Pub Date : 2025-11-07DOI: 10.1038/s41584-025-01325-7
Jessica McHugh
A new population-based study suggests that sodium–glucose cotransporter-2 (SGLT2) inhibitors — originally developed for glycaemic control — reduce the risk of autoimmune rheumatic diseases.
{"title":"SGLT2 inhibitors reduce risk of autoimmune disease","authors":"Jessica McHugh","doi":"10.1038/s41584-025-01325-7","DOIUrl":"10.1038/s41584-025-01325-7","url":null,"abstract":"A new population-based study suggests that sodium–glucose cotransporter-2 (SGLT2) inhibitors — originally developed for glycaemic control — reduce the risk of autoimmune rheumatic diseases.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 12","pages":"698-698"},"PeriodicalIF":32.7,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145455474","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}
Pub Date : 2025-11-07DOI: 10.1038/s41584-025-01318-6
Benjamin Klein, Allison C. Billi, Lisa Abernathy-Close, J. Michelle Kahlenberg
Cutaneous lupus erythematosus (CLE) is a complex inflammatory skin disease that presents either in isolation or as a frequent manifestation of systemic lupus erythematosus (SLE). CLE subtypes show clinical heterogeneity and varying associations with SLE. Histologically, CLE is characterized by interface dermatitis, a reaction pattern that involves immune-cell infiltration of the dermo-epidermal junction. In-depth characterization of both non-lesional and lesional lupus skin has reshaped our understanding of pathogenesis. Non-lesional and lesional lupus skin exhibits early and chronic upregulation of type I interferons, which drive photosensitivity, myeloid-cell recruitment and amplification of cytokine responses in both immune and non-immune cells. This detailed understanding of CLE biology has enabled the development of targeted therapies. Ongoing research to identify key pathogenic mechanisms will create opportunities for prevention of CLE and CLE-to-SLE transition. This Review discusses latest advances in the field of cutaneous lupus, including the improved understanding of disease pathogenesis and emerging targeted therapies.
{"title":"Cutaneous lupus erythematosus — from pathogenesis to targeted therapy","authors":"Benjamin Klein, Allison C. Billi, Lisa Abernathy-Close, J. Michelle Kahlenberg","doi":"10.1038/s41584-025-01318-6","DOIUrl":"10.1038/s41584-025-01318-6","url":null,"abstract":"Cutaneous lupus erythematosus (CLE) is a complex inflammatory skin disease that presents either in isolation or as a frequent manifestation of systemic lupus erythematosus (SLE). CLE subtypes show clinical heterogeneity and varying associations with SLE. Histologically, CLE is characterized by interface dermatitis, a reaction pattern that involves immune-cell infiltration of the dermo-epidermal junction. In-depth characterization of both non-lesional and lesional lupus skin has reshaped our understanding of pathogenesis. Non-lesional and lesional lupus skin exhibits early and chronic upregulation of type I interferons, which drive photosensitivity, myeloid-cell recruitment and amplification of cytokine responses in both immune and non-immune cells. This detailed understanding of CLE biology has enabled the development of targeted therapies. Ongoing research to identify key pathogenic mechanisms will create opportunities for prevention of CLE and CLE-to-SLE transition. This Review discusses latest advances in the field of cutaneous lupus, including the improved understanding of disease pathogenesis and emerging targeted therapies.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 12","pages":"703-718"},"PeriodicalIF":32.7,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145455476","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}
Pub Date : 2025-11-06DOI: 10.1038/s41584-025-01319-5
Manju Chandran, Jotheeswaran A. Thiyagarajan, Majed Alokail, Olivier Bruyère, Nicholas C. Harvey, Rene Rizzoli, Nicola Veronese, Jean-Yves Reginster
Hip fractures cause major morbidity, mortality and long-term disability among older persons worldwide. The World Health Organization has defined two key indicators within the framework of the UN Decade of Healthy Ageing to measure health system performance in providing care for older adults with hip fractures: the proportion who receive surgery within 48 h of fracture; and the proportion who receive pharmacological treatment for osteoporosis post-fracture. This Perspective article, which describes the clinical importance of these indicators, their amenability for adoption and implications for health equity, is based on findings from audits, guidelines and key literature. Numerous evidence-based solutions — for example, fracture liaison services, orhtogeriatric care models and digital tools support hip-fracture management, yet major barriers remain, such as data gaps, system preparedness and pathway variability. New or modified policies developed by national governments, ministries of health and other relevant authorities and tailored to specific geopolitical contexts are urgently needed to enable the implementation of timely surgical care and secondary fracture prevention strategies aligned with the WHO indicators. Improved health information systems to measure performance and to ensure translation to real-world changes in the lives of older people worldwide are of paramount importance. Within the framework of the UN Decade of Healthy Ageing, the World Health Organization has defined core indicators focused on timely hip-fracture management and secondary fracture prevention in people 60 years of age and over. This Perspective article examines the relevance and implementation of these indicators, and the implications of their adoption for equitable care of older people worldwide.
{"title":"WHO benchmarks for equitable hip-fracture care and osteoporosis treatment in older people","authors":"Manju Chandran, Jotheeswaran A. Thiyagarajan, Majed Alokail, Olivier Bruyère, Nicholas C. Harvey, Rene Rizzoli, Nicola Veronese, Jean-Yves Reginster","doi":"10.1038/s41584-025-01319-5","DOIUrl":"10.1038/s41584-025-01319-5","url":null,"abstract":"Hip fractures cause major morbidity, mortality and long-term disability among older persons worldwide. The World Health Organization has defined two key indicators within the framework of the UN Decade of Healthy Ageing to measure health system performance in providing care for older adults with hip fractures: the proportion who receive surgery within 48 h of fracture; and the proportion who receive pharmacological treatment for osteoporosis post-fracture. This Perspective article, which describes the clinical importance of these indicators, their amenability for adoption and implications for health equity, is based on findings from audits, guidelines and key literature. Numerous evidence-based solutions — for example, fracture liaison services, orhtogeriatric care models and digital tools support hip-fracture management, yet major barriers remain, such as data gaps, system preparedness and pathway variability. New or modified policies developed by national governments, ministries of health and other relevant authorities and tailored to specific geopolitical contexts are urgently needed to enable the implementation of timely surgical care and secondary fracture prevention strategies aligned with the WHO indicators. Improved health information systems to measure performance and to ensure translation to real-world changes in the lives of older people worldwide are of paramount importance. Within the framework of the UN Decade of Healthy Ageing, the World Health Organization has defined core indicators focused on timely hip-fracture management and secondary fracture prevention in people 60 years of age and over. This Perspective article examines the relevance and implementation of these indicators, and the implications of their adoption for equitable care of older people worldwide.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 1","pages":"62-70"},"PeriodicalIF":32.7,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41584-025-01319-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145447524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-06DOI: 10.1038/s41584-025-01309-7
Amr H. Sawalha, Durga P. Misra, Ruchika Goel, Fatma Alibaz-Oner, Kaitlin A. Quinn, Peter C. Grayson, Haner Direskeneli
Takayasu arteritis (TAK) is a rare, chronic, large-vessel vasculitis that primarily targets the aorta and its major branches, leading to vascular stenosis, occlusion and aneurysm formation. TAK, which is characterized by granulomatous inflammation of the arterial wall, predominantly affects women, with peak onset typically occurring between 20 and 40 years of age. The disease exhibits substantial geographic variability in prevalence, with emerging evidence suggesting that these differences are partly owing to variations in genetic susceptibility loci, particularly within immune-related genes; however, the role of environmental factors in the disease aetiology remains poorly understood. Non-invasive imaging techniques have become central to both diagnosis and disease monitoring. Furthermore, the development of biomarkers holds promise for more accurate assessment of disease activity. The management of TAK is evolving, driven by an improved understanding of disease pathogenesis. The growing use of biologic agents is providing new treatment options, particularly for patients with refractory or relapsing disease. By integrating these developments, this Review is aimed at serving as a comprehensive resource for clinicians and researchers dedicated to improving the understanding and management of TAK. This Review article provides an update on the pathophysiology, diagnosis and treatment of Takayasu arteritis. The authors emphasize the need for a multidisciplinary approach to the diagnosis and management of this complex disease.
{"title":"Advances in the pathophysiology, diagnosis and treatment of Takayasu arteritis","authors":"Amr H. Sawalha, Durga P. Misra, Ruchika Goel, Fatma Alibaz-Oner, Kaitlin A. Quinn, Peter C. Grayson, Haner Direskeneli","doi":"10.1038/s41584-025-01309-7","DOIUrl":"10.1038/s41584-025-01309-7","url":null,"abstract":"Takayasu arteritis (TAK) is a rare, chronic, large-vessel vasculitis that primarily targets the aorta and its major branches, leading to vascular stenosis, occlusion and aneurysm formation. TAK, which is characterized by granulomatous inflammation of the arterial wall, predominantly affects women, with peak onset typically occurring between 20 and 40 years of age. The disease exhibits substantial geographic variability in prevalence, with emerging evidence suggesting that these differences are partly owing to variations in genetic susceptibility loci, particularly within immune-related genes; however, the role of environmental factors in the disease aetiology remains poorly understood. Non-invasive imaging techniques have become central to both diagnosis and disease monitoring. Furthermore, the development of biomarkers holds promise for more accurate assessment of disease activity. The management of TAK is evolving, driven by an improved understanding of disease pathogenesis. The growing use of biologic agents is providing new treatment options, particularly for patients with refractory or relapsing disease. By integrating these developments, this Review is aimed at serving as a comprehensive resource for clinicians and researchers dedicated to improving the understanding and management of TAK. This Review article provides an update on the pathophysiology, diagnosis and treatment of Takayasu arteritis. The authors emphasize the need for a multidisciplinary approach to the diagnosis and management of this complex disease.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 12","pages":"737-751"},"PeriodicalIF":32.7,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145455477","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}
Pub Date : 2025-10-30DOI: 10.1038/s41584-025-01320-y
Jessica McHugh
Biallelic loss-of-function mutations in PLD4, as identified in five patients with SLE, lead to Toll-like receptor-driven hyperactivation of type I interferon, immune cell expansion and autoimmunity.
{"title":"PLD4 variants promote SLE via unchecked TLR activation","authors":"Jessica McHugh","doi":"10.1038/s41584-025-01320-y","DOIUrl":"10.1038/s41584-025-01320-y","url":null,"abstract":"Biallelic loss-of-function mutations in PLD4, as identified in five patients with SLE, lead to Toll-like receptor-driven hyperactivation of type I interferon, immune cell expansion and autoimmunity.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 12","pages":"697-697"},"PeriodicalIF":32.7,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145396940","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}
Pub Date : 2025-10-30DOI: 10.1038/s41584-025-01324-8
Sarah Onuora
In a phase III placebo-controlled trial, the addition of telitacicept to standard therapy led to increased clinical response rates for people with systemic lupus erythematosus.
在一项III期安慰剂对照试验中，在标准治疗中加入泰利他塞普可提高系统性红斑狼疮患者的临床反应率。
{"title":"Phase III trial of telitacicept in SLE","authors":"Sarah Onuora","doi":"10.1038/s41584-025-01324-8","DOIUrl":"10.1038/s41584-025-01324-8","url":null,"abstract":"In a phase III placebo-controlled trial, the addition of telitacicept to standard therapy led to increased clinical response rates for people with systemic lupus erythematosus.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 12","pages":"698-698"},"PeriodicalIF":32.7,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145396941","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}
Pub Date : 2025-10-23DOI: 10.1038/s41584-025-01311-z
Progress has been astonishing, but the need for personalized care can only be addressed through a universal focus on diversity and equity in rheumatology research.
取得了惊人的进展，但只有通过普遍关注风湿病研究的多样性和公平性才能满足个性化护理的需求。
{"title":"The next breakthrough in rheumatology will require prioritizing diversity","authors":"","doi":"10.1038/s41584-025-01311-z","DOIUrl":"10.1038/s41584-025-01311-z","url":null,"abstract":"Progress has been astonishing, but the need for personalized care can only be addressed through a universal focus on diversity and equity in rheumatology research.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 11","pages":"641-641"},"PeriodicalIF":32.7,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41584-025-01311-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-16DOI: 10.1038/s41584-025-01306-w
Marta Casal Moura, Peter A. Merkel, David Jayne, Maria C. Cid, Neil Basu, Bernhard Hellmich, Benjamin Terrier, Abraham Rutgers, Jennifer Gordon, Peter Verhoeven, Joyce Kullman, Carol A. Langford, Ingeborg M. Bajema, Duvuru Geetha, Fernando C. Fervenza, A. Richard Kitching, John H. Stone, Ulrich Specks, Andreas Kronbichler
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) encompasses three rare yet interrelated diseases: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). Despite increasing recognition, the diagnosis of AAV remains challenging, even in specialized medical centres, owing to its clinical heterogeneity, overlap with mimicking conditions, and the variable performance of ANCA testing. The assessment of a patient suspected of AAV requires a timely synthesis of symptoms, physical examination, laboratory tests, histopathology and imaging data to substantiate the diagnosis, exclude alternative diagnoses, assess disease activity and extent, and enable rapid initiation of appropriate therapies. Classification is similarly complex, and evolving classification systems are based on clinical phenotype, ANCA specificity or a combination of both, each with implications for disease monitoring, therapeutic decisions and trial design. Assessing disease severity and predicting prognosis are fundamental but complicated by the diverse patterns of organ involvement, relapsing–remitting course and co-morbidities. Although validated tools exist for measuring disease activity, organ damage and prognosis, many limitations remain, particularly in identifying smouldering disease, irreversible damage and risk of relapse. Emerging therapies have improved outcomes, with recovery of kidney function, better overall survival and improved glucocorticoid-related toxicity, but patients with AAV continue to experience high risks of chronic morbidity and early mortality. This Review explores current challenges and opportunities in the diagnosis, classification and prognostic assessment of AAV, and outlines a structured framework to support personalized and outcome-focused care. ANCA-associated vasculitis (AAV) includes three disease subtypes with partly overlapping clinical manifestations: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). This Review article provides an update on the diagnosis and classification of AAV, discussing parameters for assessing disease activity and predicting outcomes towards a personalized medicine approach.
{"title":"Challenges in the diagnosis, classification and prognosis of ANCA-associated vasculitis","authors":"Marta Casal Moura, Peter A. Merkel, David Jayne, Maria C. Cid, Neil Basu, Bernhard Hellmich, Benjamin Terrier, Abraham Rutgers, Jennifer Gordon, Peter Verhoeven, Joyce Kullman, Carol A. Langford, Ingeborg M. Bajema, Duvuru Geetha, Fernando C. Fervenza, A. Richard Kitching, John H. Stone, Ulrich Specks, Andreas Kronbichler","doi":"10.1038/s41584-025-01306-w","DOIUrl":"10.1038/s41584-025-01306-w","url":null,"abstract":"Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) encompasses three rare yet interrelated diseases: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). Despite increasing recognition, the diagnosis of AAV remains challenging, even in specialized medical centres, owing to its clinical heterogeneity, overlap with mimicking conditions, and the variable performance of ANCA testing. The assessment of a patient suspected of AAV requires a timely synthesis of symptoms, physical examination, laboratory tests, histopathology and imaging data to substantiate the diagnosis, exclude alternative diagnoses, assess disease activity and extent, and enable rapid initiation of appropriate therapies. Classification is similarly complex, and evolving classification systems are based on clinical phenotype, ANCA specificity or a combination of both, each with implications for disease monitoring, therapeutic decisions and trial design. Assessing disease severity and predicting prognosis are fundamental but complicated by the diverse patterns of organ involvement, relapsing–remitting course and co-morbidities. Although validated tools exist for measuring disease activity, organ damage and prognosis, many limitations remain, particularly in identifying smouldering disease, irreversible damage and risk of relapse. Emerging therapies have improved outcomes, with recovery of kidney function, better overall survival and improved glucocorticoid-related toxicity, but patients with AAV continue to experience high risks of chronic morbidity and early mortality. This Review explores current challenges and opportunities in the diagnosis, classification and prognostic assessment of AAV, and outlines a structured framework to support personalized and outcome-focused care. ANCA-associated vasculitis (AAV) includes three disease subtypes with partly overlapping clinical manifestations: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). This Review article provides an update on the diagnosis and classification of AAV, discussing parameters for assessing disease activity and predicting outcomes towards a personalized medicine approach.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 12","pages":"719-736"},"PeriodicalIF":32.7,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305455","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}
Pub Date : 2025-10-16DOI: 10.1038/s41584-025-01317-7
Filippo Fagni, Giacomo Bagni, Federica Bello, Catherine L. Hill, Aladdin J. Mohammad, Sergey Moiseev, Iacopo Olivotto, Emire Seyahi, Giacomo Emmi
{"title":"Reply to ‘Potential benefit of anticoagulation in Behçet syndrome’","authors":"Filippo Fagni, Giacomo Bagni, Federica Bello, Catherine L. Hill, Aladdin J. Mohammad, Sergey Moiseev, Iacopo Olivotto, Emire Seyahi, Giacomo Emmi","doi":"10.1038/s41584-025-01317-7","DOIUrl":"10.1038/s41584-025-01317-7","url":null,"abstract":"","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 12","pages":"755-755"},"PeriodicalIF":32.7,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305457","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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