鞘内注射甲氨蝶呤和地塞米松治疗神经精神性狼疮的临床观察

目的探讨甲氨蝶呤和地塞米松鞘内注射治疗系统性红斑狼疮（SLE）中枢神经系统损害的效果。方法对18例鞘内注射的SLE中枢神经系统损害患者治疗前后的临床表现、脑脊液、头颅CT或磁共振成像（MRI）进行对比分析,并与27例未行鞘内注射者的情况进行对照。结果18例患者中1例死亡,其他患者病情均明显改善或完全缓解;脑脊液压力明显下降,蛋白水平降低,葡萄糖升高。结论甲氨蝶呤和地塞米松鞘内注射治疗SLE中枢神经系统损害有明显效果,能提高抢救成功率,副作用轻且少,值得临床推荐使用。     

甲氨蝶呤加地塞米松鞘内注射治疗中枢神经系统狼疮

中枢神经系统狼疮(NPLE)又称狼疮性脑病,预后凶险,是系统性红斑狼疮(SLE)主要的死亡原因之一,目前除甲基强的松龙(以下简称甲强龙)和环磷酰胺冲击治疗外尚无其他安全有效治疗措施.本文观察了11例NPLE在使用甲强龙和环磷酰胺冲击治疗基础上,应用甲氨蝶呤(MTX)和地塞米松(DXM)鞘内注射的临床效果.     

鞘内注射甲氨蝶呤、地塞米松治疗神经精神狼疮的随访研究

目的 观察两种方法治疗神经精神狼疮(NPSLE)的远期疗效,并探讨NPSLE复发的危险因素.方法 36例NPSLE随机分成两组,两组均静脉冲击甲泼尼龙冲(MP)1 g 3 d,实验组联合鞘内注射甲氨蝶呤(MTX)10 mg和地塞米松(DXM)10 mg每周1次,≤3次.对照组每周应用环磷酰胺(CTX)0.4 g/1次,≤3次.观察两组1年内NPSLE的复发率和NPSLE复发时与未复发患者随访6个月和1年时系统性红斑狼疮活动指数(SLEDAI)△(不计神经精神评分)和泼尼龙维持量差异有无统计学意义.结果 1年内实验组18例患者有2例复发,对照组16例有8例复发,实验组显著低于对照组.NPSLE复发时与未复发患者随访6个月、1年时系统性红斑狼疮活动指数(SLEDAI)和泼尼龙维持量差异元统计学意义.结论 静脉冲击MP联合鞘内注射MTX和DXM治疗NPSLE复发率低;NPSLE复发与SLEDAI和泼尼龙维持量无关.     

甲基强的松龙联合甲氨蝶呤和地塞米松鞘内注射治疗神经精神狼疮37例疗效观察

目的 探讨甲基强的松龙联合鞘内注射甲氨蝶呤和地塞米松治疗神经精神狼疮的疗效及安全性.方法 37例神经精神狼疮患者为治疗组,采用甲基强的松龙500 mg静脉冲击治疗3 d,以后改为甲基强的松龙40～120 mg静脉滴注,1次/d,同时鞘内注射甲氨蝶呤(5～10 ms)+地塞米松(5～10 ms),每周1次,共2～3次.随机抽取同时期住院确诊为神经精神狼疮患者33例为对照组,给予甲基强的松龙冲击(方法同治疗组)+环磷酰胺(0.5～1.0)g/m2体表面积,每3～4周1次.观察2组临床疗效、实验室检验指标变化及药物不良反应.结果 治疗组病情缓解率、平均缓解时间均优于对照组(P<0.05),病死率小于对照组(P<0.05).2组患者治疗后红细胞沉降率、脑脊液压力均有下降,治疗组较对照组显著(P<0.05).治疗组药物不良反应少于对照组(P<0.05).结论 甲基强的松龙联合甲氨蝶呤和地塞米松治疗神经精神狼疮,短时疗效显著,并可明显改善活动指标,药物不良反应少.     

鞘内注射甲氨喋呤及地塞米松治疗中枢神经系统狼疮24例分析

目的 :探讨鞘内注射疗法对系统性红斑狼疮中枢神经系统损害的疗效。方法 :2 4例具有中枢神经系统损害的系统性红斑狼疮住院患者 ,常规治疗无效的情况下 ,鞘内注射甲氨喋呤和地塞米松。结果 :所有病例均不同程度的缓解。结论 :鞘内注射对于狼疮脑病 ,是一种行之有效的方法。     

神经精神性狼疮诊治新进展

系统性红斑狼疮（systemic lupus erythematosus，SLE）是一种可累及全身各脏器和组织的自身免疫性疾病，当其出现神经精神症状时，则称为神经精神性狼疮（neuropsychiatric systemic lupus erythematosus，NPSLE）。关于NPSLE发病率的报道不尽相同，大约为14％～80％。正因为NPSLE的发病率低及临床表现复杂，故对其诊断带来了困难。在治疗上，也应根据不同的个体，不同的临床表现选择不同的治疗方案。     

神经精神狼疮65例分析

目的探讨神经精神狼疮(NPSLE)患者的临床特点及早期诊断、早期治疗。方法回顾性分析65例NPSLE的临床表现、实验室检查、影像学表现、并发症、治疗和转归。结果 9例以神经精神症状首发,56例在SLE病程中各个阶段出现了各种神经精神症状;脑脊液检查,60%(40例)患者脑脊液蛋白升高;57例行头颅MRI检查者46例出现异常信号影,11例头颅MRI检查未见异常者CSF蛋白均升高;治疗后除1例并狼疮肾炎者死亡外,其余患者均有不同程度的缓解。结论脑脊液检查及头颅MRI结合临床可以协助NPSLE的早期诊断。早期诊断及早期合理治疗尤为重要。     

甲氨蝶呤鞘内注射致急性非心源性肺水肿1例

患者,女,25岁.因间断癫痫大发作11年,雷诺现象3年,于2001年2月12日入院.患者从1990年开始出现间断性癫痫大发作,每年发作1～2次,抗癫痫药物治疗无效.     

甲氨蝶呤鞘内注射致神经系统不良反应分析

甲氨蝶呤是临床上常用的抗代谢类抗肿瘤药,在治疗急性淋巴细胞性白血病方面具有良好的治疗效果,然而,任何一种抗肿瘤药在杀伤或抑制肿瘤细胞的过程中,都不可避免地对正常组织和细胞产生不良反应,严重者可导致死亡。本文通过回顾性分析我院2003年3月-2011年2月发生的5例由鞘内注     

儿童狼疮性肾炎合并神经精神性狼疮的危险因素

目的初步探讨狼疮性肾炎患儿并发神经精神性狼疮(NPSLE)的危险因素。方法对12例NPSLE患儿及28例无神经系统病变的狼疮患儿进行回顾性分析,先将研究变量做单因素分析,比较NPSLE患儿及非NPSLE患儿临床资料,包括起病年龄、本次发病年龄、病程、发热、蝶形红斑、关节炎、高血压、中重度贫血、血小板减少、肾功能不全等临床特点;对比两组患儿实验室资料,包括抗核抗体(ANA)、抗双链DNA抗体、补体C3等;此外对比两组患儿的治疗情况,包括是否正规使用糖皮质激素、是否用过甲强龙冲击治疗及是否同时正规应用环磷酰胺(CTX)治疗。再将有意义的变量进行多因素非条件、Logistic回归分析。结果单因素分析显示其中患儿发热、C3<0.4、激素使用不规范,CTX治疗不规范为有统计学意义的危险因素(P<0.05);甲强龙冲击为有统计学意义的保护因素。进一步行多因素非条件Logistic回归分析,结果显示,最终进入回归方程的变量为发热、C3<0.4g/L、激素使用不规范,CTX治疗不规范。其中发热(OR=1.828)、C3<0.4 g/L(OR=18.573)、激素使用不规范(OR=2.338),CTX治疗不规范(OR=31.520)与NPSLE呈正相关。结论发热、C3<0.4 g/L、激素使用不规范、CTX治疗不规范是LN患儿发生NPSLE的重要困素。对于活动评分高、补体C3明显下降的LN患儿应在早期规范使用激素,积极加用免疫抑制剂治疗。而对于治疗不规范的LN患儿,要警惕NPSLE的发生。     

甲氨蝶呤治疗系统性红斑狼疮的研究

目的评估甲氨蝶呤（MTX）治疗轻、中度活动系统性红斑狼疮（SLE）的疗效。方法专科门诊随诊患者分为：A组,MTX加小剂量激素组（泼尼松10mg／d）28例;B组,中等剂量激素组（泼尼松30mg／d）20例,观察指标包括SLE疾病活动指数评分（SLEDAI）、激素减至少剂量维持治疗时病情复发情况及药物不良反应。结果A组积分由治疗前的（9．4±2．1）降至（4．1±0．9）,B组由（8．6±2．5）降至（4.0±1．0）。两组治疗前后相比疗效差异显著（P〈0．01）,但A、B两组间疗效差异无统计学意义（P〉0．25）,激素减量至10mg／d维持后B组有8例出现病情反复,A组在总观察期有3例病情反复,两组对比差异有统计学意义（P〈0．025）。A组不良反应主要是胃肠道反应,B组以库兴综合征为主。结论MTX对轻中症SLE治疗有效,加用MTX可减少激素用量,防止长期使用偏大量激素引起相关不良反应。     

小剂量甲泼尼龙联合甲氨蝶呤和羟氯喹治疗系统性红斑狼疮的临床疗效及安全性分析

目的 评价小剂量甲泼尼龙联合甲氨蝶呤和羟氯喹治疗轻中度系统性红斑狼疮（SLE）患者的疗效及安全性。方法 96例轻到中度系统性红斑狼疮患者,按患者就诊时间分为观察组和对照组,各48例。两组患者均给予甲氨蝶呤和羟氯喹;对照组加用双氯芬酸钠（75 mg/次,2次/d）,观察组加用甲泼尼龙（4 mg/次,2次/d）,两组均治疗12周。比较两组患者的疗效和不良反应发生情况。结果 两组患者经过12周的治疗,观察组有效率为91.67%,明显高于对照组的64.58%,差异有统计学意义（P<0.05）。治疗前,两组患者间狼疮疾病活动指数（SLEDAI）、红细胞沉降率（ESR）、C反应蛋白（CRP）、补体C3水平相比,差异均无统计学意义;治疗后,两组患者的SLEDAI积分、ESR、CRP、补体C3水平均较治疗前明显改善,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组比对照组改善更明显,两组间各指标相比差异均具有统计学意义（P<0.05）。治疗后两组相比,观察组的不良反应发生率低,差异均有统计学意义（P<0.05）。结论 小剂量甲泼尼龙联合甲氨蝶呤和羟氯喹治疗系统性红斑狼疮疗效显著,安全性高,值得推广。     

B-cell-targeted therapy for systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a complex disease characterised by numerous autoantibodies and clinical involvement in multiple organ systems. The immunological events triggering the onset of clinical manifestations have not yet been fully defined, but a central role for B cells in the pathogenesis of this disease has more recently gained prominence as a result of research in both mice and humans. Both antibody-dependent and -independent mechanisms of B cells are important in SLE. Autoantibodies contribute to autoimmunity by multiple mechanisms, including immune complex-mediated type III hypersensitivity reactions, type II antibody-dependent cytotoxicity, and by instructing innate immune cells to produce pathogenic cytokines such as interferon-alpha, tumour necrosis factor and interleukin-1. Suggested autoantibody-independent B-cell functions include antigen presentation, T-cell activation and polarisation, and dendritic-cell modulation. Several of these functions are mediated by the ability of B cells to produce immunoregulatory cytokines, chemokines and lymphangiogenic growth factors, and by their critical contribution to lymphoid tissue development and organisation, including the development of ectopic tertiary lymphoid tissue. Given the large body of evidence implicating abnormalities in the B-cell compartment in SLE, a recent therapeutic focus has been to develop interventions that target the B-cell compartment by multiple mechanisms.Rituximab, a mouse-human chimeric monoclonal antibody against CD20 that specifically depletes B cells, has been studied the most extensively. Although promising open-label data await confirmation in ongoing multicentre placebo-controlled trials, a number of preliminary conclusions can be drawn. The adequacy of peripheral B-cell depletion depends on achieving high and sustained serum rituximab concentrations, pharmacokinetics that can be varied with treatment dose and factors that may affect drug clearance, such as human anti-chimeric antibodies. In SLE patients with effective B-cell depletion, the clinical response can be significant, with favourable responses observed in a diverse array of disease manifestations. Moreover, rituximab appears to have the potential to induce clinical remission in severe, refractory disease. B-cell depletion has the potential to induce disease amelioration by inhibiting autoantibody production and/or by interfering with other B-cell pathogenic functions. The fact that clinical improvement correlates with B-cell depletion and precedes by several months any decline in serum levels of relevant autoantibodies suggests a predominant effect of autoantibody-independent functions of B cells, although the subset of patients with disease remission ultimately also experience autoantibody normalisation. Significant questions remain about rituximab therapy in SLE, including the immunological determinants of treatment response and remission, the role of combination therapy, and the safety of repeated courses of rituximab. In addition, the efficacy and role of other B-cell-depleting approaches, such as humanised anti-CD20 antibodies and anti-CD22, remain to be defined.Another B-cell-targeted therapeutic approach is to block costimulatory interactions between T and B cells. Blockade of the CD40-CD40 ligand pathway has met with variable clinical benefit and unfortunate thromboembolic complications, although inhibition of the B7 pathway with cytotoxic T-lymphocyte antigen-4Ig is currently under early investigation in SLE clinical trials. Preliminary data on the treatment of SLE with belimumab, a fully human monoclonal antibody that specifically binds to and neutralises the B-lymphocyte stimulator (BLyS or B-cell-activating factor [BAFF]), are now available. In a phase II double-blind, placebo-controlled trial of the safety and efficacy of three different doses administered in addition to standard therapy, belimumab was well tolerated but reportedly did not meet primary efficacy endpoints. Blockade of BAFF is still viewed as a promising therapeutic approach and additional agents that interfere with the BAFF pathway are under study.Overall, therapies targeting B cells appear to be promising in the treatment of SLE, provide additional evidence for the importance of B cells to disease pathogenesis, and will continue to elucidate the diverse roles of B cells in this disease.     

Novel treatments for systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease that is associated with the production of autoantibodies, and with considerable morbidity and mortality. There has been much interest in developing more specific therapies for this disease, which is currently managed with immunosuppressive drugs, predominantly corticosteroids, azathioprine, methotrexate and cyclophosphamide, in combination with hydroxychloroquine. Mycophenolate mofetil has been demonstrated to be as efficacious as cyclophosphamide in patients with lupus nephritis, and is being used increasingly in the clinic despite not being licensed for this indication. Novel methods of reducing autoantibody formation in SLE include the use of mAbs that modulate and/or deplete B-cells (anti-CD22 and anti-CD20 antibodies, respectively), or that interfere with the stimulatory effects of the soluble factor B-lymphocyte stimulator (anti-BLys antibodies). Alternative approaches include the use of atacicept (Merck Serono), a transmembrane activator and calcium modulator ligand interactor (TACI)-Ig fusion protein, which inhibits B-cell stimulation by binding to BLys and a profileration-inducing ligand (APRIL), or toleragens such as abetimus. Blocking costimulatory molecule interactions, such as the CD40-CD40 ligand interaction with mAbs and the CD28-B7 interaction with a soluble cytotoxic T-lymphocyte antigen 4 (CTLA-4)-IgG1 construct (abatacept), has also been attempted as a therapeutic strategy for SLE. The most promising strategy for a new drug for SLE is belimumab (Human Genome Sciences/GlaxoSmithKline), an anti-BLys antibody, as two phase III clinical trials with this drug recently met their primary endpoints. In this review, these novel approaches to the treatment of SLE, including the potential of targeting cytokine pathways involved in autoimmunity, are discussed.     

Treatment of systemic lupus erythematosus with epratuzumab

Systemic lupus erythematosus is a prototypic autoimmune disease characterized by abnormalities in the activity of B-cells and T-cells. A novel specific treatment for autoimmune diseases is B-cell depletion with monoclonal antibodies. Epratuzumab is a monoclonal antibody that targets CD22 antigen on B-cells. Initial phase II and two terminated early phase III studies suggest that treatment of systemic lupus erythematosus with this immunomodulatory agent is effective, well tolerated and significantly improves the patient's quality of life. In vitro studies and clinical trials with non-Hodgkin lymphoma patients indicate epratuzumab can potentially serve as a complementary drug in combination therapy with another inhibitor of B-cell activity, rituximab, which is a monoclonal anti-CD20 antibody.     

以乏力为首发表现的儿童系统性红斑狼疮1例

目的 阐述以乏力为首发表现的儿童系统性红斑狼疮(SLE)病例并讨论.方法 报道1例以乏力为首发表现的儿童系统性红斑狼疮.结果 儿童系统性红斑狼疮首发症状多种多样,临床医生应加强疾病总体认识,避免漏诊、误诊.结论 儿童系统性红斑狼疮首发症状各异,临床医生需熟练掌握疾病,避免漏诊、误诊.     

Pharmacotherapy of systemic lupus erythematosus

The pharmacological management of systemic lupus erythematosus (SLE) is challenging owing to its unpredictable clinical course, the variable organ system involvement and the lack of clear understanding of disease pathogenesis. The widely used corticosteroids and immunosuppressive drugs, which can control disease activity, have serious, potentially fatal, side effects. In the last decade, a better understanding of lupus pathogenesis has led to the development of biological agents that are directed at biomarkers. However, these biologicals also exert side effects due to infections resulting from completely eliminating immune cells (e.g., B cells) or cytokine signals (e.g., interferon-α) or affecting molecular targets outside the immune system (CD40L on platelets). New biomarker-driven clinical trials are ongoing to evaluate the safety and efficacy of B-cell depletion, blocking of interferon signaling, inhibition of the mTOR pathway, and restoration of glutathione deficiency in lupus T cells.