BACKGROUND: Although hyperuricemia (HUA) is required for gout development, only a fraction of individuals with elevated serum urate progress to the disease. Metabolomic profiling may help uncover biological mechanisms an...BACKGROUND: Although hyperuricemia (HUA) is required for gout development, only a fraction of individuals with elevated serum urate progress to the disease. Metabolomic profiling may help uncover biological mechanisms and improve prediction of gout onset. METHODS: We conducted a prospective metabolomics analysis among 32,563 HUA individuals in the UK Biobank. Baseline plasma metabolites were measured, and differences between individuals who developed gout (n = 2,856) and those who did not were identified. Cox proportional hazards models with false discovery rate correction assessed metabolite-gout associations. Significant metabolites and clinical factors were selected using LASSO-Cox and stepwise regression to construct a gout risk score (GRS). Model performance was evaluated in a test set using survival analysis and time-dependent receiver operating characteristic (ROC) curves. Sensitivity and subgroup analyses, along with validation in an independent validation set and transcriptomic profiling, tested the robustness and biological relevance of results. RESULTS: The final GRS incorporated six metabolites and three clinical variables. It was strongly associated with incident gout (HR = 2.94, 95% CI 2.66-3.23), and individuals in the top quartile had markedly higher risk. The model showed stable predictive ability, with time-dependent AUCs of 0.81-0.79 in the training set and 0.85-0.79 in the test set across 1-10 years. Further validation of the GRS in the independent validation set confirmed the performance. Transcriptomic analyses independently revealed enrichment of inflammatory and lipid-metabolic pathways, consistent with the metabolites included in the GRS. CONCLUSIONS: We developed a lipid- and inflammation-related GRS that effectively predicts gout onset among HUA individuals, offering a useful tool for early risk stratification and targeted prevention. Key Points • An NMR-based metabolomics analysis identified several lipid- and inflammation-related metabolites strongly associated with incident gout among individuals with hyperuricemia. • A gout risk score integrating six metabolites and three clinical factors demonstrated robust and stable predictive performance over up to 10 years of follow-up. • Individuals in the highest quartile of the metabolite-based risk score had substantially elevated gout risk, improving early identification of high-risk subgroups. • Transcriptomic profiling revealed enrichment of inflammatory and lipid-metabolic pathways, supporting the biological plausibility of the findings.
OBJECTıVE: Our objective was to compare the clinical characteristics of heterozygous E148Q-positive familial Mediterranean fever (FMF) patients with those of E148Q/M694, M694V-homozygous, and M694V-heterozygous-positive...OBJECTıVE: Our objective was to compare the clinical characteristics of heterozygous E148Q-positive familial Mediterranean fever (FMF) patients with those of E148Q/M694, M694V-homozygous, and M694V-heterozygous-positive patients. METHODS: Tel-Hashomer classification criteria were used to diagnose FMF. Exons 2, 3, 5, and 10 MEFV mutations were evaluated using the multiplex-PCR reverse hybridization method. The Tel-Hashomer FMF severity score was taken into consideration for FMF severity. The severity score was determined taking into account the period before using colchicine. The clinical features of FMF patients with the E148Q variant were compared to those with heterozygous E148Q plus M694V, and to patients with heterozygous or homozygous M694V mutations. RESULTS: The study included 148 patients with FMF. E148Q heterozygosity was found in 14 patients (9.4%), M694V/E148Q positivity in 13 patients (8.7%), M694V heterozygosity in 49 patients (33.1%), and M694V homozygosity in 72 patients (49.6%). The disease began at an earlier age in those with M694V homozygosity compared to those with M694V heterozygosity and those with E148Q heterozygosity. However, there was no difference in disease onset age between those with M694V homozygous mutations and those with M694V/E148Q. As expected, disease severity scores, erysipelas-like erythema, and relative marriage rates were higher in those who were M694V homozygous. There was no difference between the groups in terms of fever, abdominal pain, arthritis/arthralgia, vasculitis, familial history, or frequency of ankylosing spondylitis. CONCLUSıON: Patients with heterozygous E148Q variant may exhibit main clinical features of FMF disease. Key Points • About 10% of FMF patients have heterozygot E148Q variant. • The clinical characteristics of patients with E148Q variant may be similar to those of patients with Exon 10 mutation.
OBJECTIVE: Given that rheumatoid arthritis (RA) in working-age adults poses rising global health and economic challenges, we assessed the global, regional, and national burden of RA among adults aged 15-49 years from 199...OBJECTIVE: Given that rheumatoid arthritis (RA) in working-age adults poses rising global health and economic challenges, we assessed the global, regional, and national burden of RA among adults aged 15-49 years from 1990 to 2021 and projected trends to 2050. METHODS: We analyzed Global Burden of Disease 2021 data from 204 countries. Age-standardized rates of RA incidence, prevalence, and disability-adjusted life-years (DALYs) were calculated. Decomposition analysis quantified contributions of population growth, aging, and epidemiological changes. Frontier analysis identified best-performing countries. Bayesian age-period-cohort models projected trends to 2050. RESULTS: Global RA prevalence among 15-49-year-olds increased 87.7% from 3.23 million cases (95% UI: 2.59-3.95 million) in 1990 to 6.07 million (4.90-7.36 million) in 2021. Age-standardized prevalence rose 29% (119.20 to 153.73 per 100,000). Women experienced 2.8-fold higher rates than men (228.3 vs 81.0 per 100,000). High Socio-demographic Index (SDI) countries showed triple the prevalence of low SDI countries (209 vs 65 per 100,000). Latin America recorded the highest regional rates (Andean: 420.7 per 100,000). Population growth accounted for 68% of case increases, with epidemiological changes contributing 24%. Smoking-attributable burden declined from 8.8% to 6.5% of DALYs. Projected cases will reach 7.48 million by 2050 (26.8% increase). CONCLUSION: RA burden among working-age adults has nearly doubled since 1990, with persistent inequities by sex and development level. The projected increase to 7.48 million cases by 2050 demands urgent global action, including integrating RA into chronic disease programs and expanding early diagnosis access. Key Points • RA cases in working-age adults nearly doubled from 3.23 to 6.07 million (1990-2021) • Women experience 2.8-fold higher RA rates and comprise 73% of all cases • High SDI countries show triple the prevalence of low SDI countries • Projected a 26.8% increase to 7.48 million cases by 2050 without intervention.
Ibrahim M, He E, Tran D
… +2 more, Vundamati D, Grossman J
Best Pract Res Clin Rheumatol
· 2026 May · PMID 42097966
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Lupus nephritis (LN) is the most common visceral organ manifestation of systemic lupus erythematosus (SLE). It affects approximately 50% of SLE patients, accounting for significant morbidity and mortality especially in e...Lupus nephritis (LN) is the most common visceral organ manifestation of systemic lupus erythematosus (SLE). It affects approximately 50% of SLE patients, accounting for significant morbidity and mortality especially in ethnic minorities. Building on decades of landmark trials, the field has continued to evolve. The 2024 American College Rheumatology (ACR) Lupus Nephritis guideline represents an important shift toward earlier triple therapy. The guideline also recommends routine proteinuria screening and reaffirms kidney biopsy as the diagnostic gold standard. In parallel, urinary biomarkers are emerging as potential tools to better track infrarenal pathology. Furthermore, the therapeutic pipeline continues to expand with emerging strategies targeting B-cells, cytokine receptors, and co-stimulatory mechanisms. In this article, we review updates from the ACR guideline, the emerging data on urinary biomarkers, and highlight novel targeted therapies in LN.
OBJECTIVE: To characterize adult hospitalizations for eosinophilic granulomatosis with polyangiitis (EGPA) in the United States and identify clinical and sociodemographic factors independently associated with in‑hospital...OBJECTIVE: To characterize adult hospitalizations for eosinophilic granulomatosis with polyangiitis (EGPA) in the United States and identify clinical and sociodemographic factors independently associated with in‑hospital mortality. METHODS: We conducted a retrospective analysis of the National Inpatient Sample Database (2016-2022) to identify adult EGPA hospitalizations. Demographics, comorbidities, complications, insurance type, income quartile, length of stay, and total charges were compared between survivors and nonsurvivors. Variables with p ≤ 0.2 in univariable analysis were entered into multivariable logistic regression to determine independent predictors of in‑hospital death. RESULTS: Among 12,900 EGPA hospitalizations, 355 patients died (2.75%). Nonsurvivors were older, had longer hospitalizations, and incurred higher total hospital charges. In multivariable analysis, cardiac disease (OR: 1.94; 95% CI: 1.157-3.237), central nervous system (CNS) involvement (OR: 2.91; 95% CI: 1.004-8.453), gastrointestinal (GI) disease (OR: 3.05; 95% CI: 1.159-8.042), infection (OR: 3.87; 95% CI: 2.123-7.046), interstitial lung disease (OR: 2.62; 95% CI: 1.227-5.598), and renal disease (OR: 5.20; 95% CI: 2.784-9.708) were independently associated with in‑hospital mortality. Demographic and socioeconomic variables, including sex, race/ethnicity, insurance type, and income quartile, were not independent predictors of in-hospital death. CONCLUSIONS: In this nationally representative cohort, in‑hospital mortality for EGPA was 2.75%. Renal, infectious, cardiac, CNS, GI, and pulmonary complications were strongly associated with death. These findings underscore the need for early recognition and aggressive management of organ‑threatening disease and infection in hospitalized EGPA patients.
BACKGROUND: This study aimed to evaluate physical activity levels of children with Familial Mediterranean fever (FMF), and to compare these levels with age- and sex-matched healthy peers. A secondary aim was to investiga...BACKGROUND: This study aimed to evaluate physical activity levels of children with Familial Mediterranean fever (FMF), and to compare these levels with age- and sex-matched healthy peers. A secondary aim was to investigate associations between physical activity, acute phase reactants (APRs), and disease activity scores. METHODS: This cross-sectional study enrolled FMF patients aged 9-14 years and matched healthy controls. Disease activity was assessed using Pras scores, Auto-Inflammatory Diseases Activity Index (AIDAI), and International Severity Scoring System for FMF (ISSF). Physical activity was evaluated weekly using the Physical Activity Questionnaire for Children (PAQ-C) over three months. Correlations of PAQ-C scores with APRs and disease activity parameters were analyzed at multiple time points, and repeated-measures analyses were performed. RESULTS: Overall, 140 participants were included (70 in control group and 70 in patient group). The study group had significantly lower PAQ-C scores than controls (2.75±0.71 vs. 3.37±0.54; p<0.001). Patients with exercise-related leg pain had significantly lower PAQ-C scores than those without pain (2.54±0.60 vs. 2.99±0.76; p=0.007). A significant negative correlation was found between age and PAQ-C scores in the study group (r=-0.377, p=0.001). PAQ-C scores were negatively correlated with ISSF scores (r=-0.278, p=0.020 and r=-0.288, p=0.016) and the AIDAI scores (r=-0.305, p=0.010 and r=-0.396, p<0.001) at first and the third months. CONCLUSION: This study demonstrates that children with FMF have reduced physical activity, particularly those with exercise-induced leg pain. The decline with age may reflect increased disease awareness, emphasizing the need for monitoring and promoting safe physical engagement in disease management.
OBJECTIVE: Biological treatments have transformed juvenile idiopathic arthritis (JIA) outcomes, yet their availability and cost remain challenging. We investigated the impact of 2 different health care systems on the JIA...OBJECTIVE: Biological treatments have transformed juvenile idiopathic arthritis (JIA) outcomes, yet their availability and cost remain challenging. We investigated the impact of 2 different health care systems on the JIA disease course and outcomes. MATERIALS AND METHODS: JIA patients presenting to 2 tertiary centers in Türkiye and India between January 2014 and January 2025, with ≥1 year of follow-up, were enrolled. Systemic JIA (sJIA) patients were analyzed separately due to differing management and prognosis. Data at 6 months, 1, 2, 3, and 5 years if follow-up occurred, were obtained retrospectively. RESULTS: A total of 207 patients were enrolled: 15 sJIA and 129 non-sJIA from Türkiye, and 12 sJIA and 51 non-sJIA from India. Biological disease-modifying antirheumatic drugs (bDMARDs) were prescribed significantly more often in the Turkish cohort (46% vs. 23%, p=0.001). In contrast, systemic corticosteroid use was significantly higher in the Indian cohort (26% vs. 69%, p=0.001). Initial remission was achieved more rapidly in the Turkish cohort (median month 2 vs. 4, p<0.001), and the number of patients with active joints and elevated acute-phase reactants was consistently higher in the Indian cohort throughout all follow-up periods. CONCLUSIONS: Universal health care coverage was associated with early initiation and sustained use of bDMARDs, leading to more rapid control of disease activity. In contrast, when bDMARDs were unavailable, physicians were forced to rely more heavily on systemic corticosteroids. Interestingly, JIA-related complications such as chronic joint involvement and uveitis did not significantly differ between the Turkish and Indian cohorts, possibly due to differences in ethnic and disease characteristics, survivor bias, and the limited number of patients with such complications.
OBJECTIVE: This study assessed the predictive value of TURPAID and PREDICT-crFMF scores at diagnosis for FMF50 response at the sixth month in children with Familial Mediterranean Fever (FMF) and examined their associatio...OBJECTIVE: This study assessed the predictive value of TURPAID and PREDICT-crFMF scores at diagnosis for FMF50 response at the sixth month in children with Familial Mediterranean Fever (FMF) and examined their associations with disease-activity indices and acute-phase reactants. METHODS: Children newly diagnosed with FMF according to the Eurofever/PRINTO criteria and who received colchicine treatment for at least 6 months were included. Clinical and laboratory data were retrospectively obtained from electronic medical records. Treatment response was evaluated at the 6-month follow-up visit. RESULTS: Overall, 168 children with FMF (50.6% female) were included. FMF50 response at 6 months was achieved in 64.8% of patients. PREDICT-crFMF and TURPAID scores were significantly higher in non-responders than in responders (p < 0.001 for both). Higher PREDICT-crFMF (aOR 1.240, 95% CI 1.113-1.382, p < 0.001) and TURPAID (aOR 2.009, 95% CI 1.384-2.916, p < 0.001) scores, and M694V homozygosity (aOR 3.390, 95% CI 1.700-6.760, p < 0.001) independently predicted FMF50 nonresponse. Both scores showed significant discrimination (AUC = 0.685 for PREDICT-crFMF; 0.670 for TURPAID; p < 0.001). Optimal cut-offs were ≥ 3 for PREDICT-crFMF (sensitivity 67.8%, specificity 69.7%) and > 1.5 for TURPAID (sensitivity 76.3%, specificity 54.1%). PREDICT-crFMF scores correlated with erythrocyte sedimentation rate (ESR), serum amyloid A, and disease activity indices, but not Mor score; TURPAID scores correlated with ESR and all evaluated disease activity indices. CONCLUSION: Early assessment of PREDICT-crFMF and TURPAID scores at diagnosis may help identify FMF patients at risk for colchicine resistance. Key Points • This is the first study to evaluate PREDICT-crFMF and TURPAID scores together using FMF50 as the treatment-response outcome in children with FMF. • Higher PREDICT-crFMF and higher TURPAID scores at diagnosis independently predicted failure to achieve FMF50 response at 6 months. • The significant associations of these scores with disease activity indices and inflammatory markers support their value in reflecting early inflammatory burden.
Best Pract Res Clin Rheumatol
· 2026 Mar · PMID 42086376
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Immune checkpoint inhibitors (ICI) used for the treatment of cancer can cause immune related adverse events (irAEs) when immune activation affects non-tumor tissues. Rheumatologists care for patients with a variety of rh...Immune checkpoint inhibitors (ICI) used for the treatment of cancer can cause immune related adverse events (irAEs) when immune activation affects non-tumor tissues. Rheumatologists care for patients with a variety of rheumatic irAEs; these included inflammatory arthritis (ICI-IA), polymyalgia rheumatica (ICI-PMR), and myositis (ICI-myositis) among others. Rheumatic irAEs are commonly impactful on patients' quality of life and function and sometimes can cause significant morbidity and mortality. This review will highlight the diagnosis and assessment of rheumatic irAEs. Then treatment for individual irAEs will be discussed in depth with considerations to supportive care, corticosteroid dosing and tapering, steroid sparing immunosuppression and monitoring. Finally, the safety of immunosuppression as it relates to tumor outcomes and considerations by oncologists when selecting ICI therapy will be reviewed.
Lyu X, Jahed V, Ding W
… +7 more, Sun X, Jamous R, Zheng J, Sabouri Z, Heiss C, Anees H, El Khassawna T
Clin Rheumatol
· 2026 Jun · PMID 42084706
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BACKGROUND: Gout is one of the most common inflammatory arthritides and represents a growing health burden worldwide. This study compares the disease burden of gout and its attributable risk factors between China and Eur...BACKGROUND: Gout is one of the most common inflammatory arthritides and represents a growing health burden worldwide. This study compares the disease burden of gout and its attributable risk factors between China and European Union (EU) countries from 1990 to 2023 using data from the Global Burden of Disease Study 2023 (GBD 2023). In addition, the study evaluates potential causal relationships between key risk factors and gout and projects future trends in disease burden. METHODS: Using GBD 2023 data, we analyzed the epidemiology of gout in China and EU countries. Analyses included descriptive statistics and age- and sex-specific comparisons. Joinpoint regression models were used to calculate annual percentage changes (APC) and average annual percentage changes (AAPC) to assess long-term trends. An autoregressive integrated moving average (ARIMA) model was applied to project gout burden trends in China and EU countries from 2024 to 2040. In addition, a two-sample Mendelian randomization (MR) approach was used to investigate the potential causal relationship between key risk factors and gout at the genetic level. RESULTS: In 2023, China's age-standardized incidence rate (ASIR), prevalence rate (ASPR), and disability-adjusted life year rate (ASDR) for gout were 151.27/100,000, 809.69/100,000, and 25.14/100,000, respectively, all higher than in 1990. In comparison, EU countries showed lower levels for these indicators in both 1990 and 2023. Joinpoint regression analysis demonstrated an overall increasing trend in gout burden in both China and the EU between 1990 and 2023, although China experienced a brief decline in APC between 1990 and 1994. The burden of gout was higher among males than among females. Projections suggest that ASIR, ASPR, and ASDR will continue to increase in both China and European countries between 2024 and 2040. Mendelian randomization analysis further indicated a significant positive causal relationship between body mass index (BMI) and gout. CONCLUSION: This study combines GBD 2023 epidemiological data with Mendelian randomization analysis to characterize trends in the burden of gout in China and EU countries. The findings show a continuing increase in gout burden over time, particularly in China. The identified causal association between elevated BMI and gout highlights the importance of addressing modifiable metabolic risk factors to help reduce the future burden of gout. Key Points • An increasing burden of gout could be observed in China and the European Union from 1990 to 2023. • A higher age-standardized burden of gout was observed in China than in the European Union. • Future projections indicate that the burden of gout will continue to increase through 2040. • A causal association between elevated body mass index and gout risk was supported by Mendelian randomization analysis.
A 36-year-old female patient, previously diagnosed with psoriatic arthritis and initially unresponsive to multiple treatments, experienced a subsequent asymptomatic period before developing new symptoms, including limite...A 36-year-old female patient, previously diagnosed with psoriatic arthritis and initially unresponsive to multiple treatments, experienced a subsequent asymptomatic period before developing new symptoms, including limited right-sided inflammatory lumbosacral pain and pustules on her palms and soles. Magnetic resonance imaging revealed changes consistent with osteitis. These findings prompted a reassessment of her condition, leading to a revised diagnosis of SAPHO syndrome.
BACKGROUND: Rheumatoid arthritis (RA)-related lesions, including synovitis and rheumatoid nodules, may mimic musculoskeletal tumors and cause diagnostic uncertainty. This study aimed to characterize clinical features tha...BACKGROUND: Rheumatoid arthritis (RA)-related lesions, including synovitis and rheumatoid nodules, may mimic musculoskeletal tumors and cause diagnostic uncertainty. This study aimed to characterize clinical features that distinguish true tumors from tumor-like lesions in RA patients referred for suspected bone or soft tissue tumors. METHODS: We retrospectively reviewed 70 RA patients evaluated between September 2009 and February 2025 for suspected musculoskeletal tumors. Patients were categorized as (1) newly diagnosed RA with tumor-like lesions (n=27), (2) established RA with tumor-like lesions (n=20), and (3) established RA with true tumors (n=23). Clinical characteristics, MRI findings, and histologic results were assessed. Logistic regression was used to identify factors associated with tumor diagnosis. RESULTS: Patients with true tumors were older (median 69 vs. 55 y, p<0.01) and more likely to have extra-articular lesions (96% vs. 28%, p<0.01). Synovitis-like MRI patterns-low-to-intermediate T1 and heterogeneous high T2 signals-were seen in 83% of tumor-like lesions but in only 43% of true tumors. Histologic confirmation was performed in 56% of all cases (74% of tumors vs. 47% of tumor-like lesions, p=0.03). Multivariate analysis suggested that older age (OR: 1.13, 95% CI: 1.04-1.23) and extra-articular location (OR: 434.86, 95% CI: 9.44-20,035.22) were associated with tumor diagnosis. CONCLUSIONS: Among RA patients evaluated for suspected musculoskeletal tumors, older age and extra-articular lesion location were associated with true tumor diagnosis, although the estimates showed wide confidence intervals. MRI features alone were insufficient for reliable differentiation, underscoring the continued need for histologic confirmation to ensure accurate and timely diagnosis.
INTRODUCTION: Objectives. Hip fracture is a major cause of disability and death among older adults. Arthritis is a common chronic condition that may influence fracture risk through changes in bone health, mobility limita...INTRODUCTION: Objectives. Hip fracture is a major cause of disability and death among older adults. Arthritis is a common chronic condition that may influence fracture risk through changes in bone health, mobility limitation, and falls. However, the association between arthritis duration and hip fracture risk in the Chinese population remains unclear. METHODS: Data were obtained from 9433 participants aged > 45 years in the China Health and Retirement Longitudinal Study (CHARLS). Individuals with prior hip fractures or missing key information on arthritis status or covariates were excluded. Participants were categorized by self-reported arthritis duration into four groups: none, ≤ 3 years, 4-6 years, and > 6 years. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for hip fracture risk across duration groups, adjusted for demographic characteristics, lifestyle factors, and comorbid conditions. Trend tests, Kaplan-Meier analyses, and subgroup and sensitivity analyses were performed to assess the robustness of the results. RESULTS: During nine years of follow-up, 372 hip fractures were recorded. Participants with arthritis had a higher risk of hip fracture than those without arthritis (HR 1.59, 95% CI 1.24-2.05). By arthritis duration, the hazard ratios were 1.59 (95% CI 1.11-2.28) for ≤ 3 years, 1.83 (95% CI 1.20-2.78) for 4-6 years, and 1.53 (95% CI 1.15-2.04) for > 6 years, with a significant trend across duration categories (P for trend < 0.01). Subgroup and sensitivity analyses showed consistent results. CONCLUSIONS: Self-reported arthritis was associated with an increased risk of hip fracture among Chinese adults aged > 45 years. The association varied across arthritis duration categories, with a relatively higher estimate observed in the 4-6-year group. Further studies are needed to clarify whether this pattern reflects differences in arthritis subtype, disease severity, treatment, or other unmeasured factors. Key Points • In this nationally representative cohort of Chinese adults aged >45 years, self-reported arthritis was associated with a higher risk of hip fracture. • The association varied across arthritis duration categories, with a relatively higher estimate observed in the 4-6-year group. • Further studies are needed to clarify the factors underlying this duration-specific pattern.