Yoshinori Kogata

Diagnostic Accuracy of Serum 1,3-β-d-Glucan for Pneumocystis jiroveci Pneumonia, Invasive Candidiasis, and Invasive Aspergillosis: Systematic Review and Meta-Analysis

ABSTRACT Serum 1,3-β-d-glucan (BG) assay may be helpful as a marker for the diagnosis of Pneumocystis jiroveci pneumonia (PJP) and invasive fungal infection (IFI). We conducted a systematic review to assess the diagnostic accuracy of this assay. We searched MEDLINE, Web of Science, Cochrane Collaboration databases, Ichushi-Web, reference lists of retrieved studies, and review articles. Our search included studies of serum BG assay that used (i) positive cytological or direct microscopic examination of sputum or bronchoalveolar lavage fluid for PJP and (ii) European Organization for Research and Treatment of Cancer or similar criteria for IFI as a reference standard and provided data to calculate sensitivity and specificity. Only major fungal infections such as invasive candidiasis and invasive aspergillosis were included in the IFI group. Twelve studies for PJP and 31 studies for IFI were included from January 1966 to November 2010. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (AUC-SROC) for PJP were 96% (95% confidence interval [95% CI], 92% to 98%), 84% (95% CI, 83% to 86%), 102.3 (95% CI, 59.2 to 176.6) and 0.96 (95% CI, 0.94 to 0.99), respectively. No heterogeneity was found. For IFI, the values were 80% (95% CI, 77% to 82%), 82% (95% CI, 81% to 83%), 25.7 (95% CI, 15.0 to 44.1), and 0.88 (95% CI, 0.82 to 0.93). Heterogeneity was significant. The diagnostic accuracy of the BG assay is high for PJP and moderate for IFI. Because the sensitivity for PJP is particularly high, the BG assay can be used as a screening tool for PJP.

Role of imaging studies in the diagnosis and evaluation of giant cell arteritis in Japanese: report of eight cases

The objective of this study is to clarify the characteristics and imaging results of Japanese patients with giant cell arteritis (GCA). Eight patients with biopsy-proven GCA were enrolled. Their clinical data and imaging results were retrospectively examined from their medical records. All the patients met the criteria for the classification of GCA by the American College of Rheumatology. Although the clinical manifestations are similar to those previously reported, none of the eight patients presented ocular symptoms, and half of them presented jaw claudication. Ultrasonography (US) of temporal artery showed the halo sign in all the patients. Fluorodeoxyglucose positron emission tomography (FDG-PET) was performed in four patients and indicated the presence of aortitis of the patients. US is a quick and noninvasive test to detect inflammation of temporal artery, and FDG-PET is very helpful for early diagnosis of aortitis in GCA. Awareness of the disease and appropriate imaging tests will result in diagnosis of GCA.

IgG4-related disease manifesting as pericarditis with elevated adenosine deaminase and IL-10 levels in pericardial fluid.

A 78-year-old female with massive pericardial effusion fulfilled diagnostic criteria for immunoglobulin G4 (IgG4)-related disease. Although her adenosine deaminase (ADA) level in the pericardial effusion was high, all the tests for tuberculosis infection were negative. Immunostaining of the pericardium biopsy specimen revealed remarkably increased IgG4-positive cells. This is the first report describing IgG4-related pericarditis with elevated ADA level. We also demonstrate the elevated interleukin-10 (IL-10) level in pericardial fluid and IL-10-producing T-cells in the pericardium.

THU0611 Subjective Well-Being of Japanese RA Patients Who Reach Treatment Target Is Higher than The Japanese Average

Background Subjective Well-Being (SWB) refers to a construct which includes ones emotional responses, domain satisfactions, and global judgments of life satisfaction. Many variables such as age, sex, income, employment and marital status are related to SWB. Being healthy is also an important factor of SWB. RA is a chronic illness which is considered to influence SWB. However, little is known about the impact of RA on SWB. Objectives To evaluate the SWB of Japanese RA patients and identify factors that associate with SWB. Methods This study was done in cooperation with the Cabinet Office Government of Japan Economic and Social Research Institute. This institute had previously conducted the “Well-being studies 2014” surveying the SWB of randomly selected Japanese citizens. In this survey, SWB was determined by having the participants rate their happiness between 10 (Very happy) and 0 (very unhappy). The Well-being studies 2014 also included a questionnaire consisting of 56 questions covering topics closely associated with well-being such as socioeconomic and health status. The same survey was done for RA patients at Kobe University Hospital and clinical data including disease duration, stage, class, disease activity, HAQ, complications and the therapeutic drug was also collected at the same time. Results Multivariate analysis on data including RA patients (n=339) and Japanese controls (n=7690) revealed that RA patients with high or moderate disease activity had similar SWB scores as Japanese controls. However, the SWB of RA patients with remission or low disease activity were higher than Japanese controls. Age, sex, marital status, presence of child, household income, financial leeway, working status, psychological distress (Kessler 6 scale), self-assessment of health, and social connection were all associated with SWB. Conclusions Japanese RA patients may be able to get higher SWB than Japanese controls by achieving treatment target. Disclosure of Interest None declared

AB0192 Some of The Painful RA Patients Underrate Global Health VAS at Hospitals

Background Evaluating patient global VAS is one of the most essential process in RA practice. Despite reliability of patient global VAS being highly important in clinical practice, there has been no study comparing global VAS scores obtained at hospitals and those obtained at home where patients answer anonymously. Objectives To compare the patient global VAS obtained before clinical examination in hospital with those answered anonymously at home. Methods We asked RA patients to answer and mail the EQ5D data set anonymously. EQ5D consisted of 5 component questions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and patient assessment global health VAS. EQ5D global VAS is anonymized patient global VAS evaluated at home. We compared the patient global VAS which is routinely surveyed at hospital before clinical examination with those surveyed anonymously at home. Results The anonymized VAS score was higher than those routinely evaluated at hospital (p<0.0001). Global VAS scores obtained at hospital poorly correlated with those obtained anonymously at home (r=0.426). We compared patients who had higher patient global VAS at hospital than anonymized VAS at home with patients who had lower patient global VAS at hospital than anonymized VAS at home. Pain VAS scores remained to be risk factor to be higher anonymized VAS at home than those routinely evaluated at hospital after multivariate analysis. Conclusions Discrepancy exists between patient global VAS evaluated in the hospital before clinical examination and those evaluated anonymously at home. There is a possibility that patients rating high pain VAS are underrating their global VAS scores at hospital. Disclosure of Interest None declared

SAT0461 A Retrospective Study of 88 Cases with Idiopathic Inflammatory Myositis (IIM)

Background Prognostic factors and long-term outcome including functional impairment of idiopathic inflammatory myositis (IIM) vary widely. In addition, the efficacy of immunosuppressive agents on clinical course of IIM, have not been well established. Objectives To evaluate clinical course including relapse, functional impairment and mortality rate, and the efficacy of immunosuppressive agents in polymyositis (PM), dermatomyositis (DM), and amyopathic dermatomyositis (ADM). Methods Clinical data of 88 IIM patients (33 with PM, 40 with DM, and 10 with ADM) who received induction therapy from April 2002 to July 2013 in Kobe University Hospital were collected from the medical charts. Survival rate were modeled Kaplan-Meier estimation. Functional impairment was evaluated with Health Assessment Questionnaire Disability Index (HAQ-DI). Results Interstitial lung disease (ILD) was diagnosed in 63.1% of PM, 82.5% of DM, and all the ADM patients. Rapidly progressive ILD (RP-ILD) were found none of PM, 6% of DM, and 70% of ADM patients. Ten-year survival rate estimates of PM and DM were 79.3% and 76.2%, respectively. Half of ADM patients had a fatal clinical course of RP-ILD within 4 months after onset. Ten-year survival rate estimates without relapse were 74.5% for PM and 54.6% for DM. Immunosuppressive agents were used for 68.4% of PM, 61.5% of DM, and 90% of ADM patients. Predictors of poor outcome were male sex (analysis by Cox proportional hazards model, Hazard ratio (HR) 3.38, 95% confidence interval (CI) 1.20 to 9.48), ADM (HR 9.72, 95%CI 2.28 to 41.44), pneumomediastinum (HR 3.11, 95%CI 1.02 to 9.42), dysphagia (HR 3.27, 95%CI 1.12 to 9.50), and RP-ILD (HR 12.31, 95%CI 3.54 to 42.33). Patients positive for anti-Jo-1 antibody had a higher rate of recurrence (HR 3.52, 95%CI 1.33 to 9.36). Patients treated with immunosuppressive agents tended to have lower relapse rate than those without immunosuppressive agents (log-rank test, P=0.053). Patients with ILD associated with favorable physical function (multiple logistic regression analysis, Odds Ratio (OR) 12.07, 95%CI 1.91 to 126.54). Higher age patients had statistically high HAQ-DI (OR 0.19, 95%CI 0.04 to 0.75). Conclusions Male sex, ADM, RP-ILD, pneumomediastinum and dysphagia predict the poor outcome, and anti-Jo-1 antibody-positive patients had a high relapse rate in IIM patients. Early administration of immunosuppressive agents may reduce the risk of relapse of IIM. Disclosure of Interest None declared

AB0181 Glutamate as A Metabolic Biomarker for Monitoring Disease Activity of Systemic Lupus Erythematosus

Background “Omics” technologies, which include genomics, transcriptomics, proteomics, and metabolomics, are based on the comprehensive biochemical and molecular characterization of a biological sample. Among these, metabolomics has recently developed rapidly. Metabolomics, or metabolome analysis, is the comprehensive identification and quantification of all the low-molecular-weight metabolites in a biological sample. Because metabolism closely influences the organisms phenotype, the characteristics of a disease are thought to more closely reflect alterations in the levels of metabolites than changes in gene or protein expression. Therefore, the examination of alterations in metabolite levels should help elucidate the physiological and pathological characteristics of diseases in more detail. Besides, cell metabolism is known to have a tremendous impact on the function of various immune cells. Objectives To identify novel metabolic biomarkers for diagnosing and monitoring systemic lupus erythematosus (SLE) by using gas chromatography/mass spectrometry (GC/MS). Methods Serum samples were obtained in the morning from fasting patients with SLE (n=26), rheumatoid arthritis (RA) (n=32), and healthy volunteers (n=26). Serum metabolite profiling was performed by GC/MS. The metabolic profiles of the patient and control groups were compared using multivariate statistical analysis. Results The levels of 25 metabolites were significantly different in SLE patients compared to healthy controls. The two-dimensional (2D) plot of the principal component analysis (PCA) scores showed a distinct clustering of the two groups. The corresponding 2D-PCA loadings plot and the 2D-scores plot for partial least squares-discriminant analysis (PLS-DA) loadings plot revealed that variations in the levels of glutamate, urea, tyrosine, phosphate and glycerol greatly contributed to the observed separation of the metabolite profiles of the SLE patients and healthy controls. In addition, there was a large difference in serum metabolite levels between SLE and RA, and a number of metabolites showed opposite changes between them. Furthermore, of 25 metabolites that were significantly changed in SLE, the serum level of glutamate was significantly correlated with the SLE disease activity index (SLEDAI) score and serum levels of C4 (Figure). Conclusions The pathogenesis of SLE may be accompanied by variations in the serum levels of low-molecular-weight metabolites, which supports the potential for using GC/MS-based metabolomics as a diagnostic and monitoring tool for SLE. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2294

FRI0379 Salivary Metabolomics of Primary SjÖGren's Syndrome

Background Primary Sjögrens syndrome (pSS) is an autoimmune exocrinopathy characterised by the infiltration of mononuclear cells into salivary and lacrimal glands leading to destruction of the parenchymal tissue and causing oral and ocular dryness. Omics studies such as genomics, proteomics and metabolomics have been extensively used to elucidate biological mechanisms of diseases through collective characterization and quantification of pools of biological molecules and generating molecular profiles for biospecimens. Saliva contains a variety of informative substances which may closely reflect the pathogenetic process of pSS in salivary glands. In fact, salivary proteomics from pSS patients have detected some proteins as biomarkers for pSS diagnosis. To date, metabolomics has been widely conducted and is regarded as the end point of “omics cascade” and most predictive of phenotype. However, salivary metabolomics from pSS patients has not been reported up-to-date. Objectives To compare the salivary metabolite profile between patients with pSS and healthy control (HC) subjects. Methods We obtained saliva from 12 female pSS patients (mean age 44.2±13.01) and 21 age-matched female HCs by spitting for 15 minutes. The metabolite profile of saliva specimens were analyzed by gas chromatography-mass spectrometry. The levels of metabolites were calibrated by saliva volume per 15 minutes enabling us to compare the metabolite production level of whole salivary glands for 15 minutes. Results 88 metabolites were detected by our system. 32 metabolites were decreased and only one metabolite was increased in pSS patients. Principal component analysis (PCA) revealed a loss in salivary metabolite diversity in pSS patients compared to HCs. The decrease of Glysine, Tyrosine, Uric Acid and Fucose which may reflect the destruction of salivary gland due to chronic sialoadenitis contributed to the loss of diversity. PCA amongst pSS patients revealed that pSS could be divided into two subpopulations according to their metabolite profiles and the prevalence of major salivary glanditis was different between the two subpopulations (p=0.014). Conclusions In this preliminary study, the salivary metabolite profile of pSS patients was less diverse compared to controls. Salivary metabolite profile was affected by the presence of major salivary glanditis suggesting that salivary metabolomics may serve as a prospective approach to discover the underlying pathogenesis of pSS. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1201

SAT0469 Ineffective Fracture Prevention by Bisphosphonate in Patients Undergoing High Dose Glucocorticoid Therapy with A Frax Ten Year Probability Greater than 5.8

Background High dose glucocorticoid (GC) therapy (PSL>0.8mg/kg/day) is often provided to patients with systemic rheumatic disease. GC induced osteoporosis (GIO) is a common complication of high dose GC therapy and bisphosphonate is frequently used as a first-line prevention of GIO and fragile fractures. However, some patients are still at high risk of bone fractures despite bisphosphonate administration. The World Health Organization fracture risk assessment tool (FRAX) is used to calculate the 10-year probability of major (hip, clinical spine, humerus or wrist fracture) fractures and has been recently adopted to the treatment guidelines for GIO and for assessment of fracture risk. Drugs more effective than bisphosphonate have recently become available, but it is unclear which patients with high dose GC therapy should be given the newer drugs for GIO prevention. Objectives To identify patients with high dose GC therapy at a high risk of developing fragility fracture despite bisphosphonate treatment. Methods We conducted a retrospective study on systemic rheumatic disease patients who were treated with PSL>0.8mg/kg/day at Kobe University Hospital from April 1988 to March 2012. The fracture risk at the start of high dose GC therapy was assessed by FRAX. Comparison between patients who remained fracture-free for over 5 years and those who suffered fractures within 5 years despite taking bisphosphonate were focused in particular. Results 229 (SLE 76, Vasculitis syndrome 58, PM/DM 51, AOSD 12, MCTD 7, others 25) patients were included and the mean observational period was 1819 days (95% CI 1653-1989). 57 patients (52 clinical spinal, 3 hip, 1 humerus, 1 wrist) suffered from fracture. 28 patients suffered from fracture within 5 years despite taking bisphosphonate. 94 patients were fracture-free for over 5 years with or without bisphosphonate. Receiver operating characteristic (ROC) analysis revealed that the optimal cut-off of FRAX ten year probability failing to prevent fracture over 5 years despite bisphosphonate treatment was 5.8% (Sensitivity 89.3%, Specificity 74.5%, Area under the curve 0.885). Kaplan-Meier analysis also revealed that bisphosphonate had no effect in reducing fractures in patients with FRAX5.8%. Conclusions Bisphosphonate is ineffective for preventing fractures in high-risk patients (FRAX≥5.8%) undergoing high dose GC therapy. Thus, these patients require alternative prophylactic measures for fragility fractures. Acknowledgements This work was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI grants 13390768 and Japan Osteoporosis Foundation grants. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1344