ObjectivesUveitis, psoriasis and inflammatory bowel disease (IBD) are common extra-articular manifestations (EAM) in patients with ankylosing spondylitis (AS); however, summary data of reported prevalence are lacking. The aim of the present study was to summarise the prevalence of EAMs among patients with AS and to identify underlying factors to explain potential heterogeneity of prevalence.MethodsA systematic literature search was performed (Medline, Embase and Cochrane Library) to identify relevant articles. Risk of bias was assessed and data were extracted. Pooled prevalences were calculated. Potential sources of any observed clinical or methodological heterogeneity in the estimates were explored by subgroup and metaregression analysis.ResultsIn the 156 selected articles, 143 reported the prevalence of uveitis (44 372 patients), 56 of psoriasis (27 626 patients) and 69 of IBD (30 410 patients). Substantial heterogeneity was observed in prevalence estimates among all EAMs (I2=84–95%). The pooled prevalence of uveitis was 25.8% (95% CI 24.1% to 27.6%), and was positively associated in multivariable metaregression with disease duration (β 0.05, 95% CI 0.03 to 0.08) and random selection of patients (β −0.24, 95% CI −0.43 to −0.04). The pooled prevalence of psoriasis was 9.3% (95% CI 8.1% to 10.6%). The pooled prevalence of IBD was 6.8% (95% CI 6.1% to 7.7%) and was positively associated with the percentage of women in the studies (β 0.02, 95% CI 0.00 to 0.03). Geographical area was associated in multivariable metaregressions with prevalence of all EAMs.ConclusionsEAMs are common in patients with AS. The large heterogeneity between studies can be partly explained by differences in clinical as well as methodological characteristics.

BackgroundRheumatoid arthritis (RA) is an inflammatory debilitating disease that affects the joints in the early and productive phases of an individual’s life. Several cytokines have been linked to the disease pathogenesis and are known to contribute to the inflammatory state characteristic of RA. The participation of type I interferon (IFN) in the pathogenesis of the disease has been already described as well as the identity of the genes that are regulated by this molecule, which are collectively known as the type I IFN signature. These genes have several functions associated with apoptosis, transcriptional regulation, protein degradation, Th2 cell induction, B cell proliferation, etc. This article evaluated the expression of several genes of the IFN signature in different stages of disease and their correlation with the levels of anticitrullinated protein antibodies (ACPA) anticarbamylated protein (Anti-CarP) antibodies.MethodsSamples from individuals with early and established RA, high-risk individuals (ACPA+ and ACPA−), and healthy controls were recruited at “Unidad de Artritis y Rheumatismo” (Rheumatism and Arthritis Unit) in Guadalajara Jalisco Mexico. Determinations of ACPA were made with Eurodiagnostica ACPA plus kit. Anti-CarP determinations were made according to previously described protocols. RNA was isolated, and purity and integrity were determined according to RNA integrity number >6. Gene expression analysis was made by RT-qPCR using specific primers for mRNAs of the type I IFN signature. Relative gene expression was calculated according to Livak and Schmitgen.ResultsSignificant differences in gene expression were identified when comparing the different groups for MXA and MXB (P < 0.05), also when comparing established RA and ACPA− in both IFIT 1 and G15. An increased expression of ISG15 was identified (P < 0.05), and a clear tendency toward increase was identified for HERC5. EPSTRI1, IFI6, and IFI35 were found to be elevated in the chronic/established RA and early RA (P < 0.05). Significant correlations were identified for the IFN signature genes with the levels of ACPA and anti-CarP (P < 0.05).ConclusionOur data confirm previous observations in the role of IFN signature and the pathogenesis of RA. Also, we provide evidence of an association between several genes of the IFN signature (that regulate Th2 cells and B cell proliferation) with the levels of anti-CarP antibodies and ACPA.

Objective Although blood bank–based studies have shown that rheumatoid arthritis (RA)–related autoantibodies are present before the onset of RA, information on their positive predictive value (PPV) for development of RA in healthy individuals is scarce. This study was undertaken to assess the 5‐year PPV of serum IgM rheumatoid factor (IgM‐RF) and anti–cyclic citrullinated peptide (anti‐CCP) for the development of RA among healthy relatives of patients with RA. Methods Healthy relatives of RA patients were invited to participate in a cohort study. At baseline, information on participants’ medical history was obtained, and serum levels of IgM‐RF and anti‐CCP antibodies were determined (by nephelometry and second‐generation anti‐CCP enzyme‐linked immunosorbent assay, respectively). The subjects were followed up every 4 months via a structured interview (Community Oriented Program for Control of Rheumatic Diseases [COPCORD] questionnaire). When the COPCORD questionnaire indicated possible arthritis, subjects underwent an in‐office rheumatology assessment including joint count. The study end point was defined as fulfillment of the American College of Rheumatology criteria for RA. Results Eight hundred nineteen initially healthy relatives of 252 patients with RA were included (69% female, 41% offspring, mean ± SD age 35 ± 12 years). Eleven (1.3%) were positive for both anti–CCP‐2 and RF, 12 (1.5%) only for anti–CCP‐2, and 16 (2%) only for RF. RA developed in 17 (2.1%) of the relatives during the 5‐year followup (3,313 person‐years for the seronegative group and 60.8 person‐years for the anti–CCP‐2–positive group). The PPV was 64% when both anti–CCP‐2 and RF were positive and 58% when only anti–CCP‐2 was positive. Offspring of patients with RA had an independent 3‐fold increased risk of developing RA. Conclusion Results of the present study indicate that the magnitude of risk for developing RA in healthy relatives of patients with RA can be estimated using simple routine laboratory tests.

Objective. To understand the impact of ankylosing spondylitis (AS) on work disability (WD) over 12 years compared with the general population, and explore factors predicting adverse work outcome, defined as new partial WD or reduction in working hours. Methods. Source of data was the Outcome Assessments in Ankylosing Spondylitis International Study, which includes patients from The Netherlands, France, and Belgium. Standardized WD rates over time compared to the general population were calculated using indirect standardization (Dutch patients only). Cox survival analyses identified baseline predictors as well as time-varying factors influencing adverse work outcome over 12 years. Results. Of 215 patients, 55 (26%) were full WD at baseline and 139 (65%) were at risk for adverse work outcome during followup. When compared to the general population, WD over 12 years continued to be increased in Dutch men (inci- . Time-varying predictors over 12 years were residence in The Netherlands, uveitis, and either BASFI or Bath Ankylosing Spondylitis Disease Activity Index with age and inflammatory bowel disease. Conclusion. Although WD was already prevalent at inclusion in the cohort, a substantial proportion of patients incurred further adverse work outcome over 12 years. In addition to country of residence, uveitis, age, and selfreported physical function or disease activity predicted long-term adverse work outcome.

Objective. To review the literature on contextual factors (CoFas) and their relationship to work outcomes in individuals with ankylosing spondylitis (AS). Methods. Articles that quantified the relationship between CoFas and employment status, sick leave, or presenteeism in individuals with AS were systematically identified. CoFas were classified into 5 domains for personal factors and 8 domains for environmental factors. We defined criteria for best-evidence synthesis for each CoFa domain based on the number of studies exploring that domain, and the quality of evidence of individual studies based on the risk of bias, adjustment of multivariable analyses for disease activity and physical function, and sample size. Results. Twenty-five studies met our inclusion criteria: 20 addressed employment status, 6 examined sick leave, and 3 presenteeism. For employment, there was strong evidence for the role of age, moderate evidence for related skills/abilities, the absence of work accommodations, the nature of work and absence of workplace support, and poor evidence for the role of marital status. Evidence was insufficient for sex, education, and physical environment. For sick leave and presenteeism there were too few studies to perform a best-evidence synthesis for the role of CoFas. Conclusion. Using a newly proposed set of criteria for determining the best-evidence of the association between CoFa domains and work outcome, the following factors emerged: age, related skills/abilities, work accommodations, nature of work, and workplace support. In addition to disease-related variables, these CoFa domains seem important to include when designing and interpreting studies on work outcomes.