The prevalence and severity of rheumatoid arthritis in Oslo. Results from a county register and a population survey

The objective was (1) to examine the prevalence of rheumatoid arthritis (RA) by a county patient register, (2) to cross-validate the register findings by a postal population survey, and (3) to estimate prevalences of disease subsets according to age, sex, and levels of physical disability. The study was performed within a county setting in the city of Oslo with 356,486 inhabitants between 20 and 79 years of age. Prevalence estimates were calculated from a county patient register comprising 1333 patients with RA and a population survey of 10,000 inhabitants. The overall prevalence of RA between 20 and 79 years was 0.437 (95% CI 0.413, 0.461) after adjusting for the incompleteness of the register by a factor of 1.17. Prevalences exceeding 1.0% was only found among females over 60 years. The prevalence of RA with MHAQ scores > or = 1.5 and > or = 2.0 (range 1-4) was 0.225 (95% CI 0.209, 0.243) and 0.099 (0.088, 0.111) respectively. We conclude that RA is less frequent in the city of Oslo than stated in most of the literature. The prevalence of RA with physical disability levels assumed to be associated with increased mortality is less than half of the overall prevalence of 0.4-0.5%.     

HLA-DQB1 polymorphism determines incidence, onset, and severity of collagen-induced arthritis in transgenic mice. Implications in human rheumatoid arthritis

Certain HLA-DR alleles have been associated with predisposition to human rheumatoid arthritis (RA). There is also evidence that certain HLA-DQ alleles may also be important in determining susceptibility to RA. We have previously demonstrated that mice transgenic for HLA-DQ8, a DQ allele associated with susceptibility to RA, develop severe arthritis after type II collagen immunization. To investigate the influence of polymorphic difference at the DQ loci on susceptibility to arthritis, we generated mice transgenic for HLA-DQ6, an allele associated with a nonsusceptible haplotype. The DQ6 mice were found to be resistant to collagen-induced arthritis. We also assessed the combined effect of an RA-susceptible and an RA nonassociated DQ allele by producing double-transgenic mice expressing DQ6 and DQ8 molecules, representing the more prevalent condition found in humans where heterozygosity at the DQ allele is common. The double-transgenic mice developed moderate CIA when immunized with CII when compared with the severe arthritis observed in DQ8 transgenic mice, much like RA patients bearing both susceptible and nonsusceptible HLA haplotypes. These studies support a role for HLA-DQ polymorphism in human RA.     

Epidemiology of multiple sclerosis in the county of Vestfold, eastern Norway: incidence and prevalence calculations

The county of Vestfold in the South-eastern part of Norway has undergone two incidence and prevalence surveys on multiple sclerosis. The prevalence of definite/probable MS on January 1, 1963 was 61.6/100,000. Based on the same diagnostic criteria, the present study reports a slight increase in prevalence to 86.4/100,000 on January 1st 1983. The average annual incidence was calculated for 5 years periods from 1953 to 1983. The time periods 1953-1962 and 1973-1977 showed age-adjusted incidence rates between 4.50 and 5.49/100,000 while the 10-year period 1963-1972 showed significantly lower rates. The fluctuating pattern of MS incidence and prevalence over time supports the view that MS is not a stable disease, and that exogenous factors are influencing the disease pattern.     

Oral contraceptives and rheumatoid arthritis: results from a primary care-based incident case-control study

The influence of celiprolol (beta1- and beta2-adrenoceptor partial agonist), propranolol (beta1- and beta2-adrenoceptor antagonist), and atenolol (beta1-adrenoceptor antagonist) on heart-rate variability (HRV) was assessed from Holter records in 12 normal volunteers. A combination of summary statistics and nonlinear procedures was used to assess HRV and autonomic balance. Under double-blind and randomised conditions (Latin-square design), subjects received placebo, celiprolol (200 and 800 mg), propranolol (160 mg), atenolol (50 mg), and combinations of these agents. Single oral doses of medication (at weekly intervals) were administered at 22:30 h with sleeping heart rates (HRs) recorded overnight. Compared with placebo, celiprolol (200 and 800 mg) increased the sleeping HR, the HR effect of celiprolol was different from the bradycardia after propranolol, 160 mg, and atenolol, 50 mg. Dose-response effects on HR with celiprolol were evident in the presence of atenolol, unlike those with propranolol that abolished the HR increase between celiprolol, 200 mg and 800 mg. These data were consistent with beta1-selective adrenoceptor agonism with 200 mg but agonism at both the beta1- and beta2-adrenoceptor with celiprolol, 800 mg. The action of the drugs on short-term HRV indices (rMSSD and pNN50) closely followed their effects on HR. The longer-term HRV indices (global SD, SDANN) were reduced by celiprolol but increased by propranolol and atenolol. At a fixed HR, the data dispersion (SDNN5) was higher with propranolol compared with celiprolol; however, the dispersion was not merely an HR-dependent phenomenon. A novel nonlinear approach (quadrant analysis) revealed the sequencing of cardiac accelerations and decelerations after the high correlation between adjacent intervals had been removed. Celiprolol increased the frequency of consecutive cardiac accelerations; the duration between and variance of these beat-to-beat differences shortened after celiprolol but lengthened with increased variance after propranolol and atenolol. These results demonstrated reduced HRV indices and a shift toward sympathetic dominance after the beta-adrenoceptor agonist celiprolol contrasting with increased HRV indices and parasympathetic dominance after the beta-adrenoceptor antagonists propranolol and atenolol. The implications of these findings for the treatment of patients with cardiovascular disease warrant further study.     

Decreasing incidence and prevalence of rheumatoid arthritis in Pima Indians over a twenty-five-year period

OBJECTIVE: To evaluate temporal trends in the incidence of rheumatoid arthritis (RA). METHODS: Incident cases of RA were identified among a population-based cohort of Pima Indians in Arizona over the period 1965-1990. RESULTS: Among 2,894 subjects, 78 incident cases of RA were identified. The age-adjusted incidence declined by 55% in men (Ptrend = 0.225), and by 57% in women (Ptrend = 0.017) after controlling for oral contraceptive or estrogen use and for pregnancy experience. During the same period, age-adjusted prevalence rates of active RA decreased by 29% in men (Ptrend = 0.63) and by 40% in women (Ptrend = 0.02). Fewer than 17% of subjects with known RA were taking slow-acting antirheumatic drugs (SAARDs) in 1990. CONCLUSION: The decrease in incidence and prevalence of RA in this population over such a short period implicates the involvement of an environmental factor(s), other than exogenous estrogens, in the pathogenesis of the disease. However, the possibility that the observed decrease might be explained by an increased use of SAARDs in subjects with RA cannot be excluded.     

Factors predicting outcome of rheumatoid arthritis: results of a followup study

OBJECTIVE: To determine prognostic factors in rheumatoid arthritis (RA). METHODS: One hundred thirty-two women with definite RA were followed yearly from an early phase of the disease (symptoms < 5 years) for a mean duration of 6 years. The prognostic value of the first available clinical and laboratory variables and assessments of functional ability was related to several outcome measures (physician's opinion of disease severity, disease activity, radiological abnormalities, functional ability and number of prescribed 2nd-line drugs) by single predictor analysis and by logistic regression. RESULTS: The variables most predictive for one or more of the outcome measures were number of swollen joints, Ritchie score, health assessment questionnaire score, radiographical abnormalities, positive IgM rheumatoid factor (RF), positive IgG-RF, HLA-DR4, and an elevated percentage serum agalactosyl IgG. The accuracy of predicting outcome was calculated from several combinations of these variables, and varied between 70 and 80%. The accuracy based on a combination of the commonly available variables (number of swollen joints, IgM-RF and the erosion score), closely approximated the maximal accuracy that could be achieved. CONCLUSION: The outcome of RA can be predicted by a combination of variables that are commonly available in the clinical setting.     

Long-term results of Yoshino total knee arthroplasties in rheumatoid arthritis

A review was made of 267 Yoshino total knee arthroplasties performed on 184 patients with rheumatoid arthritis between June 1978 and December 1983. The average duration of follow-up was 14.3 years. Of these patients 46.7% died during the follow-up period. The main causes of death were cardiac disease, respiratory disease and renal disease. According to the Japanese Orthopaedic Association (JOA) knee rating system, JOA scores decreased significantly with time after surgery, but remained significantly higher than the preoperative scores. The flexion angle after surgery had decreased compared with the preoperative flexion angle and decreased further 3 years after surgery and later. The cumulative survival rate was 88.6%. This rate was mainly affected by postoperative infection and aseptic loosening of the tibial components.     

The social environment and health in rheumatoid arthritis: marital quality predicts individual variability in pain severity

OBJECTIVE: To examine prospective relations between a wide array of measures of social functioning and pain, while controlling for disease duration and activity and functional grade. METHODS: As part of a larger study on health care utilization, longitudinal data were collected from 136 Dutch and 98 German outpatients on clinical status and pain. Social data included information on sexual handicap, spouse behavior, loneliness, daily emotional support, and the maintenance of pleasurable life domains. Pain severity was assessed at baseline and 12 months later with standard measures of pain and analyzed with hierarchical regressions. RESULTS: Social measures obtained at baseline were consistently associated with pain at followup. Depression was a moderate correlate of pain in the Dutch and German samples. The regressions revealed that patient reports of negative spouse behavior (such as avoidance and critical remarks) and baseline depression predicted worse pain outcome, and this association remained significant in analyses controlling for baseline pain. The level of formal education was a weak correlate of disability, emotional support, and pain. Daily emotional support and social life domains associated with positive affect had an indirect influence on outcome. The absence of strong rather than weak social ties was the component of the loneliness construct linked to pain. These associations between social prognostic factors and pain severity, however, were mediated by psychological functioning at baseline. CONCLUSION: The social environment was found to operate on the core health outcome, pain severity, via several pathways. Social functioning may be affected by rheumatoid arthritis (RA) progression, but it also appears to form a determinant of future health outcome. Not only the status of being married but also the quality of the relationship in terms of long-term stress and emotional support may be useful prognostic factors in RA.     

Effect of social deprivation on disease severity and outcome in patients with rheumatoid arthritis

OBJECTIVE: Social deprivation is now recognised to have an important impact on morbidity and mortality. This study sought to ascertain the effect of deprivation, if any, on disease severity, functional disability, and outcome in rheumatoid patients in Glasgow. METHODS: 814 patients with rheumatoid arthritis (RA) were assessed for clinical, functional, and laboratory indices of disease activity. Deprivation categories for individual patients were determined using the Carstairs index. Five year follow up is available for 440 patients. RESULTS: The study population of RA patients live largely in the most deprived areas. Patients from deprived areas have significantly poorer function at outset and at five years as defined by the Health Assessment Questionnaire (HAQ) score. This is not attributable to differences in disease duration in patients from the most deprived regions or compliance with treatment. Furthermore, these patients do not achieve over five years the initial functional level of those living in the most advantaged localities. CONCLUSION: RA patients from deprived areas have poorer function, which is associated with greater need--medical, social, and paramedical. Strategies and resources for healthcare need to be adjusted according to this variation.     

Reduction in the incidence and severity of collagen-induced arthritis in DBA/1 mice, using exogenous dehydroepiandrosterone

OBJECTIVE: To study the levels of glutathione S-transferase Alpha 1-1 and glutathione S-transferase Pi 1-1 in human preovulatory ovarian follicular fluid (FF) and pooled granulosa and cumulus cells. DESIGN: The relation of glutathione S-transferase Alpha 1-1 and glutathione S-transferase Pi 1-1 with P and 17 beta-E2 concentrations were studied. SETTING: The Department of Obstetrics and Gynecology, the Department of Gastroenterology, and the Laboratory of Endocrinology and Reproduction of the University Hospital Nijmegen in Nijmegen, the Netherlands. PATIENT(S): Infertile women participating in an IVF program. RESULT(S): Detectable amounts of glutathione S-transferase Alpha 1-1 and glutathione S-transferase Pi 1-1 were found in ovarian FF and pooled cumulus and granulosa cells. Concentrations of glutathione S-transferase Alpha 1-1 were always much higher than those of glutathione S-transferase Pi 1-1. Both ovarian FF concentrations of glutathione S-transferase Alpha 1-1 and glutathione S-transferase Pi 1-1 did not correlate with ovarian FF concentrations of 17 beta-E2 and P. CONCLUSION(S): The high FF concentrations of glutathione S-transferase Pi 1-1 and especially of glutathione S-transferase Alpha 1-1 suggest that these enzymes may play an important role in the detoxification processes in the follicles. The lack of correlation between follicular P and 17 beta-E2 and glutathione S-transferase Alpha 1-1 and glutathione S-transferase Pi 1-1 indicates that both enzymes presumably are not present as a result of the high steroid levels.     

The Groningen Activity Restriction Scale (GARS) in the evaluation of severity of rheumatoid arthritis]

The antiviral effect of amantadine (1-aminoadamantane) was tested in vitro as well as in vivo. Treatment of persistently Borna disease virus (BDV)-infected cell lines of different origin and for various length of time did not result in a general reduction of virus titer or clearance of virus from infected cells. In vivo, rats were treated with amantadine by daily oral application or by use of osmotic pumps, and in both cases treatment was started before infection. Neither route of application of the drug had any influence on the time of onset of disease, on antiviral antibody titers, on virus titer in the brain, on the severity of the inflammatory reaction in the brain, or on the severity of neurological symptoms. These experiments, although revealing negative results and obtained using a virus from a natural case of Borna disease grown after isolation in vitro for a long period of time, should caution from the general use of amantadine as a curative agent against BDV infection as has been implicated recently [Bode et al. (1997) Lancet 349:178-179].     

The prognosis of rheumatoid arthritis

Although DNA replication is a very accurate process, a small number of new mutations are generated at every cell division. The generation of a new mutation during the formation of an ovum or sperm cell can cause an early miscarriage or birth defect. The generation of new mutations during embryogenesis can cause a variety of localized birth defects. The molecular delineation of these errors in somatic and gonadal cells has clarified the basis of some birth defects, and has both refined and complicated genetic counselling for a number of paediatric conditions. The processes responsible for these new mutations are present in all cells. For this reason new mutations accumulate in all cells throughout life and contribute to the ageing process. Thus the molecular events that cause many miscarriages and birth defects are the same as those that ultimately lead to death.     

HLA-DRB1 genes and disease severity in rheumatoid arthritis. The MIRA Trial Group. Minocycline in Rheumatoid Arthritis

OBJECTIVE: To examine the effect of alleles encoding the "shared"/"rheumatoid" epitope on rheumatoid arthritis (RA) disease severity in patients who participated in the minocycline in RA (MIRA) trial. METHODS: Of 205 patients with a week-48 visit, blood was available for typing of HLA-DRB1 and HLA-DQB1 in 174 (85%) and successfully completed in 169 (82%). Baseline erosions were used to assess disease severity and new erosions at the last visit served as a proxy for progression. RESULTS: At baseline, there was no association between the presence of erosive disease or rheumatoid factor status and the dose of rheumatoid epitope (homozygous, heterozygous, none) or the specific alleles identified. At the final visit, a gradient was observed for the 3 allelic subgroups (and their gene doses) in the occurrence of new erosions among the Caucasian placebo-treated, but not the minocycline-treated, patients. A treatment group/HLA-DR4 epitope interaction was demonstrated in multivariate analyses. Approximately two-thirds of African-American patients did not have the rheumatoid epitope. CONCLUSION: HLA-DRB1 oligotyping may be useful in predicting the progression of disease in some Caucasian patients. Our study corroborates the infrequency of the epitope among African-American patients with RA.     

The use of Neoral in rheumatoid arthritis

Neoral (a microemulsion-based formulation) is an immunomodulator that possesses a more predictable and improved absorption than the conventional oral formulation (Sandimmun). The increased bioavailability of Neoral could result in improved efficacy. The pharmacokinetics of cyclosporin and efficacy of cyclosporin in rheumatoid arthritis are reviewed in this article. Current guidelines for the use of Neoral in the treatment of rheumatoid arthritis patients are outlined.     

The great toe as a clinical problem in rheumatoid arthritis

Two hundred consecutive in-patients with rheumatoid arthritis were examined for pain or deformity of the feet, and of the great toe in particular. Some abnormality occured in 196 feet and the deformities observed are presented. The symptoms that arise from these deformities are mainly derived from ill-fitting shoes, and the need for suitable foot-wear is emphasized. Two hitherto un-named entities are described namely Hallux tortus and chisel toe, since they give rise to their own shoe-fitting problems.