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Background: Gout is a common disease that is mainly caused by hyperuricemia. Although it is relatively easy to treat, adherence to drug treatment and the rate at which treatment targets are met is low.Current Concepts: For the treatment of acute gout attack, colchicine, nonsteroidal anti-inflammatory drugs, and glucocorticoids can be used alone or in combination depending on the severity of symptoms. To prevent gout attacks, patients are started on colchicine prior to or concurrent with treatment with uric acid–lowering drugs. The treatment is maintained until serum uric acid levels have returned to normal, and the patient has had no acute attacks for three to six months. Ultimately, the symptoms of gout are controlled in the long term by treating the patient’s hyperuricemia. For this purpose, allopurinol, febuxostat, and benzbromarone are used, and the side effects and contraindications for each drug should be checked. The goal for the treatment of chronic gout is to maintain a serum uric acid concentration below 6.0 mg/dL.Discussion and Conclusion: Patients visit the emergency departments of hospitals for sudden gout attacks. However, gout is a chronic disease that requires the lifelong use of uric acid–lowering agents. Therefore, it is necessary to educate patients on a serum urate-based treat-to-target approach.

Anti-nuclear antibodies (ANAs) are autoantibodies against nuclear substances or other cellular components. ANA tests are used in the diagnostic process to screen patients with suspected rheumatic or autoimmune diseases. ANA-associated diseases are characterized by a high titer of antinuclear antibodies and include systemic lupus erythematosus, systemic sclerosis, and mixed connective tissue diseases. ANA test results must be cautiously interpreted as they can be positive not only in infections and oncological diseases but also for the healthy general population. The ANA test mainly uses the indirect immunofluorescence test, and the results are expressed in terms of the final titer and pattern. The ANA test can increase diagnostic value when used in conjunction with the evaluation of disease-related clinical symptoms. (Korean J Med 2021;96:337-340)

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that affects various organs. SLE patients have an increased risk of infection compared to the general population. Immunosuppressive agents commonly used in SLE increase the risk of infection. Vaccination is a good way to reduce the risk of infection. However, some SLE patients are concerned that vaccination may worsen lupus disease activity or cause side effects. The latest SLE patient vaccination data were reviewed in this study, which focused on the safety, immunogenicity, and efficacy of influenza, pneumococcal, tetanus, hepatitis A, herpes zoster, and human papillomavirus vaccines. Korean immunization recommendations were also compared to those of other countries. (Korean J Med 2020;95:170-175)

Background Features of new bone formation (NBF) are common in tophaceous gout. The aim of this project was to develop a plain radiographic scoring system for NBF in gout. Methods Informed by a literature review, scoring systems were tested in 80 individual 1st and 5th metatarsophalangeal joints. Plain radiography scores were compared with computed tomography (CT) measurements of the same joints. The best-performing scoring system was then tested in paired sets of hand and foot radiographs obtained over 2 years from an additional 25 patients. Inter-reader reproducibility was assessed using intraclass correlation coefficients (ICC). NBF scores were correlated with plain radiographic erosion scores (using the gout-modified Sharp-van der Heijde system). Results Following a series of structured reviews of plain radiographs and scoring exercises, a semi-quantitative scoring system for sclerosis and spur was developed. In the individual joint analysis, the inter-observer ICC (95% CI) was 0.84 (0.76–0.89) for sclerosis and 0.81 (0.72–0.87) for spur. Plain radiographic sclerosis and spur scores correlated with CT measurements (r = 0.65–0.74, P < 0.001 for all analyses). For the hand and foot radiograph sets, the inter-observer ICC (95% CI) was 0.94 (0.90–0.98) for sclerosis score and 0.76 (0.65–0.84) for spur score. Sclerosis and spur scores correlated highly with plain radiographic erosion scores (r = 0.87 and 0.71 respectively), but not with change in erosion scores over 2 years (r = −0.04–0.15). Conclusion A semi-quantitative plain radiographic scoring method for the assessment of NBF in gout is feasible, valid, and reproducible. This method may facilitate consistent measurement of NBF in gout.

The efficacy and safety of febuxostat in patients with stage 4-5 chronic kidney disease (CKD) remains unclear. We evaluated the urate-lowering efficacy and renal safety of febuxostat in patients with stage 4-5 CKD not yet on dialysis, through a meta-analysis of observational studies.We performed a systematic search in PubMed, Ovid MEDLINE, Embase, and the Cochrane Library databases for observational studies of patients with advanced CKD starting febuxostat. Articles describing changes in serum urate levels and/or renal function assessed by the estimated glomerular filtration rate (eGFR) were included.Among 148 retrieved studies, five relevant observational studies with 327 patients were included in the meta-analysis. Febuxostat was administered daily at 10-120 mg for 3-12 months. Serum urate reduced in response to febuxostat (weighted mean difference, -1.85 mg/dL; 95% CI, -2.04--1.67 mg/dL; IOverall, febuxostat has acceptable urate-lowering efficacy and renal safety in patients with hyperuricemia and stage 4-5 CKD who are not yet on dialysis.

Aim The incorporation of growth factors is an effective strategy to accelerate bone induction. Bone morphogenetic protein-2 (BMP-2) promotes osteoblast differentiation and induces bone formation. Alendronate (ALN) is an osteoclast deactivation drug. We investigated the effect of serial administration of recombinant human BMP-2 (rhBMP-2) and ALN on osteoblast differentiation. Methods The effect of serial administration of rhBMP-2 (0-150 ng/mL) and ALN (0-15 µmol/L) on the viability and differentiation of a clonal murine calvarial cell line, MC3T3-E1, was evaluated at various concentrations and for different periods. The Cell Counting Kit-8 assay was used to assess cell viability. The alkaline phosphatase activity was evaluated as an indicator of osteogenic differentiation. The expression levels of runt domain-containing transcription factor 2 (Runx2) and osteopontin (OPN) were analyzed by real-time polymerase chain reaction and western blotting. Statistical analyses were performed using Student's t test. Results The serial treatment with rhBMP-2 and ALN increased the expression of the differentiation-related factors Runx2 and OPN, as well as the differentiation ability of osteoblasts compared with individual or simultaneous treatment. The osteoblasts treated with rhBMP-2 followed by ALN showed the highest differentiation. The degree of differentiation in the group treated with rhBMP-2 for 7 days followed by ALN for 3 days was increased by 1.5 times compared with that of the group treated with rhBMP-2 alone (P Conclusion These findings indicate that the serial administration of rhBMP-2 and ALN may exert osteogenic effects on osteoblastic cells via the upregulation of Runx2 and OPN.

Objectives: In this study, we aimed to evaluate the association between grape seed proanthocyanidin extract (GSPE) and rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLSs) and to investigate whether GSPE induces cell death in RA-FLSs. Materials and methods: The FLSs were isolated from RA synovial tissues. Cell viability and cell cycle staging were analyzed using a hemocytometer and flow cytometry. Caspase 3 and poly (ADP-ribose) polymerase (PARP) proteins were analyzed using Western blotting with z-VAD-fmk. Protein LC3 and polyubiquitin-binding protein p62 that were degraded by autophagy were evaluated using Western blotting with 3-methyladenine and chloroquine. Reactive oxygen species (ROS) were also evaluated. Results: When RA-FLSs were treated with GSPE, cell viability decreased, the number of cells in sub-G1 and G2/M phases increased, and the expression of pro-PARP and pro-caspase 3 proteins decreased in a concentration-dependent manner. This result was offset, when the cells were co-treated with the pan-caspase inhibitor z-VAD-fmk. The reduced cell viability, increased expression of LC3-II protein, and reduced expression of p62 protein with GSPE treatment were offset, when RA-FLSs were co-treated with GSPE and autophagy inhibitors 3-methyladenine and chloroquine. The level of ROS in RA-FLSs treated with GSPE was significantly lower than treatment with N-acetyl-cysteine, a ROS inhibitor. Conclusion: Our study results show that GSPE induces apoptotic and autophagic cell death and inhibites reactive oxygen species in RA-FLSs.

Background/Aims The safety and efficacy of febuxostat in patients with stage 4–5 chronic kidney disease (CKD) are still unclear owing to a lack of studies in these patients. Therefore, we aimed to evaluate the effect of febuxostat on renal function, general safety, and efficacy in gout patients with stage 4–5 CKD. Methods Among 739 patients who had been administered febuxostat from May 2012 to December 2016 at a single hospital in Korea, 370 patients who had been monitored for 1 year were analyzed. Serum uric acid levels and estimated glomerular filtration rate (eGFR) of patients with gouty arthritis were collected at baseline and 1 year after febuxostat administration. Results Among the 370 patients, 280 patients were stage 1–3 CKD, 63 patients were stage 4–5 CKD, and 27 patients were on dialysis. The eGFR of 63 patients with stage 4–5 CKD, excluding dialysis patients, was 19.84 ± 7.08 mL/min/1.73 m2 when they began to take febuxostat and 23.49 ± 16.67 mL/min/1.73 m2 after 12 months (p = 0.13). The urate-lowering effect after 12 months of febuxostat medication showed statistical significance (8.96 ± 2.31 mg/dL at baseline and 4.88 ± 1.68 mg/dL after 12 months, p < 0.01). The difference in incidence of adverse events among patients with stage 1–3 CKD, those with stage 4–5 CKD, and those on dialysis was not significant. Conclusions Febuxostat demonstrated renal safety and good urate-lowering efficacy in gout patients with stage 4–5 CKD, who are not yet on dialysis.

Background International rheumatology guidelines advocate a treat to serum urate target (T2T) approach for gout management. While individual studies have reported regional and national-level gout management, global patterns in gout care have not been synthesized. This study aimed to systematically review and meta-analyze global T2T care for patients with gout. Methods Electronic databases were searched for studies reporting medication and serum urate testing in patients with gout. Meta-analyses were conducted to determine the pooled proportion of patients with gout achieving pre-specified T2T indicators. Results Sixty-seven papers were included from North America (n = 31 studies), Europe (n = 22), Oceania (n = 7), Asia (n = 6), and reporting data from multiple continents (n = 1). The global pooled percentages (95% confidence interval (CI)) of patients with gout achieving T2T indicators were: 52% (45%, 59%) on urate lowering therapy (ULT), 50% (40%, 61%) on ULT receiving regular uninterrupted ULT, 53% (40%, 65%) on ULT having any serum urate testing, and 34% (28%, 41%) on ULT achieving a serum urate target. Conclusion Outside North America and Europe, there are relatively few studies about T2T care for gout management. However, available data demonstrate that a minority of people with gout receive T2T care worldwide. For those prescribed ULT, there are low rates of continuous therapy, serum urate testing, and achievement of serum urate target.

Background Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease affecting the axial skeleton and peripheral joints. The etiology of this disease remains poorly understood, but interactions between genetic and environmental factors have been implicated. The present study identified differentially expressed proteins in the synovial fluid (SF) of AS patients to elucidate the underlying cause of AS. Methods A cohort of 40 SF samples from 10 AS and 10 each of rheumatoid arthritis (RA), gout, and osteoarthritis (OA) patients were analyzed by liquid chromatography tandem mass spectrometry (LC–MS/MS) to identify differentially expressed proteins specific to AS. The label-free LC–MS/MS results were verified by western blotting. Results We identified 8 proteins that were > 1.5-fold upregulated in the SF of AS patients compared to that of the disease control groups, including HP, MMP1, MMP3, serum amyloid P-component (APCS), complement factor H-related protein 5 (CFHR5), mannose-binding lectin 2 (MBL2), complement component C9 (C9), and complement C4-A (C4A). CFHR5 and C9 were previously found in serum from AS patients, while APCS was previously found in SF as well as in serum. However, the present study has identified C4A, and MBL2 as potential AS biomarkers for the first time. The expression levels of MMP3, C9, and CFHR5 were verified in AS SF using western blotting. Conclusion We performed quantitative comparative proteomic analysis using by LC–MS/MS of the SF from four disease states: RA, gout, and OA. This systematic comparison revealed novel differentially expressed proteins in AS SF, as well as two previously reported candidate biomarkers. We further verified the expression of MMP3, C9 and CFHR5 by western blot. These proteins may serve as diagnostic or prognostic biomarkers in patients with AS, and may thus improve the clinical outcomes of this serious disease.

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

Background/aims Grape seed proanthocyanidin extract (GSPE) has been reported to have a beneficial effect on regulating inf lammation. However, the anti-inflammatory mechanism of GSPE remains unclear. The aim of this study was to verify the influence of GSPE on the Toll-like receptor 4 (TLR4)-mediated signaling pathway in the regulation of murine autoimmune arthritis. Methods Collagen-induced arthritis (CIA) was induced in dilute brown non-agouti (DBA)/1J mice. The mice were treated with GSPE (0 or 100 mg/kg) intraperitoneally. The severity of arthritis was assessed clinically, biochemically, and histologically. Immunostaining for TLR4 was performed. The expressions of TLR4 and downstream signaling molecules were analyzed by Western blot. The effect of GSPE on lipopolysaccharide (LPS)-induced TLR4 activation was also evaluated using RAW264.7 cells and fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis and from those with osteoarthritis. Results GSPE attenuated the clinical severity of arthritis and decreased histological damage. GSPE treatment reduced the number of TLR4-stained cells in the synovium of mice with CIA. GSPE also downregulated the expression of TLR4, myeloid differentiation factor 88 (MyD88) and phosphorylated IκBα synovial protein in CIA mice. Concurrently, GSPE inhibited the nuclear translocation of nuclear factor-κB (NF-κB) subunits (p65 and p50). LPS-induced TLR4 activation was suppressed by GSPE in human FLS as well as in murine macrophages in vitro. Conclusions Our results demonstrated that GSPE ameliorated CIA by regulating the TLR4-MyD88-NF-κB signaling pathway.

Background Ankylosing Spondylitis (AS), affecting 0.5% of the population, is a chronic inflammatory rheumatic disease affecting the axial skeleton and peripheral joints. When peripheral arthritis in ankylosing spondylitis (AS) develops early in the disease course it is a predictor of more aggressive disease. SF is in contact with the primary tissues affected by arthritic diseases and has been implicated in disease pathophysiology. Therefore it is an excellent source for discovery of biomarkers. Objectives We used proteomic analysis using SFs from AS patients and other arthritis patients in order to discover novel diagnostic markers for AS. Our aim was to identify differentially expressed protein mediators in synovial fluid of ankylosing spondylitis. Methods A Total of 40 SF samples from 10 AS and each 10 controls [Osteoarthritis (OA), Rheumatoid Arthritis (RA), gouty arthritis (Gout)] were collected. Liquid chromatography and tandem mass spectrometry (LC-MS/MS), to identify differentially expressed proteins based on the ratios of the extracted ion current of each protein between the four groups. Among the 9 proteins showing 1.5 fold change, 8 were verified with the exception of the abundant protein Haptoglobin (HP). Matrix metalloproteinase-1(MMP1) and Matrix metalloproteinase-3(MMP3) were used as a positive control, and the remaining 6 proteins were subjected to western blot analysis. Results We identified 9 proteins that were found to be more than 1.5-fold differentially expressed in SF of AS patients compared to control groups. Proteins such as HP, MMP1, MMP3, Serum amyloid P-component(APCS), Complement factor H-related protein 5(CFHR5), Fumarylacetoacetase(FAH), Mannose-binding lectin2(MBL2), Complement component C9(C9) and Complement C4-A(C4A) were found to be upregulated in the SF of AS patients. CFHR5 and C9 were reported in previous studies with AS serum. APCS was reported in SF as well as serum. However, FAH, C4A and MBL2 were newly discovered through this analysis. We were able to verify the unique expression level of C9 and CFHR5 in AS sample using western blot analysis compared to the other three diseases. Conclusion We performed quantitatively proteomic profiling of the respective SF sample from 4 diseases, i.e., AS, OA, RA, and GOUT, by LC-MS/MS. The systematic comparative proteomic analysis of the four groups together was carried out for the first time, leading to several differentially expressed proteins in AS. Among them, we expect C9 and CFHR5, which expression levels were confirmed by western blot analysis, can be a potential biomarker for AS. References [1] Fischer R, et al. Mol Cell Proteomics2012;11:M111.013904. [2] Bhattacharjee M, et al. Clinical Proteomics2013;10:11 Acknowledgement This research was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2017R1C1B5017278) Disclosure of Interests None declared

Background/aims Neuropsychiatric systemic lupus erythematosus (SLE) includes a broad spectrum of neurologic and psychiatric manifestations. One of the most commonly observed neuropsychiatric symptoms is headache. However, the lack of specific clinical distinctions for headache in SLE has made it difficult to elucidate its pathophysiology. The aim of this study is to evaluate the neurometabolic changes using Proton Magnetic Resonance Spectroscopy (1H-MRS) in patients with SLE who suffer from chronic daily headache (CDH). Methods SLE and fibromyalgia patients with CDH and healthy controls were recruited (n = 9, n = 5, and n = 6, respectively). 1H-MRS metabolite ratios were evaluated in bilateral basal ganglia (BG) and bilateral peritrigonal white matter (PWM). Results 1H-MRS showed a significantly decreased N-acetylaspartate (NAA)/creatine (Cr) ratio in right BG in SLE patients with CDH compared to fibromyalgia patients with CDH and normal controls (p = 0.029 and p = 0.020, respectively). Left PWM NAA/Cr and choline/Cr ratios in SLE patients with CDH were lower than those in fibromyalgia patients with CDH (p = 0.019 and p = 0.029, respectively). Conclusions This study suggests the possibility that CDH in patients with SLE might be associated with neuronal dysfunction and neurometabolic changes.

Background/Aims: We aimed to investigate the prevalence and possible causes of hypouricemia in the Korean population and to compare our findings with published results of other populations. Methods: We examined the serum uric acid levels of 30,757 subjects who had their uric acid values measured at least once during a 1-year period. All individuals with hypouricemia (serum uric acid < 2.0 mg/dL, n = 424) were reviewed with respect to medical drug history and concomitant diseases previously identified as being associated with hypouricemia. Results: The prevalence of hypouricemia was 4.14% (299/7,223) among inpatients and 0.53% (125/23,534) among outpatients, for an overall prevalence of 1.39% (424/30,757). Possible causes associated with hypouricemia were found to be solid or hematologic malignancies (n = 86), diabetes mellitus (n = 56), and therapeutic drugs (n = 29). The medications were allopurinol (n = 11), angiotensin II receptor blockers (n = 10), salicylates (n = 6), febuxostat (n = 1), and warfarin (n = 1). In the remaining 226 individuals, the cause of hypouricemia was not identified. Conclusions: Hypouricemia is relatively common in the Korean population compared to those of other countries. The possible causes associated with hypouricemia are related to underlying diseases and medications.

Background:Long noncoding RNAs (lncRNAs) have recently emerged as important biological regulators and the aberrant expression of lncRNAs has been reported in various diseases including cancer, cardiovascular disease, and diabetes mellitus. However, the role of lncRNAs in the pathogenesis of rheumatoid arthritis (RA) remains unknown.Objectives:Thus, we studied lncRNAs influenced by IL-1, which is one of the key mediators in the pathogenesis of RA, and also investigated whether regulation of NF-κB activation, which is known to be induced by IL-1, could lead to the changes of expression of those lncRNAs.Methods:Fibroblast-like synoviocytes (FLS) were obtained from the knee joints of the patients with RA. The next-generation sequencing (NGS) data were analyzed to identify differentially expressed lncRNAs between unstimulated RA FLS and IL-1-stimulated RA FLS. The expression levels of the top 5 candidates in NGS data were validated by RT-qPCR using extended number of unstimulated RA FLS and IL-1-stimulated RA FLS. IMD-0560, an inhibitor of IκB kinase (IKK) was used for the regulation of NF-κB activation. Activation and inhibition of NF-κB were confirmed by Western blotting. Changed expressions of the lncRNAs were identified by RT-qPCR.Results:NGS analysis revealed up-regulated 30 lncRNAs and down-regulated 15 lncRNAs in IL-1-treated RA FLS compared with unstimulated RA FLS. Top 5 lncRNAs were selected among 30 lncRNAs up-regulated by IL-1 in RA FLS based on fold-change with P-value cutoff. The up-regulated lncRNAs including NR_046035, NR_027783, NR_033422, NR_003133, and NR_049759 were validated by RT-qPCR. IMD-0560 inhibited phosphorylation of IκBα induced by IL-1 in RA FLS. Overexpression of lncRNAs induced by IL-1 was also inhibited by IMD-0560 in RA FLS.Conclusion:Our study revealed that IL-1 increased the expression of NR_046035, NR_027783, NR_033422, NR_003133, and NR_049759 in RA FLS. In addition, the expression of these lncRNAs was regulated by inhibition of NF-κB activation. Thus, our data suggest that the lncRNAs might be involved in the pathogenesis of RA through NF-κB signaling pathway.References:[1]Long noncoding RNAs and human disease. Trends Cell Biol. 2011 Jun;21(6):354-61.[2]A long noncoding RNA mediates both activation and repression of immune response genes. Science. 2013 Aug 16;341(6147):789-92.[3]Long noncoding RNA expression profile in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Arthritis Res Ther. 2016 Oct 6;18(1):227.Disclosure of Interests:None declared

Background High levels of serum immunoglobulin G4 (IgG4) would comprise a useful diagnostic tool in IgG4-related disease, but little information is available about IgG4 in conditions other than IgG4-related disease, including rheumatic diseases. Previous studies indicate that the elevated serum IgG4 in rheumatoid arthritis (RA) is common and disproportional to total IgG. Objectives The aim of study is to evaluate the level of serum IgG4 and IgG4/total IgG ratio in patients with RA. Methods Ninety-six patients with RA and one hundred and thirty-five non-RA controls were enrolled between March 2014 and July 2017. All samples were collected before the treatments. The levels of Serum total IgG and IgG4 were determined by nephelometric assay. The cut-off value of serum IgG4 was 135 mg/dL. Data on clinical variables and disease activity markers, such as numbers of tender and swollen joints, levels of acute phase reactants and disease activity score 28 (DAS28) were recorded in RA patients. We compared the levels of serum IgG4 and the ratio of IgG4/total IgG in rheumatoid arthritis with healthy controls and other rheumatic diseases. This study also investigated the difference the relationship between levels of serum IgG4 and disease activity in RA. Results Among 96 RA patients, the mean of serum IgG4 was 48.0±45.4 mg/dL and 6.3% had elevated serum IgG4. The mean serum IgG4/IgG ratio of RA patients was 3.5%±2.8% (range 0.2%∼16.9%). There was no patient with elevated serum IgG4 in ankylosing spondylitis, systemic lupus erythematosus, Sjogren’s syndrome, and inflammatory myositis. When the patients were divided according to clinical activity, the percentages of the positive serum IgG4 were 25% in active disease group and 4% in low activity group. However, the serum IgG4 levels of the RA patients with active disease activity were not significantly higher than those of the RA patients with low disease activity (58.3±44.3 mg/dL vs. 39.9±30.1 mg/dL). No significant relationship was observed between the ratio of IgG4/total IgG and disease activity. The IgG4 concentrations and total IgG/IgG4 ratios were similar between RA and the other autoimmune diseases (p>0.05). Conclusions Our results showed that elevated serum IgG4 in RA is relatively common. However the presence of the elevated serum IgG4 was not associated with disease activity of RA. Further investigations are needed to explore the clinical significance in a larger study population. References [1] Lin G, et al. Elevation of serum IgG subclass concentration in patients with rheumatoid arthritis. Rheumatol Int2010;30:837–40. [2] Yamamoto M, et al. Value of serum IgG4 in the diagnosis of IgG4-related disease and in differentiation from rheumatic diseases and other diseases. Mod Rheumatol2012;22:419–25. [3] Chen LF, et al. Elevated Serum IgG4 Defines Specific Clinical Phenotype of Rheumatoid Arthritis. Mediators Inflamm2014;2014:635293. Disclosure of Interest None declared

Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disorder that affects multiple organs and is fatal in some cases. Thrombotic thrombocytopenic purpura (TTP), another rare disease, is characterized by multiple organ failure and microangiopathic hemolytic anemia. TTP is an extremely rare complication of AOSD. We report a 59-year-old woman who presented with TTP that manifested after she was diagnosed with AOSD. Initially, her clinical manifestations improved with glucocorticoid therapy. However, her disease worsened and was accompanied by acute kidney injury, thrombocytopenia, hemolytic anemia, petechiae, and impaired consciousness. These clinical findings led to a diagnosis of TTP. This is the first report of AOSD complicated by TTP in Korea. Awareness of the possible development of TTP as a complication of AOSD is important for early diagnosis and treatment. (Korean J Med 2015;89:482-486)

Central Nervous System (CNS) involvement of Systemic Lupus Erythematosus (SLE) includes a broad range of neuropsychiatric syndromes. Acute Disseminated Encephalomyelitis (ADEM) is a demyelinating CNS disorder characterized by encephalopathy and multifocal lesions predominantly involving the white matter on brain magnetic resonance imaging. ADEM associated with SLE has been only rarely reported. We report an unusual case of a 17-year-old girl who developed ADEM after enteroviral infection as the first manifestation of SLE. The authors emphasize that the patient’s illness was preceded by enteroviral infection and that ADEM occurred before any other symptoms of SLE, which makes this case unique.

Background CT-P13 is approved in both European Union and United States, and licensed for use in 79 countries around the world as a biosimilar to innovator infliximab (INX). The independent registries of CT-P13 have been conducted in a number of European countries and Korea [1]. Objectives To evaluate safety and effectiveness of CT-P13 when administered in a real-life setting in active RA patients. Methods This study collected data of patients who were treated with CT-P13 from 2013 December to 2016 June. Efficacy was assessed at baseline and every 6 months thereafter using DAS28 (ESR) and/or DAS28 (CRP) and collection of adverse events (AEs) was performed. Immunogenicity was assessed at baseline, Week 30 and every year during CT-P13 treatment period. Results Total 125 patients were enrolled; 104 patients started treatment with CT-P13 (Naive group) and 21 patients (8 from INX, 13 from other anti-TNFs) switched treatment to CT-P13 (Switching group). The mean (SD) duration since RA diagnosis was 6.5 (±6.85) years for all patients. Of all patients treated with CT-P13, only 4.8% (6/125) of patients changed to other anti-TNFs. Two of six patients changed treatment within 8 month after starting CT-P13. The proportion of patients achieving clinical remission by DAS28 (ESR/CRP) increased gradually (Figure 1). DAS28 (ESR/CRP) value decreased from baseline at 6 months and it maintained thereafter (Table 1). Switching group also showed similar results that remission rate by DAS28 (CRP) was 42.9% (3/7) and mean actual value was 2.85 at 12 months. For Naive group, 50% (52/104) of patients had at least one positive anti-drug antibody result and it is consistent to other published study [2]. Overall safety summarized as the percentage of patients with at least one treatment emergent AE (TEAE) was similar or lower after switching to CT-P13 (Table 2). No cases of active tuberculosis were reported. Conclusions The overall safety profile revealed that CT-P13 is well-tolerated in patients with RA and remission rate for 24 months also showed that CT-P13 is efficacious under real world practice. References Glintborg et al. ACR 2016. Krintel et al. Rheumatology 2013. Disclosure of Interest None declared

Background and aims Rheumatoid arthritis (RA) is characterised by exaggerated synovial proliferation in which interleukin-17A (IL-17A) plays a key role. Recently several evidences support the implication of autophagy in the pathogenesis of RA. The aims of this study are (1) to evaluate whether IL-17A influences on autophagic flux in RA synovium and (2) to investigate whether the modulation of autophagy can regulate migration and proliferation of fibroblast-like synoviocytes (FLS) from the patients with RA (RA-FLS) under inflammatory milieu. Methods FLS from the patients with RA or osteoarthritis (OA) were cultured with IL-17A and/or autophagy regulators. The expression of marker proteins for autophagic flux or the formation of autophagolysosome was analysed by western blot or immunofluorescence study. A migration scratch assay was used to assess FLS migration. Proliferation of FLS was determined by the viable cell count using trypan blue. Results LC3 conversion from LC3-I to LC3-II was increased in RA-FLS than in OA-FLS. IL-17A upregulated the expression of LC3B, Atg5, Beclin1, LAMP1 in RA-FLS. The accumulation of p62 was also prominent in RA-FLS. Migration and proliferation of FLS stimulated by IL-17A was suppressed by Bafilomycin A1 which prevented the formation of autophagolysosomes. P62-silencing enhanced IL-17A-induced autophagy activation in RA-FLS. Conclusions This study reveals that IL-17A stimulates autophagy and that intervention of autophagy can control IL-17A-induced migration and proliferation of FLS. Our results also provide additional evidence for a significant role of autophagy in the pathogenesis of RA. Thus, we suggest that autophagy might be a potential therapeutic target for the management of RA.

We aimed, first, to investigate the minor allele frequencies (MAFs) of single nucleotide polymorphisms (SNPs) associated with serum uric acid (SUA) level in the Korean population and compare these with data from other ethnic groups and, second, to investigate whether the SNPs are associated with altered SUA levels. We examined the frequencies of risk alleles, investigated the MAFs of 40 previously described SNPs associated with SUA level in the Korean population (a total of 1,957 subjects), and compared results with data for other ethnic groups. We also analyzed associations with SUA concentrations based on data from genome-wide association studies in the Korean population (a total of 402 rheumatoid arthritis subjects) and tested whether polymorphism of any of the 40 SNPs associated with SUA identified previously was associated with SUA levels. The MAFs of SNPs associated with SUA level in the Korean population were quite similar to those among Japanese, but not in populations of European descent. SNP rs12734001 (PPP1R12B) proved to have the most probable association with SUA concentrations (P_trend = 2.29 × 10(-9)). We also analyzed 13 SNPs shown previously by meta-analysis to be associated with SUA, and SNP rs3741414 (INHBC) was found to have probable association with SUA level observed in the present study (P_trend = 0.01). The pattern of variants controlling SUA levels in the Korean population is not similar to that in European population. SNP rs12734001 (PPP1R12B) is significantly associated with SUA level among Koreans.

This aimed to compare the three radiographic methods of digital tomosynthesis (DT), plain radiography, and computed tomography (CT) for evaluating changes in feet of patients with chronic gouty arthritis. Two independent radiologists read the plain radiography, DT, and CT images of 30 male patients with gout. The degrees of erosion and joint space narrowing were scored using the Sharp–van der Heijde scoring method in 18 foot joints, which consisted of four proximal interphalangeal and one interphalangeal joint of the first toe, five metatarsophalangeal, five tarsometatarsal, and three naviculo-cuneiform joints of the foot. DT showed high reproducibility [0.929 for intraobserver intraclass correlation coefficient (ICC) and 0.838 for interobserver ICC]. DT showed similar results to those of CT and superior results to those of plain radiography for evaluating radiographic damage [mean total score, 8.5 ± 14.6 (±standard deviation) for plain radiography, 12.9 ± 12.4 for DT, and 12.6 ± 11.2 for CT]. This study showed that DT is a good method for evaluating radiographic changes in patients with gout. Further research is needed to apply DT to actual clinical settings.

Background/Aims Anti-C-reactive protein (CRP) antibody has been introduced as a potential biologic marker in Systemic lupus erythematosus (SLE). The aim of study is to evaluate the level of anti-CRP antibody in patients with SLE. METHODS This study investigated the relationship between levels of anti-CRP antibodies and disease activity markers, such as complement, anti-double-stranded DNA antibody, and SLE disease activity index in 34 patients with SLE. RESULTS The serum anti-CRP antibody levels of the patients with SLE were significantly higher than those of the healthy controls (11.3 ± 5.6 µg/mL vs. 9.1 ± 2.8 µg/mL). The percentages of the positive anti-CRP antibody were 52.9% in SLE and 27.8% in controls. Disease duration of SLE showed significant correlation with the anti-CRP antibody (r = 0.234, p = 0.026). However no significant relationship was observed between the levels of anti-CRP antibodies and disease activity markers. Conclusions These data show that the anti-CRP antibody levels of the patients with SLE were significantly higher than those of healthy controls. We observed that the presence of the anti-CRP anti-CRP antibody was not associated with disease activity of SLE.

We investigated the prevalence and involvement patterns of radiographic osteoarthritis (OA) with hand symptoms among Korean people and compared the difference in prevalence of hand OA between racial groups. Hand radiographs in 299 Korean subjects (266 female, 33 male) ≥40 years of age were examined, who had hand arthralgia. The study population was comprised of 206 patients who had radiographic OA at least at one hand joint. Radiographic OA (Kellgren-Lawrence scale ≥2 grades) was evaluated for 16 joints of each hand. The most prevalent OA was in the interphalangeal joints (IP) of thumb, followed by the distal interphalangeal joints (DIP) of index finger, DIP of middle and fifth finger in the frequency of order. The involvement of metacarpophalangeal joints (MP) was relatively common in 1st-3rd MP. Hand OA in Korean was higher in the thumb IP and lower in the thumb carpometacarpal joints compared with Caucasian previously reported. Moreover, the higher OA frequency of 1st-3rd MP was not in accordance with other studies in Caucasian and other Asian populations. The patterns of radiographic hand OA were symmetric (OR 15.68), clustered by ray (OR 8.69) and row (OR 6.66). In conclusion, our study showed that thumb IP and 2nd/3rd/5th DIP should be included in the assessment of radiologic hand OA in Koreans.

The purpose of the present study was to find novel loci associated with hyperuricemia using data from a genome-wide association study (GWAS) conducted on healthy Koreans. We conducted a GWAS using data from a community-based cohort study where 3,647 subjects aged 40–89 were recruited by the Korea National Institute of Health (KNIH). The community-based cohort consisted of subjects who did not suffer from any of 6 major diseases (hypertension, hyperlipidemia, diabetes, heart diseases, brain diseases, and cancers). Epidemiologic information includes 249 traits such as epidemiological surveys, physical examinations, and laboratory tests. A total of 3,647 participants, including 234 hyperuricemia cases (serum uric acid [SUA] level was 7 mg/dL or higher) and 3,413 controls, were genotyped by Illumina HumanOmni1-Quad BeadChip GWAS array at KNIH. In the multivariate regression analysis of clinical variables, significant variables associated with hyperuricemia were male gender (odds ratio [OR], 5.526; P = 3.2 × 10−10), old age (OR, 1.017; P = 0.040), high body mass index (BMI) (OR, 1.147; P = 5.4 × 10−7), current alcohol intake (OR, 2.413; P = 4.7 × 10−7), and high creatinine (OR, 1.647; P = 1.6 × 10−13). We identified a hyperuricemia susceptible loci (rs2054576 in ABCG2, OR, 1.883; P = 4.7 × 10−8) that passed a genome-wide significance threshold, adjusted by clinical variables (male, age, BMI, current alcohol, and creatinine). It was first identified that rs2054576 in ABCG2 is associated with hyperuricemia. Our results should be validated through replication studies among other Korean subjects or various ethnic groups., Graphical Abstract

Background/Aims The aim of this study was to compare the sleep quality between rheumatoid arthritis (RA) patients and healthy controls; and to evaluate the relationship between RA disease activity and sleep quality in Korea. Methods A total of 130 RA patients and 67 age- and sex-matched healthy controls were enrolled in a comparative study of sleep quality using the Pittsburgh Sleep Quality Index (PSQI). Age, gender, concomitant medication, erythrocyte sedimentation rate, serum C-reactive protein, Beck Depression Inventory second edition (BDI-II), 28 joints disease activity score (DAS28), pain visual analog scale (VAS), and PSQI were analyzed as covariates. We also analyzed the sleep quality of RA patients according to the disease activity (DAS28 ≤ 3.2, 3.2 < DAS28 < 5.1, and DAS28 ≥ 5.1, respectively). Results The total PSQI score and the frequency of poor sleep quality, were higher in the RA patients (5.62 ± 4.19, 38.5%) than in the control subjects (3.57 ± 2.17, 13.4%). The patients with poor sleep quality (PSQI > 5) were older and had a higher BDI-II and VAS score than the patients without sleep disturbance (PSQI ≤ 5). The score in subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, daytime dysfunction, total PSQI, and frequency of poor sleep quality were increased when RA activity was high. Conclusions Sleep disturbance was observed in RA patients (38.5%), and high RA disease activity was associated with poor sleep quality in Korea.

Background Behcet9s disease is a chronic, systemic vasculitis that can involve all sizes of blood vessels. Those complicated symptoms lead to the patient9s impairment of life quality as well as psychological problems. Sleep disturbance is one of the most particular concerns in patients with Behcet9s disease. It has been known that the disease activity of rheumatoid arthritis and ankylosing spondylosis is associated with the sleep quality. However, studies about the sleep quality of patients with Behcet9s disease in Korean population are limited. Objectives The purpose of this study was to find out the effects of sleep quality on Behcet9s disease in Korean population. We also investigated the relationship between depression, quality of life, other clinical findings of Behcet9s. Methods The study was performed by cross-sectional design in two tertiary hospitals. We met one hundred patients with Behcet9s disease, surveyed them face-to-face and conducted the chart review for more clinical informations. Sleep quality was assessed by the Korean version of Pittsburgh sleep quality index (PSQI). Disease activity of Behcet9s disease was evaluated by Behcet9s disease current activity form (BDCAF). Depression was assessed by the Korean version of Beck depression inventory second edition (BDI-2). Quality of life was assessed by the Korean version of the Leeds Behcet9s Disease Quality of Life Measure (BDQoL). Results Among 100 patients, median age was 51 [44.5–56.0] years, median disease duration was 77.5 [24.0–136.0] months and 31% were male. Those who met the diagnostic critera of fibromyalgia were 28 patients. The frequency of poor sleep quality (PSQI >5) was 67%. Patients with poor sleep quality tend to have higher BDI2, BDCAF and pain VAS score (P Conclusions The low quality of sleep is associated with disease activity, depression and quality of life in Korean patients with Behcet9s disease. We expect better disease control will improve the sleep quality. References Tascilar NF, Tekin NS, Ankarali H, Sezer T, Atik L, Emre U, Duysak S, Cinar F. J Sleep Res 2012;21:281–8. Melikoglu MA, Melikoglu M. Rheumatol Int 2010;30:941–6. Disclosure of Interest None declared

Background Headaches is common in patients with systemic lupus erythematosus (SLE) [1]. However, the lack of specific clinical distinctions for headache in SLE has made it difficult to elucidate its pathophysiology. Chronic daily headache (CDH) is a category of headache disorders that occurs more than 15 days per month and is associated with a profound decline in the quality of life [2]. Objectives The aim of this study is to investigate the clinical characteristics of CDH in patients with SLE and their association with disease severity and the quality of life. Methods A total of 40 consecutive patients with SLE participated in the survey. We investigated headache characteristics, visual analogue scale (VAS) for pain, and six-question headache impact test (HIT-6) to evaluate the impact of headache on the quality of life. The patients underwent required blood tests for assessment of disease activity using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Results Six patients (15%) met the criteria for CDH. The total score of HIT-6 is significantly higher in SLE patients with CDH than in those patients who suffered from headache without CDH (P=0.027). SLE patients with CDH in particular had a higher prevalence of “wish could lie down” than those who suffered from headache without CDH (P=0.017). The multivariate regression analysis indicates that the headache days per month was a predictor for headache-related disabilities. Conclusions As far as we know, this is the first study of its kind to evaluate the correlation of CDH and the quality of life in Korean patients with SLE. CDH may deteriorate the quality of life in patients with SLE. References Cuadrado MJ, Sanna G. Headache and systemic lupus erythematosus. Lupus 2003;12:943–6. Pascual J, Colas R, Castillo J. Epidemiology of chronic daily headache. Curr Pain Headache Rep 2001;5:529–36. Disclosure of Interest None declared

Background Interleukin-17A (IL-17A) plays a critical role in the pathogenesis of rheumatoid arthritis (RA), which is characterized by exaggerated synovial proliferation. Autophagy is required to prevent accumulation of cellular damage and to ensure cellular homeostasis. Dysregulated autophagy has been reported to be involved in the pathogenesis of several diseases such as cancer and infections. Here, we hypothesized that IL-17A, a key cytokine in the development of RA, might have an impact on autophagic flux and that aberrant autophagy might be involved in expansion of synovial fibroblasts in the patients with RA, which is stimulated by pro-inflammatory cytokines. Objectives The aims of this study were (1) to evaluate whether IL-17A influences on autophagic flux in the synovium of the patients with RA and (2) to investigate whether the modulation of autophagy can regulate migration and proliferation of fibroblast-like synoviocytes (FLS) from the patients with RA (RA-FLS) under inflammatory milieu. Methods Synovial tissue was obtained from the patients with RA or osteoarthritis (OA) during total knee replacement surgery. FLS was cultured with IL-17A, autophagy inducer or inhibitor. The expression of marker proteins for autophagic flux (LC3B, Beclin1, Atg5, p62) and the formation of autophagolysosome (LAMP1) were analyzed by western blot. A migration scratch assay was used to assess FLS migration in response to stimulation with IL-17A. Proliferation of FLS was determined by the viable cell count using trypan blue. Bafilomycin was used for inhibiting autophagic flux. Results The expression of autophagy markers (LC3B, Beclin1, Atg5) was increased in the synovium of the patients with RA than in that of the patients with OA. Autophagy was also enhanced in RA-FLS compared with OA-FLS. IL-17A upregulated the expression of LC3B, Atg5, Beclin1, LAMP1 in RA-FLS. In particular, IL-17A-induced accumulation of p62 was prominent in RA-FLS. Migration and proliferation of FLS stimulated by IL-17A was suppressed by the inhibition of autophagy. Conclusions This study reveals that IL-17A stimulates autophagic flux and that intervention of autophagy can control IL-17A-induced migration and proliferation of FLS. Our results also provide additional evidence for a significant role of autophagy in the pathogenesis of RA. Thus, we suggest that autophagy might be a potential therapeutic target for the management of RA. References Lin NY, Beyer C, Giessl A, et al. Autophagy regulates TNFα-mediated joint destruction in experimental arthritis. Ann Rheum Dis. 2013 May;72(5):761–8. Connor AM, Mahomed N, Gandhi R, et al. TNFα modulates protein degradation pathways in rheumatoid arthritis synovial fibroblasts. Arthritis Res Ther. 2012 Mar 14;14(2):R62. Disclosure of Interest None declared

Acute pancreatitis is a serious disease with fatality rate up to 15%. We recently experienced a case of acute pancreatitis induced by multiple drugs in a patient with ulcerative colitis. A 20-year-old female visited with abdominal pain and hematochezia and diagnosed of ulcerative colitis. Sulfasalazine and prednisolone were used. However, acute pancreatitis occurred after 4 weeks of treatment with additional azathioprine treatment. Drug-induced pancreatitis was suspected, and she was recovered with conventional therapy for acute pancreatitis. Therefore, it was proposed that acute pancreatitis was induced by azathioprine. However, after the administration of sulfasalazine, pancreatitis relapsed. Furthermore, even the re-administration of 5-ASA and azathioprine induced relapse of acute pancreatitis. We concluded that acute pancreatitis was induced by multiple drugs in this patient with ulcerative colitis.

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 Systemic erythematosus lupus (SLE) is an autoimmune disease with multi-organ involvement and diverse autoantibodies are associated with SLE [1]. Recently, many reports have suggested that anti-C reactive protein (CRP) antibody is more prevalent in patients with SLE, and the level of anti-CRP antibody increases when the disease flares up [2]. Objectives This study was performed to investigate the relationship between anti-CRP antibody and the disease activity markers in Korean patients with SLE. Methods 29 patients with SLE and 30 healthy people were enrolled between April 2014 and November 2014. The presence of anti-CRP antibody was analyzed by enzyme-linked immunosorbent assay (ELISA). Data on clinical variables and disease activity markers, such as complement, anti-dsDNA antibody, and systemic lupus erythematosus disease activity index (SLEDAI) were recorded. Results The level of serum anti-CRP antibody in SLE patients was significantly higher than that of healthy controls (p=0.035). However, anti-CRP antibody levels were not positively correlated with the complement levels, the SLEDAI score, and anti-dsDNA antibody levels. And also there was no significant difference in the level of anti-CRP antibody between the patient group with lupus nephritis and the patient group without lupus nephritis. Conclusions This study shows the presence of serum anti-CRP antibody in Korean SLE patients. But there was no significant relationship between anti-CRP antibody and disease activity, lupus nephritis. These findings are not consistent with previous study that anti-CRP antibody is a useful marker to evaluate the disease activity. References Shere Y, et al. Semin Arthritis Rheum 2004;34:501-37. Sjowall C, et al. Arthritis Res Ther 2004;6:R87-R94. Disclosure of Interest None declared

Background The evaluation of radiographic damage in inflammatory arthritis has been considered important, because structural damage of affected joints impairs the functional status of patients with various inflammatory rheumatic diseases and increases their economic problems and mortality [1, 2]. However, there has still been no relevant radiographic index for damage of affected joints in patients with chronic gouty arthritis. Modified SvdH scoring method has been proposed to be an alternative method [3], however, it seems to be so complex and also lack of relevance to use in clinical practice. Objectives The aim of this study was to develop and validate more a simple method to score radiographic damage measurement in patients with chronic gout. Methods Two independent observers read foot x-rays using the DAmagE index of GoUt score method (DAEGU score) and the modified Sharp/van der Heijde (SvdH) method. The 10 metatarsophalangeal (MTP) and 2 interphalangeal (IP) joints of the first toes of both feet from 15 patients with chronic gout were scored on plain radiography for erosion and joint space narrowing (JSN) (180 total joints). The intraobserver and interobserver reliability were analyzed by intraclass correlation coefficient (ICC) and minimal detectable change (MDC). The correlation between the DAEGU and SvdH methods was analyzed using Spearman9s correlation coefficients and Kappa coefficients. Results The intraobserver and interobserver ICCs for the DAEGU method were 0.945–0.987 and 0.993–0.996, respectively. The MDC at the 95% confidence interval (MDC95) showed 0.5–2.1 and 0.3–0.7 in the intra- and interobserver analyses, respectively. Strong positive correlations were represented between the DAEGU and SvdH methods for each radiological abnormality including erosion, JSN, and total score (correlation coefficients: r =0.870–0.985, p Conclusions This study demonstrated that the DAEGU score had a high reproducibility and strongly correlated with SvdH. The DAEGU method may provide a more easy assessment of structural damage in patients with chronic gout. References Kavanaugh A, et al. J Rheumatol 2004;31:849–55. Gladman DD, et al. Arthritis Rheum 1998;41:1103–10. Dalbeth N, et al. Arthritis Rheum 2007;57:1067-73. Disclosure of Interest None declared

Background Research on the safety and effects of febuxostat in stage 4 or 5 CKD patients is very limited. There are some studies where research on hyperuricemia patients with gout history has been conducted [1, 2], but there is little data on cases of application to patients actually in order to treat gout. Objectives This study aims to examine the clinical effects of febuxostat in cases of allopurinol-refractory hyperuricemia during treatment of gout in dialysis patients or stage 4 CKD patients. Methods Patients selected had been administered febuxostat for six months or longer because of allopurinol-refractory hyperuricemia during treatment of gout from May 2012 to February 2014. The patients met the American College of Rheumatology criteria for acute gout. The age, gender, duration of gout, cause of CKD, serum uric acid (SUA), estimated glomerular filtration rate (eGFR), creatinine, and doses of febuxostat were investigated in patients whose eGFR had been less than 45 mL/min per 1.73 m 2 among the patients before the initiation of febuxostat administration Results A total of 25 patients were enrolled. The number of stage 3b (30 ≤ eGFR Conclusions In gout treatment of dialysis patients or CKD stage 4 patients with allopurinol-refractory hyperuricemia, febuxostat inhibited gout recurrence and effectively decreased SUA during a period of six months. References Horikoshi, et al. Clin Exp Nephrol. 2013:17;149-50. Shibagaki, et al. Hypertens Res. 2014:37;919-25. Disclosure of Interest None declared