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Objective. High disease activity of ankylosing spondylitis (AS) is associated with poor sleep quality. The purpose of this study was to identify which of the representative tools for evaluating the disease activity of AS best reflect the quality of sleep. Methods. A total of 107 AS patients were enrolled in the study and the sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Age, sex, concomitant medication, erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) level, Beck Depression Inventory second edition (BDI-II), Bath ankylosing spondylitis disease activity index (BASDAI), ankylosing spondylitis disease activity score (ASDAS)-ESR, ASDAS-CRP, pain visual analog scale, Insomnia Severity Index (ISI), and Epworth Sleepiness Scale (ESS) were analyzed as covariates. Results. Overall, 65% (70/107) of subjects reported poor sleep quality (PSQI＞5). There was a positive correlation between the sleep quality and disease activity as measured by the BASDAI, ASDAS-ESR, and ASDAS-CRP. In addition, the BASDAI demonstrated good correlations with ISI, ESS, and BDI-II, respectively. However, only BASDAI showed reliable correlation with PSQI among the disease activity parameters of AS (adjusted odd ratio 5.36, p=0.023). Conclusion. BASDAI is the most reliable parameter of disease activity associated with the sleep quality in patients with AS. (J Rheum Dis 2021;28:143-149)

Background/Aims: We investigated the distribution of serum uric acid (SUA) lev els and estimated the prevalence of hyperuricemia and hypouricemia in the Kore an population. Methods: This cross-sectional study used data from the Korean Genome and Epi demiology Study and included 172,970 participants (58,981 men and 113,989 wom en) aged 40 to 79 years. Hypouricemia and hyperuricemia were defined as SUA level ≤ 2.0 mg/dL and > 7 mg/dL, respectively. The prevalence of hyperuricemia and hypouricemia was evaluated by age and sex. Results: The mean SUA levels were significantly higher in men than in women (5.71 ± 1.27 mg/dL vs. 4.21 ± 0.96 mg/dL, p < 0.001). The mean SUA levels and prevalence of hyperuricemia increased with age in women but not in men. The overall preva lence of hyperuricemia and that in men and women was 50.82, 133.25, and 8.17 per 1,000 persons, respectively; the overall prevalence of hypouricemia and that in men and women was 4.16, 1.10, and 5.75 per 1,000 persons, respectively. The prev alence of hypouricemia in men was similar across all age groups; however, that in women was the highest in the age group of 40 to 49 years and the lowest in the age group of 50 to 59 years. Conclusions: The distribution of SUA levels and prevalence of hyperuricemia and hypouricemia differed according to age and sex. Age and sex should be considered in studies on uric acid-related diseases.

Objectives Osteoporosis and fracture are known complications of systemic lupus erythematosus (SLE). We assessed the prevalence and risk factors for osteoporosis in patients with SLE. Methods A total of 155 female SLE patients were recruited retrospectively in 5 university hospitals. The bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry, and the fracture risk assessment tool (FRAX) for high-risk osteoporotic fractures was calculated with and without BMD. Results The mean age was 53.7 ± 6.8 years, and osteoporotic fractures were detected in 19/127 (15.0%) patients. The proportion of patients having a high-risk for osteoporotic fractures in the FRAX with and without BMD, and osteoporosis by the World Health Organization (WHO) criteria were 25 (16.1%), 24 (15.5%), and 51 (32.9%), respectively, and 48.0–68.6% of them were receiving treatment. On multivariate logistic analysis, nephritis (odds ratio [OR] 11.35) and cumulative dose of glucocorticoid (OR 1.1) were associated with high-risk by the FRAX with BMD, and low complement levels (OR 4.38), erythrocyte sedimentation rate (ESR) (OR 1.04), and cumulative dose of glucocorticoid (OR 1.05) were associated with osteoporosis by the WHO criteria in patients with SLE. Conclusions Among Korean female patients with SLE, the proportion of patients having a high-risk of osteoporotic fractures by the FRAX tool was 15.5%–16.1% and the proportion of patients having osteoporosis by the WHO criteria was 32.9%. In SLE, nephritis, low level of complement, ESR, and cumulative dose of glucocorticoids may contribute to fracture risk.

Objectives This study aims to assess the efficacy and safety of mycophenolate mofetil (MMF) on lung function and skin thickness in Korean patients with systemic sclerosis-interstitial lung disease (SSc-ILD) in a real-world setting. Patients and methods This retrospective, medical chart-based study was performed at four centers in South Korea and included 34 patients (2 males, 32 females; median age 50.5 years; range, 25 to 72 years) with SSc-ILD. We investigated changes in forced vital capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLCO), and modified Rodnan skin score (mRSS) according to MMF treatment for 24 months. Results The mean dose and treatment duration of MMF were 1,338.2±439.0 mg/day and 13.1±9.3 months, respectively. Although FVC decreased significantly at 15 months, FVC and DLCO did not change significantly during treatment with MMF. Median mRSS decreased significantly from 17.5 (2-40) to 10.5 (2-40) units (p

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 To investigate medication nonadherence in Korean patients with rheumatoid arthritis (RA) and analyze related factors. METHODS A total of 292 patients with RA participated in this study. Medication nonadherence, intentional or unintentional, was gauged via self-reported questionnaire. Patient perceptions of illness, treatment beliefs, and moods were measured via Brief Illness Perception Questionnaire, Beliefs about Medicines Questionnaire, and Patient Health Questionnaire-2, respectively. Demographic and clinical data were also collected. Multinomial regression analysis was used to assess the impact of demographic, clinical, and psychological factors on medication nonadherence. RESULTS The medication nonadherence rate was 54.1% (intentional, 21.6%; unintentional, 32.5%). Intentional nonadherence was reported most often in patients treated daily drugs (nonsteroidal anti-inflammatory drugs and/or disease-modifying antirheumatic drugs) (24.2%), and unintentional nonadherence was highest in patients receiving methotrexate (33.3%) (p = 0.872). In univariate analysis, beliefs in necessity and concerns of medication differed significantly in adherent and nonadherent patients (intentional or unintentional). When controlling for other factors that may impact medication nonadherence, less belief in necessity of medication (odds ratio [OR], 0.81; 95% confidence interval [CI], 0.68 to 0.95) and greater emotional response to disease (OR, 1.19; 95% CI, 1.01 to 1.40) were important predictors of intentional nonadherence. CONCLUSIONS Medication nonadherence is common in Korean patients with RA. Less belief in necessity of medication and greater emotional response to disease were identified as key factors prompting intentional nonadherence. These factors may be strategically targeted to improve medication adherence rates and subsequent clinical outcomes.

Background/Aims: Sleep disturbance is prime concern in patients with Behcet disease. The purpose of this study was to find out the effects of sleep quality, in Korean patients suffering from Behcet disease. We further investigated the relationship between depression, quality of life and the clinical findings of Behcet disease. Methods: The study was performed by the cross-sectional design. Sleep quality was assessed by the Korean version of Pittsburgh sleep quality index (PSQI). Disease activity of Behcet disease was evaluated by Behcet 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 Behcet disease quality of life measure (BDQoL). Results: Among the 100 patients studied, 42% reported poor sleep quality (PSQI ≥ 9). These patients have a higher BDI-2, total BDCAF and pain visual analogue scale (VAS) score (p < 0.001, p = 0.022, and p = 0.005). Considering BDCAF, the frequency of genital ulcer was significantly higher (p = 0.01). Behcet was higher in females. The BDQoL was lower in poor sleeper group (p = 0.004 and p < 0.001). Among 7 PSQI components, daytime dysfunction was higher in patients with high disease activity (p = 0.03). Total PSQI score were strongly correlated with BDCAF, BDI-2, BDQoL, and pain VAS score (p = 0.02, p < 0.001, p < 0.001, and p < 0.001, respectively). Conclusions: Low sleep quality is directly associated with disease activity, depression, and quality of life in Korean patients with Behcet disease.

Background: To compare the frequency of high-risk osteoporotic fracture in patients with knee OA (OA) using the fracture risk assessment tool (FRAX) and the bone mineral density (BMD). Methods: We retrospectively assessed 282 Korean patients with knee OA who visited five medical centers and 1165 healthy controls (HCs) aged &ge, 50 years without knee OA. After matching for age, sex, and body mass index, 478 subjects (239 patients with knee OA and 239 HCs) were included. Results: Based on the BMD, the frequency of osteoporosis was 40.2% in patients with knee OA and 36.4% in HCs. The predicted mean FRAX major osteoporotic fracture probabilities calculated with or without femur neck BMD differed significantly between the knee OA and HCs (6.9 &plusmn, 3.8% versus 6.1 &plusmn, 2.8%, p = 0.000 and 8 &plusmn, 3.6% versus 6.8 &plusmn, 2.3%, p &lt, 0.001, respectively). The mean FRAX hip fracture probabilities calculated with or without femur neck BMD differed significantly in the knee OA and HCs (2.1 &plusmn, 2.4% versus 1.7 &plusmn, 1.8%, p = 0.006 and 3 &plusmn, 2.3% versus 2.4 &plusmn, 1.6%, p &lt, 0.001, respectively). Conclusion: Our study suggests that FRAX may have a clinical impact on treatment decisions to reduce osteoporotic facture in patients with knee OA.

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.

Purpose The effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) and osteogenically differentiated adipose tissue-derived stem cells (ADSC) on new bone formation in high-speed distraction osteogenesis of adult rabbit cranium were investigated. Materials and Methods A total of 41 adult rabbits were used in the study. Distraction began after a 5-day latency period at a rate of 1.5 mm twice a day until 10-mm length gain was obtained both in the control group, where a bone defect was induced, and in the experimental group, in which ADSC (group A), rhBMP-2 (group B), or both (group C) were injected in the distraction gap after distraction. At 4, 8, and 12 weeks after distraction, computed tomography analysis was done to determine the bone defect dimension and bone mineral density (BMD), while histologic examination was also done to calculate bone formation ratio. Results Bone defect dimension significantly decreased in groups B and C, compared with the control group, at 4 and 12 weeks after distraction. BMD was significantly increased in groups B and C at 4 weeks. On histologic examination, bone formation ratio was significantly increased in group C only at 12 weeks. Conclusion This study suggests that the use of rhBMP-2 in combination with or without ADSC is helpful to promote bone regeneration in high-speed distraction osteogenesi s of adult rabbit cranium.

Objectives Celecoxib is a selective cyclooxygenase (COX)-2 inhibitor that is commonly used to reduce the incidence of gastrointestinal (GI) complications in patients with rheumatoid arthritis (RA). CELBESTA® is a generic equivalent to CELEBREX®, a celecoxib preparation. This study compared the efficacy and safety of CELBESTA® and CELEBREX® in patients with RA. Methods This was a multicenter, double-blind, double-dummy, active-controlled, randomized, parallel-group, non-inferiority clinical trial. The primary endpoint was a change from baseline in self-assessed pain intensity determined using a 100-mm visual analog scale after 6 weeks of treatment. Results After a washout period, 119 eligible subjects were randomized to one of two groups (CELBESTA® group, n = 61; CELEBREX® group, n = 58). CELBESTA® was not inferior to CELEBREX® because the upper limit of two-sided 95% confidence interval (CI) for the difference between the two groups (difference in the least square [LS] mean, −8.68 mm; two-sided 95% CI −16.59 mm to −0.77 mm) was less than the non-inferiority margin (10 mm). There were no significant differences in GI complications and renal toxicity. Conclusions CELBESTA® was not inferior to CELEBREX® with regard to the pain relief efficacy in RA patients, and the tolerability and safety profiles were excellent and at similar levels for both preparations.

(1) Background: We evaluated the prevalence and fracture risk of osteoporosis in patients with rheumatoid arthritis (RA), and compared the fracture risk assessment tool (FRAX) criteria and bone mineral density (BMD) criteria established by the World Health Organization (WHO). (2) Methods: This retrospective cross-sectional study, which included 479 RA patients in 5 hospitals, was conducted between January 2012 and December 2016. The FRAX criteria for high-risk osteoporotic fractures were calculated including and excluding the BMD values, respectively. The definition of high risk for fracture by FRAX criteria and BMD criteria by WHO was 10-year probability of &ge, 20% for major osteoporotic fracture or &ge, 3% for hip fracture, and T score &le, &minus, 2.5 or Z score &le, 2.0, respectively. (3) Results: The mean age was 61.7 &plusmn, 11.9 years. The study included 426 female patients (88.9%), 353 (82.9%) of whom were postmenopausal. Osteoporotic fractures were detected in 81 (16.9%) patients. The numbers of candidates for pharmacological intervention using the FRAX criteria with and without BMD and the WHO criteria were 226 (47.2%), 292 (61%), and 160 (33.4%), respectively. Only 69.2%&ndash, 77% of the patients in the high-risk group using the FRAX criteria were receiving osteoporosis treatments. The following were significant using the WHO criteria: female (OR 3.55, 95% CI 1.46&ndash, 8.63), age (OR 1.1, 95% CI 1.08&ndash, 1.13), and BMI (OR 0.8, 95% CI 0.75&ndash, 0.87). Glucocorticoid dose (OR 1.09, 95% CI 1.01&ndash, 1.17), age (OR 1.09, 95% CI 1.06&ndash, 1.12), and disease duration (OR 1.01, 95% CI 1&ndash, 1.01) were independent risk factors for fracture. (4) Conclusions: The proportion of RA patients with a high risk of osteoporotic fractures was 33.4%&ndash, 61%. Only 69.2%&ndash, 77% of candidate patients were receiving osteoporotic treatments while applying FRAX criteria. Independent risk factors for osteoporotic fractures in RA patients were age, the dose of glucocorticoid, and disease duration.

Background Several lines of evidence imply that brain-derived neurotrophic factor (BDNF) is involved in the pathophysiology of fibromyalgia (FM); in this regard, patients with FM have altered blood and cerebrospinal fluid levels of BDNF. In this study, we explored the association between BDNF gene polymorphisms and FM susceptibility and the severity of symptoms. Methods In total, 409 patients with FM and 423 healthy controls in 10 medical centers were enrolled from the Korean nationwide FM survey. The alleles and genotypes at 10 positions in the BDNF gene were genotyped. Results The allele and genotype frequencies of BDNF rs11030104 differed significantly between the patients with FM and the controls (P = 0.031). The GG genotype of rs11030104 had a protective effect against FM (P = 0.016), and the G allele of rs11030104 was negatively associated with the presence of FM compared with the A allele (P = 0.013). In comparison, although the allele and genotype frequencies of BDNF rs12273539 did not differ between the two groups, the TT genotype of BDNF rs12273539 was associated with susceptibility to FM (P = 0.038). Haplotype analyses implied that some BDNF haplotypes have a protective effect against FM. Finally, several genotypes and haplotypes of the BDNF gene contributed to specific symptoms of FM. Conclusions This study is the first to evaluate the associations between BDNF gene polymorphisms and FM. Our results imply that some BDNF single-nucleotide polymorphisms and haplotypes are associated with susceptibility to, and contribute to the symptoms of, FM.

Background Allopurinol is the most common cause of severe cutaneous adverse reactions (SCARs) in Korea due to the relatively high prevalence of the HLA-B*58:01 genotype (8%-13%). Objective We aimed to reveal the clinical characteristics and risk factors for death in allopurinol-induced SCARs in Korea. Methods We retrospectively reviewed the medical records of 106 subjects with allopurinol-induced SCARs and 639 subjects with other drug-induced SCARs who were enrolled in the Korean SCARs Registry (collected from 34 nationwide medical institutions) from January 2010 to December 2015. Results Subjects with allopurinol-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) were older and had more comorbidities, longer latent periods, longer disease durations, more deranged laboratory findings, and increased disease severity resulting in a higher mortality rate (17.6% vs 7.6%; P = .020) compared with the subjects with other drug-induced SCARs. There was no significant difference in age or mortality in drug reaction with eosinophilia and systemic symptoms (DRESS). Subjects with allopurinol-induced SJS/TEN were older and had shorter latent periods and a higher mortality rate (17.6% vs 3.7%; P = .044) than those with allopurinol-induced DRESS. In allopurinol-induced SJS/TEN, significant risk factors for death included chronic renal insufficiency, intensive care unit (ICU) admission, increased blood urea nitrogen levels on admission day, serum peak eosinophil counts, baseline and peak creatinine levels, baseline and peak alanine aminotransferase levels, and decreased lowest platelet counts. In allopurinol-induced DRESS, significant risk factors for death included ICU admission and increased glucose levels on admission day. Conclusions Allopurinol-induced SCARs have unique characteristics and poor prognoses with important predictive factors of death.

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.

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

The aim of this study was to compare anti-tumor necrosis factor-α (TNFα) treatment status in rheumatoid arthritis (RA) patients with the Korean National Health Insurance (KNHI) reimbursement eligibility criteria and with American College of Rheumatology (ACR) recommendations, Japan College of Rheumatology (JCR) guidelines and British Society for Rheumatology (BSR) guidelines. Between December 2011 and August 2012, outpatients from 17 South Korean general hospitals diagnosed with RA according to the 1987 ACR criteria were enrolled into a noninterventional, cross-sectional, observational study. Of 1700 patients (1414 female (83.2 %), mean age of 56.6 ± 12.0, mean disease duration 97.9 ± 91.8 months), 306 (18.0 %) had used anti-TNFα agents, and 224 (13.2 %) were currently using an anti-TNFα agent. Of 1394 anti-TNFα-naive patients, 32 (2.3 %) met KNHI reimbursement guidelines, 148 (10.6 %) met ACR recommendations, and 127 (9.1 %) and 126 (9.0 %) were considered eligible for anti-TNFα agents according to JCR and BSR guidelines, respectively. The main discrepancy was the higher active joint count required by the KNHI eligibility criteria. In the opinion of treating rheumatologists, the KNHI reimbursement criteria ineligibility accounted for 15.3 % (n = 213) of the reasons for not initiating anti-TNFα agents in anti-TNFα-naive group. The anti-TNFα user group showed significantly higher disease activity than the anti-TNFα-naive group based on DAS28 score. In comparison with the ACR recommendations and JCR and BSR guidelines, fewer patients met KNHI reimbursement eligibility criteria for anti-TNFα agents. The current amendment of the KNHI criteria based on DAS28 score will improve an access to biologic agents including anti-TNFα treatment for South Korean patients with active RA.

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

Objective. Failure of first-line anti-tumor necrosis factor (TNF) agents in in rheumatoid arthritis patients leads to decisions among second-line biologic agents. To better inform these decisions, the therapeutic effectiveness of rituximab is compared with other second-line biologic agents in this observational study. Methods. Between November 2011 and December 2014, study subjects were observed for 12 month periods. Patients with an inadequate response to initial anti-TNF agent received either rituximab or alternative anti-TNF agents (adalimumab/etanercept/infliximab) based on the preference of patients and physicians. The efficacy end point of this study was the change in 28-joint count Disease Activity Score (DAS28) at six and 12 months from baseline. Safety data were also collected. Results. Ninety patients were enrolled in the study. DAS28 at six months did not change significantly whether the patients were treated with rituximab or alternative anti-TNF agents in intention-to-treat analysis (n=34, -1.63±0.30 vs. n=31, -2.05±0.34) and standard population set analysis (n=31, -1.51±0.29 vs. n=24, -2.21±0.34). Similarly, the change in DAS28 at 12 months did not reach statistical significance (-1.82±0.35 in the rituximab vs. -2.34±0.44 in the alternative anti-TNF agents, p=0.2390). Furthermore, the incidences of adverse events were similar between two groups (23.5% for rituximab group vs. 25.8% for alternative anti-TNF agents group, p=0.7851). Conclusion. Despite the limitations of our study, switching to rituximab or alternative anti-TNF agents after failure of the initial TNF antagonist showed no significant therapeutic difference in DAS28 reduction. (J Rheum Dis 2017;24:227-235)

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.

We have cloned apolipophorin-III (apoLp-III) cDNA from adult fat body of Spodoptera litura. The sequence encodes a 188 amino acid polypeptide including a 22 amino acid leader peptide. The circular dichroism spectrum from the purified apoLp-III indicated a considerable content of alpha-helix. Sequence alignment showed that S. litura apoLp-III has a relatively high degree of sequence identity with the apoLps-III of lepidopteran, Manduca sexta (72%), Galleria mellonella (67%), Bombyx mori (60%). These alignments with four lepidopteran apoLps-III showed highly identical residues and conservative replacements at a degree of 86%. Levels of mRNA from last instar larval fat body and adult fat body were compared through Northern blot analysis using 32-P-labeled 704 bp apoLp-III cDNA probe. A 850 bp mRNA was detected in both stages and mRNA level of day 1 adult fat body was much higher than that of last instar larval fat body. The tissue-distribution of apoLp-III mRNA in adult ovary and testis was also examined and we confirmed the presence of apoLp-III mRNA in ovary and testis although apoLp-III was expressed in these tissues at very low levels compared with the adult fat body.

Cytomegalovirus (CMV) retinitis rarely occurs in patients with connective tissue disease. We present a rare case of CMV retinitis in a patient with dermatomyositis. A 38-year-old man was admitted due to blurred vision and floaters of right eye. He had been diagnosed with dermatomyositis and taken prednisolone and immunosuppressive agents for 10 months. He was diagnosed as having CMV retinitis based upon ophthalmologic examination, decreased CD4+T cell count, and positive IgM anti-CMV antibody. Intravenous ganciclovir was administrated with cessation of immunosuppressive agents for 40 days and the lesion did not progress. This is the first report of a CMV retinitis that developed in a patient with dermatomyositis.

Background The prevalence of restless legs syndrome (RLS) in patients with peripheral neuropathy has been reported to be higher than that of the general population in some studies, which suggests an association between neuropathy and RLS, but not all studies show increased RLS with neuropathy. These differences may reflect adequacy of the diagnosis, effects of chronic pain complicating the diagnosis, or population differences. Moreover, if there is increased risk for RLS with neuropathy, it may reflect consequences of the chronic pain rather than other aspects of diabetes mellitus (DM). Therefore, we investigated the effects of diagnosis rigor on the estimated prevalence of RLS in patients with diabetic peripheral neuropathy (DPN) and those with chronic leg pain from osteoarthritis (OA), and then we compared the RLS prevalence in these two populations with each other and with population prevalence for Korea. Methods Our study is a prospective case-control study of 199 patients with DPN and 220 patients with OA. After evaluating the presence of RLS in these subjects using the diagnostic criteria of the International RLS Study Group, we confirmed the diagnosis of RLS through face-to-face interviews using the 18-item Hopkins Diagnostic Questionnaire, which removes RLS mimics; and through independent examinations by two neurologists. Results Of the 199 subjects with DPN, 44 (22%) appeared to have RLS from their answers on the 4-item RLS diagnostic questionnaire compared to 8 (3.6%) of 220 subjects with OA. However, the prevalence of RLS in the DPN group dropped to 16 (8%) subjects but stayed at 8 (3.6%) OA subjects when using the Hopkins Telephone Diagnostic Interview (HTDI) adapted for clinical interview. The RLS prevalence determined by HTDI remained significantly higher ( P =.042) in the DPN group compared to the OA group and was twice that reported for the general Korean population (8% vs 3.9%). Among subjects with DPN, those with RLS were older (68.06±8.43years vs 62.46±11.05years; P =.049) and had higher pain scores (visual analog scale [VAS], 4.69±2.52 vs 2.72±2.12; P =.002). The quality of sleep (MOS [Medical Outcomes Study] sleep scale) and health-related quality of life (QoL) (total score on the 36-Item Short-Form Health Survey [SF-36]) showed no significant difference between the two groups. Conclusions The prevalence of RLS in patients with DPN cannot be accurately assessed with only the four diagnostic criteria interview, but the prevalence was higher than expected for Koreans from the general population prevalence and also was higher than occurred with OA patients with chronic leg pains when accurately assessed with a structured interview. Chronic leg pain from OA does not significantly complicate RLS diagnosis, and chronic pain itself does not explain the increased RLS prevalence in diabetic neuropathy.

Quetiapine is an atypical antipsychotic and has also been used in the treatment of depression. Since anti-inflammatory effects of antidepressants are well established, we hypothesized that quetiapine may also exert anti-inflammatory effects. Thus this study was designed to examine the anti-inflammatory effect of quetiapine in murine collagen-induced arthritis. Mice were immunized with collagen type II for the induction of arthritis and treated with quetiapine (10mg/kg) daily for 2weeks. Mice were divided into 3 groups: control, CIA, and CIA+quetiapine treatment. Arthritic index and paw thickness were used to compare severity of arthritis. In additions, radiological and histological assessments were employed. Anti-type II collagen-specific antibody, interleukin-6 (IL-6), interleukin-17 (IL-17), and prostaglandin E(2) (PGE(2)) were evaluated at the end of the treatment period. Both arthritic index and paw thickness were markedly improved in CIA+quetiapine treatment group compared with those in CIA groups (arthritic index; P

A 70-year-old man presented with left-sided weakness and dysarthria. His brain MRI and magnetic resonance angiography demonstrated acute infarctions in the bilateral middle cerebral artery territories in a setting of agenesis of the right internal carotid artery (ICA) with transcavernous anastomosis, a rare developmental anomaly. In this setting, atherosclerotic disease in the unilateral common carotid artery or ICA can induce acute infarctions in the bilateral anterior circulation.

BACKGROUND Skin grafting is a commonly performed procedure, but studies of changes in the levels of cytokines after skin grafting have not been reported. OBJECTIVE We examined changes in cytokines and the degree of erythema after skin grafting in pigs in the control group. Interferon alpha (IFN-α) was injected to reduce erythema, and subsequent changes in cytokines and the degree of erythema were examined in the experimental group. METHODS Vascular endothelial growth factor (VEGF), thrombospondin-1 (TSP1), and CD31 were examined using Western blot analysis and immunohistochemistry. The degree of erythema was measured at 2, 4, and 8 weeks using a chromometer. RESULTS In the control group, VEGF increased at 2 weeks and decreased at 4 and 8 weeks. TSP1 increased over time. CD31 increased to 4 weeks and decreased at 8 weeks. In the experimental group, VEGF was lower at 2 weeks and higher at 8 weeks than in the control group, TSP1 was higher at 2 weeks and lower at 8 weeks, and CD31 was lower at 4 and 8 weeks. Erythema in the experimental group was lower than that in the control group at 2 and 8 weeks. CONCLUSION IFN-α may be one of the agents that reduces erythema by suppressing excessive revascularization.

The aim of this study was to analyze the relationship between serum pro-hepcidin concentration and the anemia profiles of rheumatoid arthritis (RA) and to estimate the pro-hepcidin could reflect the disease activity of RA. RA disease activities were measured using Disease Activity Score 28 (DAS28), tender/swollen joint counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Anemia profiles such as hemoglobin, iron, total iron binding capacity (TIBC), ferritin, and transferrin levels were measured. Serum concentration of pro-hepcidin, the prohormone of hepcidin, was measured using enzyme-linked immunosorbent assay (ELISA). Mean concentration of serum pro-hepcidin was 237.6+/-67.9 ng/mL in 40 RA patients. The pro-hepcidin concentration was correlated with rheumatoid factor, CRP, ESR, and DAS28. There was a significant correlation between pro-hepcidin with tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6. The pro-hepcidin concentration was significantly higher in the patients with active RA (DAS285.1) than those with inactive to moderate RA (DAS28or =5.1). However, the pro-hepcidin concentration did not correlate with the anemia profiles except hemoglobin level. There was no difference of pro-hepcidin concentration between the patients with anemia of chronic disease and those without. In conclusion, serum concentration of pro-hepcidin reflects the disease activity, regardless of the anemia states in RA patients, thus it may be another potential marker for disease activity of RA.

This study was conducted to evaluate the diagnostic accuracy of power Doppler ultrasonography (PDU) for differentiating secondary from primary Raynaud’s phenomenon (RP), and also compared PDU with nailfold capillaroscopy (NFC) for the assessment of microvascularity in undifferentiated connective tissue disease (UCTD) patients with RP. Microvascularity in the nailfold and finger tip was evaluated using PDU with cold challenge, and the findings of PDU were classified according to the qualitative grading system before and after cold challenge. NFC was performed at the same day in all persons. The results of PDU were compared with the clinical, laboratory data, and the findings of NFC. The 14 UCTD patients with RP were included in our study. Seven patients were suspected of secondary RP in NFC examination, thus NFC yielded a correct classification into secondary RP in 50% of the UCTD patients. The PDU finding of pattern II, which is regarded as the finding of secondary RP, was observed in 12 UCTD patients with RP. Thus, PDU yielded a correct classification into secondary RP in 86% of UCTD patients. In conclusion, we confirmed that PDU has a higher correct classification rate than NFC for the diagnosing of secondary RP in UCTD patients. Our results suggest that PDU has better accuracy than NFC in differentiating secondary from primary RP, and PDU is more useful in assessing microvascular abnormalities in UCTD patients with RP.

We report a case of rapidly-progressive glomerulonephritis complicating Behcet's disease (BD). A 44-year-old male has suffered from recurrent oral ulcers and retinal vasculitis developed 2 years ago. He complained of abdominal pain and papulopustular skin lesions. Multiple ulcers were seen on the colon on colonoscopy. Routine renal work-up revealed heavy proteinuria and hematuria. Renal biopsy demonstrated crescentic glomerulonephritis. Most symptoms improved after steroid therapy, except for urinary abnormalities. At this point, intravenous monthly cyclophosphamide pulse therapy was undergone. After the sixth pulse therapy, proteinuria and hematuria were dramatically improved and renal function was well preserved.

Objective. To evaluate the prevalence of sleep disturbance in Korean patients with ankylosing spondylitis (AS), and its association with disease activity and depression. Methods. Forty patients with AS and eighty healthy controls were included in this study. Sleep quality was assessed using the Korean version of Pittsburgh sleep quality index (PSQI). Depression was assessed by the Korean version of Beck depression inventory second edition (BDI-2). Ankylosing spondylitis disease activity score-C-reactive protein (ASDAS-CRP) was used to evaluate disease activity. Patients were dichotomized into a good sleeper group (PSQI≤5) and a poor sleeper group (PSQI>5). Results. The mean total PSQI score of patients with AS was 7.23±3.84. It was higher than that of the control subjects. AS patients had higher scores in all of the PSQI components, except for the use of sleep medication. Sixty percent of the AS patients were classified as poor sleepers. The mean BASDAI, ASDAS-CRP, and BDI-2 scores of the poor sleeper group were higher than that of the good sleeper group. Significantly, higher disease activity according to ASDAS-CRP was associated with poor sleep quality and depression. Multiple regression analysis revealed that the duration of morning stiffness and depression were independent risk factors that influenced poor sleep quality. Conclusion. Sleep disturbances are prevalent amongst Korean patients with AS. Lower quality of sleep is significantly associated with higher disease activity and depression. Therefore, optimal management to improve sleep quality in patients with AS is important.

Adefovir dipivoxil (ADV) is a nucleotide used as long-term therapy of chronic hepatitis B. Many published reports have shown that long-term high-dose therapy with adefovir can be associated with proximal renal tubular dysfunction resulting in significant hypophosphatemia, renal insufficiency and osteomalacia. We have encountered two patients who developed evidence of hypophosphatemic osteomalacia while on long-term low-dose adefovir therapy for chronic hepatitis B. We report on its clinical features and its potential resolution with cessation of the drug and supplementation with phosphate. We also reviewed the other published cases associated with hypophosphatemic osteomalacia after low-dose adefovir therapy. The symptoms and the hypophosphatemia improved after cessation of the drug and supplementation with phosphate in most cases. Patients taking adefovir long-term should receive regular investigation of the phosphate level and renal function.

Polymyalgia rheumatica is an inflammatory disease affecting elderly and involving the shoulder and pelvic girdles. No epidemiological study of polymyalgia rheumatica was conducted in Korea. We retrospectively evaluated patients with polymyalgia rheumatica followed up at the rheumatology clinics of 10 tertiary hospitals. In total 51 patients, 36 patients (70.6%) were female. Age at disease onset was 67.4 yr. Twenty-three patients (45.1%) developed polymyalgia rheumatica in winter. Shoulder girdle ache was observed in 45 patients (90%) and elevated erythrocyte sedimentation rate (> 40 mm/h) in 49 patients (96.1%). Initial steroid dose was 23.3 mg/d prednisolone equivalent. Time to normal erythrocyte sedimentation rate was 4.1 months. Only 8 patients (15.7%) achieved remission. Among 41 patients followed up, 28 patients (68.3%) had flare at least once. Number of flares was 1.5 ± 1.6. The frequency of flare was significantly lower in patients with remission (P = 0.02). In Korea, polymyalgia rheumatica commonly develops during winter. Initial response to steroid is fairly good, but the prognosis is not benign because remission is rare with frequent relapse requiring long-term steroid treatment.

The objective of this study was to investigate clinical and radiographic features and gender differences in Korean patients with adult-onset ankylosing spondylitis. Multicenter cross-sectional studies were conducted in the rheumatology clinics of 13 Korean tertiary referral hospitals. All patients had a confirmed diagnosis of ankylosing spondylitis according to the modified New York criteria. Clinical, laboratory, and radiographic features were evaluated and disease activities were assessed using the Bath ankylosing spondylitis disease activity index. Five hundred and five patients were recruited. The male to female ratio was 6.1:1. Average age at symptom onset was 25.4+/-8.9 yr and average disease duration was 9.6+/-6.8 yr. Males manifested symptoms at a significantly earlier age. HLA-B27 was more frequently positive in males. Hips were more commonly affected in males, and knees in females. When spinal mobility was measured using tragus-to-wall distance and the modified Schober's test, females had significantly better results. Radiographic spinal changes, including bamboo spine and syndesmophytes, were more common in males after adjustment of confounding factors. In conclusion, we observed significant gender differences in radiographic spinal involvement as well as other clinical manifestations among Korea patients with adult-onset ankylosing spondylitis. These findings may influence the timing of the diagnosis and the choice of treatment.

Objective: This study was designed to identify prognostic determinants of radiographical severity in patients with ankylosing spondylitis (AS) living in Daegu and Kyungpook territories. Methods: One hundred-nineteen patients with AS were consecutively enrolled from four regional general hospitals. Clinical data including smoking habits, alcohol intake, disease duration, HLA-B27 positivity, involvement of peripheral joints, occupational activity, and regular exercise were investigated. Radiographical severity was assessed by the Modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Statistical analyses were performed using the independent Student's t-test, Pearson's correlation coefficient analysis, and multivariate re- gression analysis. Results: Radiographical severity, as evaluated with the mSASSS, was associated with age of disease onset (p=0.011) and disease duration (p

Systemic lupus erythematous (SLE) is an autoimmune inflammatory disease of unknown etiology which affects various parts of body. SLE can involve all parts of the heart including the pericardium, myocardium, endocardium, heart valves and coronary arteries. Cardiopathy of SLE is the third common cause of death in all patients with SLE. Although cardiopulmonary symptoms are common in SLE, symptomatic acute lupus myocarditis is a very rare and fatal complication of SLE. We report here on a 20-year-old female patient with acute myocarditis as a initial manifestation of SLE and rapidly diagnosed using echocardiogram.

Cryptococcal infection is a rare, yet well recognized complication of systemic lupus erythematosus (SLE). We present a case of mesenteric and retroperitoneal cryptococcal lymphadenitis resulting in the obstruction of the stomach and proximal duodenum in a patient suffering from SLE, while recently she did not receive any immunosuppressive treatment. A 42-yr-old woman was admitted due to high fever and diffuse abdominal pain for three weeks. Abdominal computed tomography (CT) scan showed multiple conglomerated lymphadenopathies in the retroperitoneum and the mesentery resulting in luminal narrowing of the third portion of the duodenum. Cryptococcal lymphadenitis was proven by needle biopsy and she was treated with intravenous liposomal amphotericin B, followed by oral fluconazole. After fourteen-month antifungal therapies, the clinical symptoms and follow-up images improved. This case emphasize that the intrinsic immunological defects of SLE may be directly responsible for the predisposition to fungal infections.