Audrey M. Nelson

In a population-based study, the incidence of osteoporotic fractures in patients who have been diagnosed as having rheumatoid arthritis was investigated. This incidence was found to be increased, though not dramatically so: the relative risk for hip fracture, for example, was 1.5. Univariate analyses generally indicated increased risk associated with increasing age, earlier age at diagnosis of rheumatoid arthritis, disability, impaired ambulation, steroid use, and thinness, and decreased risk associated with obesity and estrogen use. In multivariate analyses, only aging, impaired ambulation, and thinness were identified as independent risk factors.

OBJECTIVE: To identify prognostic markers that are predictive of progressive erosive disease in patients with early rheumatoid arthritis (RA). METHODS: The study involved an inception cohort of 111 consecutive patients with RA and a disease duration of <1 year. Patients were treated according to an algorithm designed to avoid overtreatment of mild disease and to accelerate treatment in patients who had continuous disease activity. Patients were evaluated for the presence of clinical and laboratory disease activity markers. We determined the frequency of CD4+,CD28(null) T cells by flow cytometry, HLA-DRB1 gene polymorphisms by polymerase chain reaction (PCR)/sequencing, and 26 single-nucleotide polymorphisms in 19 candidate genes by multiplex PCR and hybridization to an immobilized probe array. Data were analyzed using proportional odds models to identify prognostic markers predictive of erosive progression over 2 years on serial hand/wrist radiographs. RESULTS: After 2 years, disease activity in 52% of the cohort was controlled by treatment with hydroxychloroquine and nonsteroidal agents. Forty-eight percent of the patients did not develop erosions. Older age, presence of erosions at baseline, presence of rheumatoid factor, rheumatoid factor titer, and HLA-DRB1*04 alleles, particularly homozygosity for HLA-DRB1*04, were univariate predictors of radiographic progression. Promising novel markers were the frequency of CD4+,CD28(null) T cells as an immunosenescence indicator, and a polymorphism in the uteroglobin gene. CONCLUSION: Clinical disease activity in patients with early RA can frequently be controlled with nonaggressive treatment, but this is not always sufficient to prevent new erosions. Rheumatoid factor titer, HLA-DRB1 polymorphisms, age, and immunosenescence markers are predictors of poor radiographic outcome. A polymorphism in the uteroglobin gene may identify patients who have a low risk of erosive disease.

OBJECTIVE: The goal of this study was to evaluate the physical and psychosocial impact of juvenile rheumatoid arthritis (JRA) among a population-based cohort of adults who had the disease during childhood, compared with a control cohort of subjects with no history of JRA. METHODS: The Rochester Epidemiology Project database was used to identify all cases of JRA (based on the American College of Rheumatology [formerly, the American Rheumatism Association] 1977 criteria) among Rochester, Minnesota residents first diagnosed between January 1, 1960 and December 31, 1993. Controls were age- and sex-matched to the cases as of the date of diagnosis of JRA. A pretested postal survey was mailed to all adult cases (whose date of birth was before December 31, 1975) and matched controls from the same population, to obtain information on socioeconomic issues and functional status (using the Health Assessment Questionnaire and the Health Status Questionnaire). The complete medical records of all cases and controls were reviewed to obtain information on demographics and clinical manifestations of JRA. RESULTS: Of the 50 eligible cases, 44 (88%) responded to the survey. There were 102 age- and sex-matched controls (2-3 per case) who responded to the survey. Seventy-three percent of the cases had pauciarticular-onset JRA, 16% had polyarticular-onset JRA, and 11% had systemic-onset JRA. Average followup was 24.7 years and 24.5 years after the index date for cases and controls, respectively. Greater disability (P = 0.0002), more bodily pain (P = 0.0002), increased fatigue (P = 0.0112), poorer health perception (P = 0.0004), and decreased physical functioning (P = 0.0002) were reported by the cases compared with the controls. JRA cases reported significantly lower rates of employment (P = 0.015) and lower levels of exercise (P = 0.0002) than did controls. Level of educational achievement, annual income, health insurance status, and rate of pregnancy and childbirth were similar for both cases and controls. CONCLUSION: Adults who have had JRA during childhood experience long-term physical and psychosocial impairment.

OBJECTIVE: To examine trends in the incidence and prevalence of juvenile rheumatoid arthritis (JRA) in Rochester, Minnesota, over 33 years. METHODS: The diagnostic retrieval system of the Rochester Epidemiology Project was utilized to screen medical records of all Rochester residents with any potential diagnoses of JRA from 1978 to 1993 (based on the American College of Rheumatology 1977 revised criteria). In addition, all cases of JRA from our previously identified cohort from 1960-1979 were verified, and the 2 data sets were combined, resulting in an incidence cohort spanning 33 years (1960-1993). RESULTS: Of the 1,240 medical records screened, we identified 65 cases of JRA diagnosed between 1960 and 1993 (48 females, 17 males). The average followup for cases was 12.7 years (range 0-34 years) for a total of 833 person-years of observation. A bimodal distribution of age at diagnosis was observed, with peaks between 0 and 4 years and 9 and 15 years. Seventy-two percent of patients had pauciarticular-onset, 17% had polyarticular-onset, and 11% had systemic-onset disease. Progression of pauciarticular to polyarticular disease occurred in 11% of the cases. The overall age- and sex-adjusted incidence rate was 11.7 per 100,000 population (95% confidence intervals 8.7, 14.8). The incidence rate per 100,000 population was 15.0, 14.1, and 7.8 for the time periods 1960-1969, 1970-1979, and 1980-1993, respectively (P = 0.024). A 3-year, centered, moving average, which was used to display time trends in incidence, suggested a cyclical pattern, with incidence peaks in 1967, 1975, and 1987. CONCLUSION: An overall decrease in the incidence rate over the last decade was observed, most marked in the pauciarticular- and systemic-onset subtypes. This decrease, along with the observed cyclical pattern, suggest that environmental factors may influence disease frequency.