Floranne C. Ernste

The lifetime risk of adult‐onset rheumatoid arthritis and other inflammatory autoimmune rheumatic diseases

OBJECTIVE Understanding of the personal risks for rheumatoid arthritis (RA) and other rheumatic diseases remains poor, despite advances in knowledge with regard to their pathogenesis, therapeutics, and clinical impact, in part because the personal lifetime risk of developing these diseases is unknown. This study was undertaken to estimate the lifetime risk of RA, as well as other inflammatory autoimmune rheumatic diseases, including systemic lupus erythematosus, psoriatic arthritis, polymyalgia rheumatica (PMR), giant cell arteritis, ankylosing spondylitis, and Sjögrens syndrome, and to provide an overall estimate of the risk of developing inflammatory autoimmune rheumatic disease over a lifetime. METHODS Using the incidence rates obtained from our population-based studies of rheumatic diseases among residents of Olmsted County, Minnesota, and mortality rates from life tables for the general population, we estimated the sex-specific lifetime risk of rheumatic disease. RESULTS The lifetime risk of RA developing in US adults was 3.6% for women and 1.7% for men, and the lifetime risk of rheumatoid factor-positive RA was 2.4% for women and 1.1% for men. The second most common inflammatory autoimmune rheumatic disease was PMR, with a lifetime risk of 2.4% for women and 1.7% for men. The overall lifetime risk of inflammatory autoimmune rheumatic disease was 8.4% for women and 5.1% for men. CONCLUSION One in 12 women and 1 in 20 men will develop an inflammatory autoimmune rheumatic disease during their lifetime. These results can serve as useful guides in counseling patients regarding their lifetime risk of these conditions and have important implications regarding disease awareness campaigns.

Idiopathic Inflammatory Myopathies: Current Trends in Pathogenesis, Clinical Features, and Up-to-Date Treatment Recommendations

Recently, there have been important advances in the understanding of the pathophysiologic features, assessment, and management of patients with a newly diagnosed idiopathic inflammatory myopathy (IIM). Myositis-specific autoantibodies have been identified to define patient subgroups and offer prognostic implications. Similarly, proinflammatory cytokines, such as interleukin 6 and type 1 interferon-dependent genes, may serve as potential biomarkers of disease activity in adult and juvenile patients with dermatomyositis (DM). Moreover, magnetic resonance imaging has become an important modality for the assessment of muscle inflammation in adult IIM and juvenile DM. Immune-mediated necrotizing myopathies also are being recognized as a subset of IIM triggered by medications such as statins. However, confusion exists regarding effective management strategies for patients with IIM because of the lack of large-scale, randomized, controlled studies. This review focuses primarily on our current management and treatment algorithms for IIM including the care of pediatric patients with juvenile DM. For this review, we conducted a search of PubMed and MEDLINE for articles published from January 1, 1970, to December 1, 2011, using the following search terms: idiopathic inflammatory myopathies, dermatomyositis, polymyositis, juvenile dermatomyositis, sporadic inclusion body myositis, inclusion body myositis, inflammatory myositis, myositis, myopathies, pathogenesis, therapy, and treatment. Studies published in English were selected for inclusion in our review as well as additional articles identified from bibliographies.

Changes in Novel Biomarkers of Disease Activity in Juvenile and Adult Dermatomyositis are Sensitive Biomarkers of Disease Course

OBJECTIVE Muscle enzyme levels are insensitive markers of disease activity in juvenile and adult dermatomyositis (DM), especially during the active treatment phase. To improve our ability to monitor DM disease activity longitudinally, especially in the presence of immunomodulating agents, we prospectively evaluated whether interferon (IFN)-dependent peripheral blood gene and chemokine signatures could serve as sensitive and responsive biomarkers for change in disease activity in adult and juvenile DM. METHODS Peripheral blood and clinical data were collected from 51 patients with juvenile or adult DM prospectively over 2 study visits. We performed disease activity measurements and calculated whole-blood type I IFN gene and chemokine scores. We also measured serum levels of other proinflammatory cytokines, including interleukin-6 (IL-6). RESULTS Changes in juvenile and adult DM global disease activity correlated positively and significantly with changes in the type I IFN gene score before adjustment for medication use (r = 0.33, P = 0.023) and with changes in the IFN chemokine score before and after adjustment for medication use (r = 0.53, P < 0.001 and r = 0.50, P < 0.001, respectively). Changes in muscle and extramuscular visual analog scale (VAS) scores correlated positively with changes in IFN gene and chemokine scores (P = 0.002, P < 0.001, P = 0.095, P < 0.001). Serum levels of IL-6, IL-8, and tumor necrosis factor α (TNFα) correlated positively with changes in global, muscle, and extramuscular VAS scores (P < 0.05). CONCLUSION Our findings suggest that changes in type I IFN gene and chemokine scores as well as in levels of IL-6, IL-8, and TNFα may serve as sensitive and responsive longitudinal biomarkers of change in disease activity in juvenile and adult DM, even in the presence of immunomodulating agents.

Cardiovascular risk profile at the onset of psoriatic arthritis: a population-based cohort study.

The role of cardiovascular disease (CVD) risk factors in psoriatic arthritis (PsA) is poorly understood. We examined the prevalence of CVD risk factors at initial onset of PsA and compared the observed incidence of CVD events with that predicted by the Framingham Risk Score (FRS) to determine its applicability in this patient population.

Cardiovascular risk profile at the onset of psoriatic arthritis

The role of cardiovascular disease (CVD) risk factors in psoriatic arthritis (PsA) is poorly understood. We examined the prevalence of CVD risk factors at initial onset of PsA and compared the observed incidence of CVD events with that predicted by the Framingham Risk Score (FRS) to determine its applicability in this patient population.

Risk and predictors of cardiovascular disease in psoriasis: a population-based study

Background Emerging evidence suggests that severe psoriasis is associated with increased risk of cardiovascular disease. The goal of this study was to examine the risk and predictors of clinical cardiovascular events in psoriasis.

Epidemiology of Mixed Connective Tissue Disease, 1985-2014: A Population-Based Study

To characterize the epidemiology of mixed connective tissue disease (MCTD) from 1983 to 2014.

Recent advances in juvenile idiopathic inflammatory myopathies.

Purpose of reviewOngoing research continues to advance our understanding of the juvenile idiopathic inflammatory myopathies (JIIMs). We review the recent contributions from the published literature about the classification, pathogenesis, assessment, and treatment of JIIMs in basic and translational science and clinical research in 2013 through early 2014. Recent findingsLarge registries, such as the Childhood Arthritis and Rheumatology Research Alliance registry, are conducting trials to enhance our understanding of JIIMs. Ultraviolet radiation exposure 1 month prior to juvenile dermatomyositis (JDM) may trigger the onset of disease. Myositis-specific autoantibodies define clinical phenotypes in JIIMs. MRI is useful in diagnosing JDM and may be used as a disease assessment tool. Type 1 interferon genes and proteins are increasing in use as disease assessment tools, but larger, prospective, validation studies are needed. Moderate-to-intense physical activity is effective in increasing the aerobic capacity of JDM patients in remission. New criteria developed by the Paediatric Rheumatology International Trials Organization for classifying inactive disease in JDM have practical applicability to the current clinical practice and clinical trials as even after 16.8 years of symptom onset, over half of JDM patients still have active disease. SummaryThere has been significant progress in understanding the clinical characteristics, diagnostic workup, treatment, disease assessment, and prognosis of JIIM patients, but more prospective treatment trials are needed, especially in light of the paucity of the current biologic treatment agents available.

Gene Expression Profiling in Blood and Affected Muscle Tissues Reveals Differential Activation Pathways in Patients with New-onset Juvenile and Adult Dermatomyositis

Objective. To identify shared and differential molecular pathways in blood and affected muscle between adult dermatomyositis (DM) and juvenile DM, and their association with clinical disease activity measures. Methods. Gene expression of transcription factors and cytokines involved in differentiation and effector function of T cell subsets, regulatory T cells and follicular Th cells, were analyzed in the blood from 21 newly diagnosed adult and 26 juvenile DM subjects and in 15 muscle specimens (7 adult and 8 juvenile DM) using a custom RT2 Profiler PCR Array. Disease activity was determined and measured by established disease activity tools. Results. The most prominent finding was the higher blood expression of Th17-related cytokines [retinoic acid-related orphan receptor-γ, interferon regulatory factor 4, interleukin (IL)-23A, IL-6, IL-17F, and IL-21] in juvenile DM at baseline. In contrast, adult patients with DM showed increased blood levels of STAT3 and BCL6 compared with juvenile DM. In muscle, GATA3, IL-13, and STAT5B were found at higher levels in juvenile patients with DM compared with adult DM. Among 25 patients (11 adult and 14 juvenile DM) who had blood samples at baseline and at 6 months, increased expression of IL-1β, STAT3, STAT6, STAT5B, and BCL6 was associated with an improvement in global extramuscular disease activity. Conclusion. We observed differences in gene expression profiling in blood and muscle between new-onset adult and juvenile DM. Cytokine expression in the blood of juvenile patients with new-onset DM was dominated by Th17-related cytokines compared with adult patients with DM. This may reflect the activation of different Th pathways between muscle and blood.

Longitudinal Peripheral Blood Lymphocyte Subsets Correlate with Decreased Disease Activity in Juvenile Dermatomyositis

Objective: To determine the clinical characteristics and subsets of peripheral blood lymphocytes (PBL), which correlate with decreased disease activity in patients with juvenile dermatomyositis (JDM). Methods. Peripheral blood mononuclear cells from 24 patients with JDM were collected at Mayo Clinic Rochester between 2007 and 2011. These were analyzed using fluorescence-activated cell sorting and flow cytometry. Clinical disease activity was determined by visual analog scales (VAS) collected in 2 consecutive visits and correlated with PBL subsets. Results. The change in CD3+CD69+ T cells correlated with the change in global VAS scores. The change in HLA-DR- CD11c+ myeloid dendritic cells also correlated with the change in extramuscular VAS scores. There were trends toward decreased levels of HLA-DR- CD11c+ cells with decreased muscle and global VAS scores, but these did not reach significance. The change in HLA-DR- CD123+ plasmacytoid dendritic cells negatively correlated with the change in muscle VAS scores. Although not statistically significant, decreased levels of CD3-CD16- CD56+ natural killer (NK) cells and HLA-DR- CD86+ myeloid dendritic cells, and increased levels of CD16+CD56- NK cells, correlated with decreased VAS scores. Conclusion. Changes in CD3+CD69+ T cells, HLA-DR- CD11c+ myeloid dendritic cells, and HLA-DR- CD123+ plasmacytoid dendritic cells are associated with improved clinical course in JDM and could be used as markers for disease activity, but findings need to be verified in a larger, independent cohort. Lack of significant differences among most of our PBL subsets suggests that lymphocyte phenotyping may be difficult to definitively correlate with disease activity in JDM.