Kwi Young Kang

Lupus mesenteric vasculitis can cause acute abdominal pain in patients with SLE

Lupus mesenteric vasculitis (LMV) is a unique clinical entity found in patients who present with gastrointestinal manifestations of systemic lupus erythematosus, and is the main cause of acute abdominal pain in these patients. LMV usually presents as acute abdominal pain with sudden onset, severe intensity and diffuse localization. Other causes of abdominal pain, such as acute gastroenteritis, peptic ulcers, acute pancreatitis, peritonitis, and other reasons for abdominal surgery should be ruled out. Prompt and accurate diagnosis of LMV is critical to ensure implementation of appropriate immunosuppressive therapy and avoidance of unnecessary surgical intervention. The pathology of LMV comprises immune-complex deposition and complement activation, with subsequent submucosal edema, leukocytoclastic vasculitis and thrombus formation; most of these changes are confined to small mesenteric vessels. Abdominal CT is the most useful tool for diagnosing LMV, which is characterized by the presence of target signs, comb signs, and other associated findings. The presence of autoantibodies against phospholipids and endothelial cells might provide information about the likelihood of recurrence of LMV. Immediate, high-dose, intravenous steroid therapy can lead to a favorable outcome and prevent serious complications such as bowel ischemia, necrosis and perforation.

Metformin downregulates Th17 cells differentiation and attenuates murine autoimmune arthritis.

INTRODUCTION This study was undertaken to determine whether metformin has anti-inflammatory effects in the collagen antibody-induced arthritis (CAIA) murine model. The effect of metformin on Th17 cell differentiation was also investigated. METHODS CAIA mice were treated with 100 and 150 mg/kg i.p. metformin (low- and high-dose groups, respectively). Arthritis activity and histological joint destruction were studied. Flow cytometry was used to (i) determine RORγt-expressing CD4+ percentages in draining axillary lymph nodes (ALNs) from metformin-treated and untreated mice with CAIA, (ii) determine Th17 percentages in splenic CD4+ T cells cultured ex vivo for 3 days in Th17-differentiation-inducing conditions, and (iii) determine the percentages of RORγt+CD4+ T cells when normal splenic T cells from DBA/1 mice were cultured in Th17-differentiation-inducing conditions together with various metformin doses. Western blot analysis was used to assess the intracellular signaling of the metformin-treated splenocytes. RESULTS Metformin attenuated both arthritis scores and bone destruction in CAIA mice, decreased the serum levels of the pro-inflammatory cytokines, TNF-α and IL-1, and reduced the number of RORγt+CD4+ T cells in the ALNs. Splenocytes from metformin-treated CAIA mice differentiated less readily into Th17 cells upon ex vivo stimulation. Metformin treatment of normal cells cultured in Th17-differentiation-inducing conditions decreased the number of RORγt-expressing CD4+ cells in a dose-dependent manner and downregulated STAT3 phosphorylation via the AMPK pathway. CONCLUSIONS Metformin had an anti-inflammatory effect on murine autoimmune arthritis due to the inhibition of Th17 cell differentiation. Metformin may have a possible therapeutic value for treatment of rheumatoid arthritis.

Incidence of cancer among patients with systemic sclerosis in Korea: results from a single centre

Objective: The aim of this study was to determine whether the incidence of cancer has increased among patients with systemic sclerosis (SSc) in Korea. Methods: The study subjects consisted of 112 patients who had been consecutively evaluated for at least 6 months between 1990 and 2007. We retrospectively reviewed their medical records, investigated the incidence rate of cancer and compared it with that of the Korea National Cancer Centre database. Results: Nine out of 112 patients developed cancer (four males and five females). The average age at diagnosis of cancer was 56.4 years and the mean disease duration was 8.9 years. The standardized incidence ratio (SIR) for SSc patients was 4.2 [95% confidence interval (CI) 2.3–6.1], 3.7 for women (95% CI 1.2–6.2) and 6.4 for men (95% CI 1.6–11.2). Lung cancer was the most common cancer (n = 4), followed by oesophagus (n = 1), stomach (n = 1), liver (n = 1), pancreas (n = 1), and squamous cell carcinoma of unknown origin (n = 1). All patients who developed lung cancer were female and non‐small cell carcinoma in origin. The SIR of lung cancer in female patients was 23.0 (95% CI 6.0–40.0). Two out of four lung cancer patients had concomitant interstitial lung disease (ILD); all were non‐smokers. Treatment agents, autoantibodies, smoking, and lung involvement were not significantly different between SSc patients with or without cancer. Conclusion: The SIR of cancer was significantly higher in SSc patients, and especially in those who were male, than in the general population. Lung cancer was the most common cancer. Active surveillance for the detection of cancer should be performed in all SSc patients.

The paradoxical effects of TNF inhibitors on bone mineral density and radiographic progression in patients with ankylosing spondylitis

OBJECTIVES To determine the longitudinal effects of TNF inhibitors on BMD and radiographic progression in patients with AS and to assess independent factors associated with increased BMD in the lumbar spine. METHODS Sixty-three patients with AS were included. Twenty-six patients were treated with TNF inhibitors and 37 were not. BMD in the lumbar spine and right femur was measured by DXA at baseline and 1 and 2 years later. Lumbar spine radiography was performed at baseline and after 2 years. Radiographic progression was scored using the Stoke AS Spinal Score (SASSS) and the modified SASSS. Univariate and multivariate linear regression analyses were performed to identify factors independently associated with spinal BMD increase. RESULTS BMD in the lumbar spine and total proximal femur of patients receiving TNF inhibitors increased consistently over 2 years compared with that in patients not receiving TNF inhibitors (P < 0.01 and P = 0.02), and treated patients showed increased SASSS scores (P = 0.05); however, syndesmophyte development was no different between the two groups. There was a significant difference in the change of SASSS in patients treated with both TNF inhibitors and bisphosphonates compared with those treated with TNF inhibitors alone (P < 0.01). TNF inhibitor therapy and the increase in SASSS were independently associated with increased lumbar spine BMD (P = 0.009 and P < 0.001). CONCLUSION TNF inhibitors appear to be associated with increased SASSS scores and improvements in BMD. Further prospective studies with larger subject numbers are needed to validate this paradoxical role of TNF inhibitors.

Visualization and localization of rheumatoid knee synovitis with FDG-PET/CT images

We annually evaluated 18F-fluorodeoxyglucose-positrom emission tomography/ computed tomography (FDG-PET/CT) scans for three consecutive years in a patient with rheumatoid arthritis. The inflammatory activity of the rheumatoid synovium was visualized in coronal and transverse sections by FDG-PET/CT. The extent and area of the synovial inflammation was relatively well delineated, and this technique was more informative in detecting inflammation than were conventional X-rays.

S100A8/A9 as a biomarker for synovial inflammation and joint damage in patients with rheumatoid arthritis

S100A8 and S100A9 are major leukocyte proteins, known as damage-associated molecular patterns, found at high concentrations in the synovial fluid of patients with rheumatoid arthritis (RA). A heterodimeric complex of S100A8/A9 is secreted by activated leukocytes and binds to Toll-like receptor 4, which mediates downstream signaling and promotes inflammation and autoimmunity. Serum and synovial fluid levels of S100A8/A9 are markedly higher in patients with RA than in patients with osteoarthritis or miscellaneous inflammatory arthritis. Serum levels of S100A8/A9 are significantly correlated with clinical and laboratory markers of inflammation, such as C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, and the Disease Activity Score for 28 joints. Significant correlations have also been found between S100A8/A9 and radiographic and clinical assessments of joint damage, such as hand radiographs and the Rheumatoid Arthritis Articular Damage score. In addition, among known inflammatory markers, S100A8/A9 has the strongest correlation with total sum scores of ultrasonography assessment. Furthermore, baseline levels of S100A8/A9 are independently associated with progression of joint destruction in longitudinal studies and are responsive to change during conventional and biologic treatments. These findings suggest S100A8/A9 to be a valuable diagnostic and prognostic biomarker for RA.

The Effects of Antihypertensive Drugs on Bone Mineral Density in Ovariectomized Mice

The effects of several antihypertensive drugs on bone mineral density (BMD) and micro-architectural changes in ovariectomized (OVX) mice were investigated. Eight-week-old female C57/BL6 mice were used for this study. Three days after ovariectomy, mice were treated intraperitoneally with nifedipine (15 mg/kg), telmisartan (5 mg/kg), enalapril (20 mg/kg), propranolol (1 mg/kg) or hydrochlorothiazide (12.5 mg/kg) for 35 consecutive days. Uterine atrophy of all mice was confirmed to evaluate estrogen deficiency state. BMD and micro-architectural analyses were performed on tibial proximal ends by micro-computed tomography (micro-CT). When OVX mice with uterine atrophy were compared with mice without atrophy, BMD decreased (P < 0.001). There were significant differences in BMD loss between different antihypertensive drugs (P = 0.005). Enalapril and propranolol increased BMD loss in mice with atrophied uteri compared with control mice. By contrast, thiazide increased BMD in mice with uterine atrophy compared with vehicle-treated mice (P = 0.048). Thiazide (P = 0.032) and telmisartan (P = 0.051) reduced bone loss and bone fraction in mice with uterine atrophy compared with the control. Thiazide affects BMD in OVX mice positively. The reduction in bone loss by thiazide and telmisartan suggest that these drugs may benefit menopausal women with hypertension and osteoporosis.

Three-dimensional ultrasonographic application for analyzing synovial hypertrophy of the knee in patients with osteoarthritis.

Objective. The purpose of this study was to evaluate 3‐dimensional (3D) ultrasonography for the visualization of intra‐articular synovial hypertrophy in patients with osteoarthritis. Methods. Knee joints of 22 patients with osteoarthritis were examined by 3D ultrasonography, and their synovial fluids were analyzed. Ultrasonographic image patterns, vascular endothelial growth factor and transforming growth factor β concentrations in synovial fluid, and serum inflammatory markers were analyzed. Results. It was possible to visualize the intra‐articular structure by 3D ultrasonography. Three‐dimensional ultrasonography revealed various interesting stereoscopic views of the synovial structures, and the patterns of synovial proliferation ranged from simple proliferations to complex shrubby structures. Patients with a more complex and proliferative pattern in the synovium tended to have higher C‐reactive protein concentrations, but this difference was not significant (P = .09). The concentrations of vascular endothelial growth factor and transforming growth factor β in synovial fluid were significantly higher in patients with complex hypertrophy (P < .05). Conclusions. Three‐dimensional technology was useful in delineating the shape of the synovium. It may have a possible impact on future imaging in rheumatology.

A pathogenetic role for IL-21 in primary Sjögren syndrome

Advances in our understanding of the pathogenesis of primary Sjögren syndrome (pSS) characterize it as a highly complex process encompassing both the initiation of innate immunity and subsequent adaptive immune responses. IL-21 is receiving attention as a potential key player in the pathogenesis of pSS owing to its pleiotropic effects on the type I interferon signalling pathway, and newly identified roles in generation of follicular and IL-17-producing subtypes of helper T cells, as well as plasma-cell differentiation and B-cell activation. Taking into consideration the diverse biological functions of IL-21 and its clinical relevance to pSS, we propose that this cytokine has a central role in orchestrating the complex immune response in pSS. This hypothesis might provide new insight into the pathogenesis of pSS and facilitate the development of effective therapeutic strategies.

Prevalence of systemic lupus erythematosus in South Korea: an administrative database study.

Background Systemic lupus erythematosus (SLE) is a rare autoimmune disease for which a population-based survey on the prevalence of the disease in South Korea has not yet been conducted. Our goal was to estimate the nationwide prevalence of SLE. Methods The International Classification of Diseases, Tenth Revision (ICD-10) code for SLE diagnosis—M32—was tentatively given when patients were suspected to have SLE before 2009. As such, the positive predictive value (PPV) of the M32 code shown in medical bills reflecting true SLE was uncertain. We attempted to estimate the prevalence of SLE in South Korea using national administrative database data from 2004–2006. We approximated the actual number of SLE patients by analyzing a list of SLE-coded patients provided by the National Health Insurance (NHI) and Health Insurance Review and Assessment Service. Prevalence was estimated by multiplying the PPV of the M32 diagnostic code by the number of patients receiving the code. The PPV was determined by three methods: direct investigation of the medical records of patients randomly selected from the SLE-coded patients list; assessment of all SLE patients treated at 56 selected hospitals in South Korea; and extrapolation from sub-groups at a single institute to the sub-groups of the national NHI data. Results The estimated number of national SLE cases was between 9000 and 11 000, depending on the method of ascertainment, corresponding to a prevalence of 18.8–21.7 per 100 000 people. Conclusions This is the first report of a nationwide prevalence survey of SLE in South Korea. National databases may serve as a resource for epidemiologic studies of rare autoimmune diseases like SLE.