Hughes-Stovin syndrome is an exceedingly rare disorder of unknown etiology, and it is characterized by multiple pulmonary artery aneurysms and peripheral venous thrombosis. We report a case of Hughes-Stovin syndrome with complete resolution of pulmonary artery aneurysm after treatment with cyclophosphamide. A 48-year-old man presented with massive hemoptysis, fever, and weight loss of 4-month duration. Computed tomography angiography revealed multiple pulmonary arterial aneurysms of variable sizes in both lung fields. Inferior vena caval thrombosis was also noted. Despite multiple surgical procedures including embolectomy and lobectomy combined with steroid therapy, new aneurysms continued to appear with persistent hemoptysis. Thorough history and physical examination did not suggest any evidence of Behcet's disease. Hughes-Stovin syndrome was subsequently diagnosed. High-dose prednisolone combined with oral cyclophosphamide therapy was initiated. Chest radiography follow-up in 3 months revealed complete resolution of pulmonary aneurysm. No new aneurysm was detected at 15 months of follow-up.

The aim of this study is to compare the expression of TIM-3 from CD4+ T cells from rheumatoid arthritis (RA) patients and healthy controls and to evaluate the effect of galectin-9 (Gal-9) on apoptosis of CD4+ T cells in these patients. CD4+ T cells from RA patients and healthy controls were isolated from peripheral blood mononuclear cells and were activated. The expression of TIM-3 mRNA in CD4+ T cells was measured using real-time polymerase chain reaction. CD4+ T cells were activated in the presence of graded doses of Gal-9 or control, and Gal-9-induced cytotoxicity and apoptotic activity of CD4+ T cells were analyzed using MTT assays and annexin-V staining, respectively. TIM-3 mRNA expression was significantly lower in CD4+ T cells from RA patients compared with those in healthy controls (p = 0.028). CD4+ T cell survival as measured by MTT assay when incubated with Gal-9 (15 nM) was significantly higher in RA patients than in healthy controls (p = 0.002). Apoptotic activity of CD4+ T cells from healthy controls as measured by annexin staining increased with graded doses of Gal-9 (0 nM vs. 30 nM, 0 nM vs. 90 nM, p = 0.016 each). However, apoptotic activity of CD4+ T cells from RA patients did not change despite the stimulation with Gal-9. Gal-9-mediated apoptosis of CD4+ T cells is dysfunctional in RA patients. Blunted Gal-9-mediated apoptosis may be exerted through underexpression of TIM-3 that negatively regulates Th1 response. Our data suggest that TIM-3 and its interaction with Gal-9 may play an important role in the pathogenesis of RA and may represent a potential therapeutic target.

Objective: Localized scleroderma (morphea) is a rare autoimmune disease limited to the skin, characterized by cutaneous fibrosing and obstructive vasculopathy. Localized scleroderma may invade into the subcutaneous fat layer and cause permanent functional disability. Because of its rarity, there have been few clinical surveys of patients with localized scleroderma in Korea. The aim of this study was to elucidate the clinical presentation, serological data, and clinical outcomes of localized scleroderma.Methods: This was a retrospective survey conducted by reviewing available medical records during a 7 yearperiod from 2004 to 2010 in a single medical center in Jeju Island, South Korea. In total 43 patients with localized scleroderma were included.Results: Localized scleroderma occurred primarily in females (female to male ratio 2.6 : 1.0). Most patients were between 10 and 29 years of age and the mean age at diagnosis was 26.2 years. Plaque (51.2%) and linear morphea (37.2%) were most common. No case was associated with systemic scleroderma (systemic sclerosis). The most common site of plaque morphea was the trunk (47.8%). In the linear type, the most common site was head-neck (52.9%). Fluorescent antinuclear antibody was positive in 23.3% of all cases. Treatment included systemic corticosteroids, colchicine, anti-malarial agents, D-penicillamine or intralesional triamcinolone injection. Clinical improvement, including significant and partial response, was seen in only 62.8% of treated patients.Conclusion: Localized scleroderma is a chronic inflammatory condition confined to the skin. In order to exclude other conditions, thorough history taking, physical examination, serologic studies and histopathologic examinations should be conducted.

As a measure of healthcare cost containment, the total number of vials of entanercept (25 mg) that can be prescribed for patients with inflammatory arthritis is restricted in Korea. Consequently, attempts to extend the dosing interval while maintaining the efficacy have not been an uncommon clinical practice. The aim of this study was to determine if extended doing interval of etanercept can be effective in patients with ankylosing spondylitis (AS). We performed a retrospective analysis using medical records at a single tertiary hospital. One hundred and nine patients with AS and 79 patients with rheumatoid arthritis (RA) started on etanercept between November 2004 and November 2009 were identified. Etanercept (25 mg) was started with twice-weekly dosing schedule. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), C-reactive protein (CRP), and etanercept dosing interval for AS patients at 0, 3, 9, 15, 21 months were reviewed. Dosing interval for RA patients was analyzed for comparison. In AS, mean dosing interval was 4.7 +/- 2.1 days at 3 months and was increased to 12.1 +/- 7.0 days at 21 months. Despite the progressive increase in the dosing interval, the mean BASDAI declined rapidly at 3 months, and continued to decrease over 21 months. Mean CRP declined after 3 months of therapy and remained low thereafter. In RA, mean dosing interval was 4.0 +/- 1.2 days at 3 months and 5.1 +/- 1.8 days at 21 months. In conclusion, in AS, extended dosing of etanercept can be effective without compromising clinical and laboratory markers of disease activity as measured by BASDAI and CRP, respectively. Tapering of etanercept was less accommodating in RA when compared to AS.

No abstract

Lysophosphatidic acid (LPA), a major member of the bioactive lysophospholipids in serum, possesses diverse physiological activities including cell proliferation. Recently, three endothelial differentiation gene (EDG) family receptors, including EDG-2 (LPA1), EDG-4 (LPA2), and EDG-7 (LPA3), have been identified as LPA receptors. The role of LPA and their receptors in mesangial cell physiology is not clearly understood. This study examined the expression profile of EDG receptors as a function of cell density and the participation of EDG receptors in human mesangial cell proliferation by LPA. We showed that mesangial cells express all three EDG family LPA receptors in a cell density-dependent manner. EDG-7 maximally expressed at sparse cell density and minimally expressed in dense cell population. The EDG-2 expression pattern was opposite to the EDG-7. No changes in EDG-4 expression as a function of cell density were noted. DNA synthetic rate was greater in sparse cell density compared with dense cell population and followed a similar pattern with EDG-7 expression. Comparative studies in sparse and dense cell density indicated that EDG-7 was positively associated, whereas EDG-2 was negatively associated with cell proliferation rate. LPA induced mesangial cell proliferation by 1.5- to 3.5-fold. Dioctanoylglycerol pyrophosphate, an antagonist for EDG-7, almost completely inhibited mesangial cell proliferation induced by LPA. We suggest that EDG-7 regulates LPA-mediated mesangial cell proliferation. Additionally, these data suggest that EDG-7 and EDG-2 LPA receptors play a diverse role as proliferative and antiproliferative, respectively, in mesangial cells. Regulation of EDG family receptors may be importantly linked to mesangial cell-proliferative processes.

Background Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified oncoprotein that leads to cellular proliferation in cancer cells by stabilizing c-Myc protein. The effect of CIP2A in stabilizing c-Myc by inhibition of protein phosphatase 2A activity is a prerequisite step in tumor cell growth and in vivo tumor formation. We have previously shown that CIP2A is expressed in RA FLS and its expression is strongly associated with histopathological synovitis score and invasive function of RA FLS. However, the effect of CIP2A in association with c-Myc on the apoptosis of RA FLS is unknown. Objectives This study was undertaken to investigate the effect of CIP2A and c-myc on the apoptosis of RA FLS and to determine the signaling pathway through which dysfunctional apoptosis is facilitated. Methods Proliferation and apoptotic activity of RA FLS following treatment with CIP2A siRNA or control siRNA were analyzed using MTT assays and Cell Death Detection ELISA kit. c-Myc expression from RA FLS after treatment with CIP2A siRNA or control at 3, 6, 9 days interval was also determined using Western blot analysis. To evaluate which signal transduction pathways were engaged in apoptosis, caspase-3 activity and phosphorylation of the Akt kinase were also analyzed by Western blot. Results Survival of RA FLS as measured by MTT assay was significantly lower in CIP2A siRNA -treated group compared to control after 7 days (n=5, each, p=0.0221). Apoptosis of RA FLS as measured by DNA fragmentation was significantly higher in CIP2A siRNA treated group compared to control when incubated for 3, 6 and 9 days (p=0.029, p=0.021, p=0.043, respectively). C-Myc expression measured by Western blot did not change during the incubation period. Apoptosis of CIP2A siRNA-treated RA FLS was induced by activation of caspase-3 and dephosphorylation of Akt kinase, but these findings were not observed in the control siRNA-treated RA FLS. Conclusions Our data show that CIP2A expression in RA FLS is an important mediator of dysfunctional apoptosis that is independent of c-Myc stabilization. CIP2A may induce dysfunctional apoptosis of RA FLS by activation of Akt and deactivation of caspase-3. These results warrant further investigation of CIP2A as a potential pathogenetic factor and therapeutic target in RA. Disclosure of Interest None Declared

Secondary amyloidosis is a severe complication of refractory rheumatoid arthritis for which no effective treatment exists. Although the benefits of tumor necrosis factor alpha inhibitors in rheumatoid arthritis treatment are well known, their role in renal amyloidosis secondary to rheumatoid arthritis is unclear and their safety in patients with chronic kidney disease is not well reported. We present an unusual case of a 65-year-old female with moderate renal failure and severe proteinuria, who was diagnosed with secondary amyloidosis associated with refractory rheumatoid arthritis subsequent to treatment with corticosteroids, methotrexate, hydroxychlorquine, and leflunomide. She was treated with etanercept 25 mg, administered as a subcutaneous injection twice weekly for 8 months. The patient had no complications following the treatment. Treatment with etanercept led to a decrease in proteinuria and stabilization of renal function over time.