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Objective. To investigate the impact of the amendment of the Korean National Health Insurance (KNHI) reimbursement criteria for anti-tumor necrosis factor-α (TNF-α) agents based on from conventional clinical and laboratory measurements to disease activity score of 28 joints (DAS28) on treatment pattern, clinical response, and persistence rate in patients with rheumatoid arthritis (RA). Methods. This multicenter retrospective cohort study evaluated 148 RA patients eligible for the initiation of anti- TNF-α agents as the first-line biologics by either the past (n=95) or current (n=53) KNHI reimbursement criteria. Persistence was defined as the duration between the initiation and discontinuation of anti-TNFα agents. Results. In total, 106 (71.6%), 35 (23.6%), and 7 (4.7%) RA patients started treatment with adalimumab, etanercept, and infliximab, respectively. RA patients who received anti-TNF-α agents under the current reimbursement criteria had a significantly lower mean DAS28-erythrocyte sedimentation rate (ESR) (6.02 vs. 6.95, p＜0.001) and daily prednisolone-equivalent glucocorticoid dose (4.51 vs. 6.17 mg, p＜0.001) than those who received anti-TNF-α agents under the past reimbursement criteria. No significant differences in the 1-year remission rate defined by DAS28-ESR＜2.6 (17.9% vs. 30.2%, p=0.085) and the persistence rate (p=0.703) between the past and current reimbursement criteria was observed. Conclusion. Our data suggest that less active RA patients can receive reimbursement for anti-TNF-α agents under the current criteria, and the amendment of the KNHI reimbursement criteria may improve access to anti-TNF-α agents without affecting the treatment response and persistence rate. (J Rheum Dis 2020;27:159-167)

ObjectiveInsulin-like growth factor (IGF)-1 participates in modulating immunity and inflammation. Its bioactivity is controlled by six IGF-binding proteins (IGFBP-1 to IGFBP-6). In particular, the IGFBP-3 level is reportedly linked to the disease activity of rheumatoid arthritis (RA), consistent with our previous study. Therefore, the present study aimed to reproduce the previous results.ResultsThe serum IGFBP-3 level was not significantly different among the three groups according to disease activity based on the DAS28-ESR/CRP (p > 0.05) but was significantly different between the low- and high-disease-activity groups based on the DAS28-CRP (p = 0.036). Meanwhile, the interleukin-6 (IL-6) level moderately correlated with DAS28-CRP (Spearman’s rho = 0.583,p

Background Patient-centered management is becoming increasingly important in gout, but there are limited studies exploring patients' perspectives and preferences. We aimed to investigate patients' perspectives and preferences regarding gout and gout management, and their impacts on adherence to urate lowering therapy (ULT). Methods A paper-based survey was performed in patients with gout seen at the rheumatology outpatient clinics of 16 tertiary hospitals. The survey included questions regarding demographics, comorbidities, gout attacks, current treatment and adherence, and patients' perspectives and preferences regarding gout and gout management. Multivariate regression analysis was performed to determine the factors associated with ULT adherence. Results Of 809 surveyed patients with gout, 755 (94.5%) were using ULT. Among those using ULT, 89.1% had ≥ 80% adherence to ULT. Majority of the patients knew management strategies to some extent (94.8%), perceived gout as a life-long disease (91.2%), and were making efforts toward practicing at least one lifestyle modification (89.2%). Most patients (71.9%) obtained information about gout management during their clinic visits. Approximately half of the patients (53.6%) preferred managing their disease with both ULT and lifestyle modification, 28.4% preferred ULT only, and 17.4% preferred lifestyle modification only. Adherence was better in patients with older age (odds ratio [OR], 1.03), those with better knowledge of gout management strategies (OR, 3.56), and those who had preference for ULT (OR, 2.07). Conclusion Patients' perspectives and management preferences had high impacts on adherence to ULT in gout. Consideration of patients' perspectives and preferences is important for achieving the desired clinical outcome in gout., Graphical Abstract

Objectives The Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway play a key role in immune modulation, especially in the polarization of T helper cells. JAK inhibitors reduce inflammation by inhibiting the phosphorylation of STAT. We investigated whether a JAK inhibitor, tofacitinib, can reduce inflammation in a mouse model of chronic rhinosinusitis with nasal polyps (CRSwNP). Methods An eosinophilic CRSwNP model was induced using 4-week-old BALB/c mice. The therapeutic effects of topical tofacitinib were compared with the effects of triamcinolone acetonide (TAC). Polyp formation and eosinophilic infiltration were assessed by histology. Levels of phosphorylated STAT (pSTAT), eosinophil cationic protein, and eotaxin were measured by immunohistochemistry. Gene expression levels of GATA-3 was measured using quantitative PCR. The production of cytokines in sinonasal tissues, including interleukin IL-4, IL-5, IL-12, and interferon-γ, were measured using enzyme-linked immunosorbent assays (ELISA). Results Topical tofacitinib administration significantly reduced the number of polyp-like lesions and the degree of eosinophilic infiltration, with an efficacy comparable with that of systemic TAC administration. Similarly, the levels of pSTAT6, eosinophil cationic protein, and eotaxin decreased with tofacitinib treatment. Tofacitinib decreased the gene expression level of GATA-3. Lastly, tofacitinib significantly decreased IL-4 and IL-5 production to a similar extent as that by systemic or topical TAC administration. Tofacitinib, but not TAC, significantly increased the production of interferon-γ. Conclusion Topical tofacitinib administration may be an effective treatment for eosinophilic CRSwNP by inhibiting phosphorylation of STATs. Level of evidence N/A. Laryngoscope, 131:E1400-E1407, 2021.

Inflammation and trophic factors (brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor, glial cell line-derived neurotrophic factor, and insulin-like growth factor-1) are associated with depression in the general population. Rheumatoid arthritis (RA) is a chronic representative inflammatory autoimmune disease; however, the association of disease activity, pro-inflammatory cytokines, and neurotrophic factors with depression has not been sufficiently investigated. Therefore, we determined the prevalence of depression and risk factors for depression and deterioration of depressive symptoms in RA patients. In addition, we analyzed the association between disease activity, pro-inflammatory cytokines, trophic factors, and depression in RA (N = 474). Demographic and laboratory data were examined, and routine assessment of patient index data 3 (RAPID 3) and disease activity score 28-joint count C-reactive protein (DAS 28-CRP) was performed to assess disease activity of RA. Depression was measured using the Korean version of the Beck Depression Inventory-second edition (K-BDI II). A K-BDI score ≥18 was considered the cut-off for depression in accordance with a previous validation study. The serum level of pro-inflammatory cytokines and neurotrophic factors was assessed by enzyme-linked immune sorbent assay. The prevalence of depression was 32.4% in patients with RA. The severity of disease activity of RA (RAPID 3 score [OR 2.34; 95% confidence interval, CI 1.22-4.51], DAS 28-CRP [≥3.2] [OR 1.60, 95% CI 1.01-2.53]) and severity of fatigue (OR 1.26 95% CI 1.15-1.38) were associated with depression and deterioration of depressive symptoms in the multivariate analysis. Among the components of RAPID 3 and DAS 28-CRP, patient assessment for global health and abilities for daily performance were more related to depression. The level of pro-inflammatory cytokines (IL-1β, IL-6, TNF-alpha) was not related to depression. The level of BDNF was significantly lower in RA patients with depression and was negatively correlated with K-BDI II score. Depression was related with the level of fatigue, low expression of BDNF, and high RA disease activity, which was associated with impaired ability to perform activities of daily life. Strict control of fatigue and disease activity to improve one's capacity to perform daily life activities would be important to regulate depression. The level of BDNF might be one of the possible biomarkers to predict or monitor depression in patients with RA.

The purpose of this study is to investigate the effect of TSAHC [4'-(p-toluenesulfonylamido)-4-hydroxychalcone] in K/BxN serum transfer arthritis model and fibroblast-like synoviocytes of rheumatoid arthritis (RA-FLS). In in vivo experiments, TSAHC attenuated the incidence and severity of arthritis in comparison with the vehicle group. Histological findings showed that TSAHC decreased the inflammation, bone erosion, cartilage damage, and osteoclasts activity in the ankle. Furthermore, we confirmed by biochemical analysis that the observations were associated with the decreased expression of proinflammatory cytokines, matrix metalloproteinases (MMPs), and RANKL in serum and ankle. In in vitro experiments, TSAHC induced apoptosis, while it significantly suppressed tumor necrosis factor-α (TNF-α)-induced cell proliferation in RA-FLS. Moreover, TSAHC inhibited mRNA expression of TNF-α-induced interleukin (IL)-6, MMP-1, MMP-3, and MMP-13. Evaluation of signaling events showed that TSAHC inhibited the translocation and transcriptional activity of nuclear factor-kappa B (NF-κB) by regulating phosphorylated-IκB-α (p-IκB-α) and IκB-α in TNF-α-induced RA-FLS. Our results suggest that TSAHC inhibits experimental arthritis in mice and suppresses TNF-α-induced RA-FLS activities via NF-κB pathway. Therefore, TSAHC may have therapeutic potential for the treatment of RA.

AIMS To investigate demographic, clinical, laboratory, and immunological characteristics of patients with systemic lupus erythematosus (SLE) in southeastern areas of South Korea, and to perform survival analysis. METHODS We retrospectively evaluated 413 patients with SLE diagnosed in 3 tertiary rheumatology centers in South Korea from 1992 to 2016 by reviewing their medical charts. All patients fulfilled the 1997 revised American College of Rheumatology classification criteria for SLE. RESULTS Most patients were women (92%), and the mean (±standard deviation) age at diagnosis was 30.9 (±12.9) years. The most common clinical manifestation was leukopenia (74.3%), followed by lymphopenia (73.6%), arthritis (59.1%), malar rash (48.4%), thrombocytopenia (46.5%), oral ulcer (35.1%), and biopsy-proven lupus nephritis (31.2%). Anti-nuclear, anti-double-stranded DNA, anti-Smith, and anti-Ro antibodies were positive in 97.8%, 70.1%, 38.4%, and 63% of patients, respectively. Twenty (4.8%) patients died during a median follow-up of 83 months, and the cumulative 5-year and 10-year survival rates were 96.9% and 95.5%, respectively. The major causes of death were infection (50%) and lupus flare-up (50%). Male (hazards ratio [HR] = 7.19, P = .001), pleuritis and/or pericarditis (HR = 3.28, P = .012), childhood-onset (HR = 3.57, P = .012), and late-onset (HR = 4.65, P = .011) were independent risk factors for death. Compared with SLE cohorts in other ethnicities or countries, our patients tended to have a higher frequency of anti-Ro antibodies and hematologic disorders. CONCLUSION This study describes clinical features of SLE in South Korea and suggests a remarkable phenotypic heterogeneity of SLE.

OBJECTIVES:To estimate the prevalence and associated factors of rotator cuff tear (RCT) in patients with hand osteoarthritis (HOA). METHODS:Between June 2013 and December 2015, we recruited 1150 participants in rural area of South Korea. Of the 1150 participants, 307 participants with HOA were analyzed. Plain radiography of both hands, magnetic resonance imaging of both shoulders, and serum levels of high-sensitive C-reactive protein (hsCRP) and high-density lipoprotein (HDL) were obtained for all patients. HOA and RCT were diagnosed by clinical and radiologic findings. RESULTS:The prevalence of RCT in patients with HOA (192/307, 62.5%) was higher than that in those without HOA (410/827, 49.5%, p

Background Rheumatoid arthritis (RA) is an autoimmune inflammatory disease of the joints and is characterised by immune cell infiltration, synovial hyperplasia, and destruction of cartilage and underlying bone 1 . Raf kinase inhibitory protein (RKIP), an endogenous inhibitor of the extracellular signal-regulated kinase (ERK) pathway, has been implicated as a suppressor of metastasis and NF-κB pathway in cancers 2 . Objectives The NF-κB and ERK pathways are considered to be one of the most important pro-inflammatory signalling pathways in RA. Therefore, RKIP might be a potential therapeutic target for RA. However, whether and how RKIP regulates RA is not fully understood. The present study was performed to examine whether and how RKIP are differentially regulated in RA. Methods The expressions of RKIP were assessed in synovial tissue, fluid and fibroblast-like synoviocytes (FLS) from patients with RA and osteoarthritis (OA) by immunofluorescence staining and western blotting. RA- or OA-FLS were infected with either a recombinant adenoviral RKIP overexpressing vector (Ad-RKIP) or shRNA-expressing vector (Ad-shRKIP). Control cells infected with a GFP-targeted recombinant adenoviral vector (Ad-shGFP) (figure 1C). And then, we investigated the effects of RKIP on the migratory activity and invasion rates of FLS by transwell migration and invasion assay. Results Here, we show that RKIP expression is inversely correlated with RA. The levels of RKIP were significantly decreased in fibroblast-like synoviocytes (FLS), synovial fluid and synovium of RA patients compare to OA patients. And also find that migration and invasion of RA-FLS were significantly increased by the inhibition of RKIP compare to OA-FLS. Knockdown of RKIP in RA or OA-FLS resulted in a dramatic increase of MMP3 and IL6. We also found osteoclastogenesis of RAW cells were increased by the knockdown of RKIP. Conclusions Our data identify a role of RKIP in RA and suggest that further studies on the potential involvement of RKIP will be beneficial in better understanding the pathology of and providing a new target for treatment for RA. References [1] Ospelt C. Synovial fibroblasts in 2017. RMD Open2017;3(2):e000471. [2] Yesilkanal AE, Rosner MR. Raf kinase inhibitory protein (RKIP) as a metastasis suppressor: regulation of signaling networks in cancer. Crit Rev Oncog. 2014;19:447–454. [3] Noh HS, Hah YS, Ha JH, Kang MY, Zada S, Rha SY, Kang SS, Kim HJ, Park J, Byun J, Hahm JR, Shin JK, Jeong S, Lee Y, Kim DR. Regulation of the epithelial to mesenchymal transition and metastasis by Raf kinase inhibitory protein-dependent Notch1 activity. Oncotarget2016;7(4):4632–46. Disclosure of Interest None declared

Background Rheumatoid arthritis (RA) is an autoimmune inflammatory disease of the joints and is characterised by immune cell infiltration, synovial hyperplasia, and destruction of cartilage and underlying bone 1. Myeloid derived monocytes and macrophages secrete a variety of cytokines such as tumour necrosis factor-α (TNF-α), interleukin (IL)−1β and IL-6, all of which perpetuate and amplify the vicious cycle of chronic inflammatory pathways 2. Indeed, macrophage numbers in the synovium and serum levels of monocyte-derived cytokines correlate well with clinical symptoms and degree of joint damage in RA 3. Objectives We recently reported that myeloid sirtuin 6 (Sirt6) is a critical determinant of phenotypic switching and the migratory responses of macrophages 4. Given the prominent role of macrophages in rheumatoid arthritis (RA) pathogenesis 5, we tested whether myeloid Sirt6 deficiency affects the development and exacerbation of RA. Methods Arthritis was induced in wild type and myeloid Sirt6 KO (mS6KO) mice using collagen-induced and K/BxN serum transfer models. Peripheral blood mononuclear cells (PBMC) and synovial fluid macrophages were obtained from patients with RA and osteoarthritis and used for comparisons of Sirt6 expression and inflammatory activities. Results Based on clinical scores, ankle thickness, pathology and radiology, arthritis was more severe in mS6KO mice relative to wild type with a greater accumulation of macrophages in the synovium. Consistently, myeloid Sirt6 deficiency increased the migration potential of macrophages toward synoviocytes-derived chemoattractants. Mechanistically, Sirt6 deacetylates forkhead box protein O1 to trigger its nuclear export and proteasomal degradation. Lastly, PBMC and macrophages isolated from RA patients exhibited lower Sirt6 expression compared with those from osteoarthritis patients or healthy subjects and their Sirt6 activity was inversely correlated with disease severity of the patients. Conclusions Our data identify a role of myeloid Sirt6 in clinical and experimental RA and suggest that myeloid Sirt6 may be an intriguing therapeutic target. References [1] Ospelt C. Synovial fibroblasts in 2017. RMD Open 2017;3(2):e000471. [2] Gierut A, Perlman H, Pope RM. Innate immunity and rheumatoid arthritis. Rheum Dis Clin North Am2010;36(2):271–96. [3] Kinne RW, S tuhlmuller B, Burmester GR. Cells of the synovium in rheumatoid arthritis. Macrophages. Arthritis Res Ther2007;9(6):224. [4] Lee Y, Ka SO, Cha HN, et al. Myeloid sirtuin 6 deficiency causes insulin resistance in high-fat diet-fed mice by eliciting macrophage polarization toward an M1 phenotype. Diabetes2017;66(10):2659–68. [5] Lee HS, Ka SO, Lee SM, et al. Overexpression of sirtuin 6 suppresses inflammatory responses and bone destruction in mice with collagen-induced arthritis. Arthritis Rheum2013;65(7):1776–85. Disclosure of Interest None declared

Background Hyposecretion of tears and saliva is the main phenotype of primary Sjogren’s syndrome (PSS). However, the prevalence and degree of ocular and oral involvement in PSS is highly variable. Objectives The aims of this study were 1) to investigate oral and ocular signs and changes in primary SS patients, and 2) to explore possible predisposing factors for moderate to severe oral or ocular signs in primary SS. Methods We analysed 140 participants from the Korean Initiative of PSS cohort who completed a two-year follow-up oral and ocular sign test. The severity of keratoconjunctivitis sicca (KCS) was determined by the Schirmer I test (Moderate-to-severe [MS],≤5 mm/5 min; mild [Mi],>5 mm/5 min). Salivary gland dysfunction (SGD) was determined by unstimulated whole salivary flow rate (UWS) (MS, UWS Results Among the 140 participants enrolled in this study, 108 (61%) were placed in the MS-KCS/MS-SGD group, 17 (24%) were in the MS-KCS/Mi-SGD, 15 (16%) were in the Mi-KCS/MS-SGD at the two-year follow-up. The MS-KCS/Mi-SGD group was younger than the other two groups, had a lower xerostomia inventory, and lower level of β2 microglobulin. Participants in the Mi-KCS/MS-SGD group had less hyperimmunoglobulinemia, rheumatoid factor (RF), antinuclear antibodies, anti-Ro, and anti-La antibodies. Older patients and those with positive RF, anti-Ro, or anti-La antibodies at baseline were more likely to have moderate to severe KCS at the two-year follow-up. Conclusions Patients with PSS and positive RF, anti-Ro, or anti-La antibodies at baseline may benefit from regular ophthalmology exams, even if they do not have KCS at baseline or dry eye symptoms. References [1] Le Gall M, Cornec D, Pers J-O, Saraux A, Jousse-Joulin S, Cochener B, et al. A prospective evaluation of dental and periodontal status in patients with suspected Sjogren’s syndrome. Joint Bone Spine. doi:http://dx.doi.org/10.1016/j.jbspin.2015.02.015. [2] Lim SA, Nam S, Kwok SK, Park SH, Chung SH. Serologic Markers Are Associated With Ocular Staining Score in Primary Sjogren Syndrome. Cornea2015;34:1466–70. [3] Shiboski CH, Baer AN, Shiboski SC, Lam M, Challacombe S, Lanfranchi HE, et al. Natural History and Predictors of Progression to Sjogren’s Syndrome Among Participants of the Sjogren’s International Collaborative Clinical Alliance Registry. Arthritis Care Res (Hoboken)2017. doi:10.1002/acr.23264. Acknowledgements We wish to thank So Young Kim, the research nurse for the KISS cohort, for her excellent support. Disclosure of Interest None declared

Objective To identify the prevalence of and risk factors for knee pain and radiographic knee osteoarthritis (RKOA) and to investigate the relationship between decreased lower extremity muscle mass (DLEM) and knee pain severity. Methods Using data from the Korea National Health and Nutrition Examination Survey, 3,278 participants who were ≥50 years old and who underwent dual x-ray absorptiometry, plain knee radiographs and completed a knee pain questionnaire were enrolled. Lower extremity muscle mass (LEM) was defined as the sum of the fat-free soft tissue mass of the legs, and lower extremity muscle mass index (LMI) was calculated as LEM/body weight (%). DLEM was defined as an LMI more than two standard deviations below the mean of a gender-matched young reference group. Categorical variables were presented as numbers (weighted %). Results The prevalence of knee pain and RKOA were 22% (n = 721) and 34.7% (n = 1,234), respectively. Multivariate logistic regression analysis showed being female (OR 2.15, 95% CI 1.67–2.79), older (OR 1.03, 95% CI 1.01–1.04), less educated (OR 1.72, 95% CI 1.09–2.71), stiffness (OR 16.15, 95% CI 12.04–21.66), bed rest (OR 2.49, 95% CI 1.81–3.43), RKOA (OR 2.20, 95% CI 1.78–2.74) and DLEM (OR 1.54, 95% CI 1.09–2.17) were associated with knee pain. Participants with simultaneous RKOA and DLEM complained of more severe pain (pain score 7.18 ± 2.48) than those with knee pain without RKOA or DLEM (5.02 ± 2.44), those with only RKOA (6.29 ± 2.50), or those with only DLEM (6.78 ± 2.18) (P

AIM To investigate whether plain radiography is useful for assessing the changes in gouty tophi size following hypouricemic therapy. METHODS Gout was diagnosed according to the American College of Rheumatology criteria. Before and after hypouricemic treatment, serum uric acid level was measured, and plain radiography was performed to measure gouty tophi size. The tophi were graded by measuring the maximum vertical and horizontal diameters, and they were scored by adding up the scores of the grades. The vertical diameter was measured on both sides of the proximal phalanges (PPs). The horizontal diameter was measured on the lateral side of the PPs. The maximum vertical diameter measurement was graded 0-4. The maximum horizontal diameter measurement was graded 0-3. RESULTS Seven hundred first metatarsal phalangeal joints (MTPJ) of 350 patients with gout were assessed for gouty tophi. Tophi were observed using plain radiography in 174 MTPJs (24.9%) of 109 patients (31.1%). Follow-up plain radiography was performed in 60 of these patients. Before the treatment, the average serum uric acid level of these patients was 8.3 ± 1.9 mg/dL, and the average tophi score was 3.7 ± 2.5. After hypouricemic treatment, the uric acid level decreased to 5.9 ± 1.6 mg/dL (P < 0.05), and the average tophi score decreased to 1.5 ± 1.8 (P < 0.05). CONCLUSIONS This new method for measuring gouty tophi using plain radiography may be useful for evaluating changes in gouty tophi size following hypouricemic treatment.

We present a case of a 65-year-old man with psoriasis who developed autoimmune hepatitis (AIH) without receiving immunosuppressive therapy with either anti-tumor necrosis factor-α or methotrexate. The AIH had completely resolved at 2 months after prednisolone and azathioprine therapy. This case confirms the need to consider AIH in psoriasis patients who experience new elevations in liver enzymes. To our knowledge, this is first description of the development of AIH in an immunosuppressant-naive patient with psoriasis.

Background/aims To investigate the drug survival rate of tacrolimus (TAC) and analyze the potential predictors of this rate in patients with rheumatoid arthritis (RA) in routine care. Methods2018-01-16 In this retrospective longitudinal study, we enrolled 102 RA patients treated with TAC from April 2009 to January 2014 at a tertiary center in South Korea. The causes of TAC discontinuation were classified as lack of efficacy (LOE), adverse events (AEs), and others. The drug survival rate was estimated using the Kaplan-Meier method and the predictors of this rate were identified by Cox-regression analyses. Results TAC was discontinued in 27 of 102 RA patients (26.5%). The overall 1-, 2-, 3-, and 4-year TAC continuation rates were 81.8%, 78.4%, 74.2%, and 69.1%, respectively and the median follow-up period from the start of TAC was 32.5 months. The number of TAC discontinuations due to LOE, AEs, and others were 15 (55.6%), 11 (40.7 %), and 1 (3.7%), respectively. The baseline high disease activity was a significant risk factor for TAC discontinuation after adjusting for confounding factors (hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.16 to 5.35; p = 0.019). In addition, underlying interstitial lung disease was significantly associated with TAC withdrawal due to AEs (HR, 3.49; 95% CI, 1.06 to 11.46; p = 0.039). Conclusions In our study, TAC showed a good overall survival rate in patients with RA in real clinical practice. This suggests that the long-term TAC therapy has a favorable efficacy and safety profile for treating RA.

The effect of decolonization on the control of methicillin-resistant Staphylococcus aureus (MRSA) may differ depending on intensive care unit (ICU) settings and the prevalence of antiseptic resistance in MRSA.This study was conducted in a 14-bed surgical ICU over a 40-month period. The baseline period featured active surveillance for MRSA and institution of contact precautions. MRSA decolonization via chlorhexidine baths and intranasal mupirocin was implemented during a subsequent 20-month intervention period. Pre-post and interrupted time series analysis were used to evaluate changes in the clinical incidence of hospital-acquired MRSA colonization or infection. MRSA isolates were tested for the presence of qacA/B genes and mupirocin resistance.In pre-post analysis, the clinical incidence of MRSA significantly decreased by 61.6% after implementation of decolonization (P .001). Meanwhile, interrupted time series analysis showed decreases in both the level (β = -0.686; P = .210) and trend (β = -0.011; P = .819) of clinical MRSA incidence, but these changes were not statistically significant. Of 169 MRSA isolates, 64 (37.8%) carried the qacA/B genes, and 22 (13.0%) showed either low- (n = 20) or high-level (n = 2) resistance to mupirocin. Low-level mupirocin resistance significantly increased from 0%-19.4% during the study period.Although decolonization using antiseptic agents was helpful to decrease hospital-acquired MRSA rates, the emergence of antiseptic resistance should be monitored.

Introduction Gout is a chronic inflammatory disease the development of which is associated with obesity-induced metabolic abnormalities. However, a substantial number of non-obese patients (body mass index [BMI] 100 cm2 was defined as visceral fat obesity (VFO). The frequency of VFO was compared in patients and control groups. The frequencies of metabolic syndrome and related parameters were also investigated. Results BMI, waist circumference, total fat mass, serum triglycerides, and serum glucose levels were significantly greater in patients compared with controls. VFA and the prevalence of VFO was increased in gout patients compared with controls. There were positive correlations between VFA and serum triglyceride levels and serum glucose levels. Multivariate regression analysis revealed that VFO is an independent risk factor for gout (odds ratio 2.488, 95% confidence interval 1.041–4.435). In non-obese subgroup analyses (gout patients, n = 38; healthy controls, n = 150), VFA (98.7 ± 19.3 vs. 91.0 ± 16.7, P = 0.016) and the frequency of VFO (47.4 vs. 27.3%, P = 0.017) remained significantly higher in gout patients. There was no difference in either BMI or total fat mass between patients and controls in the non-obese subgroup. The prevalence of metabolic syndrome in patients with gout was 31.7% (33/104), compared with 13.2% (5/38) in the non-obese subgroup according to modified ATP III criteria. Conclusion VFO, measured using BIA, is observed more frequently in patients with primary gout compared with healthy controls, even in non-obese individuals. Therefore, VFO might more properly represent metabolic derangements in patients with gout than general obesity.

Rationale Lymph node is a preferred site for extrapulmonary tuberculosis (TB). In the thorax, mediastinal tuberculous lymph nodes can erode adjacent structures such as heart, aorta, and esophagus, forming fistula, and causing fatal consequences. However, tuberculous bronchonodal fistula as a complication of lymph node TB in adults is rarely known in terms of imaging or clinical findings. Here, a case of isolated tuberculous bronchonodal fistula appearing as the first presentation of TB in a 74-year-old male with systemic lupus erythematosus (SLE) is reported. Patient concern A 74-year-old male with SLE visited the hospital with dry cough. In family history, his son was treated for pulmonary TB 9 years previously. Laboratory test revealed increased C-reactive protein level and erythrocyte sedimentation rate. Chest computed tomography (CT) scan revealed a necrotic lymph node in the right hilar area connected to the inferior wall of the right upper lobe bronchus and the lateral wall of bronchus intermedius. Diagnoses On bronchoscopy performed under guidance of 3-dimensionally reconstructed CT image, fistula formation between the right hilar lymph node and 2 bronchi (the right upper lobe and intermediate bronchus) was confirmed. Sputum culture revealed growth of Mycobacterium tuberculosis. Intervention Anti-TB medication with isoniazid, ethambutol, pyrazinamide, and moxifloxacin for 9 months. Outcome The patient's symptom was gradually improved. Follow-up bronchoscopy performed at 3 months after starting the medication revealed decreased size of the fistula. Lessons This is a rare case of bronchonodal fistula appearing as the first presentation of TB in a 74-year-old male patient with SLE. CT provided useful information regarding the origin and progress of the disease.

The immunomodulatory effects of adipokines have been extensively studied in rheumatic diseases, and there is a paucity of information regarding their effects on bone metabolism.The aim of this study was to investigate the relationships between serum adipokines levels and radiographic progression over 2 years in patients with ankylosing spondylitis (AS).In this preliminary longitudinal study, we prospectively recruited 20 consecutive male patients with AS and 11 gender- and age-matched healthy subjects. At the baseline and 2-year follow-up, serum adiponectin, leptin, resistin, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and Dickkopf-1(DKK-1) levels were measured in AS patients using enzyme-linked immunosorbent assays; these measurements were only performed at the baseline for healthy controls. Radiographic progression was determined as the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) progression of ≥2 by comparing the baseline and 2-year follow-up radiographs.All AS patients were naive to TNF-α blockers at the enrollment and during the 2-year follow-up period and their median disease duration was 51.5 months. At the baseline, the serum resistin, TNF-α, and IL-6 levels were significantly higher in AS patients than in controls. At the 2-year follow-up, the median mSASSS of AS patients was found to be significantly increased from the baseline (8-10.5, P = .001) and 7 (35%) AS patients showed radiographic progression. In AS patients, the leptin and resistin levels were significantly higher at the 2-year follow-up than at the baseline. The baseline resistin levels and changes in leptin levels from the baseline to the 2-year follow-up were significantly higher in AS patients with radiographic progression than in those without radiographic progression (P = .002 and .024, respectively). The baseline resistin levels and the increase in leptin levels during the follow-up period significantly correlated with changes in mSASSS (ρ = 0.528 and 0.559, P = .017 and .01, respectively). No association between changes in serum adipokine levels and disease activity in AS patients was observed.Our findings suggest that leptin and resistin may contribute to the pathogenesis of new bone formation rather than to inflammatory processes and have the potential to be used as biomarkers of the structural outcome of AS.

Ten different regioisomers of C60 trimers with intact cages were studied using the empirical tight-binding (TB) total energy calculation and the semiempirical PM3, AM1, and MNDO methods. We determined the stable atomic structure and energies of 10 (C60)3 regioisomers with ETBTEC, PM3, AM1, and MNDO calculations. The dimerization of C60 is exothermic according to the density-functional-based nonorthogonal tight-binding (DF-TB) method; the semiempirical PM3, AM1, and MNDO; and the ab initio 3-21G LDA and HF calculations, but it is endothermic in both the TB and the ab initio B3LYP6-31G*//4-21G B3LYP calculations. Therefore, according to the TB calculations, the most stable regioisomer of C60 trimers is equatorial. The energies of the trans-3(C2), trans-1(D2h), trans-2(C2), trans-4(Cs), cis-1 (C3ν), cis-2(Cs), cis-3(C2), cis-1(Cs), and cis-2(C3ν) regioisomers relative to the equatorial regioisomer are 13,19, 20, 30, 66, 99, 169, 215, and 673 meV, respectively.

There is no consensus on whether it is safe to re-administer tumor necrosis factor-alpha (TNFα) inhibitors in patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS) flared after withdrawal of TNFα inhibitors due to active tuberculosis (TB). We evaluated the safety of restarting anti-TNFα therapy in patients with TNFα-associated TB. We used data of 1,012 patients with RA or AS treated with TNFα inhibitors at Seoul St. Mary's Hospital between January 2003 and July 2013 to identify patients who developed active TB. Demographic and clinical data including the results of tuberculin skin tests (TST) and interferon-γ releasing assays (IGRA) were collected. Fifteen patients developed active TB. Five cases were occurred in RA and 10 cases in AS. Nine of 15 patients had a negative TST or IGRA and 6 TST-positive patients had received prophylaxis prior to initiating anti-TNFα therapy. All patients discontinued TNFα inhibitors with starting the treatment of TB. Eight patients were re-administered TNFα inhibitors due to disease flares and promptly improved without recurrence of TB. TNFα inhibitors could be safely resumed after starting anti-TB regimen in patients with RA or AS.

Background Rotator cuff tear (RCT) and hand osteroarthritis (HOA) are commonly accompanied because they share a similar pathogenesis. However, there was no previous study investigating the relationship between RCT and HOA. Objectives To estimate the prevalence and associated factors of RCT in patients with HOA. Methods In this study, we enrolled 1150 farmers who lived in Gyeongnam province in Korea from June 2013 to December 2015. Physical examinations were performed by rheumatologists and orthopedists. Plain radiography of hands and magnetic resonance imaging (MRI) of shoulders were performed in all participants. Serum levels of high sensitive C-reactive protein (hsCRP) and high density lipoprotein (HDL) were checked. RCT was diagnosed by clinical examination and MRI findings. Diagnosis of HOA was made by the 1990 American College of Rheumatology classification criteria. Severity of HOA was defined as Kellgren–Lawrence (KL) grade ≥3 on plain radiographs. Erosive HOA was defined as having eroded 9E9 or remodelled 9R9 phase of the Verbruggen. Results The prevalence of RCT was higher in patients with HOA group (192/307, 62.5%) than those without HOA (410/827, 49.5%, p Conclusions The prevalence of RCT is high and age and serum levels of hsCRP and HDL have predictive roles in the development of RCT in HOA patients. References Jin X, Beguerie JR, Zhang W, Blizzard L, Otahal P, Jones G, Ding C. Extended report: Circulating C reactive protein in osteoarthritis: a systematic review and meta-analysis. Ann Rheum Dis 2015;74(4):703–10. Acknowledgement This study was supported by a grant of the Center for Farmer9s Safety and Health, Ministry of Agriculture, Food and Rural Affairs, Republic of Korea. Disclosure of Interest None declared

Background Various upper extremity musculoskeletal diseases (MSDs) can affect pain and disability in patients with hand osteoarthritis (HOA). However, there was no previous study investigating the relationship between upper extremity MSDs and HOA. Objectives To explore the influence of major upper extremity MSDs on pain severity and functional status of patients with HOA. Methods In this study, we enrolled 1150 farmers who lived in Gyeongnam province in Korea from June 2013 to December 2015. Physical examinations were performed by rheumatologists, orthopedists, and rehabilitation specialists. Grip powers of both hands also were evaluated. Plain radiography, a nerve conduction velocity (NCV) examination, and magnetic resonance imaging (MRI) of shoulders were performed. The Australian/Canadian Osteoarthritis Hand Index (AUSCAN) was used to assess pain severity and functional status of hand joints. The diagnosis of HOA was made by the 1990 American College of Rheumatology classification criteria. Carpal tunnel syndrome (CTS) was confirmed by NCV findings, and rotator cuff tear (RCT) was diagnosed by MRI findings. Myofascial pain syndrome (MPS) was diagnosed by palpations of myofascial trigger points. Results Of 1150 participants, 307 were diagnosed with HOA. Among HOA patients, 151 (49.7%), 192 (62.5%), and 249 (80.1%) patients had CTS, RCTs, and MPS, respectively. HOA patients with MPS showed significantly higher AUSCAN scores (350.4±285.0 vs 200.4±201.8, p Conclusions MPS has a significant impact on pain and functional status in patients with HOA. Therefore, management of coexisting MPS is the better way to improve pain and function of hand joints in patients with HOA. Acknowledgement This study was supported by a grant of the Center for Farmer9s Safety and Health, Ministry of Agriculture, Food and Rural Affairs, Republic of Korea. Disclosure of Interest None declared

A 22-year-old man was diagnosed with isolated mediastinal myeloid sarcoma which radiologically mimicked primary mediastinal lymphoma. Despite administration of standard remission induction chemotherapy with daunorubicin and cytarabine, and three cycles of intensive high-dose cytarabine-based consolidation, chemo-resistant hypermetabolic lesions were persistently detected in the highest mediastinum and in the supraclavicular area. However, complete remission and long-term survival were achieved by curative radiotherapy followed by unrelated allogeneic stem cell transplantation.

Background Farming activity is burdened work with excessive use of hands. Thus, farmers are expected to have high prevalence of hand osteoarthritis (HOA). However, there is a lack of studies investigating prevalence and characteristics of HOA in Korean farmers. Objectives To estimate the prevalence of HOA among farmers in rural areas of Korea and assess whether HOA is related to farming activity. Methods The study was carried out from June 2013 to Dec 2014 with 700 farmers in Gyeong-nam Province of Korea. Clinical evaluation for hand joints was performed by rheumatologists and the plain radiographs of both hands were taken. The Australian/Canadian Osteoarthritis Hand Index (AUSCAN) was used to assess symptoms and function of hand joints. Radiographic HOA was defined as Kellgren–Lawrence (KL) grade≥2 on plain radiographs and symptomatic HOA as KL grade≥2 with pain/aching/stiffness at the same joints. Severe HOA was defined KL grade≥3. Presence of HOA at individual level was defined as ≥1 affected joint. Results Participants comprised of 53% female and 47% male with mean age of 59.7±8.6 years. As divided types of growing crops, persimmon growers, strawberry growers, rice growers, and persimmon plus rice growers were 28.6%, 27.0%, 11.7%, 23.0%, respectively. The prevalence of radiographic, symptomatic, and severe HOA was 59.1%, 13.9%, and 24.4%, respectively. Finger joints were affected in 51.4% and thumb joints in 34.1%. Interestingly, male farmers showed high prevalence of radiographic HOA (55.9%) and symptomatic HOA (13.0%). The prevalence of HOA was similar in both hands and increased with longer duration of farming. Multiple logistic regression analysis showed a significant association of age, female sex, and body mass index with radiographic HOA. As adjusted for determinants above, rice growers were associated with an increased risk of HOA (odds ratio 3.5; 95% confidence interval 1.71 to 7.21). AUSCAN score was high in female and increased according to the severity of HOA. Conclusions The prevalence of HOA in male is high, and related to types of growing crops. Therefore, this study suggests that development of HOA is associated with farming activity. References Zhang Y, Niu J, Kelly-Hayes M, Chaisson CE, Aliabadi P, Felson DT. Prevalence of symptomatic hand osteoarthritis and its impact on functional status among the elderly: The Framingham Study. Am J Epidemiol. 2002;156(11):1021-7. Cho NH, Kim SH, Kim HA, Seo YI. The Prevalence and Risk Factors of Knee and Hand Osteoarthritis in Korea. Journal of Rheumatic Diseases. 2007;14(4):354-362. Acknowledgements This study was supported by a grant of the Center for Farmer9s Safety and Health, Ministry of Agriculture, Food and Rural Affairs, Republic of Korea. Disclosure of Interest None declared

Background Orchardists are expected to show high prevalence of upper limb musculoskeletal disorders (MSDs) due to their heavy works and working postures. However, there are no systematic studies relating upper limb MSDs in Korean orchardists. Objectives To evaluate the prevalence and characteristics of upper limb MSDs among orchardists in rural areas of Korea. Methods The study was carried out from June 2013 to May 2014 in a tertiary medical center. The physical examinations of upper extremities were performed by rheumatologists, orthopedists, and rehabilitation medicine specialists. The plain radiographs of shoulder, elbow, and hand, nerve conduction examination of upper extremities, and MRI of both shoulder were taken. The Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire was used to assess symptoms and function of upper extremities. Results Five hundred and fifty orchardists were included. Participants comprised of 49.5% female and 50.5% male with mean age of 59.5±8.1 years. The mean farming duration was 31.3±13.2 years. A total of 34 different types of upper limb MSDs were detected. The most frequent disorder was myofascial pain syndrome (80.5%) followed by rotator cuff syndrome (58.9%), hand osteoarthritis (58.0%), carpal tunnel syndrome (42.9%), and lateral epicondylitis (39.5%). Prevalence of any form of MSD was 98.5% and of three and more of MSDs was 77.3%. Participants with longer duration of farming had higher numbers of MSDs. Almost part of pruning and harvesting postures in orchard farming were loaded works for musculoskeletal systems. Total DASH score was relatively high (14.9±14.4). Conclusions Almost orchardists have upper limb MSDs. Our results suggest the need to implement interventions in orchardists to prevent MSDs. References Gomez MI, Hwang S, Stark AD, May JJ, Hallman EM, Pantea CI. An analysis of self-reported joint pain among New York farmers. J Agric Saf Health. 2003;9:143–157. Holmberg S, Stiernstrom EL, Thelin A, Svardsudd K. Musculoskeletal symptoms among farmers and non-farmers: A population based study. Int J Occup Environ Health. 2002;8:339–345. Osborne A, Blake C, Fullen BM, Meredith D, Phelan J, McNamara J, Cunningham C. Prevalence of musculoskeletal disorders among farmers: A systematic review. Am J Ind Med. 2012;55(2):143-58. Acknowledgements This study was supported by a grant of the Center for Farmer9s Safety and Health, Ministry of Agriculture, Food and Rural Affairs, Republic of Korea. Disclosure of Interest None declared

showed decreased bone destruction on radiograph (3.4±0.3 vs. 2.0±0.2, p

pISSN: 2093-940X, eISSN: 2233-4718 Copyright c 2015 by The Korean College of Rheumatology. All rights reserved. This is a Free Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited. Original Article Journal of Rheumatic Diseases Vol. 22, No. 6, December, 2015 http://dx.doi.org/10.4078/jrd.2015.22.6.366

Objectives The type III histone deacetylase SIRT1 is a critical molecule in the modulation of immune and inflammatory response through the deacetylation of various histones and non-histone proteins. However, there are limited and controversial data regarding the roles of SIRT1 in rheumatoid arthritis (RA) and its role in dendritic cells (DCs) remains unknown. Thus, this study sought to assess the role of SIRT1 in collagen-induced arthritis (CIA) using a myeloid cell-specific SIRT1 knockout (mSIRT1 KO) mouse. Methods mSIRT1 KO mice were generated using the loxP/Cre recombinase system. CIA was induced in mSIRT1 KO mice and age-matched littermate loxP control mice. Arthritis severity was assessed by clinical, radiological, and pathological scoring. The levels of various cytokines in the joints, serum, lymph nodes were determined by quantitative polymerase chain reaction and ELISA. T cells and DCs were quantified using flow-cytometry and in vitro T cell cytokines and DCs markers were also measured. Results The mSIRT1 KO mice showed significantly lower arthritis severity and joint destruction compared with control mice. The expression of inflammatory cytokines, MMPs, and ROR-γT was also reduced in mSIRT1 KO mice. These effects were paralleled by reduction of Th1, Th17, CD69-positive T cells, CD80, and CD86 positive DCs in mSIRT1 KO mice. In addition, in vitro studies showed that interferon-γ and IL-17 production by T cells and the maturation of DCs were significantly decreased in mSIRT1 KO mice. Conclusions Unlike passive K/BxN serum transfer arthritis, myeloid cell-specific deletion of SIRT1 was associated with lower arthritis severity in CIA by modulating DCs maturation and Th1 and Th17 responses. The data suggest that SIRT1 plays a complex role in RA and careful investigation of cell-specific effects is necessary to delineate possible therapeutic uses of agents targeting SIRT1. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.4188

Background Systemic lupus erythematosus (SLE) is an autoimmune disease in which various organs and tissues are damaged through abnormal immune responses mediated by tissue-binding autoantibodies and immune complex deposition. As the majority of SLE patients are women of child-bearing age, estrogen has been suggested to play an important role in the pathogenesis of SLE. One of the proposed roles of estrogen is to increase autoantibody production. IL-21, a common-γ chain cytokine, has been shown to be crucial in the differentiation of activated B cells into plasma cells. Objectives Based on these concepts, we investigated the effect of estrogen on the production of IL-21 by T cells and subsequent B cell activation in SLE patients. Methods Peripheral blood mononuclear cells (PBMCs) were obtained from peripheral blood of 23 SLE patients and 16 healthy controls. CD4+ T cells, non CD4+ T cells and B cells were isolated using microbeads. Isolated cells were treated with 17-β estradiol at various concentrations for 48hrs. The expression of IL-21 and its receptor was assessed by measuring the level of protein and mRNA using ELISA and RT-PCR, respectively. The level of immunoglobulin G was measured with specific ELISA. Results The expression of IL-21 and its receptor in serum, PBMCs, and CD4+ T cells were higher in the patients with SLE compared to healthy controls. Exposure of CD4+ T cells from SLE patients to 17-β estradiol leads to a dose-and time-dependent increase in the IL-21 expression. The increase was abolished in the presence of MAP kinase (MEK, p38, JNK) inhibitors. B cells of healthy controls showed an increased antibody production when they were co-cultured with estrogen treated CD4+ T cells of patients with SLE. Treatment with anti-IL-21 antibody abrogated the increased antibody production of the co-culture systems, suggesting the increase was mediated by IL-21 dependent manner. Conclusions Estrogen upregulates IL-21 expression of CD4+ T cells via MAPK dependent pathways in SLE patients, which in turn induces increased antibody production by B cells. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.3160

Background Leg muscle mass is related to development and progression of knee OA, and some studies suggested low leg muscle mass quantified by cross-sectional images of CT or MRI was related to knee symptoms [1,2]. However, this direct method of quantification is hard to apply to clinical practices, and it can be affected by total body mass which can confound the relationship of leg muscle mass and knee symptoms. Objectives We sought to examine if the ratio of leg to whole body muscle or fat mass by DXA relates to knee symptoms in radiographic knee OA. Methods We performed a cross-sectional study using data from the Fifth Korean National Health and Nutrition Examination Survey. We included subjects with radiographic knee OA (Kellgren-Lawrence grade≥2) and obtained degree of symptoms, body composition of both legs and the whole body using DXA and calculated the ratios of leg to whole body for muscle and fat mass. Analysis of covariance and multivariable logistic regression models were used to examine the associations of leg to whole body mass with knee symptoms adjusting for possible confounders. Results 1664 subjects were eligible for analysis. The ratio of leg to whole body muscle mass (LTWBM) was significantly lower in the group with knee pain or stiffness (30.27±0.10 vs. 30.92±0.08, p Conclusions Symptomatic knee OA was associated with reduced leg muscle mass. Local sarcopenia indicated by low leg to whole body muscle mass could be an important and useful clinical marker for symptomatic knee OA. Strategies to increase leg muscle mass might counteract having symptomatic knee OA. References Sattler, M., et al., Side differences of thigh muscle cross-sectional areas and maximal isometric muscle force in bilateral knees with the same radiographic disease stage, but unilateral frequent pain - data from the osteoarthritis initiative. Osteoarthritis Cartilage, 2012. 20(6): p. 532-40. Wang, Y., et al., Increase in vastus medialis cross-sectional area is associated with reduced pain, cartilage loss, and joint replacement risk in knee osteoarthritis. Arthritis Rheum, 2012. 64(12): p. 3917-25. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.2422

Background Ursolic acid (UA) is a pentacytclic triterpenoid compound which is ubiquitously present in plants. Objectives Based on its known anti-inflammatory and anti-oxidative effect, this study was undertaken to investigate the effect of UA on collagen-induced arthritis (CIA) and to delineate the underlying mechanism. Methods UA (150mg/kg) or 10% dimethyl sulfoxide was injected intraperitoneally three times a week to mice with CIA from the day 14 after immunization. The expressions of proinflammatory cytokines and molecules associated with oxidative stress in arthritic joints were measured by immunohistochemical staining. The number of CD4+IL-17+ cells or CD4+CD25+Foxp3+ cells or phosphorylated (p) STAT3 + cells was determined by confocal immunostaining of the spleen or flow cytometry analysis of splenocytes. The level of mRNA expression and immunoglobulin was analyzed by real time RT-PCR and ELISA, respectively. Results UA injection prevented clinical arthritis incidence and joint inflammation in mice with CIA. A significant reduction in pSTAT3 and resultant decrease in the number of Th17 was observed with UA treatment. Consistently, the expression of IL-17 and retinoic acid orphan receptor (ROR)γt was markedly reduced with UA. Although the expression of Foxp3 was unaffected, the number of Treg cells was increased with UA treatment. There was a marked reduction in type II collagen-specific immunoglobulin G production. When IL-21-or LPS-stimulated CD19+ B cells were cultured in the presence or absence of UA, the mRNA expression of markers associated with B cell activation (Bcl-6), plasma cell differentiation (Blimp-1) and isotype switching (activation-induced deaminase) was markedly reduced with UA treatment. Conclusions Our findings suggest that UA can regulate Th17 and reciprocally promote Treg cells by inhibiting expression of ROR γt and pSTAT3. UA also inhibits plasma cell differentiation, resulting in a reduction of immunoglobulin production. By targeting pathogenic Th17 and immunoglobulin production, UA may be a novel therapeutic for treatment of autoimmune arthritis and other Th17-related diseases. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3181

Background Since the concept of reprogramming mature somatic cells to generate induced pluripotent stem cells (iPSCs) was demonstrated in 2006, iPSCs have become a potential substitute for embryonic stem cells (ESCs) given their pluripotency and “stemness” characteristics, which resemble those of ESCs. Objectives We investigated to reprogram fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) to generate iPSCs using a 4-in-1 lentiviral vector system. Methods A 4-in-1 lentiviral vector containing Oct4, Sox2, Klf4, and c-Myc was transduced into RA and OA FLSs isolated from the synovia of two RA patients and two OA patients. Immunohistochemical staining and real-time PCR studies were performed to demonstrate the pluripotency of iPSCs. Chromosomal abnormalities were determined based on the karyotype. SCID-biege mice were injected with iPSCs and sacrificed to test for teratoma formation. Results After 14 days of transduction using the 4-in-1 lentiviral vector, RA FLSs and OA FLSs were transformed into spherical shapes that resembled embryonic stem cell colonies. Colonies were picked and cultivated on matrigel plates to produce iPSC lines. Real-time PCR of RA and OA iPSCs detected positive markers of pluripotency. Immunohistochemical staining tests with Nanog, Oct4, Sox2, Tra-1-80, Tra-1-60, and SSEA-4 were also positive. Teratomas that comprised three compartments of ectoderm, mesoderm, and endoderm were formed at the injection sites of iPSCs. Established iPSCs were shown to be compatible by karyotyping. Finally, we confirmed that the patient-derived iPSCs were able to differentiate into osteoblast, which was shown by an osteoimage mineralization assay. Conclusions FLSs derived from RA and OA could be cell resources for iPSC reprogramming. Disease- and patient-specific iPSCs have the potential to be applied in clinical settings as source materials for molecular diagnosis and regenerative therapy. References Takahashi K, Yamanaka S: Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006, 126:663-76. Tiscornia G, Vivas EL, Izpisua Belmonte JC: Diseases in a dish: modeling human genetic disorders using induced pluripotent cells. Nat Med 2011, 17:1570-6. Grskovic M, Javaherian A, Strulovici B, Daley GQ: Induced pluripotent stem cells–opportunities for disease modelling and drug discovery. Nat Rev Drug Discov 2011, 10:915-29. Acknowledgements This work was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A092258). Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4862

Background Gout is a chronic inflammatory disease of which the development is associated with metabolic abnormality caused by obesity. However, there are a substantial number of non-obese patients (body mass index (BMI) 100cm2 was defined as visceral fat obesity (VFO). The frequency of VFO was compared in patients and control groups. The frequency of metabolic syndrome as well as its components was investigated. Results The prevalence of metabolic syndrome in patients with gout was 31.7% (33/104) according to modified ATP III criteria. BMI (26.3±3.8 vs. 23.4±2.4 kg/m2, P

Background Anti-TNF therapy was known to increase the risk of certain infection. There are no sufficient data about the reactivation of hepatitis B virus (HBV) after anti-TNF therapy. Objectives The study was aimed to investigate the clinical course of hepatitis B in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) after the introduction of anti-TNF therapy. Methods We retrospectively reviewed to identify patients infected with HBV treated with TNF inhibitors between October, 2004 and September, 2013. For patients with HBV infection, the liver enzyme and the viral status were monitored. The HBV reactivation was defined according to the Korean guideline by hepatology. Results Of 983 patients (RA, n=536; AS, n=447) who were treated with TNF inhibitors, 23 patients (RA, n=17; AS, n=6) had comorbidities of HBV infection. Eighteen patients were treated with etanercept, three with adalimumab, and two with infliximab. Seven patients received pre-emptive antiviral prophylaxis before anti-TNF therapy: 4 with entecavir, 1 with telbivudine, 1 with tenofovir, and 1 with lamivudine. Among 23 patients with HBV infection, 4 (17.4%) patients experienced the reactivation of HBV, which occurred in 3 patients without prophylaxis and 1 patient with lamivudine prophylaxis. In the latter case, YMDD mutation was identified and addition of adefovir resulted in virological response. The other three patients were treated successfully with entecavir or tenofovir. There was no subsequent events associated with HBV infection. Conclusions This study indicates the risk of HBV reactivation after anti-TNF therapy. Careful management is mandatory for patients who planned to be treated with TNF inhibitors. References Vassilopoulos D, Calabrese LH. Management of rheumatic disease with comorbid HBV or HCV infection. Nature reviews Rheumatology. 2012 Jun;8(6):348-57 Oketani M, Ido A, Uto H, Tsubouchi H. Prevention of hepatitis B virus reactivation in patients receiving immunosuppressive therapy or chemotherapy. Hepatology research: the official journal of the Japan Society of Hepatology. 2012 Jul;42(7):627-36 Korean Association for the Study of the L. KASL Clinical Practice Guidelines: Management of chronic hepatitis B. Clinical and molecular hepatology. 2012 Jun;18(2):109-62 Acknowledgements This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI10C2020). Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5251

Background Periostin is a matricellular protein that expressed in bone, periodontal ligament, heart valve, tendon and skin. Previous study indicated that periostinis linked with several inflammatory diseases such as airway hypersensitivity, periodontal inflammation, and pulmonary fibrosis. However, there is no study to investigate the role of periostin in rheumatoid arthritis (RA). Objectives This study was performed to assess the function of periostin in K/BxN serum transfer arthritic mice. Methods Synovial tissues, serum, joint fluid, and fibroblast-like synoviocyte (FLS) were obtained from patients with RA and osteoarthritis (OA). The expression of periostin in synovial tissues was assessed by immunohistochemistry. The levels of periostin were checked by Western blot and enzyme-linked immunosorbent assay (ELISA). K/BxN serum transfer arthritis was induced in periostin knockout (KO) and age-matched wild type (WT) mice. Arthritis severity was assessed by clinical and histopathologic scoring. The levels of inflammatory cytokines in ankles and serum were measured by quantitative PCR and ELISA. The osteoclastogenesis was assessed by using bone marrow monocytes (BMM) from periostin KO or WT mice. Results Periostin was highly expressed in the synovium of RA patient than OA. The periostin levels were increased in the presence of IL-1β and TNF-α in RA-FLS. The periostin KO mice showed more severe arthritis from day 4 to day 10. The peak clinical scores were: 5.0±0.6 in WT, 7.36±0.5 in periostin KO mice; p Conclusions This study suggests that regulation of periostin contributes to pathogenesis of RA and periostin has a potential protective role in RA. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4201

Background IL-33 and its receptor, ST2, are associated with many inflammatory disorders. However, the data on IL-33/ST2 in Sjogren9s syndrome (SS) is very limited. Objectives To evaluate the expression of IL-33 and its receptor in sera and salivary tissues obtained from patients with primary Sjogren9s syndrome (pSS) and to investigate the possible relationship with clinical profiles. Methods Serum IL-33 and soluble ST2 (sST2) of 55 patients with pSS and 48 controls were determined using ELISA, and assessed for correlation with clinical profiles. The expression of IL-33/ST2 in salivary tissues was investigated by immunohistochemical (IHC) staining, and was further characterized by confocal microscopy. We also measured ST2 expression in peripheral blood mononuclear cells (PBMCs) of pSS patients, and IL-33 production in salivary glandular epithelial cell by pro-inflammatory stimuli. Results The serum levels of IL-33 and sST2 were higher in pSS patients compared to healthy controls ( P =0.018 and P P =0.029) and duration of disease ( p =0.013). Contrary to sST2, ST2 was downregulated in PBMCs obtained from pSS patients. The expression of IL-33 and ST2 was elevated in salivary gland of pSS patients with grade 2 inflammation, and decreased as inflammation progresses. In pSS patients, IL-33 was mainly observed in epithelial cells and endothelial cells of gland tissue. The production of IL-33 mRNA by salivary gland epithelial cell line was increased under stimulation with interferon-γ. Conclusions IL-33 and sST2 concentrations were elevated in sera of pSS patients, whereas ST2 in salivary gland and PBMC of pSS patients showed downregulated expression. This result suggests that IL-33/ST2 axis might have a role in the pathogenesis of pSS. References Schmitz, J., et al., IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity, 2005. 23(5): p. 479-90. Palmer, G. and C. Gabay, Interleukin-33 biology with potential insights into human diseases. Nat Rev Rheumatol, 2011. 7(6): p. 321-9. Moussion, C., N. Ortega, and J.P. Girard, The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel `9alarmin”? PLoS One, 2008. 3(10): p. e3331. Acknowledgements This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI13C0016). Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.4921

Background Gout is caused by hyperuricemia related to altered purine metabolism characterized by monosodium urate (MSU) crystals deposition into the joints, particularly the first metartarsophalangeal joint (1st MTPJ). Chronic gout is characterized by the presence of tophi, chronic granulomatous synovitis and bone erosion. As well known, bone erosion is a strong predictor of musculoskeletal disability and is strongly associated with the presence of gout tophi. The size of gout tophi can be decreased when serum urate level is maintained below 6mg/dl. Therefore tophi measurement may reflect outcome after urate-lowering therapy in chronic gout. Plain radiography remains the most widely used imaging modality in the clinical practice. In our knowledge, however, there have been no grading system for tophi on plain radiography. Objectives The aim of our study is to investigate the usefulness of new grading system for gout tophi by plain radiography. Methods 334 patients who fulfilled ACR diagnostic criteria of gout and had anteroposterior plain radiography of both 1st MTPJs included retrospectively in our study. Two rheumatologist evaluated gout tophi, soft tissue swelling, bone erosion (BE) and joint space narrowing (JSN) on plain radiography, independently. The agreement between two observer were good (k>0.08). Gout tophi were defined as increased densities which are distinct from adjacent soft tissues. They were graded by measuring maximum diameters vertically and horizontally, and scored by adding up the scores of grades. The vertical diameter of tophi was measured at both sides of proximal phalanges (PPs). The horizontal diameter was measured at lateral side of PP. The measurement of maximum vertical diameter of tophi were graded as follows: grade 0, no tophi; grade 1, the presence of tophi is suspicious; grade 2, less than half of maximum vertical diameter of PP; grade 3, half or more of and less than the maximum vertical diameter of PP; grade 4, more than the maximum vertical diameter of PP. The maximum horizontal diameter of tophi was measured including the adjacent swollen soft tissues, and graded as follows: grade 0, no tophi; grade 1, less than half of maximum horizontal diameter of PP; grade 2, half or more of and less than the maximum horizontal diameter of PP; grade 3, more than the maximum horizontal diameter of PP (Figure 1). Results 111 (33.3%) of 334 patients had abnormal findings (gout tophi; 26.9%, BE; 22.2% and JSN; 7.8%) at initial plain radiography. 43 patients showed tophi and/or soft tissue swelling on plain radiographs. 31 of 43 patients showed improvement of tophi on follow-up plain radiographs. 23 of 31 patients had less than 6 mg/dL of serum urate level after treatment. Points by new grading methods differed significantly between the patient group having 6 mg/dL or more and the patient group having less than 6 mg/dL of serum urate level after hypouricemic treatment ( p =0.05). Conclusions New grading system for gout tophi on plain radiography is useful for evaluating changes of gout tophi after hypouricemic therapy. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4164

Background Recent studies demonstrated that sodium chloride (NaCl) can be a risk factor for autoimmune disease through the induction of pathogenic IL-17 producing T helper (Th17) cells. Objectives This study was aimed to evaluate the potential effect of NaCl on Th17 differentiation in patients with rheumatoid arthritis (RA) and on the inflammation in collagen induced arthritis (CIA) model. Methods Peripheral blood mononuclear cells (PBMC) obtained from RA patients were cultured under high salt condition, and analyzed using flowcytometry to determine Th17 population. For evaluation of in vivo effect, CIA mice were fed with normal diet (control group) or high salt diet ad libitum (high salt group). Clinical assessment was performed daily based on visual scoring of paw swelling. The arthrogenic differentiation of mouse bone marrow derived cells and mouse splenocytes were evaluated with tartrate-resistant acid phosphatase (TRAP) staining and flowcytometry, respectively. Results NaCl promoted the induction of Th17 cells from PBMC in RA patients. Th17 differentiation was progressively upregulated as NaCl concentration increased upto 60 mM. Correspondingly, high salt diet exacerbated the arthritis of CIA mice. The arthritis score was considerably elevated in high salt group compared with control group. In high salt group, osteoclast differentiation represented by TRAP activity was more prominent. We also observed the increased expression of CD4+ RORrt+ cells in spleen of high salt fed mice. Conclusions This study suggests that NaCl can aggravate arthritis via Th17 differentiation. High salt condition can contribute to the development and progression of RA. References Kleinewietfeld, M., et al., Sodium chloride drives autoimmune disease by the induction of pathogenic T17 cells. Nature, 2013. Wu, C., et al., Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1. Nature, 2013. 496(7446): p. 513-7. Acknowledgements This work was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A092258). Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5138

The aim of the current study is to identify patients without osteoporosis who met the criteria of the fracture risk assessment tool (FRAX) of the National Osteoporosis Foundation (NOF) only. The incidence of fractures was investigated in patients who met only the FRAX criteria of the NOF and patients who presented osteoporosis. Five hundred and forty five patients with rheumatoid arthritis who visited a single center were recruited in Korea. In the follow-up period of median 30 months, the new onset of fractures was investigated. Of 223 patients who have no osteoporosis, 39 (17.4%) satisfied the FRAX criteria for pharmacological intervention. During the follow-up period, 2 new onset fractures occurred in patients who met only the FRAX criteria and 22 new onset fractures did in patients with osteoporosis by bone mineral density. The incidence rate for new onset fractures of patients who met only the FRAX criteria was with 295.93 per 10,000 person-years higher than in the general population with 114.99 per 10,000 person-years. Patients who met the FRAX criteria of the NOF only need pharmacological intervention because their numbers of incidence for new onset fractures are similar to those of patients with osteoporosis by BMD. Graphical Abstract Keywords: Arthritis, Rheumatoid; Osteoporosis; Fractures, Bone; BMD; FRAX INTRODUCTION Rheumatoid arthritis (RA) is a systemic inflammatory disease which is associated with osteoporosis. The incidence of osteoporosis is doubled in patients with RA compared to the general population, leading to an increased rheumatoid comorbidity (1). Several case-control studies have documented a high rate of vertebral and hip fractures in patients with RA (2,3,4). The reported fracture incidence varies widely, with some authors pointing to the doubled figures in RA. The fractures lead to chronic pain, disability, and bed-ridden morbidity, a common cause of mortality (5, 6). Glucocorticoids, high disease activity, decreased joint function, and cytokine hyperproduction drive the bone resorption and enhance the risk of falls, which is a major cause of osteoporotic fractures in patients with RA (7, 8). To prevent such fractures, it is important to identify the high-risk patients with low bone mineral density (BMD) and other clinical risk factors and prescribe pharmacological interventions at early stages of osteoporosis. Bone strength depends on its mass and quality, which are subjected to the structure and material composition (9). BMD is only partially represent the bone strength, and is not predictive of osteoporotic fractures if taken alone. Pharmacological interventions in osteoporosis due to RA are often based on the T-score values measured by dual-energy X-ray absorptiometry (DEXA), similar to the strategy applicable to the general population. However, T-score alone may not be sufficient for the risk stratification in RA. To overcome limitations of T-score, the fracture risk assessment tool (FRAX) was developed by the World Health Organization (WHO), based on a twelve powered prospective cohort studies. The FRAX tool assesses a 10-yr probability of hip and other major osteoporotic fractures (10). It takes into account ten clinical risk factors, and can be calculated with or without femoral neck BMD. In 2008, the National Osteoporosis Foundation (NOF) of the USA endorsed the FRAX tool and recommended relevant pharmacological interventions for patients, who fulfill a 10-yr probability of ≥ 20% for a major osteoporotic fracture or ≥ 3% for a hip fracture. In many countries, the FRAX tool has been proved useful over the last five years, with a few reports reflecting on the measurements in patients with RA (11,12,13). A study from Korea demonstrated the differences between the FRAX, the NOF guideline, and the Korean Health Insurance Review Agency (HIRA) regarding the candidates for pharmacological interventions (14). It appears that patients who meet the FRAX criteria are different from those who are diagnosed with osteoporosis based on BMD values (15). The FRAX criteria of the NOF are not accepted by the HIRA for the reimbursement of pharmacological interventions. Therefore the FRAX is rarely used in Korea. Inappropriate approaches to clinical risk factors for fractures and an under-treatment of osteoporosis are not the only concerns in Korea (16). The aim of this study was to investigate the frequency of osteoporosis in Korean patients with RA and to identify patients who meet the FRAX criteria for pharmacological interventions despite the absence of osteoporosis. We also aimed at evaluating the demographic characteristics and the incidence of fractures in the identified patient group.

Eosinophilic fasciitis (EF) is a rare fibrosing disorder characterized by painful swelling and induration of the limbs and trunk, characteristic histology with sclerosis and lymphocytic inflammation affecting the fascia. The cause and pathogenesis of EF are still unknown and current therapies include glucocorticoids with or without use of immunosuppressive agents. Recently, there have been several case reports documenting the efficacy of a TNF alpha inhibitor in EF following a steroid-resistant disease course. However, there has been no report on the experience in treatment of EF with a TNF alpha inhibitor in Korea. Hence, we report a case of steroid and methotrexate-resistant EF which was successfully treated with adalimumab, along with a review of the relevant articles.

We analysed the geometrical structures and energetics of exo- and endo-pentaheptofullerene-M (M=Li and Tl) complexes by using the semiempirical Hartree-Fock (HF) PM3 method. The exohedral fullerene complexes are more stable than the endohedral. The most stable isomer is the vertical one for η 5 -C 60 Ph 5 Li and the tilted one for η 5 -C 60 Ph 5 Tl.

Gastrointestinal strongyloidiasis and Cytomegalovirus infection mostly occur in patients receiving cancer chemotherapy, undergoing immunosuppressive therapy after organ transplantation, and suffering from acquired immune deficiency syndrome. A 56-year-old man was admitted to the hospital because of abdominal pain and constipation. He had a 10-year history of chronic obstructive pulmonary disease and has been treated intermittently with systemic steroid. The gastroduodenoscopic examination showed a single ulcer on the duodenal bulb and microscopic finding of the biopsy specimens from the ulcer revealed Strongyloides stercoralis and cytomegalovirus immunohistochemical stain positive intranuclear inclusion body on the mucosal surface. The patient was successfully treated with albendazole and ganciclovir.