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// Joo Mi Yi 1 , Eun-Jin Kang 1 , Hyun-Mi Kwon 1 , Jin-Han Bae 1 , Keunsoo Kang 2 , Nita Ahuja 3 , Kwangmo Yang 1 1 Research Center, Dongnam Institute of Radiological and Medical Sciences (DIRAMS), Busan, Republic of Korea 2 Department of Microbiology, Dankook University, Cheonan, Korea, Republic of Korea 3 Department of Surgery, Oncology, and Urology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Correspondence to: Joo Mi Yi, email: jmyi@dirams.re.kr Kwangmo Yang, email: kmyang@dirams.re.kr Keywords: microRNA, miR-1247, hypermethylation, tumor suppressor, pancreatic cancer Received: October 25, 2016 Accepted: February 13, 2017 Published: February 24, 2017 ABSTRACT Altered expression of microRNAs has been strongly implicated in human cancers, and growing evidence is emerging that a number of miRNAs are downregulated in cancer associated with CpG island hypermethylation. Although pancreatic cancer is one of the most malignant human cancers, the roles of miRNAs underlying the tumorigenesis of pancreatic cancer are still poorly understood. In the present study, we explored the molecular functional role of microRNA-1247 as tumor suppressor associated with epigenetic alteration in pancreatic cancer. CpG islands methylation of miR-1247 is frequently observed in various pancreatic cancer cell lines and in primary pancreatic tumors, but not in normal pancreatic tissue. Ectopic expression of miR-1247 in five pancreatic cancer cell lines results in suppressing of cell growth, proliferation, migration, and invasion in vitro and tumorigenicity of pancreatic cancer cells in vivo . Interestingly, we found one putative target gene of miR-1247, regulator of chromosome condensation 2 ( RCC2 ), harbored miR-1247 target sequences in the 3′ UTR of its mRNA. In functional studies in vitro to understand the interaction between miR-1247 and RCC2 , decreasing of RCC2 gene expression by miR-1247 was observed by immunoblotting and immunohistochemistry at both mRNA and protein levels. Moreover, luciferase reporter assay confirmed that RCC2 was a direct target of miR-1247. Taken together, our data suggest that CpG island hypermethylation of miR-1247 is responsible for its downregulation in pancreatic cancer, and ectopic expression of miR-1247 functions as a potential tumor suppressor targeting RCC2 in pancreatic cancer cells.

Objectives HLA genes are a major genetic risk factor for myositis and myositis specific antibodies (MSAs), exhibiting unique HLA backgrounds for myositis in different ethnic groups. This is the first large scale Korean study to genotype the HLA-DRB1 and -DPB1 alleles and to examine their association with myositis and MSAs. Methods HLA-DRB1 and HLA-DPB1 alleles and MSAs were examined in 179 patients with dermatomyositis (DM, n = 129) or polymyositis (PM, n = 50) and healthy controls (n = 800 for HLA-DRB1, n = 548 for HLA-DPB1). Associations between individual HLA alleles and myositis/MSA were examined. Bonferroni correction was applied for multiple testing comparing patients and controls. Results A total of 33 HLA-DRB1 and 24 HLA-DPB1 alleles were genotyped in patients and controls. MSAs were found in 67.0% of patients. Anti-MDA5 (26.8%) and anti-aminoacyl-tRNA synthetase antibodies (15.6%) were most common, followed by anti-Mi2 (9.5%) and anti-TIF1γ antibodies (8.9%). HLA-DRB1*12:02 and HLA-DRB1*14:03 were associated with DM and PM, respectively. HLA-DRB1*12:02 was associated with anti-MDA5, HLA-DRB1*08:03 with anti-ARS, HLA-DRB1*14:03 with anti-SRP, and HLA-DRB1*07:01 with anti-Mi2 antibodies. Although HLA-DRB1*13:01 was associated with anti-TIF1γ antibodies, the frequency of HLA-DRB1*13:01 was rare. HLA-DPB1*02:01 was negatively associated with myositis and PM while HLA-DPB1*17:01 was associated with anti-Mi2 positive DM. Conclusions Unique immunogenetic background was observed for Korean patients with myositis. Novel myositis susceptibility alleles, HLA-DRB1*12:02 and HLA-DRB1*14:03, were identified, together with MSA-associated HLA alleles unique to Korean patients with myositis.

Interstitial lung disease (ILD) is the most common cause of death in dermatomyositis (DM). Cyclosporine A (CsA) has shown to be effective in DM-associated ILD (DM-ILD). This study aimed to define the optimal time of CsA administration. A total of 47 patients with DM-ILD, who were treated with CsA at Seoul National University Hospital between January 1998 and June 2013, were enrolled. ILD was diagnosed based on typical chest high-resolution computed tomography (HRCT) findings. Patients with early and delayed CsA treatment were compared in regard to the mortality and ILD progression on HRCT. The early (n = 16) and the delayed treatment group (n = 31) did not differ in regard to baseline clinical characteristics including HRCT scores and pulmonary function. Patients with clinically amyopathic DM (CADM) were more common in the early treatment group. The mortality rate was significantly lower in the early treatment group than in the delayed treatment group (p = 0.009). The survival benefit of early CsA treatment remained significant even after adjusting for age, degree of dyspnea, CADM status, and the year of CsA treatment (hazard ratio 0.057, 95 % confidence interval 0.007-0.472). CsA stabilized disease progression on HRCT in the early treatment group (p = 0.738). Delay in CsA treatment is associated with a worse survival in patients with DM-ILD. Early CsA treatment should be considered at DM-ILD diagnosis especially in patients at a higher risk of developing a rapidly progressive ILD.

OBJECTIVE To develop a decision model to identify SSc-associated interstitial lung disease (ILD) patients who are eligible for watchful waiting at ILD diagnosis. METHODS One hundred and fifty-one SSc-ILD patients who received medical care at Seoul National University Hospital from 1986 to 2013 were enrolled in this retrospective cohort study. ILD was diagnosed by chest CT. Patients with and without immunosuppressive treatment were compared in terms of characteristics at ILD diagnosis to identify distinguishing variables. After multivariate analysis, a decision model for watchful waiting was formulated. Its validity was assessed by comparing the survival of patients whose management in real practice did and did not accord with the management recommended by the model. RESULTS The untreated group had better survival than the immunosuppressive treatment group (P = 0.0316, by log-rank test). The untreated group was less likely to have gastrointestinal involvement (P = 0.008) and pulmonary arterial hypertension (PAH), as determined by echocardiography) (P = 0.015) and more likely to have favourable initial forced vital capacity (P = 0.0004), favourable initial lung diffusion capacity for carbon monoxide (P = 0.0002) and a low CT grade (P < 0.001). The final watchful waiting decision model included lack of PAH and limited ILD extent on CT. Application of the model to the cohort revealed that patients who were eligible for watchful waiting (as determined by the model) and underwent this management strategy had better survival than eligible patients who underwent immunosuppressive treatment (P = 0.048, by log-rank test). CONCLUSION Watchful waiting may be effective for SSc-ILD patients who have minimal pulmonary involvement on CT and lack PAH on echocardiography at baseline.

Background T follicular helper cells (Tfh) are necessary for B-cell maturation and differentiation in the germinal centers (GC). The signaling lymphocyte activation molecule family (SLAMF) receptors on the cell surface mediate T cell:B cell interaction for formation and maintenance of GC. But it remains to be elucidated whether SLAMF is expressed in circulating T follicular helper cells (cTfh). Objectives The aim of this study was to investigate the levels of SLAMF3 and SLAMF6 on cTfh and to analyze their association with disease activity in systemic lupus erythematosus (SLE) patients. Methods Blood samples were collected from 50 SLE patients, 24 Sjogren9s syndrome (SS) patients and 25 age- and sex-matched healthy controls (HCs). In this study, CXCR5, programmed cell death protein 1 (PD-1), and CD4 were used as markers to define cTfh in peripheral blood mononuclear cells (PBMCs). The expression levels of SLMAF3 and SLMAF6 on cTfh were compared to that of circulating B cell subsets by flow cytometry. Clinical features including disease activity and laboratory tests were analyzed according to expression of SLAMF3 and SLAMF6. Results Surface expression of SLAMF6 on CD4 T cells was significantly increased in SLE patients compared to SS patients (mean fluorescence intensity [MFI], mean ± SD: 1291±319 vs 1098±147, p=0.015) and HCs (1291±319 vs 1094±243, p=0.011). But there was no difference in expression of SLAMF3 on CD4 T cells between SLE patients and SS patients or HCs. SLAMF6 expressions on cTfh cells, identified as CD4+CXCR5+PD-1+, were significantly increased in SLE patients than in SS patients (1500±270 vs 1296±140, p=0.001) and HCs (1500±270 vs 1295±161, p=0.001). SLAMF6 expressions on cTfh cells had correlation with systemic lupus erythematosus disease activity index (SLEDAI) (Spearman9s rho=0.477, p=0.001), proteinuria (rho=0.321, p=0.030) and double strand DNA (rho=0.340, p=0.026) in SLE patients. Moreover, expression levels of SLAMF6 on cTfh cells were correlated with those of several B cell subsets including total B cells (CD19+), naive B cells (CD19+CD27-IgD+) and class-switched memory B cells (CD19+CD27+IgD-). But SLAMF6 expressions of B cell subsets were not correlated with disease activity. Conclusions Surface expression of SLAMF6 was increased in cTfh cells in patients of SLE and had correlation with disease activity. References T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure. Immunity. 2013;17;39(4):770–81. Choi JY, His-enHo J, Pasoto SG, et al. Circulating follicular helper-like T cells in systemic lupus erythematosus: association with disease activity. Arthritis Rheumatol. 2015;67(4):988–99. Zhang X, Lindwall E, Gauthier C, et al. Circulating CXCR5+CD4+helper T cells in systemic lupus erythematosus patients share phenotypic properties with germinal center follicular helper T cells and promote antibody production. Lupus. 2015;24(9):909–17. Disclosure of Interest None declared

Objective To investigate the impact of dose reduction of tumor necrosis factor inhibitor (TNFi) on radiographic progression in ankylosing spondylitis (AS). Methods One hundred and sixty-five patients treated with etanercept or adalimumab were selected from a consecutive single-center observational cohort based on the availability of radiographs at baseline and after two- and/or four-years of follow up. Radiographs were assessed by two blinded readers using the modified Stokes AS Spinal Score (mSASSS). Radiographic progression in patients treated with standard-dose TNFi (standard-dose group, n = 49) was compared with patients whose dosage was tapered during the treatment (tapering group, n = 116) using linear mixed models. Results Baseline characteristics between two groups were comparable except for higher BASDAI (7.1 vs. 6.3, p = 0.003) in the standard-dose group. At two years after the treatment, mean dose quotient (S.D.) of the tapering group was 0.59 (0.17). During follow up, rate of radiographic progression in overall patients was 0.90 mSASSS units/year. Radiographic progression over time between the two groups was similar at the entire group level. However, in the subgroup of patients with baseline syndesmophytes, progression occurred significantly faster in the tapering group after the adjustment for baseline status (1.23 vs. 1.72 mSASSS units/year, p = 0.023). Results were consistent when radiographic progression was assessed by the number of newly developed syndesmophytes (0.52 vs. 0.73/year, p = 0.047). Sensitivity analysis after multiple imputation of missing radiographs also showed similar results. Conclusion A dose tapering strategy of TNFi is associated with more rapid radiographic progression in AS patients who have syndesmophytes at baseline.

Polyarteritis nodosa (PAN) has a broad spectrum of clinical presentation, since it affects small and medium-sized muscular arteries with microaneurysm formation, aneurysmal rupture with hemorrhage, thrombosis, and, consequently, organ ischemia or infarction. Although skeletal muscle involvement is well documented in patients with PAN, it can mimic more common diseases, and cause confusion and delays in diagnosis. PAN muscular involvement may have limited or early systemic forms with a benign course and excellent clinical response to corticosteroid therapy. Herein, we describe the clinical course and outcome of four unusual cases of PAN manifested by acute onset of pain and pitting edema in both lower extremities; in addition, we reviewed the relevant literature. (J Rheum Dis 2017;24:48-54)

Background Although dose tapering of tumour necrosis factor (TNF)-blockers in ankylosing spondylitis (AS) showed a comparable clinical efficacy with favourable safety and cost in some studies, there has been no investigation comparing the radiographic progression of patients with tapering regimen versus patients with standard-dose treatment. Objectives To investigate the impact of dose reduction of TNF-blockers on radiographic progression in the AS over 4 years Methods One hundred sixty five patients treated with etanercept or adalimumab were selected from single-centre, prospective observational cohort based on the availability of cervical and lumbar radiographs at baseline and after 2 and/or 4 years of the treatment. Radiographs were scored using modified Stokes AS spinal score (mSASSS) by two independent readers. Radiographic progression of patients treated with standard-dose (standard-dose group, n=49) was compared with that of patients who tapered the dosage during the TNF-blocker treatment (tapering group, n=116) using linear mixed models. Results Demographic and clinical factors at baseline between two groups were not significantly different except for higher initial BASDAI (7.1 vs. 6.3, p=0.003) in the standard-dose group. Baseline mSASSS (SD) of the standard-dose group and the tapering group were 17.3 (17.7) and 11.0 (16.0), respectively (p=0.059). At 2 years after the treatment, mean dose quotient (SD) of the tapering group was 0.59 (0.17) and time to first dose reduction (SD) was 36.6 (28.4) weeks. During the observation period, the rate of radiographic progression in the overall patients was 0.90 mSASSS unit/year. Rate of progression was significantly higher in patients with longer disease duration (≥10 years), elderly patients (≥40 years old), smokers, or patients with a hip involvement at baseline. Radiographic progression over 4 years between two treatment strategies was similar after the adjustment for baseline status. However, in the subgroup of patients who have syndesmophytes at baseline, it occurred significantly faster in the tapering group (1.30 mSASSS unit/year vs. 1.82 mSASSS unit/year, p=0.008) (figure). This result was concordant when radiographic progression was assessed by the development of new syndesmophytes (0.52/year vs. 0.73/year, p=0.047). Conclusions Dose tapering strategy of TNF-blockers is associated with more rapid radiographic progression in AS patients who have syndesmophytes at baseline. References Zavada J, et al. A tailored approach to reduce dose of anti-TNF drugs may be equally effective, but substantially less costly than standard dosing in patients with ankylosing spondylitis over 1 year: a propensity score-matched cohort study. Ann Rheum Dis 2016;75:96–102. Disclosure of Interest None declared

Background Interstitial lung disease (ILD) is associated with a significant morbidity and mortality in systemic sclerosis (SSc). Many studies have reported the association between human leukocyte antigen (HLA) alleles and increased risk of SSc, but the associated between ILD in SSc and HLA alleles remains unclear. Objectives The aim of this study was to investigate the association of HLA class I and HLA class II with ILD in Korean SSc cohort. Methods A total of 170 SSc patient (105 SSc patients with ILD and 65 SSc patients without ILD) were enrolled at Seoul National University Hospital from 1988 to 2014. Two hundred one healthy participants from Korean Marrow Donor Program (KMDP) were recruited as controls. Demographic information, clinical skin subset (limited vs. diffuse), SSc-specific autoantibodies (anti-topoisomerase I (ATA), anti-centromere (ACA), anti-ribonucleoprotein (RNP)), and internal organ involvement (ILD, pulmonary arterial hypertension, gastrointestinal, renal involvement) of the enrolled patients were characterized. ILD were diagnosed based on the findings of the chest computed tomography. HLA-A, -B, -C,-DQB1,-DRB1, and -DPB1 typing were performed PCR amplification with directly sequencing from extracted genomic DNA. Results HLA-B*52:01, C*12:02, DRB1*15:02, DPB1*09:01, and DPB1*13:01 alleles were more frequent in SSc patients with ILD than healthy controls. However, the frequencies of these genes did not differ between SSc patients with and without ILD (Table). ATA positive SSc was associated with HLA-B*52:01, C*12:02, DRB1*15:02, DPB1*09:01, and DPB1*13:01 alleles compared to ATA negative SSc and DPB1*09:01 showed the highest odds ratio for ATA (OR =23.08). Conclusions SSc patients with ILD have several specific HLA genes compared with healthy controls and the frequencies of these HLA genes were significantly higher in ATA-positive SSc as well. Therefore, ATA positivity and ILD are associated with ceratin HLA class I and II in SSc patients. References Zhou X, Lee JE, Arnett FC, Xiong M, Park MY, Yoo YK, et al. HLA-DPB1 and DPB2 are genetic loci for systemic sclerosis: a genome-wide association study in Koreans with replication in North Americans. Arthritis Rheum 2009;60:3807–14. Disclosure of Interest None declared

Background Adult onset of Still9s disease (AOSD) is a systemic inflammatory disease characterized by fever, arthritis, salmon pink rash and elevated serum inflammatory markers. The classical fever of AOSD is intermittent with a quotidian or double-quotidian pattern. However, a significant subset of AOSD exhibits persistently high fever with little temperature fluctuation. It remains unclear as to whether the certain fever pattern is associated with specific clinical manifestations. Objectives To investigate the association between fever pattern and clinical characteristics in patients with AOSD. Methods A total of 70 patients with AOSD who were treated as inpatient at Seoul National University Hospital from 2004 through 2015 were enrolled. Patients were grouped based on the fever curves on days 2, 3 and 4 using hierarchical clustering. The clinical and laboratory characteristics of the groups were compared. Results 70 patients were divided into 2 groups based on the fever curves. The group 1 with 14 patients had a higher mean temperature (38.1±0.4°C vs. 37.2±0.5°C, p Group 1 tended to be younger (38.4 ± 14.7 years vs. 46.1 ± 17.6 years, p=0.141) (Figure). Fever, arthritis, arthralgia and rash did not differ between them. However, group 1 tended to have more pericardial and lung involvement (42.9% v.s 23.2%, p=0.181). Group 1 had significantly lower platelet count (198,900 ± 68,000/μl vs. 312,900 ± 156,900/μl, p=0.0001), higher LDH (816.6 ± 376.4 IU/L vs. 477.5 ± 327.1 IU/L, p=0.002), higher mean ferritin level (27,004.1 ± 48,891.5 ug/mL vs. 6,852 ± 10,628.2 ug/mL, p=0.072) and d-dimer (9.5 ±7.9 ug/mL vs 3.3 ± 3.4 ug/mL) as compared to group 2, whereas white blood cell count, hemoglobin levels, CRP levels did note differ between the both groups. Group 1 tended to require longer time to a clinical remission (455.5 ± 850 days vs. 9.4 ± 115.7 days, p=0.137). Conclusions The unbiased analysis of fever reveals the presence of at least 2 distinctive fever patterns in AOSD. Spiking fever with higher daily variation was more often associated with higher inflammatory markers and coagulopathy and required longer treatment. Thus, fever pattern might be a prognostic factor in AOSD and AOSD patients with spiking fever might need more intensified treatment. Disclosure of Interest None declared

Background Polymyositis (PM) and dermatomyositis (DM) is known to be associated with certain HLA alleles in several ethnic groups including Caucasians, African-Americans, and the Japanese. Objectives To investigate the profile of HLA class II alleles in Korean patients with PM and DM Methods Sequencing based genotyping for HLA-DRB1 and -DPB1 was performed in 140 Korean patients with DM (n=104) or PM (n=36) and in 207 healthy controls. Associations of each HLA-DR or -DP allele with myositis or clinical subsets of myositis were examined. Results HLA-DRB1*14:54 (odds ratio [95% confidence interval] 1.05 [1.01-1.09]), -DRB1*15:02 (2.44 [1.03-5.81]), -DRB1*16:02 (1.04 [1.00-1.07], and -DPB1*09:01 (2.44 [1.03-5.81]) were found to be susceptibility alleles while HLA-DRB1*14:01 (0.93 [0.90-0.97]) and -DRB1*15:01 (0.38 [0.18-0.79]) to be protective alleles for inflammatory myositis (Table 1). In DM, HLA-DRB1*15:02 (3.14 [1.30-7.62]) and -DPB1*09:01 (2.87 [1.17-7.05]) carriers were more frequent while HLA-DRB1*14:01 (0.93 [0.90-0.97]), -DRB1*15:01 (0.30 [0.12-0.74]), and -DPB1*04:02 (0.44 [0.20-0.94]) carriers were less frequent than controls. In PM, HLA-DRB1*14:03 (6.52 [1.78-23.81]), and -DRB1*14:54 (1.13 [1.00-1.23]) carriers were more frequently observed. When PM and DM were compared, HLA-DRB1*14:03 carriers were more frequently observed in PM (5.43 [1.23-24.02]). When the association between each allele and clinical subsets was examined, patients with interstitial lung disease (ILD) carried HLA-DRβ1*04:03 (6.34 [1.35-29.76]), -DRβ1*07:01 (0.22 [0.08-0.64]), -DRβ1*09:01 (0.16 [0.05-0.60]) -DRβ1*12:02 (2.91 [1.16-8.01]) DRβ1*15:01 (0.10 [0.01-0.80]), -DPβ1*14:01 (8.90 [1.08-73.21]), and -DPβ1*17:01 (0.11 [0.01-0.92]) more frequently than patients without. DM patients with ILD showed higher frequency of HLA-DRβ1*04:05 than DM patients without ILD (4.68 [1.24-17.74]). Other associations included dysphagia with HLA-DRβ1*08:02 (6.73 [1.51-30.00]), -DRβ1*14:54 (5.19 [1.09-24.57]), and -DPβ1*03:01 (5.19 [1.09-24.57]), arthralgia with HLA-DRβ1*03:01 (4.79 [1.21-18.98]) and -DPβ1*02:01 (2.30 [1.10-4.82]), and mechanic9s hand with HLA-DRB1*08:03 (3.25 [1.12-9.45]) and -DRB1*12:02 (5.04 [1.66-15.29]). Regarding skin rashes, heliotrope rash was associated with HLA-DRβ1*09:01 (2.98 [1.05-8.46]) and -DPβ1*05:01 (0.41 [0.18-0.87]), Gottron9s papules with HLA-DRβ1*14:05 (8.77 [1.07-72.17]), -DPβ1*02:01 (2.29 [1.11-4.73]), -DPB1*02:02 (0.086 [0.01-0.67]), and -DPB1*05:01 (0.41 [0.20-0.85]), and shawl sign with HLA-DRB1*14:05 (4.67 [1.15-18.99]) and -DPB1*14:01 (4.67 [1.15-18.99]). Cancer development was associated with HLA-DRB1*12:01 (7.25 [1.65-31.89]) and -DRB1*13:02 (0.81 [0.74-0.88]). No HLA-DRB1 or -DPB1 allele was found to be associated with anti-Jo1 antibody. Conclusions Korean patients with inflammatory myositis showed a unique profile of HLA-DR and -DP alleles compared with other ethnic groups. Alleles associated with disease susceptibility were different between PM and DM. Clinical subsets, particularly ILD, showed different immunogenetic backgrounds. Disclosure of Interest None declared

Background Chemokines are multifunctional mediators that control leukocyte recruitment into the inflammatory sites and enhance immune responses. It remains to be investigated which chemokines are important in Behcet9s disease (BD). Objectives The objective of this study was to investigate serum levels of neutrophil and lymphocyte chemoattractants in BD patients and its association with disease activity and symptoms. Methods We collected sera from patients with BD (n=64) and age-, sex matched healthy controls (n=21). Serum levels of chemokines were assayed for the neutrophil chemoattractants (CXCL1 and CXCL8) and lymphocyte chemoattractants (CXCL9, CXCL10, CXCL12, CXCL13 and CXCL16) by using a multiplex assay. Behcet9s disease current activity form (BDCAF) and symptoms were evaluated at the time of blood collection. Results Serum levels of CXCL8, CXCL10 and CXCL12 were significantly higher in the BD patients than in healthy controls (p Conclusions Serum levels of CXCL8, CXCL10 and CXCL12 were significantly higher in the BD patients than in healthy controls. CXCL10 levels were correlated with number of EN in BD patients. Disclosure of Interest None declared

Background Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis of the skin and internal organs. Although interstitial lung disease (ILD) is a major cause of death in this disease, pulmonary function remains stable in a subset of SSc patients with ILD without any treatment. However, clinical characteristics in this subset of patients are not well characterized. Objectives To investigate clinical characteristics of SSc patients with ILD who do not require additional immunosuppressive treatment for ILD. Methods A total of 151 SSc patients with ILD who received medical care at Seoul National University Hospital between 1978 and 2013 were enrolled in this study. ILD was diagnosed based on chest computed tomography (CT) and the extent of ILD was semi-quantitatively graded into 1-4 (grade 1, 75% of lung involvement). Detailed baseline clinical characteristics were obtained from medical record review. Mortality was ascertained from medical record review and data from the Statistics Korea. After confirming survival benefit of untreated group versus treated group with Kaplan Meier analysis, clinical characteristics of untreated group were defined by comparison with treated group (chi-square test or Student t-test). Sensitivity test was performed by proving survival benefit of patients with the defined characteristics in the untreated group (log-rank test). Results The mean (standard deviation) age at diagnosis of 151 patients was 48.7 (12.9) years and 88.7% were women. Eighty (52.9%) patients did not receive immunosuppressive treatment for ILD, while 71 (47.0%) patients required immunosuppressive treatment, which includes cyclophosphamide (n=46), azathioprine (n=8), glucocorticoids (n=14) and others (n=3). Interestingly, median survival of non-treatment group was significantly better than treatment group during the follow-up of 1300.80 person-years (p=0.029 by log-rank test). Compared with treatment group, non-treatment group had higher baseline predicted % of forced vital capacity (FVC, 79.2±16.8% vs. 68.0±18.2, p Conclusions Watch and wait approach may be applied to patients with SSc-associated ILD with minimal pulmonary infiltrates on CT scan and absence of pulmonary arterial hypertension at ILD diagnosis. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3686

Background Interstitial lung disease (ILD) is the leading cause of death in patients with systemic sclerosis (SSc). Treatment with cyclophosphamide (CYC) for 1 year has been shown to preserve pulmonary function. However, long-term efficacy and safety of CYC treatment for more than 1 year remains to be known. Objectives To investigate efficacy and tolerability of long-term CYC treatment in SSc patients with ILD. Methods All of the SSc-associated ILD patients who have been treated with CYC for more than 1 year at Rheumatology clinic of Seoul National University Hospital between 1978 and 2013 were enrolled. The information on clinical characteristics and pulmonary function test results were obtained from medical record review. Chest computed tomography (CT) was reviewed by a radiologist and classified into 4 grades depending on the extent of lung involvement. Mortality data were obtained from medical record or mortality record from Statistics Korea. Results A total of 32 SSc patients with ILD were treated with CYC for more than 1 year with the mean treatment duration of 28.0 months (range: 12.0- 70.5 months). The mean age at diagnosis was 47.5±9.4 years and women were dominant at 84.4%. The mean functional vital capacity (FVC) at baseline was 66.0±16.0% of predicted. At baseline 18 (64.3%) patients had CT grade of 2 or more. After mean (standard deviation) follow up period of 4.1 (3.1) years, FVC remained stable with the mean increase of 2.3 (2.5) % (P=0.365, by paired t test). Furthermore, the degree of pulmonary involvement on CT did not progress. Six patients died during the follow-up; pneumonia (n=1), pulmonary hypertension (n=1), subdural hemorrhage (n=1), heart failure (n=2) and malignancy (n=1). Adverse events during CYC treatment included severe infection (n=4), cytopenia (n=4), hemorrhagic cystitis (n=1) and alopecia (n=3). Conclusions Prolonged treatment with CYC for more than 1 year is associated with stabilization of ILD in the respect of pulmonary function and extent of lung involvement on CT. Long-term maintenance treatment with CYC may be an option to treat severe ILD in SSc patients. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4302

Background Interstitial lung disease (ILD) is the most common cause of mortality in patients with dermatomyositis (DM). Cyclosporine has been reported to improve clinical outcome in some patients with DM-associated ILD. Objectives To investigate the benefit of early introduction of cyclosporine on the survival of patients with DM-associated ILD. Methods All the patients with DM-associated ILD, who were treated with cyclosporine at Seoul National University Hospital (SNUH) and Seoul National University Bundang Hospital (SNUBH) between 1990 and 2013, were enrolled. Enrolled patients were diagnosed with DM according to Bohan-Peter9s classification criteria (n=28) or with clinically amyopathic dermatomyositis (CADM) according to Sontheimer9s classification criteria (n=19). ILD was diagnosed based on the typical findings on computed tomography (CT) and relevant respiratory symptoms or signs. Kaplan-Meier survival analysis was applied to compare overall mortality rates between patients who took cyclosporine as the initial treatment and those as the delayed treatment. Cox regression analysis was used to estimate the benefit of early treatment with cyclosporine after adjusting confounding characteristics. Results Among the 47 patients who were diagnosed with DM-associated ILD, 16 patients (34.04%) received cyclosprorine initially after diagnosis and 31 patients (65.96%) received cyclosporine after the trial of other immunosuppressants such as corticosteroids, cyclophosphamide or azathioprine. The mean time of follow-up was 43.57 person-years in initial treatment group and 76.23 person-years in delayed treatment group. The mortality rate was significantly lower in the initial treatment group than the delayed treatment group (0.02 person-years vs 0.18 person-years, p=0.0092 by log-rank test). The two groups did not differ in regard to age, sex, duration of disease, presence of autoantibodies, degree of dyspnea at initial visit, initial requirement of oxygen supplement, functional vital capacity (FVC) and diffusion capacity (DLCO) on pulmonary function test (PFT) and the presence of malignancy. Only the proportion of patients with CADM was higher in the initial treatment group than in the delayed treatment group (62.53% vs 29.03%, p=0.027). Survival benefit in the initial cyclosporine treatment remained significant even after adjusting for the CADM status (HR 0.075, 95% CI 0.009 - 0.603, p=0.015 by Cox-regression analysis). Conclusions This study showed significant survival benefit of initial cyclosporine treatment in patients with DM-associated ILD. A randomized controlled study is warranted to clearly demonstrate the therapeutic benefit of early use of cyclosporine in this potentially fatal disease. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3718

Background Interstitial lung disease (ILD) is a common cause of death in patients with dermatomyositis (DM). Especially, patients with clinically amyopathic DM (CADM) have a worse outcome due to ILD which is often refractory to corticosteroids. Lung involvement as an additional target of inflammation increases the total inflammatory burden in patients with DM. Objectives To investigate whether erythrocyte sedimentation rate (ESR) elevation is associated with ILD and a worse prognosis in patients with DM. Methods All patients with DM including CADM receiving clinical care in our institution from January 2004 through June 2013 were enrolled. Patients who had shortness of breath or abnormal finding on chest radiograph underwent a high resolution computed tomography (HRCT) and pulmonary function test (PFT). ILD was diagnosed when HRCT showed typical findings compatible with ILD. Results A total of 114 DM patients were enrolled in this study. The mean age of patients at diagnosis was 49.4±12.3 years. 69.3% were female. The mean follow-up duration was 32.3±29.3 months. ILD was present in 53 (46.5%) patients. Among 28 patients with CADM, 14 (50%) had ILD. The levels of ESR were significantly higher in patients with ILD than those without ILD (49.9±23.3 vs. 34.4±24.1 mm/hr, p=0.001). The difference was more profound between the CADM patients with ILD and those without ILD (56.3±23.8 vs. 25.4±22.9 mm/hr, p=0.002). The ESR levels were inversely correlated with the forced vital capacity (r=−0.238, p=0.036) and diffusing capacity of carbon monoxide (r=−0.334, p=0.004). Further, the patents with baseline ESR ≥30mm/hr had a worse survival as compared to those with ESR Conclusions The ESR elevation at the time of DM diagnosis is associated with pulmonary impairment and a poor outcome in patients with DM. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3276

Relapsing polychondritis is an episodic, systemic inflammation of the cartilage with unknown autoimmune etiology. It leads to the destruction of cartilaginous structures of the ear, eye, nose, respiratory tract, joints, skin, and heart valve, and its presented symptoms are diverse. It can be improved mainly by corticosteroid or immunosuppressive agents. Recently, the use of biologic agents (TNF inhibitors, rituximab, tocilizumab et al) was reported from abroad. However, there is no reported case of relapsing polychondritis, which is treated by biologic agents in Korea. We report this first case of refractory relapsing polychondritis, which was improved with a treatment of Infliximab.

Correspondence to Eun Young Lee, M.D., Ph.D. Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea Tel: +82-2-2072-0852, Fax: +82-2-762-9662, E-mail: elee@snu.ac.kr Copyrightc 2013 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 피부근염에 동반된 혈전혈소판감소자색반병에서 리툭시맙 치료 1예

Objective. To assess the efficacy and safety of rituximab (RTX) on disease activity and muscle strength in patients with inflammatory myopathies refractory to conventional therapy. Methods. Four inflammatory myopathy patients who had been refractory to glucocorticoids, one or more immunosuppressive therapies and intravenous immunoglobulin were treated on an open-label basis. Each patient received two 500 mg doses of RTX 2 weeks apart in one cycle. In one patient who did not respond after the first cycle of RTX, the infusion schedule was modified by the physician. We measured muscle enzyme including CPK, LDH and assessed muscle strength individually to evaluate RTX response. Additionally anti-CD19 antibody was measured. Results. Three patients responded to the first cycle of RTX treatment with improvements in muscle enzyme and muscle strength, and then maintained physical function over the duration of several infusion cycles. In one patient, muscle enzyme did not decrease after the first cycle of RTX, and a high dose glucocorticoid was given. After modifying the treatment schedule with monthly RTX infusion, his muscle enzyme level and muscle strength improved. Anti-CD19 antibody decreased after RTX generally, but responses were variable. Herpes zoster infection occurred in two patients. Conclusion. Rituximab may be a therapeutic choice in refractory inflammatory myopathy. However a further trial is needed to confirm the efficacy and prove the safety.

Peripheral nervous system dysfunction is a rare complication in Henoch-Schonlein purpura, but it tends to recover spontaneously without treatment. A 78-year-old man who had ankylosing spondylitis presented with Henoch-Schonlein purpura associated with progressive sensorimotor polyneuropathy. He was diagnosed with chronic inflammatory demyelinating polyneuropathy, which did not improve despite intravenous immunoglobulin therapy. We describe a case of Henoch-Schonlein purpura, accompanied by chronic inflammatory demyelinating polyneuropathy in a patient with ankylosing spondylitis. (Korean J Med 2012;83:538-542)