Metabolic syndrome: prevalence and risk factors in Korean gout patients

BACKGROUND/AIMS: We performed this study to investigate associations between metabolic syndrome, chronic kidney disease (CKD), and gout. METHODS: We reviewed the medical records of 151 patients with gout at the Department of Rheumatology in Korea University Ansan Hospital. The following measures were examined: waist circumference, blood pressure, alcohol consumption, and levels of triglyceride, high density lipoprotein cholesterol, fasting serum glucose, serum uric acid (SUA), creatinine, insulin, and C-peptide. We assessed metabolic syndrome by the homeostasis model assessment of insulin resistance (HOMA-IR) index and renal function by the Modification of Diet in Renal Disease equation; patients were classified according to World Health Organization Asia-Pacific obesity criteria. RESULTS: The prevalence of metabolic syndrome in gout patients (50.8%) was higher than in non-gout patients. The mean SUA level was significantly higher in gout patients with metabolic syndrome (9.13 ± 3.15 mg/dL) than in gout patients without metabolic syndrome (8.14 ± 2.07 mg/dL). The mean SUA level was also significantly higher in patients with gout and CKD (9.55 ± 2.86 mg/dL) than in patients with gout but no CKD (7.74 ± 2.27 mg/dL). In gout patients, HOMA-IR was positively correlated with waist circumference (r = 0.409, p = 0.001). CONCLUSIONS: The prevalence of metabolic syndrome in patients with gout was 50.8%, which is higher than the prevalence in the general Korean population. Hyperuricemia in gout patients was correlated with metabolic syndrome and CKD. Insulin resistance may provide clues to better understand the relationship between metabolic syndrome, CKD, and gout.

The Role of Bile Acid Receptors in Chronic Inflammatory Diseases

With recent developments, biologic therapies has shown superior efficacy for rheumatic diseases compared with preexisting pharmacologic therapies, which are associated with high costs, non-response in certain patient groups, and severe adverse effects such as infections limiting their wide-spread use and revealing a need for the development of novel treatments. Since discovering the role of bile acid receptors in regulating inflammation, clinical trials evaluating the use of bile acid receptor agonists as a means to potentially treat various inflammatory disorders, such as alcoholic hepatitis, non-alcoholic steatohepatitis, primary biliary cirrhosis, primary sclerosing cholangitis have been ongoing. This review summarizes the results of studies on the anti-inflammatory effects and mechanisms of bile acid receptors and the results of previous to date looking at the use of bile acid receptor agonists in animal models of inflammatory disorders and clinical trials. Furthermore, we present the potentials of the bile acid receptor agonists in the treatment of inflammatory rheumatic diseases, including rheumatoid arthritis.

Gene Expression Profile in Patients with Axial Spondyloarthritis: Meta-analysis of Publicly Accessible Microarray Datasets

OBJECTIVE: To identify a gene expression signature in axial spondyloarthritis/ankylosing spondylitis (SpA/AS) and genomic pathways likely to be involved in pathogenesis of SpA/AS patients. METHODS: Four publicly accessible microarray studies from SpA/AS patients were integrated, and a transcriptomic and network-based meta-analysis was performed. This meta-analysis was compared with a published microarray study in whole blood of AS patients. RESULTS: According to our meta-analysis, 1,798 genes were differentially expressed in the whole blood of SpA/AS patients compared to healthy controls, while 674 genes were differentially expressed in the synovium of SpA/AS patients compared to healthy controls. When the whole blood meta-analysis data was compared with a published microarray study that also analyzed whole blood in SpA/AS patients, pathways involved in Toll-like receptor signaling, osteoclast differentiation, T cell receptor signaling and janus kinase–signal transducer and activator of transcription (Jak-STAT) signaling were often enriched in SpA/AS. On the other hand, eomesodermin, RUNX3, and interleukin-7 receptor (IL7R) were usually decreased in SpA/AS patients, suggesting that deficiency of these genes contributes to increased IL-17 production in AS. CONCLUSION: Several common enrichment pathways including Toll-like receptor signaling pathway, osteoclast differentiation, T cell receptor signaling pathway and Jak-STAT signaling pathway were identified in the differentially expressed genes of whole blood and synovium from SpA/AS patients, suggesting that these pathways are involved in the pathogenesis of SpA/AS.

Panenteritis as an Initial Presentation of Systemic Lupus Erythematosus / 대한소화기학회지

Lupus enteritis is a rare, severe complication of systemic lupus erythematosus (SLE), needing prompt diagnosis and proper management. However, SLE rarely presents as lupus enteritis at the time of initial diagnosis. Thus, delayed diagnosis and misdiagnosis are common. We report a case of a 25-year-old woman with lupus panenteritis. The patient had multiple hospitalizations for abdominal pain, nausea, and diarrhea, initially without any other symptoms suggestive of SLE, but was later observed to have malar rash and oral ulcers. Laboratory investigations were compatible with SLE, including positive antinuclear antibody (1:320) with speckled pattern. CT revealed diffuse hypodense submucosal thickening of the stomach, the entire small bowel, colon, appendix, and rectum. Treatment with high-dose corticosteroids followed by maintenance therapy with mycophenolate mofetil, hydroxychloroquine, and azathioprine resulted in clinical improvement. Diagnosis of lupus enteritis requires a high index of suspicion given the low incidence and nonspecific clinical findings.

A Case of Non-Hodgkin's Lymphoma of the Ocular Adnexa and Lung in a 17-year-old with Primary Sjogren's Syndrome

Sjogren's syndrome (SS) is a chronic autoimmune disorder characterized by lymphocyte-mediated destruction of exocrine glands, which produces classical symptoms of dry eyes and dry mouth. Aside from the clinical manifestations associated with exocrine glands, extraglandular features of SS include a major long-term concern for development of lymphoma. The lifetime risk of non-Hodgkin's lymphoma (NHL) in an SS patient is approximately 5% to 10%, 20 times higher than that of the normal population. This case report describes a rare occurrence of NHL in the eyelid and lung of an adolescent female with SS, whose disease activity had been monitored closely. This is the first reported case in Korea.

A Case of Massive Pulmonary Embolism in Systemic Lupus Erythematosus without Antiphospholipid Antibody

Patients with systemic lupus erythematosus (SLE) are at an increased risk of developing thromboses with antiphospholipid antibodies (aPL). The presence of aPL is related to an increased risk of thrombotic events. However, thromboembolic events can occur in SLE patients without aPL, and pulmonary emboli are rarely reported manifestations of SLE without aPL. Here, we report on a case of massive pulmonary embolism in a 58-year-old woman with aPL-negative SLE. She presented with chest pain and dyspnea, and chest computed tomography (CT) and lung perfusion ventilation scans showed pulmonary thromboembolism. She was administered thrombolytic agents, heparin, and warfarin. Two months later, no remarkable residual thromboembolism was observed on chest CT.

Clinical Significance of High Erythrocyte Sedimentation Rates in Rheumatoid Arthritis Patients Fulfilled the Remission Criteria

No abstract available.

Acute Precursor T Cell Lymphoblastic Leukemia Associated with Behcet's Disease: A Case Report

Behcet's disease is an inflammatory disorder characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. A few cases of hematologic disease in patients with Behcet's disease have been reported in the literature. However, acute precursor T cell lymphoblastic leukemia has never been described in association with Behcet's disease. We recently encountered a case of acute precursor T cell lymphoblastic leukemia in a 62-year-old man with a prior diagnosis of Behcet's disease. The patient presented with febrile neutropenia and his bone marrow biopsy revealed acute precursor T cell lymphoblastic leukemia. He was scheduled to undergo therapeutic chemotherapy, but unfortunately he died from pneumonia prior to treatment.

Leflunomide-induced Toxic Epidermal Necrolysis in a Patient with Rheumatoid Arthritis

Leflunomide was licensed for the treatment of rheumatoid arthritis in 1998 and has been available in Korea since 2003. Allergic cutaneous reactions (rash, purpura) are common (<10%) side effects of leflunomide, but severe cases such as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) are rarely reported. There has not been a report of SJS or TEN induced by leflunomide in Korea. Here we report a case of leflunomide-induced TEN in a patient with rheumatoid arthritis. Leflunomide was discontinued, and the TEN was treated with methylprednisolone, cholestyramine and immunoglobulin. The skin lesion eventually resolved over four weeks with residual post-inflammatory hyperpigmentation.

A Case of Sweet's Syndrome Associated with Rheumatoid Arthritis Involving Multiple Skin Lesions

Sweet's syndrome is a neutrophilic dermatoses characterized by the abrupt onset of fever, leukocytosis and skin lesions that are infiltrated by neutrophils. Most skin lesions are in the form of erythematous tender papules or nodules, usually affecting the upper limbs, face or neck and histologically a dense perivascular infiltrate of neutrophils without vasculitis. Sweet's syndrome can be associated with several disorders, such as inflammatory bowel disease, malignant tumors, and autoimmune diseases including rheumatoid arthritis. We report a case of Sweet's syndrome with associated rheumatoid arthritis. The patient had multiple skin lesions in her face, neck, both upper and lower extremities except trunk, and complained fever, chills and arthralgia. The result of skin biopsy showed mature neutriphil infiltration and leukocytoclasia of dermis without vasculitis, which was compatible with Sweet's syndrome.

A Case of Behcet's Disease Complicated with a Pulmonary Artery Aneurysm and Deep Vein Thrombosis, Separately

Behcet'sdisease is a chronic inflammatory disease characterized by oral ulcers, genital ulcers, uveitis, and skin lesions. Furthermore, Behcet's disease can manifest as vascular lesions, such as, those of vasculitis, venous thrombosis, or thrombophlebitis or as an arterial aneurysm. Here, the authors report the case of a pulmonary artery aneurysm and deep vein thrombosis in a 41-year-old woman with a previous diagnosis of Behcet's disease. The patient presented with hemoptysis and a cough, and was found to have a bleeding pulmonary artery aneurysm at the right lower lung. Pulmonary arteriography was performed and the aneurysm was embolized with coils. As a result, hemoptysis did not subsequently recur. However, five years later, deep vein thrombosis occurred in the left leg. Left leg pain improved after the regional infusion of thrombolytics.

A Case of Behcet's Disease Complicated with a Pulmonary Artery Aneurysm and Deep Vein Thrombosis, Separately

Behcet'sdisease is a chronic inflammatory disease characterized by oral ulcers, genital ulcers, uveitis, and skin lesions. Furthermore, Behcet's disease can manifest as vascular lesions, such as, those of vasculitis, venous thrombosis, or thrombophlebitis or as an arterial aneurysm. Here, the authors report the case of a pulmonary artery aneurysm and deep vein thrombosis in a 41-year-old woman with a previous diagnosis of Behcet's disease. The patient presented with hemoptysis and a cough, and was found to have a bleeding pulmonary artery aneurysm at the right lower lung. Pulmonary arteriography was performed and the aneurysm was embolized with coils. As a result, hemoptysis did not subsequently recur. However, five years later, deep vein thrombosis occurred in the left leg. Left leg pain improved after the regional infusion of thrombolytics.

A Case of Wegener's Granulomatosis with Central Nervous System Involvement Mimicking Lung Cancer with Brain Metastasis

Wegener's granulomatosis (WG) classically consists of necrotizing granulomatous inflammation of the upper and/or lower respiratory tract, necrotizing glomerulonephritis, and an autoimmune necrotizing systemic vasculitis affecting predominantly small vessels. We report a case of WG with central nervous system (CNS) involvement. WG is being diagnosed through pulmonary nodule biopsy. A small nodular lesion in the left posterior basal ganglia of brain being highly suspicious for granulomatosis was detected by MRI. After IV pulse cyclophosphamide and oral corticosteroid treatment for over 4 months, clinical manifestations and CNS lesions in brain MRI is improved. WG might have multiple granulomatous lesions which could be misdiagnosed due to malignancy. CNS involvement in WG is rare but careful evaluation is necessary when there are suspicious symptoms or lesions in CNS.

A Case of Refractory SAPHO Syndrome Treated with Etanercept

SAPHO syndrome, which has different skin changes and osteoarticular inflammation, is an acronym that stands for synovitis, acne, pustulosis, hyperostosis, and osteitis. Treatment of SAPHO syndrome includes non-steroidal anti-inflammatory drugs (NSAIDs), anti-rheumatic drugs, such as colchicines, corticosteroids and bisphosphonates, and disease-modifying agents. However, the treatment of SAPHO syndrome is controversial because it is a new clinical entity with unclear etiopathogenesis and inadequate clinical studies. We report a case with refractory SAPHO syndrome, which was successfully treated with a tumor necrosis factor (TNF)-alpha blocker.

A Case of Secondary Antiphospholipid Antibody Syndrome with Thyroid Cancer

Antiphospholipid antibody syndrome (APS) is defined as the presence of lupus anticoagulant antibody or anticardiolipin antibody with vascular thrombosis or pregnancy complications. APS can be associated with autoimmune disease or infectious disease. APS has also been reported in conjunction with variety of solid and hematologic malignancies. There were some reports on APS which were accompanied by hematologic malignancy, but there was no report with solid malignancy in Korea. We experienced one case of secondary APS, which was diagnosed during pre-operative evaluation of thyroid cancer. This patient had prolonged aPTT (activate partial thromboplastin time) and decreased coagulation factors which were regarded as hemophilia at first. Although the precise mechanism of the relationship between APS and cancer has not been proven thoroughly, APS can be accompanied by various malignancies. So proper screening and early detection of malignancies in APS patients are recommended.

Integrated Analysis of MicroRNA and mRNA Expression Profiles in Rheumatoid Arthritis Synovial Monocytes

OBJECTIVE: MicroRNAs (miRNAs) play important roles in many biological processes and recent studies have provided growing evidences that miRNA dysregulation might play important roles in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to investigate the contribution of miRNAs to altered gene expressions in RA. METHODS: To investigate whether the differential expression of miRNA in RA could account for the altered expression of certain genes, we compared the different expressions of miRNAs and mRNAs in rheumatoid synovial fluid monocytes with that of normal peripheral blood (PB) monocytes by using a gene expression oligonucleotide microarray and a microRNA microarray. RESULTS: Comparative analysis of the mRNA profiles showed significant different expressions of 430 genes in RA synovial monocytes, of which 303 (70%) were upregulated and 127 (30%) were downregulated, as compared with that of normal PB monocytes. Out of differentially expressed 13 miRNAs, 9 miRNAs were upregulated and 4 miRNAs were downregulated in the RA synovial monocytes. A total of 62 genes were predicted as target genes of the 13 differentially expressed miRNAs in the RA synovial monocytes. Among the 62 miRNA-targeted genes, a few genes such as GSTM1, VIPR1, PADI4, CDA, IL21R, CCL5, IL7R, STAT4, HTRA1 and IL18BP have been reported to be associated with RA. CONCLUSION: In the present study, we observed that several miRNAs are differentially expressed in RA synovial monocytes, and we suggest that these different expressions of miRNAs may regulate the expression of several genes associated with the pathogenesis of RA.

Study of the Gene Expressions in Rheumatoid Arthritis Synovial Macrophages Using Network Analysis

OBJECTIVE: We wanted to investigate the mechanisms that could account for the pathogenesis of rheumatoid arthritis, so we examined the different expressions of the genes in rheumatoid arthritis (RA) synovial fluid macrophages as compared with that of normal peripheral blood (PB) monocyte-derived macrophages using microarray and bioinformatic analysis. METHODS: We examined the expression of genes by using a gene expression oligonucleotide microarray. The differences of the gene expressions between the RA synovial macrophages and the normal PB monocytes-derived macrophages were analyzed using bioinformatic tools, including cytoscape and its plugin. RESULTS: In this study, we found that 899 genes (464 genes up-regulated and 435 genes down-regulated) were differentially expressed between the two groups. Among the 899 genes, 552 genes were included for gene ontology analysis and network analysis. Based on biological process ontology, they were categorised mainly into immune response processes, responses to stimulus and signaling and regulation of biological processes. In addition to the genes related with STAT1 and AP-1 signaling, we found that the genes involved in the antigen processing and the cell cycle are abundantly expressed in RA synovial macrophages, suggesting that these genes may play an important role in the pathogenesis of RA. CONCLUSION: Our study suggest that this approach using integration of the gene expression profile with the protein interaction data may help to find several important pathogenic mechanisms in RA.

Expression of Osteoclastogenesis-related Genes in Rheumatoid Arthritis Synovial Macrophages

OBJECTIVE: To examine the mechanism for the inhibited differentiation of osteoclasts in rheumatoid arthritis synovial CD14+ osteoclast precursors, the different expressions of the osteoclastogenesis-related genes in rheumatoid arthritis (RA) synovial fluid CD14+ osteoclast precursors were compared with those of normal peripheral blood (PB) CD14+ osteoclast precursors. METHODS: The expression of osteoclastogenesis-related genes were examined using a gene expression oligonucleotide microarray. To validate the results of the microarray analysis, the mRNA expressions of osteoclastogenesis-related genes were measured by real-time PCR. RESULTS: Comparative analysis of the mRNA profiles showed significantly different expression of osteoclastogenesis- related genes, such as MafB, Id3 and LILRB4, in the RA synovial CD14+ osteoclast precursors, compared to that of normal PB CD14+ osteoclast precursors. CONCLUSION: The expression of the osteoclastogenesis-related genes in RA synovial CD14+ osteoclast precursors is different from that of the normal PB CD14+ osteoclast precursors. These results suggest that the different expression of osteoclastogenesis-related genes might be involved in the altered osteoclastogenesis in RA synovial osteoclast precursors.

Rheumatoid Arthritis and microRNA / 대한류마티스학회지

MicroRNAs (miRNAs) are small, single-stranded, non-coding RNA molecules of 20~22 nucleotides, which are involved in many biologic functions such as development, cell proliferation, differentiation, and apoptosis. In addition to these biologic functions, recent reports have demonstrated that miRNAs play important roles in the development of the immune system and the regulation of immune responses. Dysregulation of miRNAs might be involved in the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA). Recent studies have shown that miR-146a, miR-155, and miR-203 are overexpressed in RA and that miR-124a is under expressed in RA. miR-146 downregulates the expression of IL-1 receptor associated kinase 1 and TNF receptor-associated factor 6 involved in IL-1beta signaling, and miR-155 suppresses the expression of matrix metalloproteinases 1 and 3, suggesting that these miRNAs act as negative feedback regulators of inflammation and tissue damage in RA. In this report, we review the current knowledge about miRNAs and summarize the involvement of miRNAs in RA.

Rheumatoid Arthritis and microRNA / 대한류마티스학회지

MicroRNAs (miRNAs) are small, single-stranded, non-coding RNA molecules of 20~22 nucleotides, which are involved in many biologic functions such as development, cell proliferation, differentiation, and apoptosis. In addition to these biologic functions, recent reports have demonstrated that miRNAs play important roles in the development of the immune system and the regulation of immune responses. Dysregulation of miRNAs might be involved in the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA). Recent studies have shown that miR-146a, miR-155, and miR-203 are overexpressed in RA and that miR-124a is under expressed in RA. miR-146 downregulates the expression of IL-1 receptor associated kinase 1 and TNF receptor-associated factor 6 involved in IL-1beta signaling, and miR-155 suppresses the expression of matrix metalloproteinases 1 and 3, suggesting that these miRNAs act as negative feedback regulators of inflammation and tissue damage in RA. In this report, we review the current knowledge about miRNAs and summarize the involvement of miRNAs in RA.