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At least 19 recordsLinked to original sources
PubMed2007

Neuropsychiatric events at the time of diagnosis of systemic lupus erythematosus: an international inception cohort study.

OBJECTIVE: To describe the prevalence, characteristics, attribution, and clinical significance of neuropsychiatric (NP) events in an international inception cohort of systemic lupus erythematosus (SLE) patients. METHODS: The study was conducted by the Systemic Lupus International Collaborating Clinics (SLICC). Patients were enrolled within 15 months of fulfilling the American College of Rheumatology (ACR) SLE classification criteria. All NP events within a predefined enrollment window were identified using the ACR case definitions of 19 NP syndromes. Decision rules were derived to determine the proportion of NP disease attributable to SLE. Clinical significance was determined using the Short Form 36 (SF-36) Health Survey and the SLICC/ACR Damage Index (SDI). RESULTS: A total of 572 patients (88% female) were recruited, with a mean +/- SD age of 35 +/- 14 years. The mean +/- SD disease duration was 5.2 +/- 4.2 months. Within the enrollment window, 158 of 572 patients (28%) had at least 1 NP event. In total, there were 242 NP events that encompassed 15 of 19 NP syndromes. The proportion of NP events attributed to SLE varied from 19% to 38% using alternate attribution models and occurred in 6.1-11.7% of patients. Those with NP events, regardless of attribution, had lower scores on the SF-36 and higher SDI scores compared with patients with no NP events. CONCLUSION: Twenty-eight percent of SLE patients experienced at least 1 NP event around the time of diagnosis of SLE, of which only a minority were attributed to SLE. Regardless of attribution, the occurrence of NP events was associated with reduced quality of life and increased organ damage.

Adult↗
PubMed2006

Mortality in systemic lupus erythematosus.

OBJECTIVE: To examine mortality rates in the largest systemic lupus erythematosus (SLE) cohort ever assembled. METHODS: Our sample was a multisite international SLE cohort (23 centers, 9,547 patients). Deaths were ascertained by vital statistics registry linkage. Standardized mortality ratio (SMR; ratio of deaths observed to deaths expected) estimates were calculated for all deaths and by cause. The effects of sex, age, SLE duration, race, and calendar-year periods were determined. RESULTS: The overall SMR was 2.4 (95% confidence interval 2.3-2.5). Particularly high mortality was seen for circulatory disease, infections, renal disease, non-Hodgkin's lymphoma, and lung cancer. The highest SMR estimates were seen in patient groups characterized by female sex, younger age, SLE duration <1 year, or black/African American race. There was a dramatic decrease in total SMR estimates across calendar-year periods, which was demonstrable for specific causes including death due to infections and death due to renal disorders. However, the SMR due to circulatory diseases tended to increase slightly from the 1970s to the year 2001. CONCLUSION: Our data from a very large multicenter international cohort emphasize what has been demonstrated previously in smaller samples. These results highlight the increased mortality rate in SLE patients compared with the general population, and they suggest particular risk associated with female sex, younger age, shorter SLE duration, and black/African American race. The risk for certain types of deaths, primarily related to lupus activity (such as renal disease), has decreased over time, while the risk for deaths due to circulatory disease does not appear to have diminished.

Adolescent↗
PubMed2006

Increased aortic pulse wave velocity in middle aged women with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a connective tissue disease where inflammatory activity affects several organ systems. An increased risk of cardiovascular disease has been identified in these patients, even after correction for traditional risk factors. The aim of the present study was to evaluate arterial stiffness and central hemodynamics in women with SLE in comparison to controls. Arterial tonometry was used to measure aortic (carotid-femoral) and arm (carotid-radial) pulse wave velocity (PWV), reflected pressure waves, and aortic augmentation index (AIx) in 27 women with SLE (52 to 68 years) and 27 controls. Aortic PWV was higher in women with SLE than controls, 9.8 m/s versus 8.2 m/s (P < 0.01), after correction for mean arterial pressure and body mass index, 9.5 m/s versus 8.5 m/s (P < 0.05). Other parameters were similar, arm PWV, 8.4 versus 8.5 m/s, AIx 34 versus 33% and calculated central aortic pulse pressure 48 versus 43 mmHg, in SLE and controls, respectively (NS). Aortic PWV was positively associated to C-reactive protein (CRP) and complement factor 3 (C3). Women with SLE have increased stiffness of their elastic central arteries. This may be one factor contributing to the increased cardiovascular risk seen in this cohort.

Aorta↗
PubMed2005

An international cohort study of cancer in systemic lupus erythematosus.

OBJECTIVE: There is increasing evidence in support of an association between systemic lupus erythematosus (SLE) and malignancy, but in earlier studies the association could not be quantified precisely. The present study was undertaken to ascertain the incidence of cancer in SLE patients, compared with that in the general population. METHODS: We assembled a multisite (23 centers) international cohort of patients diagnosed as having SLE. Patients at each center were linked to regional tumor registries to determine cancer occurrence. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers. Cancers expected were determined by multiplying person-years in the cohort by the geographically matched age, sex, and calendar year-specific cancer rates, and summing over all person-years. RESULTS: The 9,547 patients from 23 centers were observed for a total of 76,948 patient-years, with an average followup of 8 years. Within the observation interval, 431 cancers occurred. The data confirmed an increased risk of cancer among patients with SLE. For all cancers combined, the SIR estimate was 1.15 (95% confidence interval [95% CI] 1.05-1.27), for all hematologic malignancies, it was 2.75 (95% CI 2.13-3.49), and for non-Hodgkin's lymphoma, it was 3.64 (95% CI 2.63-4.93). The data also suggested an increased risk of lung cancer (SIR 1.37; 95% CI 1.05-1.76), and hepatobiliary cancer (SIR 2.60; 95% CI 1.25, 4.78). CONCLUSION: These results support the notion of an association between SLE and cancer and more precisely define the risk of non-Hodgkin's lymphoma in SLE. It is not yet known whether this association is mediated by genetic factors or exogenous exposures.

Adult↗
PubMed2005

Non-Hodgkin's lymphoma in systemic lupus erythematosus.

BACKGROUND: Recent evidence supports an association between systemic lupus erythematosus (SLE) and non-Hodgkin's lymphoma (NHL). OBJECTIVES: To describe demographic factors, subtypes, and survival of patients with SLE who develop NHL. METHODS: A multi-site cohort of 9547 subjects with definite SLE was assembled. Subjects at each centre were linked to regional tumour registries to determine cancer cases occurring after SLE diagnosis. For the NHL cases ascertained, descriptive statistics were calculated, and NHL subtype frequency and median survival time of patients determined. RESULTS: 42 cases of NHL occurred in the patients with SLE during the 76,948 patient-years of observation. The median age of patients at NHL diagnosis was 57 years. Thirty six (86%) of the 42 patients developing NHL were women, reflecting the female predominance of the cohort. In the patients, aggressive histological subtypes appeared to predominate, with the most commonly identified NHL subtype being diffuse large B cell (11 out of 21 cases for which histological subtype was available). Twenty two of the patients had died a median of 1.2 years after lymphoma diagnosis. CONCLUSIONS: These data suggest aggressive disease in patients with SLE who develop NHL. Continuing work should provide further insight into the patterns of presentation, prognosis, and aetiology of NHL in SLE.

Adult↗
PubMed2004

EULAR randomised controlled trial of pulse cyclophosphamide and methylprednisolone versus continuous cyclophosphamide and prednisolone followed by azathioprine and prednisolone in lupus nephritis.

OBJECTIVE: To compare the efficacy and side effects of intermittent pulse cyclophosphamide plus methylprednisolone with continuous oral cyclophosphamide plus prednisolone, followed by azathioprine, in patients with proliferative glomerulonephritis caused by systemic lupus erythematosus (SLE). METHODS: A multicentre randomised controlled trial was conducted between June 1992 and May 1996 involving eight European centres. All patients satisfied the American College of Rheumatology criteria for SLE and had biopsy proven proliferative lupus nephritis. All received corticosteroids in addition to cytotoxic drugs, as defined in the protocol, for two years. The trial was terminated after four years as recruitment was disappointing. RESULTS: 32 SLE patients with lupus nephritis were recruited: 16 were randomised to intermittent pulse cyclophosphamide and 16 to continuous cyclophosphamide plus azathioprine. Mean duration of follow up was 3.7 years in the continuous group (range 0 to 5.6) and 3.3 years in the pulse group (range 0.25 to 6). Three patients were excluded from the pulse therapy group as they were later found to have pure mesangial glomerulonephritis. Two patients in the continuous therapy group developed end stage renal failure requiring dialysis, but none in the intermittent pulse therapy (p = 0.488; NS). There were similar numbers of side effects and withdrawals from treatment in both groups. There were three deaths: two in the intermittent pulse therapy group and one in the continuous therapy group. CONCLUSIONS: There was no statistically significant difference in efficacy and side effects between the two regimens. Infectious complications occurred commonly, so careful monitoring is required during treatment.

Administration, Oral↗
PubMed2004

ACR classification criteria for systemic lupus erythematosus: complement components.

Complement is involved in the pathogenesis of systemic lupus erythematosus (SLE) and has also a seemingly paradoxical protective role in the development of the disease. Low levels of components within the classical pathway of complement especially C1q, C4 and C3 have a high specificity for SLE diagnosis and should be considered as promising for inclusion in classification criteria of SLE.

Biomarkers↗
PubMed2004

Abnormal mechanical properties of larger arteries in postmenopausal women with systemic lupus erythematosus.

There is limited knowledge of potential defects in arterial wall properties in female systemic lupus erythematosus (SLE) patients without manifest cardiovascular disease (CVD) and significant atherosclerotic lesions. The aim of the present study was to investigate the mechanical properties of larger vessels in these patients and to compare them with healthy controls. B-mode ultrasound was used to assess vessel wall structure and to exclude presence of plaque. The ankle/brachial pressure index was measured to exclude occlusive arterial disease. An ultrasound echo-tracking system was used to determine stiffness of the abdominal aorta, common carotid artery (CCA) and popliteal artery (PA) in 39 female patients with SLE and 55 female, healthy controls. SLE had an independent effect on stiffening of the CCA (P = 0.01) and PA (P = 0.005). In addition, larger vessel diameters were observed in the CCA (P = 0.002) after adjustments for the effects of mean arterial pressure and age. Thus, this investigation demonstrated an increased arterial stiffness and signs of premature vascular ageing in the SLE patients without manifest cardiovascular disease and without significant atherosclerotic lesions. The results of this study indicate that other mechanisms besides atherosclerosis might be involved in the pathogenesis of arterial stiffening in SLE patients.

Age Factors↗
PubMed2004

Outcome of incomplete systemic lupus erythematosus after 10 years.

The objective was to identify cases of incomplete systemic lupus erythematosus (SLE) within a defined population in southern Sweden, risk factors for development of complete SLE (> or = 4 classification criteria) and study outcome of the patients. During prospective retrieval of SLE cases within a defined population in southern Sweden, 28 patients (26 women, two men) with incomplete SLE (< 4 ACR criteria) were identified between 1981 and 1992. All patient records were reviewed and clinical and laboratory data were extracted from standardized formats. Organ damage was defined according to the SLICC/ACR damage index. During follow-ups, 16 of 28 patients developed complete SLE (median 13 years; range 10-20 years). The time to develop complete SLE varied between one and ten years with a median time of 5.3 years. Three patients were anti-DNA positive at inclusion; only one of them developed complete SLE. False positive Wasserman reaction and anti-cardiolipin antibodies (aCl) were only found in patients who developed complete SLE (P < 0.04; Fisher exact test). Six patients had malar rash from the start and they all had complete SLE at follow-up (P < 0.04; Fisher exact test). Of eight patients with arthritis, three developed complete SLE. Thrombocytopenia was only found in two patients, both developing complete disease. At follow-up, patients that developed complete SLE had high SLICC damage scores (mean 1.5) compared with patients that remained as incomplete SLE (mean 0.16). In conclusion, in this follow-up study of patients with incomplete SLE 57% developed complete disease after a median time of 5.3 years. Malar rash and aCl were predictors of complete SLE. Individuals that developed complete SLE were more prone to organ damage.

Adolescent↗
PubMed2003

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.

Adolescent↗
PubMed2003

The ACR nomenclature for CNS lupus revisited.

Neuropsychiatric systemic lupus erythematosus (NPSLE) involves a wide range of peripheral and central nervous system manifestations. These manifestations are complex and their pathophysiology is poorly understood. NPSLE can precede the onset of lupus or occur at any time during its course. The American College of Rheumatology (ACR) developed a standardized nomenclature system providing case definitions for the neuropsychiatric syndromes of systemic lupus erythematosus (SLE) to facilitate and enhance patient classification and reporting requirements in clinical research. Estimates of NPSLE prevalence have ranged widely and most are based on research conducted before the introduction of ACR case definitions. This paper reviews the early experience with the ACR nomenclature use and possible future directions for its improvement. The identification and categorization of the major neuropsychiatric syndromes in SLE using ACR case definitions seems to be adequate, however the mildest and most subjective of the syndromes are the most problematic. Even if the definitions in their present form might have drawbacks the only way forward is further use of ACR nomenclature, pooling data from different populations, and collection of experience as a basis for improvement. The acquisition of normative data for ethnic, age and sex stratification would extend their usefulness.

Female↗
PubMed2002

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.

Activities of Daily Living↗
PubMed2002

Risk factors for developing systemic lupus erythematosus: a case-control study in southern Sweden.

OBJECTIVE: To explore the risk factors that have been suggested to be associated with the development of SLE. METHODS: A case-control study was performed and a questionnaire was developed to obtain the data. Consecutive female incident cases diagnosed between 1981 and 1999 in a defined geographical area in southern Sweden were included. Controls, matched for calendar year of birth, were selected randomly from the same area. In total, 85 cases and 205 controls agreed to participate. The questionnaire included questions about formal education, body weight and height, medical history, family history of autoimmune diseases, exposure to ultraviolet radiation, animals, hair-colouring dyes, alfalfa (lucerne) sprouts, smoking and alcohol habits, history of physical traumata, blood transfusion, silicone breast implants, exogenous oestrogens, other medication, and significant negative life events. RESULTS: Using a multivariate model, a history of hypertension [odds ratio (OR)=3.7, 95% confidence interval (CI) 1.4-9.8], drug allergy (OR=3.6, 95% CI 1.4-9.5), a type I/II sun-reactive skin type (OR=2.3, 95% CI 1.1-4.8) and a family history of SLE (OR=6.8, 95% CI 1.4-32) were all significantly associated with an increased risk of developing SLE, whereas consumption of alcohol was inversely associated with the risk of SLE (use of alcohol very seldom, OR=1.0; 1-150 g/month, OR=0.4, 95% CI 0.2-1.0; >150 g/month, OR=0.2, 95% CI 0.1-0.5). A suggested association with increased SLE risk was seen for smoking (OR=1.8, 95% CI 0.9-3.6) and blood transfusions (OR=2.3, 95% CI 0.9-5.8). Neither exposure to exogenous oestrogen nor exposure to hair-colouring dyes was associated with SLE. CONCLUSIONS: Risk factors of both exogenous and endogenous origin were identified in this population-based series of SLE patients.

Adolescent↗
PubMed2001

Malignancies during follow-up in an epidemiologically defined systemic lupus erythematosus inception cohort in southern Sweden.

The objective of this study was to identify all malignancies in an inception cohort of SLE patients in southern Sweden and compare with the observed frequencies and spectrum of malignancies in the general population. All adult incidence cases of SLE in a defined population during the period 1981-1996 were retrieved from a prospective database and the cases were followed to endpoint or through 1998. The SLE cohort registry was aggregated with the National Cancer Registry to identify all malignancies by date, type and outcome. Standardized morbidity rates (SMR) were calculated based on the sex- and age-matched general population of the region. Sixteen malignancies occurred in 13 patients out of a total of 116 SLE patients observed for 1086 patient-years. The SMR for all cancers detected was 2.24 (confidence interval 0.6-5.7) for males and 1.02 (confidence interval 0.4-2.1) for females and thus indicative of no general increase in malignancies. However, the SMR for non-Hodgkin lymphoma was 11.63 (confidence interval 1.4-42.0), for pulmonary cancer 5.55 (confidence interval 0.7-20.1) and prostatic cancer 6.41 (confidence interval 1.3-18.7) all significantly increased. The increase in prostatic carcinoma disappeared when only cases occurring after a latency period of 3y after SLE diagnosis were included. In this comprehensive inception cohort of SLE no increase in relative risk of malignancy overall was found, but the frequencies of non-Hodgkin lymphoma and pulmonary cancer were increased, possibly also the frequency of prostatic carcinoma.

Aged↗
PubMed2000

The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index for Systemic Lupus Erythematosus International Comparison.

OBJECTIVE: To compare patients with systemic lupus erythematosus (SLE) from different centers with respect to demographics and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) scores, and to assess whether the SLICC/ACR DI changed over time, and whether initial DI scores were related to outcome. METHODS: Members of SLICC completed DI scores and patient demographics on patients followed in their centers. Information was provided at 2, 5-10, and > 10 years of followup. Data were entered on computer and analyzed on SPSS/PC+ and SAS using descriptive statistics and analysis of variance. RESULTS: Information for 1297 patients within 2 years of first clinic visit was submitted from 8 centers. There were 1187 women and 110 men with a mean age at diagnosis of SLE of 32 years. Seven hundred sixty-two were Caucasian, 423 were black, and the remainder were of other races. There were more blacks in the American centers than in Canadian or European centers. Five centers provided information for the 3 time periods. The DI increased over time. Ninety-nine patients had died. Higher SLICC/ACR DI scores were documented in patients who went on to die. CONCLUSION: The SLICC/ACR DI is a valid measure for damage in SLE.

American Medical Association↗
PubMed2000

Novel roles of complement in systemic lupus erythematosus--hypothesis for a pathogenetic vicious circle.

We propose that impaired complement function enhances a pathogenetic vicious circle in SLE. In this process, induction and clearance of apoptotic cells is central. Apoptosis could be triggered by various etiological factors, such as infection, UV light, and drug reactions. Clearance of apoptotic material is reduced when complement function is impaired. Apoptosis leads to increased exposure of nuclear antigens to the immune system, to which estrogenic hormones could contribute. This could in turn lead to activation of autoreactive B cells, autoantibody production, and immune complex formation, all of which is accelerated by hypocomplementemia. Immune complexes may, at least partly via complement dependent mechanisms, accelerate apoptosis.

Apoptosis↗
PubMed2000

Incidence studies of systemic lupus erythematosus in Southern Sweden: increasing age, decreasing frequency of renal manifestations and good prognosis.

OBJECTIVE: To identify all new cases of systemic lupus erythematosus (SLE) within a defined area in Southern Sweden with validated methods of retrieval, and to compare 2 cohorts assembled during 1981-86 and 1987-91. METHODS: The catchment area, the health care district of Lund-Orup, had during 1981-91 a mean adult population (> 15 years of age) of 172,300 individuals. During 1987-91 we identified 379 individuals with potential SLE diagnosis from diagnosis registers and from central laboratory databases. Out of these, 121 had a previously known SLE diagnosis. All patient records were reviewed and patients with possible SLE not already known at the SLE unit were invited and examined. Organ damage was recorded as the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index. RESULTS: Forty-one new SLE cases were diagnosed during 1987-91, giving a median annual incidence of 4.8/100,000 inhabitants, with a median age at diagnosis of 47 years. The incidence is similar to that found 1981-86 (4.5/100,000/year) in the same population using the same methods for retrieval. Age and sex-specific incidence 1981-91 was notably highest at the age of 65-74 (14.1/100,000/year) in women and age 65-74 (3.2/100,000/year) in men. The point prevalence on December 31, 1986, was a 42/100,000 and on December 31, 1991, 68/100,000. The 5 year survival was 93% and 10 year survival 83%. While overall survival was not decreased, 10 year survival was slightly reduced compared with an age and sex matched healthy population (p = 0.03). In the 1987-91 cohort the sensitivity of the American Rheumatism Association criteria was 92.7% and the specificity was 94%. The frequency of renal manifestations was decreased in the latter cohort. The damage rate was highest during the first year and then constant during a 5 year followup, and was similar in the 2 cohorts. Damage that related to atherosclerosis was common and cardiovascular disease was the most common cause of death. CONCLUSION: The incidence of SLE in Sweden was notably constant during the 11 years 1981-91. Mortality was low and only late mortality (> 10 years disease duration) exceeded that in an age and sex matched control population. Atherosclerosis was the main cause of damage and mortality. Specificity and sensitivity of the ACR classification criteria are high in this epidemiologically recruited cohort.

Adolescent↗