Neuropsychiatric Syndromes in Systemic Lupus Erythematosus: A Meta-Analysis
TL;DR: A meta-analysis of relevant publications found that NP syndromes were estimated to exist in more than half of SLE patients, and the most prevalent manifestations were headache, mood disorders, and cognitive dysfunction.
About: This article is published in Seminars in Arthritis and Rheumatism.The article was published on 2011-08-01. It has received 286 citations till now. The article focuses on the topics: Lupus vasculitis.
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16 Jun 2016
TL;DR: The 10-year mortality has improved and toxic adverse effects of older medications such as cyclophosphamide and glucocorticoids have been partially offset by newer drugs such as mycophenolate mofetil and glucose-sparing regimes.
Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect many organs, including the skin, joints, the central nervous system and the kidneys. Women of childbearing age and certain racial groups are typically predisposed to developing the condition. Rare, inherited, single-gene complement deficiencies are strongly associated with SLE, but the disease is inherited in a polygenic manner in most patients. Genetic interactions with environmental factors, particularly UV light exposure, Epstein-Barr virus infection and hormonal factors, might initiate the disease, resulting in immune dysregulation at the level of cytokines, T cells, B cells and macrophages. Diagnosis is primarily clinical and remains challenging because of the heterogeneity of SLE. Classification criteria have aided clinical trials, but, despite this, only one drug (that is, belimumab) has been approved for use in SLE in the past 60 years. The 10-year mortality has improved and toxic adverse effects of older medications such as cyclophosphamide and glucocorticoids have been partially offset by newer drugs such as mycophenolate mofetil and glucocorticoid-sparing regimes. However, further improvements have been hampered by the adverse effects of renal and neuropsychiatric involvement and late diagnosis. Adding to this burden is the increased risk of premature cardiovascular disease in SLE together with the risk of infection made worse by immunosuppressive therapy. Challenges remain with treatment-resistant disease and symptoms such as fatigue. Newer therapies may bring hope of better outcomes, and the refinement to stem cell and genetic techniques might offer a cure in the future.
737 citations
TL;DR: The manifestation and pathogenesis of NPSLE is reviewed, focusing on the features that might aid identification of potential biomarkers, which are needed to improve prediction of disease outcomes and guide treatment.
Abstract: Systemic lupus erythematosus (SLE) is a complex clinical syndrome, elements of which remain poorly understood. Although recognized over 140 years ago when Kaposi recorded the systemic nature and manifestations of the disease, CNS involvement represents one of the least understood aspects of SLE. This knowledge gap remains despite the fact that up to 75% of adults and children with SLE will, at some point over the course of the disease and to different extents, experience the various disabling effects of neuropsychiatric SLE (NPSLE). Indeed, after decades of research, our understanding of the underlying pathophysiology of NPSLE, in particular, remains limited. Numerous factors contribute to the immune dysfunction that occurs in SLE, including genetic, environmental and hormonal influences, and the contributory or predisposing components that lead to neurological tropism of disease in some patients have not been clearly demonstrated. Features of NPSLE pathogenesis that might be directly linked to clinical manifestations have been identified; however, the complexity and variety of NPSLE symptoms and the clinical overlap with other psychiatric disorders continue to make accurate diagnosis difficult and time-consuming. Thus, efforts to define biomarkers of NPSLE are needed to improve prediction of disease outcomes and guide treatment. In this article, we review the manifestation and pathogenesis of NPSLE, focusing on the features that might aid identification of potential biomarkers.
202 citations
TL;DR: The prevalence of depression and anxiety was high in adult SLE patients and indicated that rheumatologists should screen for depression and Anxiety in their patients, and referred them to mental health providers in order to identify effective strategies for preventing and treating depression and anxious patients.
Abstract: Systemic lupus erythematosus (SLE) patients are at high risk for depression and anxiety. However, the estimated prevalence of these disorders varies substantially between studies. This systematic review aimed to establish pooled prevalence levels of depression and anxiety among adult SLE patients. We systematically reviewed databases including PubMed, Embase, PsycINFO, and the Cochrane database library from their inception to August 2016. Studies presenting data on depression and/or anxiety in adult SLE patients and having a sample size of at least 60 patients were included. A random-effect meta-analysis was conducted on all eligible data. A total of 59 identified studies matched the inclusion criteria, reporting on a total of 10828 adult SLE patients. Thirty five and thirteen methods of defining depression and anxiety were reported, respectively. Meta-analyses revealed that the prevalence of major depression and anxiety were 24% (95% CI, 16%-31%, I2 = 95.2%) and 37% (95% CI, 12%–63%, I2 = 98.3%) according to clinical interviews. Prevalence estimates of depression were 30% (95% CI, 22%–38%, I2 = 91.6%) for the Hospital Anxiety and Depression Scale with thresholds of 8 and 39% (95% CI, 29%–49%, I2 = 88.2%) for the 21-Item Beck Depression Inventory with thresholds of 14, respectively. The main influence on depression prevalence was the publication years of the studies. In addition, the corresponding pooled prevalence was 40% (95% CI, 30%–49%, I2 = 93.0%) for anxiety according to the Hospital Anxiety and Depression Scale with a cutoff of 8 or more. The prevalence of depression and anxiety was high in adult SLE patients. It indicated that rheumatologists should screen for depression and anxiety in their patients, and referred them to mental health providers in order to identify effective strategies for preventing and treating depression and anxiety among adult SLE patients. Current Meta-analysis PROSPERO Registration Number: CRD 42016044125
. Registered 4 August 2016.
179 citations
Additional excerpts
...Previous meta-analyses have assessed the prevalence of the 19 NP syndromes defined by the American College of Rheumatology (ACR) in 1999 among SLE patients [30]....
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TL;DR: Current understanding of its pathogenesis is described, along with novel therapies and diagnostic tools that could eventually improve the management of NPSLE, which remains highly challenging to diagnose and treat.
Abstract: Patients with systemic lupus erythematosus (SLE) frequently show symptoms of central nervous system (CNS) involvement, termed neuropsychiatric SLE (NPSLE). The CNS manifestations of SLE are diverse and have a broad spectrum of severity and prognostic implications. Patients with NPSLE typically present with nonspecific symptoms, such as headache and cognitive impairment, but might also experience devastating features, such as memory loss, seizures and stroke. Some features of NPSLE, in particular those related to coagulopathy, have been characterized and an evidence-based treatment algorithm is available. The cognitive and affective manifestations of NPSLE, however, remain poorly understood. Various immune effectors have been evaluated as contributors to its pathogenesis, including brain-reactive autoantibodies, cytokines and cell-mediated inflammation. Additional brain-intrinsic elements (such as resident microglia, the blood-brain barrier and other neurovascular interfaces) are important facilitators of NPSLE. As yet, however, no unifying model has been found to underlie the pathogenesis of NPSLE, suggesting that this disease has multiple contributors and perhaps several distinct aetiologies. This heterogeneity presents a challenge for clinicians who have traditionally relied on empirical judgement in choosing treatment modalities for patients with NPSLE. Improved understanding of this manifestation of SLE might yield further options for managing this disease.
178 citations
TL;DR: The old and the new regarding epidemiology, pathophysiology, diagnosis, and management of neuropsychiatric systemic lupus erythematosus are described.
Abstract: Neuropsychiatric symptoms affect nearly half of the patients with systemic lupus erythematosus; however, the effect on disease severity, quality of life, and prognosis is tremendous. Symptoms of neuropsychiatric systemic lupus erythematosus may range from mild diffuse ones, to acute life threatening events. Although the underlying mechanisms are still largely unraveled, several pathogenic pathways are identified, such as antibody-mediated neurotoxicity, vasculopathy due to anti-phospholipid antibodies and other mechanisms, and cytokine-induced neurotoxicity. In the current review, we describe the old and the new regarding epidemiology, pathophysiology, diagnosis, and management of neuropsychiatric systemic lupus erythematosus. The possible link between neuropsychiatric symptoms and specific mechanisms may help to facilitate our understanding of the disease in the future, thus allowing for better treatment strategies.
147 citations
Cites background or methods from "Neuropsychiatric Syndromes in Syste..."
...However, it should be noted that up to 60% of NPSLE patients may have oligoclonal bands in their CSF, and evidence suggesting demyelination on imaging is not rare [5]....
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...Cognitive impairment is highly prevalent among lupus patients, ranging from 20 to 80% [5,55]....
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...[5] performed a meta-analysis of studies assessing NPSLE prevalence....
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...The fact that numerous autoantibodies are detected in SLE patients, and particularly in NPSLE, as well as the association between specific autoantibodies and certain manifestations suggest that their presence is linked directly to pathogenesis [5,7,8]....
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References
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TL;DR: This paper examines eight published reviews each reporting results from several related trials in order to evaluate the efficacy of a certain treatment for a specified medical condition and suggests a simple noniterative procedure for characterizing the distribution of treatment effects in a series of studies.
33,234 citations
TL;DR: It is concluded that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity, and one or both should be presented in publishedMeta-an analyses in preference to the test for heterogeneity.
Abstract: The extent of heterogeneity in a meta-analysis partly determines the difficulty in drawing overall conclusions. This extent may be measured by estimating a between-study variance, but interpretation is then specific to a particular treatment effect metric. A test for the existence of heterogeneity exists, but depends on the number of studies in the meta-analysis. We develop measures of the impact of heterogeneity on a meta-analysis, from mathematical criteria, that are independent of the number of studies and the treatment effect metric. We derive and propose three suitable statistics: H is the square root of the chi2 heterogeneity statistic divided by its degrees of freedom; R is the ratio of the standard error of the underlying mean from a random effects meta-analysis to the standard error of a fixed effect meta-analytic estimate, and I2 is a transformation of (H) that describes the proportion of total variation in study estimates that is due to heterogeneity. We discuss interpretation, interval estimates and other properties of these measures and examine them in five example data sets showing different amounts of heterogeneity. We conclude that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity. One or both should be presented in published meta-analyses in preference to the test for heterogeneity.
25,460 citations
TL;DR: A checklist contains specifications for reporting of meta-analyses of observational studies in epidemiology, including background, search strategy, methods, results, discussion, and conclusion should improve the usefulness ofMeta-an analyses for authors, reviewers, editors, readers, and decision makers.
Abstract: ObjectiveBecause of the pressure for timely, informed decisions in public health
and clinical practice and the explosion of information in the scientific literature,
research results must be synthesized. Meta-analyses are increasingly used
to address this problem, and they often evaluate observational studies. A
workshop was held in Atlanta, Ga, in April 1997, to examine the reporting
of meta-analyses of observational studies and to make recommendations to aid
authors, reviewers, editors, and readers.ParticipantsTwenty-seven participants were selected by a steering committee, based
on expertise in clinical practice, trials, statistics, epidemiology, social
sciences, and biomedical editing. Deliberations of the workshop were open
to other interested scientists. Funding for this activity was provided by
the Centers for Disease Control and Prevention.EvidenceWe conducted a systematic review of the published literature on the
conduct and reporting of meta-analyses in observational studies using MEDLINE,
Educational Research Information Center (ERIC), PsycLIT, and the Current Index
to Statistics. We also examined reference lists of the 32 studies retrieved
and contacted experts in the field. Participants were assigned to small-group
discussions on the subjects of bias, searching and abstracting, heterogeneity,
study categorization, and statistical methods.Consensus ProcessFrom the material presented at the workshop, the authors developed a
checklist summarizing recommendations for reporting meta-analyses of observational
studies. The checklist and supporting evidence were circulated to all conference
attendees and additional experts. All suggestions for revisions were addressed.ConclusionsThe proposed checklist contains specifications for reporting of meta-analyses
of observational studies in epidemiology, including background, search strategy,
methods, results, discussion, and conclusion. Use of the checklist should
improve the usefulness of meta-analyses for authors, reviewers, editors, readers,
and decision makers. An evaluation plan is suggested and research areas are
explored.
17,663 citations
TL;DR: In this paper, the role and limitations of retrospective investigations of factors possibly associated with the occurrence of a disease are discussed and their relationship to forward-type studies emphasized, and examples of situations in which misleading associations could arise through the use of inappropriate control groups are presented.
Abstract: The role and limitations of retrospective investigations of factors possibly associated with the occurrence of a disease are discussed and their relationship to forward-type studies emphasized. Examples of situations in which misleading associations could arise through the use of inappropriate control groups are presented. The possibility of misleading associations may be minimized by controlling or matching on factors which could produce such associations; the statistical analysis will then be modified. Statistical methodology is presented for analyzing retrospective study data, including chi-square measures of statistical significance of the observed association between the disease and the factor under study, and measures for interpreting the association in terms of an increased relative risk of disease. An extension of the chi-square test to the situation where data are subclassified by factors controlled in the analysis is given. A summary relative risk formula, R, is presented and discussed in connection with the problem of weighting the individual subcategory relative risks according to their importance or their precision. Alternative relative-risk formulas, R I , R2, Ra, and R4/ which require the calculation of subcategory-adjusted proportions ot the study factor among diseased persons and controls for the computation of relative risks, are discussed. While these latter formulas may be useful in many instances, they may be biased or inconsistent and are not, in fact, overages of the relative risks observed in the separate subcategories. Only the relative-risk formula, R, of those presented, can be viewed as such an average. The relationship of the matched-sample method to the subclassification approach is indicated. The statistical methodolo~y presented is illustrated with examples from a study of women with epidermoid and undifferentiated pulmonary ccrclnomc.e-J. Nat. Cancer Inst, 22: 719748, 1959.
14,433 citations
TL;DR: These principles are discussed, along with the practical steps in performing meta-analysis, which allow a more objective appraisal of the evidence than traditional narrative reviews, provide a more precise estimate of a treatment effect, and may explain heterogeneity between the results of individual studies.
Abstract: Meta-analysis is a statistical procedure that integrates the results of several independent studies considered to be “combinable.”1 Well conducted meta-analyses allow a more objective appraisal of the evidence than traditional narrative reviews, provide a more precise estimate of a treatment effect, and may explain heterogeneity between the results of individual studies.2 Ill conducted meta-analyses, on the other hand, may be biased owing to exclusion of relevant studies or inclusion of inadequate studies.3 Misleading analyses can generally be avoided if a few basic principles are observed. In this article we discuss these principles, along with the practical steps in performing meta-analysis.
Meta-analysis should be viewed as an observational study of the evidence. The steps involved are similar to any other research undertaking: formulation of the problem to be addressed, collection and analysis of the data, and reporting of the results. Researchers should write in advance a detailed research protocol that clearly states the objectives, the hypotheses to be tested, the subgroups of interest, and the proposed methods and criteria for identifying and selecting relevant studies and extracting and analysing information.
As with criteria for including and excluding patients in clinical studies, eligibility criteria have to be defined for the data to be included. Criteria relate to the quality of trials and to the combinability of treatments, patients, outcomes, and lengths of follow up. Quality and design features of a study can influence the results.4 5 Ideally, researchers should consider including only controlled trials with proper randomisation of patients that report on all initially included patients according to the intention to treat principle and with an objective, preferably blinded, outcome assessment.6 Assessing the quality of a study …
2,040 citations