To critically evaluate the current evidence on the role of vitamin D in inflammatory rheumatic diseases, including its association with disease activity, potential immunomodulatory effects, and the clinical impact of supplementation. A narrative review was conducted based on a comprehensive search of MEDLINE, Cochrane Library, and Epistemonikos databases up to October 2025. Eligible studies included randomized controlled trials, observational studies, systematic reviews, and meta-analyses evaluating vitamin D status and/or supplementation in adult patients with inflammatory rheumatic diseases. Evidence was synthesized qualitatively, prioritizing study design and level of evidence. Vitamin D deficiency is highly prevalent across inflammatory rheumatic diseases and is associated with higher disease activity, fatigue, and poorer musculoskeletal outcomes. Experimental data support immunomodulatory effects; however, clinical evidence remains heterogeneous. Randomized controlled trials demonstrate that supplementation effectively corrects deficiency and is safe, with modest improvements in disease activity and fatigue mainly in patients with low baseline 25(OH)D levels. In contrast, large trials and Mendelian randomization studies do not support a causal role of vitamin D in disease onset or sustained remission. Meta-analyses show small and inconsistent benefits, limited by heterogeneity in study design, dosing regimens, and populations. Vitamin D deficiency is a common and clinically relevant finding in inflammatory rheumatic diseases. While supplementation reliably restores adequate levels and may provide modest clinical benefits in deficient patients, current evidence does not support a causal or disease-modifying role. Maintaining serum 25(OH)D ≥30 ng/mL remains advisable for skeletal health, whereas its immunological benefits require further investigation through well-designed randomized trials.
Rheumatic and musculoskeletal diseases (RMDs) confer an increased cardiovascular risk beyond traditional factors, with peripheral artery disease (PAD) being an important source of morbidity and disability in these patients. This review summarizes current evidence on PAD across RMDs, including rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid syndrome, systemic sclerosis, polymyalgia rheumatica, psoriatic arthritis, and primary Sjögren's syndrome. Physiopathological mechanisms involved include persistent inflammation, immune dysregulation, and the presence of pathogenic autoantibodies. Protective humoral responses have also been linked to reduced CV risk and may serve as future biomarkers. Clinical studies reveal variable PAD prevalence across diseases but consistent high underdiagnosis. Optimal management requires aggressive CV risk control, including lipid-lowering, immunomodulatory, and biologic therapies. This review underscores PAD as a distinct and clinically relevant manifestation of systemic autoimmunity, calling for targeted screening and prevention strategies in rheumatic populations.
Rheumatic heart disease (RHD) arises from acute rheumatic fever (ARF) following group A streptococcal infection. While its prevalence has declined in high-income regions, it remains a major health burden in low-resource settings. This research investigated the burden of RHD from 1990 to 2021, utilizing data from the Global Burden of Disease (GBD) 2021 study. Publicly available data were analysed to determine absolute counts, age-standardised rates, and percentage changes in prevalence, disability-adjusted life years (DALYs), and deaths from 1990 to 2021. In 2021, global RHD cases numbered 54,785,119, with an age-standardised prevalence rate of 684.2 per 100,000, reflecting a 12.6% increase since 1990. Deaths totalled 373,345, with an age-standardised rate of 4.5 per 100,000, marking a 56.2% decline over the period. In 2021, Eritrea (1,865.4) had the highest prevalence rate and Finland (17.4) the lowest. In 2021, Micronesia reported the highest death rate (9.6 per 100,000), and Guatemala the lowest (0.2). Females exhibited higher prevalence rates across all ages, peaking in the 25-29 age range. Although prevalence declined with age, it remained higher in females than among males. The relationship between the Sociodemographic Index (SDI) and RHD burden was non-linear, peaking at an SDI of 0.42, before declining sharply. RHD remains a major public health challenge, characterised by rising prevalence and significant health and economic impacts. Despite reductions in mortality and DALY rates, the increasing prevalence underscores the urgent need for improved prevention and management strategies.
Seven previously undescribed terpenoids (1-7) and sixteen known terpenoids (8-23) were isolated from Euphorbia milii Ch. des Moulins. Among the undescribed terpenoids, there is one eremophilane-type sesquiterpenoid: (4R,5R,7R)-7β-hydroxy-eremophil-1(10),11-diene-2-one (1); one abietane-type diterpenoid: 9-hydroxycaudicifolin (2); one taxane-type diterpenoid: euphominoid Q (3); three norrosane-type diterpenoids: 19-norrosa-5,15-diene-3α,4β-dihydroxy-1,6-dione (4), 19-norrosa-5,15-diene-3α,4α-dihydroxy-1,6-dione (5), 19-norrosa-1,5,15-triene-3α,4α-diol (6); and one taraxerane triterpenoid: aleuritolic acid-3-cis-p-hydroxycinnamate (7). The structures of these compounds were elucidated including nuclear magnetic resonance (NMR), mass spectrometry, X-ray single-crystal diffraction, and Calculated 13C-NMR. Among them, euphominoid Q (3) represents a rare 6/12-fused taxane-type diterpenoid, while 19-norrosa-5,15-diene-3α,4β-dihydroxy-1,6-dione (4) and 19-norrosa-5,15-diene-3α,4α-dihydroxy-1,6-dione (5) are epimers. In vitro bioactivity assays revealed that 9-hydroxycaudicifolin (2) and caudicifolin (20), two abietane-type diterpenoids with anti-rheumatic potential, exhibited stronger inhibitory effects on the production of the inflammatory cytokine NO at 50 μM than the positive control celecoxib. Furthermore, both compounds inhibited the proliferation of MH7A cells, which are synovial fibroblasts derived from rheumatoid arthritis patients. Preliminary observations indicated that compound 2 could induce apoptosis in MH7A cells, arrest the cell cycle of MH7A cells at the G2 phase in a concentration-dependent manner.
Involvement of hands is a frequent finding in polymyalgia rheumatica (PMR) and can lead to misclassification as late-onset rheumatoid arthritis (RA). To compare the inflammatory pattern as shown by contrast-enhanced MRI (ceMRI) of hand involvement in PMR to seropositive RA (RA+). MRIs of patients diagnosed with PMR and clinically suspected hand involvement and with RA+, matched for age/sex, were analysed retrospectively. Synovitis, osteitis and erosions of metacarpophalangeal (MCP) joints 2-5 plus tenosynovitis of flexor/extensor compartments were evaluated using the Rheumatoid Arthritis MRI Score. For assessment of periarticular inflammation around MCP joints, a semi-quantitative scoring was introduced. Distribution of synovitis scores differed significantly between the groups with mostly minor and occasionally moderate synovitis in PMR versus uniformly distributed total scores in RA+. Scores of periarticular inflammation were significantly higher in PMR. Tenosynovitis of extensors and flexors was prevalent in both groups, but flexor tenosynovitis was significantly more prevalent in PMR. Detection of erosions and osteitis was absent in PMR cases but prevalent in RA+ (all p<0.001). A combination of minor to moderate synovitis together with severe periarticular inflammation of an MCP joint represented a characteristic finding in PMR and, if evident in at least one MCP joint, differentiated the groups with a sensitivity and specificity of 78.4% and 78.4%, respectively. Specificity improved to 90.2% at the expense of sensitivity (70.6%) when this characteristic inflammatory pattern was present in more than one MCP joint per hand. Hand involvement in PMR could be clearly differentiated in ceMRI from RA+ by the intensity of periarticular inflammation of MCP joints.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) such as semaglutide (SEM) and tirzepatide (TZP) were initially approved for type 2 diabetes management but are increasingly used for weight loss. Limited data exist on real-world use among patients with rheumatic and musculoskeletal diseases (RMDs). This study aimed to describe characteristics and trends in SEM and TZP initiation among individuals with RMDs and to identify factors associated with weight loss. We conducted a retrospective analysis using the American College of Rheumatology's Rheumatology Informatics System for Effectiveness registry. Adults with RMD prescribed SEM or TZP between 2018 and 2024 were included. Patients with an evaluation and management visit before first GLP-1 RA prescription were classified as new users. The primary outcome was percent change in body weight from baseline to 12 months. Multivariable linear regression assessed factors associated with percent weight change, and logistic models identified predictors of ≥5%, ≥10%, and ≥15% weight loss. Among 60,198 patients with RMD treated with GLP-1 RAs (72% SEM), 80.5% were female, and 54.9% had diabetes; the mean age was 57.0 years, and body mass index was 36.4. GLP-1 RA use increased from 0.1% in 2018 to 6.8% in 2024. At 12 months, SEM and TZP users lost 5.8% and 8.2% of body weight, respectively. TZP users lost 2.2% (95% confidence interval [CI] 1.9-2.5) more weight than SEM users, and those without diabetes lost 1.8% (95% CI 1.5-2.1) more than those with diabetes. GLP-1 RA use is increasing among patients with RMD and is associated with clinically meaningful weight loss, particularly with TZP and in individuals without diabetes.
暂无摘要（点击查看详情）
暂无摘要（点击查看详情）
Musculoskeletal health is essential to health, well-being, and independence across the life course. Musculoskeletal conditions including inflammatory joint diseases, osteoarthritis, back pain, osteoporosis, and fragility fractures are among the greatest causes of disability globally imposing a major burden on health and social care and economic impact also through lost productivity. Despite effective ways of preventing, treating, and rehabilitating these problems, lack of priority results in avoidable disability and costs. We consider how the expert community, through lived and learnt experience, can together influence health policy and health priorities, nationally and globally.
暂无摘要（点击查看详情）
The purpose of the authors' narrative review was to outline the current literature regarding the use of ultrasound in main rheumatic disorders and summarize the updates, specifically about rheumatoid arthritis, psoriatic arthritis, and crystal-induced arthropathies. The authors searched on PubMed for articles discussing the major updates regarding the role of ultrasound in the previously mentioned rheumatic conditions. The authors have provided the updated definitions, new criteria, and diagnostic scores. In rheumatology's dynamic landscape, this review provides valuable insights for researchers and clinicians on ultrasound's role in improving patient care and outcomes in rheumatic diseases.
Indigenous populations have rich traditional care systems but have endured complex interactions with colonial states, and the resulting sociopolitical disparities continue to affect their health outcomes. In this article, the epidemiology and disease burden of rheumatic diseases affecting global Indigenous populations are discussed, along with a presentation of how determinant factors influence the existing landscape for arthritis care delivery. This article proposes how rheumatology care providers can deliver services aligned with Indigenous world views and realities to improve care quality. It also provides examples of community-driven interventions that have advanced outcomes for Indigenous peoples living with arthritis conditions.
To investigate associations between cardiometabolic comorbidities and clinical characteristics, prescription patterns and retention of first biologic/targeted synthetic disease-modifying anti-rheumatic drug (b/tsDMARD) in patients with psoriatic arthritis (PsA). Patients with PsA initiating a first b/tsDMARD treatment in 2015 or later were identified in eight European rheumatology registries. Patients with information on five cardiometabolic comorbidities (obesity, dyslipidaemia, diabetes, hypertension, ischaemic heart disease) at treatment start (baseline) were included. All analyses were conducted according to patients' comorbidity burden (count: 0/1/≥2) and status (presence/absence of each comorbidity). Patient characteristics and prescription patterns were described. Twelve-month treatment retention rates were estimated and compared using Kaplan-Meier plots, log-rank tests and multivariable Cox regression analyses. Among 5299 patients, 36% had at least one cardiometabolic comorbidity. Patients with comorbidity were older, had higher disease activity and more disability. Regardless of comorbidity, most patients were prescribed a tumour necrosis factor inhibitor (76%). The use of interleukin-17 inhibitors increased with comorbidity burden (0/1/≥2 comorbidities: 13%/18%/19%), whereas Janus kinase inhibitor use declined (2.3%/1.6%/0.8%). Retention rates were marginally lower with higher comorbidity burden (80%/76%/78%) (log-rank, p=0.036) and obesity (absent 79% vs present 77%) (log-rank, p=0.04). The risk of treatment withdrawal was only marginally higher in patients with higher comorbidity burden (one comorbidity: HR 1.19; 95% CI 1.02 to 1.40; ≥2 comorbidities: HR 1.18; 0.98 to 1.42). Patients with cardiometabolic comorbidities had higher disease activity at treatment initiation of the first b/tsDMARD. Prescription patterns varied with comorbidity burden. Cardiometabolic comorbidity burden, especially obesity, was associated with marginally lower treatment retention.
Given chronic pain remains a major public health concern and focus of national prevention and management objectives, this study examined temporal trends, a complementary prevalence-burden framework, and multilevel correlates of chronic pain and high-impact chronic pain across demographic, sociodemographic, health-related, mental health, and health care access, utilization, and affordability domains. Pooled data from 2019, 2021, and 2023 National Health Interview Survey (N=91,001 adults) were analyzed using survey-weighted logistic regression models sequentially adjusted by domain and fully adjusted for all covariates. Chronic pain prevalence increased from 20.5% in 2019 to 24.3% in 2023, while high-impact chronic pain rose from 7.5% to 8.5%. In fully adjusted models, higher odds of chronic pain were observed among adults aged ≥25 years, those experiencing socioeconomic disadvantage (unemployment, and poverty), individuals reporting poor self-rated health, rheumatic conditions, and frequent anxiety or depressive symptoms, and those reporting greater health care utilization and cost-related barriers to care and prescriptions. Sensitivity analyses using high-impact chronic pain as the outcome demonstrated similar or stronger associations across age groups and for socioeconomic disadvantage, depressive symptoms, health care utilization, and affordability barriers. These findings suggest that rising chronic pain and high-impact chronic pain are closely linked not only to socioeconomic and mental health factors, but also to health care access, utilization, and affordability context, supporting more equitable screening, care planning, and pain management strategies. PERSPECTIVE: Chronic pain affects more than one in five U.S. adults and is closely linked with socioeconomic disadvantage, mental health symptoms, healthcare utilization, and affordability barriers. Distinguishing prevalence from burden helps identify subgroups for screening and case finding while informing resource allocation, care planning, and more equitable pain care.
To evaluate the effects of 2 years of low-dose glucocorticoid (GC) treatment on bone mineral density and fracture risk in patients with rheumatoid arthritis (RA). We performed a protocolised (dx.doi.org/10.17504/protocols.io.6qpvr3ombvmk/v1) systematic literature review and individual participant data meta-analysis of randomised trials in early and established RA, which compared GCs at ≤7.5 mg prednisone equivalent/day with placebo or standard of care. All patients could receive background treatment with disease-modifying antirheumatic drugs. Changes in lumbar spine and femoral bone density and participants with ≥1 clinical fracture over 2 years in intention-to-treat analyses were coprimary endpoints. Main analyses were based on one-stage models; I² was estimated from two-stage models. Missing data were handled using multiple imputation. Several sensitivity analyses assessed the robustness of our results. Out of 2336 articles, five out of six identified trials provided individual participant data (1112 participants). Greater bone loss was observed at the lumbar spine in the GC compared with the control group (-0.021 g/cm²; 95% CI -0.037 to -0.005; p=0.034; I²=31%) but not at the femur (0.004 g/cm²; 95% CI -0.008 to 0.016; p=0.47; I²=0%). Subgroup analyses did not reveal groups particularly susceptible to GC-induced bone loss at the lumbar spine. 35 participants experienced ≥1 fracture; fracture risk was comparable in both groups. Sensitivity analyses yielded consistent results. Low-dose GCs, used for 2 years to treat RA, lead to bone loss at the lumbar spine but not at the femur.
In the decades of the 1980s and 1990s, before the onset of biologic therapies for rheumatoid arthritis (RA) management, there was a significant number of patients who did not achieve remission or low disease activity (LDA), due to limited therapeutic choices. At that time, only some conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs), along with steroids, were used. Nowadays, despite the progress of RA management with the introduction of biologic (b) and targeted synthetic (ts) DMARDs, which showed significant clinical improvement and retardation of radiological damage, unmet needs of RA treatment still exist. On the other hand, the concept of treat-to-target (T2T) approach and tight control monitoring of disease activity, are considered now the cornerstone for achieving remission or LDA in RA patients. Several clinical trials confirmed the efficacy and safety of csDMARDs using the tight control and T2T strategies. Methotrexate is the fundamental drug for RA management and in combination with other csDMARDs, with or without steroids, it has proven to be efficacious and safe and less expensive in comparison to newer biologic therapies. Furthermore, MTX demonstrated cardioprotective effects and reduced the risk of cardiovascular events in RA patients Therefore, there is a potential for improving treatment strategies with conventional therapies in the management of early RA. Optimal and early use of csDMARDs controls disease activity similarly to biologic therapies and is less expensive.
Rheumatology in Africa faces significant systemic challenges, including underfunding, limited training opportunities, specialist shortages, and scarce diagnostics and treatments. These barriers perpetuate poor outcomes for rheumatic and musculoskeletal disease patients, especially in underserved regions. This article highlights how South-South collaboration yields training partnerships, regional excellence hubs, e-learning, and patient advocacy. It offers contextually relevant sustainable solutions, such as successful initiatives in Nigeria, Ghana, Kenya, and Ethiopia, illustrating how African-led networks strengthen services and develop leaders while reducing brain drain. Addressing funding, policy, and infrastructure gaps is critical to achieving equitable rheumatology care and building resilient, locally driven capacity pan-continent.
TL1A is a proinflammatory cytokine in the tumor necrosis factor (TNF) superfamily that signals via DR3 on T helper cells, innate lymphoid cells, and fibroblasts. Dysregulated TL1A signaling has been hypothesized to affect multiple immune-mediated diseases, with clinical proof of concept demonstrated in ulcerative colitis and Crohn's disease. We characterized the binding affinity, specificity, structure, pharmacodynamics, pharmacokinetics, and toxicity profiles of SPY002 and SPY072, two novel extended half-life monoclonal antibodies that inhibit TL1A. SPY002 and SPY072 demonstrated selective, high-affinity binding to human TL1A (KD ≈ 31-35 pM) and potent functional inhibition of DR3 signaling. Based on Fc modifications, SPY002 and SPY072 showed attenuated Fc effector function and increased FcRn binding at acidic pH (5.8). Both antibodies exhibited enhanced PK profiles in nonhuman primates, resulting in predicted human half-lives that support quarterly or biannual dosing. In toxicity studies, no drug-related adverse effects were observed with either antibody at exposures >10 times those anticipated in clinical trials. In a rat collagen-induced arthritis model, anti-TL1A antibody treatment effectively reduced arthritis severity, with similar efficacy to the TNF antagonist etanercept. In humanized mouse Imiquimod-induced psoriasis and 2,4,6‑trinitrobenzene sulfonic acid colitis models, anti-TL1A demonstrated similar efficacy to anti-IL-23 and anti-TNF antibodies. These findings characterize two novel extended half-life TL1A antibodies and support the ongoing Phase 2 clinical development of SPY002 and SPY072 for immune-mediated diseases such as inflammatory bowel disease and rheumatic diseases.
Sinomenii Caulis (SC), a traditional ethnic herb, is derived from the dried stems of Sinomenium acutum (Thunb.) Rehd. et Wils. and Sinomenium acutum (Thunb.) Rehd. et Wils. var. cinereum Rehd. et Wils. SC is extensively documented in the Chinese Pharmacopoeia for its traditional use in dispelling wind and dampness, as well as alleviating symptoms associated with rheumatic disorders, such as joint swelling and pruritus. SC contains a diverse array of alkaloids, among which sinomenine (SIN) is recognized as its primary quality marker. This review aims to provide an updated analysis and summary of the botany, ethnopharmacology, phytochemistry, pharmacological activities, toxicity, quality control, clinical applications, and novel preparations of SC. Special emphasis is placed on elucidating the anti-rheumatoid arthritis mechanisms of SC, providing multidimensional reference for future in-depth research and the efficient utilization of SC. Literature related to SC was retrieved, compiled, and analyzed utilizing multiple databases, including Web of Science, PubMed, ScienceDirect, Wiley Library, China National Knowledge Infrastructure (CNKI) and ancient texts and research reports up to April 2026. To date, a total of 403 chemical constituents have been identified from SC, comprising 212 alkaloids, 142 volatile components, 19 phenylpropanoids, 7 triterpenoids, 9 quinones, 5 sterols, 4 butenolides, and 6 other compounds. Among these, SIN has been demonstrated pronounced efficacy in diverse pharmacological activities, including anti-inflammation, anti-tumor, neuroprotection, organ protection, immunomodulation, analgesia, and other pharmacological effects. SIN is widely used in clinical settings due to its favorable pharmacological properties, characterized by minimal side effects, a wide safety margin, mild gastrointestinal reactions, and rapid resolution of symptoms upon discontinuation of treatment. Furthermore, this review identifies current research limitations and future directions, laying the groundwork for further exploration, pharmaceutical applications, and product development of SC. A comprehensive literature review shows that SC has multiple pharmacological activities and has special therapeutic effects on rheumatoid arthritis. However, current research focuses on the pharmacology of each component and rarely explores interactions or synergistic effects. Therefore, further research should focus on toxicology, pharmacokinetic studies of herbal drug interactions, and quality control in order to improve the safety and clinical application of SC. These efforts will promote quality standardization, new drug development, and clinical translation to advance the medical applications of SC.
Systemic lupus erythematosus (SLE) patients are complex with multisystem organ involvement and often organ damage due to the disease and its treatment. This review aims to shed light on surgical outcomes in SLE patients and how these can be optimized in the perioperative setting. SLE patients often require various surgical procedures as a direct result of their disease. Several studies, the majority orthopedic, have reported the often-increased incidence of infectious, thrombotic, hemorrhagic and other postoperative outcomes in SLE patients compared to controls, as well as the role of lupus activity, severity, comorbidities, and glucocorticoids (GC) in predicting poor outcomes. Unfortunately, most publications are limited by retrospective design, small numbers or lack of granular information on lupus activity and its treatment. Nevertheless, recent guidelines for the treatment of SLE and the perioperative management of immunosuppressive therapies (IST) in patients with rheumatic diseases undergoing hips/knee arthroplasty have been published and have filled an important gap in the management of these patients. Achievement of remission or low lupus activity by escalating IST and GC taper to prednisone doses ≤ 5-7.5 mg/day is recommended in general and in the perioperative setting. Severe SLE patients actively treated for organ involvement may be allowed to continue IST perioperatively, but others may withhold IST. Careful multidisciplinary planning of elective surgeries, considering disease activity, severity, and comorbidities, as well as prudent perioperative GC, IST and anticoagulant management, should optimize outcomes in SLE patients. Large prospective studies of SLE patients undergoing common surgeries should facilitate further progress.