KOBIO, the First Web-based Korean Biologics Registry Operated With a Unified Platform Among Distinct Disease Entities

The KOrean College of Rheumatology BIOlogics and targeted therapy (KOBIO) registry is a nationwide observational cohort that captures detailed data on exposure of patients to biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs). This registry was launched in December 2012 with an aim to prospectively investigate clinical manifestations and outcomes of patients with rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis who initiated a biologic or targeted synthetic DMARD or switched to another. Demographic data, disease activity, current treatment, adverse events, terms based on Medical Dictionary for Regulatory Activities, and so on are registered for patients who are then followed up annually in a web-based unified platform. The KOBIO registry also recruits and collects data of patients with RA on conventional DMARDs for comparison. As of today, more than 5,500 patients were enrolled from 47 academic and community Rheumatology centers across Korea. The KOBIO registry has evolved to become a powerful database for clinical research to improve clinical outcomes and quality of treatment.

KOBIO, the First Web-based Korean Biologics Registry Operated With a Unified Platform Among Distinct Disease Entities

The KOrean College of Rheumatology BIOlogics and targeted therapy (KOBIO) registry is a nationwide observational cohort that captures detailed data on exposure of patients to biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs). This registry was launched in December 2012 with an aim to prospectively investigate clinical manifestations and outcomes of patients with rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis who initiated a biologic or targeted synthetic DMARD or switched to another. Demographic data, disease activity, current treatment, adverse events, terms based on Medical Dictionary for Regulatory Activities, and so on are registered for patients who are then followed up annually in a web-based unified platform. The KOBIO registry also recruits and collects data of patients with RA on conventional DMARDs for comparison. As of today, more than 5,500 patients were enrolled from 47 academic and community Rheumatology centers across Korea. The KOBIO registry has evolved to become a powerful database for clinical research to improve clinical outcomes and quality of treatment.

The Effects of Sex and Estrogen on Radiographic Progression of Ankylosing Spondylitis in Korean Patients

. Ankylosing spondylitis (AS) is a chronic inflammatory disease with obvious male preponderance. Males show more severe radiographic manifestations compared with females. This study aimed to evaluate the effects of sex and estrogen on the radiographic progression of AS. Methods. A total of 101 patients with AS were included in this study. All of the radiographs were scored using the modified Stoke AS Spine Score (mSASSS). Serum levels of 17β-estradiol (E2), dickkopf-1 (Dkk1), and leptin were detected by enzyme-linked immunosorbent assay. The generalized estimating equations model was used to evaluate factors associated with spinal radiographic progression. Results. The mean age at disease onset was 27.3±10.7 years, and 16 patients (15.8%) were female. In the multivariable analysis, body mass index (β-coefficient=0.12; β=0.047) and levels of Dkk1 (β-coefficient=−0.11; β＜0.001), and female (β-coefficient=−1.40; β=0.001) were associated with radiographic progression. Among male patients with AS, baseline C-reactive protein (β=0.11; β=0.005) and mSASSS (β=0.21; p=0.030) were also associated with radiographic progression. E2 and leptin levels were not significantly related to the radiographic progression. Conclusion. Although female patients were associated with less radiographic progression in AS, there was no significant relationship between serum estrogen level and radiographic progression. Results of current study suggests that genetic factors or other environmental factors associated with female may influence radiographic progression in patients with AS.

Hyperuricemia is Associated With an Increased Prevalence of Metabolic Syndrome in a General Population and a Decreased Prevalence of Diabetes in Men

. Elevated uric acid is associated with cardiovascular disease and metabolic syndrome. However, uric acid is also an antioxidant with beneficial effect on comorbidities. The aim of this study was to evaluate the relationship of serum uric acid with diabetes, metabolic syndrome, and cardiovascular disease in a Korean adult population. Methods. A total of 5,887 (weighted n=40,251,868) participants aged ≥19 years from the 2016 Korean National Health and Nutrition Examination Survey were included for analysis. Weighted prevalence and odds ratio (OR) of comorbidities were analyzed according to the presence of hyperuricemia and uric acid quartile. Results. Participants of both sexes with hyperuricemia showed higher prevalence of metabolic syndrome, hypertension, hypertriglyceridemia, and obesity than those without hyperuricemia. After adjusting for socioeconomic and lifestyle characteristics, hyperuricemia was associated with a decreased prevalence of diabetes mellitus in men (OR: 0.44, 95% confidence interval [CI]: 0.28∼0.72, p=0.001) and a decreased prevalence of myocardial infarction or angina (OR: 0.25, 95% CI: 0.08∼0.75, p=0.013) in women. Hyperuricemia was significantly associated with an increased prevalence of metabolic syndrome in both men (OR: 1.81, 95% CI: 1.33∼2.45, p＜0.001) and women (OR: 1.95, 95% CI: 1.22∼ 3.13, p=0.006). Conclusion. Hyperuricemia was associated with a decreased prevalence of diabetes mellitus in men and a decreased prevalence of myocardial infarction or angina in women. Hyperuricemia was associated with an increased prevalence of metabolic syndrome in both men and women.

The Practice Guideline for Vaccinating Korean Patients With Autoimmune Inflammatory Rheumatic Disease

To develop a clinical practice guideline for vaccination in patients with autoimmune inflammatory rheumatic disease (AIIRD), the Korean College of Rheumatology and the Korean Society of Infectious Diseases developed a clinical practice guideline according to the clinical practice guideline development manual. Since vaccination is unlikely to cause AIIRD or worsen disease activities, required vaccinations are recommended. Once patients are diagnosed with AIIRD, treatment strategies should be established and, at the same time, monitor their vaccination history. It is recommended to administer vaccines when the disease enters the stabilized stage. Administering live attenuated vaccines in patients with AIIRD who are taking immunosuppressants should be avoided. Vaccination should be considered in patients with AIIRD, prior to initiating immunosuppressants. It is recommended to administer influenza, Streptococcus pneumoniae, hepatitis A, hepatitis B, herpes zoster, measles-mumps-rubella virus, human papillomavirus, and tetanus-diphtheria-pertussis vaccines in patients with AIIRD; such patients who planned to travel are generally recommended to be vaccinated at the recommended vaccine level of healthy adults. Those who live in a household with patients with AIIRD and their caregivers should also be vaccinated at levels that are generally recommended for healthy adults.

The Practice Guideline for Vaccinating Korean Patients with Autoimmune Inflammatory Rheumatic Disease

To develop a clinical practice guideline for vaccination in patients with autoimmune inflammatory rheumatic disease (AIIRD), the Korean College of Rheumatology and theKorean Society of Infectious Diseases developed a clinical practice guideline according to the clinical practice guideline development manual. Since vaccination is unlikely to cause AIIRD or worsen disease activities, required vaccinations are recommended. Once patients are diagnosed with AIIRD, treatment strategies should be established and, at the same time, monitor their vaccination history. It is recommended to administer vaccines when the disease enters the stabilized stage. Administering live attenuated vaccines in patients with AIIRD who are taking immunosuppressants should be avoided. Vaccination should be considered in patients with AIIRD, prior to initiating immunosuppressants. It is recommended to administer influenza, Streptococcus pneumoniae, hepatitis A, hepatitis B, herpes zoster, measlesmumps- rubella virus, human papillomavirus, and tetanus-diphtheria-pertussis vaccines in patients with AIIRD; such patients who planned to travel are generally recommended to be vaccinated at the recommended vaccine level of healthy adults. Those who live in a household with patients with AIIRD and their caregivers should also be vaccinated at levels that are generally recommended for healthy adults.

Early Detection of Pulmonary Hypertension in Connective Tissue Disease

No abstract available.

Korean Guideline for the Prevention and Treatment of Glucocorticoid-induced Osteoporosis

BACKGROUND: To develop guidelines and recommendations to prevent and treat glucocorticoid (GC)-induced osteoporosis (GIOP) in Korea. METHODS: The Korean Society for Bone and Mineral Research and the Korean College of Rheumatology have developed this guideline based on Guidance for the Development of Clinical Practice Guidelines ver. 1.0 established by the National Evidence-Based Healthcare Collaborating Agency. This guideline was developed by adapting previously published guidelines, and a systematic review and quality assessment were performed. RESULTS: This guideline applies to adults aged ≥19 years who are using or plan to use GCs. It does not include children and adolescents. An initial assessment of fracture risk should be performed within 6 months of initial GC use. Fracture risk should be estimated using the fracture-risk assessment tool (FRAX) after adjustments for GC dose, history of osteoporotic fractures, and bone mineral density (BMD) results. All patients administered with prednisolone or an equivalent medication at a dose ≥2.5 mg/day for ≥3 months are recommended to use adequate calcium and vitamin D during treatment. Patients showing a moderate-to-high fracture risk should be treated with additional medication for osteoporosis. All patients continuing GC therapy should undergo annual BMD testing, vertebral X-ray, and fracture risk assessment using FRAX. When treatment failure is suspected, switching to another drug should be considered. CONCLUSIONS: This guideline is intended to guide clinicians in the prevention and treatment of GIOP.

Korean Guideline for the Prevention and Treatment of Glucocorticoid-induced Osteoporosis

OBJECTIVE: To develop guidelines and recommendations to prevent and treat glucocorticoid-induced osteoporosis (GIOP) in Korea. METHODS: The Korean Society for Bone and Mineral Research and the Korean College of Rheumatology developed this guideline based on Guidance for the Development of Clinical Practice Guidelines version 1.0 established by the National Evidence-Based Healthcare Collaborating Agency. This guideline was developed by adapting previously-published guidelines, and a systematic review and quality assessment were conducted. RESULTS: This guideline applies to adults aged 19 years or older who are using or plan to use glucocorticoids (GCs), but does not include children and adolescents. An initial assessment of fracture risk should be performed within 6 months of initial GC use. Fracture risk should be estimated using FRAX (Fracture Risk Assessment Tool) with adjustments for GC dose, previous osteoporotic fracture history, and bone mineral density (BMD) results. All patients taking more than 2.5 mg/day prednisolone or equivalent for more than 3 months are recommended to take adequate calcium and vitamin D. Patients at moderate to high fracture risk should be treated with additional osteoporosis medication. All patients continuing GC therapy should receive an annual BMD measurement, vertebral X-ray, and fracture risk assessment using FRAX. When a treatment failure is suspected, switching to another drug should be considered. CONCLUSION: This guideline is intended to provide guidance for clinicians in prevention and treatment of GIOP.

Outcome in Patients with Fever of Unknown Origin whose ¹⁸Fluoro-Deoxyglucose Positron Emission Tomography/Computerized Tomography Finding is Non-Diagnostic

Prognosis has not been known for patients with fever of unknown origin (FUO) whose ¹⁸fluoro-deoxyglucose (¹⁸F-FDG) positron emission tomography/computerized tomography (PET/CT) finding is non-diagnostic. A total of eight patients with FUO that underwent ¹⁸F-FDG PET/CT were retrospectively identified January 2016 - June 2017 in a tertiary hospital in Korea. Of these, two patients were diagnosed with microscopic polyangitis and Kikuchi's disease and one patient was transferred to another hospital. Of five patients whose diagnoses were not confirmed, four patients received non-steroidal anti-inflammatory drug and/or low dose steroid and symptoms disappeared. Our study suggests that outcome of patients with FUO whose ¹⁸F-FDG PET/CT finding is non-diagnostic would be favorable.

Outcome in Patients with Fever of Unknown Origin whose ¹⁸Fluoro-Deoxyglucose Positron Emission Tomography/Computerized Tomography Finding is Non-Diagnostic

Prognosis has not been known for patients with fever of unknown origin (FUO) whose ¹⁸fluoro-deoxyglucose (¹⁸F-FDG) positron emission tomography/computerized tomography (PET/CT) finding is non-diagnostic. A total of eight patients with FUO that underwent ¹⁸F-FDG PET/CT were retrospectively identified January 2016 - June 2017 in a tertiary hospital in Korea. Of these, two patients were diagnosed with microscopic polyangitis and Kikuchi's disease and one patient was transferred to another hospital. Of five patients whose diagnoses were not confirmed, four patients received non-steroidal anti-inflammatory drug and/or low dose steroid and symptoms disappeared. Our study suggests that outcome of patients with FUO whose ¹⁸F-FDG PET/CT finding is non-diagnostic would be favorable.

Cardiovascular and Gastrointestinal Effects of Etoricoxib in the Treatment of Osteoarthritis: A Systematic Review and Network Meta-analysis

OBJECTIVE: To estimate the cardiovascular (CV) and gastrointestinal (GI) risks of etoricoxib in the treatment of osteoarthritis (OA) compared to a placebo and other non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: A systematic review of randomized, controlled trials (RCTs) of etoricoxib were performed. Bayesian network meta-analysis was used over a duration of 12 weeks. The incidence of CV and GI events for a duration ≥26 weeks were also tabulated and presented using descriptive statistics. RESULTS: From this search, 10 studies were identified. Of these, 6 and 5 RCTs that measured the CV and GI events at 12 weeks were included in meta-analysis. They showed that etoricoxib did not increase the CV events compared to the placebo or NSAIDs during the 12 week period (odds ratio [OR]=0.59 compared to celecoxib, OR=0.89 with ibuprofen, OR=0.70 with placebo, and OR=2.16 with naproxen). The risk of GI events was comparable to that of most comparators, with the exception of naproxen, which had a significantly lower risk of GI events (OR=0.18) during the 12 week period. For a duration ≥26 weeks, the incidence of CV and GI events with etoricoxib increased with increasing duration. CONCLUSION: Etoricoxib is an alternative short-term treatment option for OA, showing comparable CV and GI complications to other NSAIDs. Nevertheless, further studies will be needed to elucidate the long-term safety of etoricoxib in the treatment of OA.

Relapsing Polychondritis with Central Nervous System Involvement: Experience of Three Different Cases in a Single Center

Relapsing polychondritis (RP) is an autoimmune disorder characterized by inflammation in cartilaginous structures including the ears, noses, peripheral joints, and tracheobronchial tree. It rarely involves the central nervous system (CNS) but diagnosis of CNS complication of RP is challenging because it can present with varying clinical features. Herein we report 3 cases of relapsing polychondritis involving CNS with distinct manifestations and clinical courses. The first patient presented with rhombencephalitis resulting in brain edema and death. The second patient had acute cognitive dysfunction due to limbic encephalitis. He was treated with steroid pulse therapy and recovered without sequelae. The third patient suffered aseptic meningitis that presented as dementia, which was refractory to steroid and immune suppressive agents. We also reviewed literature on CNS complications of RP.

Autoantibodies as Biomarkers of Systemic Lupus Erythematosus

No abstract available.

Baseline Characteristics of the Korean Registry of Pulmonary Arterial Hypertension

Despite recent advances in understanding of the pathobiology and targeted treatments of pulmonary arterial hypertension (PAH), epidemiologic data from large populations have been limited to western countries. The aim of the Korean Registry of Pulmonary Arterial Hypertension (KORPAH) was to examine the epidemiology and prognosis of Korean patients with PAH. KORPAH was designed as a nationwide, multicenter, prospective data collection using an internet webserver from September 2008 to December 2011. A total of 625 patients were enrolled. The patients' mean age was 47.6 +/- 15.7 yr, and 503 (80.5%) were women. The diagnostic methods included right heart catheterization (n = 249, 39.8%) and Doppler echocardiography (n = 376, 60.2%). The etiologies, in order of frequency, were connective tissue disease (CTD), congenital heart disease, and idiopathic PAH (IPAH) (49.8%, 25.4%, and 23.2%, respectively). Patients with WHO functional class III or IV at diagnosis were 43.4%. In total, 380 (60.8%) patients received a single PAH-specific treatment at the time of enrollment, but only 72 (18.9%) patients received combination therapy. Incident cases during the registry represented 297 patients; therefore, the incidence rate of PAH was 1.9 patients/yr/million people. The 1st-, 2nd-, and 3rd-yr estimated survival rates were 90.8%, 87.8%, and 84.4%, respectively. Although Korean PAH patients exhibited similar age, gender, and survival rate compared with western registries, they showed relatively more CTD-PAH in the etiology and also systemic lupus erythematosus among CTD-PAH. The data suggest that earlier diagnosis and more specialized therapies should be needed to improve the survival of PAH patients.

A Case of Axial Spondyloarthropathy in a Patient with Human Immunodeficiency Virus Infection

Human immunodeficiency virus (HIV) infection is a global pandemic affecting more than 2.9 million people. Aside from opportunistic infections and malignancies, it involves multiple organs, resulting in many complications, and frequently shows various rheumatic manifestations. With improving survival of patients due to the development of highly active anti-retroviral therapy, the number of HIV-infected patients with rheumatic complications is certain to increase. However, reports on HIV induced rheumatic manifestations in Korean patients are limited. On the other hand, spondyloarthropathy is the most common form of inflammatory arthropathy in HIV associated rheumatic manifestations and is frequently accompanied by peripheral arthritis and enthesitis, while axial skeletal involvement is a rare presentation. Herein we report on a 46-year-old man with HIV infection presenting with an axial spondyloarthropathy who was treated successfully with nonsteroidal anti-inflammatory drug, sulfasalazine, and low dose steroid.

Cryoglobulinemia with a Digital Gangrene from Monoclonal Gammopathy of Undetermined Significance

No abstract available.

Prediction for TNF Inhibitor Users in RA Patients According to Reimbursement Criteria Based on DAS28

OBJECTIVE: The purpose of this study is to examine the difference between the numbers of patients in rheumatoid arthritis (RA) who are eligible to TNF inhibitors by the past Korean National Health Insurance reimbursement guideline and by the disease activity score with 28-joint assessment (DAS28) based criteria. METHODS: Data were obtained from a multi-center registry for biologics users in Korean RA patients, BIOlogics Pharmacoepidemiologic StudY (BIOPSY). DAS28 was calculated based on either ESR or CRP, and DAS28 of more than 5.1 or between 3.2 and 5.1 with radiographic changes was defined as a cut-off point for the initiation of TNF inhibitors. For the maintenance criteria, we used both of improving in DAS28 score (>1.2) and low disease activity (DAS 28<3.2). Differences between the numbers in each step by two criteria were described with Chi-square test and Kappa agreement. RESULTS: Of the 489 patients in BIOPSY, 299 were included in this study. Among them, 278 patients (93.0%) were eligible of TNF inhibitors when we applied the new initiation criteria with DAS28-ESR, and 244 patients (81.6%) were indicated for TNF inhibitors with DAS28-CRP. For the maintenance criteria, a low disease activity (DAS28<3.2) in 3 months after starting TNF inhibitors is too strict for achieving (33.6% with DAS28-ESR and 50.0% with DAS28-CRP). Instead, decreasing DAS28 by more than 1.2 is more reasonable as a tool for deciding early responsiveness of TNF inhibitors in RA patients (81.2% both with DAS28-ESR and DAS28-CRP). CONCLUSION: Our results show that the candidates for TNF inhibitors will be enormously changed according to a change in the reimbursement criteria. To define appropriate patients to receive TNF inhibitors, a further study with regard to the impact of changes in the reimbursement criteria on the outcomes of RA patients will be required.

A Case of Behcet's Disease Complicated by IgA Nephropathy

Behcet's disease (BD) is a rare, multisystemic disorder characterized by vasculitis. Although renal involvement rarely coexists with BD, several types of renal involvements have been reported: amyloidosis, glomerulonephritis and vascular involvement. Herein, we report a rare case of BD complicated with IgA nephropathy (IgAN). A 42-year-old woman visited the hospital due to joint pains and painful subcutaneous nodules. Based on her medical history of recurrent orogenital ulcers, arthritis, enteral ulcers, erythema nodosum-like skin lesions, and a positive pathergy test, we diagnosed her with BD. To evaluate proteinuria, we performed a renal biopsy. The patient was diagnosed with BD complicated with IgAN, and treated with a low dosage of steroid, colchicine, as well as angiotensin II type I receptor blockers. Although renal involvement in BD is rare, it is important to periodically perform renal function assessments in patients with BD involving abnormal urine results.

A Case of Skin Sclerosis Associated with Docetaxel Chemotherapy for Non-Small Cell Lung Cancer

A 64-year-old woman was diagnosed with non-small cell lung cancer. Her disease was stage 4 (T2N2M1) with squamous cell carcinoma. She had been treated with docetaxel and carboplatin. After a completion of 11 cycle of chemotherapy, edema appeared on both feet and had spread rapidly up to the pretibial area without response to diuretics. Sclerotic changes and pigmentation followed but both knees and other parts of the body were spared. There was no evidence of vascular occlusions. On serologic tests, antinuclear, anti-centromere, and anti-topoisomerase I antibodies were all negative. A skin biopsy revealed diffuse infiltration of lymphocytes and discretely thickened collagen bundles in the superficial dermis. After discontinuing docetaxel chemotherapy, she was treated with prednisolone and D-penicillamine and sclerotic changes on the lower legs were improved.