Neuropsychiatric Manifestations Of Systemic Lupus Erythematosus

This volume brings together investigators working on the clinical problem of neuropsychiatric systemic lupus erythematosus, as well as neuroscientists from other disciplines. The presentations provide a current overview and access to a better understanding of cellular events in ischemia, the hypothalamic pituitary adrenal (HPA) axix and hypothalamic pituitary gonadal (HPG) axis changes in systemic inflammation, and the protective and toxic effects of glucocorticoids on the brain. The articles invoke discussion and generate future strategies for diagnosis and therapy.

Neuropsychiatric manifestation in systemic lupus erythematosus (NPSLE) is one of the most recalcitrant complications of the disease. According to the 1999 ACR nomenclature and case definitions, diffuse psychiatric/neuropsychological syndromes in NPSLE (anxiety disorder, acute confusional state, cognitive dysfunction, mood disorder, psychosis) (diffuse NPSLE) present psychiatric manifestations unlike neurologic syndromes (focal NPSLE) originating from focal CNS lesions, such as cerebrovascular disease, demyelinating syndrome, headache, aseptic meningitis, chorea, seizures and myelopathy. A number of studies have reported that diffuse NPSLE is usually associated with the presence of autoantibodies against neuronal cells in serum as well as in cerebrospinal fluid (CSF). Moreover, IL-6 has been shown to be elevated in CSF of patients with diffuse NPSLE. Recently, it has been demonstrated that the severity of blood-brain barrier damages plays a crucial role in the development of acute confusional state, the severest form of diffuse NPSLE through the accelerated entry of larger amounts of autoantibodies to NMDA receptor subunit NR2 into the CNS. Since the importance of autoantibodies in the NPSLE has been now evident, such an aggressive treatment, especially B cell depleting therapy, would make sense in that it would reduce the levels of pathogenic autoantibodies, leading to a better prognosis of NPSLE. As far as we know, no single book specifically dedicated to NPSLE alone has been published as yet. As mentioned above, NPSLE constitutes a vastly expanding field of research with increasing numbers of papers published annually. Therefore, we believe that an effort to collect and critically review these publications is invaluable. Such an effort will provide an important contribution to basic researchers as well as clinicians working in the field of neurology, rheumatology, psychiatry and internal medicine fields.

The scope of this contributed volume is to provide an overview of the latest translational research in the field of lupus pathogenesis, with particular emphasis on how these discoveries progress in parallel with therapeutic drug development. Systemic lupus erythematosus (SLE) is a multifaceted disease with a number of well-defined immune pathways that are dysregulated, resulting in an immune-mediated chronic inflammatory injury at target organs. As knowledge of these pathways evolves to provide opportunities for targeted drug therapy and lays the foundation for personalized medicine, clinicians and researchers need to keep up with the ever-expanding medical literature. This book will critically appraise the current understanding of important immunological pathways that contribute to the pathogenesis of lupus. We will review the role of interferons as part of the innate immune defects that perpetuate the loss of self-tolerance in SLE. B cell hyperactivity, as a defining hallmark of SLE, and different strategies of B cell targeted therapy will be discussed. The role of co-stimulation or immune checkpoint molecules in activating B and T cells will be reviewed, as well as other cytokines that serve in the amplification loop promoting a more proinflammatory Th1 or Th17 responses. Intracellular targets, such as signaling molecules in the JAK/STAT pathway, or a variety of kinases and proteasomes, can cause a cascading downstream effect of transcriptional responses that are important in SLE. Immune homeostasis can also be restored by bolstering the naturally occurring anti-inflammatory mechanisms. Glucocorticoid, as a potent natural anti-inflammatory hormone, can mediate its effects by recruiting histone deacetylase that serve to repress gene transcription. Glucocorticoid-induced leucine zipper is a gene upregulated by glucocorticoid that can be a potential target for development of anti-inflammatory strategy. Finally, T regulatory cells can be utilized to help restore to immune tolerance and are amongst the latest focus of therapeutic development in SLE.

Systemic lupus erythematosus, the prototype of an autoimmune disorder, may affect several organs and may run a chronic course between relapse and remission. This book covers important aspects of the disease, including epidemiology, pathophysiology, and neuropsychiatric manifestations, including basic science and clinical features and management. In affected patients, the fundamental problem of fertility is reassessed including the risk of the disease, the possibility of fetal loss, the safety of drugs during pregnancy, and the current diagnostic and suggested therapeutic strategies of reproductive medicine. Finally, the issue of pathogenesis is revisited with a thorough description of animal models in relation to physiology and potential novel therapies.

This detailed, practical textbook focuses on immune mediated disorders of the nervous system with particular focus on systemic autoimmune disorders. Divided into three sections, the first discusses the neuroanatomical and pathophysiologic basis of immune mediated disorders of the nervous system. Following this are 25 chapters devoted to individual clinical conditions. To conclude, the final section explains what is known about the mechanisms of immunomodulatory treatments and practical points about monitoring patients on these treatments. Neurorheumatology: A Comprehensive Guide to Immune Mediated Disorders of the Nervous System bridges the gaps among different branches of medicine and is an indispensable resource for rheumatologists and neurologists looking to develop a firm understanding of these dynamic disorders

A strong clinical emphasis is present throughout this volume from the first section of commonly presenting problems through to the section addressing problems shared with a range of other clinical sub-specialties.

This completely updated and expanded 2nd edition of Systemic Lupus Erythematosus, A Manual includes topics not covered previously with contributors who are at the forefront of each specific topic and with a global appeal. Each chapter is short and is presented critically with selected references, which should be valuable to a wider audience. This book combines basic with clinical science to help internists and specialists in the diagnosis and management of patients with SLE. It is a quick referral for people in the pharmaceutical industry in their efforts to bring much-needed drugs. It provides all the needed information to basic researchers old and new alike, who wish to enter the field of lupus and systemic autoimmunity in general. Focused state-of-the-art chapters prepared by top-notch experts in the field Latest understanding of cellular, molecular, biochemical aspects of disease pathogenesis Advanced aspects of genetic, microbiome, environmental, hormonal, and immunological contribution to the expression of the disease Current understanding of clinical features of the disease Recent efforts to develop new treatments