Rheumatoid Arthritis: Barrett E

Barton A, Platt H, Salway F, Symmons D, Barrett E, Bukhari M, Lunt M, Zeggini E, Eyre S, Hinks A, Tellam D, Brintnell B, Ollier W, Worthington J, Silman A. · University of Manchester, UK. · Ann Rheum Dis. · Pubmed #14962963 links to  free full text

Abstract: BACKGROUND: Tumour necrosis factor alpha (TNFalpha) is a powerful inflammatory mediator in rheumatoid and other types of inflammatory arthritis. Polymorphisms within the TNFalpha gene have previously been investigated to determine their role in the aetiopathogenesis of rheumatoid arthritis (RA), but it is unclear whether reported associations are with susceptibility to, or severity of, disease. OBJECTIVE: To examine the association between both individual TNFalpha single nucleotide polymorphisms (SNPs) and haplotypes with the development and severity of erosions by 5 years in patients with inflammatory polyarthritis (IP). METHODS: 438 patients from the Norfolk Arthritis Register observational inception cohort of patients with IP were x rayed 5 years after disease onset. They were genotyped for nine SNPs mapping to the TNFalpha gene, using a SNaPshot primer extension assay. Haplotypes were constructed in patients with IP, who were compared for the presence and extent of erosions at 5 years. RESULTS: No association between individual TNFalpha SNPs or haplotypes in the patients who developed erosions at 5 years compared with those who remained non-erosive was found. Restricting analysis to patients who satisfied ACR criteria for RA by 5 years did not affect the conclusions. CONCLUSION: The TNFalpha gene does not seem to be associated with severity as assessed by erosive outcome at 5 years in patients with IP.

Symmons D, Turner G, Webb R, Asten P, Barrett E, Lunt M, Scott D, Silman A. · ARC Epidemiology Unit, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK. · Rheumatology (Oxford). · Pubmed #12096230 links to  free full text

Abstract: BACKGROUND: It is 40 yr since the last age- and sex-specific estimates of the prevalence of rheumatoid arthritis (RA) for the UK were published. Since then the classification criteria for RA have been revised and there has been evidence of a fall in the incidence of RA, especially in women. OBJECTIVES: To estimate the age- and sex-specific point prevalence of RA (defined as fulfilment of a modification of the 1987 ACR classification criteria for RA on the day of assessment). The estimate was made in the primary care setting in Norfolk, UK. METHODS: A stratified random sample was drawn from seven age and gender bands. The 7050 individuals selected were mailed a screening questionnaire. Positive responders were invited to attend for a clinical examination. The sample was matched against the names in the Norfolk Arthritis Register (NOAR), a register of incident cases of inflammatory polyarthritis which has been in existence since 1990. RESULTS: The overall response rate was 82%. Sixty-six cases of RA were identified. Extrapolated to the population of the UK, the overall minimum prevalence of RA is 1.16% in women and 0.44% in men. A number of incident cases of RA previously notified to NOAR were not identified as cases in the survey because they had entered into treatment-induced remission. In addition, some cases who failed to attend for examination had significant disability. These prevalence figures are therefore an underestimate. CONCLUSIONS: The prevalence of RA in women, but not in men, in the UK may have fallen since the 1950s.

Wiles N, Dunn G, Barrett E, Silman A, Symmons D. · ARC Epidemiology Unit, University of Manchester Medical School, Manchester, UK. · J Clin Epidemiol. · Pubmed #11027930 No free full text.

Abstract: OBJECTIVES: To investigate whether the relationship between demographic and disease-related variables and disability is constant during the first five years of inflammatory polyarthritis (IP) and to identify the contribution from involvement of specific joint areas to overall disability. METHODS: 684 patients referred to the Norfolk Arthritis Register were followed for five years using the Health Assessment Questionnaire (HAQ). The relationship between disability and demographic and clinical variables was analyzed using a multi-level modelling approach. RESULTS: Female gender, older age at symptom onset (> or = 64 years), joint involvement at six specific sites, joint tenderness and the number of deformed joints were all independently associated with disability (HAQ > or = 1.00). Similar results were obtained using a more stringent cut-off (HAQ > or = 1.50) or when analysis was restricted to the 325 patients who satisfied the 1987 ARA list criteria for rheumatoid arthritis. CONCLUSION: Disability, as measured by the HAQ, was associated with a large number of independent factors over the first five years of disease.

Silman A, Harrison B, Barrett E, Symmons D. · ARC Epidemiology Unit, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK. · Ann Rheum Dis. · Pubmed #10666175 links to  free full text

Abstract: OBJECTIVES: To determine whether there is any evidence that there are spatial clusters of rheumatoid arthritis in particular, and inflammatory arthritis in general. METHODS: Setting was a population based incidence register of inflammatory arthritis: the Norfolk Arthritis Register (NOAR). All cases identified between 1990-1995 were mapped to place of residence. Statistical evidence of clustering was determined by calculating Poisson probabilities in putative areas. RESULTS: Three clusters were identified including one small area (population 85) where five unrelated cases developed during this time period. There was no obvious greater disease homogeneity within clusters and no common environmental factors were identified. CONCLUSION: Rare clusters of inflammatory polyarthritis do occur. Their significance and cause remain to be elucidated.

Harrison B, Thomson W, Symmons D, Ollier B, Wiles N, Payton T, Barrett E, Silman A. · University of Manchester, UK. · Arthritis Rheum. · Pubmed #10524690 links to  free full text

Abstract: OBJECTIVE: There are conflicting data concerning the role of HLA-DRB1 alleles in disease outcome in early rheumatoid arthritis. The exact role of these alleles in short-term outcome is determined in this large, prospective, population-based study. METHODS: We recruited 532 patients with inflammatory polyarthritis from the Norfolk Arthritis Register and typed their sera for HLA-DRB1 alleles using polymerase chain reaction-based methods. Disease outcome was assessed at 2 years in terms of persistent joint inflammation, functional disability, and radiologic erosions. Results are expressed as risk ratios (RR) with 95% confidence intervals (95% CI). RESULTS: There was no influence of HLA-DRB1 alleles, in any combination, on the likelihood of disease persistence, and only a modest effect on functional disability (Health Assessment Questionnaire score > or = 1). The most obvious effect was on the development of erosions (RR 1.9, 95% CI 1.4-2.6 for those who carried at least 1 DRB1 shared epitope [SE] allele), with slightly greater effects for those who were homozygous for SE-bearing alleles (RR 2.5, 95% CI 1.8-3.6). This effect of HLA-DRB1 was restricted to patients whose sera were negative for rheumatoid factor. Among patients with erosions, HLA-DRB1 had no influence on the severity of radiologic damage (defined as the number of eroded joints, or total Larsen score). CONCLUSION: These data do not support routine HLA-DRB1 screening of patients with early arthritis to identify those at risk for subsequent severe disease.

Wiles N, Symmons DP, Harrison B, Barrett E, Barrett JH, Scott DG, Silman AJ. · University of Manchester Medical School, UK. · Arthritis Rheum. · Pubmed #10403260 links to  free full text

Abstract: OBJECTIVE: To examine the effect of delay between symptom onset and notification to an arthritis register and the effect of application of the American College of Rheumatology (ACR; formerly, the American Rheumatism Association) 1987 criteria in a cumulative manner on estimates of the incidence of rheumatoid arthritis (RA). METHODS: General practitioners and/or hospital consultants in the Norwich Health Authority, Norfolk, UK, notified the Norfolk Arthritis Register (NOAR) of all patients who had onset of inflammatory polyarthritis (swelling of > or =2 joints) during 1990. The patients were assessed within 2 weeks of notification and annually thereafter. The ACR 1987 criteria for RA were applied at each assessment. Age- and sex-specific incidence rates were calculated. RESULTS: If up to 12 months elapsed from symptom onset to notification to NOAR and the ACR criteria were applied at the baseline assessment, RA incidence estimates, age-adjusted to the population of England and Wales, were 30.8/100,000 for women and 12.7/100,000 for men. If up to 5 years elapsed from symptom onset to notification, these estimates rose by 45% for women and 36% for men. If up to 5 years elapsed between symptom onset and notification and the criteria were applied cumulatively, the estimates rose by 75% and 93% for women and men, respectively, compared with the 1-year data, reaching 54.0/100,000 for women and 24.5 per 100,000 for men. CONCLUSION: Accurate estimation of the incidence of RA requires long-term followup of patients who present with undifferentiated inflammatory polyarthritis. The highest age-adjusted estimates from this study are probably the best that are available.

Wiles N, Barrett J, Barrett E, Silman A, Symmons D. · ARC Epidemiology Research Unit, University of Manchester, UK. · J Rheumatol. · Pubmed #10229399 No free full text.

Abstract: OBJECTIVE: To determine whether disability in patients with early inflammatory polyarthritis (IP) can be charted or "tracked" over time. The disability score was also adjusted in an attempt to exclude the influence of current disease activity, with the aim of ascertaining that component of disability relating to other factors such as psychosocial factors and joint damage. METHODS: Four hundred thirty-three patients with early IP referred to the Norfolk Arthritis Register (NOAR) were followed annually using the Health Assessment Questionnaire (HAQ) for 5 years. HAQ scores at each year were divided into quartiles. The number of patients remaining in the same quartile from year to year was examined. The relationship between disease activity, assessed by swollen and tender joint counts, and HAQ was modelled, with the residual HAQ attributed to psychosocial factors and joint damage. RESULTS: From year to year, there was considerable within-individual variation in quartile, with only 48-65% of patients remaining in the same quartile. With increasing time, a greater proportion of patients remained in the same quartile. A statistically valid activity-adjusted HAQ score could not be computed. CONCLUSION: Disability in patients with early IP cannot be easily tracked over time. It is therefore not appropriate to construct longitudinal reference charts for disability in the early years, although it may be feasible for more established disease.