英利昔单抗-抗TNF—α嵌合性单克隆抗体治疗银屑病

英利昔单抗是一种鼠-人嵌合性单克隆抗体，他能通过结合肿瘤坏死因子(TNF)-α可溶性跨膜成分，抑制其与受体的结合而中和其生物活性。近来，在用英利昔单抗治疗其他相关疾病如Crohn病、银屑病性关节炎时发现银屑病皮损得到改善。且已有报道用英利昔单抗和甲氨蝶呤联合治疗银屑病取     

肿瘤坏死因子α拮抗剂所致皮肤不良反应及对策

肿瘤坏死因子α（TNF-α）是一种重要的细胞因子,在很多炎症性疾病中发挥重要作用。TNF-α拮抗剂作为生物制剂,近年来越来越多地用于类风湿关节炎、强直性脊柱炎［１］、克罗恩病、银屑病性关节炎、银屑病等疾病的治疗中。目前在我国上市的TNF-α拮抗剂包括益赛普（etanercept）、英夫利西单抗（infliximab）、阿达木单抗（adalimumab）三种,还有两种新型的TNF-α拮抗剂--赛妥珠（certolizumab）和戈利木（golimumab）已在国外上市。TNF-α拮抗剂的疗效与不良反应在既往的文献中已有较多报道,本文仅就其诱发的皮肤不良反应及对策做一综述……     

皮肤肿瘤患者血清肿瘤坏死因子-α活性检测

本文采用生物学活性方法,测定23例良性皮肤病和19例皮肤癌以及15例健康对照组血清TNFα,并对5例皮肤癌患者进行动态观察。其结果,皮肤良性肿瘤和皮肤癌患者血清TNTα水平显著高于健康对照组(P<0.01)。5例皮肤癌患者,经治疗后TNFα水平明显下降。     

细胞因子制剂相关的皮肤不良反应

细胞因子(cytokine)是细胞分泌的具有生物活性的小分子蛋白物质的统称。在很多情况下,各种免疫细胞之间的相互作用是由细胞因子介导的,它们在机体免疫反应中的作用相当广泛而复杂。近10年来随着重组细胞因子技术的发展,重组细胞因子已经成功用于临床,成为生物应答调节剂(biologicalresponsem odifier,BRM)中的一类重要的治疗制剂^[1]。     

阿达木单抗治疗银屑病的研究进展

银屑病是一种免疫介导的慢性炎症性疾病,对患者的生活质量造成很大影响。阿达木单抗是完全人源化抗肿瘤坏死因子-α的单克隆抗体,通过拮抗肿瘤坏死因子-α起作用,在美国被批准用于银屑病性关节炎、中重度斑块状银屑病等。阿达木单抗治疗银屑病起效较快、有较高的疗效,无特定的器官毒性、多数患者能够耐受,是一种较有发展前景的药物,但长期使用的安全性需要进一步观察。     

肿瘤坏死因子α抑制剂在皮肤科的应用

肿瘤坏死因子α是由多种细胞分泌的一种炎性因子,其抑制剂目前市场上有3种:英利昔单抗、依那西普及阿达木单抗.在皮肤科领域,美国食品药物管理局仅批准本类药物用于银屑病及银屑病性关节炎的治疗.但近年来越来越多的研究证实,TNF-α抑制剂可用于更多类型皮肤疾病的治疗,并成功治疗了如化脓性汗腺炎、坏疽性脓皮病和毛发红糠疹等多种其他类型的炎症性皮肤病.为此,概述肿瘤坏死因子α抑制剂在治疗皮肤疾病中的应用进展.     

凋亡学说与皮肤疾病

1　定义　细胞凋亡又称程序性细胞死亡 (ＰｒｏｇｒａｍｍｅｄＣｅｌｌｄｅａｔｈ .ＰＣＤ) ,是一种受基因控制的明显不同于坏死细胞死亡的细胞自灭过程。2　历史　 195 1年Ｇｌｕｃｋｓｍａｒｍ已观察并报告了这一现象 ,1972年ｋｅｒｒ首先提出凋亡的概念。凋亡原文ａｐｏｐｌｏｓｉｓ来源于希腊文、意为凋落的树叶。Ｋｅｒｒ并报告基底细胞癌的生长与细胞凋亡有关。 1974年Ｗｅｃｄｏｎ在病理切片中发现了胶样小体为凋亡小体 (ａｐｏｐｔｏｔｉｃｂｏｄｙ)。目前已知细胞凋亡受基因控制 ,是一种调控的细胞死亡过程 ,可以是生理性的 ,也可…     

抗α肿瘤坏死因子新靶点的进展

α肿瘤坏死因子是介导炎症反应和免疫反应的细胞因子,具有广泛的生物学活性。近年来,国内外抗α肿瘤坏死因子药物的研究进展迅速。从抑制α肿瘤坏死因子、肿瘤坏死因子前体生成、拮抗已经释放的肿瘤坏死因子作用方面简要介绍了目前研究的几个主要靶点及相关药物。     

疫苗相关的皮肤不良反应

【摘要】 疫苗作为预防疾病的重要措施,为人类预防各种传染病起到了巨大的作用,可产生有益的“免疫反应”,也可以产生不利甚至造成损害的不良反应,部分不良反应表现在皮肤。疫苗相关的皮肤不良反应临床表现多样机制复杂,本文主要阐述疫苗相关的皮肤不良反应的现状,有助于理解和认识疫苗不良反应的发生机制和不同的临床表现形式。     

肿瘤坏死因子-α与银屑病发病相关研究的Meta分析

目的评价细胞因子肿瘤坏死因子(TNF)-α与银屑病的关系。方法检索Cochrane图书馆、MEDLINE、CBMdisc等电子资料库,纳入所有研究TNF-α与银屑病关系的对照试验进行Meta分析。由3名评价者共同评价纳入研究质量。结果共纳入33个研究,993例银屑病患者,710例正常人。所有研究均未描述具体的随机方法及其使用的检测方法的特异度。银屑病组的血清(或血浆)中TNF-α浓度明显高于对照组[SMD1.04,95%CI(0.62,1.45)],细胞培养上清中稍高于对照组[SMD0.82,95%CI(0.10,1.55)]。结论现有研究结果显示,银屑病与TNF-α升高有关,但由于纳入研究存在选择偏倚、混杂偏倚和测量偏倚的中高度可能性,势必影响结果的可靠性,期待将来高质量的临床对照试验提供高质量的证据。     

Ischaemic/reperfusion injury:Role of infliximab

Ischaemia/reperfusion(I/R) injury is an underlying complex interrelated patho-physiological process which effects the outcome of many clinical situations, in particular transplantation. Tumor necrosis factor(TNF)-α is a pleiotropic inflammatory cytokine; a trimeric protein encoded within the major histocompatibility complex which plays a pivotal role in this disease process. This review is based at looking into an update, particularly the new insights in the mechanisms of action of TNF antagonist such as infliximab. Infliximab may thus play a dual role in the field of transplantation where it might not only down regulate the I/R injury, it may also have a beneficial role in the reduction of acute rejection.     

Segmental vitiligo after infliximab use for rheumatoid arthritis - A case report

The tumor necrosis factor alpha is a cytokine related to immune and inflammatoryprocesses by acting on different parts of the body. It is secreted by several celltypes including macrophages, lymphocytes, monocytes, neutrophils, dendritic cells,among others. Infliximab is a chimeric monoclonal antibody that specifically binds tosoluble and transmembrane tumor necrosis factor alpha form blocking its action. Inrheumatoid arthritis it is used because the cytokines that cause inflammation in thisdisease are regulated by tumor necrosis factor alpha and IL-1. We report the case ofa 46-year-old patient with rheumatoid arthritis who developed segmental vitiligoafter two months using infliximab. The event aims to alert to the existence of thisadverse effect that can be induced with the use of this medication.     

英夫利西单抗治疗重度斑块状银屑病的疗效和安全性及其对PD-1、PD-L1表达的影响

目的:探讨英夫利西单抗治疗重度斑块状银屑病的疗效和安全性及其对银屑病皮损组织中程序性死亡蛋白1（PD-1）及程序性死亡蛋白配体1（PD-L1）表达的影响。方法:2019年2-4月收集就诊于上海市皮肤病医院的17例重度斑块状银屑病患者,在第0、2、6、14、22、30、38、46周给予5 mg/kg英夫利西单抗静脉滴注治...     

Cutaneous manifestations of bartonellosis

Bartonellosis are diseases caused by any kind of Bartonella species. The infection manifests as asymptomatic bacteremia to potentially fatal disorders. Many species are pathogenic to humans, but three are responsible for most clinical symptoms: Bartonella bacilliformis, Bartonella quintana, and Bartonella henselae. Peruvian wart, caused by B. bacilliformis, may be indistinguishable from bacillary angiomatosis caused by the other two species. Other cutaneous manifestations include maculo-papular rash in trench fever, papules or nodules in cat scratch disease, and vasculitis (often associated with endocarditis). In addition, febrile morbilliform rash, purpura, urticaria, erythema nodosum, erythema multiforme, erythema marginatus, granuloma annularis, leukocytoclastic vasculitis, granulomatous reactions, and angioproliferative reactions may occur. Considering the broad spectrum of infection and the potential complications associated with Bartonella spp., the infection should be considered by physicians more frequently among the differential diagnoses of idiopathic conditions. Health professionals and researchers often neglected this diseases.     

Hidradenitis suppurativa responding to treatment with infliximab

A series of four cases of severe recalcitrant hidradenitis suppurativa treated with infliximab is presented. All patients had failed to respond to prior medical and surgical management. Baseline Quantiferon‐TB Gold and chest radiograph were carried out before commencement of treatment. No patients had associated Crohn's disease. All patients received induction infusions of infliximab 5 mg/kg at weeks 0, 2 and 6, followed by eight weekly maintenance infusions. The total number of infusions varied between 4 and 6. Skin photography with Sartorius scoring was used to evaluate response to treatment. All patients experienced marked improvement in their disease activity, with a mean 48% improvement in Sartorius score after one infusion (week 2, P < 0.01), and 70% improvement after three infusions (week 14, P < 0.01). Time to relapse following cessation of therapy ranged from 6 weeks to 4 months. Further studies examining the efficacy of infliximab and its effect on the course of the disease, particularly relating to long‐term management, are required.     

尖锐湿疣患者外周血白细胞分泌肿瘤坏死因子的体外研究

目的 研究尖锐湿疣复发与个体肿瘤坏死因子(TNF-α)分泌能力之间的关系,探讨尖锐湿疣的复发遗传基础。方法 利用体外多次传代培养的B淋巴母细胞样细胞株(LCL)作为TNF产生细胞,采用生物活性检测法检测LCL在LPS刺激下分泌TNF的能力。结果 实验结果显示尖锐湿疣患者组(包括复发患者和未复发患者)LCL的TNF分泌能力与正常人对照组差异无显著性(30.14%±12.27%与34.06%±12.06%,P=0.1136);而尖锐湿疣复发组的TNF分泌能力明显低于尖锐湿疣未复发组(24.75%±7.51%与36.62%±10.96%,P=0.00016);与正常人对照组比较,尖锐湿疣复发组的TNF分泌能力明显低下(P=0.00054),尖锐湿疣未复发组则与正常人对照组差异无显著性(P=0.3517)。结论 在清除治疗后残留HPV病毒的过程中,TNF参与的细胞免疫机制可能发挥重要作用。     

银屑病患者抗肿瘤坏死因子α治疗前后血清抗核抗体、抗dsDNA抗体及抗ENA抗体的变化

目的：观察银屑病患者接受抗肿瘤坏死因子α制剂治疗后抗核抗体（ANA）、抗dsDNA抗体和抗可提取性核抗原（ENA）抗体的变化。方法回顾分析32例银屑病患者,其中13例使用英夫利西单抗治疗,19例使用依那西普治疗。英夫利西单抗组第0、2、6周各用药1次,此后每隔8周用药,于每次用药前检测患者ANA、抗dsDNA抗体及ENA的情况和临床症状的变化。依那西普组每周用药2次,每3~6个月检测患者ANA、抗dsDNA抗体及ENA的情况和临床症状的变化。采用银屑病皮损面积和严重度指数（PASI）75、疾病活动评分（DAS）28评估临床疗效,间接免疫荧光法检测血清ANA水平,免疫印迹法和ELISA法检测抗dsDNA抗体水平,免疫印迹法检测抗ENA抗体水平。结果32例银屑病患者临床症状有不同程度缓解。32例抗TNF?α治疗的患者中有7例（21.9%）出现自身抗体,其中英夫利西单抗组中4例治疗（8.3±5.1）个月后出现自身抗体,3例ANA阳性,3例ENA阳性;依那西普组中3例治疗（9.0±3.0）个月后出现自身抗体,3例ANA阳性,1例ENA阳性。结论部分银屑病患者接受抗肿瘤坏死因子α制剂治疗后可出现自身抗体。     

Acute renal artery occlusion following infliximab infusion

We report the case of a 44-year-old male patient who presented with acute renal artery occlusion, 3 d after first injection of infliximab for steroid refractory attack of ulcerative colitis. Extensive work-up provided no evidence of predisposing factors for arterial thrombosis. Infliximab was thus suspected in the genesis of thrombosis, based on both intrinsic and extrinsic criteria. At month 3 after thrombosis with ongoing anticoagulation, angio-tomodensitometry showed complete revascularization of the left renal artery with renal atrophy. Renal function remained normal and the patient was still in steroid free remission on mercaptopurin monotherapy at maximal follow-up. Few thromboembolic events have been described with anti- tumor necrosis factor (TNF) agents, but it is the first case reported of renal artery thrombosis after infliximab infusion. In addition, we review thrombosis associated with anti-TNF agents.     

Cutaneous side-effects of treatment with lithium (author's transl)]

This paper describes the cutaneous side-effects which appeared in 5 patients under Lithium medication for manic-depressive disease: 2 cases with facial and dorsal acne, 1 case with generalized pruritus with burning sensations on the tongue and tumefaction of the lips, 1 case with endogenous generalized psoriasis and 1 case with palmo-plantar hyperkeratosis, ichthyosis and associated with euthyroid goitre. The lithium content of the tissues was assayed by flame spectrophotometry of calcinated biopsy material taken from the epidermis, the dermis and the subcutaneous adipose tissue from 4 of our 5 cases. An experimental investigation was carried out in guinea pigs fed with lithium salts during 6 months. The cation was assayed in samples of epidermis, dermis and perirenal adipose tissue. A study of the accumulation of lithium in epidermal, dermal and adipose tissue is thus added to the studies already published regarding the accumulation of this ion in other tissues.     

重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗中毒性表皮坏死松解症的临床疗效观察

【摘要】 目的 评价重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白（rhTNFR：Fc）治疗由药物引起的中毒性表皮坏死松解症（TEN）的疗效及安全性。方法 2009—2018年于苏州大学附属第二医院等8个中心纳入22例TEN患者,男10例、女12例,年龄22 ~ 75岁。采用rhTNFR：Fc 25 mg/次皮下注射治疗,首剂加倍,每3天1次,连续治疗6 ~ 8次。治疗前及治疗后第4、7、10、13、16、19、22、25天评估患者药疹面积和严重程度指数（DASI）评分、DASI改善指数（DASI50、DASI75、DASI90）;微量样本多指标流式蛋白定量技术检测外周血及疱液TNF-α水平。治疗过程中监测患者体温、皮疹变化及肝肾功能,记录不良事件。统计分析采用重复测量方差分析、配对t检验及Pearson相关分析。结果 22例患者中,未合并感染的20例在首次治疗后24 ~ 72 h体温停止升高,48 ~ 120 h恢复正常。22例首次治疗后24 ~ 48 h控制水疱新发,48 ~ 96 h皮肤颜色由鲜红色转为暗紫色,2周后皮损基本恢复正常。治疗2 ~ 4周,19例肝功能异常患者丙氨酸转氨酶及天冬氨酸转氨酶水平恢复正常。治疗4 ~ 13 d,7例肾功能异常者肌酐、尿素氮得到控制。治疗过程中,22例患者DASI评分逐渐下降（F = 532.81,P＜0.01）,从治疗前53.64 ± 8.67降至治疗25 d时的2.05 ± 1.21（t = 26.60,P < 0.001）。治疗第10天,22例（100%）改善达DASI50;治疗第19天,22例（100%）改善达DASI75;治疗第25天,20例（90.90%）改善达DASI90。22例患者外周血TNF-α水平随治疗时间的延长逐渐降低,从治疗前（33.95 ± 27.90） ng/L降至第25天时（2.38 ± 0.79） ng/L。治疗前15例患者疱液TNF-α水平为（111.99 ± 99.41） ng/L,疱液/外周血TNF-α比值1.83 ~ 28.21。治疗前,22例患者血清TNF-α水平与DASI评分无明显相关性（P = 0.10）,15例患者疱液TNF-α水平与DASI评分呈正相关（r = 0.59,P = 0.02）。治疗过程中未发现各种急性不良反应。22例患者均完成治疗并痊愈出院,出院后随访6个月未见复发及各种并发症。结论 rhTNFR：Fc是治疗由药物引起的TEN有效及安全的药物。