{"title":"Interleukin (IL)‐5, Eosinophils and IL‐5 Pathway Inhibitors in Eosinophilic Granulomatosis with Polyangiitis.","authors":"Alvise Berti, Christian Pagnoux","doi":"10.1002/art.43409","DOIUrl":"https://doi.org/10.1002/art.43409","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"54 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ji Soo Kim,Rachel S Wallwork,Carrie Richardson,Adrianne Woods,Monica Mukherjee,Steven Hsu,Julie J Paik,Christopher A Mecoli,Laura K Hummers,Fredrick M Wigley,Scott L Zeger,Ami A Shah
BACKGROUNDCardiac involvement in systemic sclerosis (SSc) is a leading cause of death. We sought to investigate predictors of incident left ventricular systolic dysfunction (LVSD) and cardiac recovery in SSc.METHODS2,303 patients in the Johns Hopkins Scleroderma Center Research Registry and 13,209 echocardiograms were analyzed. We identified predictors associated with incident LVSD defined by transitions in left ventricular (LV) ejection fraction (EF) states (EF≥50% declining to <50% and EF>35% dropping to ≤35% [severe LVSD]) by fitting multivariate logistic regression models with time-varying and invariant variables. Variables associated with cardiac recovery were identified by fitting multivariate logistic regression models using important variables identified from random forest analysis.RESULTSMale sex, Black race, diffuse skin disease, higher mRSS, echocardiographic evidence of pulmonary hypertension (PH), kidney disease, and atrial fibrillation (AFib) were associated with increased odds of incident LVSD (EF<50%), while anti-centromere and anti-topoisomerase-1 were protective. Male sex, higher mRSS, PH, skeletal myopathy, kidney disease, AFib, and anti-Ku antibodies were associated with higher odds of incident severe LVSD (EF≤35%). For previous EF<50%, tendon friction rubs were associated with lower odds of cardiac recovery, and anti-RNA polymerase III (POLR3) with higher odds. For previous EF≤35%, diabetes was associated with lower odds of recovering to EF>35%.CONCLUSIONSDistinct demographic, SSc-specific and cardiac characteristics associate with increased risk of incident LVSD in SSc, with skeletal myopathy and anti-Ku antibodies being important risk factors for severe disease. Some patients improve, which is more likely in anti-POLR3-positive patients.
{"title":"Identification of risk factors for incident left ventricular systolic dysfunction and predictors of cardiac recovery in patients with systemic sclerosis.","authors":"Ji Soo Kim,Rachel S Wallwork,Carrie Richardson,Adrianne Woods,Monica Mukherjee,Steven Hsu,Julie J Paik,Christopher A Mecoli,Laura K Hummers,Fredrick M Wigley,Scott L Zeger,Ami A Shah","doi":"10.1002/art.43408","DOIUrl":"https://doi.org/10.1002/art.43408","url":null,"abstract":"BACKGROUNDCardiac involvement in systemic sclerosis (SSc) is a leading cause of death. We sought to investigate predictors of incident left ventricular systolic dysfunction (LVSD) and cardiac recovery in SSc.METHODS2,303 patients in the Johns Hopkins Scleroderma Center Research Registry and 13,209 echocardiograms were analyzed. We identified predictors associated with incident LVSD defined by transitions in left ventricular (LV) ejection fraction (EF) states (EF≥50% declining to <50% and EF>35% dropping to ≤35% [severe LVSD]) by fitting multivariate logistic regression models with time-varying and invariant variables. Variables associated with cardiac recovery were identified by fitting multivariate logistic regression models using important variables identified from random forest analysis.RESULTSMale sex, Black race, diffuse skin disease, higher mRSS, echocardiographic evidence of pulmonary hypertension (PH), kidney disease, and atrial fibrillation (AFib) were associated with increased odds of incident LVSD (EF<50%), while anti-centromere and anti-topoisomerase-1 were protective. Male sex, higher mRSS, PH, skeletal myopathy, kidney disease, AFib, and anti-Ku antibodies were associated with higher odds of incident severe LVSD (EF≤35%). For previous EF<50%, tendon friction rubs were associated with lower odds of cardiac recovery, and anti-RNA polymerase III (POLR3) with higher odds. For previous EF≤35%, diabetes was associated with lower odds of recovering to EF>35%.CONCLUSIONSDistinct demographic, SSc-specific and cardiac characteristics associate with increased risk of incident LVSD in SSc, with skeletal myopathy and anti-Ku antibodies being important risk factors for severe disease. Some patients improve, which is more likely in anti-POLR3-positive patients.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"1 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Disease-specific mortality statistics are useful measures of disease burden. Population-based studies from a few United States counties have reported mortality in systemic autoimmune diseases (SAID). However, due to substantial differences in the population structure of these counties as well as relatively small numbers of SAID deaths in these counties, it is difficult to extrapolate their findings to assess the SAIDs' national burden. In this regard, national mortality databases offer a large reference population, which is hard to assemble in individual SAIDs. However, two concerns are persistently raised regarding mortality databases for SAIDs: misclassification and under-recording. While misclassification of SAIDs is common in health records and administrative databases, it appears to be rare on death certificates among decedents that did not have a SAID. However, SAIDs are under-recorded in death certificates. The under-recording of SAIDs does not differ by sex and race/ethnicity, but it is common in elderly that die of cardiovascular diseases, neoplasms, and chronic obstructive pulmonary disease. SAIDs' under-recording may occur, because it may be difficult to assign a specific SAID manifestation or treatment complication responsible for death. Furthermore, a SAID is commonly listed as a contributing cause, rather than as the underlying cause of death, on death certificates, which advocates using the multiple-causes-of-death database for SAIDs. Nevertheless, until we have large-scale prospective outcomes data, mortality data from the National Vital Statistics System offer the valuable estimates of SAIDs' national burden, which can be used for setting research priorities, healthcare policy planning, resource allocation, and precision public health.
{"title":"National Mortality Databases to Assess Disease Burden in Systemic Autoimmune Diseases: A Valuable Resource, But with Limitations.","authors":"Ram Raj Singh","doi":"10.1002/art.43410","DOIUrl":"https://doi.org/10.1002/art.43410","url":null,"abstract":"Disease-specific mortality statistics are useful measures of disease burden. Population-based studies from a few United States counties have reported mortality in systemic autoimmune diseases (SAID). However, due to substantial differences in the population structure of these counties as well as relatively small numbers of SAID deaths in these counties, it is difficult to extrapolate their findings to assess the SAIDs' national burden. In this regard, national mortality databases offer a large reference population, which is hard to assemble in individual SAIDs. However, two concerns are persistently raised regarding mortality databases for SAIDs: misclassification and under-recording. While misclassification of SAIDs is common in health records and administrative databases, it appears to be rare on death certificates among decedents that did not have a SAID. However, SAIDs are under-recorded in death certificates. The under-recording of SAIDs does not differ by sex and race/ethnicity, but it is common in elderly that die of cardiovascular diseases, neoplasms, and chronic obstructive pulmonary disease. SAIDs' under-recording may occur, because it may be difficult to assign a specific SAID manifestation or treatment complication responsible for death. Furthermore, a SAID is commonly listed as a contributing cause, rather than as the underlying cause of death, on death certificates, which advocates using the multiple-causes-of-death database for SAIDs. Nevertheless, until we have large-scale prospective outcomes data, mortality data from the National Vital Statistics System offer the valuable estimates of SAIDs' national burden, which can be used for setting research priorities, healthcare policy planning, resource allocation, and precision public health.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"125 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shreya Billa,Sho Fukui,Misti L Paudel,Takahiro Suzuki,Ryosuke Imai,Yuntae Kim,Takehiro Nakai,Hiromichi Tamaki,Mitsumasa Kishimoto,Hilde S Ørbo,Sara K Tedeschi,Hyon K Choi,Masato Okada,Daniel H Solomon
OBJECTIVESHyperuricemia (HU) and gout are common in post-menopausal women. We aimed to identify the longitudinal changes in serum urate (SU) levels during and after the menopausal transition and its interaction with coexisting SU-modifying conditions.METHODSThis longitudinal study included Japanese women who underwent annual medical examinations from April 2004 to September 2024 and had at least one visit before and after self-reported menopause. Menopausal transition stages were categorized into pre-menopause, peri-menopause (5 years prior to and up to the menopause), and post-menopause. Longitudinal changes in SU and HU (SU ≥6.8 mg/dL or taking medications for gout/HU) were examined by interrupted time-series analyses and evaluated across stratified subgroups.RESULTSWe analyzed 8,169 eligible participants with 93,511 visits over a median follow-up of 13.8 years. SU levels gradually increased during pre-menopause, rose sharply over peri-menopause, and stabilized in post-menopause. Compared to pre-menopause, the mean SU level was 0.41 mg/dL (95% CI: 0.38, 0.43) higher in post-menopause. HU prevalence increased from <1.0% during pre-menopause to 4-5% during post-menopause. Compared to pre-menopause, the associations of a low estimated glomerular filtration rate (<60 mL/min/1.73 m2) and a high body mass index (≥25 kg/m2) with HU were greater in post-menopause; HU was observed in approximately 18% of overweight or obese women at menopause.CONCLUSIONSSU levels rapidly increase during peri-menopause and are already elevated by the time of menopause. Maintaining a normal body weight and preserving kidney function prior to menopause may decrease postmenopausal HU and potentially prevent subsequent gout in women.
{"title":"Longitudinal Changes in Serum Urate Levels from Pre-menopause through Post-menopause: Interrupted Time-Series Analyses.","authors":"Shreya Billa,Sho Fukui,Misti L Paudel,Takahiro Suzuki,Ryosuke Imai,Yuntae Kim,Takehiro Nakai,Hiromichi Tamaki,Mitsumasa Kishimoto,Hilde S Ørbo,Sara K Tedeschi,Hyon K Choi,Masato Okada,Daniel H Solomon","doi":"10.1002/art.43406","DOIUrl":"https://doi.org/10.1002/art.43406","url":null,"abstract":"OBJECTIVESHyperuricemia (HU) and gout are common in post-menopausal women. We aimed to identify the longitudinal changes in serum urate (SU) levels during and after the menopausal transition and its interaction with coexisting SU-modifying conditions.METHODSThis longitudinal study included Japanese women who underwent annual medical examinations from April 2004 to September 2024 and had at least one visit before and after self-reported menopause. Menopausal transition stages were categorized into pre-menopause, peri-menopause (5 years prior to and up to the menopause), and post-menopause. Longitudinal changes in SU and HU (SU ≥6.8 mg/dL or taking medications for gout/HU) were examined by interrupted time-series analyses and evaluated across stratified subgroups.RESULTSWe analyzed 8,169 eligible participants with 93,511 visits over a median follow-up of 13.8 years. SU levels gradually increased during pre-menopause, rose sharply over peri-menopause, and stabilized in post-menopause. Compared to pre-menopause, the mean SU level was 0.41 mg/dL (95% CI: 0.38, 0.43) higher in post-menopause. HU prevalence increased from <1.0% during pre-menopause to 4-5% during post-menopause. Compared to pre-menopause, the associations of a low estimated glomerular filtration rate (<60 mL/min/1.73 m2) and a high body mass index (≥25 kg/m2) with HU were greater in post-menopause; HU was observed in approximately 18% of overweight or obese women at menopause.CONCLUSIONSSU levels rapidly increase during peri-menopause and are already elevated by the time of menopause. Maintaining a normal body weight and preserving kidney function prior to menopause may decrease postmenopausal HU and potentially prevent subsequent gout in women.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"126 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fangying Wu,Zihan Yang,Yanwen Sheng,Xinyi Xu,Mingchun Yang
{"title":"Is Serum Uric Acid a Mere Bystander or an Active Player in Osteoarthritis Pathogenesis?","authors":"Fangying Wu,Zihan Yang,Yanwen Sheng,Xinyi Xu,Mingchun Yang","doi":"10.1002/art.43407","DOIUrl":"https://doi.org/10.1002/art.43407","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"57 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sjögren disease (SjD) is a common systemic autoimmune disorder characterized by inflammation of the exocrine glands, resulting in dryness. Patients frequently exhibit extraglandular manifestations affecting various organ systems. To date, there are no FDA-approved disease-modifying therapies for SjD. In this review, we explore the expanding field of SjD endotyping as a tool to enhance patient stratification, prognostication, and clinical decision-making. SjD endotypes driven by heightened B cell activity are linked to increased lymphoma risk. B cells play a central role in SjD pathogenesis by producing autoantibodies, presenting antigens, and releasing pro-inflammatory cytokines. These functions contribute not only to autoimmunity but also to lymphomatous transformation. We illustrate these concepts through the case of a patient with SjD who developed parotid MALT lymphoma after years of recurrent glandular swelling-highlighting a common yet challenging scenario for practicing rheumatologists. Using this case as a framework, we examine the pathobiology of B cells in SjD that drive autoreactivity and lymphomagenesis. Finally, we review emerging B cell-targeted therapies that reflect a broader shift in the SjD treatment landscape from symptomatic management to targeted therapies grounded in disease immunopathology.
{"title":"Sjögren Disease-B Cells at the Brink: From Autoimmunity to Lymphomagenesis and the Rise of Novel B Cell-Targeted Therapies.","authors":"Rachael A Gordon,Sara S McCoy","doi":"10.1002/art.43404","DOIUrl":"https://doi.org/10.1002/art.43404","url":null,"abstract":"Sjögren disease (SjD) is a common systemic autoimmune disorder characterized by inflammation of the exocrine glands, resulting in dryness. Patients frequently exhibit extraglandular manifestations affecting various organ systems. To date, there are no FDA-approved disease-modifying therapies for SjD. In this review, we explore the expanding field of SjD endotyping as a tool to enhance patient stratification, prognostication, and clinical decision-making. SjD endotypes driven by heightened B cell activity are linked to increased lymphoma risk. B cells play a central role in SjD pathogenesis by producing autoantibodies, presenting antigens, and releasing pro-inflammatory cytokines. These functions contribute not only to autoimmunity but also to lymphomatous transformation. We illustrate these concepts through the case of a patient with SjD who developed parotid MALT lymphoma after years of recurrent glandular swelling-highlighting a common yet challenging scenario for practicing rheumatologists. Using this case as a framework, we examine the pathobiology of B cells in SjD that drive autoreactivity and lymphomagenesis. Finally, we review emerging B cell-targeted therapies that reflect a broader shift in the SjD treatment landscape from symptomatic management to targeted therapies grounded in disease immunopathology.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"4 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sharon Dowell,Brittany Banbury,Christopher Jenkins,Emily E Holladay,Fenglong Xie,Jingyi Zhang,Grace C Wright,Jeffrey R Curtis,Gail S Kerr
OBJECTIVETo evaluate the association of neighborhood deprivation and structural barriers with disease burden in racial and ethnic subsets of patients with psoriatic arthritis (PsA).METHODSPsA patients in the ACR RISE registry with reported race, region, and ≥3 years of follow-up, were evaluated. Demographic factors, disease activity measures, social deprivation, defined by the area deprivation index (ADI) and therapeutic agents were stratified by race. Subgroup analyses were conducted to examine demographic and clinical characteristics across residential areas graded by the Home Owners' Loan Corporation (HOLC), from 'Best' (HOLC 1 - predominantly White residents) to 'Hazardous' (HOLC 4 or redlined - predominantly Black residents) based on investment risk.RESULTSThe cohort included 21,429 predominantly female (57.7%), obese (56.1% BMI>30) PsA patients with median age 55 (12.8) years. High social deprivation was prevalent among Black patients (25.7 % vs. 2.3% Asian, 12.5% White and 17.3% Other), as was High Disease Activity (HDA, 40.2% vs. 25.8% Asian, 29.6% White, and 33.5% Other). Approximately 7% of PsA patients lived in HOLC-graded districts. Smoking, obesity, high social deprivation, federal insurance and HDA were more prevalent in patients in HOLC 4 areas compared to HOLC 1 areas. HOLC 4 patients also had longer median [IQR] periods of HDA (105.0 [0, 690] person-days) and fewer days in remission (1.0 [0, 5457] person-days).CONCLUSIONIn the US, Black PsA patients have prevalent HDA and high social deprivation. Additionally, the enduring effects of structural racism appear to negatively influence PsA disease characteristics of patients living in historically redlined areas.
{"title":"The Influence of Race, Ethnicity and Historical Redlining on Psoriatic Disease Burden and Clinical Outcomes.","authors":"Sharon Dowell,Brittany Banbury,Christopher Jenkins,Emily E Holladay,Fenglong Xie,Jingyi Zhang,Grace C Wright,Jeffrey R Curtis,Gail S Kerr","doi":"10.1002/art.43397","DOIUrl":"https://doi.org/10.1002/art.43397","url":null,"abstract":"OBJECTIVETo evaluate the association of neighborhood deprivation and structural barriers with disease burden in racial and ethnic subsets of patients with psoriatic arthritis (PsA).METHODSPsA patients in the ACR RISE registry with reported race, region, and ≥3 years of follow-up, were evaluated. Demographic factors, disease activity measures, social deprivation, defined by the area deprivation index (ADI) and therapeutic agents were stratified by race. Subgroup analyses were conducted to examine demographic and clinical characteristics across residential areas graded by the Home Owners' Loan Corporation (HOLC), from 'Best' (HOLC 1 - predominantly White residents) to 'Hazardous' (HOLC 4 or redlined - predominantly Black residents) based on investment risk.RESULTSThe cohort included 21,429 predominantly female (57.7%), obese (56.1% BMI>30) PsA patients with median age 55 (12.8) years. High social deprivation was prevalent among Black patients (25.7 % vs. 2.3% Asian, 12.5% White and 17.3% Other), as was High Disease Activity (HDA, 40.2% vs. 25.8% Asian, 29.6% White, and 33.5% Other). Approximately 7% of PsA patients lived in HOLC-graded districts. Smoking, obesity, high social deprivation, federal insurance and HDA were more prevalent in patients in HOLC 4 areas compared to HOLC 1 areas. HOLC 4 patients also had longer median [IQR] periods of HDA (105.0 [0, 690] person-days) and fewer days in remission (1.0 [0, 5457] person-days).CONCLUSIONIn the US, Black PsA patients have prevalent HDA and high social deprivation. Additionally, the enduring effects of structural racism appear to negatively influence PsA disease characteristics of patients living in historically redlined areas.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"16 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Old techniques still have relevance in personalised predictive medicine.","authors":"Kristina E N Clark,Christopher P Denton","doi":"10.1002/art.43402","DOIUrl":"https://doi.org/10.1002/art.43402","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"68 21-22 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145133908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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