C反应蛋白及降钙素原测定在系统性红斑狼疮活动与合并感染鉴别诊断中的作用

目的 通过分析系统性红斑狼疮(SLE)病情活动和合并感染患者的临床和血清学特点,探讨对疾病活动和感染有鉴别意义的指标.方法 收集2009年6月至2011年6月在我院住院的系统性红斑狼疮患者46例的临床资料进行回顾性分析,比较病情活动未合并感染者(未感染组28例)和合并感染者(感染组18例及同期门诊SLE稳定期患者对照组30例)的发热、皮疹、口腔溃疡、脏器损害等临床表现,同时分析患者的C反应蛋白(CRP)、血清降钙素原(PCT)、红细胞沉降率(ESR)、24h尿蛋白定量、补体C3、C4、免疫球蛋白、血清蛋白电泳、自身抗体等的变化.结果 SLE合并感染组患者的CRP与PCT均明显高于SLE未合并感染组及对照组[(52±15)mg/L比(17±6)、(7±2)mg/L;(1.80±1.16)μg/L比(0.26±0.24)、(0.11±0.08)μg/L,均P＜0.01].SLE合并感染组IgG、IgA、IgM、C3、C4补体、24 h尿蛋白及系统性红斑狼疮疾病活动指数评分与SLE未合并感染组差异均无统计学意义(均P＞0.05).结论 CRP、PCT在SLE合并感染时明显升高.在SLE活动时CRP大多正常或略高,但少数患者,尤其合并浆膜炎者的CRP水平可较高.CRP、PCT对于鉴别SLE活动与合并感染有重要的临床应用价值.     

妊娠合并系统性红斑狼疮68例临床特点及护理

系统性红斑狼疮（systemic lupus erythematosus，SLE）是一种多脏器多系统损害并伴多种免疫学指标异常的自身免疫性疾病，好发于生育期妇女。SLE患者虽然可以妊娠、分娩，但疾病常累及胎盘，易使胎儿宫内窘迫、发育迟缓，甚至致胎儿死亡；妊娠和分娩又会使SLE病情复发、加重。因此，对妊娠合并SLE的患者进行合理的治疗和护理一直是产科的一项重要课题，现将68例妊娠合并SLE患者护理经过总结如下。     

系统性红斑狼疮患者合并感染的危险因素分析

目的:探讨系统性红斑狼疮(SLE)合并感染的危险因素。方法:采用回顾性调查方法,通过单因素和多因素logistic回归方法对合并感染的SLE患者的病例资料、实验室检查、病情活动性和治疗经过进行分析。结果:SLE患者合并感染的发生率为51.4%,感染发生的常见部位为呼吸道和泌尿道,条件致病菌感染有增加趋势。多因素分析表明激素冲击治疗、年龄、应用广谱抗生素、住院时间延长、病情活动性与感染的发生密切相关(P<0.05)。结论:感染是SLE患者常见合并症,也是导致患者死亡的重要原因。特殊治疗方法、病情活动以及抗生素的不合理应用与感染的发生有直接关系。有效的预防和控制感染可以改善SLE患者的预后。     

Toll 样受体9在系统性红斑狼疮患者高人乳头瘤病毒感染中的作用

目的：初步探讨 TLR9在 SLE、HPV、SLE＋HPV 感染患者宫颈上皮细胞中的表达及意义。方法行子宫颈液基细胞学检查（LCT）的患者20例,均分为如下四组：SLE 组、SLE＆HPV 组、HPV 组、正常对照组四组：LCT 其中一份用于 LCT 检查,剩余的标本用于高危型人乳头瘤病毒（HR-HPV）及低危型人类乳头瘤病毒（LR－HPV）检测;另一份用于流式鉴定及胞内 TLR9受体检测。结果合并 HPV 阳性的患者其 SLEDAI 疾病活动性评分6（4～7）显著高于 HPV 阴性组2（0～3）,且更容易合并器官损伤,其中 SLE＆HPV 组共5例（100％）合并器官损伤≥2,而 SLE 组仅2例（40％）：合并 HPV 感染的 SLE 患者其病情复发指数 flare5例（100％）也明显高于 HPV阴性患者1例（20％）;同样,SLE＆HPV 组患者全部为 Anti—dsDNA 阳性（100％）,而 SLE 组仅1例（20％）阳性。流式 cytokeratin＋CD45-设门鉴定的上皮细胞内 TLR9表达的平均荧光强度,SLE＆HPV 组＜SLE 组＜ HPV 组＜正常对照组。结论下调的 TLR9受体可能与 HPV 逃避宿主免疫防御从而导致病情长期潜伏相关;作为核酸病毒,HPV 可能通过核酸特异性的 TLR9激活固有免疫和调节免疫系统,导致病情发作或者非活动性 SLE 的复发;多种因素包括病毒感染本身、药物因素以及病情活动复发均可致 SLE 患者体内 HPV 持续易感。     

神经精神性狼疮的处理(附6例报告)

系统性红斑狼疮（SLE）出现神经精神症状称神经精神性狼疮（NPL）是SLE病情严重的表现，一般发生于疾病的晚期及病情的活动期。在用糖皮质激素（简称激素）治疗过程中可诱发药物性神经精神症状，且与激素用量和疗程呈正相关。当SLE患者出现NPL，必须鉴别是SLE侵犯脑部所致还是由激素引起的副反应，尤其是以精神异常表现为主时，两者之间的鉴别是临床医生十分棘手的问题。本文将6例NPL的临床表现、处理、转归等报告如下。临床资料一、一般资料：本文6例SLE病人全部符合美国风湿病协会1982年提出的诊断修订标准。均为女性。年龄17～…     

系统性红斑狼疮合并肺部感染临床分析

系统性狼疮(SLE)是以自身免疫缺陷,多系统损害为特征的一种疾病,其治疗依赖激素及免疫抑制剂,因而感染成为此疾病的常见并发症,其中尤以肺部感染最为多见,现将52例SLE合并肺部感染总结如下。     

系统性红斑狼疮合并结核56例的饮食护理

系统性红斑狼疮（SLE）是一种临床表现有多系统损害症状的慢性系统性自身免疫性疾病。SLE患者大多存在免疫功能低下，容易并发结核。无论是结核还是SLE，饮食护理均是护理工作的重要内容，两种疾病同时发病后其饮食更为复杂多变，必须有专业的饮食护理，以促进疾病康复。笔者长期致力于这方面的工作，现总结对SLE合并结核患者的饮食护理经验，报道如下：     

系统性红斑狼疮并发新型隐球菌脑膜炎的临床研究

目的探讨系统性红斑狼疮（SLE）并发新型隐球菌脑膜炎的危险因素、临床特点及防治措施。方法回顾性分析8例SLE合并新型隐球菌脑膜炎的临床资料。结果 SLE患者的免疫功能低下、疾病的活动以及激素、免疫抑制剂或细胞毒性药、滥用抗生素以及肾功能异常,促进真菌繁殖,是其发病的主要危险因素。结论重视病情演化,及时诊断及正确合理的治疗有助于改善SLE合并新型隐球菌脑膜炎患者的预后。     

系统性红斑狼疮合并结核56例的饮食护理

系统性红斑狼疮(SLE)是一种临床表现有多系统损害症状的慢性系统性自身免疫性疾病[1]。SLE患者大多存在免疫功能低下,容易并发结核[2]。无论是结核还是SLE,饮食护理均是护理工作的重要内容,两种疾病同时发病后其饮食更为复杂多变,必须有专业的饮食护理,以促进疾病康复。笔者长期致力于这方面的工作,现总结对SLE合并结核患者的饮食护理经验,报道如下:     

硫唑嘌呤是系统性红斑狼疮患者新型隐球菌感染的危险因素

系统性红斑狼疮（SLE）复发和死亡的首要原因是感染。侵袭性真菌感染是一组疾病的统称,包括隐球菌、组织胞浆菌、曲霉菌和念珠菌感染。目前关于SLE患者侵袭性真菌感染情况的报道和研究几乎没有,SLE合并侵袭性真菌感染的相关因素也未明确。针对这一情况,JP Vinicki等人进行了一项研究,比较分析SLE合并侵袭性真菌感染组和未合并侵袭性真菌感染组,从而确定SLE患者合并侵袭性真菌感染组的危险因素,     

Emergence of targeted immune therapies for systemic lupus

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease, characterised by flares of rampant inflammation that can threaten, in an unpredictable manner, almost any organ in the body. Current standard of care is largely empiric, involving the use of corticosteroids and toxic immune suppressive agents that are widely acknowledged to have unacceptable side effects for long-term use. Recently, there have been significant advances in understanding the nature of some fundamental immune imbalances underlying the complicated clinical manifestations of SLE. Nevertheless attempts to develop and test more targeted, and potentially safer immune-modulating drugs for lupus have encountered significant obstacles, due to the lack of validated biological markers for disease flare and remission, and difficulties in the clinical assessment of the heterogeneous patients. In support of renewed interest in drug development for lupus, large collaborative groups have formed, and efforts are underway to develop objective biomarkers for SLE as well as to improve the standardisation and reproducibility of clinical outcome measures in multi-centre trials.     

Upcoming biological therapies in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune condition with unpredictable course, intermingled with flares and periods of remission. Although the prognosis of the disease has improved in the past decades, current therapies are still associated with treatment-related complications. Recently, there has been major progress in the understanding of the pathogenesis of SLE, paving the way for the development of new biological agents, potentially revolutionizing the treatment of SLE.This review summarizes available data on novel biological therapies for SLE, focusing on recent results from clinical trials.As a result of treatment strategies based upon an individualized therapeutic approach, it is hoped that the clinical view of SLE will change from a severe autoimmune disease to a condition in which significant damage, mortality and treatment related complications can be prevented in the majority of SLE patients.     

Treat-to-target in systemic lupus erythematosus: are we there yet?

The treat-to-target (T2T) strategy has proven benefits in several chronic medical illnesses including rheumatoid arthritis. Whether the T2T principle can be applied to SLE has become a recent topic of discussion. A European panel of rheumatologists agrees that treatment of SLE should target at multiple goals that include control of disease activity, prevention of disease flares, minimization of disease or treatment related comorbidity, and improvement of quality of life. Therapy of SLE should aim at remission or when remission cannot be achieved, the lowest possible disease activity that is assessed by a validated lupus activity index and/or organ-specific markers. However, owing to the clinical heterogeneity of SLE, there is still no consensus on the definition of remission or low disease activity state in individual organ-systems. In real life, agents readily available for therapy switching in SLE are limited. Moreover, no disease activity index is universally agreed upon for disease monitoring to make therapeutic decisions. Currently, clinical parameters for the assessment and monitoring of lupus renal disease appear to be more objective and evidence-based. A therapeutic target in terms of proteinuria and/or other renal parameters should be tested in randomized controlled trials for the proof of the T2T concept in SLE.     

Emerging therapies in systemic lupus erythematous: from clinical trial to the real life

Systemic lupus erythematous (SLE) is a chronic autoimmune disease characterised by multisystem involvement and a relapsing remitting course. SLE is a highly heterogeneous condition, with wide variations in both the presentation and severity of disease and the biological markers identified.

The use of biologics in SLE has lagged behind that of other rheumatological conditions such as rheumatoid arthritis, in part due to the diverse clinical manifestations of SLE, making it difficult to design appropriate trials for novel treatments. As such, broad immunosuppressive treatment regimens are still widely used in SLE. Nevertheless, in recent years, elucidation of some aspects of SLE pathogenesis have allowed the development of therapies targeted at molecular mediators of SLE. This review provides an update of biological available therapies and those currently under development.     

Targeted B-cell depletion therapy in childhood-onset systemic lupus erythematosus: progress to date

Childhood-onset systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease associated with significant morbidity and mortality with lupus nephritis being a major prognostic factor. Children with SLE tend to have more severe hematologic and renal involvement compared with adults. Although the morbidity and mortality have greatly improved over the last 20 years, recent studies show that there are still associated major risks from under treatment (with resultant severe flares of disease activity) and over treatment (with additional medication adverse effects including risks of severe infection; many of these patients have inherent abnormal complement pathways).Therapies used to treat children with SLE need to be individualized based on multiorgan involvement, severity of disease, history of disease flares, and knowledge of recent relevant clinical, hematologic, and immunologic parameters. These medications need to be the most effective treatments, allowing normal growth, development, fertility, and the avoidance of severe toxicity and future malignancies. Many toxic effects of current medications range from the well described Cushingoid features of corticosteroids to the gastrointestinal adverse effects of mycophenolate mofetil.In vitro studies have shown that rituximab causes B-cell depletion by mechanisms involving antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, and direct signaling leading to apoptosis. As the adverse effect profile of B-cell depletion with rituximab has been well described in adults and children with oncologic and other autoimmune diseases, initial pilot studies using rituximab in patients with refractory SLE have been carried out according to different protocols. Evidence to date in open studies demonstrates that targeted B-cell depletion therapy can be safe and efficacious as an addition to standard immunosuppressant agents in refractory childhood-onset and adult-onset disease. Although there are positive outcomes in using this therapy, caution is necessary with respect to minimizing the number of doses and treatments given to reduce the incidence of developing human anti-chimeric antibodies.The next phase for the clinical and research community are multicenter randomized controlled trials of rituximab in severe childhood SLE, such as a comparative trial of rituximab versus intravenous cyclophosphamide in patients both at presentation and with exacerbations of disease activity.     

LJP-394 (abetimus sodium) in the treatment of systemic lupus erythematosus

Renal disease is one of the most severe aspects of systemic lupus erythematosus (SLE), potentially leading to irreversible kidney failure. The standard of care for severe lupus nephritis involves the use of high-dose corticosteroids, cyclophosphamide and other immunosuppressive drugs. Although these drugs are effective in controlling disease activity in the majority of patients, up to 25% of patients treated with cyclophosphamide-based protocols develop renal insufficiency and end-stage renal disease, and treatment discontinuation is associated with the occurrence of flares. Furthermore, these therapies are associated with a high incidence of short- and long-term side effects. LJP-394 (abetimus sodium) is an investigational agent specifically designed to decrease anti-dsDNA antibody levels, and it is under development for the prevention of nephritic flares in patients with SLE since the early 1990s. The drug has been evaluated in 13 clinical trials that evaluated > 800 patients with SLE, over a 10-year time span. It is likely that LJP-394 might have a role in the prevention of renal flares in SLE patients, and if the initial data is confirmed in an ongoing trial, this drug could represent either a substitute for immunosuppressive drugs or could allow a reduction of their dose, thereby reducing the risks of short- and long-term side effects. This paper reviews the principal aspects of chemistry, pharmacokinetics, efficacy and safety of LJP-394, and analyses studies on animal models and clinical studies conducted in the last few years.     

Emerging biological therapies for systemic lupus erythematosus

Introduction: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with unpredictable disease course, intermingled with periods of remission and exacerbation. Current therapies for SLE are not ideal in terms of efficacy and toxicity. Although the prognosis of the disease has improved in the past decades, further improvement is hindered by the occurrence of organ damage as a result of persistent disease activity and treatment-related complications. Novel biological therapies targeting at higher treatment efficacy and fewer adverse effects are being developed.

Areas covered: This review summarizes recent data on novel biological therapies for SLE. The pitfalls of clinical trial design and future directions of the development of SLE therapeutics are discussed.

Expert opinion: The variable therapeutic response observed in SLE reflects the clinical and immunological heterogeneity of the disease. The treatment plan of SLE patients should be individualized, with the target of quenching out disease activity, minimizing disease flares, and treatment related morbidities. Despite the disappointment of recent clinical trials, avenues are being opened for novel agents that intervene at different levels of the pathophysiological cascade of SLE. With the availability of a new treatment armamentarium, it is hoped that the survival rate and quality of life of SLE patients can continue to improve.     

系统性红斑狼疮的疾病成本研究

系统性红斑狼疮是一种多系统、多器官受累的自身免疫性疾病。患者长期处于威胁生命的疾病复发和临床缓解交替出现的慢性过程之中。由疾病本身导致的长期治疗费用及丧失劳动能力引起的收入减少给个人及社会带来了极大的经济负担。研究和总结影响系统性红斑狼疮疾病成本的影响因素,评价增加疾病负担的风险,对于指导系统性红斑狼疮的临床治疗和节约社会卫生资源有着重要的意义。     

Antimalarial drugs in systemic lupus erythematosus: use in pregnancy.

The 4-aminoquinoline radical containing antimalarial drugs are also used in the management of various connective tissue diseases including systemic lupus erythematosus (SLE) and rheumatoid arthritis. These agents are particularly useful for the management of inflammatory polyarthritis and skin disease. By raising the pH in intracellular compartments, these drugs interfere with normal phagocytic function which consequently enables them to interfere with antigen processing. Other actions include inhibition of platelet aggregation, this is advantageous in patients with phospholipid antibodies (aPL) which are known to predispose patients to recurrent arterial and venous clinical thrombotic events. Hydroxychloroquine has also been demonstrated to reduce serum lipid levels including cholesterol, triglycerides and low density lipoproteins. As it is now known that patients with SLE are at risk for accelerated artherogenesis and premature heart disease, this action may be an added benefit for these patients. The use of the 4-aminoquinoline radical containing antimalarial drugs during pregnancy is controversial. It is known that these agents can cross the placenta and are deposited in fetal pigmented tissues. These findings have led to the recommendation that these agents should be discontinued in pregnancy for patients with connective tissue diseases even though they have long been recommended for malarial prophylaxis in pregnant women travelling to malarial infested areas. Flares of SLE disease have been documented when these agents are discontinued and as flares of SLE disease activity are known to be detrimental to pregnancy outcome in patients with SLE, it is our opinion that these drugs should not be discontinued during pregnancy in a patient with lupus, particularly when the known terminal elimination half life is 1 to 2 months.     

Serum and urinary cytokine levels of SLE patients

Systemic lupus erythematosus (SLE) is a chronic, relapsing, polysystemic autoimmune disease with various clinical signs. The prognosis of SLE patients is influenced by neuropsychiatric and renal involvement. Lupus nephritis (LN) is present in 40-60% of patients. Classical laboratory parameters are not sensitive and specific in prediction renal flares, over the last few years there has been a growing interest in searching novel lupus biomarkers predicting future flares. Our goal was to detect serum and urinary level of cytokines in 36 patients with lupus nephritis (34 female and 2 male, mean age: 43.36 +/- 11.53 years), 23 patients with SLE without renal involvement (19 women and 4 men, mean age: 54 +/- 8.71) (both groups followed by the 3rd Department of Internal Medicine, Division of Clinical Immunology, University of Debrecen) and 30 healthy controls (23 female and 7 male, mean age: 45.5 +/- 12.4). Serum IL-1 (interleukin), IL-2 (both p < 0.05), IL-6, IL-13 and IFN-gamma (p < 0.001) levels were significantly higher in lupus nephritis patients, as compared to patients with SLE without renal involvement and healthy controls. Urinary level of IL-1 and TNF-alpha were significantly higher in SLE patients without renal disease (p = 0.012 and p < 0.001), while urinary IFN-gamma was significantly higher in LN patients (p = 0.002). Measurement of IL-6 level in SLE patients could help to predict future renal involvement of SLE patients.