Won-Woo Kim

Lupus enteritis: clinical characteristics, risk factor for relapse and association with anti-endothelial cell antibody

The study was undertaken to evaluate clinical and laboratory characteristics of patients with lupus enteritis and to investigate its association with anti-endothelial cell antibodies (AECAs). Systemic lupus erythematosus (SLE) patients who were admitted to Kangnam St. Marys Hospital with complaints of acute abdominal pain from January 1990 to July 2006 were reviewed retrospectively. The clinical features, laboratory data and prognosis of these patients were analyzed. Among the 706 SLE patients admitted during the study period, 87 were found to admit for acute abdominal pain. Among them, 41 patients were identified with lupus enteritis. The SLE disease activity index score at admission and the mean prednisolone dose administered during the last three months prior to admission were significantly higher in patients with lupus enteritis than those with other causes (P < 0.001, P = 0.036). Serum anti-endothelial cell antibody (AECA-IgG) titer was also significantly higher in patients with lupus enteritis than those with other manifestations or healthy controls (P = 0.040, P < 0.001). Four out of 13 recurrent patients had pre-existing anti-phospholipid syndrome (APS), whereas only one out of 28 non-recurrent patients had pre-existing APS (P = 0.028). Most of the patients with lupus enteritis showed good response to high-dose intravenous steroids and there was no death directly associated with lupus enteritis. Lupus (2007) 16, 803—809.

Adult respiratory distress syndrome in systemic lupus erythematosus: causes and prognostic factors: a single center, retrospective study

To determine the causes and prognostic factors of Adult Respiratory Distress Syndrome (ARDS) in patients with systemic lupus erythematosus (SLE). Methods: Among 544 Korean SLE patients, who were followed in the Lupus Clinic of the Catholic Medical Center from 1993 to 1997, patients diagnosed as ARDS were examined retrospectively. During the study period, non-SLE patients with ARDS were investigated and then compared to SLE patients with ARDS in terms of clinical variables. Results: Nineteen patients with SLE were revealed to have a history of ARDS (3.5%) and 13 (68.4%) of 19 patients died. Death related to ARDS was found in 34.2% of all deaths (n = 38) from SLE during the study period. The frequency and causes of ARDS were as follows; 9 sepsis or bacteremia (47.4%), 2 miliary tuberculosis (10.5%), 2 invasive pulmonary aspergillosis (10.5%), 2 acute pulmonary alveolar hemorrhage syndrome (10.5%), 1 acute lupus pneumonitis (5.3%), 1 massive hemorrhage due to placenta previa (5.3%), 1 aspiration pneumonitis (5.3%), 1 disseminated intravascular coagulation associated with systemic vasculitis (5.3%). The main organisms in sepsis were gram negative bacilli (61.5%) The median steroid dose administered 1 month before ARDS was significantly higher in patients (n = 13) with infectious ARDS compared to those (n = 6) with ARDS due to other causes (P = 0.038). Comparison of the laboratory and clinical variables between the survivors (n = 6) and the deceased (n = 13) showed that the survivors had lower SLAM indices at presentation (P = 0.004) and APACHE (Acute Physiology, Age, Chronic Health Evaluation) III scores within 24 h after diagnosis of ARDS (P = 0.024) than the deceased. The APACHE III scores correlated well with the SLAM indices (r = 0.615, P = 0.007). Non-SLE patients with ARDS during the study period were selected for comparison to SLE patients with ARDS. Age at the onset of ARDS was younger in SLE (n = 19) compared to non-SLE (n = 190) (P < 0.001). Duration from ARDS onset to death was shorter in SLE patients (P < 0.001). The mortality from ARDS tended to be higher in SLE patients (P = NS). The first-day APACHE III score was significantly higher in deceased SLE patients (n = 13) compared to deceased non-SLE patients (n = 105) (P = 0.001). Conclusions: ARDS was a common premortem event of SLE and showed a high fatality rate in SLE. The most common cause of ARDS in Korean patients with SLE was sepsis by gram negative bacilli. ARDS in SLE developed at a younger age, and progressed more rapidly compared to ARDS in general. The SLAM index and APACHE III score could be useful to predict the prognosis of ARDS in SLE.

Diffuse alveolar hemorrhage in systemic lupus erythematosus: risk factors and clinical outcome: results from affiliated hospitals of Catholic University of Korea:

This study was undertaken to investigate clinical characteristics of diffuse alveolar hemorrhage (DAH) in patients with systemic lupus erythematosus (SLE) and to determine risk factors and clinical outcomes of DAH in SLE patients. Among the 1521 patients with SLE admitted between January 1993 and June 2009 to affiliated hospitals of Catholic University of Korea, 21 SLE were admitted for DAH. The inclusion criteria for DAH was defined as new infiltrates on chest radiographs, an acute hemoglobin drop of at least 1.5 g/dl in the absence of an obvious source of bleeding, and one or more of the following signs: hemoptysis, hypoxemia, bronchoscopic or biopsy evidence of DAH. Included as disease controls were 83 SLE patients, matched for age and sex, who were admitted for other manifestations. Data based on medical records were analyzed retrospectively. There were no significantly differing demographic characteristics between SLE patients with DAH and those with other manifestations. Multivariate analysis demonstrated coexisting neuropsychiatric lupus (p = 0.002) and high SLE disease activity index scores (SLEDAI > 10) as independent risk factors in the development of DAH (p = 0.029). Among the 21 SLE patients with DAH, 13 died during the admission period (in-hospital mortality rate: 61.9%). Mortality was associated with infection and requirements of mechanical ventilation. Collectively, SLE patients who have neuropsychiatric manifestations or are in the active stage of the disease have an increased risk for developing DAH. Due to the high mortality of SLE patients with DAH, early recognition of risk factors and appropriate intervention is essential.

Circulating osteoprotegerin levels are elevated and correlated with antiphospholipid antibodies in patients with systemic lupus erythematosus

Patients with antiphospholipid syndrome (APS) have an increased risk for the development of thrombotic complications. Recent studies indicate that osteoprotegerin (OPG) acts as an important molecule in the development of vascular diseases. The aim of the present study was to examine the association between serum OPG levels and APS manifestations in patients with SLE. Seventy-nine patients with SLE and ninety-two healthy controls, matched for age and sex, were included in this study. Serum levels of OPG, monocyte chemoattractant protein(MCP)-1 and soluble E-selectin were determined by ELISA. At the time of serum sampling, various clinical and laboratory parameters were assessed. We found that serum levels of OPG were significantly higher in patients with SLE than in healthy controls (1236 ± 82 vs 967 ± 37 pg/mL, P = 0.003). Particularly, serum OPG levels were significantly higher in SLE patients with APS than those without (1615 ± 191 vs 1171 ± 91 pg/mL, P = 0.006). Serum OPG levels correlated with titres of IgG anti-cardiolipin antibody (P = 0.026) and anti-β2-glycoprotein I antibody (P < 0.001). Moreover, serum OPG also correlated with serum levels of sE-selectin (P = 0.002), which is an endothelial cell activation marker, and MCP-1 (P = 0.003), a well known chemokine implicated in thrombogenesis. Collectively, serum OPG levels were increased in SLE patients with APS and correlated with titres of antiphospholipid antibodies, suggesting that OPG might be linked to the development of APS.

Treatment with cyclosporin switching to hydroxychloroquine in patients with rheumatoid arthritis

OBJECTIVE To investigate the therapeutic benefit of cyclosporin A (CSA) switching to hydroxychloroquine (HCQ) in patients with rheumatoid arthritis (RA). METHODS Thirty four patients with RA who displayed residual inflammation and disability despite partial responses to prior maximal tolerated doses of methotrexate, were included. All were treated with a staged approach using CSA for 24 weeks to induce clinical improvement, followed by HCQ for 16 weeks to maintain the improvement. Seven ACR core set measures were evaluated every four to eight weeks. RESULTS During a 40 week open trial, 27/34 patients completed the study. CSA treatment significantly reduced the tender joints score, swollen joints score, visual analogue pain scale, patients or doctors global assessment, patients self assessed disability, and C reactive protein. Compared with the time of entry into the trial, patients who switched from CSA to HCQ still possessed significantly lower levels of most variables, determined at 28, 32, and 40 weeks. According to the ACR 20% improvement definition, 15/27 (56%) patients had improved at 24 weeks after CSA treatment, and 14/27 (52%) remained improved at 16 weeks after the change to HCQ. Frequent side effects, such as hypertrichosis, gastrointestinal trouble, and hypertension, were noted during CSA treatment, but most of these disappeared after switching to HCQ. The mean levels of blood pressure and serum creatinine were significantly increased during CSA treatment, but returned to normal after changing to HCQ. CONCLUSIONS The data suggest that CSA switching to HCQ treatment may be an effective strategy for patients with RA partially responding to methotrexate, particularly those with toxicity due to CSA.

Prediction of subclinical atherosclerosis by serum osteoprotegerin in premenopausal women with systemic lupus erythematous: correlation of osteoprotegerin with monocyte chemotactic protein-1

Objective Patients with systemic lupus erythematosus (SLE) have increased risk for cardiovascular disease. Previous studies disclosed the association of serum osteoprotegerin (OPG) with the presence of symptomatic atherosclerosis in the general population and several disease conditions. We thus investigated the association between serum OPG levels and subclinical atherosclerosis in premenopausal SLE patients. Methods Serum OPG levels and carotid artery intima-media thickness (IMT) were measured in 181 premenopausal SLE patients and age-matched 85 control subjects. Traditional cardiovascular risk factors and SLE-related factors were analyzed. Results Patients with SLE had significantly increased serum OPG levels (1086 versus 517 pg/ml, p < 0.001) and carotid IMT (0.63 versus 0.45 mm, p < 0.001) compared with control subjects. Carotid IMT significantly increased across the quartiles of OPG. Logistic regression analysis revealed that compared to the lowest OPG quartile, the odds ratio (OR, 95% confidence interval) for increased carotid IMT in quartile 2, 3, and 4 was 1.126 (1.013–1.801), 1.562 (1.268–2.799), and 4.460 (1.126–7.128), respectively, after multiple adjustments (p for trend across quartiles < 0.001). These associations remained significant after further adjustment for inflammatory parameters. Interestingly, serum monocyte chemotactic protein-1 (MCP-1) levels were positively correlated with serum OPG levels (γ = 0.332, p < 0.001). Parallel analysis showed that serum MCP-1 was also an independent predictor of carotid IMT incrassation, but this association was lost when serum OPG was included in the model. Conclusion Serum OPG levels were increased and correlated with serum MCP-1 levels in premenopausal SLE patients. Increased serum OPG was independently associated with subclinical atherosclerosis in these patients.

SAT0227 Urinary heparanase activity is elevated in patients with lupus nephritis and correlate with protein excretion

Background The heparin sulphate proteoglycans (HSPGs) in the glomerular basement membrane (GBM) play an important role in the charge-selective permeability of the glomerular filter. The β-D-endoglycosidase heparanase has been proposed to be important in the pathogenesis of proteinuria by selectively degrading the negatively charged side chains of HSPGs within the GBM in various forms of glomerulonephritis. Objectives To evaluate plasma and urinary activity of heparanase and to determine association between its levels and proteinuria in patients with lupus nephritis Methods Plasma from 50 patients with systemic lupus erythematosus and 10 normal healthy subjects were collected. The clinical and laboratory data of the patients were obtained at the time of sampling. Thirty three patients had a history of lupus nephritis and their urine was also collected. Proteinuria was defined as more than 0.5 g/day. Heparanase activity of plasma and urine was determined by a commercially available kit. Results Plasma heparanase activity was significantly elevated in SLE patients compared to controls (745.2±112.5 vs. 203.6±87.1 mIU/ml, p =0.039). Twenty five of patients with lupus nephritis showed significant proteinuria and their heparanase activity was not different from those without proteinuria (607.0±123.1 vs. 700.8±224.3 mIU/ml, p =0.725). On the other hand, urinary heparanase activity of patients with proteinuria was significantly elevated compared with those of patients without proteinuria (1092.1±334.2 vs. 93.3±42.8 mIU/ml, p =0.008). Moreover, urinary heparanase activity was positively correlated with 24 hours protein excretion (γ =0.546, p =0.016). Urinary heparanase activity showed an inverse correlation with complement haemolytic activity (CH50) (γ = -0.454, p =0.030) and had a tendency to associate negatively with C3 and C4 complement levels (γ = -0.331, p =0.123 and γ = -0.299, p =0.166, respectively). Conclusions Urinary heparanase activity was elevated in patients with lupus nephritis and reflect the urinary protein excretion, suggesting a potential role in the pathogenesis of proteinuria in lupus nephritis. Disclosure of Interest None Declared

THU0181 Serum level of SYNDECAN-1 is associated with disease activity in patients with systemic lupus erythematosus

Background Syndecan-1 (SDC1), a transmembrane heparan-sulfate glycoprotein, is predominantly expressed by plasma cells and is a receptor for a proliferation-inducing ligand (APRIL). SDC1 is readily shed and released into plasma under certain pathologic conditions and remains biologically active to affect cellular behaviour of plasma cells. Plasma cells are effector cells producing pathogenic autoantibodies in systemic lupus erythematosus (SLE). Objectives To evaluate serum SDC1 concentration and to determine association between its levels and certain clinical manifestation in patients with SLE Methods Serum samples from 127 patients with SLE and 24 normal healthy controls were assayed for SDC1 and APRIL by enzyme linked immunosorbent assay. Medical records were thoroughly reviewed for clinical features and serologic values. Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Results Serum SDC1 levels were significantly elevated in patients with SLE compared to controls (61.2±6.5 versus 31.4±4.5 ng/ml, P <0.001). The level was correlated positively with anti-double stranded DNA (dsDNA) antibody titer and SLEDAI score (r =0.263, P =0.004, and g =0.231, P =0.012, respectively), but negatively with C3 and CH50 levels (r = -0.247, P =0.007 and r = -0.201, P =0.034, respectively). In particular, elevated levels of serum SDC1 were associated with the presence of active proteinuria (>0.5 gm/day) in SLE patients with lupus nephritis. Moreover, serum SDC1 levels had significant correlation with level of APRIL, which was known as surrogate marker of disease activity (r =0.507, P <0.001). Conclusions Serum SDC1 levels are elevated and correlated with markers of disease activity in patients with SLE, suggesting that serum SDC1 could be used as a potential marker of disease activity in patients with SLE. Disclosure of Interest None Declared

SAT0042 Low-Density Lipoprotein Cholesterolemia as a Novel Risk Factor for Radiographic Progression of Rheumatoid Arthritis: A Single Centered Prospective Study

Background Dyslipidemia has been implicated in a variety of musculoskeletal disease including rheumatoid arthritis (RA). Evidence is emerging that there might be a pathogenic interaction among inflammation, dyslipidemia, and adipokines. Objectives We prospectively investigated the association of cumulative lipid levels with radiographic progression. Methods Two hundred-forty two RA patients regularly underwent plasma cholesterol assessment at four-time visits. Disease activity parameters, including ESR, CRP, DAS28, and hands/feet X-rays were also serially monitored in these patients. The cumulative inflammatory burden and lipid levels were estimated by the time-integrated value. Serum leptin and adiponectin concentrations were determined by ELISA. Results When patients were divided into three groups according to time-integrated lipid levels, 3rd tertile of LDL cholesterol and/or triglyceride had persistently higher ESR and CRP levels. In parallel, a more rapid radiographic progression over 2 years was observed in patients with higher LDL cholesterol and/or triglyceride. In multivariate analysis, time-integrated LDL cholesterol was independently associated with the radiographic progression after adjustments for potential confounders. Particularly, the risk of radiographic progression was 5.6-fold in a subgroup with both 3rd tertiles of LDL cholesterol and triglyceride. Moreover, LDL cholesterol synergistically increased the adjusted probability of radiographic progression in patients with high serum leptin levels, but not in those without. Conclusions Our data demonstrate that LDL cholesterolemia is a novel serum marker to predict radiographic progression of RA, which seems to be related to circulatory leptin levels. We suggest that a personalized and more aggressive anti-rheumatic therapy is required for dyslipidemic subgroups in RA patients. Disclosure of Interest None Declared