Coffee, tea, and caffeine consumption and risk of rheumatoid arthritis: results from the Iowa Women's Health Study

OBJECTIVE: To evaluate whether coffee, tea, and caffeine consumption are risk factors for rheumatoid arthritis (RA) onset among older women. METHODS: These factors were evaluated in a prospective cohort study that was initiated in 1986 and that included 31,336 women ages 55-69 years without a history of RA. Risk factor data were self-reported using a mailed questionnaire. Through 1997, 158 cases of RA were identified and validated against medical records. The relative risk (RR) and 95% confidence interval (95% CI) were used as the measures of association and were adjusted for age, alcohol use, smoking history, age at menopause, marital status, and the use of hormone replacement therapy. RESULTS: Compared with those reporting no use, subjects drinking > or =4 cups/day of decaffeinated coffee were at increased risk of RA (RR 2.58, 95% CI 1.63-4.06). In contrast, women consuming >3 cups/day of tea displayed a decreased risk of RA (RR 0.39, 95% CI 0.16-0.97) compared with women who never drank tea. Caffeinated coffee and daily caffeine intake were not associated with the development of RA. Multivariable adjustment for a number of potential confounders did not alter these results. The associations of RA onset with the highest categories of decaffeinated coffee consumption (RR 3.10, 95% CI 1.75-5.48) and tea consumption (RR 0.24, 95% CI 0.06-0.98) were stronger in women with seropositive disease compared with those with seronegative disease (RR 1.54, 95% CI 0.62-3.84 and RR 0.93, 95% CI 0.27-3.20, respectively). CONCLUSION: Decaffeinated coffee intake is independently and positively associated with RA onset, while tea consumption shows an inverse association with disease onset. Further investigations of decaffeinated coffee and tea intake as arthritis risk factors are needed to verify these findings and explore their biologic basis.     

Coffee consumption and risk of rheumatoid arthritis

OBJECTIVE: Recent reports have suggested an association between consumption of coffee or decaffeinated coffee and the risk of rheumatoid arthritis (RA), although data are sparse and somewhat inconsistent. Furthermore, existing studies measured dietary exposures and potential confounders only at baseline and did not consider possible changes in diet or lifestyle over the followup period. We studied whether coffee, decaffeinated coffee, total coffee, tea, or overall caffeine consumption was associated with the risk of RA, using the Nurses' Health Study, a longitudinal cohort study of 121,701 women. METHODS: Information on beverage consumption was assessed with a food frequency questionnaire (FFQ) that was completed every 4 years, from baseline in 1980 through 1998. Among the 83,124 women who completed the FFQ at baseline, the diagnosis of incident RA (between 1980 and 2000) was confirmed in 480 women by a connective tissue disease screening questionnaire and medical record review for American College of Rheumatology criteria. Relationships between intake of various beverages and the risk of RA were assessed in age-adjusted models and in multivariate Cox proportional hazards models including the cumulative average intake of each beverage during the followup period, adjusted for numerous potential confounders. In addition, for direct comparisons with prior reports, multivariate analyses were repeated using only baseline beverage information. RESULTS: We did not find a significant association between decaffeinated coffee consumption of >/=4 cups/day (compared with no decaffeinated coffee consumption) and subsequent risk of incident RA, in either an adjusted multivariate model (relative risk [RR] 1.1, 95% confidence interval [95% CI] 0.5-2.2) or a multivariate model using only baseline reports of decaffeinated coffee consumption (RR 1.0, 95% CI 0.6-1.7). Similarly, there was no relationship between cumulative caffeinated coffee consumption and RA risk (RR 1.1, 95% CI 0.8-1.6 for >/=4 cups per day versus none) or between tea consumption and RA risk (RR 1.1, 95% CI 0.7-1.8 for >3 cups/day versus none). Total coffee and total caffeine consumption were also not associated with the risk of RA. CONCLUSION: In this large, prospective study, we find little evidence of an association between coffee, decaffeinated coffee, or tea consumption and the risk of RA among women.     

Relationship among the HLA-DRB1 shared epitope,smoking, and rheumatoid factor production in rheumatoid arthritis

OBJECTIVE: Rheumatoid factor (RF) production in rheumatoid arthritis (RA) is generally associated with more severe disease. In some studies, RF production has been associated with carriage of HLA-DRB1 alleles encoding the RA-associated shared epitope (SE). Patients who smoke are also more likely to be RF positive. In this study, we investigated whether the association between RF production and smoking was influenced by carriage of the SE. METHODS: The smoking histories of 371 RA patients attending a hospital clinic were recorded. RF levels and SE status were determined for every patient, and the associations between the SE, smoking, and RF production were examined. HLA-DRB1 typing was performed using polymerase chain reaction. Results were analyzed using chi-square tests and logistic regression analysis. RESULTS: Patients who had ever smoked were significantly more likely to be RF positive than nonsmokers (odds ratio 2.2, P < 0.0001). This remained significant (P = 0.003) after correction for age, sex, and disease duration in a logistic regression model. An association was also found between RF positivity and carriage of the SE (P = 0.03, after correction for age, sex, and disease duration), but significance was reduced or lost after correction for previous or current smoking (P = 0.05 and 0.09, respectively). Examination of the major SE phenotypes in this RA population by multivariate logistic regression analysis revealed that only DRB1*0401 was associated with RF positivity, and that this was independent of the influence of smoking. CONCLUSION: Our data confirm that RF production in RA patients is associated with smoking. This does not appear to depend on an HLA-DR-restricted immune response. The association of the SE with RF positivity is primarily due to HLA-DRB1*0401. This appears to be independent of the association with smoking, although smoking further increases the likelihood of RF production in DRB1*0401 patients.     

The effects of tobacco smoking and rheumatoid factor seropositivity on disease activity and joint damage in early rheumatoid arthritis

OBJECTIVE: To study the effect of tobacco smoking and rheumatoid factor (RF) isotypes on disease activity and joint damage in early rheumatoid arthritis (RA). METHODS: One hundred early RA patients were followed prospectively for 2 yr. They were evaluated at recruitment and at 6 and 24 months. Sociodemographic information included smoking history, and radiographs of hands and feet were obtained. RF was monitored by IgM- and IgA-specific RF enzyme-linked immunosorbent assay and by agglutination, and serial measurements were also obtained for C-reactive protein. The influence of tobacco smoking and RF positivity on disease outcome was evaluated using multivariate analysis. Covariates for the regression analysis included sex, age, coffee consumption and IgA-RF positivity. RESULTS: A gradient of increase in disease activity was observed from never smokers to former smokers to current smokers during the 2 yr of observation, defined by number of swollen joints (SJC), tender joints (TJC) and visual analogue scale for pain (P<0.001, P=0.02 and P=0.005, respectively), but smoking status did not influence radiological progression. Ever smokers were more often IgA RF positive (P<0.05). IgA RF-positive patients had more active disease (SJC P=0.002, TJC P=0.01) and showed more radiological progression (P<0.0001) compared with IgA RF-negative patients. Of the RF-positive patients 22% had elevated IgM RF without IgA RF and these patients showed similar disease activity and radiological joint progression to the RF-negative patients. None of these associations were explained by possible confounders. CONCLUSION: Tobacco smoking has an adverse effect on patients with early RA and this is possibly immunologically mediated. IgM RF does not predict poorer prognosis in RA unless it is associated with a concomitant elevation of IgA RF.     

Smoking, rheumatoid factor isotypes and severity of rheumatoid arthritis

OBJECTIVES: Smokers have an increased incidence of rheumatoid factor (RF) and rheumatoid arthritis (RA) and one report has also indicated that smoking may also adversely influence the severity of RA. METHODS: Sixty-three women with advanced RA answered a structured questionnaire that included detailed information about their smoking history. The women were also evaluated clinically and radiologically. RESULTS: Heavy smoking (>/= 20 pack-yr) was associated with rheumatoid nodules (P: = 0.01), a higher HAQ score (P: = 0.002) and a lower grip strength (P: = 0.01). Smoking was also associated with more radiological joint damage (P: = 0.02). A positive correlation was observed between smoking and RF levels, in particular IgA RF and a combined elevation of IgM and IgA RF. CONCLUSIONS: Smoking has an adverse effect on disease progression in patients with RA. An association was also observed between smoking and those RF types that predispose to RA and have the highest diagnostic specificity for this disease.     

Blood transfusion, alcohol use, and anthropometric risk factors for rheumatoid arthritis in older women

OBJECTIVE: To evaluate whether blood transfusion, alcohol use, or anthropometric characteristics are risk factors for rheumatoid arthritis (RA) in older women. METHODS: These factors were evaluated in a prospective cohort study that was initiated in 1986, and included 31,336 women aged 55-69 years without a history of RA. Risk factor data were self-reported using a mailed questionnaire. Through 1997, 158 cases of RA meeting at least 4 of 7 American College of Rheumatology criteria were identified and validated by medical record review. The relative risk (RR) and 95% confidence interval (CI) were used as the measure of association, and were adjusted for the potential confounding effects of age, marital status, smoking history, age at menopause, and use of estrogen replacement therapy. RESULTS: History of blood transfusion was inversely associated with RA (multivariate RR = 0.72; 95% CI 0.48-1.08), and this association was stronger for rheumatoid factor (RF) positive disease (RR = 0.59; 95% CI 0.35-1.00). There were no associations for use of medications for hyper- or hypothyroidism or adult onset diabetes. Anthropometric factors (height, weight, body mass index, body fat distribution), leisure time physical activity, and alcohol use were not associated with risk of RA. CONCLUSION: A history of blood transfusion was inversely associated with RA, particularly RF positive RA. Anthropometric factors, physical activity, and alcohol use did not influence the risk of RA in this cohort of older women.     

Smoking is a strong risk factor for rheumatoid nodules in early rheumatoid arthritis

OBJECTIVE: To examine whether smoking is a risk factor for rheumatoid nodules in early rheumatoid arthritis, and if so to determine the quantitative effect of smoking. METHODS: From a cohort (n = 1589) in a structured programme for follow up of newly diagnosed cases of rheumatoid arthritis (symptoms of swollen joints < or =12 months), 112 individuals with rheumatoid nodules at inclusion were identified. Nodular patients were each compared with two age and sex matched controls without nodules from the same cohort. A detailed self administered tobacco use questionnaire was answered by 210 patients (63%). RESULTS: Seventy patients were current smokers, 71 former smokers, and 69 had never smoked. Current smoking and former smoking were more common in patients with rheumatoid nodules compared with controls (86% v 59%) in both sexes. Positive rheumatoid factor (RF) was found more often among cases with nodules than controls (78% v 64%). Using detailed information from the questionnaires with conditional logistic regression analyses, ever having smoked was associated with an increased risk of the presence of rheumatoid nodules (odds ratio (OR) = 7.3 (95% confidence interval, 2.3 to 23.6); p = 0.001). The risk of having nodules was not obviously dose dependent when smoking duration as well as smoking amount were examined. A stratified analysis showed that only RF positive smokers had an increased risk of rheumatoid nodules. Smoking was associated with rheumatoid nodules among both men (p = 0.006) and women (p = 0.001). Tobacco use other than smoking (n = 31) was not associated with an increased risk of nodules (OR = 0.8 (0.2 to 3.4); p = 0.813). CONCLUSIONS: There is a strong association between smoking and rheumatoid nodules in early seropositive rheumatoid arthritis.     

Rheumatoid factor tests in the diagnosis and prediction of rheumatoid arthritis.

Four assays of rheumatoid factor (RF) have been measured on serum from 213 individuals from 13 families containing at least two sufferers from classical or definite rheumatoid arthritis (RA). Families were not uniformly RF positive or negative, and there was no evidence that non-RA RF positivity was inherited. Four individuals developed definite RA over a two year period, showing that the family members were at increased risk of RA. IgG RF and latex RF assays predicted the RA in the four cases. An association of RF positivity in RA with DR4 was observed, but this may be related to disease severity.     

Smoking history and serum cotinine and thiocyanate concentrations as determinants of rheumatoid factor in non-rheumatoid subjects

OBJECTIVES: Smoking is associated with false-positive rheumatoid factor (RF). We explored the dose-response relationship of this association, using smoking history and serum cotinine and thiocyanate concentrations as measures of tobacco exposure. METHODS: A total of 6947 men and women aged 30 yr or over and free of clinical arthritis were included in the Mini-Finland Health Survey carried out between 1978 and 1980. Detailed histories of smoking and RF (sensitized sheep cell agglutination test) were obtained in the basic examination. In 2000, serum cotinine and thiocyanate were determined from serum samples collected at baseline and stored at -20 degrees C. A cut-off point of 100 microg/l was used for serum cotinine and 10 micromol/l for thiocyanate to indicate active smoking. RESULTS: There was a close association between smoking and strongly positive RF. After adjustment for age, sex, coffee consumption and region, the odds ratios (95% confidence intervals in brackets) in current smokers and in those who had quit smoking were 3.94 (2.04-7.61) and 2.71 (1.33-5.53), respectively, compared with those who had never smoked. Among current smokers, the intensity, duration or tertiles of pack-years of smoking were not related to RF. No relationship between serum cotinine or thiocyanate and RF positivity was observed within the subgroups of current smokers and those who had quit. Among those who reported that they had never smoked but who nevertheless had serum cotinine levels at least 100 microg/l, the adjusted odds ratio of strongly positive RF was 4.48 (1.48-13.50) compared with people who had never smoked and whose serum cotinine levels were less than 100 microg/l. CONCLUSIONS: The results are not in line with the hypothesis of a dose-response relationship between smoking exposure and RF positivity.     

Association of HLA-C3 and smoking with vasculitis in patients with rheumatoid arthritis

OBJECTIVE: To compare HLA-C genotypes and smoking habits in patients with vasculitis or other severe extraarticular manifestations of rheumatoid arthritis (ExRA) with those in RA patients without extraarticular disease. METHODS: Patients were recruited from a large research database of patients with RA at the Mayo Clinic, from 2 Swedish cohorts of prevalent RA cases, and from a regional Swedish early RA cohort. Patients with severe ExRA (n = 159) and control patients with RA but no history of ExRA (non-ExRA controls) (n = 178) were matched for duration of RA and for clinical center. Data on smoking at RA onset, rheumatoid factor (RF) status, and antinuclear antibodies (ANAs) were extracted from the medical records. Polymerase chain reaction-based HLA-C genotyping was performed using a sequence-specific primer kit. RESULTS: The distribution of HLA-C alleles was significantly different between patients with RA-associated vasculitis and non-ExRA controls (P = 0.014). This was mainly due to a positive association of the HLA-C3 allele with vasculitis (allele frequency 0.411 in vasculitis patients versus 0.199 in non-ExRA controls; P < 0.001) and a decreased frequency of HLA-C7 (0.122 and 0.243, respectively; P = 0.018). The association between HLA-C3 and vasculitis was not due to linkage disequilibrium with HLA-DRB1. Smoking (P = 0.001), RF positivity (P < 0.0001), and presence of ANAs (P < 0.0001) were all associated with ExRA. HLA-C3 and smoking were both significant predictors of vasculitis in a multivariate model. CONCLUSION: Vasculitis in RA is associated with HLA-C3. Smoking is an independent predictor of vasculitis and other types of severe ExRA. Our results suggest that these variables are among the genetic and environmental factors that contribute significantly to the pathomechanisms of systemic RA.     

Relationship among the HLA–DRB1 shared epitope,smoking, and rheumatoid factor production in rheumatoid arthritis

Objective

Rheumatoid factor (RF) production in rheumatoid arthritis (RA) is generally associated with more severe disease. In some studies, RF production has been associated with carriage of HLA–DRB1 alleles encoding the RA‐associated shared epitope (SE). Patients who smoke are also more likely to be RF positive. In this study, we investigated whether the association between RF production and smoking was influenced by carriage of the SE.

Methods

The smoking histories of 371 RA patients attending a hospital clinic were recorded. RF levels and SE status were determined for every patient, and the associations between the SE, smoking, and RF production were examined. HLA–DRB1 typing was performed using polymerase chain reaction. Results were analyzed using chi‐square tests and logistic regression analysis.

Results

Patients who had ever smoked were significantly more likely to be RF positive than nonsmokers (odds ratio 2.2, P < 0.0001). This remained significant (P = 0.003) after correction for age, sex, and disease duration in a logistic regression model. An association was also found between RF positivity and carriage of the SE (P = 0.03, after correction for age, sex, and disease duration), but significance was reduced or lost after correction for previous or current smoking (P = 0.05 and 0.09, respectively). Examination of the major SE phenotypes in this RA population by multivariate logistic regression analysis revealed that only DRB1*0401 was associated with RF positivity, and that this was independent of the influence of smoking.

Conclusion

Our data confirm that RF production in RA patients is associated with smoking. This does not appear to depend on an HLA–DR‐restricted immune response. The association of the SE with RF positivity is primarily due to HLA–DRB1*0401. This appears to be independent of the association with smoking, although smoking further increases the likelihood of RF production in DRB1*0401 patients.

     

Lack of association of antineutrophil cytoplasmic antibodies with joint failure as indicated by joint surgery in rheumatoid arthritis

Aim: The objective of this study was to investigate a possible association in rheumatoid arthritis (RA) of perinuclear antineutrophil cytoplasmic antibodies (pANCA) and joint failure requiring joint surgery as a well‐defined functional end point. Methods: 188 patients with RA according to the American College of Rheumatology criteria, with a mean duration of disease of 18 years, were enrolled in a cross‐sectional study. Patients were assessed for history of joint surgery, previous/current therapies, function according to the modified Health Assessment Questionnaire (mHAQ), rheumatoid factor (RF) and clinical and laboratory parameters of disease activity. ANCA were detected using indirect immunofluorescence. Results: Overall, 36.7% of patients were pANCA positive (including atypical pANCA) and 35.1% of patients had a history of joint surgery. There was no association between the presence of pANCA and joint surgery. No association was demonstrated between ANCA status and other prognostic markers such as RF, previous or current therapies and disease activity or function. Conclusion: No association between pANCA and joint surgery was demonstrated in this cohort of RA patients.     

Antifilaggrin antibodies within "normal" range predict rheumatoid arthritis in a linear fashion

OBJECTIVE: Increasing attention has been paid to the significance of antifilaggrin antibodies (AFA) in rheumatoid arthritis (RA). We studied the prediction of RA by AFA in serum specimens from the period prior to the onset of clinical RA. METHODS: A case-control study was nested within a Finnish cohort of 19.072 adults who had neither arthritis nor a history of it at the baseline examination during 1973-77. Pre-illness serum specimens for the assay of AFA by ELISA, using filaggrin purified from human skin as the antigen, were available from 124 of the 126 patients who had developed RA by late 1989. Of the incident cases 89 were positive for rheumatoid factor (RF). Three controls per each incident case were individually matched for sex, age, and municipality. RESULTS: Pre-illness serum AFA level was found to be directly proportional to the risk of RF positive RA. The odds ratio (95% confidence interval) in the highest quintile compared to the lowest quintile was 5.4 (2.2-13.6). In the subgroup of subjects positive for RF at baseline the figure was 24 (4.0-140). AFA did not predict the development of RF negative RA. A close association of the same order of magnitude between RF and AFA was noted in the pre-illness sera and in the control sera. CONCLUSION: AFA still within the "normal" range predicts RA in a linear fashion. AFA and RF are associated markers of the rheumatoid immunological process.     

Coffee or tea consumption and the risk of rheumatoid arthritis: a meta-analysis

The aim of this study was to analyze published results for an association between coffee or tea intake and the development of rheumatoid arthritis (RA). We investigated the evidence for a relationship between coffee or tea consumption and the development of RA by performing a meta-analysis of the published results. Five studies (three cohort and two case–control studies) including 134,901 participants (1,279 cases of RA and 133,622 noncases) were considered in the meta-analysis. Meta-analysis of the cohort studies revealed a trend of an association between total coffee intake and RA incidence (relative risk [RR] of the highest versus the lowest group?=?4.148, 95 % confidence interval [CI]?=?0.792–21.73, p?=?0.092). Meta-analysis of case–control studies showed a significant association between total coffee intake and RA incidence (RR?=?1.201, 95 % CI?=?1.058–1.361, p?=?0.005). Combining the data of the cohort and case–control studies showed a significant association between total coffee intake and RA incidence (RR?=?2.426, 95 % CI?=?1.060–5.554, p?=?0.036). Meta-analysis stratified by seropositivity indicated a significant association between coffee consumption and seropositive RA risk (RR?=?1.329, 95 % CI?=?1.162–1.522, p?=?3.5?×?10^?5), but not seronegative RA risk (RR?=?1.093, 95 % CI?=?0.884–1.350, p?=?0.411). No association was found between tea intake and RA incidence (RR?=?0.880, 95 % CI?=?0.624–1.239, p?=?0.463). This meta-analysis of 134,901 participants (most of the participants were controls) suggests that high coffee consumption is associated with an elevated risk of RA development. The association between coffee and RA was found in seropositive RA, but not in seronegative RA.     

Mortality risk associated with rheumatoid arthritis in a prospective cohort of older women: results from the Iowa Women's Health Study

OBJECTIVE: To determine whether rheumatoid arthritis (RA) is associated with excess mortality among older women. METHODS: RA associated mortality was examined in a prospective cohort study that was started in 1986, and included 31 336 women aged 55-69 years without a history of RA at baseline. Up to 1997, 158 cases of RA were identified and validated against medical records. The relative risk (RR) and 95% confidence interval (CI) were calculated as measures of association between RA onset and subsequent mortality (overall and cause-specific) using Cox proportional hazards regression. RESULTS: Compared with non-cases, women developing RA during follow up had a significantly increased mortality risk (RR=1.52; 95% CI 1.05 to 2.20). Mortality was higher among rheumatoid factor (RF) positive cases (RR=1.90; 95% CI 1.24 to 2.92) than among RF negative cases (RR=1.00; 95% CI 0.45 to 1.99). There were trends towards increased proportions of RA related deaths from infection (RR=3.61; 95% CI 0.89-14.69) and circulatory disease (RR=1.46; 95% CI 0.76 to 2.81) but not malignancy (RR=0.97; 95% CI 0.46 to 2.04). CONCLUSIONS: RA was associated with significantly increased mortality in a cohort of older women, and the association appeared to be restricted to those with RF positive disease.     

Independent association of rheumatoid factor and the HLA-DRB1 shared epitope with radiographic outcome in rheumatoid arthritis

OBJECTIVE: Findings of a recent study suggested that HLA-DRB1 alleles encoding the rheumatoid arthritis (RA) "shared epitope" (SE) were not predictive of erosive damage at 2 years in patients with early inflammatory arthritis who were rheumatoid factor (RF) positive, but were predictive in those who were RF negative. The present study was undertaken to determine whether RF status was also important in the association between the SE and radiographic outcome in patients with longstanding RA. METHODS: The association between radiographic outcome, HLA-DRBI, and RF status was examined in 299 RA patients with established disease (5-30 years). Radiographic outcome was measured by scoring radiographs of the hands and feet using the standard radiographs of Larsen. HLA-DRB1 typing was performed using polymerase chain reaction methodology. Results were stratified by RF status and analyzed by multiple regression. RESULTS: An association between radiographic severity and the SE was found in RF-, but not RF+, patients. RF- patients carrying an SE allele had higher Larsen scores than RF- patients lacking the SE, although there was no association with SE dosage. The mean Larsen score was significantly higher in RF+ patients than in RF- patients, but there were no differences between RF+ patients with 0, 1, or 2 SE alleles. Multiple regression analysis confirmed independent associations of RF and SE positivity with radiographic outcome. No significant associations were found between RF and the SE, or RF and individual SE alleles. CONCLUSION: Our data indicate that RF and the SE are independently associated with radiographic outcome in RA. In RF+ patients with longstanding RA, there is no apparent association between the presence of the SE and radiographic damage. However, in RF-patients, although radiographic outcome is generally less severe, there is an association between severity and presence of the SE.     

Association of rheumatoid factors and anti-filaggrin antibodies with severity of erosions in rheumatoid arthritis

OBJECTIVES: To evaluate and to compare the association of two types of autoantibodies-rheumatoid factors (RF) and anti-filaggrin antibodies (AFA)-with clinical severity and joint damage progression in rheumatoid arthritis (RA) patients. METHODS: In a cross-sectional study, we determined RF and AFA titres in 199 RA patients and 65 controls. Erosions apparent on X-rays were quantified using the Larsen score in 143 patients, and the distribution of these scores was studied according to disease duration in patients who were positive and negative for RF and AFA. RESULTS: RF were detected in 72% and AFA in 47% of RA patients. AFA were highly specific for RA (100%). RF positivity was correlated with the presence of subcutaneous nodules, sicca syndrome and the severity of erosions for a given disease duration. AFA positivity was correlated only with the presence of the HLA-DRB1 shared epitope. CONCLUSIONS: Since no significant correlation was observed between joint damage progression and AFA positivity, the determination of AFA does not appear to be useful in assessing the prognosis of RA. However, AFA, which appear early in RA, could be helpful for the diagnosis of RA in patients who do not fulfil four American College of Rheumatology criteria.     

The effect of smoking on clinical, laboratory, and radiographic status in rheumatoid arthritis

OBJECTIVE: (1) To determine the degree to which rheumatoid factor (RF) positivity is associated with smoking; (2) to determine the quantitative effect of smoking and smoking length on the concentration of RF in all patients, and, in the seropositive patients separately, determining if a "dose-response" effect exists; (3) to investigate these relationships in men and women to clarify whether the effect of smoking is similar in both sexes; (4) to determine the effect of smoking, controlling for RF, on a variety of measures of disease status, severity, and activity. METHODS: Six hundred ten consecutive patients with rheumatoid arthritis seen for routine clinical care provided information on their smoking history. All underwent a complete joint examination, completed a series of health status questionnaires, provided information concerning pulmonary illnesses, underwent determinations for RF and erythrocyte sedimentation rate (ESR), and had hand radiographs. RESULTS: RF concentration was linearly related to the number of years smoked. This association was present in both sexes, but was stronger in men. Smoking was similarly related to rheumatoid nodule formation. A nonlinear relationship was found between smoking and radiographic abnormalities as determined by the Larsen method, even controlling for RF. Similarly, pulmonary illness was independently related to smoking and RF. No effect of smoking was seen on disease process variables such as ESR, pain, joint count, global severity, or functional ability. CONCLUSION: Quantitative relationships exist between smoking extent and RF positivity, RF concentration, nodule formation, radiographic progression, and pulmonary disease. These 3 latter effects are independent of RF positivity or concentration. Smoking does not contribute to alterations in disease activity measures, but appears to play a role in overall severity of disease.     

Nodular disease in rheumatoid arthritis: association with cigarette smoking and HLA-DRB1/TNF gene interaction

OBJECTIVE: To investigate the association of nodular disease in rheumatoid arthritis (RA) with smoking, seropositivity, and polymorphisms at HLA-DRB1 and TNF loci. METHODS: Consecutive patients with RA (n = 420) attending a hospital clinic were examined for the presence of subcutaneous nodules. Rheumatoid factor (RF) status and HLA-DRB1 genotype were determined on every patient, and their smoking history was recorded. TNFa microsatellite polymorphisms were examined in a subgroup of 144 patients. The relationships between smoking, RF status, HLA-DRB1 genotype, TNFa microsatellite polymorphism, and the presence of nodules were examined using chi-square tests and logistic regression analyses. RESULTS: Current smokers were more likely to have nodular disease than those who had never smoked (OR 1.8, 95% CI 1.0-2.9). An association was also found between RF positivity and nodular disease (OR 2.2, 95% CI 1.2-3.8) that remained significant after correction for current smoking. A combination of current smoking and seropositivity increased the risk of nodular disease (OR 3.9, 95% CI 1.7-9.1). Analysis of HLA-DRB1 genotypes in this RA population revealed that only DRB1*0401 homozygotes were associated with nodular disease, and that this was independent of the influence of smoking and seropositivity. Individual TNFa microsatellite alleles were not associated with the presence of nodules, but an interactive effect was found between the TNF a6 allele and homozygosity for DRB1*0401. CONCLUSION: Our data indicate that nodular disease in RA is independently associated with current cigarette smoking, seropositivity, and homozygosity for HLA-DRB1*0401. The latter association involves a possible interaction with the TNF a6 microsatellite allele.     

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.