Beverley Harrison

Estimating the incidence of rheumatoid arthritis: Trying to hit a moving target

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.

Environmental risk factors for the development of psoriatic arthritis: results from a case control study

Objective: To identify potential risk factors for the onset of inflammatory arthritis (IA) in a large cohort of patients with psoriatic arthritis (PsA) of recent onset. Methods: We recruited cases with psoriasis and an onset of IA within the past 5 years. Controls were patients who had psoriasis but no arthritis. We assessed potential factors associated with the development of IA using a detailed postal questionnaire. An unmatched analysis adjusted for age and gender was performed. Exposure was censored in the controls at a “dummy-date” assigned randomly in proportion to the percentage of cases developing IA in any given year. Results: We studied 98 cases and 163 controls. Exposures showing a positive association before the onset of IA in patients with psoriasis were: rubella vaccination (OR (95% CI) = 12.4 (1.2 to 122)), injury sufficient to require a medical consultation (2.53 (1.1 to 6.0)), recurrent oral ulcers (4.2 (2.0 to 9.0)) and moving house (2.3 (1.2 to 4.4)). Cases were also more likely to have experienced a fractured bone requiring hospital admission (50% vs 9%, p = 0.040). Conclusions: We found a number of environmental exposures associated with the onset of IA in subjects with psoriasis. The strongest associations were with trauma thereby adding to the hypothesis of a “deep Koebner phenomenon” in PsA. Our data also suggest that exposure of the immune system to certain infection-related triggers may also be of relevance. Further studies are needed to verify these observations and to examine potential immunological mechanisms that underlie them.

Quantifying the exact role of HLA-DRB1 alleles in susceptibility to inflammatory polyarthritis: results from a large, population-based study.

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.

The association of cigarette smoking with disease outcome in patients with early inflammatory polyarthritis.

OBJECTIVE Cigarette smoking is known to increase rheumatoid factor (RF) and nodule formation in patients with rheumatoid arthritis (RA). In this study, we examined the influence of smoking on disease outcome at 3 years among patients newly presenting with inflammatory polyarthritis (IP). METHODS We studied 486 patients with IP who were referred to the Norfolk Arthritis Register, of whom 323 (67%) satisfied the American College of Rheumatology 1987 criteria for RA. Smoking status was assessed at baseline. Disease outcome was assessed at 3 years, using measures of joint inflammation, functional disability, and radiologic damage. The influence of smoking on disease outcome was explored using logistic regression techniques, with patients who had never smoked as the referent group. Results are expressed as odds ratios (ORs), with their 95% confidence intervals (95% CIs). RESULTS Current smokers were significantly more likely to be RF positive at baseline (47%) than were ex-smokers (34%) and never smokers (31%). After 3 years, rheumatoid nodules were significantly more common in smokers (13%) compared with ex-smokers/never smokers (4%), a relationship which persisted after adjusting for age and sex (OR 4.07, 95% CI 1.38-12). In contrast, after adjusting for age and sex, current smokers had significantly fewer swollen joints (OR 0.61, 95% CI 0.37-0.98). However, smoking status had no influence on the development of erosions or functional disability. CONCLUSION Despite smokers being more likely to develop nodules and to be RF positive, current smokers did not have higher levels of radiologic damage, and had fewer swollen joints. We hypothesize that this could be due to either the effect of cigarette smoking on the inflammatory response or other factors (e.g., reduced physical activity in smokers) which may limit joint inflammation and damage.

A simple algorithm to predict the development of radiological erosions in patients with early rheumatoid arthritis : prospective cohort study

Abstract Objective: To produce a practical algorithm to predict which patients with early rheumatoid arthritis will develop radiological erosions. Design: Primary care based prospective cohort study. Setting: All general practices in the Norwich Health Authority, Norfolk Subjects: 175 patients notified to the Norfolk Arthritis Register were visited by a metrologist soon after they had presented to their general practitioners with inflammatory polyarthritis, and again after a further 12 months. All the patients satisfied the American Rheumatism Associations 1987 criteria for rheumatoid arthritis and were seen by a metrologist within six months of the onset of symptoms. The study population was randomly split into a prediction sample (n = 105) for generating the algorithm and a validation sample (n = 70) for testing it. Main outcome measures: Predictor variables measured at baseline included rheumatoid factor status, swelling of specific joint areas, duration of morning stiffness, nodules, disability score, age, sex, and disease duration when the patient first presented. The outcome variable was the presence of radiological erosions in the hands or feet, or both, after 12 months. Results: A simple algorithm based on a combination of three variables—a positive rheumatoid factor test, swelling of at least two large joints, and a disease duration of more than three months—was best able to predict erosions. When the accuracy of this algorithm was tested with the validation sample, the erosion status of 79% of patients was predicted correctly. Conclusions: A simple algorithm based on three easily measured items of information can predict which patients are at high risk and which are at low risk of developing radiological erosions.

The influence of HLA–DRB1 alleles and rheumatoid factor on disease outcome in an inception cohort of patients with early inflammatory arthritis

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.

Time to first occurrence of erosions in inflammatory polyarthritis: Results from a prospective community‐based study

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.

Low frequency of recent parvovirus infection in a population-based cohort of patients with early inflammatory polyarthritis

OBJECTIVE To determine the contribution of human parvovirus B19 infection in explaining the incidence of early inflammatory polyarthritis (IP) in a population. SETTING The Norfolk Arthritis Register (NOAR) is a community-based programme aiming to ascertain all new cases of IP arising in a population that lead to attendance at primary care. SUBJECTS 147 newly ascertained subjects with IP with a disease duration of less than 16 weeks. METHODS Full clinical appraisal of all subjects who were followed up for three years. B19 IgM assayed with a third generation antibody capture enzyme immunoassay. RESULTS Only four (2.7%) patients had evidence of recent B19 infection, only one of whom did not satisfy criteria for rheumatoid arthritis (RA). CONCLUSION B19 infection does not explain more than a small proportion of either RA or undifferentiated IP cases occurring in the population.

The existence of geographical clusters of cases of inflammatory polyarthritis in a primary care based register

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.

Diagnostic evaluation of classification criteria for RA and reactive arthritis

We read with interest the recent article by Hulsemann and Zeidler,1 in which the 1987 American College of Rheumatology (ACR) classification criteria for rheumatoid arthritis (RA) were evaluated for their ability to identify patients with a clinical diagnosis of RA among 217 patients referred to an early arthritis clinic. The authors concluded that the 1987 ACR criteria can be used to make a diagnosis of RA in this setting. In this study, the “gold standard” against which the criteria were tested was an “expert diagnosis” made by one of the authors when the patient was first seen (within one year of symptom onset). However, the main difficulty facing the rheumatologist for patients with early disease is that patients who ultimately develop RA appear clinically similar to those who have self limiting disease or other forms of inflammatory arthritis. It is therefore too early to make an accurate diagnosis at this stage. More importantly, RA is a heterogeneous disease with a prognosis which varies from complete symptom remission to severe disability. Therefore simply categorising patients into those who do and do not have “RA” is not necessarily important when considering which patients require early treatment. Although the authors made a clinical diagnosis without using the classification criteria, it is likely that the diagnoses were informed by their knowledge of the individual components of the criteria. Therefore the high sensitivity (90%) they reported means that most of the patients with a clinical diagnosis of RA will have had seropositive, erosive, polyarticular disease with hand involvement. Whereas we have no problem in recognising these patients as having RA, it represents only one end of the spectrum. The proportion of patients with “undifferentiated arthritis” in this …