Thorbjörn Jónsson

Epidemiology of Dupuytren's disease: Clinical, serological, and social assessment. The Reykjavik Study

Dupuytrens disease or palmar fibromatosis is a common disabling hand disorder, mainly confined to Caucasians of northwestern European origin. The prevalence of Dupuytrens disease and possible risk factors related to the disease were evaluated in a random sample of 1297 males and 868 females, aged 46 to 74 years. Blood samples were collected and biochemical parameters were evaluated. The possible relation between the disease and clinical, social, and biochemical parameters were estimated with age-adjusted univariate logistic regression analysis. Altogether 19.2% of the males and 4.4% of the female participants had clinical signs of Dupuytrens disease. The prevalence increased with age, from 7.2% among males in the age group 45-49 years up to 39.5% in those 70-74 years old. The more severe form of the disease, finger contractures, was found in 5.0% of the men and 1.4% had required operation, while this was rarely seen among women. In men elevated fasting blood glucose (P < 0.04), low body weight, and body mass index were significantly correlated with the presence of the disease (P < 0.001). Dupuytrens disease was common among heavy smokers (P = 0.02) and those having manual labor as occupation (P = 0.018). These results show that Dupuytrens disease is common in the Icelandic population and occupation and lifestyle seem to be related to the disease.

Effect of rheumatoid factor on mortality and coronary heart disease

Objective An association between rheumatoid factor (RF) and increased mortality has been described in individuals with rheumatoid arthritis. The objective of this study was to determine the effect of RF on mortality and coronary heart disease (CHD) in the general population. Methods Subjects were participants in a population-based study focused on cardiovascular disease who attended for a study visit during the years 1974–84. RF was measured and information obtained on cardiovascular risk factors, joint symptoms and erythrocyte sedimentation rate (ESR). The subjects were followed with respect to mortality and incident CHD through 2005. Adjusted comparison of overall survival and CHD event-free survival in RF-positive versus RF-negative subjects was performed using Cox proportional hazards regression models. Results Of 11 872 subjects, 140 had positive RF. At baseline RF was associated with diabetes mellitus and smoking and inversely associated with serum cholesterol. RF-positive subjects had increased all-cause mortality (HR 1.47, 95% CI 1.19 to 1.80) and cardiovascular mortality (HR 1.57, 95% CI 1.15 to 2.14) after adjusting for age and sex. Further adjustment for cardiovascular risk factors and ESR only modestly attenuated this effect. An increase in CHD among the RF-positive subjects did not reach statistical significance (HR 1.32, 95% CI 0.96 to 1.81, adjusted for age and sex). Subjects with RF but without joint symptoms also had increased overall mortality and cardiovascular mortality (HR for overall mortality 1.33, 95% CI 1.01 to 1.74, after adjustment). Conclusion In a general population cohort, RF was associated with increased all-cause mortality and cardiovascular mortality after adjustment for cardiovascular risk factors, even in subjects without joint symptoms.

A prospective study on the incidence of rheumatoid arthritis among people with persistent increase of rheumatoid factor

OBJECTIVES To study the stability of rheumatoid factor (RF) increases and to compare the incidence of rheumatoid arthritis (RA) in people with transient or persistent increase of one or more RF isotypes. METHODS From an original cohort of nearly 14 000 participants in a population study, 135 previously RF positive persons were recruited in 1996 and evaluated according to the 1987 ACR criteria. The observation time ranged from 9–22 years (mean 16.5). Blood samples were obtained from all participants at entry and again in 1996. RESULTS About 40% of the participants who had only one raised RF isotype in the original sample had become RF negative in 1996 compared with only 15% of those with increase of two or three RF isotypes (p=0.002). The seven participants who developed RA during the study period all had persistently raised RF. Six of the 54 participants with more than one RF isotype raised in 1996 developed RA, corresponding to an annual incidence of 0.67%, which was 7.5 times higher than observed in the other participants (p=0.045). CONCLUSION Symptom free persons with persistently raised RF have greatly increased risk of developing RA. This suggests that dysregulation of RF production is a predisposing factor in RA.

Does smoking stimulate rheumatoid factor production in non-rheumatic individuals ?

Smoking has been associated with increased incidence of rheumatoid arthritis (RA), joint damage and positive rheumatoid factor (RF). Here we report an analysis of the association between smoking and IgM, IgG and IgA RF in a cohort of non‐rheumatic individuals participating in a prospective longitudinal study of the incidence and significance of elevated RF. From the initial cohort of nearly 14,000 randomly selected individuals aged 52–80 years, 109 RF‐positive and 187 RF‐negative non‐rheumatic participants were recruited. All participants were tested for RF at least twice at an interval ranging from 4 to 13 years. Of the RF‐negative participants 21.9% were active smokers compared to 34.1% of IgM RF‐positive (p=0.035), 20.8% of IgG RF‐positive (N.S.) and 34.4% of IgA RF‐positive participants (p=0.047). Smoking was most prevalent (44.8%) amongst participants with elevation of both IgM and IgA RF (p=0.008), and smokers were also significantly more likely to have a persistent elevation of RF than non‐smokers (p=0.024). These findings indicate that smoking may influence the immune system, leading to increased production of IgM and IgA RF.

Population study of the importance of rheumatoid factor isotypes in adults.

Blood samples collected from 13,858 randomly selected subjects participating in a health survey in Iceland from 1974 to 1983 were tested for rheumatoid factor. Samples that were positive in a sensitive RF screening test were analysed further by the Rose-Waaler technique and an isotype specific enzyme linked immunosorbent assay (ELISA). In 1987 the 173 available participants who were RF positive and 156 matched RF negative controls were evaluated clinically for rheumatoid diseases. RF levels and isotype patterns were more persistent in the patients with rheumatoid arthritis (RA) than in RF positive subjects who did not have overt RA. The prevalence of RA was only 19% in the participants who were RF positive in 1987. Forty per cent of the participants who had a persistent (four to 13 years) increase of IgA RF combined with either IgM or IgG RF were diagnosed as having RA. A positive correlation was found between RF levels and various manifestations of RA. This association was stronger for the IgA and IgG RF isotypes than for IgM RF. Excluding RF positivity as a diagnostic parameter, RA was diagnosed in 33 of the participants and 20 (61%) of these patients had increased levels of IgM and IgA RF. Patients with RA with bone erosions in their hands had higher levels of IgA RF than patients without erosions, but an association was not found between bone erosions and other RF isotypes. None of the RF negative participants who were symptom free when the original blood sample was taken developed RA during the four to 13 year follow up period. In contrast, five symptom free RF positive participants developed RA during this period. These five patients had all had increased levels of at least two RF isotypes before the onset of their symptoms. It is concluded that the IgA and IgG RF isotypes have a closer association with the clinical parameters of RA than IgM RF. Furthermore, increases in RF can precede clinical manifestations of RA and this applies in particular to the IgA and IgG RF isotypes.

Rheumatoid Factor Isotypes, Disease Activity and the Outcome of Rheumatoid Arthritis Comparative Effects of Different Antigens

The value of rheumatoid factor (RF) isotypes for assessing rheumatoid arthritis (RA) remains debatable. We investigated whether using different antigens to measure RF alters the relationships between RF isotypes and clinical variables. The association between IgA and IgM RF, disease activity, and cumulative anatomical joint damage in RA was studied in 140 patients. The RF isotypes were measured using both rabbit IgG and horse IgG as antigens. Cumulative anatomical damage was assessed radiologically using Larsens score and disease activity was determined by C-reactive protein (CRP), the health assessment questionnaire (HAQ), and a combined disease activity score (DAS). Patients positive for IgA RF and IgM RF against rabbit IgG had significantly higher disease activity and more radiological damage than negative patients. With horse IgG as antigen these differences were smaller or absent. Patients positive for only IgM RF had milder disease than patients positive for IgA RF with or without IgM RF. The clinical relationships of RF isotypes are related to the antigen used. Measuring IgA RF against rabbit IgG provides most information about disease activity, functional impairment and joint damage.

Eighteen years follow-up study of the clinical manifestations and progression of Dupuytren's disease

OBJECTIVE To evaluate the clinical manifestations and progression of Dupuytrens disease. METHODS In 1981-82 a total of 1297 men were examined for Dupuytrens disease, and of these 19.2% had the disease. In 1999 those with signs of the disease in 1981-82 were invited for a follow-up study. As controls symptom free individuals from the study in 1981-82 were invited. RESULTS A total of 53 individuals from the control group had developed Dupuytrens disease in 1999. Men with palmar nodules/fibrous cord in 1981-82 were more likely to develop contracted fingers than those without Dupuytrens disease. Patients with young age at disease onset more often required operations than those with later onset. Of the men who had been operated 70% still had finger contractures in 1999. CONCLUSION The incidence of Dupuytrens disease is high in elderly men. Dupuytrens disease is progressive in nature and most operated patients have recurrent finger contractures.Objective: To evaluate the clinical manifestations and progression of Dupuytrens disease. Methods: In 1981-82 a total of 1297 men were examined for Dupuytrens disease, and of these 19.2% had the disease. In 1999 those with signs of the disease in 1981-82 were invited for a follow-up study. As controls symptom free individuals from the study in 1981-82 were invited. Results: A total of 53 individuals from the control group had developed Dupuytrens disease in 1999. Men with palmar nodules/fibrous cord in 1981-82 were more likely to develop contracted fingers than those without Dupuytrens disease. Patients with young age at disease onset more often required operations than those with later onset. Of the men who had been operated 70% still had finger contractures in 1999. Conclusion: The incidence of Dupuytrens disease is high in elderly men. Dupuytrens disease is progressive in nature and most operated patients have recurrent finger contractures.

Raised IgA Rheumatoid Factor (RF) but not IgM RF or IgG RF is Associated with Extra-articular Manifestations in Rheumatoid Arthritis

In rheumatoid arthritis (RA) seropositivity has been associated with poor prognosis including bone erosions and extra-articular manifestations. However, findings have been conflicting on the association between individual rheumatoid factor (RF) isotypes and extra-articular manifestations. In this study the occurrence of extra-articular manifestations was examined in the context of the RF isotype patterns rather than individual RF isotypes. IgM, IgG and IgA RF was measured by ELISA in 74 patients with RA and the findings correlated with the presence or absence of extra-articular manifestations. Of the IgA RF positive patients 80% had one or more extra-articular manifestations. In contrast, only 21% of patients with raised IgM and/or IgG RF but normal IgA RF had some extra-articular manifestations and 27% of the seronegative patients. It is concluded that the previously reported association between raised RF and extra-articular manifestations in RA can largely be attributed to the IgA RF isotype.

Increased total mortality and cancer mortality in men with Dupuytren's disease: a 15-year follow-up study.

The aim of the present study was to evaluate the mortality rate and causes of death of individuals with Dupuytrens disease. In 1981/82, as part of The Reykjavík Study, a general health survey, 1297 males were examined for clinical signs of Dupuytrens disease. Based on the clinical evaluation the participants were classified into three groups: (1) those with no signs of Dupuytrens disease were referred to as the reference cohort; (2) those with palpable nodules in the palmar fascia were classified as having stage 1; and (3) those who had contracted fingers or had been operated on due to contractures were classified as having stage 2 of Dupuytrens disease. In 1997, after a 15- year follow-up period, the mortality rate and causes of death were investigated in relation to the clinical findings from 1981/82. Information about causes of death were obtained from the National Icelandic Death Registry and the Icelandic Cancer Registry. During the follow-up period, 21.5% (225/1048) of the reference cohort were deceased compared to 29.9% (55/184) of those with stage 1 and 47.7% (31/65) of those with stage 2 of Dupuytrens disease. When adjusted for age, smoking habits and other possible confounders, individuals with stage 2 of the disease showed increased total mortality [hazard ratio (HR) = 1.6; 95% CI 1.1-2.4]. Cancer deaths were increased (HR = 1.9; CI 1.0-3.6). In contrast, participants with stage 1 of Dupuytrens disease did not show increased mortality. A moderate but non-significant increase in cancer incidence was observed among individuals with stage 2 of Dupuytrens disease (HR = 1.5; 95% CI 0.9-2.4, P = 0.15). The study showed increased total mortality of individuals with Dupuytrens disease stage 2, where 42% of the excess in mortality could be attributed to cancer deaths.

Dupuytren's disease, alcohol consumption and alcoholism

OBJECTIVE To assess the relation between alcohol consumption and Dupuytrens disease. DESIGN The participants were recruited from a previous study on Dupuytrens disease carried out in 1981-82 as part of a cohort study. Men with Dupuytrens disease in the former study and a control group were invited. The groups were matched for age and smoking habits. SETTINGS The study took place at the Heart Preventive Clinic in Reykjavik. PATIENTS Of 244 invited participants, 193 (79.1%) responded to the invitation; 137 had Dupuytrens disease and 56 were disease-free. Participants were examined for the presence of Dupuytrens disease and answered a questionnaire about alcohol habits. MAIN OUTCOME MEASURES Alcoholism, alcohol consumption and signs of Dupuytrens disease. RESULTS Of the Dupuytrens group, 19 (13.9%) had been treated for alcoholism or were heavy drinkers compared to 8 (14.3%) of those without Dupuytrens disease (NS). Little or moderate alcohol consumption was reported in 78.1% of the Dupuytrens patients compared to 73.2% of the controls (NS). Total abstainers from alcohol were 11 (8.0%) in the Dupuytrens group compared to 7 (12.5%) in the control group (NS). CONCLUSION Our findings do not support a positive association between the use of alcohol and Dupuytrens disease.Objective - To assess the relation between alcohol consumption and Dupuytrens disease. Design - The participants were recruited from a previous study on Dupuytrens disease carried out in 1981-82 as part of a cohort study. Men with Dupuytrens disease in the former study and a control group were invited. The groups were matched for age and smoking habits. Settings - The study took place at the Heart Preventive Clinic in Reykjavik. Patients - Of 244 invited participants, 193 (79.1%) responded to the invitation; 137 had Dupuytrens disease and 56 were disease-free. Participants were examined for the presence of Dupuytrens disease and answered a questionnaire about alcohol habits. Main outcome measures - Alcoholism, alcohol consumption and signs of Dupuytrens disease. Results ? Of the Dupuytrens group, 19 (13.9%) had been treated for alcoholism or were heavy drinkers compared to 8 (14.3%) of those without Dupuytrens disease (NS). Little or moderate alcohol consumption was reported in 78.1% of the Dupuytrens patients compared to 73.2% of the controls (NS). Total abstainers from alcohol were 11 (8.0%) in the Dupuytrens group compared to 7 (12.5%) in the control group (NS). Conclusion ? Our findings do not support a positive association between the use of alcohol and Dupuytrens disease.