Outcome of neuropsychiatric systemic lupus erythematosus within a defined Swedish population: increased morbidity but low mortality

OBJECTIVE: To investigate the outcome of neuropsychiatric involvement in systemic lupus erythematosus patients (NPSLE) recruited from a defined population. METHODS: All cases of adult SLE diagnosed during 1981-1995 within the Lund-Orup Health Care District were followed prospectively and neuropsychiatric manifestations were recorded. The SLICC/ACR (Systemic Lupus International Collaborating Clinics/American College of Rheumatology) Damage Index, mortality and working incapacity were recorded as measures of outcome. RESULTS: NPSLE manifestations developed in 38% (44/117) of the patients. A high rate of organ damage (SLICC/ACR Damage Index) was recorded in the NPSLE patients (P<0.001). Compared with patients without neuropsychiatric involvement, NPSLE patients were treated more intensively, with glucocorticoids (P<0.01) and cytostatic drugs (P<0.01). When compared with the normal population in the same area, the NPSLE patients had a higher rate of working incapacity (relative risk 4.0, 95% confidence interval 2.06-6.96), whereas mortality was not increased (standardized mortality rate 1.4, 95% confidence interval 0.5-3.0). CONCLUSIONS: SLE patients with neuropsychiatric involvement have an increased rate of organ damage and a high degree of working incapacity, which illustrates the severity of disease in this subgroup.     

Increased serum levels of soluble fractalkine (CX3CL1) correlate with disease activity in rheumatoid vasculitis

OBJECTIVE: To determine levels of soluble fractalkine (sFkn) in rheumatoid arthritis (RA) patients with and without rheumatoid vasculitis (RV), and to assess the relationship of sFkn levels to disease activity. METHODS: Serum was obtained from 98 RA patients (54 without vasculitis, 36 with extraarticular manifestations but without histologically proven vasculitis, and 8 with histologically proven vasculitis) and from 38 healthy individuals. Levels of sFkn were measured by enzyme-linked immunosorbent assay. Expression of Fkn and CX(3)CR1 was quantified by real-time polymerase chain reaction. Vasculitis disease activity was assessed using the Birmingham Vasculitis Activity Score and the Vasculitis Activity Index. RESULTS: Serum sFkn levels were significantly higher in patients with RA than in controls and were significantly higher in RA patients with RV than in those without vasculitic complications. Statistically significant correlations were observed between serum sFkn levels in RA patients and levels of C-reactive protein, rheumatoid factor, immune complex, and complement. In the RV group, sFkn levels also correlated with disease activity. Immunohistochemical analysis indicated that Fkn levels were associated mainly with endothelial cells in vasculitic arteries. In addition, expression of CX(3)CR1 messenger RNA was significantly greater in peripheral blood mononuclear cells from patients with active RV than in those from other RA patients or controls. Notably, serum sFkn levels were significantly diminished following successful treatment and clinical improvement. CONCLUSION: These findings suggest that Fkn and CX(3)CR1 play crucial roles in the pathogenesis of RV and that sFkn may serve as a serologic inflammatory marker of disease activity in RA patients with vasculitis.     

Relationship between clinical factors and neuropsychiatric manifestations in systemic lupus erythematosus

Neuropsychiatric symptoms are often seen in patients with systemic lupus erythematosus (SLE). To investigate the relationship between involvement of the nervous system and clinical factors, including autoantibodies and the activity of SLE, we retrospectively reviewed 25 patients with neuropsychiatric SLE (NPSLE, mean age: 35.2±12.2 years). As controls 37 SLE patients without neuropsychiatric manifestations (mean age: 31.8±15.8 years) were employed in this study. At the onset no significant differences were seen in any clinical factors between the patients and the controls except for serum antinuclear antibodies. In relapse, the patients with NPSLE showed significantly lower levels of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores without neuropsychiatric evaluation (p<0.0001), erythrocyte sedimentation rate (ESR, p<0.005), and antinuclear and anti-double-stranded DNA antibodies (p<0.005) and higher WBC values (p<0.05) than at the onset. Also in the patients with relapsing NPSLE similar significant differences were seen in these parameters between onset and relapse (p<0.005). Despite a lack of significant differences, the cerebrospinal fluid showed lower values in cell counts, total protein, and IgG in relapse than at onset. These results suggest that there are no clinical factors that predict the development of NPSLE and that relapse can occur with low disease activity in the nervous system even with an inactive state of other organ involvement. Since NPSLE may suddenly relapse with a slight change in common disease activation markers, including inflammatory reactions, autoantibodies, and complements in serum and CSF findings, adequate corticosteroid and/or immunosuppressive agents should be given at the onset and gradually be tapered after recovery, while looking out for recurrence.     

Increased serum matrix metalloproteinase 9 levels in systemic lupus erythematosus patients with neuropsychiatric manifestations and brain magnetic resonance imaging abnormalities

OBJECTIVE: To evaluate whether serum matrix metalloproteinase 9 (MMP-9) levels are associated with neuropsychiatric manifestations, particularly cognitive dysfunction, as evaluated by neuropsychological testing and brain magnetic resonance imaging (MRI) abnormalities in patients with systemic lupus erythematosus (SLE). METHODS: MMP-9 determinations were made in 44 patients with SLE and 43 healthy controls who underwent a clinical neurologic and neuropsychological investigation in order to identify neuropsychiatric manifestations. Cerebral MRI scans with volumetric estimation of intracranial cerebrospinal fluid spaces, T1-weighted lesions, and T2-weighted lesions were performed for all subjects. SLE activity was assessed by the European Consensus Lupus Activity Measure (ECLAM) index, and accumulated neuropsychiatric abnormality was assessed by the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology damage index. RESULTS: No significant difference was found in serum MMP-9 levels between the overall group of SLE patients and controls. However, SLE patients who had at least 1 neuropsychiatric manifestation (NPSLE patients) had significantly higher serum MMP-9 concentrations than did SLE patients without neuropsychiatric syndromes (P = 0.009). Among patients with NPSLE, those with cognitive deficits had significantly higher concentrations of serum MMP-9 than did those with normal cognitive function (P = 0.027). Furthermore, serum MMP-9 levels had a significant positive correlation with the volumes of T1-weighted and T2-weighted lesions in the brain MRI (P = 0.031 and P = 0.015, respectively). The concentration of serum MMP-9 correlated significantly with the SLICC index but not with the ECLAM index. CONCLUSION: Elevated levels of serum MMP-9 in patients with SLE may reflect neuropsychiatric involvement, particularly cognitive dysfunction. The serum MMP-9 concentration may be associated with small- vessel cerebral vasculopathy and increased risk of cerebral ischemic events in patients with SLE.     

The reliability of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index in patients with Systemic Lupus Erythematosus

Objective. To test the reliability of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in the assessment of patients with SLE. Methods. Ten patients with SLE, representing a spectrum of damage and activity, were included. Each patient was examined by 6 of 10 physicians from 5 countries, representing 10 lupus clinics. The SLICC/ACR Damage Index was used to assess accumulated damage, and the SLEDAI was used to assess disease activity. The order of the patients and physicians was randomized according to a Youden square design. Results. The SLICC/ACR Damage Index detected differences among patients (P < 0.001). There was no detectable observer difference (P = 0.933), and there was no order effect (P = 0.261). Similar results were obtained with the SLEDAI. There was concordance in the SLICC/ACR Damage Index among observers, despite a wide spectrum of disease activity detected by the SLEDAI. Conclusion. Physicians from different centers are able to assess patients with SLE in a reproducible way, using the SLEDAI to assess disease activity and the SLICC/ACR Damage Index to assess accumulated damage.     

Skin is the most frequently damaged system in recent-onset systemic lupus erythematosus in a tropical region

The objective of this study was to evaluate the early damage as measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) in Brazilian systemic lupus erythematosus (SLE) patients with disease duration of 2 and 3 years and to evaluate the possible association between SLICC/ACR DI score and sociodemographic and clinical data. The SLICC/ACR DI was measured in 54 patients with SLE according to the ACR criteria for SLE and a mean (SD) disease duration of 29 (3.8) months. The patients were provided by outpatient clinics and hospitals of the public health network and private clinics in the city of Natal in Brazil. The SLICC/ACR DI scores for each type of organ damage, prevalence of damage within organ systems, and the association with sociodemographic variables were assessed. Disease duration was considered as the time from diagnosis until the study. Organ damage was present in 18 (33%) of the 54 patients while 36 patients (67%) had no damage. The skin (11%), renal (9%), and pulmonary (7.4%) systems were the most frequently involved, followed by the neuropsychiatric and musculoskeletal systems, premature gonadal failure, and diabetes. The most frequent individual items on the SLICC/ACR DI were scarring chronic alopecia and pleural fibrosis. No association was demonstrated between organ damage (SLICC/ACR scores) and sociodemographic and clinical variables. Early organ damage demonstrated in Brazilian patients with SLE was similar to other populations studied in the world, despite a low socioeconomic status. In contrast to reports in other studies, a cutaneous lesion was the most frequent cause of damage in our patients.     

The heterogeneity of neuropsychiatric systemic lupus erythematosus is reflected in lack of association with cerebrospinal fluid cytokine profiles

The objective was to study the occurrence of autoantibodies and cytokines in serum and cerebrospinal fluid (CSF) in neuropsychiatric systemic lupus erythematosus (NPSLE). In total, 28 consecutive patients with NPSLE and 16 systemic lupus erythematosus (SLE) patients without neuropsychiatric involvement (non-NPSLE) were studied. IFN-alpha, IL-6, IL-10, soluble terminal complement complex (TCC), anti-ribosomal P protein antibodies (anti-P) and anti-cardiolipin antibodies (aCL) were measured in serum and CSF by immunoassays. Analyses of white blood cell differential count, CSF-albumin/serum-albumin ratio, IgG-index in CSF and isoelectric focusing in serum and CSF were also performed. CSF specimens from 23 healthy individuals were used as controls. IFN-alpha was elevated in the CSF of 5 of 28 NPSLE patients compared to three of 14 among the non-NPSLE patients. IL-6 was elevated in CSF in three of 26 NPSLE patients. Normal concentration of IL-10 was found in CSF in all 27 NPSLE-patients analysed. IFN-alpha in serum was elevated in 18 of 28 NPSLE patients. No distinct clinical phenotype was related to elevated cytokine concentration in serum or CSF. One patient with cerebral involvement complicated by progressive multifocal leukoencephalopathy displayed a very high IFN-alpha concentration in serum. High concentration of TCC was present in CSF from only one patient with systemic vasculitis and focal cerebral symptoms. In conclusion, the results of this study suggest that the diagnostic value of serum and CSF concentrations of IFN-alpha, IL-10, IL-6 and TCC is limited in unselected neuropsychiatric SLE, probably due to the heterogeneity of NPSLE pathogenesis.     

Elevated levels of serum sCXCL16 in systemic lupus erythematosus; potential involvement in cutaneous and renal manifestations

The aim of this study was to investigate the levels and clinical significance of serum soluble chemokine (C-X-C motif) ligand 16 (sCXCL16) in patients with systemic lupus erythematosus (SLE), as well as the sCXCL16 molecule’s associations with disease activity and organ damage. Thirty-five patients with SLE, 16 patients with rheumatoid arthritis (RA), and 15 healthy controls were included in this study. The demographic and clinical features of the patients were recorded. The serum levels of sCXCL16 were determined. Disease activity was assessed using the SLE Disease Activity Index (SLEDAI), and organ damage was evaluated with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI). The serum levels of sCXCL16 in the patients with SLE were higher than those in the patients with RA (P?=?0.002) or healthy controls (P?P?=?0.008). Positive correlations were identified between serum sCXCL16 concentrations and both SLEDAI (r?=?0.564; P?r?=?0.396; P?=?0.018). Both SLEDAI (P?=?0.021) and serum levels of CXCL16 (P?=?0.023) decreased after conventional treatment in 12 initial onset cases of SLE patients. Elevated serum sCXCL16 levels were discovered in the SLE patients with cutaneous (P?=?0.006) and renal involvement (P?=?0.032). Soluble CXCL16 may become a useful serological marker of disease activity and skin and renal involvement in SLE patients; thus, it may be used for evaluation of therapeutic interventions.     

Cigarette smoking and disease activity in systemic lupus erythematosus

OBJECTIVE: To investigate the effect of cigarette smoking on disease activity and cumulative organ damage in systemic lupus erythematosus (SLE). Methods. Extensive clinical and demographic variables, including current and previous cigarette smoking, were collected from 111 SLE patients using a detailed interview-administered questionnaire. Disease activity was estimated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Cumulative organ damage was measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR). Smoking status was correlated with disease activity and cumulative organ damage, while statistically adjusting for the individual effects of potentially confounding demographic and clinical variables using analysis of variance followed by Fisher's least significant difference method. Results. Current smokers demonstrated significantly higher (p < 0.001) SLEDAI scores (15.6 +/- 7.8) than ex-smokers (9.63 +/- 6.00), and never smokers (9.03 +/- 5.75). This association remained significant (p = 0.001) after adjusting for all covariates, including ethnicity, education level, income level, alcohol use, age of onset of SLE, current age, mean duration of SLE, marital status, and hydroxychloroquine therapy. Current smokers also demonstrated significantly (p = 0.003) higher scores for both the neurological and non-neurological components of SLEDAI. There was no significant difference in the SLICC/ACR scores across the various smoking groups, although there was a trend for more severe disease in current smokers. Conclusion. Cigarette smoking is associated with increased disease activity in SLE. These data further establish the association of SLE with cigarette smoking, and suggest that individuals with SLE should avoid all exposure to tobacco products.     

Relationship between elevated cerebrospinal fluid levels of plasminogen activator inhibitor 1 and neuronal destruction in patients with neuropsychiatric systemic lupus erythematosus

Objective

A homeostatic imbalance between coagulation and fibrinolysis might occur intrathecally in neuropsychiatric systemic lupus erythematosus (NPSLE). However, there are no published data on levels of fibrinolytic factors in the cerebrospinal fluid (CSF) of patients with NPSLE. The present study was undertaken to assess CSF levels of fibrinolytic molecules, including urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), D‐dimer, and plasminogen activator inhibitor 1 (PAI‐1), in SLE patients with clinically verified neuropsychiatric involvement and to compare these levels with those in SLE patients without neuropsychiatric involvement and in healthy subjects.

Methods

Levels of uPA, tPA, and PAI‐1 were assessed in CSF from 94 patients with SLE (33 who had NPSLE, 56 who did not have NPSLE, and 5 who were positive for antiphospholipid antibody [not included in the NPSLE or non‐NPSLE group]) and from 53 age‐matched controls. Patients were evaluated clinically, with magnetic resonance imaging of the brain, analyses of neuronal/glial degradation products in CSF, and neuropsychiatric testing.

Results

In the group of patients with NPSLE, intrathecal PAI‐1 levels were significantly elevated compared with levels in SLE patients without overt neuropsychiatric involvement (P < 0.05) and in healthy controls (P < 0.001). In contrast, intrathecal levels of uPA did not differ significantly. Intrathecal levels of PAI‐1 correlated significantly with CSF levels of interleukin‐6 (IL‐6) (r = 0.34, P < 0.001) and IL‐8 (r = 0.33, P < 0.001). Importantly, increased PAI‐1 and D‐dimer levels were observed in SLE patients who had pathologically elevated levels of glial fibrillary acidic protein, neurofilament triplet protein, and tau protein in CSF.

Conclusion

Intrathecal release of PAI‐1 is increased in patients with NPSLE. This results in impaired fibrinolysis, which might contribute to neuronal and astrocytic damage in NPSLE.

     

Clinical features and outcome of neuropsychiatric lupus in Chinese: analysis of 240 hospitalized patients

Neuropsychiatric (NP) events are severe manifestations of systemic lupus erythematosus (SLE) and relate to poor outcome. The aims of this study are to investigate the NP manifestations of SLE and to identify the predictive factors for clinical outcome. There was a retrospective review of 240 hospital patients with primary NP events of SLE (NPSLE) from 1990 to 2004. Neuropsychiatric manifestations, SLE disease activity index (SLEDAI) score, System lupus International Collaborating Clinic/American College of Rheumatology Damage Index (SLICC/ACR-DI) score, magnetic resonance imaging (MRI) findings, treatment and mortality rate were included for analysis. From this group of patients, 15 NP syndromes were identified. The most frequent manifestation was headache, followed by seizure. The mean SLEDAI and SLICC/ACR-DI scores were 19.9 +/- 6.9 and 3.5 +/- 1.6, respectively. Abnormal MRI features were found in 67% (61/91) patients. At least one intrathecal (IT) injection of methotrexate (MTX) plus dexamethasone (DXM) was administered to 109 (45.4%) patients. High dose (1 g) intravenous methylprednisolone pulse therapy (IVMP) was administered to 167 (69.5%) patients. Multifactor analysis revealed that high SLICC/ACR-DI scores and sets of concurrent NP symptoms were independently associated with poor outcome, whereas pulse IVMP and IT injection of MTX plus DXM were protective factors against poor outcome. From our data, NPSLE is heterogeneous and is usually associated with high disease activity and organ damage scores. High SLICC/ACR-DI score and having more than two sets of NP symptoms are the predictors for poor outcome, whereas pulse IVMP and IT injection of MTX plus DXM can improve the prognosis.     

Urinary soluble VCAM-1 in systemic lupus erythematosus: a clinical marker for monitoring disease activity and damage

OBJECTIVE: To determine the urinary levels of soluble vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in patients with systemic lupus erythematosus (SLE) and to assess their relationship with clinical and laboratory features and the degree of activity and damage associated with the disease. METHODS: The study sample included 24 consecutive patients with SLE. 24-hour urine samples were collected for the determination of soluble VCAM-1 and ICAM-1 levels by ELISA. Disease activity was defined by the SLE Disease Active Index (SLEDAI) and disease outcome by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ ACR) damage index. RESULTS: The urinary soluble VCAM-1 level was significantly higher in patients with SLE compared to normal controls (32.35+/-34.27 vs. 4.66+/-3.8 ng/mg creatinine, p = 0.0005) and statistically significantly correlated with disease activity (SLEDAI), a low serum C3 level, decreased creatinine clearance and albuminuria, as well as with disease damage (SLICC/ACR damage index). In contrast, the urinary soluble ICAM-1 level was not significantly higher in the patients' group compared with the controls (4.5+/-5.19 vs. 2.72+/-2.31 ng/mg creatinine, p=0.2), but was statistically significantly correlated with hematuria and albuminuria. CONCLUSION: Our data suggest that the urinary level of soluble VCAM-1 significantly correlates with overall disease activity and damage scores, but not with nephritis in SLE.     

Cerebrospinal fluid and serum prolactin in systemic lupus erythematosus with and without central nervous system involvement

Aim: Recent research has shown that prolactin (PRL) may participate in the pathogenesis of systemic lupus erythematosus (SLE) and hyperprolactinemia may be related to disease activity. The current study investigated both serum and cerebrospinal fluid (CSF) PRL in SLE patients and their possible relationship to central nervous system (CNS) involvement. Methods: Prolactin levels were determined by immunoradiometric assay. Serum PRL levels were detected in 80 patients with SLE and 25 matched healthy controls. Disease activity was scored by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). CSF PRL levels were detected in seven cases of CNS involving SLE, eight cases of non‐CNS involved inactive SLE and eight cases of non‐SLE CNS disorders. Results: Hyperprolactinemia was present in 40% of SLE patients. Serum PRL levels were significantly correlated with SLEDAI scores. There was no significant difference in serum PRL levels between SLE patients with or without CNS involvement, but the mean CSF PRL levels were higher in CNS‐involved SLE patients than in non‐CNS‐involved SLE and non‐SLE patients. There was no significant correlation between serum and CSF PRL levels. Conclusions: Our results suggest that high serum PRL levels correlate with active disease in SLE, but not with CNS involvement. CSF PRL levels in SLE patients correlate with CNS involvement, which indicates that CSF PRL may be involved in the pathogenesis of CNS‐SLE.     

Lymphopenia is associated with neuropsychiatric manifestations and disease activity in paediatric systemic lupus erythematosus patients

OBJECTIVES: To investigate if lymphopenia is associated with clinical manifestations, disease activity and prognosis in systemic lupus erythematosus (SLE). METHODS: The charts of 186 paediatric patients with SLE diagnosed between 1985 and 2006 in a medical centre were retrospectively reviewed. Lymphocyte counts were recorded at the time of SLE diagnosis and SLE flares. Global disease activity was quantified by the SLE Disease Activity Index (SLEDAI). Cumulative organ damage was assessed by the ACR/Systemic Lupus International Collaborating Clinics (SLICC) damage index. RESULTS: Lymphopenia (<1500/mm(3)) and marked lymphopenia (<500/mm(3)) was observed in 62.8 and 12.2% at the time of SLE diagnosis. At the time of SLE diagnosis, lymphopenia was significantly associated with oral ulcers, leucopenia, anti-dsDNA antibodies and C4 decrease. At the time of flares, lymphopenia was significantly associated with anti-dsDNA antibodies, methylprednisolone pulse therapy, disease activity and organ damage. Using multivariate logistic regression, marked lymphopenia was independently associated with neuropsychiatric manifestations [odds ratio (OR) 7.41, 95% confidence interval (CI) 1.99-27.0], and protective from LN (OR 0.13, 95% CI 0.03-0.53). CONCLUSIONS: Lymphopenia at SLE flares is associated with disease activity and organ damage. Marked lymphopenia is independently associated with neuropsychiatric manifestations.     

系统性红斑狼疮患者血浆单核细胞化学吸引蛋白-1检测及其临床意义

目的 分析血浆单核细胞化学吸引蛋白-1(MCP-1)水平与系统性红斑狼疮(SLE)脏器受累及病情严重性的关系,探讨检测血浆MCP-1水平的临床意义.方法 采用酶联免疫吸附试验(ELISA)法检测95例SLE患者血浆MCP-1水平,并与21名健康体检者对照.结果 血浆MCP-1水平在SLE患者为(849±289)pg/ml,显著高于健康对照组的(426±266)pg/ml(P<0.01);在SLE患者,血浆MCP-1水平在有狼疮肾炎(LN)者明显高于无LN患者(P<0.01),并发狼疮脑病的患者也明显高于无中枢神经系统损害的患者(P相似文献   

Raised monocyte chemotactic protein-1 (MCP-1)/CCL2 in cerebrospinal fluid of patients with neuropsychiatric lupus

BACKGROUND: An imbalance in cytokine homoeostasis is thought to have a key role in the neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE), and recently, a role for chemokines has been noted. OBJECTIVE: To compare concentrations of monocyte chemotactic protein-1 (MCP-1)/CCL2 in cerebral spinal fluid (CSF) of patients with SLE, and with and without neuropsychiatric symptoms. METHODS: CSF was obtained from 185 patients with SLE: 96 with NPSLE and 89 patients with SLE without neuropsychiatric symptoms (non-NPSLE patients). MCP-1/CCL2 concentrations were measured with an ELISA. RESULTS: The average concentration of CSF MCP-1/CCL2 in patients with NPSLE was 1959 pg/ml, and in non-NPSLE patients 712 pg/ml. The average MCP-1/CCL2 concentration was significantly higher in the NPSLE group than in the non-NPSLE group (p<0.001). In one representative patient with NPSLE, MCP-1/CCL2 levels in the CSF decreased in parallel with a decline in neuropsychiatric symptoms. CONCLUSIONS: CSF MCP-1/CCL2 levels are higher in patients with NPSLE than in non-NPSLE patients. MCP-1/CCL2 may have an important role in the expression of NPSLE. These results indicate that CSF MCP-1/CCL2 reflects an inflammatory activity in the brain, suggesting that it might be used as a diagnostic tool and a monitor for therapeutic responses in patients with NPSLE.     

Predictors of neuropsychiatric damage in systemic lupus erythematosus: data from the Maryland lupus cohort

OBJECTIVE: To identify factors predictive of significant neuropsychiatric (NP) damage in systemic lupus erythematosus (SLE). METHODS: One hundred and thirty patients with SLE were followed at the University of Maryland Lupus Clinic from 1992 until 2003. NP manifestations were defined according to the revised American College of Rheumatology (ACR) nomenclature and case definitions for NP-SLE syndromes. Disease activity was measured using the SLE Disease Activity Index (SLEDAI), organ damage using the Systemic Lupus International Collaborating Clinics Damage Index SLICC/ACR (SDI); NP damage (NPDI) was measured with the corresponding domain of the SDI. At end of study period, 64 patients exhibited no NP damage (NPDI = 0) and 66 patients developed significant NP damage (defined as NPDI > or =1). The baseline features for these two patient groups were compared, and variables found to be significantly different were examined by multivariable analyses to determine their contribution to NP damage. RESULTS: Significant NP damage is common in SLE; mortality is infrequent and the cause of death is unrelated to NP damage. Independent predictors of significant NP damage were disease activity, Caucasian ethnicity and the presence of antiphospholipid antibodies and anti-Ro/SSA antibody. Certain clinical features at baseline predicted specific NP damage. For example, higher disease activity at baseline was predictive of psychosis and cognitive impairment, anti-dsDNA was predictive of polyneuropathy, and antiphospholipid antibodies were predictive of seizures and cerebrovascular accidents. CONCLUSIONS: In this longitudinal SLE cohort, significant cumulative NP damage occurred. Early aggressive therapy targeted towards NP manifestations may prevent the occurrence of NP damage.     

Study of anti-apolipoprotein A-I antibodies and paraoxonase 1 activity in systemic lupus erythematosus patients; correlation with disease activity and damage indices

IntroductionSystemic lupus erythematosus (SLE) patients have an increased risk of atherosclerosis. Identification of at-risk patients and the pathogenesis of atherosclerosis in SLE remain elusive. Paraoxonase 1 (PON1) and anti-apolipoprotein A-I antibody (anti-Apo A-I) appear to have a potential role in premature atherosclerosis in SLE.Aim of the workTo assess two novel risk factors of atherosclerosis in SLE patients; PON1 activity, and anti-Apo A-I antibody levels, in order to elucidate any possible correlation between both of them, and to demonstrate their relations to disease activity disease activity as well as disease related damage.Patients and methodsForty SLE female patients and 40 apparently healthy volunteers were included in this study. Anti-Apo A-I antibody levels and PON1 activity levels were assessed. Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaboration Clinics (SLICC)/American College of Rheumatology (ACR) damage index were preformed to all patients.ResultsCompared with controls, SLE patients showed significantly lower PON1 activity and significantly higher titers of anti Apo A-I. Anti-Apo A-I antibody titers correlated inversely with PON1 activity. Elevated titers of anti-Apo A-I antibody and reduced PON1 activity were related to increased SLEDAI and (SLICC/ACR) damage index scores.ConclusionThere is a decreased PON1 activity and formation of anti-Apo A-I antibodies in SLE patients and both of them correlated with disease activity as well as disease-related damage. PON1 activity and anti-Apo A-I antibodies might be involved in the pathogenesis of premature atherosclerosis in SLE patients.     

Disease activity, damage and survival in Mexican patients with acute severe systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a clinical syndrome of varying severity. Although the survival and prognosis of SLE have steadily improved, there is a group of patients who present an acute fatal outcome despite aggressive therapy. We designed this study to evaluate the factors associated with mortality in patients with acute severe SLE. During 2004-06, 41 Mexican SLE patients that could not be managed in the out-patient clinic and with acute severe major organ system involvement [nephritis, severe thrombocytopenia (platelet count below 20 000 per microL) acute neuropsychiatric pulmonary, gastrointestinal or cardiac disease and generalized vasculitis] were studied. During the first admission, disease activity (SLE Disease Activity Index (SLEDAI), SLE Activity Measured), damage [SLE International Collaborating Clinics (SLICC)], and therapy were assessed. Survival using Kaplan-Meier curves, odd ratios with 95% confidence interval and logistic regression analysis were used to determine risk factors for mortality. Ninety percent were female with a mean age of 29 +/- 19 years and mean disease duration of 21 +/- 9 months. The principal causes of first admission were renal (27%), SNC (22%) and cardiopulmonary (15%). After a mean follow-up of 9.7 +/- 6 months, 16 (39%) patients died. Deceased patients had significantly higher SLEDAI (P = 0.004), and SLICC (P = 0.03) scores. The manifestations associated with mortality were renal disease activity (odds ratio, OR 4.6, confidence interval, CI 95% 1.0-20.6), infections (OR 3.2 CI 95% 2.0-5.3) and thrombocytopenia (OR 4.0, CI 95% 1.0-15.9). The survival at 9.7 months was 72, 62 and 50% in patients with an SLEDAI score of 3-10, 11-20 and > or =21, respectively. The SLEDAI score, the presence of damage and infection were associated with death in patients with acute severe SLE.