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Purpose: Hydroxychloroquine is widely used for long-term treatment of rheumatic diseases, but the drug can trigger irreversible toxic retinopathy. We studied the prevalence of, and the risk factors for, hydroxychloroquine retinopathy in rheumatic patients with dry eye symptoms and we introduce a representative case.Methods: We retrospectively studied a cohort of 133 rheumatological patients who had taken hydroxychloroquine for at least 12 months and who visited our ophthalmology clinic with dry eye symptoms from April 2016 to December 2021. Hydroxychloroquine retinopathy was diagnosed via fundus photography, spectral-domain optical coherence tomography, the Humphrey visual field test, autofluorescence fundus photography, and multifocal electroretinography. The principal outcomes were the prevalence of retinopathy at the first screening and the risk factors.Results: Of the 133 patients, hydroxychloroquine retinopathy was diagnosed in seven (5.2%) at the first screenings. The Mann-Whitney U-test revealed that older age; higher daily doses; longer dosing duration; greater cumulative doses; and higher daily and cumulative doses/kg were statistically significant in terms of retinopathy development. On multivariate logistic regression analysis, the average daily dose (odds ratio [OR] 6.02; 95% confidence interval [CI] 1.64-22.12, 100 mg increments) and duration of dosing (OR 3.39; 95% CI 1.19-9.62, 5 years increments) remained statistically significant (P = 0.021, P = 0.007 respectively)Conclusions: Ophthalmologists should enquire about any history of hydroxychloroquine therapy, and perform a retinal examination, when encountering dry eye in patients with rheumatic disease. Early detection of hydroxychloroquine retinopathy followed by discontinuation of hydroxychloroquine is the only way to prevent visual loss. High daily drug doses and long dosing durations are risk factors for retinopathy.

Little is known about the nature of relationships between sleep disturbance and influencing factors in rheumatoid arthritis. The purpose of this study was to identify factors that influence sleep disturbance and to evaluate mediating effects of depression on sleep disturbance. A nonexperimental, descriptive, correlational study design was adopted. One hundred patients with rheumatoid arthritis were recruited. Inflammatory status and levels of pain, fatigue, functional disability, depression, and sleep disturbance were measured. The factors that directly influenced sleep disturbance were gender, rheumatoid arthritis duration, serum C-reactive protein level, fatigue, and depression. Depression was found to have mediating effects on the relationships between sleep disturbance and arthritis symptoms. Pain, fatigue, and depression were found to have significant direct or indirect impacts on sleep disturbance. Our findings may improve understanding of sleep disturbance and aid the development of effective nursing management strategies for patients with rheumatoid arthritis suffering from sleep disturbance.

BACKGROUND Ankylosing spondylitis (AS) is strongly associated with the human leukocyte antigen (HLA) B27 haplotype. In regions where conventional polymerase chain reaction for HLA typing is available for antigens such as HLA B27 or HLA B51, it is common to perform the HLA B27 test for evaluation of AS. While HLA B27-associated clustered occurrences of AS have been reported in families, we report the first case series of HLA B51-related occurrences of AS in a family. CASE SUMMARY A father and his daughters were diagnosed with AS and did not have the HLA B27 haplotype. Although they were positive for HLA B51, they exhibited no signs of Behçet’s disease (BD). Of the five daughters, one had AS, and three, including the daughter with AS, were positive for HLA B51. The two daughters with the HLA B51 haplotype (excluding the daughter with AS) exhibited bilateral grade 1 sacroiliitis, whereas the daughters without the HLA B51 haplotype did not have sacroiliitis. Thus, this Korean family exhibited a strong association with the HLA B51 haplotype and clinical sacroiliitis, irrespective of the symptoms of BD. CONCLUSION It is advisable to check for HLA B51 positivity in patients with AS/spondyloarthropathy who test negative for HLA B27.

We aimed to investigate how systemic bone metabolism was affected after 1 year of treatment with tumour necrosis factor (TNF) inhibitors in rheumatoid arthritis (RA) patients.A total of 29 seropositive RA patients not treated for osteoporosis were enrolled and TNF inhibitors were administered for a year. Bone mineral density (BMD) at the lumbar spine, femur neck, and total hip was measured at baseline and 12 months after anti-TNF treatment. Blood samples were collected at baseline and 6 and 12 months after anti-TNF treatment and osteoclasts were cultured on bone slices. Weight was the strongest factor influencing systemic bone loss. Patients were categorised into two groups: obese (body mass index (BMI) ≥25 kg/m2) and non-obese (BMI25 kg/m2).All patients showed decreased BMD at all sites. The obese group showed relatively little change in BMD, although the non-obese group showed significant decreases in BMD at all sites after 1 year of treatment with TNF inhibitors. Resorption pits created by osteoclasts decreased at 6 months and increased at 12 months in the non-obese group, while the obese group presented with steadily decreasing sizes of resorption pits at all-time points. Levels of receptor activator of nuclear factor kappa B ligand were significantly decreased at 12 months compared to baseline in the obese group, while they were increased in the non-obese group.One year of treatment with TNF inhibitors failed to halt systemic bone loss in RA patients, but obesity may have protective effects against bone loss.

Epidemiological studies on inflammatory myopathies (IMs) show widely variable results, and studies on Asians are lacking. Despite emerging interest in the cardiovascular disease (CVD) risk associated with IMs, the prevalence of CVD in IM patients and its impact on mortality remain unclear. We conducted a nationwide, population-based study on the incidence, mortality, and associated major CVD events of IMs in the Republic of Korea over 11 years. Using the nationwide, population-based National Health Insurance claims database and the Rare Intractable Disease registration programme, we estimated incidence, mortality, and CVD occurrence. Survival was examined using the Kaplan–Meier method. Mortality rate in IMs with CVD was analysed by Cox proportional hazards regression. There were 3014 incident cases, 640 of whom died during the study period. The mean annual incidence was 7.16/106. Dermatomyositis (DM) and polymyositis (PM) had 5 year survival rates of 76.8% and 79.3%, respectively. Cardiovascular events occurred in 155 patients and 40.6% of IM patients with CVD died. Acute myocardial infarction in men had the highest risk of any CVD event in both DM [standardized incidence ratio (SIR) 4.2, 95% confidence interval (95% CI) 2.4–7.2] and PM (SIR 3.5, 95% CI 1.8–7.0). Haemorrhagic stroke had the highest hazard ratio (HR) in both DM (HR 2.31, 95% CI 1.13–4.70) and PM patients (HR 2.10, 95% CI 1.03–4.27) compared with the general population with CVD. We found persistently low incidence, poor survival, and high major CVD incidence in IMs, and increased mortality in IMs with CVD.

As the prevalence of gout and hyperuricemia increases, the comorbidities of gout and hyperuricemia have become a public health burden. In particular, risks of cardiovascular disease (CVD)-related complications are increasing. However, a few guidelines exist for the management of hyperuricemia. This cross-sectional study aimed to investigate the association of serum uric acid with CVD risk in the general population of Korean adults. We examined cross-sectional data from the first and second years of the seventh Korea National Health and Nutrition Examination Survey 2016&ndash, 2017. Among 16,277 participants, 8781 were analyzed. We estimated the CVD risk using a 10-year CVD risk score prediction formula. There was a significant association of serum uric acid with 10-year CVD risk scores after adjusting for physical activity, body mass index, serum creatinine, and alcohol consumption in both sexes (p &lt, 0.001). In the fitted fractional polynomial model, an approximate U-shaped association between serum uric acid levels and 10-year CVD risk scores was found in men. At the serum uric acid level of 6.9 mg/dL, the CVD risk was lowest. An approximate J-shaped association between serum uric acid levels and 10-year CVD risk scores was found in women. Our study showed that hyperuricemia was associated with an increased CVD risk. Hypouricemia was also associated with an increased CVD risk in men. We, therefore, recommend proper management of uric acid levels in the general population to reduce CVD risks.

Osteoarthritis (OA) has a multifactorial etiology that includes oxidative stress. Oxidative balance score (OBS) is a well-known indicator of oxidative stress. However, the association between OBS and OA has not been assessed. Thus, this study aimed to investigate the associations of OBS with OA and quality of life (QOL) in patients with OA. By using data from the Korea National Health and Nutrition Examination Survey VI, patients previously diagnosed and/or treated by a physician were considered to have OA regardless of the affected joints. The control group was defined as participants without any form of chronic arthritis. OBS was calculated by combining 10 pro-oxidant and antioxidant factors through a baseline nutritional and lifestyle assessment. Higher OBS scores indicated a predominance of antioxidant exposure. Multivariable logistic regression was used to estimate the adjusted odds ratios (ORs) for OA, and the EuroQoL five-dimensional questionnaire (EQ5D) was used in patients with OA after adjusting for demographic factors and comorbidities. Among the 14,930 participants, 296 patients with OA, and 1,309 controls were included in the analysis. In the age- and sex-adjusted model, the OR of the total OBS for OA was significant. In the full model adjusted for age, sex, education, income, and comorbidities, the total OBS for OA was not significant. Only the non-dietary pro-oxidant OBS had a significant inverse association with OA. The patients with OA who had a high EQ5D score had a higher total OBS than those with a low EQ5D score. The OR of the total OBS for a high EQ5D score was 1.14 in the multivariable logistic regression model. As we analyzed the OBS as a categorical variable (reference = Q1), the ORs of the Q2, Q3, and Q4 (highest) total OBS were 1.43, 2.71, and 2.22, respectively. In the fully adjusted model, the total OBS was not associated with OA. However, a positive association was observed between the total OBS and QOL in the patients with OA, indicating that antioxidative status was associated with better QOL in patients with OA.

Background Patients with ankylosing spondylitis (AS) have a higher risk of cardiovascular disease. Atherosclerosis is a main pathological process of cardiovascular disease and calcified plaque is a characteristic feature of atherosclerosis. Inflammation plays a potential role in vascular calcification. There is no previous study revealing the mechanism of vascular calcification in AS. Objectives We investigated the relationship between vascular calcification and inflammation in patients with AS. Methods Sixteen male patients aged over 20 years with AS were enrolled. They fulfilled the modified New York criteria and each of their ankylosing spondylitis disease activity score was more than 2.1. Sex and age matched nine healthy controls were also recruited. Mouse MOVAS (American Type Culture Collection, ATCC®, CRL-2797TM) vascular smooth muscle cells were stabilized in maintenance medium for 24 hours. Then the amount of serum equivalent to 10% of maintenance medium from subjects was added and cells were stimulated for another 72 hours. We exchanged this medium with calcification medium every third day and cells were cultured for another 11 days. After 2 weeks, cells were stained with Alizarin Red S and the optical density (OD) was measured while being compensated by cell viability. For Western blotting, cells were stabilized for 24 hours and stimulated for another 72 hours through the same procedure as that of Alizarin Red S staining. Then we measured the level of protein expression in PPAR-gamma, beta-catenin, TNF-a, interleukin (IL)-23, and MMP7. Results The level of OD of MOVAS cells treated with serum from AS patients (19.503 ± 6.422, mean ± SD) was significantly higher than that from controls (12.724 ± 5.746) (P=0.027, Mann-Whitney test). The level of MMP7 expression of MOVAS cells treated with serum from AS patients (1.921 ± 0.702) was significantly higher than that from controls (0.779 ± 0.191) (P=0.000, Mann-Whitney test). The level of beta-catenin expression of MOVAS cells treated with serum from AS patients (1.292 ± 0.356) was significantly higher than that from controls (0.887 ± 0.310) (P=0.025). There was negative correlation between PPAR-gamma and TNF-a (rho=-0.762, p=0.028, Spearman rank correlation coefficient), and between PPAR-gamma and IL-23 (rho=-0.601, p=0.039); positive correlation between MMP7 and TNF-a (rho=0.833, p=0.010), and between MMP7 and IL-23 (rho=0.797, p=0.002). Conclusion Serum from AS patients showed increased calcification of vascular smooth muscle cells than serum from controls. The level of vascular calcification marker from vascular smooth muscle cells treated with serum from AS patients was significantly higher than that from controls. There were negative relationship between inflammatory markers and inhibitory marker of vascular calcification but positive relationship between inflammatory markers and stimulatory marker of vascular calcification. These findings suggest that vascular calcification by inflammation could be an important cause of cardiovascular disease in AS patients. Acknowledgement This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education (NRF-2017R1D1A1B03030825) Disclosure of Interests Seung Yun Lee: None declared, Seong-Ryul Kwon: None declared, Su-Ah Yoon: None declared, Kyong-Hee Jung: None declared, Won Park Consultant for: Celltrion, Inc, Shin-Goo Park: None declared, Mie Jin Lim: None declared

목적: 저자들은 골다공증 치료를 받지 않고 있는 류마티스관절염 환자들에서 골다공증의 위험 요인과 골밀도 검사의 적절한 간격을 알아보고자 하였다. 방법: BMD 측정을 두 번 이상 실시받고, 골다공증을 진단받지 않은 40세 이상의 류마티스 관절염 환자 511명을 후향적으로 조사하였다. 이들을 기저치 BMD가 정상(T-score >-1), 경증 골감소(-1 ≥ T-score > -1.5), 중등도 골감소(-1.5 ≥T-score > -2), 중증 골감소(-2 ≥ T-score > -2.5)의 4군으로 분류하였다. 각 군에서 10%의 환자가 골다공증 또는 골절이 발생되는 기간을 추정하였다. 결과: 총 관찰 기간은 2,214인-년이었고 평균 4.3인-년이었다. 각 군에서 10%의 환자가 골다공증 또는 골절이 발생되는기간은 정상군은 10년 이상, 경증군은 4.3년, 중등도군은 2.5년, 중증군은 1.5년이었다. 결론: 초기 BMD 측정의 T-score가 추후 골다공증이 발생의 가장 강력한 인자였다. 그러므로 류마티스 관절염 환자에서 초기 BMD의 결과에 따른 다음 검사의 적절한 간격 조정이 필요하다.

Objective The full effect of anti-TNF therapy on new bone formation is still in debate in spondylitis fields. We sought to obtain circulating osteoblast-lineage cells in peripheral blood from ankylosing spondylitis (AS) patients and healthy control subjects, and to evaluate the effect of TNF-α on osteoblastogenesis in patients with AS before and after infliximab therapy. Methods Sixteen male patients with AS slated for infliximab therapy and 19 controls were recruited. We cultured osteoblast-lineage cells from peripheral blood and measured the optical density of their alizarin red S staining. We also measured serum P1NP (procollagen type 1 N-terminal propeptide) as an early osteoblast differentiation marker, osteocalcin as a late osteoblast differentiation marker, and inflammatory markers. Results There were significantly more circulating osteoblast-lineage cells in patients than in controls. The number of circulating osteoblast-lineage cells and optical density of Alizarin S staining decreased 14 weeks after infliximab therapy (p=0.028); serum level of P1NP decreased, but that of osteocalcin increased (p=0.002 and 0.007 respectively). Conclusion Our data reveals first, TNF-α stimulates osteoblastogenesis before infliximab therapy in patients with AS; second, infliximab therapy resolves early inflammation, but allows mature osteoblast differentiation in late inflammation. The culture of osteoblast-lineage cells in peripheral blood may be a candidate for a new modality with which study spondylitis and other autoimmune diseases. Funding This study is supported by grant from the National Research Foundation of Korea (NRF-2014R1A1A2058007) to Dr. S-R Kwon

The object of this study was to evaluate the effect of uric acid lowering therapy in reducing the new development of comorbidities and the frequency of acute attacks in gout patients. We retrospectively reviewed patients who were diagnosed to have gout with at least 3 yr of follow up. They were divided into 2 groups; 53 patients with mean serum uric acid level (sUA)

The full effect of anti-TNF therapy on new bone formation is still in debate in spondylitis fields. We sought to obtain circulating osteoblast-lineage cells in peripheral blood from ankylosing spondylitis (AS) patients and healthy control subjects, and to evaluate the effect of before and after anti TNF-α therapy on osteoblastogenesis in patients with AS.Sixteen male patients with AS slated for infliximab therapy and 19 controls were recruited. We cultured osteoblast-lineage cells from peripheral blood and measured the optical density of their Alizarin red S staining. We also measured serum P1NP (procollagen type 1 N-terminal propeptide) as an early osteoblast differentiation marker, osteocalcin as a late osteoblast differentiation marker, and inflammatory markers.There were significantly more circulating osteoblast-lineage cells in patients than in controls. The number of circulating osteoblast-lineage cells and optical density of Alizarin red S staining decreased 14 weeks after infliximab therapy (p=0.028); serum level of P1NP decreased, but that of osteocalcin increased (p=0.002 and 0.007, respectively).Our data reveals that first, the circulating osteoblast-lineage cells are recoverable and increased in AS patients, and also that they decrease after infliximab therapy; second, infliximab therapy resolves early inflammation, but allows mature osteoblast differentiation in late inflammation. The culture of osteoblast-lineage cells in peripheral blood may be a candidate for a new modality with which to study spondylitis and other autoimmune diseases.

Objective.To investigate natural killer (NK) cell proportions, NK cell cytotoxicity, and interleukin 18 (IL-18) expression, in patients with adult-onset Still’s disease (AOSD).Methods.Forty-five patients with AOSD (active = 22, inactive = 23) and 32 healthy controls were included. The proportions of NK cells among peripheral blood mononuclear cells were assessed by flow cytometry. IL-18 and IL-18-binding protein (IL-18BP) concentrations were measured by ELISA. Twenty-four patients with AOSD and 18 controls were examined for cytotoxic activity of NK cells by co-incubating NK cells with NK-sensitive K562 cells. The association of NK cell function with clinical and laboratory measures was investigated.Results.The proportions of NK cells were significantly lower in patients with active AOSD than in patients with inactive disease and controls. NK cell cytotoxic function was significantly lower in patients with AOSD than in controls. NK cell proportions and cytotoxic functions were reexamined in 11 and 6 patients, respectively, after treatment. Low NK cell proportion and cytotoxic dysfunction were improved with clinical improvements of the patients. IL-18 and IL-18BP levels were much higher in patients with active AOSD than in controls. NK cell cytotoxic functions were consistently low and IL-18 and IL-18BP levels were constantly high in patients with AOSD, regardless of disease activity.Conclusion.Low NK cell proportion, defective cytotoxic function, and elevated IL-18 levels may be significant features of AOSD. After resolution of the acute phase, low NK cell proportion was recovered and NK cell cytolytic function was restored along with clinical improvement. These findings possibly contribute to immunologic abnormalities in AOSD.

To the Editor, Systemic sclerosis (SSc) is a multisystem autoimmune disease characterized by microvascular disease and fibrosis. Despite advances in its early diagnosis, the mortality rate associat...

Diagnosis of adult-onset Still's disease (AOSD) is difficult because of a lack of pathognomonic findings and markers. The aim of this study was to investigate the efficacy of interleukin (IL)-18 and free IL-18 in the diagnosis and follow-up of patients with AOSD.Levels of inflammatory cytokines, IL-18, IL-18 binding protein (IL-18BP), and free IL-18 were compared in 80 AOSD patients and 90 controls. The AOSD patients were divided into active and inactive groups according to disease activity, and the inactive patients were subdivided into a remission subgroup and a low disease activity subgroup. We compared erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), ferritin, IL-18, and free IL-18 as disease activity markers in the AOSD patients. Serial serum levels of activity markers were measured in 52 of the 80 AOSD patients at 3- to 6-month intervals.There were significantly higher levels of IL-18 and free IL-18 in the AOSD patients than in the controls. IL-18 and free IL-18 were significantly higher in the active group than the inactive group (p0.001 for all). Unlike other activity markers, IL-18 and free IL-18 levels in the low disease activity subgroup were significantly higher than those in the remission subgroup within the inactive group (p = 0.004 and 0.005, respectively). During serial follow-up, ferritin and IL-18 showed a significant decrease in the responder and remission subgroup.IL-18 might be an efficient marker for diagnosis and follow-up of AOSD and might also be a useful predictor of remission, especially in clinically inactive patients.

Background Systemic sclerosis (SSc) is a complex multi-organ autoimmune disease with chronic and heterogeneous clinical manifestations. There is an unmet need for a new biomarker for early diagnosis and classification of SSc. Recent technical advancements have indicated several biomarkers for SSc; among these, platelet factor 4 (PF4), also known as CXCL4, was suggested by a large-cohort proteomic study 1 . PF4 is a chemokine released from activated platelets and is involved in coagulation, inflammation, and angiogenesis, which are influential in SSc pathogenesis. Therefore, PF4 may be an effective biomarker for SSc. Objectives To investigate the efficacy of PF4 as a biomarker for the diagnosis, activity and severity of patients with SSc. Methods Thirty-nine SSc patients (36 female and 3 male; mean age, 58.8±10.42 years; mean disease duration, 7.15±3.92 years; 11 diffuse cutaneous SSc cases and 28 limited cutaneous SSc cases) and 30 healthy controls (HC; 25 female and 5 male; mean age, 46.43±14.43 years) were enrolled. To estimate the circulating PF4 level, levels of platelet poor plasma (PPP) PF4 as well as serum PF4 were measured using an ELISA kit (R&D, Minneapolis, USA). SSc patients were divided into 2 subgroups according to disease activity and based on the presence/absence of interstitial lung disease (ILD), pulmonary hypertension, digital ulcers, and autoantibodies (anti-centromere Ab and anti-Scl70 Ab). Differences between SSc and HC groups were compared by Student9s t -test, and the subgroups were compared using the Mann-Whitney test. Predictive values of serum PF4 and PPP PF4 for SSc diagnosis were evaluated by the area under the receiver operating characteristic curve (AUROC). Results Serum PF4 levels of SSc were lower than those of HC (SSc, 5143.3±1777.5 ng/mL; HC, 5927.4±1348.5 ng/mL; p =0.048) but no significant differences were observed PPP PF4 levels (SSc, 407.2±486.6 ng/mL; HC, 297.3±141.5 ng/mL; p =0.187) between SSc patients and controls. Moreover, no significant differences were observed between active and inactive SSc subgroups and between subgroups with/without ILD, pulmonary hypertension, digital ulcers, and autoantibodies. The AUROC for serum PF4 and PPP PF4 levels was 0.628 (0.497–0.76, cuff of value 3998.5 ng/mL) and 0.491 (0.367–0.65, cuff of value 511.1 ng/mL), respectively. Conclusions In Korean patients with SSc, both serum PF4 and PPP PF4 levels are not efficient biomarkers for SSc diagnosis and do not appear to be associated with clinical activity and severity. References van Roon JA, Tesselaar K, Radstake TR. Proteome-wide analysis and CXCL4 in systemic sclerosis. N Engl J Med. 2014;370(16):1563–4. Disclosure of Interest None declared

Background Systemic sclerosis (SSc) is a complex multi-organ autoimmune disease that is caused by inflammation, vasculopathy and fibrosis. Clinical heterogeneity, unpredictable course, high mortality and resistance to treatment make physicians still frustrated. Recently, there are unmet needs of useful biomarkers for diagnosis, disease activity and severity of SSc. Metabolomics is expected to be a useful tool for the identification of biomarkers and new therapeutic targets. Several researchers have applied metabolomics to autoimmune diseases such as systemic lupus erythematosus, and rheumatoid arthritis. Objectives To identify the biomarker candidates for the diagnosis of SSc using metabolomic analysis. Methods Fifty-five patients (48 females (87%); mean age 59.30 ± 11.44 years; disease duration 6.92 ± 4.36 years; 11 diffuse cutaneous SSc, 44 limited cutaneous SSc) and thirty age, gender matched healthy controls (HCs) were enrolled. Serum samples after 8 h of fasting were stored at -80° and analysed using nuclear magnetic resonance (NMR)-based metabolomics. Results Multivariate analysis showed metabolic differences between SSc and HCs using partial least squares discrimination analysis (PLS-DA: R2Y=0.654, Q2=0.482) and orthogonal partial least squares discrimination analysis (OPLS-DA: R2Y=0.83, Q2=0.674) (Figure 1). We identified nine discriminatory metabolites (p Conclusions There are considerable differences in the serum metabolomic characteristics between SSc and HCs. We expect that metabolomic analysis can be a useful tool for identification of potential diagnostic biomarkers of SSc. Disclosure of Interest None declared

Objective. This study examines the effects of tumor necrosis factor (TNF) blockade on markers of bone metabolism in peripheral blood from active rheumatoid arthritis (RA) patients. Methods. Eighteen patients (16 women, 2 men) aged 50 years (range 37-63 years), with persistently active RA (mean disease duration 7 years) were studied. Most took methotrexate (mean dose 12.5 mg) and all except one received corticosteroid (mean dose 5.7 mg). Four were treated with etanercept, eight received adalimumab and six received infliximab. Before and six months after taking TNF blockers, blood was sampled to obtain peripheral blood mononuclear cells (PBMCs), and serum bone turnover markers and acute phase reactants were measured. PBMCs were seeded and cultured to produce osteoblastic lineage cells and osteoclasts. Results. The formation of calcified nodules by osteoblastic lineage cells from PBMC increased from 205.7±196.3 μmol/well at the baseline to 752.5±671.9 μmol/well after TNF blockade (p＜0.024). The serum levels of bone formation markers, including bone specific alkaline phosphatase and osteocalcin also increased. The number of circulating osteoclasts and area of bone resorption pits made by osteoclasts were reduced after TNF blockade. Conclusion. The activity of circulating osteoblastic lineage cells increased after TNF blockade, whereas peripheral osteoclastogenesis tended to be suppressed. This is the first study of cultured human peripheral osteoblastic lineage cells in RA patients. Given that peripheral bone formation is difficult to study using radiologic methods, culture of these cells may provide a new modality for studying bone metabolism in RA. (J Rheum Dis 2016;23:356-362)

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent episodes of fever accompanied by peritonitis, pleuritis, arthritis, or erysipelas-like erythema. It is known to occur mainly among Mediterranean and Middle Eastern populations such as non-Ashkenazi Jews, Arabs, Turks, and Armenians. FMF is not familiar to clinicians beyond this area and diagnosing FMF can be challenging. We report a 22-yr old boy who presented with fever, arthalgia and abdominal pain. He had a history of recurrent episodes of fever associated with arthalgia which would subside spontaneously or by antipyretics. Autosomal recessive periodic fever syndromes were suspected. Immunoglobulin D (IgD) level in the serum was elevated and DNA analysis showed complex mutations (p.Glu148Gln, p.Pro369Ser, p.Arg408Gln) in the MEFV gene. 3D angio computed tomography showed total thrombosis of splenic vein with partial thrombosis of proximal superior mesenteric vein, main portal vein and intrahepatic both portal vein. This is a case of FMF associated with multiple venous thrombosis and elevated IgD level. When thrombosis is associated with elevated IgD, FMF should be suspected. This is the first adult case reported in Korea.

Angioimmunoblastic T cell lymphoma (AITL) is a rare non-Hodgkin lymphoma that presents with pro- found immune dysfunction and immunodeficiency. The clinical and laboratory findings associated with AITL are similar to those of rheumatic disease, and AITL has been reported to be concurrent in patients with several rheumatic diseases. We present one case of AITL occurring in a patient with ankylosing spondylitis (AS) after treatment with etanercept. Constitutional symptoms and aggravation of peripheral arthritis in elderly AS patients may be due not only to flare-ups of AS but also to other complicating diseases, such as lymphoma. Although the occurrence of lymphoma in AS patients treated with etanercept has only rarely been reported, clinicians should keep in mind that instances of aggravation of peripheral arthritis in elderly AS patients occurring after immunosuppressant treatment may be due to other complicating systemic diseases such as AITL, rather than the rheumatic disease itself. Further study is needed in order to investigate whether or not using a TNF-a blocker such as etanercept increases the risk of lymphoma, especially for cases associated with Epstein- Barr virus.

Objective.Genetic factors account for more than 90% of overall susceptibility to ankylosing spondylitis (AS), and recent studies have focused on non-major histocompatibility complex genes. Vitamin D binding protein (DBP) is a highly polymorphic protein that transports vitamin D and its metabolites. In addition to its sterol binding capacity, DBP has many other roles in the inflammatory and immune systems, and has been reported to be associated with autoimmune diseases. We investigated the association between DBP polymorphisms and susceptibility to AS.Methods.This case-control study was conducted in 223 patients with AS and 239 ethnically matched controls who were genotyped for 8 single-nucleotide polymorphisms (SNP) in the DBP and its promoter. Genomic DNA was isolated from peripheral blood leukocytes using the standard phenolchloroform method, and the GoldenGate assay was used for genotyping.Results.No significant association was found between the susceptibility to AS and DBP polymorphisms. In a subgroup analysis of patients with AS, G alleles at rs222016 and rs222020 (OR 0.63, 95% CI 0.42–0.95, p = 0.03; OR 0.63, 95% CI 0.42–0.95, p = 0.03, respectively) and A allele at rs3733359 (OR 0.59, 95% CI 0.39–0.90, p = 0.01) showed the decreased risk of peripheral arthritis. G allele at rs4752 showed increased risk of uveitis (OR 2.04, 95% CI 1.12–3.72, p = 0.02). On the haplotype analyses, haplotype 2 (AGGA) protected against the development of peripheral arthritis (p = 0.01) and haplotype 3 (GAAG) was associated with an increased likelihood of uveitis (p = 0.02).Conclusion.DBP gene polymorphisms are associated with the development of peripheral arthritis and uveitis in Korean patients with AS. Given the influence of different DBP variants on the immune system, larger-scale studies are warranted to elucidate the role of DBP in the pathogenesis of AS.

Monckeberg’s sclerosis (MS) is one of the non-inflammatory vascular diseases characterized by calcification of the media of small and medium-sized muscular arteries, but is distinct from atherosclerosis. We present a case of MS that was incidentally detected by plain X-ray in a patient with systemic sclerosis. We took CT angiographs of the patient’s lower extremities for the differential diagnosis of vascular calcification, which was confirmed. To determine if systemic sclerosis is a risk factor for MS, we reviewed plain X-rays from 43 well-documented systemic sclerosis patients, but we did not detect any cases of MS. We therefore conclude that systemic sclerosis may not be a risk factor for MS.

Background Many authors tried to elucidate the relationship among the inflammation, osteoblast activity or new bone formation, and adipogenesis in patients with ankylosing spondylitis (AS). But the results were disappointing. Objectives We investigated the relationship among the inflammation, osteoblast activity or new bone formation, and adipogenesis in patients with AS by novel cell culture technique of osteoblast in peripheral blood and other methods. Methods Male sixteen individuals with AS were enrolled. They met modified New York criteria and were candidates for infliximab therapy. Sex and age matched nineteen controls were also recruited. Peripheral blood mononuclear cells were collected and cultured in growth medium. Once cell multi-layering has been observed (about 7 days), cells were transferred to differentiation medium and cultured for 3 weeks. Cells were then fixed and stained with alizarin S stain to detect any calcified nodules. The optical density (OD) of alizarin S was measured for quantitative analysis. We evaluated the numbers, the differences and relationship of 1) the numbers of circulating osteoblast precursors in peripheral blood, 2) the OD of alizarin S red staining of circulating osteoblast precursors, 3) P1NP (total procollagen type 1 N-terminal propeptide), c-terminal telopeptide (CTX), osteocalcin, triglyceride, low density lipoprotein cholesterol (LDL), apolipoprotein A-1, apolipoprotein B, lipoportein (a) with enzyme linked immunosorbent assay (ELISA), 4) erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) before and after 14 week infliximab therapy, 5) bone densitometry (BMD) before infliximab therapy in patients with AS. Results The number of osteoblast precursor cells and optic density of alizarin S were decreased after infliximab therapy (p=0.028 for optic density of alizarin S). The serum level of P1NP was decreased after infliximab therapy (p=0.002). The serum level of triglyceride was tend to increased, but that of lipoprotein (a) was decreased (p=0.07, p=0.007 separately). There were positive correlation between the BASDAI and the serum level of triglyceride (r =0.666, p=0.005), ESR and lipoprotein (a) (r =0.594, p=0.015), CRP and CTX (r =0.648, p=0.012), CRP and P1NP (r =0.631, p=0.016); negative correlation between BASDAI and femur total T score of BMD (r = -0.79, p=0.006) before infliximab therapy. They showed positive correlation between the difference of the serum level of LDL and that of osteocalcin (r =0.566, p=0.022), Alizarin S OD and apoprotein B (r =0.943, p=0.005), Alizarin S OD and osteocalcin (r =0.829, p=0.042); negative correlation between the difference of the serum level of LDL and ESR (r = -0.614, p=0.011) before and after infliximab therapy. Conclusions The circulating osteoblasts in peripheral blood and the serum level of P1NP were decreased significantly after 14 weeks of infliximab therapy. This result could be indirect evidence that infliximab therapy appeared to diminish osteoblast activity or new bone formation in patients with AS. There were strong relationship among inflammation, osteoblast activity, and adipogenesis before and after infliximab therapy in patients with AS. Disclosure of Interest S.-R. Kwon Grant/research support from: From Celltrion, Korea, Republic of, W. park: None declared, M.-J. Son: None declared, M.-J. Lim: None declared, K.-H. Jung: None declared

Background Digital ulcer (DU) is a significant cause of pain, functional disability and quality-of-life impairment in patients with systemic sclerosis (SSc). DU can occur even in patients with very early/early SSc (called the “window of opportunity” of SSc). Therefore, the identification of risk factors of DU can improve the SSc outcome. Several large cohort studies have reported risk factors of DU in SSc [1]. However, the risk factors of DU in patients with SSc have not been described in Korea yet. Objectives To determine the prevalence and risk factors of DU in Korean patients with SSc. Methods Ninety consecutive SSc patients with at least 6 months of follow-up were enrolled from January 2014 to December 2014 in tertiary hospital rheumatism center. Demographic data, clinical characteristics, internal organ involvements, comorbidities, laboratory findings, and disease-specific factors were obtained through medical records and patients interviews, retrospectively. Results Thirty-seven patients (41%) had a history or present digital ulceration and 43% of them had recurrent DU. Patients with DU were thin, had higher modified Rodnan skin score (mRSS), showed frequent pigmentation, microsomia, finger flexion contracture, acroosteolysis and calcinosis. They had anti-Scl 70 antibody, advanced nailfold capillary changes (active and late pattern) and interstitial lung disease more frequently than in patients without DU (Table 1.). In a multiple logistic regression analysis, mRSS (OR =1.178, 95% C.I. =1.06-1.31, p-value =0.002) was the sole risk factor of DU. A nailfold capillary microscopic finding was the only risk factor of recurrence of DU (p-value =0.025). Conclusions In Korean SSc patients, Rodnan skin score is a risk factor of DU and advanced nailfold capillary change is a risk factor for recurrent DU. We need more attention to treat those SSc patients with high mRSS and advanced nailfold capillary change. References Silva I, Almeida J, Vasconcelos C. A PRISMA-driven systematic review for predictive risk factors of digital ulcers in systemic sclerosis patients. Autoimmun Rev. 2015;14(2):140-152 Disclosure of Interest None declared

SAPHO syndrome, characterized by synovitis, acne, pustulosis, hyperostosis, and osteitis is rare compared to other spondyloarthropathies. It is also difficult to diagnose, and treatment methods have not yet been fully identified. Approximately 72% of patients are diagnosed with at least one other disease before a final diagnosis of SAPHO syndrome. In addition, SAPHO syndrome is subject to a delayed diagnosis period of 4.5 to 9.1 years. Medications such as non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs, and tumor necrosis factor inhibitors are used in treatment of SAPHO syndrome. Bisphosphonate is also used for refractory SAPHO syndrome; however, most reports on this relate to intravenous injection of medication. The authors experienced and subsequently reported on a case involving a patient with SAPHO syndrome accompanied by fracture and infection of the left second finger who was treated with the oral biphosphonate, alendronate. (J Rheum Dis 2015;22:313-316)

Eosinophilic granulomatosis with polyangiitis (EGPA), previously called Churg-Strauss syndrome, is an anti-neutrophil cytoplasmic antibody associated vasculitis, accompanied by asthma, hypereosinophilia, nonfixed pulmonary infiltrates, and sinusitis. Peripheral neuropathy is common in patients with EGPA; however, a few cases of EGPA with central nervous system (CNS) involvement have been reported. A 45-year-old female referred for right side weakness and posterior neck pain was diagnosed as EGPA with subarachnoid hemorrhage and mononeuritis multiplex. She was effectively treated with a high dose glucocorticoid, cyclophosphamide, and intravenous immunoglobulin. EGPA with CNS involvement is uncommon and causes significant morbidity and mortality. Therefore more rapid and accurate diagnostic evaluation may be required. EGPA should be considered in patients with neurological symptoms and hypereosinophilia. (J Rheum Dis 2015;22:190-194)

Although it is difficult to reach a diagnosis in patients who complain of pain or sensitivity to cold in their hands, Raynaud's phenomenon is most often suspected in such cases. Symptoms of Raynaud’s phenomenon include pallor, cyanosis, and redness following cold exposure. Glomus tumors can also increase patients’ sensitivity to cold. In this case, our patient complained of symptoms indicative of Raynaud’s phenomenon. Although treatment of Raynaud’s phenomenon improved the symptoms, pain persisted in the fourth finger of the left hand. We diagnosed the patient with a glomus tumor and, after surgical treatment, the patient’s symptoms improved. Here, we have also reviewed and discussed a number of reports of glomus tumors associated with Raynaud’s disease. Diagnosing a glomus tumor in the hand may take some time, and the diagnosis could be further delayed if accompanied by Raynaud’s phenomenon. Although glomus tumors are rare, we suggest that clinical awareness is important for early diagnosis and treatment. (Korean J Med 2014;87:765-770)

Background Adult onset Still’s disease (AOSD) is a rare inflammatory disorder of unknown etiology that classified into three patterns. The treatment of AOSD has been empirical and the information predicted outcome is lack. Objectives The objective of this study is to evaluate the clinical features and responses to therapy in Korean AOSD patients. Methods We retrospectively reviewed medical records of one hundred thirty-seven Korean patients with AOSD satisfied Yamaguchi’s criteria at one tertiary hospital from 2005 to 2011. Results 83.3% was female, and the average age of diagnosis is 37.1 years old. Median period of follow-up is 59.0 months. Thirty-seven patients (27.0%) are monocyclic, sixty-eight patients (49.6%) are polycyclic and thirty-two patients (23.4%) are chronic articular pattern. Clinical manifestations were: fever 89.8%, arthritis 66.4%,evanescent rash 62.8%, abnormal liver function test 62.8%, leukocytosis 55.3%, hyperferritinemia 43.1%, myalgia 38% and sore throat 35.8 et al. There was no correlation between disease pattern and clinical manifestations except level of serum ferritin between monocyclic and polycyclic pattern. Average of modified Pouchot’s score at disease onset was 4.9±1.7 and statistically correlated with monocyclic and polycyclic patterns. Prescriptions were: glucocorticoid (GC) 80.9%, methotrexate (MTX) 73.8%, leflunomide 34%, cyclosporine (CsA) 32.6%, hydroxychloroquine (HCQ) 26.2%, azathioprine (AZA) 5.7%, anti-TNF blockers 7.8% (etanercept 5, adalimumab 2, infliximab 6) and intravenous immunoglobulin 3.5%. Almost patients were treated with combination of GC and/or immune suppressants. Combination of MTX and GC were 18%. The rates of these combination plus additional leflunomide, CsA or HCQ were 20.3%, 17.6% and 9.5% respectively. The rates of combination were GC with CsA 7.2%, GC with HCQ 2.7%, GC with leflunomide 1.8% and GC with AZA 1.4% respectively. The response rates were GC 76.1%, MTX 70.2%, leflunomide 68.8%, CsA 52.3 and anti-TNF blocker 72.7%. Four cases made an attempt to treat with anakinra or tocilizumab. GC response was correlated with disease remission (p-value Conclusions Polycyclic pattern of AOSD is more common in this study. Ferittin and modified Pouchot’s score could be considered as predictors of disease pattern but not sufficient. GC and MTX were effective treatments like previous studies. Additionally leflunomide could be used effectively in the presence of arthritis in combination with MTX rather than CsA. Disclosure of Interest None Declared

Background While smoking exposure has been causally linked to rheumatoid arthritis, the relationship between smoking and the development of systemic lupus erythematosus (SLE) is less clear. The major studies in patients with SLE included did not have statistically significant associations and one outlying study increased the risk for SLE in a predominately Hispanic population. Objectives We investigated whether HLA-DRB1 risk alleles, smoking, or the combination contribute to the development of SLE and whether smoking influences the production of autoantibodies in a Korean population. Methods A total of 877 women from BAE SLE cohort, who fulfilled the American College of Rheumatology 1997 revised criteria for SLE, and 976 healthy women were recruited in a Korean population. Four-digit HLA-DRB1 typing was performed by a conventional PCR-SBT method. Information about smoking history was obtained through a questionnaire by face-to-face interviews. Odds ratios (OR) with a 95% confidence interval (CI) were calculated. Results The DRB1*1501 and *0803 alleles were associated with SLE susceptibility, using the relative predispositional effects according to controlling the Bonferroni method [OR 1.82 (95% CI: 1.44-2.03), p=4.45$× $10 -7 and OR 1.81 (95% CI: 1.40-2.34), p=4.77×10 -6 ). The smoking had significant effects on the development of SLE [OR 2.50 (95% CI: 1.48-4.21), p=6.23×10 -4 ] adjusted for age and HLA-DRB1 risk alleles. The combination of smoking and HLA risk allele increased the risk for SLE 5.7-fold, compared with nonsmokers without carrying HLA-DRB1 risk alleles. However, interactions between HLA-DRB1 risk alleles and smoking were not observed.We found no significant relationship between smoking and the production autoantibodies, such as anti-Sm, ds-DNA, anti-Ro, anti-La, anti-RNP, or anti-phospholipid antibody in patients with SLE. Conclusions We demonstrated that smoking increases systemic lupus erythematosus susceptibility in individuals carrying the HLA-DRB1 risk alleles. Disclosure of Interest None Declared

Background Lupus nephritis (LN) is one of the major manifestations of systemic lupus erythematosus (SLE) which need aggressive immunosuppressive treatments. Objectives The aim of this study was to investigate which therapeutic modalities were used for LN and whether response rate between therapeutics was different or not. Methods One hundred sixth nine patients with LN on biopsy, who followed up more than at least 6 months after diagnosis, were included from multicenters in Korea between 2000 and 2010. We retrospectively analyzed the clinicopathologic data using WHO or ISN/RPS, therapeutics, and responses based on 2006 ACR remission criteria. Poor outcome was defined as chronic renal failure (GFR Results The mean age at the time of diagnosis of LN was 31.2 years and 41.1 months was followed. The proportion of class II, III, IV, and V was 14 (8%), 58 (34%), 63 (37%), and 34 (20%), respectively. Induction therapeutic modalities were different between classes of LN; the most common therapeutics for class IV was cyclophosphamide NIH regimen [CYC(NIH)] 50%, followed by mycophenolate mofetil (MMF) 33% and CYC Euro regimen [CYC(EUR)] 13%, in contrast to CYC(NIH) 41%, and azathioprine (AZA) 24% for class III, and cyclosporine(CS) 47%, and CYC(NIH) 21%] for class V. In addition, therapeutics for maintenance were also different between classes; MMF 42.2% and AZA 22% for class IV, AZA 43% and MMF 25% for class III, and CS 44% and MMF 20% for class V. Complete or partial response after induction therapy was achieved in 83%, 74%, and 79% of patients with class III, class IV, and class V, respectively. The response rate between induction therapeutics for LN classes was not significantly different. Poor outcome defined by chronic renal failure was observed in 4.1% (n=7) of patients, and was significantly associated with poor induction response (OR 30.1 [3.2-284.1]) and 1-year response (OR 16.0 [2.1-123.3]). Conclusions Response to current therapeutics for each class of LN was favorable, regardless of therapeutic regimens. With appropriate induction therapy according to baseline renal function and histological class, remission to induction therapy was important factor for renal survival. Disclosure of Interest None Declared

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent episodes of fever accompanied by peritonitis, pleuritis, arthritis, or erysipelas-like erythema. It is known to occur mainly among Mediterranean and Middle Eastern populations such as non-Ashkenazi Jews, Arabs, Turks, and Armenians. FMF is not familiar to clinicians beyond this area and diagnosing FMF can be challenging. We report a 22-yr old boy who presented with fever, arthalgia and abdominal pain. He had a history of recurrent episodes of fever associated with arthalgia which would subside spontaneously or by antipyretics. Autosomal recessive periodic fever syndromes were suspected. Immunoglobulin D (IgD) level in the serum was elevated and DNA analysis showed complex mutations (p.Glu148Gln, p.Pro369Ser, p.Arg408Gln) in the MEFV gene. 3D angio computed tomography showed total thrombosis of splenic vein with partial thrombosis of proximal superior mesenteric vein, main portal vein and intrahepatic both portal vein. This is a case of FMF associated with multiple venous thrombosis and elevated IgD level. When thrombosis is associated with elevated IgD, FMF should be suspected. This is the first adult case reported in Korea.

Intestinal duplications are rare developmental abnormalities that may occur anywhere in the gastrointestinal tract. The possibility of a malignant change occurring in these duplications is very low. We present a case of adenocarcinoma arising in a duplication of the cecum. A 41-year-old male patient was admitted because of a palpable abdominal mass. Abdominal computed tomography revealed a 6-cm, peripheral wall-enhanced, round, cystic mass in the cecal area. Excision of the mesenteric mass and a right hemicolectomy was performed. Upon histologic examination, the patient was diagnosed with adenocarcinoma arising in a duplication of the cecum.

A 56-year-old man presented with a 3-day history of pain and swelling of the right knee. He had a history of renal stone, chronic renal failure and liver cirrhosis. He did not have a history of trauma. The right knee showed marked swelling, local heating and tenderness. The serum creatinine level was 1.85 mg/dL (reference, 0.4∼1.5 mg/dL) and uric acid level was 10.1 mg/dL (reference 3.0∼8.3 mg/dL). Acute phase reactants showed elevations including erythrocyte sedimentation rate of 28 mm/hr by the Westergren method, 7.16 mg/dL (reference, 0.0∼0.3 mg/dL) of C-reactive protein. The creatinine clearance (22.6 mL/min, reference 75.0∼125.0 mL/min) and the renal excretion of uric acid (490 mg/day, reference 250∼750 mg/day) were decreased in 24-hour urine anlalysis. AP view of both knees showed an osteolytic lesion with bony defect and fragment on the superolateral portion of the right patella (arrow, Figure 1A). Skyline view showed a similar lesion on the lateral portion of the right patella and

Etanercept is a soluble receptor fusion protein that inhibits tumor necrosis factor-alpha(TNF-α). The receptor is used widely in the treatment of ankylosing spondylitis, rheumatoid arthritis, sarcoidosis and other indications. For sarcoidosis, it potentially suppresses granuloma formation with TNF-α blocking. On the other hand, recent studies have suggested that paradoxical sarcoidosis can be induced by TNF-α antagonists in some cases. A 42-yearold woman, who was treated with etanercept due to ankylosing spondylitis for 5 years, was admitted because of right suprahilar lymphadenopathy on chest radiography. Chest computed tomography revealed an enlargement of supraclavicular, paratracheal, mediastinal lymph nodes. She was diagnosed with sarcoidosis on the supraclavicular lymph node biopsy, which was non-caseating epithelioid cell granuloma and excluded from similar diseases. She was treated for sarcoidosis with prednisolone instead of etanercept.

환 자: 11세 여자 주 소: 1년 6개월 전부터 지속된 오른쪽 고관절 통증 병 력: 과거력에서 외상의 기왕력은 없었으며 가 족력에서 특이 사항은 없었다. 타병원에서 상기 주 소로 치료를 받았으나 증상의 호전이 없어 전원 되 었다. 통증은 야간에 심해져 자다 깰 정도였고 통증 으로 인해 보행 시 파행이 동반되었다. 검사 소견: 적혈구침강속도 6 mm/hr, C-반응단백 0.3 미만으로 정상 소견이었다. 항 CCP 항체, 류마 티스인자와 HLA B27 모두 음성이었다. 방사선 소견: 고관절 단순 방사선 사진에서 좌측 에 비해 우측의 고관절 경부가 넓어져 있고 약1cm 의 음영이 증가된 핵(nidus)이 관찰되었다(그림 1A). 전신 뼈 스캔에서 우측 대퇴골 경부에 방사성동위원 소의 흡수가 증가되어있으며 전자간 지역(intertrochanteric area)에 반응성 변화를 보이고 있었다(그림 1B). 컴퓨터단층촬영에서 우측 대퇴골 경부에 약 1.3 cm 크기의 경화가 동반된 핵이 관찰되었다(그림 2A, B). 고관절 자기공명영상에서 T1, T2 영상에서 약 1 cm 크기의 저음영의 핵이 관찰되며 주변으로 골수의 부 종, 연부 조직 부종, 활액막염이 관찰되었다(그림 3A, B). 치 료: 비스테로이드성 소염진통제를 1년 이상 복용하고 있는 상태임에도 통증이 지속되므로 수술 이나 고주파 열치료(radiofrequency ablation)을 고려하 고 있다.

Acquired hemophilia is a rare disease caused by an autoimmune reaction to coagulation factor VIII, The mortality rate of this disease is very high (8∼22%). Clinical manifestations are different from congenital hemophilia. Various diseases are associated with acquired hemophilia, including autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis (RA), tumors, inflammatory bowel disease, psoriasis, asthma, diabetes, acute hepatitis B or C, and drug reactions. However, the underlying cause is unknown in approximately 50% of cases. A few cases of acquired hemophilia with RA have been published. However, no cases have been reported in Korea. We had a patient with longstanding RA and acquired hemophilia who was suffering from upper and lower extremity purpura with a deep intramuscular hematoma. The patient was successfully treated using cyclophosphamide combined with steroid.

Objective: Inflammatory cytokines may play important roles in the pathogenesis of adult onset Still's disease. The enhanced expression of IL-18 was reported in the bone marrow of a Japanese systemic onset juvenile rheumatoid arthritis patient but not in the other organs. To date, there are very few studies relating the bone marrow and AOSD. This study examined the bone marrow findings as well as TNF-α and IL-18 expression in the bone marrow of AOSD patients. Methods: A retrospective study was performed on 15 AOSD patients who had undergone a bone marrow examination at a university hospital. The clinical and laboratory findings, as well as the bone marrow findings, were analyzed. Immunohistochemistry of IL-18 and TNF-α in bone marrow was performed. Results: The bone marrow cellularity and myeloid/erythroid cell ratio showed no correlation with the clinical and laboratory findings. TNF-α was expressed at 0.8∼9.8% and IL-18 was expressed at 0.4∼9.8% of bone marrow cells. Cytokine expression was not associated with the clinical patterns of AOSD. The platelet count correlated with the bone marrow TNF-α expression but TNF-α did not correlate with IL-18 expression.

A chronic expanding hematoma (CEH) in the thorax is a rare and specific condition of chronic empyema. CEHs in the thorax are often associated with tuberculosis and/or previous surgical procedures. While the incidental detection of a pleural mass and dyspnea are common clinical manifestations, a few cases present with hemoptysis. We encountered a case of CEH in the thorax. This case is unique in that it developed without a prior history of tuberculosis or surgery and presented with massive hemoptysis accompanied by bronchopleural fistula. We report the third case of CEH in the thorax in Korea with a summary of the clinical characteristics of previous cases. (Tuberc Respir Dis 2008;65:216-221)