Rheumatoid Arthritis: Harrison B

Ollier WE, Harrison B, Symmons D. · ARC Epidemiology Unit, University of Manchester Medical School, Oxford Road, Manchester, M13 9PT, UK. · Best Pract Res Clin Rheumatol. · Pubmed #11358413 No free full text.

Abstract: Inflammatory polyarthritis can be a self-limiting disease, develop into rheumatoid arthritis (RA) or differentiate into another form of chronic arthritis. It remains a clinical and scientific challenge to understand the relationship between these phenotypes, determine their aetiologies and predict the course and outcome for individual patients. Even patients labelled as having RA show a wide spectrum of clinical phenotypes. Disease definition is a major problem in studying the aetiology of RA as currently used classification criteria were derived using patients with established disease. RA is thought to result from the combination of genetic susceptibility and exposure to an appropriate environmental trigger. The genetic component is probably oligogenic. The association with HLA has been known for over 25 years. RA is now thought to be associated with a conserved sequence of amino acids in a number of HLA-DRB1 alleles, called the RA shared epitope. However, the shared epitope appears to be associated with RA chronicity and severity more than with susceptibility. Other potential RA susceptibility genes include IL-1, aromatase, corticotropin-releasing hormone and a region on the X chromosome. Hormonal and reproductive factors also influence RA susceptibility and severity. RA is more common in women than men, especially before the menopause. Men may be protected by hormonal factors and require a stronger genetic component to develop disease. Although infectious triggers of RA have long been suspected, no definitive evidence has been obtained. Previous blood transfusion, smoking and obesity are also possible risk factors. Chronicity and remission are important aspects of the natural history of early RA. Although we can identify patients at risk of adverse prognosis with some accuracy, we remain unable to predict remission. Functional disability and radiological damage are the most studied outcomes in RA. Radiological damage often occurs early in the course of RA, but patients may show erosion for the first time several years after symptom onset. Many studies have demonstrated a relationship between HLA and features of severe RA in established patients. This appears to be related to gene dosage.

Harrison B, Symmons D. · Withington Hospital, Manchester, UK. · Rheumatology (Oxford). · Pubmed #10986297 links to  free full text

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Symmons D, Harrison B. · ARC Epidemiology Unit, University of Manchester Medical School, Oxford Road, Manchester and East Cheshire NHS Trust, Macclesfield and. Withington Hospital, Manchester, UK. · Rheumatology (Oxford). · Pubmed #10952736 links to  free full text

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Bukhari M, Harrison B, Lunt M, Scott DG, Symmons DP, Silman AJ. · University of Manchester, UK. · Arthritis Rheum. · Pubmed #11407682 links to  free full text

Abstract: OBJECTIVE: To examine the time of occurrence of first radiographic erosions in a cohort of patients with inflammatory polyarthritis. METHODS: Patients were recruited through the Norfolk Arthritis Register, which follows up patients annually. Patients with features of rheumatoid arthritis (other than erosions) sufficient, together with erosions, to meet the American College of Rheumatology (formerly, the American Rheumatism Association) 1987 revised criteria were requested to undergo radiographic examinations of the hands and feet at the first and/or second annual followup visits. All patients were requested to undergo radiographic examinations at the fifth annual followup visit. The most recent erosion-free radiograph was identified for 416 eligible patients, and these data were used to derive the duration of disease since the recalled date of onset of first symptoms. The rate of occurrence of first erosions was then determined (as a cumulative prevalence and as an incidence rate using Poisson regression) from analysis of followup films. Patients were assumed to be free of erosions at symptom onset. RESULTS: The cumulative prevalence of erosions in patients whose first film was obtained 12-24 months after disease onset was 36%, equivalent to an incidence rate of 24.5/1,000 patient-months. We identified 3 analysis groups of patients who were free of erosions based on films obtained 12-24 months, 24-36 months, and 36-60 months since the recalled date of onset of first symptoms. New erosions were observed in all 3 groups, with cumulative prevalences of 23%, 28%, and 47%, respectively. These were equivalent to first-erosion incidence rates/1,000 patient-months of 5.4 (95% confidence interval [95% CI] 3.8-83), 6.8 (95% CI 4.7-10.0), and 13.0 (95% CI 8.9-19.2), respectively. CONCLUSION: Many patients with erosive disease first develop their erosions >2 years from disease onset.

Berthelot JM, Klarlund M, McGonagle D, Bernelot-Moens HJ, Calin A, Harrison B, Schumacher HR, Kaarela K, Drosos AA, Hülsemann JL, Koh WH, Konttinen YT, Punzi L, Tanimoto K, Williams HJ, Wolfe F, Zerbini CA, Saraux A, Anonymous00239. · Department of Rheumatology, Nantes University Medical School, CHU Nantes, France. · J Rheumatol. · Pubmed #11361225 No free full text.

Abstract: OBJECTIVE: To determine how experts would classify 10 early-arthritis cases (7 atypical) and to study discrepancies in diagnoses relative to ACR criteria for rheumatoid arthritis (RA) or ESSG criteria for spondyloarthropathy (SpA). METHODS: Ten real cases (5 met ACR criteria for RA, 6 ESSG criteria for SpA, 3 both and 2 neither) followed for 28.5 +/- 4.8 months were sent as paper cases to 20 international and 12 French experts. Each expert selected a diagnosis among 8 possible choices and rated it on a 0-10 confidence scale. For each case, 3 analog scales (0-100 mm) were used to indicate the probability of RA, SpA or undifferentiated arthritis (UA). RESULTS: Experts often disagreed about diagnoses (up to 5 different diagnoses for a given case, with a mean of 3.9 per case). Similarly, expert opinions on probabilities for RA and SpA differed widely, with great overlap between confidence for RA, SpA and UA. Fulfilment of ACR or ESSG criteria was poorly related to the experts' diagnosis and evaluation of probabilities for RA and SpA. However, UA was a relatively infrequent choice (19%). CONCLUSIONS: There was no general consensus about the nosology of early RA and SpA. Classification of atypical early arthritis was not resolved by currently available criteria for RA and SpA. This may have implications for therapy in early 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.

Thomson W, Harrison B, Ollier B, Wiles N, Payton T, Barrett J, Symmons D, Silman A. · Epidemiology Research Unit, Manchester University Medical School, UK. · Arthritis Rheum. · Pubmed #10211891 links to  free full text

Abstract: OBJECTIVE: To accurately determine the contributions of HLA-DRB1 alleles in explaining susceptibility to inflammatory polyarthritis in a large, true population-based cohort of new-onset cases. METHODS: A cohort of 680 consecutive patients with inflammatory polyarthritis, of whom 404 satisfied the American College of Rheumatology (ACR) criteria for rheumatoid arthritis (RA), was recruited from the population-based Norfolk Arthritis Register. All cases were compared with 286 local population controls. A standardized clinical assessment was performed on all patients. HLA-DRB1 phenotypes, including DR4 subtypes, were determined using a semiautomated, reverse dot-blot method. Results were expressed as odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: There was only a modest association (OR 1.8, 95% CI 1.4-2.4) between inflammatory polyarthritis and the presence of any shared epitope (SE) allele; the strongest individual risk was with DRB1*0404 (OR 3.5, 95% CI 1.8-6.8). Comparison of the genotypes demonstrated that the effect of being SE homozygous (OR 2.1, 95% CI 1.5-3.0) was only moderately greater than the effect of being SE heterozygous (OR 1.3, 95% CI 1.1-1.6). The exception to this was genotypic combinations that included HLA-DRB1*0404, which exhibited ORs ranging up to 18.0. There were no differences between either the phenotype or genotype data when the patients were stratified by RA status (defined by the ACR criteria). In contrast, the associations were substantially stronger in patients who were positive for rheumatoid factor. CONCLUSION: Previous studies had not been able to clarify whether the influence of HLA-DRB1 on RA was related to disease susceptibility or to disease severity and progression. These data on a unique population-based incident cohort suggest only weak effects on susceptibility, with the exception of the clearly distinct influence of HLA-DRB1*0404.