension (HTN), and hyperlipidemia (HLD), might contribute to these events. While antiphospholipid antibodies (aPLs) are sometimes present, their role in GCA-related thrombosis remains uncertain.

Materials and methods: Seventy-five patients with biopsy-confirmed GCA were recruited, and 1-time blood samples were collected to assess for aPL. Cardiovascular risk factors (e.g., HTN, diabetes, HLD, and atrial fibrillation) at study visit and thrombotic events (pulmonary embolism, deep vein thrombosis, transient ischemic attack, stroke, and visual ischemia) throughout follow-up were abstracted from medical records. Chi-square tests and Cox models were used to evaluate associations between aPLs and these events and their risk factors.

Results: In this cohort of 75 GCA patients, 25 (33%) had at least 1 positive aPL, with anticardiolipin IgM being the most common. Visual ischemia occurred in 19 (25%) patients. There was no significant association between visual ischemia and cardiovascular risk factors, but there was a significant association between anti-beta-2 glycoprotein I IgM and visual ischemia (P = .048) as well as between aB2GPI IgG and the development of PE/DVT (P = .0035). Overall, 16 experienced a composite thrombotic event, with only aB2GPI IgG associated with higher ischemic event rates.

Conclusion: Although aPL might be prevalent among GCA, there were minimal associations between aPL isotypes and GCA thrombotic events. Further studies are needed to confirm aPL prevalence in GCA and explore anticoagulation's potential role in patients with visual ischemia and positive aPL. Cite this article as: Hasbani GE, Crowson C, Snyder M, Warrington K, Koster M. Cardiovascular risk factors and antiphospholipid antibodies in giant cell arteritis-related thrombosis. Arch Rheumatol. 2025;40(4):422-426.

Background/aims: To investigate the use of thoracic ultrasound (US) in the assessment of the pleura in connective tissue disease (CTD).

Materials and methods: The clinical, radiologic, and demographic data were recorded f rom patients who were diagnosed as having CTD at least 1 year before the study. Thoracic US was performed for pleural assessments in all patients who met the inclusion criteria. The thickness of the parietal and visceral layers of the pleura and pleural space was measured in milli-meters and recorded in both the CTD and healthy control groups, and data f rom the CTD group were compared with those f rom the healthy control group.

Results: A total of 86 participants, 44 (51.2%) with CTD and 42 (48.8%) healthy volunteers, were included in the study. There were 37 (84.1%) females with a mean age of 55.1 ± 11.1 years in the CTD group and 23 (54.8%) females with a mean age of 56 ± 11.8 years in the control group. In the CTD group, the mean parietal pleural thickness, visceral pleural thickness, and pleural space were 0.61 ± 0.16 mm, 0.61 ± 0.17 mm, and 0.77 ± 0.5 mm, respectively, and in the control group, these values were 0.42 ± 0.08 mm, 0.44 ± 0.09 mm, and 0.47 ± 0.15 mm, respectively (P < .001).

Conclusion: Pleural thickness was increased in patients with CTD com-pared with healthy controls. The lungs are among the target organs in CTD, and US is a non-invasive and radiation-f ree imaging modality that can be used in the assessment of pleural involvement.

Background/aims: Serum uric acid (SUA) is a potential risk factor for renal involvement in systemic lupus erythematosus (SLE). However, the impact of cumulative SUA levels on subsequent renal involvement in premenopausal women remains unclear. The association between cumulative SUA levels and the development of subsequent renal involvement in premenopausal patients with SLE was evaluated.

Materials and methods: A retrospective review of 112 premenopausal women with newly diagnosed SLE, and no renal involvement at diagnosis was conducted in a tertiary medical center. Clinical characteristics at diagnosis and during follow-up were compared between patients who developed subsequent renal involvement and those who did not. Timeaveraged SUA (TA-SUA) was calculated from the area under the curve during follow-up. Cox proportional hazards analysis was performed to evaluate the factors associated with subsequent renal involvement.

Results: The median TA-SUA level among 112 patients was 4.2 mg/dL (IQR, 3.8-4.8). During a median follow-up of 4.4 years, 25 patients developed subsequent renal involvement. The proportion of patients with TA-SUA level ≥4.2 mg/dL was higher in patients with subsequent renal involvement than in those without (84.0% vs. 46.0%, P = .001). In multivariate Cox analysis, TA-SUA level ≥4.2 mg/dL was associated with a higher risk of subsequent renal involvement (hazard ratio 6.389, P = .014). Systemic lupus erythematosus disease activity index score and the presence of anti-Smith antibodies at diagnosis were also associated with subsequent renal involvement.

Conclusion: High TA-SUA levels are independently associated with an increased risk of subsequent renal involvement in premenopausal patients with SLE, underscoring the importance of cumulative SUA levels. Cite this article as: Choi SJ, So MW, Yoo KD, Lee SG, Choi SW, Lim DH. Association between time-averaged serum uric acid level and subsequent renal involvement in premenopausal patients with systemic lupus erythematosus. Arch Rheumatol. 2025;40(4):427-434.

The human gut microbiome is a pivotal regulator of systemic immunity and a central factor in the pathogenesis of rheumatic diseases. An imbalance in this microbial community, known as "dysbiosis," can trigger and perpetuate autoimmune responses through the "gut-joint axis." A key mechanism underpinning this connection is increased intestinal permeability ("leaky gut"), which facilitates the translocation of microbial products like lipopolysaccharide into the systemic circulation, thereby provoking chronic inflammation. Concurrently, dysbiosis disrupts the critical homeostatic balance between pro-inflammatory Th17 cells and regulatory T cells, an immunological hallmark of conditions such as rheumatoid arthritis (RA), ankylosing spondylitis, and systemic lupus erythematosus (SLE). Specific microbial signatures, including the expansion of Prevotella copri in RA and Ruminococcus gnavus in SLE, are emerging as potential diagnostic biomarkers. This deeper understanding is paving the way for innovative therapeutic strategies. Interventions aimed at modulating the gut microbiota, such as targeted diets, probiotics, prebiotics and fecal microbiota transplantation, represent a promising frontier for the personalized management of rheumatic diseases. This review explores the foundational mechanisms linking the microbiome to autoimmunity and discusses the clinical potential of harnessing the gut-joint axis to improve patient outcomes.

Background/aims: Monosodium urate (MSU) is a key contributor to gout development, primarily by triggering innate inflammatory responses. Given the known role of miR-23a-5p in regulating inflammation, this study aimed to investigate the molecular mechanisms through which miR23a-5p influences MSU-induced gout inflammation.

Materials and methods: Monosodium urate was used to model gouty inflammation in THP-1 cells and Sprague-Dawley (SD) rats. In vivo, 15 SD rats were randomly divided into the control, model, model + miR-23a mimic, model + interleukin (IL)-17A, and model + miR-23a mimic + IL-17A groups. In vitro, the model cells were treated with miR-23a mimics, IL-17A, or both. TargetScan predicted that miR-23a-5p might target IL-17A, which was verified using a dual-luciferase reporter system. Subsequently, IL-17A and miR-23a-5p mRNA levels, as well as NLR family pyrin domain containing 3 (NLRP3) inflammasome-related factors (IL-1β, IL-6, NLRP3, IL-18, ASC, and caspase-1), were quantified using quantitative polymerase chain reaction, immunohistochemistry, enzyme-linked immunosorbent assay, and western blotting. Hematoxylin and eosin (H&E) staining was performed to observe pathological changes in rat ankles. Additionally, flow cytometry was conducted to quantify Th17 cells in rat blood.

Results: Both in vivo and in vitro, miR-23a-5p expression was downregulated, whereas IL-17A expression was upregulated in the gout models. The H&E staining revealed that miR-23a-5p mimic treatment alleviated gout symptoms, whereas IL-17A treatment exacerbated these symptoms. Direct interaction between miR-23a-5p and IL-17A was validated using a dual-luciferase reporter assay. Moreover, flow cytometry analysis showed that miR-23a-5p overexpression inhibited Th17 cell differentiation. Additionally, miR-23a-5p suppressed NLRP3 inflammasome activation by targeting IL-17A. Correspondingly, the expression of proinflammatory proteins such as IL-1β, IL-6, NLRP3, IL-18, and caspase-1 was downregulated by miR-23a-5p and upregulated by IL-17A treatment.

Conclusion: This study demonstrated that miR-23a-5p alleviates MSUinduced gouty inflammation by directly targeting IL-17A. Through this regulation, miR-23a-5p suppresses NLRP3 inflammasome activation, highlighting its potential as a therapeutic target for gout. Cite this article as: Yuan X, Lin C, Zhang Y, He H, Li L. MiR-23a-5p alleviates gouty inflammation by targeting interleukin-17A and inhibiting NLR family pyrin domain containing 3 inflammasome activation. Arch Rheumatol. 2025;40(4):443-451.

Background/aims: This study aimed to assess the potential of syndecan-1 levels as a biomarker for diagnosing cardiovascular diseases and atherosclerosis in patients with Behçet's disease.

Materials and methods: After estimating the required sample size, 56 patients with Behçet's disease and 56 age- and sex-matched controls were enrolled in the study. Carotid intima-media thickness (cIMT) was measured by a single radiologist using an appropriate technique. Syndecan-1 levels were determined with an Syndecan-1 human ELISA kit (CLOUD CLONE, USCN). The test system showed a correlation coefficient of 0.99 between expected and actual values, with a detection limit of around 0.01 ng/mL. The intra-assay coefficient of variation (CV) was under 10%, and the inter-assay CV was under 12%.

Results: The data obtained from the study showed that syndecan-1 levels (P < .002) and cIMT measurements (P < .015) were significantly higher in patients with Behçet's disease compared to the healthy control group. Additionally, correlation analysis revealed a significant negative relationship between syndecan-1 levels and cIMT. In a stepwise multiple regression analysis, a strong independent relationship was found between cIMT and age (beta [β] = 0.474, P < .001), syndecan-1 (β = 0.302, P = .007), and low-density lipoprotein (β = 0.219, P = .050).

Conclusion: Syndecan-1 levels were higher in patients with Behçet's disease compared to controls, and increased syndecan-1 may slow the progression of subclinical atherosclerosis. This study is a preliminary investigation. Further detailed studies are needed. Cite this article as: Kadıyoran C, Diydem Yılmaz P, Hakan Göktepe M, et al. Syndecan-1 as a biomarker for cardiovascular risk in patients with Behçet's disease. Arch Rheumatol. 2025;40(4):435-442.

Background/aims: Sarcopenia is known to worsen clinical outcomes in osteoarthritis, particularly in weight-bearing joints, yet its relationship with symptom burden in hand osteoarthritis has not been well established. This study explored the relationship between sarcopenia, hand pain, and functional status in patients with hand osteoarthritis.

Materials and methods: A retrospective analysis was conducted on 1139 patients aged ≥40 years with radiographically confirmed hand osteoarthritis. Sarcopenia was defined as the ratio of muscle mass to body mass index, measured via bioelectrical impedance analysis. Hand pain and function were assessed using the Australian/Canadian Osteoarthritis Hand Index, and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaires. Sex-specific multivariable linear regression models were constructed, adjusting for demographic and lifestyle covariates.

Results: In males, lower appendicular skeletal muscle mass/body mass index was significantly associated with higher DASH scores (estimate: -10.664, P = .006). A significant association with higher Australian/Canadian Osteoarthritis Hand Index scores was also observed (estimate: -26.236, P = .030). Lower upper-extremity muscle mass/body mass index was likewise associated with higher DASH scores in males (estimate: -41.074, P = .013). In females, none of the associations reached statistical significance.

Conclusion: These findings suggest that sarcopenia contributes to increased pain and disability in hand osteoarthritis, highlighting the clinical importance of preserving muscle mass in its management. Cite this article as: Lee H, Lee S-I, Cheon Y-H, et al. Association of sarcopenia with pain and disability in hand osteoarthritis: a retrospective, cross-sectional, single-center study. Arch Rheumatol. 2025;40(4):492-498.

Background/aims: This study aimed to investigate the relationship between obesity indices and non-alcoholic fatty liver disease (NAFLD) in patients with ankylosing spondylitis (AS).

Materials and methods: A total of 170 patients with AS were included in this observational study with both prospective and retrospective components. Anthropometric measurements (height, weight, waist circumference [WC]) were prospectively recorded by the investigators during routine clinical visits. Obesity indices, including body mass index (BMI), WC, and waist-to-height ratio (WHtR), were calculated. Non-alcoholic fatty liver disease was diagnosed based on existing abdominal ultrasonography reports. Laboratory data, including liver enzymes, lipid profiles, and inflammatory markers, were retrospectively collected. The diagnostic performance of WC for NAFLD was assessed using receiver operating characteristic (ROC) curve analysis.

Results: Non-alcoholic fatty liver disease was detected in 57% of AS patients. Higher BMI and WHtR were significantly associated with both the prevalence and severity of NAFLD (P < .001). Patients with NAFLD exhibited significantly higher levels of C-reactive protein, triglycerides, and alanine aminotransferase, as well as lower high-density lipoprotein levels, compared to those without NAFLD (P < .05). Additionally, the aspartate aminotransferase/alanine aminotransferase ratio was <1 in 66% of NAFLD patients, suggesting its potential as a biochemical marker for NAFLD in AS. The ROC analysis identified WC cutoff values of 100 cm for males and 90 cm for females, demonstrating high sensitivity and specificity in predicting NAFLD.

Conclusion: Obesity is strongly associated with NAFLD in AS patients. Body mass index and WHtR may serve as valuable indicators for assessing hepatic steatosis risk. Routine metabolic evaluations, including obesityrelated parameters and liver enzyme levels, could facilitate the early detection of NAFLD in AS patients. Further prospective studies are warranted to clarify the causal relationship between obesity and liver involvement in AS. Cite this article as: Kutluk O, Dabak NE, Yucel AA, Alparslan AS, H, Cay F. The association between obesity indices and non-alcoholic fatty liver disease in patients with ankylosing spondylitis. Arch Rheumatol. 2025;40(4):482-491.

Background/aims: Fibromyalgia (FM) is a chronic disease characterized by widespread pain. An increased cardiovascular risk has been suggested in these patients. The aim was to investigate the cardiovascular risk factors in these patients.

Materials and methods: Patients with primary FM consecutively were prospectively recruited from a tertiary medical center in Taiwan. As the control group, individuals without FM who had undergone a health checkup examination were recruited. Their traditional cardiovascular risk factors, carotid intima-media thickness (IMT), and the presence of metabolic syndrome were then determined. Metabolic dysfunction-associated steatotic liver disease (MASLD) and the severity of hepatic steatosis (the Saverymuttu and Hamaguchi scores) were both determined by sonography. Multivariate logistic and linear regression were used to compare groups of subjects.

Results: A total of 66 FM patients and 116 controls were recruited. Between FM patients and controls, comparable cardiovascular risk factors were found, including carotid IMT and metabolic syndrome. FM patients had a higher proportion of central adiposity when compared with the controls, with an odds ratio of 6.1 (95% CI: 2.9, 13.1). Fibromyalgia patients had a more severe hepatic steatosis, if present, as determined by the Hamaguchi score. In female subjects, FM patients had a higher proportion of MASLD when compared with the controls, with an odds ratio of 2.8 (95% CI: 1.3, 6.1). The disease severity was associated with left IMT value and lipid blood levels in FM patients.

Conclusion: Fibromyalgia patients had a higher proportion of central adiposity and more severe hepatic steatosis when compared with the controls. Those patients with more severe FM symptoms likely had a higher cardiovascular risk. Metabolic dysfunction-associated steatotic liver disease merits more attention in FM patients. Cite this article as: Chen C, Chen Y, Chen D, Yang S, Tang K. Metabolic syndrome and metabolic dysfunction-associated steatotic liver disease in fibromyalgia. Arch Rheumatol. 2025;40(4):452-458.

Background/aims: Patients with axial spondyloarthritis (axSpA) who fail tumor necrosis factor inhibitors (TNFi) represent a treatment-refractory subgroup with limited options. Real-world evidence (RWE) on the effectiveness and safety of selective Janus kinase 1 (JAK1) inhibition in this setting remains scarce. This study aimed to evaluate the 52-week real-world effectiveness, persistence, and safety of upadacitinib in TNFi-refractory axSpA patients.

Materials and methods: In this retrospective, single-center study, 45 Turkish axSpA patients with prior TNFi failure received upadacitinib 15 mg daily and were assessed at weeks 12, 24, and 52. Effectiveness outcomes included Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Health Assessment Questionnaire (HAQ), Visual Analog Scale for pain, and Assessment of SpondyloArthritis International Society (ASAS) 20/40/70 responses analyzed with non-responder imputation (NRI). Treatment persistence was evaluated by Kaplan-Meier analysis, predictors of discontinuation by Cox regression, and safety outcomes as incidence per 100 patient-years (PY).

Results: Mean age was 48.1 years; 53.3% were male; 68.9% human leukocyte antigen B27 positive. At week 52, BASDAI and ASDAS decreased significantly (both P < .001), with parallel improvements in BASFI, BASMI, HAQ, and pain. The ASAS20/40/70 responses were achieved by 75.6%, 60.0%, and 26.7% of patients (NRI). Drug retention was 75.6% at 1 year; discontinuations occurred due to adverse events (AEs) (4.4%), treatment failure (11.1%), patient decision (6.7%), and pregnancy (2.2%). Prior interleukin-17 inhibitor (IL-17i) exposure (HR 3.88) and multiple TNFi use (HR 3.02) predicted shorter drug survival. Across 38.3 PY, no serious infections, malignancies, or thromboembolic events were observed; AEs were infrequent and manageable.

Conclusion: Upadacitinib provided sustained improvements in disease activity, function, and patient-reported outcomes in TNFi-refractory axSpA, with favorable persistence and safety. Despite limitations of the retrospective, single-center design and modest sample size, these findings complement pivotal trials and global real-world data and represent the first RWE of upadacitinib use in Türkiye, supporting JAK1 inhibition as a therapeutic option in difficult-to-treat populations. Cite this article as: Bakay U, Duran Tİ. Real-world effectiveness and safety of upadacitinib in tumor necrosis factor-inhibitor refractory axial spondyloarthritis: 52-week outcomes from a single-center cohort. Arch Rheumatol. 2025;40(4):465-473.