Comparison of the 1987 American College of Rheumatology and the 2010 American College of Rheumatology/European League against Rheumatism criteria for classification of rheumatoid arthritis in the Nurses' Health Study cohorts.

Performance of rheumatoid arthritis (RA) classification by the 2010 American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) criteria, compared to the 1987 ACR criteria, has not been assessed in population-based cohorts in which disease identification is by mailed questionnaire. Women followed in the Nurses' Health Study and Nurses' Health Study II cohorts self-reported new doctor-diagnosed RA on biennial questionnaires. Two RA experts reviewed medical records of 128 new RA self-reports to obtain individual 1987 and 2010 criteria and arrived at a consensus opinion. We compared agreement in classification by the two criteria sets (kappa), and calculated sensitivity and specificity, with reviewers' opinion as gold standard. Ninety-eight (77%) participants were classified as RA by reviewers' consensus opinion; 98 (77%) fulfilled 1987 criteria, while 79 (63%) fulfilled 2010 criteria. Seventy-two (56%) were classified as RA by both sets, 21 (16%) by neither, 26 (20%) by only 1987 criteria, and 9 (7%) by only 2010 criteria. Kappa for concordance was 0.36 (95% CI 0.20-0.53). Compared to reviewer's opinion, sensitivity and specificity were 0.93 and 0.77 for 1987 criteria, and 0.79 and 0.87 for 2010 criteria. Participants fulfilling 1987 criteria only were more likely to be seronegative. In these prospective population-based cohorts, significant discordance between 1987 ACR and 2010 ACR/EULAR criteria for classifying RA exists. Using the 2010 ACR/EULAR criteria alone had decreased sensitivity, and seronegative RA cases would be excluded in particular. Combined use of both will be necessary to maximize inclusion and allow sensitivity analyses.

High resolution computed tomography pattern of usual interstitial pneumonia in rheumatoid arthritis-associated interstitial lung disease: Relationship to survival.

PURPOSE: Interstitial lung disease is a common extra-articular manifestation of rheumatoid arthritis (RA-ILD) and is associated with significant morbidity and mortality. However, limited data exist regarding predictors of mortality. We sought to examine the prognostic value of the high-resolution computed tomography (HRCT) patterns in patients with RA-ILD. MATERIALS AND METHODS: RA-ILD patients with HRCT patterns of usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP) were identified among a longitudinal cohort of individuals evaluated at National Jewish Health. A total of 158 subjects were included in the study. For each subject, the earliest available HRCT was reviewed independently by two expert thoracic radiologists blinded to clinical data. HRCT patterns were classified as demonstrating definite UIP, possible UIP, or NSIP. Kaplan-Meier curves were generated and survival was compared among the three patterns using a log rank test for trend. RESULTS: One hundred subjects (63%) had HRCT findings classified as definite UIP, 23 (15%) as possible UIP and 35 (22%) as NSIP. No difference in survival was seen between subjects with definite UIP versus those with possible UIP. The combined group of subjects with either definite- or possible UIP had significantly worse survival than those with NSIP (log-rank p = 0.03). CONCLUSIONS: In patients with RA-ILD, patients with either definite UIP or possible UIP have equally poor survival when compared to those with an NSIP pattern.

Anti-citrullinated peptide autoantibodies, human leukocyte antigen shared epitope and risk of future rheumatoid arthritis: a nested case-control study.

INTRODUCTION: The aim of this study was to characterize anti-citrullinated peptide antibody (ACPA) serostatus in pre-clinical rheumatoid arthritis (RA) with and without Human Leukocyte Antigen-Shared Epitope (HLA-SE) alleles. METHODS: We identified 192 women in the Nurses' Health Study cohorts with blood samples obtained 4 months to 17 years prior to medical record-confirmed RA diagnosis. Three controls were selected matched on age, cohort, menopausal status and post-menopausal hormone use. Reactivities to 18 ACPAs were measured using a custom BioPlex platform. We used conditional logistic regression to calculate the relative risk (RR) of RA for any ACPA-positive and peptide-specific ACPA-positive and examined RRs by time between blood draw and RA onset. Measures of multiplicative and additive interaction between any ACPA-positive and HLA-SE were calculated. RESULTS: All ACPAs by peptide groups were significantly associated with RA risk, RRs ranged from 4.7 to 11.7. The association between ACPA and RA varied over time with the strongest association in those with blood draw less than 5 years before onset (RR 17.0 [95% CI 5.8 to 53.7]) and no association 10 or more years prior to onset (RR 1.4 [95% CI 0.5 to 4.3]). Individuals with both HLA-SE and any ACPA-positive had the highest risk of RA. HLA-SE-positive RA cases showed reactivity to more ACPA types than HLA-SE negative (χ2 test for trend, P = 0.01). CONCLUSIONS: There is increasing ACPA reactivity up to 10 years before RA onset with the strongest association within 5 years of RA onset. The magnitude of the response to ACPAs, in combination with the presence of HLA-SE, is most important for identifying those individuals with the highest risk of RA.

Epstein-Barr virus serologic abnormalities and risk of rheumatoid arthritis among women.

BACKGROUND: Epstein-Barr virus (EBV) infection and the immune response may be involved in the pathogenesis of rheumatoid arthritis (RA). Past studies have suggested an association between EBV and RA. METHODS: We studied the association between EBV serologies and RA risk in a nested case-control study in the Nurses' Health Study (NHS) cohorts. We confirmed incident RA cases from 1990 to 2002 by questionnaire and medical record review. Each incident case with blood collected prior to RA symptoms was matched with a healthy participant by time of day and date of blood collection, birth year, menopausal status and postmenopausal hormone use. Immunofluorescence assays measured serologic EBV responses: viral capsid antigen, early-antigen-diffuse and early antigen-complex (restricted and diffuse), Epstein Barr nuclear antigen (EBNA)-1, EBNA-2 and cytomegalovirus (CMV), as control. All were reported as titers, except CMV, which was reported as positive or negative. Antinuclear antibody positive samples were excluded. Elevated EBV antibody titers were defined as the upper 20% (or nearest titer) among controls. Conditional logistic regression analyses modeled RA risk associated with elevated EBV titers or the presence/absence of CMV, further adjusted for pack-years smoking and alcohol intake. RESULTS: Eighty-seven incident RA cases were identified. Mean time to RA after blood draw was 6.2 (± 3.5) years in NHS and 1.9 (± 0.6) years in NHS II. Antibody titers against EBV were not significantly different between pre-RA cases and controls. CONCLUSIONS: In this prospective study of women, we observed no association between EBV serologies and RA risk.

Identification of undiagnosed inflammatory arthritis in a community health fair screen.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.