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Herpes zoster or shingles is a common cutaneous disorder caused by the reactivation of latent varicella-zoster virus dormant in the cranial nerve or dorsal root ganglia. It usually manifests as a dermatomal distribution of a vesicular eruption that can cause significant morbidity (1). Herpes zoster is known to be more frequent in patients with conditions that depress cell-mediated immunity, including malignancy, HIV, transplantation, immunosuppressive disorders and treatment with immunosuppressants (2). The overall rate of herpes zoster in patients with rheumatoid arthritis (RA) is increased compared to the general population, with a greater risk in individuals using traditional disease modifying antirheumatic drugs (DMARDs) or biologic therapies (3). Use of prednisone in RA is an important predisposing factor for herpes zoster, and its use in conjunction with DMARDs increases the risk beyond that seen with the DMARDs alone (4). Many unanswered questions remain regarding the relationship between RA and reactivation of herpes zoster, and how RA related disease features, treatment and herpes zoster prevention measures might be addressed to avoid recurrent and complicated herpes zoster in these patients. We performed a population-based study to assess the incidence, time trends, risk factors and severity of herpes zoster in a well defined population of patients with RA. This information should serve the eventual goal of identifying possible strategies that could be employed to minimize the risk of development of herpes zoster in patients with RA.

Objective.To examine longterm visit-to-visit blood pressure (BP) variability in patients with rheumatoid arthritis (RA) versus non-RA subjects and to assess its effect on cardiovascular (CV) events and mortality in RA.Methods.Clinic BP measures were collected in a population-based incident cohort of patients with RA (1987 American College of Rheumatology criteria met between January 1, 1995, and January 1, 2008) and non-RA subjects. BP variability was defined as within-subject SD in systolic and diastolic BP.Results.The study included 442 patients with RA (mean age 55.5 yrs, 70% females) and 424 non-RA subjects (mean age 55.7 yrs, 69% females). Patients with RA had higher visit-to-visit variability in systolic BP (13.8 ± 4.7 mm Hg) than did non-RA subjects (13.0 ± 5.2 mm Hg, p = 0.004). Systolic BP variability declined after the index date in RA (p < 0.001) but not in the non-RA cohort (p = 0.73), adjusting for age, sex, and calendar year of RA. During the mean followup of 7.1 years, 33 CV events and 57 deaths occurred in the RA cohort. Visit-to-visit systolic BP variability was associated with increased risk of CV events (HR per 1 mm Hg increase in BP variability 1.12, 95% CI 1.01–1.25). Diastolic BP variability was associated with all-cause mortality in RA (HR 1.14, 95% CI 1.03–1.27), adjusting for systolic and diastolic BP, body mass index, smoking, diabetes, dyslipidemia, and use of antihypertensives.Conclusion.Patients with RA had higher visit-to-visit systolic BP variability than did non-RA subjects. There was a significant decline in systolic BP variability after RA incidence. Higher visit-to-visit BP variability was associated with adverse CV outcomes and all-cause mortality in RA.

Objective.To examine trends in the rates of serious infections among patients diagnosed with rheumatoid arthritis (RA) in 1995–2007 compared to rates previously reported from the same geographical area diagnosed 1955–1994.Methods.A population-based inception cohort of patients with RA in 1995–2007 was assembled and followed through their complete medical records until death, migration, or December 31, 2008. All serious infections (requiring hospitalization or intravenous antibiotics) were recorded. Person-year (py) methods were used to compare rates of infection.Results.Among 464 patients with incident RA in 1995–2007, 54 had ≥ 1 serious infection (178 total). These were compared to 609 patients with incident RA in 1955–1994 (290 experienced ≥ 1 serious infection; 740 total). The rate of serious infections declined from 9.6 per 100 py in the 1955–1994 cohort to 6.6 per 100 py in the 1995–2007 cohort. Serious gastrointestinal (GI) infection rates increased from 0.5 per 100 py in the 1955–1994 cohort to 1.25 per 100 py in the 1995–2007 cohort. Among patients with a history of serious infection, the rate of subsequent infection increased from 16.5 per 100 py in 1955–1994 to 37.4 per 100 py in 1995–2007. There was an increase in the rate of serious infections in patients who received biologic agents, but this did not reach significance.Conclusion.Aside from GI infections, the rate of serious infections in patients with RA has declined in recent years. However, the rate of subsequent infections was higher in recent years than previously reported.

Background Erratic blood pressure (BP) has been linked to increased risk of cardiovascular (CV) events and death in the general population. The impact of BP variability on CV events and mortality in RA is much less studied. Objectives To examine long-term visit-to-visit BP variability in RA vs non-RA subjects and to assess the impact of BP variability on CV events and all-cause mortality in RA. Methods The study included a population-based incident cohort of RA patients (1987 ACR criteria first met between 1980 and 2007) and a cohort of non-RA subjects of similar age and sex. All available clinic BP measures were collected from the medical records. BP variability was defined as within-subject standard deviation (SD) in systolic and diastolic BP. Cox models were used to examine the effect of BP variability on CV events (i.e. hospitalized/silent myocardial infarction, CV mortality, heart failure, ischemic heart disease, angina, or revascularization procedures) and all-cause mortality in RA. Results 452 RA patients (mean age 55.5 years, 31% males) and 436 non-RA subjects (mean age 55.7 years, 31% males) had ≥1 BP measure and were included. During the mean follow-up of 7.1±2.7 years in RA and 7.2±2.6 years in the non-RA cohort there were 13,470 BP measures in RA and 9,476 in the non-RA subjects (median: 24.0 measures/subject in RA and 16.5 in non-RA cohort). Median time between the measurements: 30 days in RA vs 27 in the non-RA cohort (p=0.93). The mean systolic BP at RA incidence/index date was higher in RA vs non-RA cohort (131.2±18.7 mmHg vs 128.2±19.3 mm Hg, p=0.018); the mean diastolic BP was similar in RA (75.1±10.9 mm Hg) vs non-RA cohort (75.6±11.0 mm Hg, p=0.53). There were 290 (64%) patients with hypertension in RA vs 241 (55%) in the non-RA cohort at index date. The proportion of hypertensive subjects on antihypertensive drugs was similar in RA and non-RA cohort at index date (33% vs 30%, respectively, p=0.52) and during the follow-up (33% vs 31% at 10 years, respectively, p=0.20). Patients with RA had higher visit-to-visit variability in systolic BP (13.8±4.7 mm Hg), but not diastolic BP, than the non-RA subjects (13.0±5.2 mm Hg, p=0.004). During the follow-up, 33 CV events and 57 deaths occurred in the RA cohort. Higher visit-to-visit BP variability was associated with increased risk of CV events (systolic BP: hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.04-1.29; diastolic BP: HR 1.15, 95%CI 1.02-1.30) and all-cause mortality in RA (systolic BP: HR 1.10, 95%CI 1.03-1.17; diastolic BP: HR 1.22, 95%CI 1.11-1.34). Adjusting for systolic and diastolic BP, body mass index and smoking at index date, and for time dependent covariates (i.e. diabetes, dyslipidemia, use of antihypertensives), systolic BP variability remained associated with the risk of CV events (HR 1.15, 95%CI 1.02-1.3); diastolic BP variability was associated with all-cause mortality (HR 1.14, 95%CI 1.03-1.27). Conclusions Patients with RA had higher long-term visit-to-visit variability of systolic BP than non-RA subjects. Higher visit-to-visit variability in systolic and diastolic BP was associated with adverse CV outcomes and all-cause mortality in RA, suggesting the need for increased awareness of adverse outcomes in RA patients with unstable BP. Disclosure of Interest None Declared

Objective: We investigated ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 motif, member 13) messenger RNA levels as a biomarker of disease features in systemic lupus erythematosus. Methods: We measured and compared messenger RNA (mRNA) levels of ADAMTS13 in peripheral blood cells in patients with systemic lupus erythematosus and healthy control subjects by whole-genome microarray. We retrospectively analyzed the correlations of ADAMTS13 mRNA expression with clinical features, laboratory parameters, therapeutic features, and disease activity (according to the Systemic Lupus Erythematosus Disease Activity Index). We also examined the association of three single nucleotide polymorphisms (rs4962145, rs2285467, and rs685523) of the ADAMTS13 gene with patient characteristics. Results: In 309 patients, the median ADAMTS13 mRNA expression levels were significantly higher in blood cells of systemic lupus erythematosus patients than in 23 healthy controls ( p = .03). Notably, ADAMTS13 mRNA expression levels were significantly higher in systemic lupus erythematosus patients with a history of stroke ( p = .02) or transient ischemic attack ( p = .02). Among the three single nucleotide polymorphisms analyzed, rs2285467 was significantly associated with stroke ( p = .03) and anticardiolipin antibodies ( p = .04). Conclusions: Increased expression of ADAMTS13 mRNA in blood cells is associated with the presence of ischemic cerebrovascular disease in systemic lupus erythematosus patients and suggests a potential role for ADAMTS13 in the pathogenesis of ischemic cerebrovascular disease in these patients.

Introduction It remains challenging to predict the outcomes of therapy in patients with rheumatoid arthritis (RA). The objective of this study was to identify immune response signatures that correlate with clinical treatment outcomes in patients with RA. Methods A cohort of 71 consecutive patients with early RA starting treatment with disease-modifying antirheumatic drugs (DMARDs) was recruited. Disease activity at baseline and after 21 to 24 weeks of follow-up was measured using the Disease Activity Score in 28 joints (DAS28). Immune response profiling was performed by analyzing multi-cytokine production from peripheral blood cells following incubation with a panel of stimuli, including a mixture of human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) lysates. Profiles identified via principal components analysis (PCA) for each stimulus were then correlated with the ΔDAS28 from baseline to follow-up. A clinically meaningful improvement in the DAS28 was defined as a decrease of ≥1.2. Results A profile of T-cell cytokines (IL-13, IL-4, IL-5, IL-2, IL-12, and IFN-γ) produced in response to CMV/EBV was found to correlate with the ΔDAS28 from baseline to follow-up. At baseline, a higher magnitude of the CMV/EBV immune response profile predicted inadequate DAS28 improvement (mean PCA-1 scores: 65.6 versus 50.2; P = 0.029). The baseline CMV/EBV response was particularly driven by IFN-γ (P = 0.039) and IL-4 (P = 0.027). Among patients who attained clinically meaningful DAS28 improvement, the CMV/EBV PCA-1 score increased from baseline to follow-up (mean +11.6, SD 25.5), whereas among patients who responded inadequately to DMARD therapy, the CMV/EBV PCA-1 score decreased (mean -12.8, SD 25.4; P = 0.002). Irrespective of the ΔDAS28, methotrexate use was associated with up-regulation of the CMV/EBV response. The CMV/EBV profile was associated with positive CMV IgG (P