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Rachelle Donn - One of the best experts on this subject based on the ideXlab platform.
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linkage and association studies of discoidin domain receptor 1 ddr1 single nucleotide polymorphisms snps in juvenile Oligoarthritis
Rheumatology, 2004Co-Authors: Eleftheria Zeggini, Wendy Thomson, A M Reginato, A Prais, William Mclean, Rachelle DonnAbstract:OBJECTIVES: Multiple independent juvenile Oligoarthritis susceptibility loci have been identified within the major histocompatibility complex (MHC), including HLA-A, HLA-DRB1 and an as yet unlocalized effect in the centromeric class I region. The discoidin domain receptor 1 (DDR1) gene resides within this region and codes for a receptor tyrosine kinase that plays an important role in regulating cell attachment to collagen, chemotaxis, proliferation and matrix metalloproteinase (MMP) production. DDR1 expression in chondrocytes has not been investigated. The objectives of this study were to investigate expression of DDR1 in healthy chondrocytes and to identify linkage and association of this candidate gene with juvenile Oligoarthritis. METHODS: A set of 135 simplex juvenile idiopathic arthritis families consisting of one affected child and healthy parent(s) and 199 healthy unrelated individuals were genotyped for six single nucleotide polymorphisms (SNPs) within the DDR1 gene using the primer extension SNaPshot(TM) method. Single-point and multipoint transmission disequilibrium tests were carried out with the ETDT and TDTPHASE packages. Allele frequency comparisons between cases and controls were carried out with the chi(2) test. DDR1 expression was investigated in normal articular cartilage by RT-PCR and immunofluorescence methods. RESULTS: No linkage and association with any of the six SNPs or their haplotypic combinations were observed in the families studied. No significant differences were observed in allele frequencies between patients and controls. DDR1 expression was found in normal articular cartilage by RT-PCR and by immunofluorescence. CONCLUSIONS: The DDR1 SNPs examined are not involved in susceptibility to juvenile Oligoarthritis.
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linkage and association studies of single nucleotide polymorphism tagged tumor necrosis factor haplotypes in juvenile Oligoarthritis
Arthritis & Rheumatism, 2002Co-Authors: Eleftheria Zeggini, William E R Ollier, Wendy Thomson, Dominic P Kwiatkowski, Anna Richardson, Rachelle DonnAbstract:Objective The presence of increased levels of tumor necrosis factor (TNF) in serum and synovial fluid of patients and the encouraging outcome of anti-TNF therapy have implicated TNFα in the etiopathogenesis of juvenile Oligoarthritis. Although the locus is polymorphic, no study has investigated all TNF single-nucleotide polymorphisms (SNPs) with respect to disease. The aim of this study was to examine the association of multiple TNF SNPs with juvenile Oligoarthritis and to construct and analyze SNP-tagged TNF haplotypes. Methods A total of 144 simplex families consisting of parent and affected child, as well as 88 healthy, unrelated control subjects were available for study. In these individuals, 9 polymorphic positions of TNF were typed by a high-throughput genotyping method based on the SNaPshot assay. The chi-square and extended transmission disequilibrium tests were used to test for association and linkage, respectively. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were also calculated. Haplotype-tagging SNPs (htSNPs) for the locus were identified by ordering the haplotypes according to their frequencies. Results The study detected association of several TNF SNPs and established linkage of the locus to juvenile Oligoarthritis. The most significant association observed was between the intronic +851 TNF SNP and the persistent Oligoarthritis subgroup (OR 3.86, 95% CI 1.6–9.2). Haplotype data mining showed that only 4 of the 9 SNPs need to be typed in order to capture the most frequent TNF haplotypes. Conclusion The TNF locus is linked and associated with juvenile Oligoarthritis. Information on the htSNPs can be useful in genetic studies of diseases in which TNF may be of relevance.
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evidence for linkage of hla loci in juvenile idiopathic Oligoarthritis independent effects of hla a and hla drb1
Arthritis & Rheumatism, 2002Co-Authors: Eleftheria Zeggini, Rachelle Donn, William E R Ollier, Wendy ThomsonAbstract:Objective Although multiple associations between HLA loci and juvenile Oligoarthritis have previously been documented, evidence for linkage of HLA loci in Oligoarthritis in UK Caucasians with juvenile idiopathic arthritis (JIA) has not been described. The aim of this study was to investigate linkage of HLA–A, B, and DRB1 in UK Caucasian JIA patients with Oligoarthritis. Methods One hundred forty-two families comprising affected offspring and their parents (45 with one parent available and 97 with both parents available) were typed for HLA–A, B, and DRB1 by polymerase chain reaction–sequence-specific oligonucleotide probe. Single-point and multipoint analyses were performed using various modifications of the extended transmission disequilibrium test. Linkage disequilibrium (LD) analysis was performed using the EH-Plus system. Results Linkage to HLA–A and HLA–DRB1 was seen in Oligoarthritis and in the International League of Associations for Rheumatology–defined subgroups of persistent Oligoarthritis and extended Oligoarthritis. Linkage to HLA–A, B, and DRB1 was also observed in female patients with Oligoarthritis. Linkage of the HLA loci seemed to be attributable to maternal preferential transmission of alleles. Furthermore, LD patterns between the HLA–A, B, and DRB1 loci were investigated. HLA–A and HLA–DRB1 were confirmed as independent susceptibility loci for Oligoarthritis. Conclusion This is the first study to establish linkage of HLA–A and HLA–DRB1 in Oligoarthritis and to show that the 2 loci contribute independently to disease. Further studies are being performed to determine whether it is these loci or other genes in LD with them that are responsible for susceptibility to Oligoarthritis in UK Caucasian patients with JIA.
Paul Emery - One of the best experts on this subject based on the ideXlab platform.
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fri0275 long term follow up of an early Oligoarthritis cohort shows that early aggressive intervention leads to drug free remission after 10 years results from the loto study
Annals of the Rheumatic Diseases, 2013Co-Authors: Concepcion Castillogallego, Michael J Green, Sibel Zehra Aydin, Sharmin Nizam, Paul Emery, H MarzoortegaAbstract:Background Oligoarthritis is as an inflammatory arthritis affecting ≤4 joints. It represents either an early clinical presentation or a unique disease phenotype within the group of the SpA. Oligoarthritis typically affects young people causing high morbidity and has a variable. We have previously reported on the effect of early intervention with intra-articular corticosteroids and sulfasalazine (SSZ) in a cohort of patients presenting with an Oligoarthritis of recent onset with 80% of patients achieving clinical remission after 52 weeks. We now report on the long-term outcome of this cohort after 10 years. Objectives To report the rate of disease persistence/clinical remission in the long-term follow up of the Leeds cohort of early Oligoarthritis. Methods Cross-sectional follow up of patients who participated in two previous interventional studies [1, 2]. Subjects were invited to either attend for a single study visit or a telephone consult. Presence/absence of any musculoskeletal symptoms and current diagnosis was recorded. Blood tests for inflammatory markers and radiographs of SIJs or any relevant joints were performed only if clinically indicated to establish a diagnosis if persistent clinical symptoms. Results The initial cohort comprised of a total of 117 patients, of whom 5 were deceased. An invitation letter was sent out to 112 patients (95.7%). Follow up data are available from a total of 74 patients (63.3%) [mean (SD) disease duration at presentation 13.8 (1.8) months; with a disease duration of 13 (3) years at follow up] of whom 22 (29.8%) attended for a follow up visit; 28 (37.8%) were assessed via telephone consult and 24 (32.4%) had data extracted from the clinical notes. Analysis of the attenders show that 47 patients (63.5%) had had persistent arthritis since the end of the previous studies (19.5% were RF positive; 33.3% antiCCP positive and 32.4% HLA B27 positive). The majority (74%) had received joint steroid injections ± SSZ as previous study protocols. Only 17% had a monoarticular presentation. The majority of patients (83%) had an oligoarticular pattern at disease presentation which was maintained over time in 68%. Fifteen percent (15%) had developed mixed phenotype with axial and peripheral joint involvement. 36.5% of patients (4% and 17.4% RF and HLA-B27 positive respectively) had remained asymptomatic in this time with no hospital follow up. The majority of these (57.7%) had an oligoarthritic pattern at presentation (42.3% monoarthritis), 65.4% had received intra-articular steroids in the previous studies. Conclusions Ten year follow up of an early Oligoarthritis cohort shows that over a third of patients attending for review are in drug free clinical remission. The majority had received joint steroid injections ± SSZ early on in their disease onset suggesting that early intervention may lead to clinical remission. These results can throw important insights into the pathogenesis of this condition and provide useful guidance for clinicians managing these patients. References Green, M., et al. Arthritis & Rheumatism, 2001. 44(5): p. 1177-1183. Marzo-Ortega, H., et al. Arthritis & Rheumatism, 2007. 57 (1): p. 154-160. Disclosure of Interest None Declared
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ten year follow up of spa related Oligoarthritis involving the knee the presence of psoriasis but not hla b27 or baseline mri bone oedema predicts outcome
Rheumatology, 2012Co-Authors: Alexander N Bennett, Michael J Green, Paul Emery, H Marzoortega, Ai Lyn Tan, Elizabeth M A Hensor, Dennis McgonagleAbstract:Objective. Bone marrow oedema (BMO) and HLA-B27 are poor prognostic factors in axial SpA, and psoriasis is a poor prognostic factor in small-joint polyarthropathy. The aim of this study was to investigate the influence of HLA-B27, MRI BMO and psoriasis on long-term outcomes in early SpA-related knee joint Oligoarthritis. Methods. Patients with SpA-related Oligoarthritis with knee involvement were recruited. Baseline assessment included ESSG criteria, RF, HLA-B27 and MRI. The degree of MRI BMO was determined on fat-suppression sequences and scored using the whole-organ magnetic resonance imaging score (WORMS) (range 045). Patients were treated at the discretion of their rheumatologist and followed up for 10 years. Outcome assessments included joint counts, functional and symptomatic questionnaire, CRP and radiographic assessment for OA. Results. Forty-four patients were recruited [mean age 32 years (range 1559 years), 70% male] with a mean disease duration at baseline of 9.75 months (148 months). Twenty-six (59%) patients (mean age 43 years, 65% male) returned for follow-up after a mean of 10 years (range 8.412.6 years). Ten (38%) patients had persistent clinical synovitis and 31% of knees had secondary radiographic OA. Global outcome was poor/very poor in 69% of cases. The only factor predicting outcome at 10 years was psoriasis, but neither HLA-B27 nor BMO. PsA patients had significantly worse global outcome compared with ReA (P = 0.036), and significantly worse symptomatic (P = 0.001) and functional (P = 0.001) outcome compared with other subtypes.
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a randomized controlled trial of early intervention with intraarticular corticosteroids followed by sulfasalazine versus conservative treatment in early Oligoarthritis
Arthritis Care and Research, 2007Co-Authors: H Marzoortega, Michael J Green, Richard J Wakefield, Susanna M Proudman, Annemaree Keenan, Paul EmeryAbstract:Objective To determine the outcome after 52 weeks of early intervention with intraarticular corticosteroid injections followed by sulfasalazine versus conservative therapy in patients with recent-onset Oligoarthritis in a randomized controlled trial. Methods Patients with ≤4 joints with clinical synovitis (disease duration ≤12 months) were randomized to early intervention (EI) with intraarticular methylprednisolone into all synovitic joints or to conservative treatment (CT) with nonsteroidal antiinflammatory drugs alone. Sulfasalazine was administered in both groups for persistent disease or disease that evolved into a polyarthritis. Primary outcome was complete response (CR) defined as the absence of synovitis at 52 weeks. Secondary outcomes included CR at weeks 4 and 12, function (Health Assessment Questionnaire), pain (0–100-mm visual analog scale), and work status. Results Fifty-nine patients (34 men, 25 women; mean age 32.9 years; median early morning stiffness 30 minutes) were randomized. At baseline, two-thirds reported that they were work impaired. At 52 weeks, 81% of patients in the EI group achieved CR compared with 57% in the CT group (χ2 = 3.833, 1 df, P = 0.05). In addition, 45% of patients in the EI group received sulfasalazine as opposed to 14% in the CT group (χ2 = 5.156, 1 df, P = 0.019). There were no differences in physical disability or work impairment between the treatment groups. Conclusion Oligoarthritis has a significant impact on function and work ability. Patients treated with EI using intraarticular corticosteroids followed by sulfasalazine therapy if resistant demonstrated reduced synovitis 12 months after treatment compared with those initially treated with more conservative therapy.
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should Oligoarthritis be reclassified ultrasound reveals a high prevalence of subclinical disease
Annals of the Rheumatic Diseases, 2004Co-Authors: Richard J Wakefield, Michael J Green, Helena Marzoortega, Susanna M Proudman, Dennis Mcgonagle, P G Conaghan, Wayne Gibbon, Paul EmeryAbstract:Objective: To determine the prevalence of subclinical synovitis using ultrasound (US) imaging of both painful and asymptomatic joints, in patients with early ( Methods: Eighty patients underwent a detailed clinical assessment by two physicians. All painful joints were identified, which were immediately scanned by a sonographer. In the last 40 patients, an additional standard group of joints was scanned to establish the prevalence of synovitis in asymptomatic joints. Results: In 80 patients, 644 painful joints (with and without clinical synovitis) were identified and each underwent a US assessment. Of these joints, 185 had clinical synovitis, of which, US detected synovitis in only 79% (147/185). In the other 38 joints US demonstrated tenosynovitis instead of synovitis in 12 joints and possible, but not definite, synovitis in 11 joints. Fifteen joints were, however, normal on US. In 459 joints that were not clinically synovitic, US detected synovitis in 33% (150/459). In 64% (51/80) of patients, US detected synovitis in more joints than clinical examination and in 36% (29/80) of patients, US detected a polyarthritis (>6 joints). Of the 826 asymptomatic (non-painful) joints scanned, 13% (107/826) had US detected synovitis. Conclusion: Sonography detected more synovitis than clinical examination in patients with Oligoarthritis. In almost two thirds of patients there was evidence of subclinical disease while one third could be reclassified as polyarticular. These findings suggest that a definition of Oligoarthritis based purely on clinical findings may be inappropriate, which may have important implications for disease management.
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predictors of outcome in patients with Oligoarthritis results of a protocol of intraarticular corticosteroids to all clinically active joints
Arthritis & Rheumatism, 2001Co-Authors: Michael J Green, Helena Marzoortega, Richard J Wakefield, Paul Astin, Susanna M Proudman, Philip G Conaghan, Lesley Hordon, Paul EmeryAbstract:Objective To determine the outcome and the factors that predict the persistence of synovitis following intraarticular corticosteroid injections in patients with recent-onset Oligoarthritis. Methods Fifty-one patients with ≤5 joints with synovitis (disease duration ≤12 months) were treated with intraarticular injections of methylprednisolone into all joints with clinical synovitis. Predictors of outcome were sought, with the primary end point a complete response (no synovitis on clinical examination) at 12 weeks. Results Patient's and physician's assessments of disease activity, the swollen joint count, and function (by Health Assessment Questionnaire) were all significantly improved at 12 weeks (P < 0.001). Twenty-nine patients (57%) were judged to have had a complete response at 2 weeks. The best predictor of response at 12 and 26 weeks was the presence or absence of synovitis at 2 weeks (P = 0.002 and P = 0.004, respectively). At 52 weeks of followup, nearly 50% of the patients still had evidence of synovitis. Conclusion Intraarticular corticosteroids are an effective treatment for early Oligoarthritis, but there is still a high level of long-term morbidity. Failure to respond by 2 weeks indicates a high likelihood of persistent disease, and this is relevant when producing management guidelines and selecting patients for studies focusing on early intervention.
Michael J Green - One of the best experts on this subject based on the ideXlab platform.
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long term follow up of an early Oligoarthritis cohort shows that early aggressive intervention leads to drug free remission after 10 years results from the loto study
International Journal of Clinical Rheumatology, 2017Co-Authors: Concepcion Castillogallego, Michael J Green, Sibel Zehra Aydin, Sharmin Nizam, Paul Emery Helena MarzoortegaAbstract:Objective: To report the long-term outcome in the long-term follow up of the Leeds Early Oligoarthritis Cohort. Methods: Cross-sectional follow up of patients who participated in two previous interventional studies. Subjects were invited to either attend for a single study visit or a telephone consults. Presence/absence of any musculoskeletal symptoms and current diagnosis was recorded. Blood tests for inflammatory markers and radiographs of SIJs or any relevant joints were performed only if clinically indicated to establish a diagnosis if persistent clinical symptoms. Results: Follow up data were available from 63.3% (n=74 patients) of the initial cohort (n=117 patients) [mean SD disease duration at presentation 11.8 ± 1.8 months; disease duration at follow up: 13 ± 3 years]. Of these 74 patients, 63.51% (n=47) had persistent arthritis since the end of the previous studies (19.5% were RF positive; 33.3% anti-CCP positive and 32.4% HLA-B27 positive). The majority (75%) had received joint steroid injections sulfasalazine on the original study protocols. Oligoarthritis was still the predominant articular pattern in 68% of the patients at follow up and over a third of patients (36.5%) were in clinical remission (4% and 17.4% RF and HLA-B27 positive respectively). Conclusion: Ten-year follow up of an early Oligoarthritis cohort shows that over a third of patients attending for review are in drug free clinical remission.
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fri0275 long term follow up of an early Oligoarthritis cohort shows that early aggressive intervention leads to drug free remission after 10 years results from the loto study
Annals of the Rheumatic Diseases, 2013Co-Authors: Concepcion Castillogallego, Michael J Green, Sibel Zehra Aydin, Sharmin Nizam, Paul Emery, H MarzoortegaAbstract:Background Oligoarthritis is as an inflammatory arthritis affecting ≤4 joints. It represents either an early clinical presentation or a unique disease phenotype within the group of the SpA. Oligoarthritis typically affects young people causing high morbidity and has a variable. We have previously reported on the effect of early intervention with intra-articular corticosteroids and sulfasalazine (SSZ) in a cohort of patients presenting with an Oligoarthritis of recent onset with 80% of patients achieving clinical remission after 52 weeks. We now report on the long-term outcome of this cohort after 10 years. Objectives To report the rate of disease persistence/clinical remission in the long-term follow up of the Leeds cohort of early Oligoarthritis. Methods Cross-sectional follow up of patients who participated in two previous interventional studies [1, 2]. Subjects were invited to either attend for a single study visit or a telephone consult. Presence/absence of any musculoskeletal symptoms and current diagnosis was recorded. Blood tests for inflammatory markers and radiographs of SIJs or any relevant joints were performed only if clinically indicated to establish a diagnosis if persistent clinical symptoms. Results The initial cohort comprised of a total of 117 patients, of whom 5 were deceased. An invitation letter was sent out to 112 patients (95.7%). Follow up data are available from a total of 74 patients (63.3%) [mean (SD) disease duration at presentation 13.8 (1.8) months; with a disease duration of 13 (3) years at follow up] of whom 22 (29.8%) attended for a follow up visit; 28 (37.8%) were assessed via telephone consult and 24 (32.4%) had data extracted from the clinical notes. Analysis of the attenders show that 47 patients (63.5%) had had persistent arthritis since the end of the previous studies (19.5% were RF positive; 33.3% antiCCP positive and 32.4% HLA B27 positive). The majority (74%) had received joint steroid injections ± SSZ as previous study protocols. Only 17% had a monoarticular presentation. The majority of patients (83%) had an oligoarticular pattern at disease presentation which was maintained over time in 68%. Fifteen percent (15%) had developed mixed phenotype with axial and peripheral joint involvement. 36.5% of patients (4% and 17.4% RF and HLA-B27 positive respectively) had remained asymptomatic in this time with no hospital follow up. The majority of these (57.7%) had an oligoarthritic pattern at presentation (42.3% monoarthritis), 65.4% had received intra-articular steroids in the previous studies. Conclusions Ten year follow up of an early Oligoarthritis cohort shows that over a third of patients attending for review are in drug free clinical remission. The majority had received joint steroid injections ± SSZ early on in their disease onset suggesting that early intervention may lead to clinical remission. These results can throw important insights into the pathogenesis of this condition and provide useful guidance for clinicians managing these patients. References Green, M., et al. Arthritis & Rheumatism, 2001. 44(5): p. 1177-1183. Marzo-Ortega, H., et al. Arthritis & Rheumatism, 2007. 57 (1): p. 154-160. Disclosure of Interest None Declared
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ten year follow up of spa related Oligoarthritis involving the knee the presence of psoriasis but not hla b27 or baseline mri bone oedema predicts outcome
Rheumatology, 2012Co-Authors: Alexander N Bennett, Michael J Green, Paul Emery, H Marzoortega, Ai Lyn Tan, Elizabeth M A Hensor, Dennis McgonagleAbstract:Objective. Bone marrow oedema (BMO) and HLA-B27 are poor prognostic factors in axial SpA, and psoriasis is a poor prognostic factor in small-joint polyarthropathy. The aim of this study was to investigate the influence of HLA-B27, MRI BMO and psoriasis on long-term outcomes in early SpA-related knee joint Oligoarthritis. Methods. Patients with SpA-related Oligoarthritis with knee involvement were recruited. Baseline assessment included ESSG criteria, RF, HLA-B27 and MRI. The degree of MRI BMO was determined on fat-suppression sequences and scored using the whole-organ magnetic resonance imaging score (WORMS) (range 045). Patients were treated at the discretion of their rheumatologist and followed up for 10 years. Outcome assessments included joint counts, functional and symptomatic questionnaire, CRP and radiographic assessment for OA. Results. Forty-four patients were recruited [mean age 32 years (range 1559 years), 70% male] with a mean disease duration at baseline of 9.75 months (148 months). Twenty-six (59%) patients (mean age 43 years, 65% male) returned for follow-up after a mean of 10 years (range 8.412.6 years). Ten (38%) patients had persistent clinical synovitis and 31% of knees had secondary radiographic OA. Global outcome was poor/very poor in 69% of cases. The only factor predicting outcome at 10 years was psoriasis, but neither HLA-B27 nor BMO. PsA patients had significantly worse global outcome compared with ReA (P = 0.036), and significantly worse symptomatic (P = 0.001) and functional (P = 0.001) outcome compared with other subtypes.
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a randomized controlled trial of early intervention with intraarticular corticosteroids followed by sulfasalazine versus conservative treatment in early Oligoarthritis
Arthritis Care and Research, 2007Co-Authors: H Marzoortega, Michael J Green, Richard J Wakefield, Susanna M Proudman, Annemaree Keenan, Paul EmeryAbstract:Objective To determine the outcome after 52 weeks of early intervention with intraarticular corticosteroid injections followed by sulfasalazine versus conservative therapy in patients with recent-onset Oligoarthritis in a randomized controlled trial. Methods Patients with ≤4 joints with clinical synovitis (disease duration ≤12 months) were randomized to early intervention (EI) with intraarticular methylprednisolone into all synovitic joints or to conservative treatment (CT) with nonsteroidal antiinflammatory drugs alone. Sulfasalazine was administered in both groups for persistent disease or disease that evolved into a polyarthritis. Primary outcome was complete response (CR) defined as the absence of synovitis at 52 weeks. Secondary outcomes included CR at weeks 4 and 12, function (Health Assessment Questionnaire), pain (0–100-mm visual analog scale), and work status. Results Fifty-nine patients (34 men, 25 women; mean age 32.9 years; median early morning stiffness 30 minutes) were randomized. At baseline, two-thirds reported that they were work impaired. At 52 weeks, 81% of patients in the EI group achieved CR compared with 57% in the CT group (χ2 = 3.833, 1 df, P = 0.05). In addition, 45% of patients in the EI group received sulfasalazine as opposed to 14% in the CT group (χ2 = 5.156, 1 df, P = 0.019). There were no differences in physical disability or work impairment between the treatment groups. Conclusion Oligoarthritis has a significant impact on function and work ability. Patients treated with EI using intraarticular corticosteroids followed by sulfasalazine therapy if resistant demonstrated reduced synovitis 12 months after treatment compared with those initially treated with more conservative therapy.
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should Oligoarthritis be reclassified ultrasound reveals a high prevalence of subclinical disease
Annals of the Rheumatic Diseases, 2004Co-Authors: Richard J Wakefield, Michael J Green, Helena Marzoortega, Susanna M Proudman, Dennis Mcgonagle, P G Conaghan, Wayne Gibbon, Paul EmeryAbstract:Objective: To determine the prevalence of subclinical synovitis using ultrasound (US) imaging of both painful and asymptomatic joints, in patients with early ( Methods: Eighty patients underwent a detailed clinical assessment by two physicians. All painful joints were identified, which were immediately scanned by a sonographer. In the last 40 patients, an additional standard group of joints was scanned to establish the prevalence of synovitis in asymptomatic joints. Results: In 80 patients, 644 painful joints (with and without clinical synovitis) were identified and each underwent a US assessment. Of these joints, 185 had clinical synovitis, of which, US detected synovitis in only 79% (147/185). In the other 38 joints US demonstrated tenosynovitis instead of synovitis in 12 joints and possible, but not definite, synovitis in 11 joints. Fifteen joints were, however, normal on US. In 459 joints that were not clinically synovitic, US detected synovitis in 33% (150/459). In 64% (51/80) of patients, US detected synovitis in more joints than clinical examination and in 36% (29/80) of patients, US detected a polyarthritis (>6 joints). Of the 826 asymptomatic (non-painful) joints scanned, 13% (107/826) had US detected synovitis. Conclusion: Sonography detected more synovitis than clinical examination in patients with Oligoarthritis. In almost two thirds of patients there was evidence of subclinical disease while one third could be reclassified as polyarticular. These findings suggest that a definition of Oligoarthritis based purely on clinical findings may be inappropriate, which may have important implications for disease management.
Eleftheria Zeggini - One of the best experts on this subject based on the ideXlab platform.
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linkage and association studies of discoidin domain receptor 1 ddr1 single nucleotide polymorphisms snps in juvenile Oligoarthritis
Rheumatology, 2004Co-Authors: Eleftheria Zeggini, Wendy Thomson, A M Reginato, A Prais, William Mclean, Rachelle DonnAbstract:OBJECTIVES: Multiple independent juvenile Oligoarthritis susceptibility loci have been identified within the major histocompatibility complex (MHC), including HLA-A, HLA-DRB1 and an as yet unlocalized effect in the centromeric class I region. The discoidin domain receptor 1 (DDR1) gene resides within this region and codes for a receptor tyrosine kinase that plays an important role in regulating cell attachment to collagen, chemotaxis, proliferation and matrix metalloproteinase (MMP) production. DDR1 expression in chondrocytes has not been investigated. The objectives of this study were to investigate expression of DDR1 in healthy chondrocytes and to identify linkage and association of this candidate gene with juvenile Oligoarthritis. METHODS: A set of 135 simplex juvenile idiopathic arthritis families consisting of one affected child and healthy parent(s) and 199 healthy unrelated individuals were genotyped for six single nucleotide polymorphisms (SNPs) within the DDR1 gene using the primer extension SNaPshot(TM) method. Single-point and multipoint transmission disequilibrium tests were carried out with the ETDT and TDTPHASE packages. Allele frequency comparisons between cases and controls were carried out with the chi(2) test. DDR1 expression was investigated in normal articular cartilage by RT-PCR and immunofluorescence methods. RESULTS: No linkage and association with any of the six SNPs or their haplotypic combinations were observed in the families studied. No significant differences were observed in allele frequencies between patients and controls. DDR1 expression was found in normal articular cartilage by RT-PCR and by immunofluorescence. CONCLUSIONS: The DDR1 SNPs examined are not involved in susceptibility to juvenile Oligoarthritis.
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linkage and association studies of single nucleotide polymorphism tagged tumor necrosis factor haplotypes in juvenile Oligoarthritis
Arthritis & Rheumatism, 2002Co-Authors: Eleftheria Zeggini, William E R Ollier, Wendy Thomson, Dominic P Kwiatkowski, Anna Richardson, Rachelle DonnAbstract:Objective The presence of increased levels of tumor necrosis factor (TNF) in serum and synovial fluid of patients and the encouraging outcome of anti-TNF therapy have implicated TNFα in the etiopathogenesis of juvenile Oligoarthritis. Although the locus is polymorphic, no study has investigated all TNF single-nucleotide polymorphisms (SNPs) with respect to disease. The aim of this study was to examine the association of multiple TNF SNPs with juvenile Oligoarthritis and to construct and analyze SNP-tagged TNF haplotypes. Methods A total of 144 simplex families consisting of parent and affected child, as well as 88 healthy, unrelated control subjects were available for study. In these individuals, 9 polymorphic positions of TNF were typed by a high-throughput genotyping method based on the SNaPshot assay. The chi-square and extended transmission disequilibrium tests were used to test for association and linkage, respectively. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were also calculated. Haplotype-tagging SNPs (htSNPs) for the locus were identified by ordering the haplotypes according to their frequencies. Results The study detected association of several TNF SNPs and established linkage of the locus to juvenile Oligoarthritis. The most significant association observed was between the intronic +851 TNF SNP and the persistent Oligoarthritis subgroup (OR 3.86, 95% CI 1.6–9.2). Haplotype data mining showed that only 4 of the 9 SNPs need to be typed in order to capture the most frequent TNF haplotypes. Conclusion The TNF locus is linked and associated with juvenile Oligoarthritis. Information on the htSNPs can be useful in genetic studies of diseases in which TNF may be of relevance.
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evidence for linkage of hla loci in juvenile idiopathic Oligoarthritis independent effects of hla a and hla drb1
Arthritis & Rheumatism, 2002Co-Authors: Eleftheria Zeggini, Rachelle Donn, William E R Ollier, Wendy ThomsonAbstract:Objective Although multiple associations between HLA loci and juvenile Oligoarthritis have previously been documented, evidence for linkage of HLA loci in Oligoarthritis in UK Caucasians with juvenile idiopathic arthritis (JIA) has not been described. The aim of this study was to investigate linkage of HLA–A, B, and DRB1 in UK Caucasian JIA patients with Oligoarthritis. Methods One hundred forty-two families comprising affected offspring and their parents (45 with one parent available and 97 with both parents available) were typed for HLA–A, B, and DRB1 by polymerase chain reaction–sequence-specific oligonucleotide probe. Single-point and multipoint analyses were performed using various modifications of the extended transmission disequilibrium test. Linkage disequilibrium (LD) analysis was performed using the EH-Plus system. Results Linkage to HLA–A and HLA–DRB1 was seen in Oligoarthritis and in the International League of Associations for Rheumatology–defined subgroups of persistent Oligoarthritis and extended Oligoarthritis. Linkage to HLA–A, B, and DRB1 was also observed in female patients with Oligoarthritis. Linkage of the HLA loci seemed to be attributable to maternal preferential transmission of alleles. Furthermore, LD patterns between the HLA–A, B, and DRB1 loci were investigated. HLA–A and HLA–DRB1 were confirmed as independent susceptibility loci for Oligoarthritis. Conclusion This is the first study to establish linkage of HLA–A and HLA–DRB1 in Oligoarthritis and to show that the 2 loci contribute independently to disease. Further studies are being performed to determine whether it is these loci or other genes in LD with them that are responsible for susceptibility to Oligoarthritis in UK Caucasian patients with JIA.
H Marzoortega - One of the best experts on this subject based on the ideXlab platform.
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fri0275 long term follow up of an early Oligoarthritis cohort shows that early aggressive intervention leads to drug free remission after 10 years results from the loto study
Annals of the Rheumatic Diseases, 2013Co-Authors: Concepcion Castillogallego, Michael J Green, Sibel Zehra Aydin, Sharmin Nizam, Paul Emery, H MarzoortegaAbstract:Background Oligoarthritis is as an inflammatory arthritis affecting ≤4 joints. It represents either an early clinical presentation or a unique disease phenotype within the group of the SpA. Oligoarthritis typically affects young people causing high morbidity and has a variable. We have previously reported on the effect of early intervention with intra-articular corticosteroids and sulfasalazine (SSZ) in a cohort of patients presenting with an Oligoarthritis of recent onset with 80% of patients achieving clinical remission after 52 weeks. We now report on the long-term outcome of this cohort after 10 years. Objectives To report the rate of disease persistence/clinical remission in the long-term follow up of the Leeds cohort of early Oligoarthritis. Methods Cross-sectional follow up of patients who participated in two previous interventional studies [1, 2]. Subjects were invited to either attend for a single study visit or a telephone consult. Presence/absence of any musculoskeletal symptoms and current diagnosis was recorded. Blood tests for inflammatory markers and radiographs of SIJs or any relevant joints were performed only if clinically indicated to establish a diagnosis if persistent clinical symptoms. Results The initial cohort comprised of a total of 117 patients, of whom 5 were deceased. An invitation letter was sent out to 112 patients (95.7%). Follow up data are available from a total of 74 patients (63.3%) [mean (SD) disease duration at presentation 13.8 (1.8) months; with a disease duration of 13 (3) years at follow up] of whom 22 (29.8%) attended for a follow up visit; 28 (37.8%) were assessed via telephone consult and 24 (32.4%) had data extracted from the clinical notes. Analysis of the attenders show that 47 patients (63.5%) had had persistent arthritis since the end of the previous studies (19.5% were RF positive; 33.3% antiCCP positive and 32.4% HLA B27 positive). The majority (74%) had received joint steroid injections ± SSZ as previous study protocols. Only 17% had a monoarticular presentation. The majority of patients (83%) had an oligoarticular pattern at disease presentation which was maintained over time in 68%. Fifteen percent (15%) had developed mixed phenotype with axial and peripheral joint involvement. 36.5% of patients (4% and 17.4% RF and HLA-B27 positive respectively) had remained asymptomatic in this time with no hospital follow up. The majority of these (57.7%) had an oligoarthritic pattern at presentation (42.3% monoarthritis), 65.4% had received intra-articular steroids in the previous studies. Conclusions Ten year follow up of an early Oligoarthritis cohort shows that over a third of patients attending for review are in drug free clinical remission. The majority had received joint steroid injections ± SSZ early on in their disease onset suggesting that early intervention may lead to clinical remission. These results can throw important insights into the pathogenesis of this condition and provide useful guidance for clinicians managing these patients. References Green, M., et al. Arthritis & Rheumatism, 2001. 44(5): p. 1177-1183. Marzo-Ortega, H., et al. Arthritis & Rheumatism, 2007. 57 (1): p. 154-160. Disclosure of Interest None Declared
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ten year follow up of spa related Oligoarthritis involving the knee the presence of psoriasis but not hla b27 or baseline mri bone oedema predicts outcome
Rheumatology, 2012Co-Authors: Alexander N Bennett, Michael J Green, Paul Emery, H Marzoortega, Ai Lyn Tan, Elizabeth M A Hensor, Dennis McgonagleAbstract:Objective. Bone marrow oedema (BMO) and HLA-B27 are poor prognostic factors in axial SpA, and psoriasis is a poor prognostic factor in small-joint polyarthropathy. The aim of this study was to investigate the influence of HLA-B27, MRI BMO and psoriasis on long-term outcomes in early SpA-related knee joint Oligoarthritis. Methods. Patients with SpA-related Oligoarthritis with knee involvement were recruited. Baseline assessment included ESSG criteria, RF, HLA-B27 and MRI. The degree of MRI BMO was determined on fat-suppression sequences and scored using the whole-organ magnetic resonance imaging score (WORMS) (range 045). Patients were treated at the discretion of their rheumatologist and followed up for 10 years. Outcome assessments included joint counts, functional and symptomatic questionnaire, CRP and radiographic assessment for OA. Results. Forty-four patients were recruited [mean age 32 years (range 1559 years), 70% male] with a mean disease duration at baseline of 9.75 months (148 months). Twenty-six (59%) patients (mean age 43 years, 65% male) returned for follow-up after a mean of 10 years (range 8.412.6 years). Ten (38%) patients had persistent clinical synovitis and 31% of knees had secondary radiographic OA. Global outcome was poor/very poor in 69% of cases. The only factor predicting outcome at 10 years was psoriasis, but neither HLA-B27 nor BMO. PsA patients had significantly worse global outcome compared with ReA (P = 0.036), and significantly worse symptomatic (P = 0.001) and functional (P = 0.001) outcome compared with other subtypes.
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a randomized controlled trial of early intervention with intraarticular corticosteroids followed by sulfasalazine versus conservative treatment in early Oligoarthritis
Arthritis Care and Research, 2007Co-Authors: H Marzoortega, Michael J Green, Richard J Wakefield, Susanna M Proudman, Annemaree Keenan, Paul EmeryAbstract:Objective To determine the outcome after 52 weeks of early intervention with intraarticular corticosteroid injections followed by sulfasalazine versus conservative therapy in patients with recent-onset Oligoarthritis in a randomized controlled trial. Methods Patients with ≤4 joints with clinical synovitis (disease duration ≤12 months) were randomized to early intervention (EI) with intraarticular methylprednisolone into all synovitic joints or to conservative treatment (CT) with nonsteroidal antiinflammatory drugs alone. Sulfasalazine was administered in both groups for persistent disease or disease that evolved into a polyarthritis. Primary outcome was complete response (CR) defined as the absence of synovitis at 52 weeks. Secondary outcomes included CR at weeks 4 and 12, function (Health Assessment Questionnaire), pain (0–100-mm visual analog scale), and work status. Results Fifty-nine patients (34 men, 25 women; mean age 32.9 years; median early morning stiffness 30 minutes) were randomized. At baseline, two-thirds reported that they were work impaired. At 52 weeks, 81% of patients in the EI group achieved CR compared with 57% in the CT group (χ2 = 3.833, 1 df, P = 0.05). In addition, 45% of patients in the EI group received sulfasalazine as opposed to 14% in the CT group (χ2 = 5.156, 1 df, P = 0.019). There were no differences in physical disability or work impairment between the treatment groups. Conclusion Oligoarthritis has a significant impact on function and work ability. Patients treated with EI using intraarticular corticosteroids followed by sulfasalazine therapy if resistant demonstrated reduced synovitis 12 months after treatment compared with those initially treated with more conservative therapy.
