Rheumatoid Arthritis: Vandenbroucke JP

Dijkmans BA, van Schaardenburg D, van der Horst-Bruinsma IE, Reesink HW, Vandenbroucke JP, Boers M. · VU Medisch Centrum, afd. Reumatologie, Postbus 7057, 1007 MB Amsterdam. · Ned Tijdschr Geneeskd. · Pubmed #15819133 No free full text.

Abstract: In some conditions e.g. osteoporosis, hypertension and hypercholesterolaemia, certain phenomena precede manifestation of the disease and preventive measures can be taken long before the disease presents itself. In the same way systemic lupus erythematosus (SLE) and rheumatoid arthritis can be explored. Recently, studies have been published on healthy blood donors, who later developed SLE or rheumatoid arthritis, and in whom specific autoantibodies could be demonstrated. In SLE the autoantibodies are not specific enough to develop preventive strategies, but in rheumatoid arthritis in particular there are specific antibodies against cyclic citrullinated peptides (anti-CCP-antibodies) which are very specific. A clinical trial has been initiated in which HLA-DR4-positive people with raised autoantibody concentrations are given 1-2 intramuscular injections of dexamethasone with the aim of halving the antibody concentration and in the long term lowering the incidence of rheumatoid arthritis.

de Buck PD, de Bock GH, van Dijk F, van den Hout WB, Vandenbroucke JP, Vliet Vlieland TP. · Department of Rheumatology C1-R, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands. · Int Arch Occup Environ Health. · Pubmed #16710710 No free full text.

Abstract: OBJECTIVES: To study the occurrence and duration of sick leave as potential risk factors for permanent job loss after 24 months among 112 individuals with chronic arthritis and a disease related problem at work. METHODS: Data collection was embedded in a multicentre randomised controlled trial in which the cost-effectiveness of a multidisciplinary job retention vocational rehabilitation programme for employees with chronic arthritis and a disease related problem at work was compared to usual outpatient care. Sick leave (complete or partial) was defined as absenteeism reported to the employer and permanent job loss as receiving a full work disability pension or unemployment. The association between sick leave at baseline and job loss after 24 months was investigated by multivariate logistic regression analysis, including those variables that were univariately significantly associated with job loss after 24 months. RESULTS: At baseline, 60 of the 112 subjects (54%) were on sick leave, with a mean duration of 18.7 weeks, in half of these patients the sick leave was complete. After 24 months, 26 of the 112 patients (23%) had lost their job. The presence of complete sick leave (OR 4.74, 95% CI 1.86-12.07) and the depression score of the hospital anxiety and depression scale (OR 1.18, 95% CI 1.02-1.36) were significantly and independently associated with job loss after 2 years follow-up. CONCLUSION: The occurrence of complete sick leave was found to be an independent risk factor for job loss in patients with chronic arthritis who have a disease related problem at work.

Nielen MM, van Schaardenburg D, Reesink HW, Twisk JW, van de Stadt RJ, van der Horst-Bruinsma IE, de Gast T, Habibuw MR, Vandenbroucke JP, Dijkmans BA. · Jan van Breemen Institute, Amsterdam, The Netherlands. · Arthritis Rheum. · Pubmed #15334453 links to  free full text

Abstract: OBJECTIVE: We previously reported that approximately half of the patients with rheumatoid arthritis (RA) have specific serologic abnormalities (elevated serum concentrations of IgM rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies) starting several years before the onset of symptoms. In this study, the presence of serologic signs of inflammation in patients with preclinical RA was investigated with serial measurements of C-reactive protein (CRP). METHODS: Seventy-nine patients (61% female; mean age at onset of symptoms 51 years) who had been blood donors before the onset of RA were identified. Frozen serum samples from each donor were retrieved, together with 1 sample from a control donor matched for age, sex, and date of donation. CRP was measured using a highly sensitive latex-enhanced assay. The dates of donation were categorized into 15 1-year periods preceding the onset of RA symptoms. For each period, the median CRP levels in the patient and control groups were compared using the Mann-Whitney U test. The course of CRP concentrations over time in the patient group was estimated with random coefficient analysis. RESULTS: A median of 13 samples (range 1-51) per patient were available; the earliest donation was made a median of 7.5 years (range 0.4-14.5 years) before the onset of symptoms. A total of 1,078 patient samples and 1,071 control samples were tested. For all 1-year periods, the median CRP concentration was increased in the patient group compared with the control group, but this difference was statistically significant only for the periods 0-1 year, 1-2 years, and 4-5 years before the onset of symptoms. The CRP concentration increased significantly over time in patients with preclinical RA; levels were slightly higher in the group of patients who had serologic abnormalities before the onset of symptoms than in those without such serologic abnormalities. CONCLUSION: After observing specific serologic abnormalities 5 years before the onset of RA symptoms, we now report increased levels of CRP in blood donors in whom RA later developed; these increases were most common within the 2 years before the onset of symptoms. The preclinical increase in CRP levels was observed both in donors with and in those without serologic abnormalities.

Nielen MM, van Schaardenburg D, Reesink HW, van de Stadt RJ, van der Horst-Bruinsma IE, de Koning MH, Habibuw MR, Vandenbroucke JP, Dijkmans BA. · Jan van Breemen Institute, Amsterdam, The Netherlands. · Arthritis Rheum. · Pubmed #14872479 links to  free full text

Abstract: OBJECTIVE: Autoantibodies have been demonstrated in single serum samples from healthy subjects up to 10 years before they developed rheumatoid arthritis (RA). However, the time course for the development of antibodies before onset of clinical RA is unknown, nor is it known which antibody, or combinations of antibodies, might be most sensitive or specific for predicting future development of the disease. The present study was undertaken to investigate this. METHODS: Patients with RA who had been blood donors before the onset of disease symptoms were enrolled. Frozen serum samples from each donor were retrieved, together with 2 serum samples from controls matched for age, sex, and date of donation. All samples were tested for IgM rheumatoid factor (IgM-RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies. RESULTS: Seventy-nine patients with RA (62% female; mean age at onset of symptoms 51 years) were included. A median of 13 samples (range 1-51) per patient were available; the earliest samples had been collected a median of 7.5 years (range 0.1-14.5) before the onset of symptoms. Thirty-nine patients (49%) were positive for IgM-RF and/or anti-CCP on at least one occasion before the development of RA symptoms, a median of 4.5 years (range 0.1-13.8) before symptom onset. Of the 2,138 control samples, 1.1% were positive for IgM-RF, and 0.6% were positive for anti-CCP. CONCLUSION: Approximately half of patients with RA have specific serologic abnormalities several years before the onset of symptoms. A finding of an elevated serum level of IgM-RF or anti-CCP in a healthy individual implies a high risk for the development of RA. We conclude that IgM-RF and anti-CCP testing with appropriately high specificity may assist in the early detection of RA in high-risk populations.