Connective Tissue Disease Screening Questionnaire Research Articles

Prevalence of systemic lupus erythematosus-related symptoms assessed by using the Connective Tissue Disease Screening Questionnaire in a large population-based cohort

BackgroundTo assess the prevalence of self-reported SLE-related symptoms associated with demographic and biochemical data and connective tissue disease (CTD)-related autoantibodies in a large population-based cohort.MethodsParticipants of the Dutch Lifelines population...

Arthritis autoantibodies in individuals without rheumatoid arthritis: follow-up data from a Dutch population-based cohort (Lifelines).

ObjectivesTo assess whether the presence of arthritis autoantibodies alongside IgG ACPA predicts clinically suspect arthralgia in ACPA-positive subjects without RA.MethodsIn the population-based Lifelines cohort (n = 40 136), 308 IgG ACPA-positive individuals without RA were present. Serum levels of IgA ACPA, IgA and IgM RF, and IgG anti-carbamylated antibodies were measured at baseline. Individuals were divided based on the Connective tissue disease Screening Questionnaire after 2 years follow-up. Antibodies to Porphyromonas gingivalis were determined at baseline and related to presence of periodontitis and joint complaints at 2 years follow-up.ResultsOf 308 subjects 53.6% were also seropositive for IgA ACPA, 42.2% for IgM RF, 23.7% for IgA RF and 13.6% for anti-carbamylated antibodies. We defined 75 persons with clinically suspect arthralgia at risk for RA based on CTD Screening Questionnaire at follow-up. Significantly more seropositivity for IgM RF and higher levels of IgG ACPA, IgA ACPA and IgM RF were found in clinically suspect arthralgia compared with no-clinically suspect arthralgia. In multivariate logistic regression correcting for age, gender and never smoking, positivity for three or more extra autoantibodies was significantly associated with clinically suspect arthralgia. Although levels of anti-P. gingivalis were not different between groups, they were significantly correlated to levels of both RFs, and both ACPAs in clinically suspect arthralgia.ConclusionsACPA-positive individuals without RA who develop clinically suspect arthralgia have more and higher levels of other arthritis autoantibodies at baseline. Levels of anti-P. gingivalis are not related to self-reported periodontitis or clinically suspect arthralgia, but are correlated to arthritis autoantibodies in clinically suspect arthralgia.

Cross-cultural adaptation of the connective tissue disease screening questionnaire and development of a Chinese version in a multi-ethnic Asian population.

To cross-culturally adapt the Connective Tissue Disease (CTD) Screening Questionnaire (CSQ) in a multi-ethnic Asian population in Singapore. An expert panel of accredited rheumatologists evaluated the content validity of the original CSQ. Consenting participants newly referred from primary care to a rheumatology specialist outpatient clinic for evaluation of possible CTDs were studied. Cognitive debriefing interviews (CDIs) using the original CSQ were conducted with English-speaking participants, with modifications made based on their inputs and in discussion with a second expert panel (rheumatologists and the CSQ developers). Forward and back translations of the adapted English version were reviewed by the second expert panel. The common translation produced was tested in CDIs with Chinese-speaking participants. Adapted English and Chinese versions were pilot tested in a separate group of newly referred patients. Content validity of the original CSQ was confirmed by the expert panel. A total of 30 and 15 participants were recruited for English and Chinese CDIs, respectively. Alternative terms and explanatory notes were added to difficult medical terms in the adapted English CSQ. A further explanatory note was added to one difficult item, and English medical terms were retained in the Chinese version. Pilot testing of the adapted CSQ was performed on 116 participants, which exhibited an overall sensitivity and specificity of 71% and 58%, respectively, in identifying CTDs. The adapted CSQ demonstrated satisfactory sensitivity in the pilot testing and appears to be a promising tool for facilitating early identification of CTDs in the multi-ethnic Asian population. • Early identification and management of patients with CTDs is crucial given their high disease burden and short "windows of opportunity." • High reliability and validity of original CSQ and its cross-culturally adapted versions have been reported; however, the CSQ has not been validated in Southeast Asia where CTDs are associated with higher morbidity and mortality compared to other countries. • Our cross-culturally adapted CSQ demonstrated satisfactory sensitivity in identifying CTDs in the multi-ethnic Asian population.

Screening characteristics for enrichment of individuals at higher risk for transitioning to classified SLE.

Further prospective study is needed to elucidate the etiology and natural history of systemic lupus erythematosus development. The clinical complexity of this heterogeneous disease makes study design challenging. Our objective was to ascertain useful screening factors for identifying at-risk individuals for follow-up rheumatologic assessment or inclusion in prospective studies. We attempted to re-contact 3823 subjects with a family history of systemic lupus erythematosus, who did not meet American College of Rheumatology systemic lupus erythematosus classification at a baseline study visit; 436 agreed to follow-up participation an average of 6.3 years after baseline. In total, 56 of these individuals had transitioned to classified systemic lupus erythematosus (≥ 4 cumulative American College of Rheumatology criteria, verified by medical record review) by the time of follow up. Generalized estimating equations assessed associations between our dichotomous outcome of transitioning to systemic lupus erythematosus with baseline characteristics, including ANA positivity, Connective Tissue Disease Screening questionnaire systemic lupus erythematosus score, and number of American College of Rheumatology criteria. We analyzed predictive accuracy of characteristics on transitioning. ANA positivity, Connective Tissue Disease Screening questionnaire systemic lupus erythematosus score categorization of possible or probable systemic lupus erythematosus, and greater number of American College of Rheumatology criteria at baseline were each associated with transitioning to systemic lupus erythematosus classification. Being ANA positive and having confirmed immunologic criteria at baseline had the highest positive predictive value and specificity for transitioning to systemic lupus erythematosus. American College of Rheumatology Connective Tissue Disease Screening questionnaire systemic lupus erythematosus score categorization of possible or probable systemic lupus erythematosus had a better positive predictive value, negative predictive value, sensitivity, and specificity than ANA positivity. Given limited resources, identifying individuals for follow up based on the systemic lupus erythematosus portion of the Connective Tissue Disease Screening questionnaire could be an efficient way to identify family members at highest risk of disease transition.

Discerning Risk of Disease Transition in Relatives of Systemic Lupus Erythematosus Patients Utilizing Soluble Mediators and Clinical Features.

Systemic lupus erythematosus (SLE) and other autoimmune diseases cause significant morbidity. Identifying populations at risk of developing SLE is essential for curtailing irreversible inflammatory damage. The aim of this study was to identify factors associated with transition to classified disease that would inform our understanding of the risk of SLE. Previously identified blood relatives of patients with SLE, who had <4 American College of Rheumatology (ACR) classification criteria for SLE at baseline, were enrolled in this follow-up study (n = 409 unaffected relatives). Participants provided detailed family, demographic, and clinical information, including the SLE-specific portion of the Connective Tissue Disease Screening Questionnaire (SLE-CSQ). Serum and plasma samples were tested for the presence of lupus-associated autoantibodies and 52 soluble mediators. Generalized estimating equations (GEEs) were applied to identify factors predictive of disease transition. Of the 409 unaffected relatives of SLE patients, 45 (11%) had transitioned to classified SLE at follow-up (mean time to follow-up 6.4 years). Relatives who transitioned to SLE displayed more lupus-associated autoantibody specificities and higher SLE-CSQ scores (P < 0.0001) at baseline than did relatives who did not transition. Importantly, those who had developed SLE during the follow-up period also had elevated baseline plasma levels of inflammatory mediators, including B lymphocyte stimulator, stem cell factor (SCF), and interferon-associated chemokines (P ≤ 0.02), with concurrent decreases in the levels of regulatory mediators, transforming growth factor β (TGFβ), and interleukin-10 (P ≤ 0.03). GEE analyses revealed that baseline SLE-CSQ scores or ACR scores (number of ACR criteria satisfied) and plasma levels of SCF and TGFβ, but not autoantibodies, were significant and independent predictors of SLE transition (P ≤ 0.03). Preclinical alterations in levels of soluble mediators may predict transition to classified disease in relatives of SLE patients. Thus, immune perturbations precede SLE classification and can help identify high-risk relatives for rheumatology referral and potential enrollment in prevention trials.

Soluble mediators and clinical features predict transition to systemic lupus erythematosus classification in previously unaffected relatives of SLE patients (HUM3P.243)

Abstract Healthy relatives of lupus patients have an increased risk of developing SLE, but predictors and mechanisms of disease transition are unknown. Unaffected relatives of SLE patients (n=409) were enrolled in this follow-up study to identify factors associated with transition to SLE. Participants provided detailed demographic and clinical information, including the Connective Tissue Disease Screening Questionnaire (CSQ). Medical records were reviewed for ACR classification criteria. Plasma samples were tested for the presence of autoantibodies and soluble mediators. Forty-five relatives (11%) transitioned to classified SLE during follow-up (mean time = 6.4 years) who had more autoantibodies (p&amp;lt;0.0001) and higher pre-classification (baseline) CSQ scores (p&amp;lt;0.0001). Relatives who transitioned also had elevated baseline levels of inflammatory mediators, including BLyS, SCF, and IFN-associated chemokines (p&amp;lt;0.05), with concurrent decreased regulatory mediators, including TGF-β and IL-10 (p&amp;lt;0.05). Logistic regression analysis revealed that baseline ACR and CSQ scores (but not autoantibodies), and baseline plasma levels of SCF and TGF-β were significant and independent predictors of SLE transition. Thus, perturbations in immune-mediated processes precede SLE clinical classification and can help identify unaffected relatives at highest risk of future SLE classification for early intervention studies.

Altered soluble mediator levels and systemic lupus erythematosus-specific Connective Tissue Disease Screening Questionnaire (CSQ) scores differentiate unaffected relatives of lupus patients from healthy individuals with no family history of SLE (CCR4P.214)

Abstract Identifying populations at risk of SLE who remain unaffected would provide insights for potential disease prevention. Using a unique resource of SLE patient family members, first degree relatives (FDRs) of SLE patients (n = 154) with plasma samples available from previous genetic studies and who remained unaffected at follow-up evaluation (mean time = 6.8 years) were matched to healthy individuals unrelated to SLE patients (Controls). FDRs and Controls provided clinical and demographic information, and completed screening questionairres at baseline (BL) and follow-up (FU). BL and FU plasma samples were assessed for autoantibody production and soluble mediators. FDRs had significantly higher BL and FU CSQ scores (p&amp;lt;0.0001), but no difference in the number of positive autoantibodies compared to Controls. FDRs had significant (p &amp;lt; 0.01) increases in 38 (of 52) soluble mediators at BL and FU, including IFN-associated chemokines, TNFR ligands, and regulatory mediators (p&amp;lt;0.002). Levels of MIP-1α (p=0.008), MIG (p=0.019), GROα (p=0.001), ICAM-1 (p=0.007), and VEGF (p=0.004), along with CSQ scores (p=0.010), best distinguished FDRs from Controls in logistic regression models. These alterations are present despite lack of progression to classified SLE, suggesting that multiple perturbations in immune-mediated inflammatory processes present in FDRs of SLE patients may be offset by inhibitory factors.

Alcohol consumption and risk of incident rheumatoid arthritis in women: a prospective study.

To evaluate the association of alcohol consumption with the risk of rheumatoid arthritis (RA) in 2 large prospective cohorts, the Nurses' Health Study (NHS) and NHSII. The NHS was established in 1976 and enrolled 121,701 female registered nurses in the US. The NHSII began in 1989, enrolling 116,430 female nurses. Lifestyle and environmental exposures were collected through biennial questionnaires. Alcohol consumption was assessed with a food frequency questionnaire, which was completed every 4 years. Incident RA cases were identified using a connective tissue disease screening questionnaire and a medical record review. Separate Cox proportional hazards models were used to estimate hazard ratios (HRs) after adjusting for potential confounders in the NHS and NHSII. The pooled HR from 2 cohorts was estimated using a DerSimonian and Laird random-effects model. Among 1.90 million person-years from 1980 to 2008, 580 incident cases of RA were diagnosed in the NHS cohort, and among 1.78 million person-years from 1989 to 2009, 323 incident cases of RA were diagnosed in the NHSII cohort. Compared to no use, the pooled multivariable adjusted HR for alcohol use of 5.0-9.9 gm/day was 0.78 (95% confidence interval [95% CI] 0.61-1.00). For seropositive RA cases, the association appeared stronger (HR 0.69 [95% CI 0.50-0.95]). In addition, women who drank beer 2-4 times a week had a 31% decreased risk compared to women who never drank beer. We found a modest association between long-term moderate alcohol drinking and reduced risk of RA. Future studies are needed to confirm our findings in other populations.

Implementation of the Connective Tissue Screening Questionnaire in Northeast Pennsylvania to Identify Comorbidities of Connective Tissue Diseases in Subjects With Systemic Lupus Erythematosus

Previous studies have described an increased risk of developing an additional connective tissue disease (CTD) when one such ailment is present. We examine here the likelihood that individuals with systemic lupus erythematosus (SLE) screen positive for one or more of the following five autoimmune CTDs: Sjögren's syndrome, scleroderma, rheumatoid arthritis, dermatomyositis/polymyositis, and mixed connective tissue disorder. Five hundred SLE-diagnosed subjects were asked to complete a CTD screening questionnaire (CSQ). The results were analyzed according to the set of diagnostic criteria given by the American College of Rheumatology to identify probable cases of each CTD. Significant standardized prevalence ratios and comorbidities indicate an increased risk for the other autoimmune CTDs. In all, 96% of the subjects screened positive for at least one additional CTD, and 13% screened positive for at least two additional CTDs. We see that the SLE-diagnosed population may benefit from further attention regarding the presence of additional CTDs, which may further inform treatment strategies. We also see the application of the CSQ as a potentially important tool for clinical practice, and we describe the present study's limitations along with possible ways that these can be addressed.

Low‐dose aspirin in the primary prevention of rheumatoid arthritis: The women's health study

Low-dose aspirin may reduce the risk of developing rheumatoid arthritis (RA) through its effect on cyclooxygenase activity and its antioxidant pathways. Previous randomized trial data have demonstrated a beneficial effect of low-dose aspirin in reducing other inflammatory diseases, such as asthma and colorectal adenomas, but no trial has evaluated the role of aspirin in RA prevention. The Women's Health Study is a randomized, double-blind, placebo-controlled trial conducted between 1992 and 2004 designed to evaluate the risks and benefits of low-dose aspirin (100 mg every other day) and vitamin E in the primary prevention of cardiovascular disease and cancer among 39,876 female health care professionals age > or =45 years throughout the US. After excluding women with RA at baseline, 39,144 women were evaluated for the present study. A definite diagnosis of RA was assessed during followup by self-report and confirmed using a connective tissue disease screening questionnaire, followed by a medical record review by a rheumatologist for American College of Rheumatology criteria. During an average followup of 10 years, 106 women developed definite RA (48 women in the aspirin group and 58 in the placebo group). There was a nonsignificant risk for RA (relative risk [RR] 0.83, 95% confidence interval [95% CI] 0.56-1.21; P = 0.33) associated with aspirin. There were 64 seropositive RA cases (60%) and 42 seronegative RA cases (40%). Aspirin also had no significant effect on either seropositive RA (RR 1.0, 95% CI 0.61-1.63) or seronegative RA (RR 0.62, 95% CI 0.33-1.15). One hundred milligrams of aspirin taken every other day was not associated with a significant reduction in the risk of developing RA among women in a randomized, double-blind, placebo-controlled trial.

Identification of undiagnosed inflammatory arthritis in a community health fair screen

To identify individuals with undiagnosed inflammatory arthritis (IA) and rheumatoid arthritis (RA) in a community health fair screen, and to establish in a health fair setting the diagnostic accuracy of combinations of the Connective Tissue Disease Screening Questionnaire (CSQ) and autoantibody testing for IA. Screening for IA/RA was performed at health fair sites using a combination of the CSQ, joint examination, rheumatoid factor, and anti-cyclic citrullinated peptide (anti-CCP) antibody testing. IA was defined as > or =1 swollen joint suggestive of synovitis on joint examination by a trained clinician. Six hundred one subjects were screened; 51.0% participated because of joint symptoms (pain, stiffness, or swelling). Eighty-four subjects (14.0%) had > or =1 swollen joint, designated as IA on joint examination. Of the 601 subjects screened, 9 (1.5%) had IA and met > or =4 of 7 American College of Rheumatology criteria for RA but had no prior diagnosis of RA, and 15 (2.5%) had IA and RF and/or anti-CCP positivity, suggesting early RA. The diagnostic accuracy of combinations of the CSQ and autoantibody testing for the identification of IA yielded maximal sensitivity, specificity, and positive and negative predictive values of 95.3%, 99.2%, 71.4%, and 97.7%, respectively. Health fair screening may be an effective approach for the identification of individuals with undiagnosed IA/RA. A combination of the CSQ and autoantibody testing alone has clinically useful diagnostic accuracy for the detection of IA. Decisions regarding which methodology to use for future health fair IA/RA screening will depend on goals of screening and funding.

Comparison of threshold cutpoints and continuous measures of anti-cyclic citrullinated peptide antibodies in predicting future rheumatoid arthritis.

Anti-cyclic citrullinated peptide (anti-CCP) antibodies are strongly associated with increased risk of rheumatoid arthritis (RA).While the anti-CCP level is commonly dichotomized for clinical use, the best threshold for and utility of the titer as a continuous variable to predict development of RA are uncertain. Using data from the Nurses' Health Study and Nurses' Health Study II longitudinal cohorts, we examined the sensitivity, specificity, and hazard of RA at various thresholds of the anti-CCP. Incident RA was confirmed using the Connective Tissue Disease Screening Questionnaire and medical record review in 93 women from among 62,437 participants with blood samples. Three controls per case were randomly chosen, matching on cohort, age, and menopausal status. Stored plasma was tested for anti-CCP antibodies with the second-generation Diastat ELISA. Five threshold values were assessed for sensitivity, specificity, and time to diagnosis of RA. Hazard of RA was assessed with conditional logistic regression models adjusting for smoking and reproductive factors. Using the suggested threshold of >5 U/ml for anti-CCP positivity, specificity was 100%, but sensitivity was only 28%. A threshold of >2 U/ml had a higher sensitivity (51%), and similar specificity (80%), with an odds ratio of 11.2 (95% confidence interval 4.7-26.9) for RA. Anti-CCP level as an ordinal variable was strongly associated with time to RA onset, with higher values predicting shorter time to RA onset. A lower threshold for anti-CCP positivity was more sensitive in predicting RA development. Higher ranges of the level were informative in predicting time to RA onset.

Vitamin E in the primary prevention of rheumatoid arthritis: The women's health study

Vitamin E supplements may reduce the risk of developing rheumatoid arthritis (RA) through antioxidant effects. Although previous observational studies have investigated this question, no randomized trial data are available. The Women's Health Study is a randomized, double-blind, placebo-controlled trial designed to evaluate the benefits and risks of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer among 39,876 female health professionals age > or = 45 years throughout the US, conducted between 1992 and 2004. After excluding women with self-reported RA at baseline, 39,144 women were included in the present study. The primary end point, definite RA, was confirmed using a connective tissue disease screening questionnaire, followed by medical record review for American College of Rheumatology criteria. During an average followup of 10 years, 106 cases of definite RA occurred, 50 in the vitamin E group and 56 in the placebo group. Sixty-four (60%) RA cases were rheumatoid factor positive and 42 (40%) were rheumatoid factor negative. There was no significant association between vitamin E and risk of definite RA (relative risk [RR] 0.89, 95% confidence interval [95% CI] 0.61-1.31). There were also no significant risk reductions for either seropositive RA (RR 0.64, 95% CI 0.39-1.06) or seronegative RA (RR 1.47, 95% CI 0.79-2.72). Six hundred IU of vitamin E supplements taken every other day is not associated with a significant reduction in the risk of developing RA among women in a randomized, double-blind, placebo-controlled trial.

RheumaCheck: Entwicklung und Evaluation eines deutschsprachigen Rheuma-Screening Instruments

Early diagnosis of inflammatory rheumatic diseases is important for patients' prognosis and outcome. The mean time delay of 1 to 5 years in Germany between the initial symptoms and the first rheumatologist contact should be reduced. Efficiency of patient questionnaires for the identification of inflammatory rheumatic diseases has been demonstrated in other countries. The aim of our study was to develop a patient questionnaire in German identifying inflammatory rheumatic diseases with a high sensitivity and specificity as well as a high positive predictive value. The RheumaCheck questionnaire was developed by adoption of the FDA-approved Connective Tissue Disease Screening Questionnaire. 1448 patients (195 controls, 437 patients suspicious for and 816 patients with known inflammatory rheumatic diseases) recruited by rheumatologists and general practitioners answered the questionnaire that additionally assessed comorbidities and sociodemographic data. A predictive algorithm was calculated. Mean age of the complete group (73.1% female) was 52.5 +/- 15.1 years. 53.1% had no comorbidity. Application of the algorithm yields a high sensitivity (77.6%) and specificity (79.9%). The area under the ROC curve was 0.85 (p < 0.0001). Being aware of a possible high rate of false true results RheumaCheck is a simple, efficient instrument easily filled out by patients. It can identify the group of patients that needs further investigation, care and assessment by a rheumatologist leading to earlier diagnosis and therapy. A web version of RheumaCheck is provided on www.rheuma-check.de .

Protein, iron, and meat consumption and risk for rheumatoid arthritis: a prospective cohort study

A recent prospective study showed that higher consumption of red meat and total protein was associated with increased risk for inflammatory polyarthritis. We therefore prospectively examined the relationship between diet (in particular, protein, iron, and corresponding food sources) and incident rheumatoid arthritis (RA) among 82,063 women in the Nurses' Health Study. From 1980 to 2002, 546 incident cases of RA were confirmed by a connective tissue disease screening questionnaire and medical record review for American College of Rheumatology criteria for RA. Diet was assessed at baseline in 1980 and five additional times during follow up. We conducted Cox proportional hazards analyses to calculate the rate ratio of RA associated with intakes of protein (total, animal, and vegetable) and iron (total, dietary, from supplements, and heme iron) and their primary food sources, adjusting for age, smoking, body mass index, and reproductive factors. The multivariate models revealed no association between RA and any measure of protein or iron intake. In comparisons of highest with lowest quintiles of intake, the rate ratio for total protein was 1.17 (95% confidence interval 0.89–1.54; P for trend = 0.11) and for total iron it was 1.04 (95% confidence interval 0.77–1.41; P for trend = 0.82). Red meat, poultry, and fish were also not associated with RA risk. We were unable to confirm that there is an association between protein or meat and risk for RA in this large female cohort. Iron was also not associated with RA in this cohort.

High sensitivity, specificity and predictive value of the Connective Tissue Disease Screening Questionnaire among urban African-American women

The Connective Tissue Disease Screening Questionnaire (CSQ), developed to screen populations for SLE and other CTDs, has been validated in a predominantly Caucasian population with hospital-based controls. We aimed to test the performance characteristics of the CSQ in an urban, predominantly African-American population. The CSQ was administered by interview to women recruited for a study of environmental risk factors and SLE, including 99 cases with SLE validated by medical record review and 202 healthy controls recruited from the community. Overall, 88% of subjects had African heritage, 6% were Hispanic and 4% were non-Hispanic Caucasian. Controls were more likely to report African heritage than cases (91% versus 82%, P = 0.001). Sensitivity for detecting SLE was 88% and specificity was 91%. In this study, where the prevalence of SLE was 33%, predictive value of a positive CSQ was 82% and predictive value of a negative CSQ was 94%. The CSQ has slightly lower sensitivity but greater specificity for SLE in an urban, predominantly African-American population with community-based controls compared with a Caucasian population with hospital-based controls. These results suggest that the CSQ has adequate sensitivity and specificity and could be used in population studies to screen African-American women for SLE.

Do breast‐feeding and other reproductive factors influence future risk of rheumatoid arthritis?: Results from the Nurses' Health Study

To explore the contribution of female hormonal factors occurring prior to the onset of rheumatoid arthritis (RA), such as age at menarche, parity, age at first birth, breast-feeding, use of oral contraceptives (OCs), irregular menstrual cycles, and postmenopausal hormone (PMH) use, to the subsequent development of RA in a large female cohort. We studied female reproductive and hormonal risk factors for RA in a cohort of 121,700 women enrolled in the longitudinal Nurses' Health Study. The diagnosis of incident RA (between 1976 and 2002) in 674 women was confirmed by a connective tissue disease screening questionnaire and blinded medical record review for American College of Rheumatology criteria. Sixty percent of the patients with RA were rheumatoid factor positive. The relationship between potential risk factors, including age, age at menarche, parity, age at first birth, total lifetime history of breast-feeding, use of OCs, and irregular menstrual cycles and the multivariate-adjusted risk of RA was estimated using Cox proportional hazards models. Using a multivariate model that adjusted for age, body mass index, smoking, parity, and other hormonal factors, we observed a strong trend for decreasing risk of RA with increasing duration of breast-feeding (P for trend = 0.001). For women who breast-fed (compared with parous women who did not breast-feed), the risk ratios (RRs) and 95% confidence intervals (95% CIs) were as follows: breast-feeding for < or =3 total months, RR 1.0 (95% confidence interval [95% CI] 0.8-1.2); for 4-11 total months, RR 0.9 (95% CI 0.7-1.1); for 12-23 total months, RR 0.8 (95% CI 0.6-1.0); and for > or =24 total months, RR 0.5 (95% CI 0.3-0.8). Very irregular menstrual cycles were associated with an increased risk of RA (RR 1.4, 95% CI 1.0-2.0). Age at menarche < or =10 years was associated with an increased risk of seropositive RA (RR 1.6, 95% CI 1.1-2.4) but not significantly associated with risk of RA. Parity, total number of children, age at first birth, and OC use were not associated with an increased risk of RA in this cohort. In this large cohort, breast-feeding for >12 months was inversely related to the development of RA. This apparent effect was dose-dependent, with a significant trend toward lower risk with longer duration of breast-feeding. Irregular menstrual cycles and earlier age at menarche increased the risk of RA. Other reproductive hormonal factors were not associated with RA risk.

Coffee consumption and risk of rheumatoid arthritis.

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. 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. 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. 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.

A connective tissue disease screening questionnaire for population studies

To develop a technique to screen populations for potential connective tissue disease (CTD), we mailed a 30-item questionnaire to 253 randomly selected patients with systemic lupus erythematosus, rheumatoid arthritis, scleroderma, polymyositis, dermatomyositis, mixed connective tissue disease (MCTD), or Sjögren's syndrome and to 340 randomly selected control subjects. The response rate after four mailings was 71% for case subjects and 54% for control subjects. Test-retest reliability for detection of any CTD was 0.82. Sensitivity for specific CTDs was 83 to 96% and specificity was 83 to 93%. The positive predictive value for any CTD (assuming an overall prevalence of 1.3%) was 5.5%; negative predictive value was 99.7%. The CTD Screening Questionnaire has high sensitivity and specificity for screening large populations.

Thrombocytopenic purpura and chickenpox.

<h3>Objective.</h3> Anti-cyclic citrullinated peptide (anti-CCP) antibodies are strongly associated with increased risk of rheumatoid arthritis (RA).While the anti-CCP level is commonly dichotomized for clinical use, the best threshold for and utility of the titer as a continuous variable to predict development of RA are uncertain. <h3>Methods.</h3> Using data from the Nurses’ Health Study and Nurses’ Health Study II longitudinal cohorts, we examined the sensitivity, specificity, and hazard of RA at various thresholds of the anti-CCP. Incident RA was confirmed using the Connective Tissue Disease Screening Questionnaire and medical record review in 93 women from among 62,437 participants with blood samples. Three controls per case were randomly chosen, matching on cohort, age, and menopausal status. Stored plasma was tested for anti-CCP antibodies with the second-generation Diastat™ ELISA. Five threshold values were assessed for sensitivity, specificity, and time to diagnosis of RA. Hazard of RA was assessed with conditional logistic regression models adjusting for smoking and reproductive factors. <h3>Results.</h3> Using the suggested threshold of &gt; 5 U/ml for anti-CCP positivity, specificity was 100%, but sensitivity was only 28%. A threshold of &gt; 2 U/ml had a higher sensitivity (51%), and similar specificity (80%), with an odds ratio of 11.2 (95% confidence interval 4.7–26.9) for RA. Anti-CCP level as an ordinal variable was strongly associated with time to RA onset, with higher values predicting shorter time to RA onset. <h3>Conclusion.</h3> A lower threshold for anti-CCP positivity was more sensitive in predicting RA development. Higher ranges of the level were informative in predicting time to RA onset.