Pub Date : 2024-02-22DOI: 10.1016/j.jbspin.2024.105710
Nurmuhammed Tas , Hayri Ogul , Mecit Kantarci
{"title":"Intersection syndrome","authors":"Nurmuhammed Tas , Hayri Ogul , Mecit Kantarci","doi":"10.1016/j.jbspin.2024.105710","DOIUrl":"10.1016/j.jbspin.2024.105710","url":null,"abstract":"","PeriodicalId":54902,"journal":{"name":"Joint Bone Spine","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chimeric Antigen Receptor T-cell therapy (CAR-T), currently employed routinely for treating B-cell malignancies, has emerged as a groundbreaking approach in addressing severe autoimmune diseases, especially for systemic lupus erythematosus (SLE). The immunological rationale for targeting B lymphocytes in autoimmune diseases is well-established, demonstrating success in numerous autoantibody-mediated autoimmune conditions through targeted therapies over several years. However, this approach has often proven ineffective in the context of systemic lupus erythematosus. Recent data on CAR-T usage in lupus, revealed promising results including rapid and prolonged remission without treatment, highlighting the potential of CAR-T therapy in severe lupus cases. This article provides a comprehensive overview of CAR-T cells, tracing their evolution from hematological malignancies to their recent applications in autoimmune disorder, especially in lupus. Clinical trials within a regulated framework are now imperative to assess the procedural aspects in order to validate the considerable promise of CAR-T cell therapy in the field of autoimmune diseases. This includes evaluating safety and long-term efficacy and security of the procedure, the benefit-risk ratio in the field of autoimmunity, the availability and cost-related issues associated with this emerging cellular therapy procedure.
嵌合抗原受体 T 细胞疗法(CAR-T)是目前治疗 B 细胞恶性肿瘤的常规疗法,在治疗严重的自身免疫性疾病,尤其是系统性红斑狼疮(SLE)方面,它已成为一种开创性的方法。在自身免疫性疾病中靶向 B 淋巴细胞的免疫学原理已经确立,多年来,通过靶向疗法成功治疗了许多自身抗体介导的自身免疫性疾病。然而,这种方法在治疗系统性红斑狼疮时往往被证明无效。最近有关CAR-T疗法在狼疮中应用的数据显示了令人鼓舞的结果,包括无需治疗即可快速、长期缓解,这凸显了CAR-T疗法在重症狼疮病例中的潜力。本文全面概述了CAR-T细胞,追溯了其从血液恶性肿瘤到最近应用于自身免疫性疾病(尤其是狼疮)的演变过程。目前,必须在规范的框架内进行临床试验,以评估程序方面的问题,从而验证CAR-T细胞疗法在自身免疫性疾病领域的巨大前景。这包括评估该疗法的安全性、长期疗效和安全性、自身免疫领域的收益风险比、与这一新兴细胞疗法相关的可用性和成本问题。
{"title":"CAR-T cells for treating systemic lupus erythematosus: A promising emerging therapy","authors":"Aurélien Guffroy , Léa Jacquel , Blandine Guffroy , Thierry Martin","doi":"10.1016/j.jbspin.2024.105702","DOIUrl":"10.1016/j.jbspin.2024.105702","url":null,"abstract":"<div><p>Chimeric Antigen Receptor T-cell therapy (CAR-T), currently employed routinely for treating B-cell malignancies, has emerged as a groundbreaking approach in addressing severe autoimmune diseases, especially for systemic lupus erythematosus (SLE). The immunological rationale for targeting B lymphocytes in autoimmune diseases is well-established, demonstrating success in numerous autoantibody-mediated autoimmune conditions through targeted therapies over several years. However, this approach has often proven ineffective in the context of systemic lupus erythematosus. Recent data on CAR-T usage in lupus, revealed promising results including rapid and prolonged remission without treatment, highlighting the potential of CAR-T therapy in severe lupus cases. This article provides a comprehensive overview of CAR-T cells, tracing their evolution from hematological malignancies to their recent applications in autoimmune disorder, especially in lupus. Clinical trials within a regulated framework are now imperative to assess the procedural aspects in order to validate the considerable promise of CAR-T cell therapy in the field of autoimmune diseases. This includes evaluating safety and long-term efficacy and security of the procedure, the benefit-risk ratio in the field of autoimmunity, the availability and cost-related issues associated with this emerging cellular therapy procedure.</p></div>","PeriodicalId":54902,"journal":{"name":"Joint Bone Spine","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1297319X24000137/pdfft?md5=03000e067efd3a9296d5f64849f41585&pid=1-s2.0-S1297319X24000137-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-07DOI: 10.1016/j.jbspin.2024.105704
Tristan Pascart , Vincent Ducoulombier , Charlotte Jauffret
Early-onset gout (EOG) is characterized by the occurrence of the first symptoms of gout at an unusually young age, usually < 40 years. The aim of this review is to provide an overview of the epidemiology, clinical presentation and prognosis, association with comorbidities and specific management of EOG. A particularly high proportion of patients with EOG come from ethnic groups with stronger genetic factors, such as populations in the Pacific and Taiwan, who therefore have the highest prevalence of gout overall. The clinical presentation and severity of gout are broadly similar between EOG and common gout, although a longer disease duration exacerbates the disease, which more often tends to become polyarticular. Patients suffering from EOG develop metabolic comorbidities commonly associated with gout earlier in life, although those tend to be less frequent at the time of diagnosis. Some international guidelines recommend early treatment of EOG patients with urate-lowering therapies.
早发性痛风(EOG)的特点是在异常年轻时就出现痛风的首发症状,通常为
{"title":"Early-onset gout","authors":"Tristan Pascart , Vincent Ducoulombier , Charlotte Jauffret","doi":"10.1016/j.jbspin.2024.105704","DOIUrl":"10.1016/j.jbspin.2024.105704","url":null,"abstract":"<div><p>Early-onset gout (EOG) is characterized by the occurrence of the first symptoms of gout at an unusually young age, usually <<!--> <!-->40 years. The aim of this review is to provide an overview of the epidemiology, clinical presentation and prognosis, association with comorbidities and specific management of EOG. A particularly high proportion of patients with EOG come from ethnic groups with stronger genetic factors, such as populations in the Pacific and Taiwan, who therefore have the highest prevalence of gout overall. The clinical presentation and severity of gout are broadly similar between EOG and common gout, although a longer disease duration exacerbates the disease, which more often tends to become polyarticular. Patients suffering from EOG develop metabolic comorbidities commonly associated with gout earlier in life, although those tend to be less frequent at the time of diagnosis. Some international guidelines recommend early treatment of EOG patients with urate-lowering therapies.</p></div>","PeriodicalId":54902,"journal":{"name":"Joint Bone Spine","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1297319X24000150/pdfft?md5=6db44cb39405b51dd5059a915e2b4cfd&pid=1-s2.0-S1297319X24000150-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-07DOI: 10.1016/j.jbspin.2024.105703
Simon Cadiou , Rachel Tuil , Benoît Le Goff , Emmanuel Hoppé , Denis Mulleman , Camille Langbour , Estelle Le Pabic , Laurie Charret , Helene Cormier , Raphael Lecomte , Cédric Arvieux , Pascal Guggenbuhl , With help from the CRIOGO (Centre de Référence des Infections Ostéo-articulaires du Grand Ouest) Study Team [Corporate Author] and the network of rheumatologists from the Grand Ouest “VICTOR HUGO” [Corporate Author]
Objective
Septic arthritis of the Facet Joints (SAFJ) is a rare condition. Little data has been published on the subject. We aimed to describe the clinical, biological and imagery presentations, as well as the course of this rare infection.
Methods
We included patients hospitalized between January 1st, 2016 and December 31th, 2019, in the Departments of Infectious Diseases or Rheumatology in 5 French centres in the CRIOGO network. We defined septic arthritis according to Newman's criteria and facet joint arthritis using imagery.
Results
Sixty-five patients were included, predominantly males (64.6%), with a mean age of 68.1 years. The mean time to diagnosis was 25.0 days. The principal symptoms at diagnosis were acute back pain (95.2%) and fever (76.9%). Neurological symptoms were present for 60.7% of the patients, including 16.4% motor deficit or cauda equina syndrome. SAFJ was located on the lumbosacral spine (73.4%) and was rarely multifocal (4.7%). Bacteriological identification was performed by blood cultures in 84.4% of the cases, and the pathogen was mainly Staphylococcus aureus (49.2%). Infective endocarditis was present for 26.9% of patients assessed by echocardiography. On MRI, soft tissue abscess or inflammation, epiduritis and epidural abscess were present in 87.1%, 66.7% and 33.9% of cases, and the pathogen was significantly more frequently Staphylococcus aureus. Mortality reached 9.2%, 18.5% and 23% at one, two, and three years respectively.
Conclusion
SAFJ is a rare but severe disease. Microbiological diagnosis is primarily made on blood cultures, and S. Aureus was the main pathogen. Our results highlight the fact that SAFJ is associated with high morbidity and mortality, and with infective endocarditis.
{"title":"Septic arthritis of the facet joint is also a severe vertebral infection: A multicenter retrospective study of 65 patients","authors":"Simon Cadiou , Rachel Tuil , Benoît Le Goff , Emmanuel Hoppé , Denis Mulleman , Camille Langbour , Estelle Le Pabic , Laurie Charret , Helene Cormier , Raphael Lecomte , Cédric Arvieux , Pascal Guggenbuhl , With help from the CRIOGO (Centre de Référence des Infections Ostéo-articulaires du Grand Ouest) Study Team [Corporate Author] and the network of rheumatologists from the Grand Ouest “VICTOR HUGO” [Corporate Author]","doi":"10.1016/j.jbspin.2024.105703","DOIUrl":"10.1016/j.jbspin.2024.105703","url":null,"abstract":"<div><h3>Objective</h3><p>Septic arthritis of the Facet Joints (SAFJ) is a rare condition. Little data has been published on the subject. We aimed to describe the clinical, biological and imagery presentations, as well as the course of this rare infection.</p></div><div><h3>Methods</h3><p>We included patients hospitalized between January 1st, 2016 and December 31th, 2019, in the Departments of Infectious Diseases or Rheumatology in 5 French centres in the CRIOGO network. We defined septic arthritis according to Newman's criteria and facet joint arthritis using imagery.</p></div><div><h3>Results</h3><p>Sixty-five patients were included, predominantly males (64.6%), with a mean age of 68.1 years. The mean time to diagnosis was 25.0 days. The principal symptoms at diagnosis were acute back pain (95.2%) and fever (76.9%). Neurological symptoms were present for 60.7% of the patients, including 16.4% motor deficit or cauda equina syndrome. SAFJ was located on the lumbosacral spine (73.4%) and was rarely multifocal (4.7%). Bacteriological identification was performed by blood cultures in 84.4% of the cases, and the pathogen was mainly <em>Staphylococcus aureus</em> (49.2%). Infective endocarditis was present for 26.9% of patients assessed by echocardiography. On MRI, soft tissue abscess or inflammation, epiduritis and epidural abscess were present in 87.1%, 66.7% and 33.9% of cases, and the pathogen was significantly more frequently <em>Staphylococcus aureus</em>. Mortality reached 9.2%, 18.5% and 23% at one, two, and three years respectively.</p></div><div><h3>Conclusion</h3><p>SAFJ is a rare but severe disease. Microbiological diagnosis is primarily made on blood cultures, and <em>S. Aureus</em> was the main <em>pathogen.</em> Our results highlight the fact that SAFJ is associated with high morbidity and mortality, and with infective endocarditis.</p></div>","PeriodicalId":54902,"journal":{"name":"Joint Bone Spine","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-02DOI: 10.1016/j.jbspin.2024.105701
Gökhan Tonkaz , Cemre Akdeniz , Mehmet Tonkaz , Duygu Erkal Tonkaz , Tumay Bekci
{"title":"A rare case of intraosseous calcaneal lipoma with calcific and cystic components","authors":"Gökhan Tonkaz , Cemre Akdeniz , Mehmet Tonkaz , Duygu Erkal Tonkaz , Tumay Bekci","doi":"10.1016/j.jbspin.2024.105701","DOIUrl":"10.1016/j.jbspin.2024.105701","url":null,"abstract":"","PeriodicalId":54902,"journal":{"name":"Joint Bone Spine","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139668632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01DOI: 10.1016/j.jbspin.2024.105700
Mohamed-Yacine Khitri, Jérôme Hadjadj, Arsène Mekinian, Vincent Jachiet
VEXAS (Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a recently described autoinflammatory syndrome, mostly affecting men older than 50 years, caused by somatic mutation in the UBA1 gene, a X-linked gene involved in the activation of ubiquitin system. Patients present a broad spectrum of inflammatory manifestations (fever, neutrophilic dermatosis, chondritis, pulmonary infiltrates, ocular inflammation, venous thrombosis) and hematological involvement (macrocytic anemia, thrombocytopenia, vacuoles in myeloid and erythroid precursor cells, dysplastic bone marrow) that are responsible for a significant morbidity and mortality. The therapeutic management is currently poorly codified but is based on two main approaches: controlling inflammatory symptoms (by using corticosteroids, JAK inhibitor or tocilizumab) or targeting the UBA1-mutated hematopoietic population (by using azacitidine or allogeneic hematopoietic stem cell transplantation). Supportive care is also important and includes red blood cell or platelet transfusions, erythropoiesis stimulating agents, thromboprophylaxis and anti-infectious prophylaxis. The aim of this review is to provide a current overview of the VEXAS syndrome, particularly focusing on its pathophysiological, diagnostic and therapeutic aspects.
{"title":"VEXAS syndrome: An update","authors":"Mohamed-Yacine Khitri, Jérôme Hadjadj, Arsène Mekinian, Vincent Jachiet","doi":"10.1016/j.jbspin.2024.105700","DOIUrl":"10.1016/j.jbspin.2024.105700","url":null,"abstract":"<div><p>VEXAS (Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a recently described autoinflammatory syndrome, mostly affecting men older than 50 years, caused by somatic mutation in the <em>UBA1</em> gene, a X-linked gene involved in the activation of ubiquitin system. Patients present a broad spectrum of inflammatory manifestations (fever, neutrophilic dermatosis, chondritis, pulmonary infiltrates, ocular inflammation, venous thrombosis) and hematological involvement (macrocytic anemia, thrombocytopenia, vacuoles in myeloid and erythroid precursor cells, dysplastic bone marrow) that are responsible for a significant morbidity and mortality. The therapeutic management is currently poorly codified but is based on two main approaches: controlling inflammatory symptoms (by using corticosteroids, JAK inhibitor or tocilizumab) or targeting the <em>UBA1</em>-mutated hematopoietic population (by using azacitidine or allogeneic hematopoietic stem cell transplantation). Supportive care is also important and includes red blood cell or platelet transfusions, erythropoiesis stimulating agents, thromboprophylaxis and anti-infectious prophylaxis. The aim of this review is to provide a current overview of the VEXAS syndrome, particularly focusing on its pathophysiological, diagnostic and therapeutic aspects.</p></div>","PeriodicalId":54902,"journal":{"name":"Joint Bone Spine","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139673731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01DOI: 10.1016/j.jbspin.2024.105698
Medeea Badii , Viola Klück , Orsolya Gaal , Georgiana Cabău , Ioana Hotea , Valentin Nica , Andreea M. Mirea , Anca Bojan , Mihnea Zdrenghea , HINT Consortium , Boris Novakovic , Tony R. Merriman , Zhaoli Liu , Yang Li , Cheng-Jian Xu , Cristina Pamfil , Simona Rednic , Radu A. Popp , Tania O. Crişan , Leo A.B. Joosten
Objective
Hyperuricaemia is necessary for gout. High urate concentrations have been linked to inflammation in mononuclear cells. Here, we explore the role of the suppressor of cytokine signaling 3 (SOCS3) in urate-induced inflammation.
Methods
Peripheral blood mononuclear cells (PBMCs) from gout patients, hyperuricemic and normouricemic individuals were cultured for 24 h with varying concentrations of soluble urate, followed by 24 h restimulation with lipopolysaccharides (LPS) ± monosodium urate (MSU) crystals. Transcriptomic profiling was performed using RNA-Sequencing. DNA methylation was assessed using Illumina Infinium® MethylationEPIC BeadChip system (EPIC array). Phosphorylation of signal transducer and activator of transcription 3 (STAT3) was determined by flow cytometry. Cytokine responses were also assessed in PBMCs from patients with JAK2 V617F tyrosine kinase mutation.
Results
PBMCs pre-treated with urate produced more interleukin-1beta (IL-1β) and interleukin-6 (IL-6) and less interleukin-1 receptor anatagonist (IL-1Ra) after LPS simulation. In vitro, urate treatment enhanced SOCS3 expression in control monocytes but no DNA methylation changes were observed at the SOCS3 gene. A dose-dependent reduction in phosphorylated STAT3 concomitant with a decrease in IL-1Ra was observed with increasing concentrations of urate. PBMCs with constitutively activated STAT3 (JAK2 V617F mutation) could not be primed by urate.
Conclusion
In vitro, urate exposure increased SOCS3 expression, while urate priming, and subsequent stimulation resulted in decreased STAT3 phosphorylation and IL-1Ra production. There was no evidence that DNA methylation constitutes a regulatory mechanism of SOCS3. Elevated SOCS3 and reduced pSTAT3 could play a role in urate-induced hyperinflammation since urate priming had no effect in PBMCs from patients with constitutively activated STAT3.
{"title":"Regulation of SOCS3-STAT3 in urate-induced cytokine production in human myeloid cells","authors":"Medeea Badii , Viola Klück , Orsolya Gaal , Georgiana Cabău , Ioana Hotea , Valentin Nica , Andreea M. Mirea , Anca Bojan , Mihnea Zdrenghea , HINT Consortium , Boris Novakovic , Tony R. Merriman , Zhaoli Liu , Yang Li , Cheng-Jian Xu , Cristina Pamfil , Simona Rednic , Radu A. Popp , Tania O. Crişan , Leo A.B. Joosten","doi":"10.1016/j.jbspin.2024.105698","DOIUrl":"10.1016/j.jbspin.2024.105698","url":null,"abstract":"<div><h3>Objective</h3><p>Hyperuricaemia is necessary for gout. High urate concentrations have been linked to inflammation in mononuclear cells. Here, we explore the role of the suppressor of cytokine signaling 3 (SOCS3) in urate-induced inflammation.</p></div><div><h3>Methods</h3><p>Peripheral blood mononuclear cells (PBMCs) from gout patients, hyperuricemic and normouricemic individuals were cultured for 24<!--> <!-->h with varying concentrations of soluble urate, followed by 24<!--> <!-->h restimulation with lipopolysaccharides (LPS)<!--> <!-->±<!--> <!-->monosodium urate (MSU) crystals. Transcriptomic profiling was performed using RNA-Sequencing. DNA methylation was assessed using Illumina Infinium® MethylationEPIC BeadChip system (EPIC array). Phosphorylation of signal transducer and activator of transcription 3 (STAT3) was determined by flow cytometry. Cytokine responses were also assessed in PBMCs from patients with <em>JAK2 V617F</em> tyrosine kinase mutation.</p></div><div><h3>Results</h3><p>PBMCs pre-treated with urate produced more interleukin-1beta (IL-1β) and interleukin-6 (IL-6) and less interleukin-1 receptor anatagonist (IL-1Ra) after LPS simulation. In vitro, urate treatment enhanced <em>SOCS3</em> expression in control monocytes but no DNA methylation changes were observed at the <em>SOCS3</em> gene. A dose-dependent reduction in phosphorylated STAT3 concomitant with a decrease in IL-1Ra was observed with increasing concentrations of urate. PBMCs with constitutively activated STAT3 (<em>JAK2 V617F</em> mutation) could not be primed by urate.</p></div><div><h3>Conclusion</h3><p>In vitro, urate exposure increased <em>SOCS3</em> expression, while urate priming, and subsequent stimulation resulted in decreased STAT3 phosphorylation and IL-1Ra production. There was no evidence that DNA methylation constitutes a regulatory mechanism of SOCS3. Elevated SOCS3 and reduced pSTAT3 could play a role in urate-induced hyperinflammation since urate priming had no effect in PBMCs from patients with constitutively activated STAT3.</p></div>","PeriodicalId":54902,"journal":{"name":"Joint Bone Spine","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1297319X24000095/pdfft?md5=bb1140b5d46106c938d331e9e33bb207&pid=1-s2.0-S1297319X24000095-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139668515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01DOI: 10.1016/j.jbspin.2024.105697
Robin Jacquot , Laurent Kodjikian , Roland Chapurlat , Pascal Sève
Spondyloarthritis (SpA) encompasses a group of chronic inflammatory disorders of the joints frequently associated with uveitis in almost a quarter of cases. SpA-related uveitis typically affects the eye anterior chamber with sudden onset, causing pain, redness, photophobia, and blurred vision. Ophthalmologists will describe an acute anterior unilateral uveitis. Most patients present with episodic acute anterior non-granulomatous uveitis and retain excellent visual acuity. However, systemic treatments are recommended in the event of frequent relapses (2–3/year) or in rare cases of sight-threatening with ocular complications. The improved understanding of the pathogenesis of SpA has led to the management of this disease by biologics. Here, we review the main data regarding the opportunity to target specific components in inflammatory pathways for the treatment of SpA-related uveitis. These therapies are recommended for long-term control when uveitis relapses occur too frequently despite conventional systemic treatments. Significant benefits have been obtained with the tumor necrosis factor-α inhibitors (TNFis), particularly infliximab and adalimumab. Paradoxically, a high number of uveitis occurrences have been shown on etanercept. Mixed results have been demonstrated with interleukin-17 antagonists (secukinumab) and interleukin-12/interleukin-23 antagonists (ustekinumab) in cases of failure of TNFis. JAK inhibitors seem to be a valuable class of medications for these patients in the future. Although SpA-related uveitis is typically managed with conventional local and/or systemic treatments, these biological/targeted therapies may provide avenues to control both the underlying SpA and uveitis manifestations. Thus, a close collaboration between patients, rheumatologists, internists, and ophthalmologists is needed to optimally manage ocular inflammation in SpA.
{"title":"Targeted therapies for uveitis in spondyloarthritis: A narrative review","authors":"Robin Jacquot , Laurent Kodjikian , Roland Chapurlat , Pascal Sève","doi":"10.1016/j.jbspin.2024.105697","DOIUrl":"10.1016/j.jbspin.2024.105697","url":null,"abstract":"<div><p>Spondyloarthritis (SpA) encompasses a group of chronic inflammatory disorders of the joints frequently associated with uveitis in almost a quarter of cases. SpA-related uveitis typically affects the eye anterior chamber with sudden onset, causing pain, redness, photophobia, and blurred vision. Ophthalmologists will describe an acute anterior unilateral uveitis. Most patients present with episodic acute anterior non-granulomatous uveitis and retain excellent visual acuity. However, systemic treatments are recommended in the event of frequent relapses (2–3/year) or in rare cases of sight-threatening with ocular complications. The improved understanding of the pathogenesis of SpA has led to the management of this disease by biologics. Here, we review the main data regarding the opportunity to target specific components in inflammatory pathways for the treatment of SpA-related uveitis. These therapies are recommended for long-term control when uveitis relapses occur too frequently despite conventional systemic treatments. Significant benefits have been obtained with the tumor necrosis factor-α inhibitors (TNFis), particularly infliximab and adalimumab. Paradoxically, a high number of uveitis occurrences have been shown on etanercept. Mixed results have been demonstrated with interleukin-17 antagonists (secukinumab) and interleukin-12/interleukin-23 antagonists (ustekinumab) in cases of failure of TNFis. JAK inhibitors seem to be a valuable class of medications for these patients in the future. Although SpA-related uveitis is typically managed with conventional local and/or systemic treatments, these biological/targeted therapies may provide avenues to control both the underlying SpA and uveitis manifestations. Thus, a close collaboration between patients, rheumatologists, internists, and ophthalmologists is needed to optimally manage ocular inflammation in SpA.</p></div>","PeriodicalId":54902,"journal":{"name":"Joint Bone Spine","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1297319X24000083/pdfft?md5=8a9e90ec9cb0be405064b4d849ad3002&pid=1-s2.0-S1297319X24000083-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139668533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To assist the development of future treatments in systemic sclerosis (SSc), the development of reliable outcome measures is pivotal. We aimed to evaluate the use of high-resolution peripheral quantitative CT (HR-pQCT) for visualization and gradation of acro-osteolysis (AO) and calcinosis compared to conventional hand radiographs (CR) in patients with SSc.
Methods
HR-pQCT scans of the 2nd to 4th fingers, CR, nail fold capillaroscopy, and a clinical examination were conducted. Images were reviewed for the presence and degree of AO and calcinosis according to semiquantitative grading scales.
Results
Forty patients were included. Fourteen had AO according to CR, whereas HR-pQCT revealed AO in 18 patients. The sensitivity and specificity of classifying patients as having AO by HR-pQCT when CR was used as reference were 93% (95% CI: 66–99%) and 80% (95% CI: 59–93%), respectively. By CR and with HR-pQCT as reference, the sensitivity and specificity were 72% (95% CI: 47–90%) and 95% (95% CI: 76–99%). Patients with AO had more or larger calcifications than patients without AO according to the proposed HR-pQCT grading system, with a median grade of 2 (IQR: 1–3) versus 0 (IQR: 0–1) (P < 0.01). Grade 3 changes were observed exclusively in patients with AO (n = 6/14, 42.9%). Assessment of AO and calcinosis by HR-pQCT demonstrated moderate to excellent test-retest reliability.
Conclusion
HR-pQCT allowed precise and reliable classification and grading of acro-osteolysis and acral calcinosis. The modality could prove helpful for detecting and monitoring these lesions as well as facilitating early diagnosis and guide treatment of these patients.
{"title":"High-resolution peripheral quantitative computed tomography for the assessment of acro-osteolysis and calcinosis in patients with systemic sclerosis","authors":"Frederik Cosedis Enevoldsen , Josephine Therkildsen , Rasmus Klose-Jensen , Amanda Lynggaard Elkjær , Esben Uggerby Næser , Rikke Fuglsang Klicman , Katja Thorup Aaen , Klaus Henrik Søndergaard , Ellen-Margrethe Hauge","doi":"10.1016/j.jbspin.2024.105699","DOIUrl":"10.1016/j.jbspin.2024.105699","url":null,"abstract":"<div><h3>Objective</h3><p>To assist the development of future treatments in systemic sclerosis (SSc), the development of reliable outcome measures is pivotal. We aimed to evaluate the use of high-resolution peripheral quantitative CT (HR-pQCT) for visualization and gradation of acro-osteolysis (AO) and calcinosis compared to conventional hand radiographs (CR) in patients with SSc.</p></div><div><h3>Methods</h3><p>HR-pQCT scans of the 2nd to 4th fingers, CR, nail fold capillaroscopy, and a clinical examination were conducted. Images were reviewed for the presence and degree of AO and calcinosis according to semiquantitative grading scales.</p></div><div><h3>Results</h3><p>Forty patients were included. Fourteen had AO according to CR, whereas HR-pQCT revealed AO in 18 patients. The sensitivity and specificity of classifying patients as having AO by HR-pQCT when CR was used as reference were 93% (95% CI: 66–99%) and 80% (95% CI: 59–93%), respectively. By CR and with HR-pQCT as reference, the sensitivity and specificity were 72% (95% CI: 47–90%) and 95% (95% CI: 76–99%). Patients with AO had more or larger calcifications than patients without AO according to the proposed HR-pQCT grading system, with a median grade of 2 (IQR: 1–3) versus 0 (IQR: 0–1) (<em>P</em> <!--><<!--> <!-->0.01). Grade 3 changes were observed exclusively in patients with AO (<em>n</em> <!-->=<!--> <!-->6/14, 42.9%). Assessment of AO and calcinosis by HR-pQCT demonstrated moderate to excellent test-retest reliability.</p></div><div><h3>Conclusion</h3><p>HR-pQCT allowed precise and reliable classification and grading of acro-osteolysis and acral calcinosis. The modality could prove helpful for detecting and monitoring these lesions as well as facilitating early diagnosis and guide treatment of these patients.</p></div>","PeriodicalId":54902,"journal":{"name":"Joint Bone Spine","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1297319X24000101/pdfft?md5=ef2044e81d3fdc292275557d0796dfa0&pid=1-s2.0-S1297319X24000101-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139668826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}