Mortality in systemic sclerosis.

Systemic sclerosis is a rare and potentially devastating connective tissue disease. It is highly heterogeneous in terms of clinical presentation, extent and severity of organ involvement, immunologic abnormalities, and clinical course. Although clinical outcomes appear to have improved in recent years, the disease continues to cause substantial excess mortality. In this review, we have systematically collected the published studies addressing the mortality burden in patients with scleroderma in comparison with the general population, as well as studies exploring the most important potential predictors of mortality. Results of these studies are presented and discussed, with emphasis on methodological limitations. Suggestions are made for the design, conduct, and reporting of further research on these themes.

Suicide attempts in patients with systemic lupus erythematosus.

BACKGROUND: Suicide and suicide attempts, although well recognised in patients with systemic lupus erythematosus (SLE), have been commented on relatively little. OBJECTIVE: To obtain a better understanding of the reasons for suicidal behaviour in patients with SLE. METHODS: The records of 300 patients with SLE were reviewed to identify completed or attempted suicides. RESULTS: Five patients made seven attempts at suicide over a 20 year follow up period; one of them was fatal. All of those attempting suicide had a history of neuropsychiatric SLE (NPSLE) presenting with depression and they made the attempts soon after the onset of NPSLE (median time 12.5 months). Two patients had appreciable disease activity at the time of the suicide attempt. Lymphopenia was present in five suicide attempts. Anti-SSA/Ro antibodies were detected in three patients, none of whom had anti-SSB/La. All patients apart from one responded to treatment for depression; the remaining female patient made two subsequent suicide attempts, with a fatal outcome despite intensive treatment. CONCLUSION: Greater awareness of the risk of suicide in patients with psychiatric manifestations of SLE may help to reduce the incidence of this potentially fatal phenomenon.

Bias in uncontrolled therapeutic trials in rheumatology due to selection of populations with extreme characteristics.

OBJECTIVE: To assess the prevalence of biases from selection of patients with extreme characteristics in recent uncontrolled therapeutic studies in rheumatology. METHODS: We hand searched 4 major rheumatology journals for uncontrolled trials published in 1997 or 1998 that measured therapeutic efficacy by comparing one or more variables at followup vs at baseline. We evaluated the susceptibility to bias from random measurement error and natural variability for variables used for defining eligibility that overlap with those used for defining outcomes. RESULTS: Twenty-five studies were analyzed. In 22 studies, the eligibility criteria were related to the outcome criteria and defined a patient population with extreme characteristics. Only 3 studies clearly reported that they had performed a baseline measurement separate from the screening (eligibility) measurement. The remaining 19 reports (76%) might be susceptible to bias: in 7, identical variables were used for eligibility criteria and outcomes; 3 used outcome variables that were also used for characterizing eligibility along with other criteria; 2 used specific eligibility variables that were part of composite outcome scores; and 7 selected patients on the basis of vague descriptors of disease severity, while disease severity was also the outcome. CONCLUSION: Several recent uncontrolled trials of therapeutic interventions in rheumatology are subject to biases stemming from the selection of patients with extreme characteristics. Baseline evaluations separate from the screening measurements should be performed and eligibility criteria and outcomes should be carefully defined.

Spontaneous rupture of the spleen: an unusual complication of systemic lupus erythematosus.

Although splenic abnormalities are widely recognised in patients with lupus, spontaneous rupture of the spleen is rare. We describe a patient whose spleen ruptured spontaneously 19 years after the onset of her disease, and compare this case with four others that have been described in the previous literature. Possible contributing factors to this rupture are discussed.

Predictors of clinical outcome and radiologic progression in patients with neuropsychiatric manifestations of systemic lupus erythematosus.

PURPOSE: We sought to identify the predictors of clinical outcome and of the evolution of cerebral abnormalities in patients with neuropsychiatric systemic lupus erythematosus (SLE). SUBJECTS AND METHODS: Thirty-two patients with SLE (including 14 with the antiphospholipid syndrome) who had been hospitalized with primary neuropsychiatric disease were observed prospectively for at least 2 years. Laboratory and clinical characteristics and data from magnetic resonance imaging (MRI) studies obtained during the hospitalization and 2 years later were evaluated. We ascertained nonreversible or new MRI changes and clinical outcomes, including neuropsychiatric events, during follow-up. RESULTS: Cranial MRI scans on admission were abnormal in 26 (81%) of the 32 patients. Patients with the antiphospholipid syndrome were more likely to have focal cerebral white matter lesions (odds ratio [OR] = 12, 95% confidence interval [CI]: 2.0 to 72). After 2 years, neuropsychiatric deficits substantially improved in 22 (69%) of the patients, stabilized in 6 (19%), and deteriorated in 4 (12%). The number of prior neuropsychiatric events was associated with persistent MRI lesions (OR = 4.8 per each event, 95% CI: 1.1 to 21) and unfavorable clinical outcome (OR = 4.3 per each event, 95% CI: 1.4 to 13) at 2 years. The antiphospholipid syndrome also predicted an unfavorable clinical outcome at 2 years (OR = 11, 95% CI: 1.7 to 65). CONCLUSIONS: Among patients with SLE who have neuropsychiatric disease, prior neuropsychiatric events and the antiphospholipid syndrome increase the risk of adverse outcomes.

Risk factors for central nervous system involvement in systemic lupus erythematosus.

We investigated risk factors for central nervous system (CNS) involvement in systemic lupus erythematosus (SLE), in 32 such patients individually matched 1 : 3 to 96 control SLE patients without CNS events. Univariate analysis showed that CNS involvement was significantly associated with the antiphospholipid syndrome (APS) as well as its features: arterial thrombosis, recurrent fetal loss, livedo reticularis and IgG anticardiolipin (aCL) antibodies in high titres. Other potential associations included cutaneous vasculitic lesions, thrombocytopenia, positive ANA, anti-SS-B/La and low serum levels of C(3) and C(4) complement components, while articular manifestations and discoid rash were significantly less common in patients with neuropsychiatric (NP) disease. In multivariate modeling, CNS involvement was strongly associated with cutaneous vasculitic lesions OR 33, 95% CI 1.5-720) and arterial thromboses (OR 13, 95%CI 0.82-220), and negatively related to the presence of articular manifestations (OR 0.015, 95%CI 0.00-0.17) and discoid rash (OR 0.004, 95%CI 0.00-0.35). Associations with APS-related arterial thromboses and vasculitis point to the importance of arterial vascular pathophysiology in the pathogenesis of NP disease in SLE. Patients with articular manifestations and discoid rash are at very low risk of NP events. Patients with an adverse SLE disease profile may require closer observation and may be the target group for studying pre-emptive interventions.

Systemic lupus erythematosus in Greece. Clinical features, evolution and outcome: a descriptive analysis of 292 patients.

The purpose of this study was the descriptive analysis of patients with systemic lupus erythematosus (SLE) with a particular focus on initial clinical features, evolution and outcome of disease, prevalence of clinical and serological manifestations and identification of clinicoserological associations indicative of renal and CNS involvement. The methodology applied was the following: retrospective analysis of the clinical charts of 292 unselected patients (246 female (84.2%) and 46 male (15.7%)) with SLE examined between 1982 and 1992. Multivariate analysis and hierarchical log linear models were used to examine for clinicoserological associations. Descriptive analysis was based on the prevalence of main clinicoserological features and disease outcome. The outcome was examined on the basis of the number of flares, the presence of chronic renal failure, the presence of central nervous system (CNS) involvement with subsequent disability and deaths. Flares were considered the severe alterations in disease status, requiring additional therapy to be controlled. The disease begins most frequently in the second and third decade of life with cutaneous and joint manifestations, while renal and CNS involvement developed later. The prevalence of serious renal, pulmonary and CNS involvement as well as the prevalence of RF, anti-Sm and anti-nRNP antibodies remain low. Multivariate analysis revealed the associations of renal involvement with leukopenia and serositis, of anti-Sm with leukopenia, of secondary Sjogren's syndrome with RF and of thromboembolic events with anticardiolipin antibodies. Patients with childhood onset SLE have a higher tendency for developing renal involvement than adult onset SLE patients. In addition, anti-Ro(SSA) antibodies were associated with anti-La(SSB) and RF, while anti-Sm antibodies were associated with anti-nRNP and RF. Flares occurred with a frequency of 0.07 per patient per year. Only 63.6% of flares were accompanied by positive anti-dsDNA reactivities. Reported deaths were 0.0047 per patient per year. Hierarchical log linear models indicated that the main variables of the disease were sufficient to describe our disease model and that the order of the interaction between the variables was insignificant. We conclude that the prevalence of various clinical features associated with SLE is similar, although the prevalence of CNS and pulmonary involvement as well as anti-Sm and anti-nRNP antibodies are less prominent in Greek SLE patients than that reported in the literature. The various clinicoserological associations detected do not appear to be of major significance as they are not powerful enough to subgroup the disease.