摘要:

Purpose of reviewYoung women with systemic lupus erythematosus have strikingly high rates of coronary heart disease. Current knowledge indicates that atherosclerosis is an active inflammatory and immune-mediated process. Therefore, the chronic inflammation and immune dysregulation characteristic of systemic lupus erythematosus undoubtedly contribute to the accelerated vascular disease seen in these patients. Carefully considering what is known about atherogenesis in the general population will provide clues to unraveling the complexity of why systemic lupus erythematosus and atherosclerosis are linked so frequently.Recent findingsInflammation is involved in all aspects of atherogenesis from the initial endothelial “response to injury,” to foam cell formation leading to the atherosclerotic lesion, to the rupture of the “vulnerable” fibrous cap, resulting in the acute coronary syndrome and potentially in death. The authors review how factors commonly seen in systemic lupus erythematosus or inherent to the underlying disease mechanism may contribute to each of the stages of atherogenesis.SummaryOur focus on the causes of vascular disease in systemic lupus erythematosus must now include nontraditional risk factors such as immune and inflammatory mediators. With the advent of noninvasive screening tools for atherosclerosis, we are better equipped to measure subclinical vascular disease and associated risk factors, including immune and inflammatory mediators. When considering strategies for preventing premature cardiovascular disease in systemic lupus erythematosus, modifying immune and inflammatory risk factors will likely become a major component of the program in addition to modifying the current traditional risk factors.

ISSN:1040-8711    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Immunosuppressive drugs have become the gold standard for the treatment of major organ involvement in systemic lupus erythematosus. The use of immunosuppressive therapy in systemic lupus erythematosus carries significant risks for infection. This article reviews infectious complications in systemic lupus erythematosus, focusing on effects of immunosuppressive therapy. Patients with systemic lupus erythematosus appear to carry an intrinsically increased risk for infection. Recent studies support this notion further by showing increased risk for serious infections in patients with systemic lupus erythematosus who had mannose-binding lectin deficiency associated with homozygous mannose-binding lectin variant alleles. Patients with systemic lupus erythematosus who were homozygous for mannose-binding lectin variant alleles had a fourfold increase in the incidence of infections, requiring hospitalization. In terms of extrinsic risk factors for infection, use of steroids and cyclophosphamide are the strongest risk factors. The effect of these drugs on infection is also dose dependent. The incidence of infectious complications in patients treated with mycophenolate mofetil, a newly used immunosuppressive drug in systemic lupus erythematosus, appears less frequent compared with cyclophosphamide. Herpes zoster is still the most common viral infection in patients with systemic lupus erythematosus treated with cyclophosphamide and mycophenolate mofetil. Overall data indicate that patients with systemic lupus erythematosus may have intrinsically increased risks for infection that are augmented by immunosuppressive therapies. Cyclophosphamide, in particular in combination with high-dose glucocorticoids, has the strongest effect in suppressing the immune responses against microorganisms. Careful monitoring of infectious complications is warranted in patients with systemic lupus erythematosus receiving immunosuppressive therapies, in particular those on high-dose glucocorticoids and cytotoxic drugs.

ISSN:1040-8711    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The neonatal lupus syndromes, although quite rare, provide an excellent opportunity to examine disease from bench to bedside. During the past year numerous publications have reported basic and clinical research. Although anti-SSA/Ro-SSB/La antibodies are detected in more than 85% of mothers whose fetuses are identified with conduction abnormalities in a structurally normal heart, when clinicians applied this testing to their pregnant patients, the risk for a woman with the candidate antibodies to have a child with congenital heart block was at or below one in 50. Although the precise pathogenic mechanism of antibody-mediated injury remains unknown, it is clear that the antibodies alone are insufficient to cause disease, and fetal factors are likely contributory.In vivoandin vitroevidence supports a pathologic cascade involving apoptosis of cardiocytes, surface translocation of Ro and La antigens, binding of maternal autoantibodies, secretion of profibrosing factors from the scavenging macrophages, and transdifferentiation of cardiac fibroblasts to a myofibroblast scarring phenotype. Cross-reactivity of anti-52-kD SSA/Ro antibodies with a serotoninergic cardiac receptor, 5-hydroxytryptamine (HT)4, has been suggested but remains unconfirmed. The spectrum of cardiac abnormalities continues to grow, with varying degrees of block identifiedin uteroand reports of late-onset cardiomyopathy (some of which display endocardial fibroelastosis). Moreover, there is now clear documentation that incomplete blocks (including those improvingin uterowith dexamethasone) can progress postnatally, despite the clearance of the maternal antibodies from the neonatal circulation. Better echocardiographic measurements that identify first-degree blockin uteromay be the optimal means of approaching pregnant women at risk. Prophylactic therapies, including treatment with intravenous immunoglobulin, await larger trials. Reassuringly, most children with neonatal lupus syndromes do not develop rheumatic diseases, although follow-up is limited to late adolescence. To further efforts both at the bench and bedside, national research registries established in the United States and Canada are critical.

ISSN:1040-8711    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The purpose of this review is to discuss recent developments in the biology and biochemistry of the T cells in mice and humans with systemic lupus erythematosus. T cells that recognize self-antigens are present in systemic lupus erythematosus and normal organisms. It is obvious, though, that an autoimmune environment should be present to disrupt anergy and instigate a response that might cause disease. The environment that lifts anergy is defined by distinct molecular aberrations that include rewiring of the T cells. Aberrant transcription of genes that encode proteins involved in autoimmunity can be traced to abnormal expression and activation of transcription factors and promoter methylation intensity. Only certain components of the autoimmune response can be linked to pathologic changes in the target organ that might be dictated by additional local factors. The works reviewed imply that self-peptides might be considered to reestablish lost tolerance, whereas correction of the aberrant biochemistry might normalize T cell function and limit disease.

ISSN:1040-8711    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewUntil recently, systemic lupus erythematosus has been viewed mainly as a B-cell disease resulting from altered T cell–B cell interactions. The recognition of the fundamental role of dendritic cells in the control of tolerance and immunity led to the hypothesis that systemic lupus erythematosus may be driven through unabated dendritic cell activation. This review summarizes the recently uncovered role of dendritic cell subsets and one of their products, interferon-&agr;, in the pathophysiology of systemic lupus erythematosus.Recent findingsCD14+ monocytes isolated from the blood of patients with systemic lupus erythematosus, but not those from healthy individuals, act as dendritic cells. Their activation is driven by circulating interferon-&agr; that may come from one of the dendritic cell subsets (ie, plasmacytoid dendritic cells that infiltrate systemic lupus erythematosus skin lesions). Although only a fraction of patients with active systemic lupus erythematosus show circulating interferon-&agr;, blood mononuclear cells from all of them display an interferon-&agr; signature.SummaryThe disease model that the authors propose places interferon-&agr; at the center of the immunologic abnormalities observed in systemic lupus erythematosus, and poses interferon-&agr; and/or interferon-&agr;-producing cells as novel targets for therapy in this disease. The authors surmise that type I interferon antagonists will bring systemic lupus erythematosus patients the relief that tumor necrosis factor antagonists brought to patients with rheumatoid arthritis.

ISSN:1040-8711    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Systemic lupus erythematosus is a complex, multisystem autoimmune disease characterized by production of high-titer autoantibodies directed against ubiquitously expressed self-antigens. Autoantigens in systemic lupus erythematosus are highly diverse in terms of structure and location in control cells, but become clustered in and on the surface blebs of apoptotic cells. The past several years have provided significant evidence that the apoptotic cell plays a central role in tolerizing B cells and T cells to both tissue-specific and ubiquitously expressed self-antigens, and may drive the autoimmune response in systemic autoimmune disease. The authors review the significant recent advances in this area. Recent studies suggest that predisposing factors to subsequent development of systemic autoimmunity may be the incomplete induction of tolerance to apoptotic antigens, potentially through abnormal apoptotic signaling and effector pathways, decreased apoptotic cell clearance, or abnormal signaling thresholds on responding lymphocytes. In such genetically susceptible hosts, proinflammatory events at the host–environment–immune system interface that lead to the binary change in the response to apoptotic material from tolerance to immunity may be responsible for initiation of autoimmunity and subsequent disease amplification. Such pathways may be amenable to therapeutic and preventive interventions.

ISSN:1040-8711    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Although a modified European–American consensus classification of Sjögren syndrome has been introduced during the last year, the etiopathogenesis of this disease characterized by chronic lymphocytic inflammation, impaired function, and, finally, destruction of the salivary and lacrimal glands as well as systemic manifestations remains to be elucidated. Recent insights into the pathogenesis of Sjögren syndrome resulting from immunogenetic, hormonal, and epidemiologic evaluations as well as animal andin vitrostudies are highlighted by this review. Evidence confirms that lymphocytic disturbances, including ectopic germinal center formation and aberrations of cellular signaling play a significant role in Sjögren syndrome. Although some of these features are unique to Sjögren syndrome, others are also found in a number of systemic autoimmune diseases, such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. The underlying cause of Sjögren syndrome remains largely enigmatic. However, distinct characteristics may provide the basis for the classification of the disease entities. Finally, an enhanced risk of lymphomagenesis is a well-known hallmark of primary Sjögren syndrome, indicating the central role of derangement of lymphocyte regulation. As demonstrated by the introduction of the new targeted therapeutic approaches in rheumatoid arthritis, solid insights into the pathogenesis of Sjögren syndrome may pave the way toward new therapeutic approaches.

ISSN:1040-8711    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:1040-8711    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

This review discusses the recent literature on pain conditions in children that should be of interest to rheumatologists. The focus of the review is therefore on musculoskeletal pains in children, particularly chronic or recurrent musculoskeletal pain. Articles that have a broader focus on pain are discussed when these are likely to be of general interest to rheumatologists. Chronic or recurrent pain in childhood is common and can be caused by a wide variety of conditions, several of which are discussed here. The importance of being able to measure pain in children has been emphasized repeatedly in the recent literature. With increased understanding of how to evaluate pain in children has come the recognition that pain in children is multifactorial and that even when there are obvious “organic” causes of the pain (such as arthritis), psychosocial factors are critical in how pain is perceived, and they influence the extent to which pain leads to dysfunction. There is also increasing evidence that cognitive-behavioral therapies are effective in managing chronic pain in children. The frequency of back pain in children is increasingly recognized, and the role of children's work and play, carrying heavy backpacks, and sitting for long periods of time at computers in causing back pain is of interest. The studies reviewed here add to an increasingly rich and informative literature on musculoskeletal and other chronic pain in children, and they help emphasize the importance of proper evaluation and management of pain in children.

ISSN:1040-8711    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewSystemic-onset juvenile idiopathic arthritis is a severe and steroid-dependent disease that sometimes progresses to a fatal disease, macrophage activation syndrome. The investigation of proinflammatory cytokine levels revealed the increases of interleukin 6 in serum of systemic-onset disease. To avoid the disease progression and the adverse events of high-dose corticosteroids, it might be a reasonable treatment strategy to inhibit the formation of interleukin 6/interleukin 6 receptor complex to block the binding to gp130 receptor, a biologically active receptor for interleukin 6.Recent findingsContinuously elevated levels of interleukin 6 in serum may play an important role in manifesting the clinical symptoms and signs of systemic-onset juvenile idiopathic arthritis, including spiking fever, rash, arthritis, and serositis. The characteristic fever spikes parallel interleukin 6 levels. A long-term exposure of high levels of interleukin 6 brings children severe growth impairment, which was strongly suggested by the recent establishment of interleukin 6 transgenic mice.SummaryThis review will provide the evidences of the relation between the imbalance of interleukin 6 homeostasis and systemic-onset juvenile idiopathic arthritis. Also reviewed will be the author's recent trials of anti interleukin 6 receptor antibody, named temporally as MRA, for children with acute systemic disease intractable to long-term, high-dose, corticosteroid therapy. MRA would be a therapeutic modality for children with systemic-onset juvenile idiopathic arthritis intractable to high-dose corticosteroids.

ISSN:1040-8711    

出版商:OVID    

年代:2003

数据来源: OVID