Effect of severe neuropsychiatric manifestations on short-term damage in systemic lupus erythematosus

OBJECTIVE: To determine the effect of severe neuropsychiatric (SNP) manifestations on short-term damage and the time of their presentation, in young patients with systemic lupus erythematosus (SLE) of short disease duration. METHODS: One hundred thirty patients with SLE, hospitalized because of noninfectious SNP manifestations (n = 65) or other reasons (n = 65) were studied. Clinical information, including SLE characteristics, laboratory test results, treatment, disease activity, and damage, was gathered from the medical chart at 3 different dates: the index hospitalization, the closest visit prior to and one year after hospitalization. RESULTS: Demographic and SLE characteristics were comparable in patients with SNP manifestations and controls, including age at SLE diagnosis, 26.1 +/- 11.0 vs 25.7 +/- 11.2 years (p = 0.84). SNP manifestations developed early during the course of SLE, 2.5 +/- 5.2 years. At the visit prior to the hospitalization, disease activity was mild and similar in both patient groups. During hospitalization, patients who developed SNP manifestations reached higher SLE Disease Activity Index scores than controls (p < 0.0001) and also received more aggressive treatment. One year after the hospitalization, disease activity, treatment, and mortality did not differ between the 2 patient groups; however, the increase in damage was higher among the patients with SNP manifestations than controls [0.95 +/- 0.16 (95% CI 0.64-1.26) vs 0.24 +/- 0.09 (95% CI 0.07-0.41), p < 0.0001]. CONCLUSION: SNP manifestations occur early during the course of SLE and add a significant increase in damage compared to non-NP manifestations.     

Systemic lupus erythematosus in adults is associated with previous Epstein-Barr virus exposure

OBJECTIVE: The possible molecular mimicry of the Epstein-Barr virus (EBV) peptide PPPGRRP by the peptide PPPGMRPP from Sm B'/B of the human spliceosome is consistent with the possibility that EBV infection is related to the origin of systemic lupus erythematosus (SLE) in some patients. Association of EBV exposure with SLE was therefore tested for and subsequently found in children and adolescents (odds ratio [OR] 49.9, 95% confidence interval [95% CI] 9.3-1,025, P < 10(-11)). These results were confirmed at the level of EBV DNA (OR > 10, 95% CI 2.53-infinity, P < 0.002). Much smaller seroconversion rate differences were found against 4 other herpes viruses. Herein, we extend these studies to adults and test the hypothesis that EBV infection is associated with adult SLE. METHODS: We selected 196 antinuclear antibody-positive adult SLE patients (age > or =20 years) and 2 age-, race-, and sex-matched controls per patient. SLE patients and matched controls were tested for evidence of previous infection with EBV, cytomegalovirus (CMV), herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), or varicella-zoster virus (VZV) by standardized enzyme-linked immunosorbent assays. RESULTS: Of the 196 lupus patients tested, all but 1 had been exposed to EBV, while 22 of the 392 controls did not have antibodies consistent with previous EBV exposure (OR 9.35, 95% CI 1.45-infinity, P = 0.014). No differences were observed between SLE patients and controls in the seroconversion rate against CMV, HSV-2, or VZV. CONCLUSION: These new data from adults, along with the many suggestive features of EBV infection, are consistent with the contribution of this infection to the etiology of SLE.     

Elevation of serum CXCL13 in SLE as well as in sepsis

Recent studies have demonstrated that CXCL13 serum levels correlate significantly with systemic lupus erythematosus (SLE) disease activity. However, experimental studies show that CXCL13 production can also be induced by bacterial exposure as well as in response to inflammatory cytokines. This report asks whether CXCL13 serum levels are elevated in patients with evidence of bacterial infections and whether there is a correlation with the C-reactive protein (CRP) levels or the severity of illness in critically ill patients. CXCL13 levels were compared in 39 patients with active SLE (without concomitant infection), 40 non-SLE patients with sepsis, and 40 healthy controls by enzyme-linked immunosorbent assay (ELISA) methodology. We also tested storage conditions and freeze-thaw cycles for stability of CXCL13 in serum samples. Our studies demonstrated that the median CXCL13 serum levels were significantly elevated in patients with SLE [median 83?pg/ml (interquartile range 38-366)] or sepsis [359?pg/ml (151-459)] compared with healthy controls [32?pg/ml (27-41), p?相似文献   

Pregnancy outcome in 396 pregnancies in patients with SLE in Saudi Arabia

The aim of this study was to examine the pregnancy outcomes in patients with systemic lupus erythematosus (SLE) and the effect of SLE flare and treatment on pregnancy outcomes. We performed a retrospective evaluation of all pregnancies occurring in patients with SLE during the 27-year period from 1980 to 2006. Of the 319 women with SLE planning pregnancy after SLE onset, 176 (55.2%) conceived resulting in 396 pregnancies. Live births were significantly lower in proportion (70.2% vs. 85.7%) and more likely to end in fetal deaths (29.7% vs. 14.2%) and preterm births (26.7% vs. 5.8 %) in pregnancies occurring after SLE onset than in pregnancies occurring before SLE onset (p < 0.0001). With respect to different disease manifestations, we found that fetal loss was significantly higher in patients with antiphospholipid (aPL) antibodies than without (p < 0.001). Preterm deliveries were significantly more frequent in patients with lupus nephritis, anti-Ro/SSA antibodies, hypertension, history of intravenous cyclophosphamide treatment and aPL than those without these features (p < 0.05). Neonates with intrauterine growth retardation (IUGR) neonates were more common in hypertensive and Raynaud's-positive pregnancies (p < 0.05). SLE flares occurred in 30.8% pregnancies. There was increased risk of fetal loss, preterm births and IUGR in pregnancies with SLE exacerbations than without (p < 0.05). Prednisolone was found to improve the rate of live births, although it was also a predictor of prematurity. The predictors of pregnancy loss were lupus nephritis (odds ratio (OR) 7.3), aPL (OR 3.9), and SLE flares in pregnancy (OR 1.9). There was higher risk of preterm deliveries in patients with lupus nephritis (OR 18.9), anti-Ro antibodies (OR 13.9), hypertension (OR 15.7) and SLE flares (OR 2.5). IUGR was found to be associated with hypertension (OR 37.7), Raynaud's (OR 12.3), and SLE flares (OR 4.2). In conclusion, pregnancies in SLE patients with active lupus nephritis, anti-Ro/SSA antibodies, aPL, hypertension, Raynaud's phenomenon, active disease at conception and SLE exacerbations are at a higher risk of adverse pregnancy outcomes. It is important to carefully plan pregnancy, and experienced rheumatologists and obstetricians should monitor SLE patients in pregnancy and postpartum.     

Brachial endothelial function is impaired in patients with systemic lupus erythematosus

OBJECTIVE: To verify if endothelial function is impaired in pre-menopausal women with systemic lupus erythematosus (SLE) and whether endothelial dysfunction is related to disease duration, cumulative prednisone dose, antimalarial use, anticardiolipin antibody (aCL), hypertension, Raynaud's phenomenon, disease activity score, and vasculitis. METHODS: Using high-resolution ultrasound, we measured the diameter of brachial artery at rest, during reactive hyperemia, and after glyceryl trinitrate (GTN). We compared 69 pre-menopausal female patients with SLE (mean age 29 +/- 8 years) with 35 age and sex-matched controls (mean age 29 +/- 6 years), The mean disease duration was 72 months. RESULTS: There was no significant difference in baseline brachial artery diameter. The flow-mediated dilation (endothelial dependent dilation) was significantly impaired in SLE patients when compared to controls (5.0 +/- 5.0% vs 12.0 +/- 6.0%, p < 0.001), even in the subgroup of patients without coronary artery disease risk factor (4.5 +/- 4.0% vs 12.0 +/- 6.0%, p < 0.001). The GTN induced dilation (endothelial independent dilation) was significantly lower in the aCL positive SLE patients when compared to the controls (11.9 +/- 4.0% vs 16.3 +/- 6.0%, p < 0.05). The endothelium-dependent dilation was not related to disease duration, cumulative prednisone dose, antimalarial use, anticardiolipin antibody, hypertension history, Raynaud's phenomenon, SLE disease activity score or vasculitis. CONCLUSION: This is the first study using brachial artery ultrasound imaging to evaluate endothelium function in SLE. Patients with SLE presented lower flow mediated dilation (endothelium dependent dilation) than sex and age-matched controls, even in patients without traditional cardiovascular risk factors and this may represent an early atherosclerotic process.     

Frequency of adverse drug reactions in patients with systemic lupus erythematosus

OBJECTIVE: The literature suggests that patients with systemic lupus erythematosus (SLE) have a higher frequency of adverse drug reactions (ADR). We performed this case control study to compare the prevalence of ADR in patients with SLE and controls with inflammatory arthritis. METHODS: We surveyed 249 patients, 145 with SLE and 104 age and sex matched controls with other types of inflammatory arthritis, such as rheumatoid arthritis (RA), probable RA, and psoriatic arthritis. We asked about exposure and ADR to the following classes of drugs: (1) beta-lactam antibiotics, (2) sulfonamides, (3) other antibiotics, (4) disease modifying antirheumatic drugs (DMARD), and (5) nonsteroidal antiinflammatory drugs (NSAID). Personal and family atopic histories were obtained. The 2 groups were obtained from a single rheumatologic practice and had similar characteristics and drug exposures. RESULTS: The response rate was 63% in the SLE patients and 64% in the control group. The mean age was 47.8 +/- 1.5 years in patients with SLE and 46.1 +/- 1.7 years in controls (p < 0.51). Ninety-two percent of SLE patients and 88% of controls were female (p < 0.42). Both groups had been exposed similarly to all antibiotics, as there were no significant differences between groups (exposure to sulfa antibiotics 53% in SLE patients vs 46% in controls), and to NSAID (84% SLE group vs 93% controls). Few patients from the SLE group had DMARD exposure, with the exception of plaquenil (65% SLE group vs 30% controls; p < 0.0001) and azathioprine (18% SLE group vs 4% controls; p < 0.006). There were between-groups differences with respect to total number of ADR with sulfa antibiotics (exposed had 25/48 reactions in SLE group vs 6/31 in controls; p < 0.003), but not with other drugs. Most ADR to sulfa antibiotics were cutaneous (rash). Subjects with an allergic or atopic history had more ADR (p < 0.0005). There were no differences between SLE patients and controls in having an allergic history (p < 0.88). Subjects with a positive family history of allergies were more likely to have ADR (p < 0.0043). SLE patients and controls with a personal versus family history of environmental allergies did not differ in having ADR (p < 0.16 and p < 0.83, respectively). CONCLUSION: Both intolerances and true allergic reactions were not dissimilar in patients with SLE compared to controls with inflammatory arthritis, with the exception of cutaneous reactions to sulfa antibiotics in SLE patients. This has not been the experience of other investigators (with increased ADR with several antibiotics in SLE groups) who used healthy, best friend, and relative controls with dissimilar frequencies of drug exposures. Perhaps differences observed in the past (where SLE patients have more ADR than healthy controls) are true of other inflammatory arthritis subjects (who have different drug exposures than healthy individuals) rather than just SLE. Differences could also exist in the pharmacogenetics, as our sample population was mostly Caucasian.     

The use of health-care resources in obesity-hypoventilation syndrome

OBJECTIVE: To document health-care utilization (ie, physician claims and hospitalizations) in patients with obesity-hypoventilation syndrome (OHS), for 5 years prior to the diagnosis and for 2 years after the diagnosis and initiation of treatment. DESIGN: Retrospective observational cohort study. SETTING: University-based sleep disorders center in Manitoba, Canada. Patients and control subjects: Twenty OHS patients (mean [+/- SD] age, 52.7 +/- 9.5 years; body mass index [BMI], 47.3 +/- 11.0 kg/m(2); PaCO(2), 59.7 +/- 13.8 mm Hg; PaO(2), 51.6 +/- 12.4 mm Hg) were matched to two sets of control subjects. First, each case was matched to 15 general population control subjects (GPCs) by age, gender, and geographic location, and, second, each case was matched to a single obese control subject (OBC) who was matched using the same criteria as for the GPCs, plus the measurement of BMI. Measurements and results: In the 5 years before diagnosis, the 20 OHS patients had (mean +/- SE) 11.2 +/- 1.8 physician visits per patient per year vs 5.7 +/- 0.8 (p < 0.01) visits for OBCs and 4.5 +/- 0.4 (p < 0.001) visits for GPCs. OHS patients generated higher fees, $623 +/- 96 per patient per year for the 5 years prior to diagnosis compared to $252 +/- 34 (p < 0.001) for OBCs and $236 +/- 25 (p < 0.001) for GPCs. OHS patients were much more likely to be hospitalized than were subjects in either control group in the 5 years prior to diagnosis (odds ratio [OR] vs GPCs, 8.6) (95% confidence interval [CI], 5.9 to 12.7); OR vs OBCs, 4.9 (95% CI, 2.3 to 10.1). In the 2 years after diagnosis and the initiation of treatment (usually continuous positive airway pressure or bilevel positive airway pressure), there was a significant linear reduction in physician fees. In the 2 years after the initiation of treatment, there was a 68.4% decrease in days hospitalized per year (5 years before treatment, 7.9 days per patient per year; after 2 years of treatment, 2.5 days per patient per year [p = 0.01]). CONCLUSIONS: OHS patients are heavy users of health care for several years prior to evaluation and treatment of their sleep breathing disorder; there is a substantial reduction in days hospitalized once the diagnosis is made and treatment is instituted.     

Systemic lupus erythematosus in adults is associated with previous Epstein‐Barr virus exposure

Objective

The possible molecular mimicry of the Epstein‐Barr virus (EBV) peptide PPPGRRP by the peptide PPPGMRPP from Sm B′/B of the human spliceosome is consistent with the possibility that EBV infection is related to the origin of systemic lupus erythematosus (SLE) in some patients. Association of EBV exposure with SLE was therefore tested for and subsequently found in children and adolescents (odds ratio [OR] 49.9, 95% confidence interval [95% CI] 9.3–1,025, P < 10⁻¹¹). These results were confirmed at the level of EBV DNA (OR > 10, 95% CI 2.53–∞, P < 0.002). Much smaller seroconversion rate differences were found against 4 other herpes viruses. Herein, we extend these studies to adults and test the hypothesis that EBV infection is associated with adult SLE.

Methods

We selected 196 antinuclear antibody–positive adult SLE patients (age ≥20 years) and 2 age‐, race‐, and sex‐matched controls per patient. SLE patients and matched controls were tested for evidence of previous infection with EBV, cytomegalovirus (CMV), herpes simplex virus types 1 and 2 (HSV‐1 and HSV‐2), or varicella‐zoster virus (VZV) by standardized enzyme‐linked immunosorbent assays.

Results

Of the 196 lupus patients tested, all but 1 had been exposed to EBV, while 22 of the 392 controls did not have antibodies consistent with previous EBV exposure (OR 9.35, 95% CI 1.45–∞, P = 0.014). No differences were observed between SLE patients and controls in the seroconversion rate against CMV, HSV‐2, or VZV.

Conclusion

These new data from adults, along with the many suggestive features of EBV infection, are consistent with the contribution of this infection to the etiology of SLE.

     

Association of reduced CD4 T cell responses specific to varicella zoster virus with high incidence of herpes zoster in patients with systemic lupus erythematosus

OBJECTIVE: To examine whether the high incidence of herpes zoster in patients with systemic lupus erythematosus (SLE) is associated with the frequency of memory T cells specific to varicella zoster virus (VZV). METHODS: Whole blood samples from 47 subjects [24 patients with SLE, 11 with rheumatoid arthritis (RA) as a disease control, and 12 healthy negative controls] were stimulated with VZV antigen, stained for surface CD4 and CD8 and intracellularly stained for the cytokines interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin 4 (IL-4), and IL-10, followed by flow cytometry analyses. Correlations of VZV-specific T cell frequencies with the clinical status of patients were analyzed. RESULTS: Percentage of IFN-gamma-positive CD4 T cells was significantly lower in patients with SLE (0.043 +/- 0.009%) than in RA (0.102 +/- 0.019%) and healthy controls (0.126 +/- 0.025%) upon VZV stimulation. A similar pattern was seen in TNF-alpha-positive CD4 T cell responses. These low frequencies of VZV-specific CD4 T cells in patients with SLE were significantly related with disease activity (r = -0.435, p = 0.043). CONCLUSION: These data suggest that the high incidence of herpes zoster in patients with SLE was related to the intrinsic defects in controlling VZV reactivation, and thus VZV-specific CD4 T cell frequency could be another practical risk factor of herpes zoster in patients with SLE.     

High prevalence of immunoglobulin A antibody against Epstein-Barr virus capsid antigen in adult patients with lupus with disease flare: case control studies

OBJECTIVE: Systemic lupus erythematosus (SLE) is a severe autoimmune disease with rare remission and recurrent flare. Epstein-Barr virus (EBV) infection has been reported to be strongly associated with SLE in the United States, but with an inconclusive role in Asia. We investigated the role of EBV infection in patients with SLE in Taiwan, with one of the highest population densities in Asia. METHODS: We conducted case-control studies to test whether EBV infection was associated with adult SLE in Taiwan. In the first study, 36 adults with SLE and 36 sex and age matched controls were enrolled for examination of serum IgG, IgM, and IgA antibody against EBV-virus capsid antigen (EBV-VCA). In the second study, another 36 adult lupus cases and 36 matched controls were enrolled to confirm the high prevalence of IgA antibody against EBV-VCA found in the first study. Further, both groups of SLE patients were combined to analyze the association between the existence of IgA antibody against EBV-VCA and disease activity (determined by SLEDAI score) and disease flare in patients with SLE. RESULTS: In the first study, IgA antibody against EBV-VCA was the only marker with significantly higher prevalence in adults with SLE compared to healthy adults (36.1% vs 5.6%; p < 0.005). In the second study, we confirmed that the prevalence of IgA antibody against EBV-VCA was indeed higher in adults with SLE (38.9% vs 2.8%; p < 0.001). With further analysis (pooling analysis), adult SLE patients with IgA antibody against EBV-VCA had higher disease activity compared to SLE patients without IgA antibody against EBV-VCA (SLEDAI 7.8 +/- 6.6 vs 3.3 +/- 2.1; p < 0.001). SLE patients with flare showed much higher prevalence of IgA antibody against EBV-VCA compared to those without flare (81.3% vs 25.0%; p < 0.001). CONCLUSION: This is the first evidence that IgA antibody against EBV-VCA is strongly associated with disease flare in SLE patients. It suggests that EBV reactivation may contribute toward the disease flare of SLE.     

The A-1087IL-10 allele is associated with cardiovascular disease in SLE

The risk of cardiovascular disease (CVD) in SLE patients is very high. It is therefore surprising that IL-10 has been discussed both as pathogenic in SLE and as an atheroprotective cytokine. In contrast, TNF is believed to be atherogenic and we recently reported that raised activity in the TNF-system is implicated in SLE-related CVD. Twenty-six (aged 52 +/- 8 years) female patients with SLE and a history of CVD (myocardial infarction, angina, stroke or claudication) were compared with 26 age-matched SLE patients without CVD (SLE controls) or 26 age-matched population controls. The -1087IL-10 gene polymorphism was determined by PCR with restriction endonuclease mapping. Serum IL-10 and TNF-levels were determined by ELISA. The A allele frequency of -1087IL-10 gene in SLE/CVD was higher than in SLE controls (0.62 versus 0.42, p < 0.05). Ten (38%) of 26 SLE/CVD exhibited IL-10 AA genotype compared with five (19%) of 26 SLE controls. Serum IL-10 and TNF-levels were raised in SLE/CVD compared with SLE controls or population controls (p < 0.001). Furthermore, in SLE/CVD, a significantly reduced IL-10:TNF ratio was observed in patients with IL-10 AA genotype compared with AG or GG genotype (0.56 versus 0.77 versus 1.24, p < 0.05). In SLE controls and population controls, individuals with IL-10 GG genotype tended to have higher IL-10:TNF ratio. In conclusion, the A-1087IL-10 allele which has been reported to cause a lower capacity for IL-10 production could contribute to CVD in SLE. Furthermore, the IL-10 AA genotype is associated with reduced ratio of atheroprotective to atherogenic cytokines in SLE patients with CVD.     

Effect of antimalarial agents on the fasting lipid profile in systemic lupus erythematosus

OBJECTIVE: To ascertain the relative effect of antimalarial (AM) agents on fasting lipid fractions in patients with systemic lupus erythematosus (SLE). METHODS: The study was cross sectional including all patients with SLE who were seen in our lupus clinic with fasting lipid profiles measured as part of evaluation from November 1995 to March 1999. RESULTS: A total of 123 patients with a mean age of 45.3 years and mean disease duration 13.4 years were studied; 73.2% were taking prednisone with a mean +/- SD dose of 10.9 +/- 9.2 mg/day, 48.0% were taking AM, and 30.8% were taking both. In the entire group, patients taking AM had a 12.5% lower total cholesterol (TC) (5.11 +/- 1.27 vs 5.84 +/- 1.23; p = 0.002), 22.1% lower very low density lipid-cholesterol (VLDL-C) (0.66 +/- 0.40 vs 0.85 +/- 0.39; p = 0.01), and 15.7% lower LDL-C (3.01 +/- 1.14 vs 3.58 +/- 1.10; p = 0.007). For patients taking prednisone, those taking concomitant AM (n = 38) had significantly lower TC (5.26 +/- 1.30 vs 5.99 +/- 1.29; p = 0.01), VLDL-C (0.65 +/- 0.39 vs 0.85 +/- 0.41; p = 0.02), and LDL-C (3.05 +/- 1.20 vs 3.69 +/- 1.09; p = 0.01) than those without AM (n = 48). For patients taking < or = 10 mg/day prednisone, TC (4.69 +/- 0.88 vs 5.74 +/- 1.20; p < 0.001), VLDL-C (0.61 +/- 0.37 vs 0.83 +/- 0.44; p = 0.05), and LDL-C (2.57 +/- 0.76 vs 3.49 +/- 1.04; p < 0.001) were still lower in patients with concomitant AM (n = 22) than those without AM (n = 36). CONCLUSION: TC, VLDL-C, and LDL-C levels were significantly lower in patients taking AM, including patients taking concomitant prednisone. Thus AM may have beneficial effects in SLE in addition to disease suppression.     

Angiotensin-converting enzyme gene polymorphism and vascular manifestations in Korean patients with SLE

Systemic lupus erythematosus (SLE) is an inflammatory multisystem disease of unknown etiology with immunologic aberrations. Many studies have shown that genetic and environmental factors are implicated in the development of SLE. Angiotensin-converting enzyme (ACE) affects various immune phenomena through the renin-angiotensin and kallikrein-kininogen systems by creating angiotensin II and inactivating bradykinin. We investigated the correlation between insertion/ deletion polymorphism of the ACE gene and the clinical manifestations of SLE, especially vascular involvement and lupus nephritis. Two-hundred and eleven Korean patients fulfilling the ACR criteria and 114 healthy subjects were enrolled. The ACE genotype was determined by polymerase chain reaction using genomic DNA from peripheral blood. The nephritis patients were classified by the WHO classification. In addition, the activity and chronicity index were used to assess the severity of renal involvement. We evaluated vascular involvement by the presence or absence of hypertension, Raynaud's phenomenon, livedo reticularis, antineutrophil cytoplasmic antibody and the SLICC/ACR Damage Index. The gene frequency of ACE gene polymorphism was as follows: II 39 vs 34%, ID 41 vs 50%, DD 20 vs 16% in SLE patients and controls, respectively. There was no difference in genotype frequency between both groups. There were no significant differences between the distribution of ACE gene genotypes and lupus nephritis and its related parameters, including WHO classification, activity index, chronicity index, renal dysfunction and amount of 24 h urinary protein. The ACE genotypes and alleles did not affect the presence of vascular manifestations evaluated, but the frequency of DD genotype was significantly low in SLE patients with Raynaud's phenomenon compared to those without Raynaud's phenomenon (P = 0.002 for ACE ID vs DD and II, OR 2.7, 95% CI 1.43-5.09; P=0.023 for ACE DD vs ID and II, OR 0.33, 95% CI 0.12-0.89). Also skewing from DD to II genotype was noted in patients with anti-Sm antibody compared to those without anti-Sm antibody (P = 0.025 for ACE DD vs ID and II, OR 0.21, 95% CI 0.05-0.93). The onset age of serositis was older in patients with the ID genotype than the others (ID= 34.5+/-10.8, II + DD = 25.6+/-10.2, P= 0.002). Also the onset age of malar rash was older in patients with II genotype than the others (II=26.7+/-8.4, ID+DD=21.3+/-9.0; P=0.021). The patients with I allele showed a significantly higher frequency of serositis (P = 0.022). Taken together, the I/D polymorphisms of ACE gene did not affect susceptibility of SLE, lupus nephritis and the vascular manifestations, including Raynaud's phenomenon, in Korean SLE patients, although the DD genotype was negatively associated with Raynaud's phenomenon among SLE patients. However, it would be valuable to evaluate the role of other genes potentially related to vascular events, such as endothelin, nitric oxide or angiotensin II receptor as well as ACE gene.     

Increased concentration of proatherogenic inflammatory cytokines in systemic lupus erythematosus: relationship to cardiovascular risk factors

OBJECTIVE:. To examine the hypothesis that patients with systemic lupus erythematosus (SLE) have increased concentrations of interleukin-6 (IL-6), IL-8, and monocyte chemoattractant protein-1 (MCP-1) and that these cytokines are associated with coronary risk factors and atherosclerosis. METHODS: Plasma IL-6, MCP-1, and serum IL-8 (pg/ml) concentrations were measured in 74 patients with SLE and in 85 controls. Clinical characteristics, homocysteine, lipids, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and coronary artery calcification as detected by electron beam computed tomography were measured. RESULTS: IL-6 (13.2 +/- 13.8 pg/ml vs 6.7 +/- 3.2 pg/ml, p < 0.001) and MCP-1 (264.2 +/- 581.8 pg/ml vs 131.0 +/- 63.7 pg/ml, p < 0.001) concentrations were higher in patients with lupus than in controls. IL-8 concentrations did not differ between patients and controls (p = 0.86). In patients, IL-6 concentrations were correlated with CRP (p < 0.001), ESR (p < 0.001), SLE disease activity index (SLEDAI, p = 0.003), and body mass index (BMI, p = 0.003). IL-6 concentrations were inversely correlated with HDL cholesterol (p = 0.01). MCP-1 concentrations were correlated with SLEDAI (p = 0.01), ESR (p = 0.04), and triglycerides (p = 0.03). After controlling for age, sex, disease activity, SLICC damage index, smoking status, and systolic blood pressure, IL-6 was associated with coronary calcification (odds ratio, OR = 1.07, p = 0.035). Similar models found no association between MCP-1 or IL-8 with coronary artery calcification. CONCLUSION: Patients with SLE have increased concentrations of IL-6 and MCP-1. These cytokines are associated with increased inflammation, BMI, and adverse lipid profiles. IL-6 is associated with burden of atherosclerosis in SLE.     

Risk factors associated with mortality in systemic lupus erythematosus. A case-control study in a tertiary care center in Mexico City

OBJECTIVE: To identify the mortality risk factors in a group of Mexican patients with SLE. METHODS: A case-control autopsy study in a tertiary care center in Mexico, City. Patients with SLE who died during 1958 to 1994 with an autopsy study were selected as cases, and alive patients matched by age (+/- 3 years), decade of SLE onset, and disease duration (+/- 5 years) were defined as controls. Clinical charts were reviewed looking at clinical variables. SLE disease activity was evaluated with the MexSledai index, and SLE disease severity with the Severity Index. Variables were classified as present at any moment during the follow-up and 3 months before death in cases or cut-off date in controls. Statistical analysis: matched univariate and multivariate analysis by multiple logistic regression were performed, and the results were presented as odds ratio and 95% confidence intervals (OR, 95%CI). RESULTS: 76 matched pairs of patients were studied. Age, gender, and years offormal education were similar in the cases and controls. Variables associated with mortality three months before death were: lung involvement OR= 15.6, 95%CI (4.8-50.3), p<0.001; severe thrombocytopenia 9.6 (2.9-31.7), p<0.001; heart involvement 5.8 (2.6-13.0), p<0.001; and the severity index (cases 8.8 mu, 2.4 sigma vs controls 3.5, 2.0, respectively) 2.2 (1.5-3.4), p<0.001. Variables associated with mortality detected at any moment before death were kidney involvement 2.16 (1.09-4.29), p<0.02; the steroid therapeutic index 2.3 (1.2-4.5), p<0.001; number of previous admissions 2.4 (1.4-4.3), p<0.001; the MEX-SLEDAI index (cases 21.6 mu 6.3 sigma vs controls 12.6, 5.8), 1.2 (1.1-1.3), p<0.001; and the number of severe infections 14.4 (4.4-46.2), p<0.001. Protective variables were skin involvement 0.1 (0.3-0.6), p<0.001; daily dose of chloroquine (cases 3.9 mu, 24.1 sigma vs controls 39.4, 60.0 mg), p <0.0001 and the time from thefirst SLE symptom to the patient's demise or the cut-off date 0.7(0.6-0.9), p<0.001. Multiple logistic regression showed that the model which best explained mortality consisted of a severity index 2.6 (1.7-3.8), p<0.001; heart disease 6.5 (1.5-28.2), p=0.01, and steroid therapeutic index 3.3 (1.6-6.6), p=0.001. CONCLUSIONS: An active SLE with multi-organic involvement, steroids and infections were associated with mortality in Mexican patients with lupus attended in a tertiary care center A protective effect of cutaneous disease and chloroquine use was observed.     

Incidence of nosocomial infections in adult patients undergoing extracorporeal membrane oxygenation

Introduction

Critically ill patients requiring extracorporeal membrane oxygenation (ECMO) are at increased risk for developing nosocomial infections owing to their underlying disease process along with numerous invasive monitoring devices.

Altered levels of adipocytokines in association with insulin resistance in patients with systemic lupus erythematosus

OBJECTIVE: The metabolic syndrome, closely associated with cardiovascular disease, is characterized by increased insulin resistance (IR). Although accelerated atherosclerosis is frequently observed in systemic lupus erythematosus (SLE), the prevalence and significance of IR remain to be elucidated. We evaluated IR in association with plasma concentrations of adipocytokines in patients with SLE. METHODS: Outpatients with SLE (n = 37) and healthy controls (n = 80) were studied. A value of the homeostasis model assessment index (HOMA-IR) > 2.0 was considered to be IR. Plasma concentrations of adiponectin and tumor necrosis factor-a (TNF-a) were measured by ELISA and leptin by radioimmunoassay. RESULTS: HOMA-IR indices of the SLE patients were significantly higher than those of controls (2.3 +/- 2.3 vs 1.3 +/- 1.0, respectively; p < 0.01), although both groups exhibited a similar body mass index. The prevalence of hypertension and diabetes mellitus was significantly higher in patients with SLE compared with controls (48.6% vs 8.8% and 10.8% vs 0%). Twelve SLE patients (32%) with IR exhibited significantly higher incidence of hypertension and current proteinuria than SLE patients without IR. Plasma leptin, TNF-a, and, unexpectedly, adiponectin levels were higher in SLE patients than controls (adiponectin, 13.7 +/- 5.0 vs 9.5 +/- 3.9 microg/ml). Among the SLE patients, patients with IR showed significantly lower adiponectin levels than patients without IR (10.9 +/- 4.6 vs 15.4 +/- 4.4 microg/ml). Serum levels of adiponectin were significantly correlated inversely with HOMA-IR in SLE patients. CONCLUSIONS: Elevated levels of adiponectin in SLE, despite inverse correlation with IR, suggest the possible involvement of adiponectin in IR and alterations in its effect on insulin sensitivity.     

Non-tuberculous mycobacterial infection in patients with systemic lupus erythematosus

OBJECTIVES: Patients with systemic lupus erythematosus (SLE) are susceptible to opportunistic infections. To examine the clinical manifestations of non-tuberculous mycobacterial (NTM) infections with those of Mycobacterium tuberculosis (MTB) infections in SLE patients. METHODS: Medical records of a cohort of 725 SLE patients were reviewed for previous NTM infections. Demographic characteristics, predisposing factors and clinical outcomes were compared with patients who had previous MTB infections (n = 39). RESULTS: Eleven (nine female and two male) cases were identified (prevalence 1.5%). The mean +/- S.D. age at the time of infection was 42.8 +/- 13.9 yrs, 9.3 +/- 5.8 yrs after the onset of SLE. The mean +/- S.D. time taken from onset of symptoms to the diagnosis of NTM infection was 5.7 +/- 7.2 months. Sites of involvement included skin and soft tissue (n = 8), chest (n = 2) and disseminated infection (n = 1). NTM infections were more likely to involve extrapulmonary sites (P = 0.006), presented in patients with longer lupus disease duration (P < 0.001), occurred in older patients (P < 0.001) and in those who had a higher cumulative dose of prednisolone (P = 0.01) than MTB infections. Using a stepwise logistic regression, disease duration was found to be the only independent predictive factor (P = 0.005) for NTM infections. Ten (25.6%) patients with MTB infections but none of the patients with NTM infections presented concomitantly at the onset of SLE (P = 0.09). There were no differences in the recurrence rate (P = 0.64) and frequency of disseminated infections (P = 0.40) between NTM and MTB infections. CONCLUSIONS: NTM infections tended to develop in SLE patients later in their disease course than MTB infections. A high index of suspicion is required for its diagnosis.     

Chemokine receptor CCR2/CCR5 polymorphism in Spanish patients with systemic lupus erythematosus

OBJECTIVE: To investigate the possible association of CCR2 and CCR5 chemokine receptor gene polymorphisms with the susceptibility, clinical features, and the outcome of systemic lupus erythematosus (SLE). METHODS: We studied 276 patients with SLE and 194 ethnically matched healthy controls. Patients were stratified according to their clinical features and outcome. Genotyping of 190 (A/G) CCR2 and D32CCR5 was performed using polymerase chain reaction techniques. RESULTS: No association between the polymorphisms studied and susceptibility to SLE was found. However, when patients were stratified according to their clinical features, an increase in the frequency of individuals bearing D32CCR5 among patients with anti-dsDNA antibodies was found [15.1% vs 6.4% in negative patients (p = 0.03, pcorr > 0.05, OR 2.61, 95% CI 1.04-7.40) and 8% in controls (p = 0.04, pcorr > 0.05, OR 1.97, 95% CI 0.97-4.11)]. Moreover, a significant increase in the frequency of D32CCR5 individuals was observed among patients with biopsy-proven nephritis [20.5% vs 8.5% in patients without nephritis (p = 0.03, pcorr > 0.05, OR 2.79, 95% CI 0.93-7.70) and 8% in controls (pFisher = 0.04, pcorr > 0.05, OR 2.87, 95% CI 0.97-7.82)]. Regarding the outcome, a higher median severity index was found among patients bearing D32CCR5 (33.5 +/- 17.9 vs 26.6 +/- 17.1 in CCR5/CCR5 individuals; p = 0.04). CONCLUSION: Polymorphisms of CCR2 and CCR5 do not seem to be involved in susceptibility to SLE, although a slight contribution of the CCR5 polymorphism in the production of anti-dsDNA autoantibodies, in the development of lupus nephritis, and in the outcome of the disease could be postulated.     

Treatment of osteoarthritis of the hip and knee: a comparison of NSAID use in patients for whom surgery was and was not recommended

OBJECTIVE: To determine if NSAID use was different between OA (hip and/or knee) patients treated surgically to those treated medically. METHODS: We conducted a case control study, in which cases (n = 433) had had a total joint replacement within a two-year period, while controls (n = 195) had seen a rheumatologist or orthopedic surgeon, and not been recommended for surgery. Current and previous NSAID use was surveyed. RESULTS: Cases were older than controls (70 vs. 64 years, p < 0.0001), and were more likely to have OA in the hips (45% vs. 21%, p < 0.0001), to have severe OA (p < 0.0001), and to be male (42% vs. 28%, p < 0.0008). Potential confounding variables were statistically adjusted using logistic regression. Although disease duration was similar in cases and controls (9.8 years), cases had tried fewer NSAIDs (1.3 +/- 0.05 vs. 2.3 +/- 0.08 in controls, p < 0.0001). Cases were less likely to have taken any NSAID (86% vs. 94% of controls; OR 0.40, p < 0.007) or to have had intra-articular steroids (OR 0.19, p < 0.0001). Two or more NSAIDs were used (ever) in 38% of cases vs. 70% of controls (p < 0.0001); and 3 or more NSAIDs in 5% vs. 38% (p < 0.0001). Women were less apt to have obtained total joint replacements (OR 0.62, p < 0.0001), including TKRs even when adjusting for severity of OA. CONCLUSIONS: NSAIDs are used less by orthopedic surgeons than rheumatologists in our centre. Some subjects were offered a joint replacement without even a failure of medical management. The reasons for differences in prescribing trends are unknown. Referral biases may exist.