帕博利珠单抗致严重免疫相关皮肤不良反应的文献分析

目的: 探讨帕博利珠单抗致Stevens-Johnson综合征(SJS)、中毒性表皮坏死松懈症(TEN)严重皮肤反应的临床特点,旨在为临床合理使用帕博利珠单抗提供参考。方法: 检索中国知网、维普、万方、PubMed、Web of Science 和Medline 等数据库,收集整理自数据库建库至2022年2月关于帕博利珠单抗致SJS/TEN的个案报道,分析该药致SJS/TEN的临床特点。结果: 共收集25例病例,其中帕博利珠单抗致SJS病例13例,TEN7例,SJS/TEN重叠征5例。3种类型SJS/TEN反应中TEN发生最早,中位发生时间为16(3,39)d;其次为SJS/TEN重叠征,发生时间为30(22.5,115)d;SJS反应最晚为55(7,106.5)d。25例中有22例(88.0%)伴随着黏膜受累,17例(68.0%)在黏膜受累或皮肤脱落之前出现前驱性皮疹。25例患者24例(96.0%)接受了全身性糖皮质激素治疗,9例(36.0%)接受静脉注射免疫球蛋白,4例(16.0%)接受免疫抑制剂。最终,25例患者中17例(68.0%)好转或痊愈,5例(20.0%)死亡,3例(12.0%)预后未知。结论: 帕博利珠单抗可诱发SJS/TEN,应注意黏膜损伤,异常皮疹等可能为SJS/TEN发生信号,除了全身性糖皮质激素治疗以外,静脉注射免疫球蛋白和环孢素治疗证实是有益补充。     

Common and uncommon adverse cutaneous reactions to erlotinib: a study of 20 Chinese patients with cancer

Objective: This study presented common lesions with systemic toxicities and uncommon adverse cutaneous reactions such as anaphylactic dermatitis in patients undergoing treatment with erlotinib for the benefit of practicing dermatologists and oncologists.

Methods: Adverse cutaneous reactions associated with erlotinib were reported in 20 Chinese patients with cancer.

Results: Adverse cutaneous reactions reported included six cases of anaphylactic dermatitis, 12 cases of acneiform rash, nine cases of xerosis, five cases of nail changes and four cases of hair changes. One case of anaphylactic dermatitis manifested as erythema with swelling on the face and neck, and others as erosive and scaly erythema on the fold of skin, or red macules, papules, plaques and pigmentation on the whole body. Clinical details indicated anaphylactic reactions, including a high percentage of eosinophils in the peripheral blood, eosinophilic infiltration in the dermis layer and good response to antihistamines and topical steroids. Systemic toxicities accompanied by cutaneous reactions occurred in five patients including one case of anaphylactic dermatitis and four cases of acneiform rash. Elevated hepatic enzymes were observed among all the patients with grade-3 or grade-4 acneiform rashes. One patient with anaphylactic dermatitis and one with acneiform rash discontinued erlotinib administration due to severe lesions, high fever or severe elevation of hepatic enzymes.

Conclusions: Anaphylactic cutaneous reactions caused by erlotinib are rarely described hitherto. Systemic toxicities should be emphasized especially in cases with severe skin disorders. Timely detection and appropriate early intervention in patients who develop severe cutaneous reaction while on erlotinib therapy should be considered clinically.     

司库奇尤单抗相关皮肤不良反应文献病例分析

目的：分析司库奇尤单抗所致皮肤药物不良反应（cutaneous adverse drug reactions,CADR）的发生发展特点,为临床安全合理用药提供参考。方法：检索中国知网（CNKI）、维普（VIP）、万方、PubMed和Web of Science数据库收载的司库奇尤单抗致CADR的病例报告和病例系列报告并进行分析。结果：收集司库奇尤单抗致CADR的个案报道16篇共18例,其中男性6例（33.33%）,女性12例（66.67%）,年龄分布以40岁以上居多（12例,66.67%）,发生时间主要集中在用药120 d以内（15例,83.33%）,CADR类型主要为感染相关（6例,33.33%）和免疫相关（11例,61.11%）2大类。患者经停药或减量和/或对症处理后均好转。结论：对于存在皮肤损伤、慢性感染、特异性皮炎及炎性肠病病史患者,应加强司库奇尤单抗使用后3个月内的药学监护,尤其应重点关注40岁以上人群,避免严重CADR的发生,保证临床用药安全。     

信迪利单抗相关皮肤不良反应文献分析

目的 分析信迪利单抗引起的皮肤药物不良反应（CADR）的发生特点与治疗转归,为临床合理使用信迪利单抗提供参考。方法 检索中国知网（CNKI）、万方、维普（VIP）、PubMed等数据库收载的信迪利单抗致CADR的文献报道并进行数据分析。结果 收集信迪利单抗导致CADR的个案报道15篇,涉及患者15例,其中男性9例（60.00%）,女性6例（40.00%）,年龄分布以50岁以上居多（11例,73.33%）,发生时间主要集中在用药84 d以内（14例,93.33%）,CADR类型以中毒性表皮坏死松解症和大疱性类天疱疮最常见,分别有6例（40.00%）和2例（13.33%）。13例患者经停药和/或对症处理后均好转,1例患者因Stevens-Johnson综合征死亡,1例患者因中毒性表皮坏死松解症死亡。结论 信迪利单抗可诱发CADR,应注意红斑、黏膜损伤、皮疹、水疱等可能为CADR发生的信号,除了全身性糖皮质激素治疗以外,静脉注射用人免疫球蛋白和肿瘤坏死因子-α(TNF-α)抑制剂也可作为CADR的补充治疗。     

新型冠状病毒疫苗相关的皮肤不良反应分析

目的探讨巢湖市接种新型冠状病毒疫苗(新冠疫苗)后皮肤不良反应( CADRs)的发生情况。方法选取 2021年 1― 12月在安徽医科大学附属巢湖医院就诊的接种新冠疫苗后发生 CADRs病人 270例,并对其临床资料进行统计分析。结果 270例 CADRs病人中男 112例( 41.48%)女 158例( 58.52%)年龄范围为 4~90岁,年龄( 44.04±21.41)岁; CADRs发生时间主要集中在新冠疫苗接种后7d内(216例,8,0.0%); CADRs类型,主要包括荨麻疹( 85例, 31.48%)、接种部位局部红肿( 80例,29.63%)、非特异性皮疹( 78例, 28.89%)等;根据药物不良反应关联度评价,将皮疹表现类型分为很可能、可能及不明确三种,其中很可能的皮疹( 80例, 29.63%)、可能( 177例, 65.56%)、不明确( 13例, 4.81%)。根据引起皮肤不良反应的疫苗种类分为灭活疫苗( 142例, 52.60%)、重组疫苗( 128例, 47.40%);引起 CADRs的新冠疫苗接种剂次以第 1剂次居多( 178例, 65.92%)。结论接种新冠疫苗后发生的 CADRs中,以接种灭活疫苗多见,第 1剂次居多,多见于中年女性,临床症状以荨麻疹表现最常见。所有病人经有效治疗均痊愈,且不遗留后遗症。应正确看待疫苗接种引起的 CADRs,鼓励全员积极接种疫苗,共筑免疫屏障。     

HLA-B*1502等位基因与中国南方汉族癫痫患者拉莫三嗪皮肤不良反应关联性的Meta分析

目的:系统评价HLA-B*1502等位基因与中国南方汉族拉莫三嗪所致皮肤不良反应(LTG-cADRs)的关联性。方法:通过计算机全面检索PubMed、Embase、The Cochrane Library、中国期刊全文数据库(CNKI)、中国科技期刊全文数据库(VIP)、万方数字化期刊全文库(WanFang Data),检索时间截止2015年 5月31日,并采用STATA SE 12.0软件进行Meta分析。结果:共纳入7个病例对照研究,107例LTG-cADRs癫痫患者,包括25例史蒂文斯-约翰逊综合征/中毒性表皮坏死松解症(SJS/TEN)患者,1例药物超敏反应(HSS)患者,81例斑丘疹(MPE)患者,213例拉莫三嗪耐受(LTG-Tolerant)癫痫患者,Meta分析结果显示,在中国南方汉族癫痫患者中HLA-B*1502等位基因与LTG-SJS/TEN存在显著相关性(OR=4.44,95% CI:1.66~11.87, P=0.003)。而HLA-B*1502等位基因与LTG-MPE不存在显著相关性(OR=0.85,95% CI:0.29~2.48, P=0.759)。结论:在中国南方汉族人群中,HLA-B*1502等位基因与LTG-cADRs存在一定的关联性。     

福建汉族人群服用别嘌醇引起严重皮肤不良反应与HLA-B*5801关联性

目的:探讨福建汉族人群服用别嘌醇引起严重皮肤不良反应(SCADRs)与标志基因HLA-B*5801关联性。方法:收集2012年1月—2013年5月期间福建汉族人群中有服用别嘌醇史住院患者的血液样本,经皮肤科确诊为单一别嘌醇所致SCADRs的患者8例归入别嘌醇重症药疹组,包括剥脱性皮炎(ED)3例,斯-约综合征(SJS)1例,中毒性表皮坏死松解症(TEN)1例,SJS /TEN 3例。期间抽取服用别嘌醇14 d以上未出现皮肤不良反应的患者16例归入耐受组。健康人群318名归入健康对照组。入组患者DNA用聚合酶链-限制性长度多态性法进行标志基因检测,聚合酶链-直接测序法验证检测结果。分析该地区人群服用别嘌醇致SCADRs与HLA-B*5801的关联性。结果:重症药疹组与耐受组患者在性别、年龄、药物过敏史、肾功能、日剂量及药物暴露天数之间均无统计学差异(P>0.05)。别嘌醇重症药疹组100.0%(8/8)患者携带HLA-B*5801基因,别嘌醇耐受组18.8%(3/16)携带(OR=65.57,95% CI:6.7~641.94,敏感度100%,特异度81%,P=0.000 2),福建健康汉族人群20.4%(65/318)携带(OR=65.79,95% CI:13.71-315.77,P=0.000 1)。结论:福建汉族人群服用别嘌醇所致SCADRs与携带HLA-B*5801关联性较高,提示该基因检测结果阳性患者应尽量避免服用别嘌醇,以降低发生严重不良反应的风险。     

碘海醇致严重不良反应65例文献分析

目的：了解碘海醇致严重不良反应（ADR）的情况,分析其特点和相关因素,促进临床合理用药。方法：采用文献学计量方法,对国内公开报道的65例碘海醇致严重ADR进行总结性分析。结果：碘海醇致严重ADR中,全身性损害41例,神经系统损害10例,呼吸系统损害8例,泌尿系统损害3例,皮肤附件、血液及消化系统损害各1例。结论：碘海醇致全身性、神经系统、呼吸系统损害较为多见,占总ADR分别为63.08%,15.38%,12.31%;碘海醇ADR前3位依次为过敏性休克、神经系统和呼吸系统损害,占总ADR78.46%。     

35例沙利度胺致药品不良反应/不良事件国内文献分析

目的：探讨沙利度胺致药品不良反应/不良事件（ADR/ADE）的一般特点和规律,为临床合理用药提供参考。方法：通过检索1989-2016年《中国期刊全文数据库》和维普数据库,对收集到的35例沙利度胺致ADR/ADE的文献报道进行统计分析。结果：沙利度胺所致的ADR/ADE多发生在中老年患者（37.14%）;ADR/ADE临床表现居前三位的是：皮肤及其附件损害（26.47%）、心血管系统损害（22.06%）、泌尿系统损害（10.30%）。经与药品说明书对比,发现有重度心动过缓、尿失禁、严重皮肤损害、内分泌紊乱等在药品说明书不良反应项相关风险中提示不足。结论：重视沙利度胺所致新的、严重的ADR/ADE,加强用药监测,以确保患者用药安全。     

127例药物不良反应分析

目的:分析引起不良反应的药物临床表现及防治。方法:回顾性分析临床用药发生不良反应的情况。结果:127例不良反应中,心血管药物77例,占60.63％;其它为内分泌、激素药物22例,占17.32％;抗生素11例,占8.66％;抗癌药3例,占2.36%;其它14例,占11.02％。重症不良反应48例,占37.79％;死亡6例,占4.72％.结论:心血管药物可能引致较严重的不良反应。     

喹诺酮类药物致Stevens-Johnson综合征和中毒性表皮坏死松解症文献分析

目的:分析喹诺酮类药物致Stevens-Johnson综合征(SJS)和中毒性表皮坏死松解症(TEN)不良反应的发生情况,为临床合理用药提供参考.方法:通过PubMed、Web of Science、Springer、Embase、Scopus、万方期刊论文数据库、维普期刊数据库、中国知网(CNKI)、中国生物医学文献...     

注射用生长抑素致严重不良反应2例

注射用生长抑素在临床应用广泛。恶心、呕吐、腹泻、口唇麻木、过敏、心律失常等为其常见的不良反应。本文报道２例生长抑素所致的药物不良反应,分别为生长抑素致心肌缺血及严重血糖降低,以期为临床应用提供参考。     

Frequency and cost of serious adverse drug reactions in a department of general medicine

Aims To assess the frequency and cost of drug reactions causing or prolonging hospitalization.
Methods All patients admitted to an internal medicine ward over 6 months were evaluated to identify serious adverse reactions. The number of drug classes on admission or at the time of the adverse drug reaction (ADR) was counted. Excess ADR-related hospital stay was computed using a) raw excess duration of hospital stay, b) correction of duration of hospital stay by age, sex, and number of drug classes, and c) estimation by investigator of excess hospital stay.
Results Three hundred and twenty-nine patients were evaluated: 212 male, 117 female, mean age 57.2 (males: 52.2, females: 66.2 ( P <0.05)), range 17–95 years. They stayed a total of 3720 hospital days (mean stay 11.3 days). 298 had no ADR (mean age 55.8, taking a mean of 2.7 drug classes, 10.7 days hospital stay); 31 had ADRs: in 10, the ADR caused admission in patients with a mean age of 84 ( P <0.01 vs the two other groups), taking 6.3 drug classes, who stayed a mean of 15.1 days; 21 occurred in hospital in patients with a mean age of 63.6, taking 4.2 drug classes ( P <0.01), who stayed a mean of 19.2 days ( P <0.01 vs patients without ADRs). In four the ADR was fatal (13% of ADRs, 40% of deaths). Raw ADR-related excess hospital stay was 318 days (8.6% of all hospital days), after multivariate correction 282 days (7.6% of all hospital days), and with investigator estimation 197 days (5.3% of all hospital days). Point prevalence of ADRs at admission was 3%, incidence rate in hospital was 5.6/1000 patient-days.
Conclusions 3% of the admissions were related to ADRs. In addition, 6.6% of hospitalized patients had significant ADRs. Between 5 and 9% of hospital costs were related to ADRs. In 24 of the 31 patients with ADRs (77%), these were related to the pharmacological properties of the involved drugs, and may possibly have been avoidable.     

Expression and inducibility of drug-metabolizing enzymes in preneoplastic and neoplastic lesions of rat liver during nitrosamine-induced hepatocarcinogenesis

The expression, inducibility, and regulation of four different cytochrome (cyt.) P-450 isoenzymes (PB₁, PB₂, MC₁, and MC₂) NADPH-cytochrome P-450 reductase, the glutathione transferases (GSTs) B and C and microsomal epoxide hydrolase (mEH_b) have been studied during nitrosamine-induced hepatocarcinogenesis using immunohistochemical techniques. The investigations revealed basic differences in the expression of the individual drug metabolizing enzymes in the course of neoplastic development. While the two GSTs and mEH_b were increased in all preneoplastic and benign neoplastic lesions, the levels of the distinct cyt. P-450 isoenzymes were characteristically different from each other. Following initial changes in the expression of these enzymes in early preneoplastic lesions (i. e., increase of cyt. P-450 PB₁ versus slight decrease of the other cyt. P-450 isoenzymes), a continuous reduction of all cyt. P-450 isoenzymes was observed during the further course of hepatocarcinogenesis. In progressed neoplastic nodules, all cyt. P-450-isoenzymes and NADPH cyt. P-450 reductase were decreased to varying extents.Treatment of animals with inducers of the monooxygenase system, such as phenobarbital, 3-methylcholanthrene and polychlorinated biphenyls, led to a rather heterogenous pattern of enzyme alterations in preneoplastic and neoplastic lesions. Following administration of phenobarbital, some islets responded to the same degree as the surrounding tissue, others were less or not at all inducible and a few of the lesions showed a prominent increase in cyt. P-450 PB₂ and NADPH-cyt. P-450 reductase levels. The interesting finding that these two enzymes always showed concurrent changes may be indicative of a common regulation. Similar to phenobarbital, an induction of cyt. P-450 isoenzymes within carcinogen-induced lesions was also observed following administration of 3-methyl-cholanthrene or polychlorinated biphenyls.The results demonstrate that drug-metabolizing enzymes are abnormally regulated in carcinogen-induced lesions. The multiplicity of enzyme deviations within individual lesions and especially the enzyme inducibility strongly suggest that the focal enzyme alterations result from genotoxic effects of the carcinogen on regulatory systems of a higher order rather than from mutational events in individual structural genes.Dedicated to Professor Dr. Herbert Remmer on the occasion of his 65th birthday     

536例头孢菌素类抗生素不良反应报告分析

目的 通过监测分析2004年1月-2005年12月山西省药品不良反应中心收到的药品不良反应报告中头孢菌素类抗生素所致不良反应及其相关因素，提示应正确使用头孢素类抗生素，以减少不良反应的发生。方法 采用回顾性调查方法对收到的头孢菌素类抗生素所致536例不良反应报告进行统计分折。结果 不良反应涉及药品18种，排前3位的是头孢曲松、头孢哌酮、头孢噻肟。药品不良反应累及人体的9个系统，比例最高的不良反应为变态反应。分析头孢菌素类抗生素的主要不良反应发生机制，为临床正确使用提供理论依据。结论 应关注头孢菌素类抗生素的不良反应，提高合理用药水平。     

南京地区358例严重药品不良反应/事件分析

目的 分析南京地区严重药品不良反应/事件的发生规律和特点,为推进药品不良反应监测工作和临床合理用药提供参考。方法 从国家药品不良反应监测系统库南京市药品不良反应监测中心调取并筛选2017年接收的严重药品不良反应/事件数据,将患者性别、年龄、怀疑药品名称、严重不良反应/事件名称、过程描述等信息进行统计分析。结果 358份严重药品不良反应/事件报告中,新的严重的不良反应占23.18%。60岁以上患者占48.60%。抗感染药物和抗肿瘤药物发生率较高,分别为115例（32.12%）和80例（22.35%）。静脉滴注为主要的给药方式（294例,82.12%）。在累及器官、系统中,全身性损害发生频次最高（195频次,28.97%）,其次为呼吸系统损害。结论 本次分析中严重药品不良反应/事件与患者年龄、给药途径、药品种类有关。医疗机构、经营企业和生产企业应加强严重药品不良反应/事件的监测,促进合理用药。     

HLA-A*31:01等位基因与拉莫三嗪所致皮肤不良反应关联性的Meta分析

目的：近年来,多项研究探讨了人类白细胞抗原HLA-A*31：01等位基因与抗癫痫药拉莫三嗪（LTG）所致皮肤型药物不良反应（cADRs）的关联性,但目前尚无确定的结论。因此,本研究拟通过一项Meta分析来系统评价HLA-A*31：01等位基因与拉莫三嗪所致皮肤不良反应（LTG-cADRs）的关联性。方法：通过计算机全面检索生物医学文献库PubMed、Embase、The Cochrane Library、Medline、CNKI、VIP和万方数据库,检索时间截止至2018年7月24日,纳入探讨了HLA-A*31：01与LTG-cADRs相关性的研究,并采用RevMan 5.3软件进行Meta分析。结果：共纳入5项病例对照研究,123例LTG-cADRs癫痫患者,137例拉莫三嗪耐受（LTG-Tolerant）癫痫患者,2 837例正常人群。Meta分析结果显示,在与LTG-Tolerant组的比较中,HLA-A*31：01基因型与LTG所致的cADRs存在显著相关性（OR=2.87,95% CI：1.11~7.40,P=0.03）。而在与正常人群组的比较中,HLA-A*31：01基因型与LTG所致的cADRs不存在显著相关性（OR=1.34,95% CI：0.34~5.28,P=0.67）。结论：本研究证明,HLA-A*31：01基因型可能是LTG所致cADRs的遗传风险因素。     

739例心血管类药物不良反应分析

目的:调查心血管类药物ADR的临床特点及产生原因。方法:从1998年～2001年4月公开发行的国内70余种医药学期刊中收集到心血管类药物不良反应个案776例,其中符合药物不良反应判定标准的739例,按照不良反应类别进行归纳、统计和分析。结果:心血管类药物的不良反应共涉及人体7个系统,其中呼吸系统所占的比例最大(29.8%);涉及相关药物六大类,以ACEI类药物较为常见(230例);重度不良反应46例,死亡15例,死亡占2.03％;51岁以上年龄组的不良反应(78.9％)高于其 他年龄组;口服给药(65.5％)较其他给药途径发生的比例高。结论:心血管类药物ADR的发生与药物的药理作用、给药途径、合并用药及患者的年龄、个体差异、饮食习惯等有关。