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Paul Emery - One of the best experts on this subject based on the ideXlab platform.
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bone loss in very early inflammatory back pain in undifferentiated Spondyloarthropathy a 1 year observational study
Annals of the Rheumatic Diseases, 2010Co-Authors: G Haugeberg, A N Bennett, Dennis Mcgonagle, Paul Emery, Helena MarzoortegaAbstract:Objective Bone loss in patients with inflammatory back pain (IBP) suspicious of early undifferentiated Spondyloarthropathy is poorly defined. The aim of this study was to examine changes in bone mineral density (BMD) at the hip, lumbar spine and hand in patients with early IBP and to look for possible biomarkers associated with this change. Methods In 30 patients with early IBP, clinical data were collected and BMD assessed using dual energy x-ray absorptiometry at baseline, 6 and 12 months. Further imaging performed included MRI of the sacroiliac joints (SIJs) and spine at baseline and x-rays of the SIJs at baseline and after 8 years. Results After 12 months no significant reduction in hip, spine and hand BMD was seen at the group level. However, hip bone loss was found to be associated with raised baseline C-reactive protein levels, baseline MRI bone marrow oedema of the SIJs and the presence of radiographic sacroiliitis after 8 years. No association was found with change in spine and hand BMD. Conclusion Systemic bone loss in the hip is an early feature of the inflammatory disease process in patients with IBP in undifferentiated Spondyloarthropathy and is related to disease activity. These data highlight the importance of aggressive intervention in the early stages of disease in undifferentiated Spondyloarthropathy.
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the fatty romanus lesion a non inflammatory spinal mri lesion specific for axial Spondyloarthropathy
Annals of the Rheumatic Diseases, 2010Co-Authors: A N Bennett, Paul Emery, Helena Marzoortega, Amer Rehman, Elizabeth M A Hensor, Dennis McgonagleAbstract:Background Fatty changes at vertebral corners have been reported on MRI in ankylosing spondylitis but the distribution or specificity of these lesions to early axial Spondyloarthropathy (axial-SpA) has not been determined. Objective To assess the diagnostic utility of fatty Romanus lesions (FRLs) for axial-SpA in a population with chronic back pain. Methods Axial-skeleton TI SE and fat-suppressed MRI were performed on 174 patients with back pain and 11 controls. MRI lesions including FRLs were scored blind. An imaging diagnosis was given on MRI findings alone and compared with the ‘gold standard’ treating doctor9s diagnosis. Results Twenty-nine patients had FRLs: 31% (20/64) of patients with Spondyloarthropathy, 13% (6/45) with degenerative arthritis, 4% (2/45) with spinal malignancy, 5% (1/20) with ‘other’ diagnoses; none of 11 normal subjects had FRLs. The majority of the FRLs in SpA 60% (135/226) were present in the thoracic spine. The diagnostic utility of FRLs for SpA (likelihood ratio (LR) = 4.7) was significantly (p Conclusion This study defines the FRL as a diagnostic imaging feature of axial-SpA, which may be useful where inflammatory changes are absent on fat-suppression MRI and where radiography is normal.
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how to diagnose axial Spondyloarthropathy early
Annals of the Rheumatic Diseases, 2004Co-Authors: Nick Barkham, Dennis Mcgonagle, Helena Marzoortega, Paul EmeryAbstract:A proposed algorithmic approach may be useful in the early detection of AS Physicians’ perceptions of the spondyloarthropathies are changing. Ankylosing spondylitis (AS), the prototype of this group, has traditionally been considered a rare disease with few therapeutic options. In addition, diagnosis is difficult, sometimes delayed for decades, mainly owing to the lack of sensitivity of the traditional imaging method, radiography, to detect the hallmark of AS, sacroiliitis. Also, the widespread perception of these diseases as “innocuous” or having a good outcome has hampered the development of protocols for defining early disease and identifying those patients who would benefit from early treatment. It is now clear that these assumptions are incorrect. Ankylosing spondylitis is more common than previously estimated, with some studies suggesting a prevalence as high as 1%.1 Importantly it affects people at a time when they are economically active (most commonly in the third decade), and the disease has a major impact on a person’s ability to work. Recent evidence from a survey from our group shows that a high proportion of patients with AS still in work have major problems suggesting imminent job loss.2 In addition, the assumption of a good clinical outcome has recently been challenged, with 70% of patients progressing to fusion of the spine by 10–15 years.3,4 Mortality is also increased by 1.5–4 times that of the general population,5and a …
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enthesitis in Spondyloarthropathy
Current Opinion in Rheumatology, 1999Co-Authors: Dennis Mcgonagle, Helena Marzoortega, Muhammad Asim Khan, Philip Oconnor, Wayne Gibbon, Paul EmeryAbstract:Inflammation at the insertions of ligaments, tendons, or joint capsules to bone, which is termed enthesitis, is a characteristic feature of Spondyloarthropathy. Because of the relative inaccessibility of the enthesis, the inflammatory, microbiologic, and immunologic events at that site have been poo
Bruce M Rothschild - One of the best experts on this subject based on the ideXlab platform.
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Primate Spondyloarthropathy.
Current rheumatology reports, 2020Co-Authors: Bruce M RothschildAbstract:Spondyloarthropathy is a common occurrence in Old World primates, with only limited presence in New World monkeys. Clearly distinguished from rheumatoid arthritis, this erosive arthritis afflicts 20% of great apes, baboons, and rhesus macaques and had been increasing in frequency. Habitat-dependent infectious agent diarrhea-induced reactive arthritis is implicated on a background of genetic predisposition. A gorilla-derived therapeutic preventative approach has possible application in human clinical medicine.
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Diffuse Idiopathic Skeletal Hyperostosis: Addressing Confusion with Ankylosing Spondylitis/Spondyloarthropathy
SN Comprehensive Clinical Medicine, 2020Co-Authors: Bruce M RothschildAbstract:Diffuse idiopathic skeletal hyperostosis (DISH) is an idiopathic florid enthesial reaction, especially recognized in the presence of ossification of the anterior longitudinal ligament of the spine. It is essentially an asymptomatic phenomena, rather than a disease. DISH, however, is not the only phenomenon responsible for florid enthesial reaction and recognition of such reaction, and it is important to assure that hypervitaminosis A (idiopathic or iatrogenic) or Spondyloarthropathy is not actually responsible for the ossification. The paravertebral ossification in DISH is separate in space from the vertebral body, allowing it to be distinguished from the syndesmophytes of Spondyloarthropathy, which produce anulus fibrosis ossification. The presence of erosion and fusion of zygapophyseal and costovertebral joints in Spondyloarthropathy also facilitates distinguishing between the two phenomena. One seeks abnormalities on X-rays in attempting to explain the source of a patient’s back pain. It is critical however to determine whether a given radiologic finding (e.g., DISH) actually could be responsible. In the case of DISH, it is not and its recognition should not deter the healthcare provider from pursuing a complete evaluation.
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Intestinal Flora Modification of Arthritis Pattern in Spondyloarthropathy.
Jcr-journal of Clinical Rheumatology, 2015Co-Authors: Bruce M RothschildAbstract:BackgroundThe reactive form of Spondyloarthropathy appears inducible by exposure to agents of infectious diarrhea, but do those organisms represent the tip of the iceberg, as indicated by renewed interest in gastrointestinal flora? Prevalence of Spondyloarthropathy (20% of chimpanzees [Pan] and 28%
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The association of sacroiliac joint bridging with other enthesopathies in the human body.
Spine, 2007Co-Authors: Smadar Peleg, Youssef Masharawi, Nili Steinberg, Bruce M Rothschild, Israel HershkovitzAbstract:Study Design. A descriptive study of the association between sacroiliac joint (extra-articular) bridging and other enthesopathies. Objectives. To examine the relationship between sacroiliac joint bridging with other entheseal reaction sites in the skeleton, and its prognostic value in spinal diseases. Summary of Background Data. Sacroiliac joint bridging is considered a hallmark of spinal diseases (e.g., ankylosing spondylitis). Nevertheless, its association with other enthesopathies has never been quantified and analyzed. Methods. A total of 289 human male skeletons with sacroiliac joint bridging and 127 without (of similar demographic structure) were evaluated for the presence of entheseal ossification, cartilaginous calcification, and other axial skeleton joint fusion (a total of 18 anatomic sites). The presence of diffuse idiopathic skeletal hyperostosis and Spondyloarthropathy was also recorded. Results. Sacroiliac joint bridging was strongly associated with entheseal reactions in other parts of the body. Of the sacroiliac joint bridging group, 24.91% had diffuse idiopathic skeletal hyperostosis, and 8.05% had Spondyloarthropathy. Conclusions. The presence of sacroiliac joint bridging indicates an intensive general entheseal process in the skeleton.
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Etiology of reactive arthritis in Pan paniscus, P. troglodytes troglodytes, and P. troglodytes schweinfurthii
American Journal of Primatology, 2005Co-Authors: Bruce M Rothschild, Frank J RühliAbstract:The character of arthritis has not received the same attention in Pan paniscus as it has in P. troglodytes. Reactive arthritis (a form of Spondyloarthropathy) in the latter has been considered to be either a sexually transmitted or an infectious-agent diarrhea-related disorder. The unique sexual promiscuity of P. paniscus enables us to distinguish between those hypotheses. The macerated skeletons of 139 adult P. paniscus, P. troglodytes troglodytes, and P. troglodytes schweinfurthii were macroscopically analyzed for osseous and articular pathologies. The sex of the animal was recorded at the time of acquisition. Twenty-one percent of the P. paniscus, 28% of the P. t. troglodytes, and 27% of the P. t. schweinfurthii specimens had peripheral and central joint erosive disease characteristic of Spondyloarthropathy. Subchondral pauciarticular distribution and reactive new bone clearly distinguish this disease from rheumatoid arthritis, osteoarthritis, and direct bone/joint infection. The fact that P. paniscus and P. t. troglodytes were similar in terms of disease frequency makes the notion of sexual transmission unlikely. While the frequencies of Spondyloarthropathy were indistinguishable among all species/subspecies studied, the patterns of joint involvement were disparate. The Pan paniscus and P. t. troglodytes home ranges are geographically separate. We assessed possible habitat factors (e.g., exposure to specific infectious agents of diarrhea) by comparing P. paniscus and P. t. troglodytes with P. t. schweinfurthii. The latter shared similar patterns and habitats (separated by the Congo River) with P. paniscus. The explanation offered for habitat-specific patterns is differential bacterial exposure-most likely Shigella or Yersinia in P. paniscus and P. t. schweinfurthii.
Dennis Mcgonagle - One of the best experts on this subject based on the ideXlab platform.
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bone loss in very early inflammatory back pain in undifferentiated Spondyloarthropathy a 1 year observational study
Annals of the Rheumatic Diseases, 2010Co-Authors: G Haugeberg, A N Bennett, Dennis Mcgonagle, Paul Emery, Helena MarzoortegaAbstract:Objective Bone loss in patients with inflammatory back pain (IBP) suspicious of early undifferentiated Spondyloarthropathy is poorly defined. The aim of this study was to examine changes in bone mineral density (BMD) at the hip, lumbar spine and hand in patients with early IBP and to look for possible biomarkers associated with this change. Methods In 30 patients with early IBP, clinical data were collected and BMD assessed using dual energy x-ray absorptiometry at baseline, 6 and 12 months. Further imaging performed included MRI of the sacroiliac joints (SIJs) and spine at baseline and x-rays of the SIJs at baseline and after 8 years. Results After 12 months no significant reduction in hip, spine and hand BMD was seen at the group level. However, hip bone loss was found to be associated with raised baseline C-reactive protein levels, baseline MRI bone marrow oedema of the SIJs and the presence of radiographic sacroiliitis after 8 years. No association was found with change in spine and hand BMD. Conclusion Systemic bone loss in the hip is an early feature of the inflammatory disease process in patients with IBP in undifferentiated Spondyloarthropathy and is related to disease activity. These data highlight the importance of aggressive intervention in the early stages of disease in undifferentiated Spondyloarthropathy.
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the fatty romanus lesion a non inflammatory spinal mri lesion specific for axial Spondyloarthropathy
Annals of the Rheumatic Diseases, 2010Co-Authors: A N Bennett, Paul Emery, Helena Marzoortega, Amer Rehman, Elizabeth M A Hensor, Dennis McgonagleAbstract:Background Fatty changes at vertebral corners have been reported on MRI in ankylosing spondylitis but the distribution or specificity of these lesions to early axial Spondyloarthropathy (axial-SpA) has not been determined. Objective To assess the diagnostic utility of fatty Romanus lesions (FRLs) for axial-SpA in a population with chronic back pain. Methods Axial-skeleton TI SE and fat-suppressed MRI were performed on 174 patients with back pain and 11 controls. MRI lesions including FRLs were scored blind. An imaging diagnosis was given on MRI findings alone and compared with the ‘gold standard’ treating doctor9s diagnosis. Results Twenty-nine patients had FRLs: 31% (20/64) of patients with Spondyloarthropathy, 13% (6/45) with degenerative arthritis, 4% (2/45) with spinal malignancy, 5% (1/20) with ‘other’ diagnoses; none of 11 normal subjects had FRLs. The majority of the FRLs in SpA 60% (135/226) were present in the thoracic spine. The diagnostic utility of FRLs for SpA (likelihood ratio (LR) = 4.7) was significantly (p Conclusion This study defines the FRL as a diagnostic imaging feature of axial-SpA, which may be useful where inflammatory changes are absent on fat-suppression MRI and where radiography is normal.
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how to diagnose axial Spondyloarthropathy early
Annals of the Rheumatic Diseases, 2004Co-Authors: Nick Barkham, Dennis Mcgonagle, Helena Marzoortega, Paul EmeryAbstract:A proposed algorithmic approach may be useful in the early detection of AS Physicians’ perceptions of the spondyloarthropathies are changing. Ankylosing spondylitis (AS), the prototype of this group, has traditionally been considered a rare disease with few therapeutic options. In addition, diagnosis is difficult, sometimes delayed for decades, mainly owing to the lack of sensitivity of the traditional imaging method, radiography, to detect the hallmark of AS, sacroiliitis. Also, the widespread perception of these diseases as “innocuous” or having a good outcome has hampered the development of protocols for defining early disease and identifying those patients who would benefit from early treatment. It is now clear that these assumptions are incorrect. Ankylosing spondylitis is more common than previously estimated, with some studies suggesting a prevalence as high as 1%.1 Importantly it affects people at a time when they are economically active (most commonly in the third decade), and the disease has a major impact on a person’s ability to work. Recent evidence from a survey from our group shows that a high proportion of patients with AS still in work have major problems suggesting imminent job loss.2 In addition, the assumption of a good clinical outcome has recently been challenged, with 70% of patients progressing to fusion of the spine by 10–15 years.3,4 Mortality is also increased by 1.5–4 times that of the general population,5and a …
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enthesitis in Spondyloarthropathy
Current Opinion in Rheumatology, 1999Co-Authors: Dennis Mcgonagle, Helena Marzoortega, Muhammad Asim Khan, Philip Oconnor, Wayne Gibbon, Paul EmeryAbstract:Inflammation at the insertions of ligaments, tendons, or joint capsules to bone, which is termed enthesitis, is a characteristic feature of Spondyloarthropathy. Because of the relative inaccessibility of the enthesis, the inflammatory, microbiologic, and immunologic events at that site have been poo
Helena Marzoortega - One of the best experts on this subject based on the ideXlab platform.
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bone loss in very early inflammatory back pain in undifferentiated Spondyloarthropathy a 1 year observational study
Annals of the Rheumatic Diseases, 2010Co-Authors: G Haugeberg, A N Bennett, Dennis Mcgonagle, Paul Emery, Helena MarzoortegaAbstract:Objective Bone loss in patients with inflammatory back pain (IBP) suspicious of early undifferentiated Spondyloarthropathy is poorly defined. The aim of this study was to examine changes in bone mineral density (BMD) at the hip, lumbar spine and hand in patients with early IBP and to look for possible biomarkers associated with this change. Methods In 30 patients with early IBP, clinical data were collected and BMD assessed using dual energy x-ray absorptiometry at baseline, 6 and 12 months. Further imaging performed included MRI of the sacroiliac joints (SIJs) and spine at baseline and x-rays of the SIJs at baseline and after 8 years. Results After 12 months no significant reduction in hip, spine and hand BMD was seen at the group level. However, hip bone loss was found to be associated with raised baseline C-reactive protein levels, baseline MRI bone marrow oedema of the SIJs and the presence of radiographic sacroiliitis after 8 years. No association was found with change in spine and hand BMD. Conclusion Systemic bone loss in the hip is an early feature of the inflammatory disease process in patients with IBP in undifferentiated Spondyloarthropathy and is related to disease activity. These data highlight the importance of aggressive intervention in the early stages of disease in undifferentiated Spondyloarthropathy.
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the fatty romanus lesion a non inflammatory spinal mri lesion specific for axial Spondyloarthropathy
Annals of the Rheumatic Diseases, 2010Co-Authors: A N Bennett, Paul Emery, Helena Marzoortega, Amer Rehman, Elizabeth M A Hensor, Dennis McgonagleAbstract:Background Fatty changes at vertebral corners have been reported on MRI in ankylosing spondylitis but the distribution or specificity of these lesions to early axial Spondyloarthropathy (axial-SpA) has not been determined. Objective To assess the diagnostic utility of fatty Romanus lesions (FRLs) for axial-SpA in a population with chronic back pain. Methods Axial-skeleton TI SE and fat-suppressed MRI were performed on 174 patients with back pain and 11 controls. MRI lesions including FRLs were scored blind. An imaging diagnosis was given on MRI findings alone and compared with the ‘gold standard’ treating doctor9s diagnosis. Results Twenty-nine patients had FRLs: 31% (20/64) of patients with Spondyloarthropathy, 13% (6/45) with degenerative arthritis, 4% (2/45) with spinal malignancy, 5% (1/20) with ‘other’ diagnoses; none of 11 normal subjects had FRLs. The majority of the FRLs in SpA 60% (135/226) were present in the thoracic spine. The diagnostic utility of FRLs for SpA (likelihood ratio (LR) = 4.7) was significantly (p Conclusion This study defines the FRL as a diagnostic imaging feature of axial-SpA, which may be useful where inflammatory changes are absent on fat-suppression MRI and where radiography is normal.
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how to diagnose axial Spondyloarthropathy early
Annals of the Rheumatic Diseases, 2004Co-Authors: Nick Barkham, Dennis Mcgonagle, Helena Marzoortega, Paul EmeryAbstract:A proposed algorithmic approach may be useful in the early detection of AS Physicians’ perceptions of the spondyloarthropathies are changing. Ankylosing spondylitis (AS), the prototype of this group, has traditionally been considered a rare disease with few therapeutic options. In addition, diagnosis is difficult, sometimes delayed for decades, mainly owing to the lack of sensitivity of the traditional imaging method, radiography, to detect the hallmark of AS, sacroiliitis. Also, the widespread perception of these diseases as “innocuous” or having a good outcome has hampered the development of protocols for defining early disease and identifying those patients who would benefit from early treatment. It is now clear that these assumptions are incorrect. Ankylosing spondylitis is more common than previously estimated, with some studies suggesting a prevalence as high as 1%.1 Importantly it affects people at a time when they are economically active (most commonly in the third decade), and the disease has a major impact on a person’s ability to work. Recent evidence from a survey from our group shows that a high proportion of patients with AS still in work have major problems suggesting imminent job loss.2 In addition, the assumption of a good clinical outcome has recently been challenged, with 70% of patients progressing to fusion of the spine by 10–15 years.3,4 Mortality is also increased by 1.5–4 times that of the general population,5and a …
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enthesitis in Spondyloarthropathy
Current Opinion in Rheumatology, 1999Co-Authors: Dennis Mcgonagle, Helena Marzoortega, Muhammad Asim Khan, Philip Oconnor, Wayne Gibbon, Paul EmeryAbstract:Inflammation at the insertions of ligaments, tendons, or joint capsules to bone, which is termed enthesitis, is a characteristic feature of Spondyloarthropathy. Because of the relative inaccessibility of the enthesis, the inflammatory, microbiologic, and immunologic events at that site have been poo
Jonathan P Sherlock - One of the best experts on this subject based on the ideXlab platform.
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the critical role of interleukin 23 in Spondyloarthropathy
Molecular Immunology, 2014Co-Authors: Jonathan P Sherlock, Christopher D BuckleyAbstract:Abstract The spondyloarthropathies represent highly enigmatic conditions and although their clinical features, anatomical distribution of disease and genetic predisposing factors have been known for some time, a unified concept of the basic pathobiology underlying these illnesses has remained undefined. Recently progress has been made because numerous independent studies have converged upon IL-23 as a central cytokine in Spondyloarthropathy and the mechanism and sites of action of this cytokine have now become much clearer. These findings enable the rational design of therapeutic strategies which it is hoped will profoundly modify the progression of these diseases. We will review the anatomical sites affected and the evidence for the importance of IL-23 in these conditions, before drawing these lines of investigation together to propose a model for the unified understanding of Spondyloarthropathy.
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interleukin 23 a promising therapeutic target in seronegative Spondyloarthropathy
Current Opinion in Pharmacology, 2013Co-Authors: Jonathan P SherlockAbstract:Particular therapeutic challenges are raised by the spondyloarthropathies which represent a key area of unmet medical need. Recent investigations have shown that these conditions are characterised both by altered responsiveness to interleukin(IL)-23 and expansion of IL-23 responsive cells as well as increased production of IL-23. The gut in particular has emerged as a key site of IL-23 production, and gut inflammation is known to be strongly clinically associated with these conditions. Moreover, HLA-B27, which is strongly associated with Spondyloarthropathy, has also been shown to stimulate IL-23 production. The view is thus emerging that dysregulation of IL-23 biology is a unifying feature of Spondyloarthropathy, suggesting that treatments targeting this cytokine are likely to be highly efficacious.
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interleukin 23 is critical in the pathogenesis of Spondyloarthropathy and acts on a novel population of interleukin 23r entheseal resident cells
The Lancet, 2013Co-Authors: Jonathan P Sherlock, Barbara Joyceshaikh, Scott Turner, Manjiri Sathe, Jeff Grein, Daniel M Gorman, Edward P Bowman, Terrill K McclanahanAbstract:Abstract Spondyloarthropathy is characterised by inflammation, bone erosion, and new bone formation at the entheseal insertions of tendons and ligaments to bone. Lack of understanding of the underlying mechanisms that drive entheseal disease has seriously inhibited design of therapeutics. Although anti-tumour necrosis factor (TNF) therapy reduces signs and symptoms of inflammation, residual inflammation continues and bone growth is not inhibited. This suggests that TNF is not the optimum target to modify entheseal disease. We previously demonstrated that interleukin (IL) 23 is pivotal in autoimmune inflammation. Recently, genetic variants in the IL-23 receptor (IL23R) have been associated with development of Spondyloarthropathy. Moreover, HLA-B27 (present in 90% of patients with ankylosing spondylitis) as well as associated bowel inflammation have been shown to induce IL-23 expression. However, the site and mechanism of action of IL23 are unknown and the reason why such dysregulation of IL23 is associated with inflammation specifically at the enthesis has been inexplicable. We now demonstrate that the entheses and aortic root contain a novel population of resident IL23R+ T cells, which allow the tissue to rapidly respond to IL23. Intravital microscopy reveals that these cells display an extremely restricted entheseal localisation and are absent from synovium and tendon proper. The cells express the molecule PLZF, which allows them to respond to cytokines extremely rapidly, and indeed entheses respond within hours to IL23 in vitro. Moreover, IL-23 expression in vivo in mice is sufficient by itself to rapidly induce the hallmark features of Spondyloarthropathy with development of exceedingly specific enthesitis, aortitis, and typical bone erosion and new bone formation. The highly restricted distribution of IL23R+ cells provides the fundamental basis for the anatomical localisation of inflammation observed in Spondyloarthropathy, as well as allowing a unified understanding of the genetic associations. These findings suggest that neutralisation of IL23 may be a truly disease modifying therapeutic approach. Funding Merck.
