药物超敏综合征的遗传易感性研究进展

药物超敏综合征是一类严重的药物不良反应,患者有发热、皮肤损害、嗜酸粒细胞升高、淋巴结肿大及肝脏受累等,流行病学调查发现其死亡率高达10%~20%。近年来,研究发现药物超敏综合征的发生与个体的遗传易感性,尤其是某些人类白细胞抗原(HLA)等位基因有关。本文综述了卡马西平,别嘌呤醇,氨苯砜,阿巴卡韦及奈韦拉平所致药物超敏综合征的遗传易感性研究进展。     

药物不良反应的流行病学和发病机制研究进展

按照WHO国际药物监测合作中心的规定,药物不良反应（adverse drug reactions, ADR）指正常剂量的药物用于预防、诊断、治疗疾病或调节生理机能时出现的有害的和与用药目的无关的反应,约占所有住院原因的3% ～ 6%［１］。药疹也称药物性皮炎,即皮肤药物不良反应（cutaneous adverse drug reactions, cADR）,指药物进入人体后引起的皮肤和黏膜反应,是临床上最常见的药物不良反应。普通药疹包括发疹型、荨麻疹型、固定型等类型。重型药疹即严重皮肤不良反应（severe cutaneous adverse reactions, SCAR）,指皮损广泛、伴有系统损害的皮肤药物不良反应,包括Stevens-Johnson综合征（SJS）、中毒性表皮坏死松解症（TEN）、药物超敏综合征（DHS）、伴嗜酸性粒细胞增多和系统症状的药疹（DRESS）,最近急性泛发性发疹性脓疱病（AGEP）也被归于SCAR之列［2］……     

药物超敏反应综合征的护理体会

<正>药物超敏反应综合征(drug hypersensitivity syndrome.DHS)是一种伴随着药物的严重不良反应。是以全身广泛出皮疹,发热,淋巴结增大,嗜酸性粒细胞增多及肝、肾损害等多器官受累为特征的一种全身反应综合征。磺胺类药物、别嘌呤醇和抗惊厥类药物是最常引起DHS的药物。是一种严重的药物     

药物超敏综合征

药物超敏综合征（Drug—induced hypersensitivity syndrome,DIHS）,又称为伴嗜酸粒细胞增多和系统症状的药疹（drug rash with eosinophilia and systemic symptoms,DRESS）或药物引起的迟发性多器官超敏综合征（drug—induced delayed multiorgan hypersensitivity syndrome,DIDMOHS）,是一种具有发热、皮疹及内脏受累三联征的急性严重性药物不良反应。     

抗癫痫药物诱发高敏综合征1例临床分析

目的提升医务人员对于药物复杂不良反应的分析、监护和救治能力。方法以拉莫三嗪及丙戊酸钠先后引发的皮疹、红细胞形态学异常和药物高敏综合征的一名患者为例,介绍其起病及治疗过程,并分析其可能原因。结果考虑本例为拉莫三嗪及丙戊酸钠先后引发的新型、严重不良反应。结论通过对药物复杂不良反应病例的监护管理,能够提升疾病治疗水平,降低药源性疾病带来的损害。     

血液灌流联合血液透析治疗别嘌醇所致药物超敏反应综合征一例

别嘌醇引起药物超敏反应综合征（DIHS）又称为DRESS综合征（drug rash with eosinophilia and systemic symptoms）是一种由别嘌醇诱发的以急性广泛的皮损,伴发热、肝、肾、肺等多脏器受累、淋巴结肿大为特征的严重全身性药物不良反应。我们于2012年12月收治1例,现报道如下……     

药疹的发病机制进展

正皮肤是药物不良反应最常见的靶器官之一[1]。皮肤受累的药物不良反应俗称"药疹",大多数药疹是一个良性病程。然而有2%的药疹却是严重而致命的,称为"重症药疹",特指以下4种:Stevens-Johnson综合征(SJS)、中毒性表皮坏死松解症(TEN)、急性泛发性发疹性脓疱病(AGEP)、伴嗜酸性粒细胞增多和系统反应的综合征(DRESS)。近年来,对药疹病理生理学机制的研究取得了较大的进展,主要包括以下     

二甲胺四环素引起的严重不良反应

常用于长期治疗寻常痤疮的二甲胺四环素除了可引起恶心、呕吐、眩晕、光敏反应、色素沉着和皮疹外,文献报道还可引起虽然少见但严重的不良反应有肺炎、肝毒性、Sweet综合征、超敏反应综合征(HSR)、血清病样反应(SSLR)和药物诱发的狼疮(DIL)等。为了识别这些严重的不良反应,作者报道了HSR、SSLR和DIL     

布洛芬混悬液致药物超敏反应综合征1例

正药物超敏反应综合征(drug-induced hypersensitivity syndrom,DIHS)是一种临床较为少见的严重药物不良反应。DIHS主要由别嘌醇、卡马西平、苯妥英钠等少数药物引起,曾有布洛芬引起DIHS的报道,而由布洛芬混悬液所致患者尚未发现有文献报道。布洛芬混悬液的不良反应有过敏性休克、消化道出血、粒细胞减少症、高热惊厥等。笔者收治了1例由布洛芬混悬液所致的DIHS,现报告如下。     

卡马西平致药物超敏反应综合征1例

药物超敏反应综合征(Drug Hypersensitivity Svndrom,DHS)是一种严重的药物不良反应,具有发热、皮疹及内脏受累三联症状的急性、潜在致死性特异不良药物反应,称之为DHS,临床上少见,我院于2009年11月收治1例,现报道如下.     

寻常型银屑病患者171例阿维A治疗相关不良反应及停药原因分析

目的:分析寻常型银屑病患者阿维A治疗相关药物不良反应（ADR）及停药原因。方法:收集广西医科大学第一附属医院2014—2019年使用阿维A治疗的寻常型银屑病患者292例,回顾性分析其中符合纳入与排除标准且能够定期随访的193例患者的临床资料,统计用药期间出现的ADR及停药原因。结果:193例中171例出现519例次AD...     

Adverse drug reactions in dermatology

Adverse drug reactions (ADRs) – that is, unintended and harmful responses to medicines – are important to dermatologists because many present with cutaneous signs and because dermatological treatments can cause serious ADRs. The detection of ADRs to new drugs is often delayed because they have a long latency or are rare or unexpected. This means that ADRs to newer agents emerge only slowly after marketing. ADRs are part of the differential diagnosis of unusual rashes. A good drug history that includes details of drug dose, time‐course of the reaction and factors that may make the patient more susceptible, will help. For example, Stevens–Johnson syndrome with abacavir is much commoner in patients with HLA‐B*5701, and has a characteristic time course. Newer agents have brought newer reactions; for example, acneiform rashes associated with epidermal growth factor receptor inhibitors such as erlotinib. Older systemic agents used to treat skin disease, including corticosteroids and methotrexate, cause important ADRs. The adverse effects of newer biological agents used in dermatology are becoming clearer; for example, hypersensitivity reactions or loss of efficacy from antibody formation and progressive multifocal leucoencephalopathy due to reactivation of latent JC (John Cunningham) virus infections during efalizumab treatment. Unusual or serious harm from medicines, including ADRs, medication errors and overdose, should be reported. The UK Yellow Card scheme is online, and patients can report their own ADRs.     

Adverse cutaneous drug eruptions and HIV: a clinician's global perspective

Adverse drug reactions (ADRs) are common and mostly avoidable. Some ADRs cannot as yet be predicted, but at-risk populations/patients and high-risk drugs are identifiable. HIV-infected patients are at risk of developing cutaneous ADRs, especially Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug hypersensitivity syndrome. Multiple factors of causation variably present in patients with HIV infection best explain the pathogenesis of these cutaneous ADRs. When no effective alternate therapy is available, drug rechallenge in HIV-infected patients can be attempted with little morbidity or mortality if done according to rationalized protocols.     

Life-threatening acute adverse cutaneous drug reactions

Adverse cutaneous reactions to drugs are frequent, affecting 2% to 3% of all hospitalized patients. Fortunately, only about 2% of adverse cutaneous reactions are severe and very few are fatal. Stevens-Johnson syndrome and toxic epidermal necrolysis are severe life-threatening diseases with a mortality rate reaching 30%, and only prompt recognition and diagnosis, withdrawal of the offensive drug, and referral to an intensive care unit or burn care unit might improve the prognosis and save the patient's life. Drug eruption with eosinophilia and systemic symptoms syndrome, formerly termed drug hypersensitivity syndrome, is a rather distinct severe adverse drug reaction (ADR) characterized by eruption, fever, lymph node enlargement, and single or multiple organ involvement, with a high morbidity and a mortality rate of 10%. These severe ADRs, together with serum sickness-like syndrome, are discussed in this review. Other severe reactions, such as anaphylaxis and vasculitis, are discussed elsewhere in this issue. Although most of the readers, particularly those in the outpatient arena, will not be treating these patients, they are the ones who will see them first, diagnose them, realize the potential danger in their condition, and refer them to the appropriate treatment venue. Therefore, dermatologists should be familiar with these conditions and be prepared to handle them adequately.     

Causality Assessment of Cutaneous Adverse Drug Reactions

Background

Cutaneous adverse drug reactions (ADRs) are the most common adverse reactions attributed to drugs. A systematic and effective approach to a patient with suspected drug eruption allows for prompt recognition, classification and treatment of cutaneous ADRs. A standardized and effective approach for objective causality assessment is necessary to make consistent and accurate identification of ADRs.

Objective

Although the Naranjo algorithm is the most widely used assessment tool, it contains many components which are not suitable for clinical assessment of ADRs in Korea. The purpose of this study is to compare correlations of the Naranjo algorithm and the Korean algorithm to evaluate usefulness of both algorithms in order to make a causal link between drugs and cutaneous ADRs. In addition, this study classifies the clinical types and causative agents of cutaneous ADRs.

Methods

The authors retrospectively reviewed the clinical types and laboratory findings of patients who were diagnosed with cutaneous ADRs in the dermatology clinic at Gil hospital. One hundred forty-one patients were enrolled in this evaluation. The causal relationship of ADRs was assessed by using the Naranjo algorithm and Korean algorithm (version 2.0).

Results

A cross-tabulation analysis was applied to the Naranjo algorithm and Korean algorithm (version 2.0). Simple correlation analysis and a Bland-Altman plot were used for statistical analysis. Correlation analysis confirmed that the two assessment algorithms were significantly correlated. Exanthematous eruptions (68.8%), Stevens- Johnson syndrome (10.6%), and urticaria (8.5%) were the most common types of cutaneoues ADRs. The most common causative agents were antibiotics/antimicrobials, antipyretics/non-steroidal anti-inflammatory drugs, and central nervous system depressants.

Conclusion

The Naranjo algorithm and Korean algorithm (version 2.0) were significantly correlated with each other, and thus reliable assessment methods to determine cutaneous ADRs.     

Drug eruptions in the mature patient

The world’s population is now ageing at an unprecedented rate. Declining fertility and improved health and longevity have generated rising numbers and proportions of the older population in most parts of the world. With advancing age, however, comes an increasing incidence of disease (comorbidity or multimorbidity), an increasing use of medications (polypharmacy), and consequently an increase in adverse drug reactions (ADRs). Age-related changes in pharmacodynamics and pharmacokinetics (eg, volumes of drug distribution, metabolism and clearance, altered drug responsiveness and toxicity) and greater vulnerability to ADRs are other reasons for the higher incidence of ADRs in the elderly compared with young adults. Because the clinical patterns of ADRs are very similar for all age groups, including the elderly, the present review will deal mainly with statistics and numbers, rather than the clinical and/or disease patterns.     

Cutaneous adverse drug reactions seen in a tertiary hospital in Johor,Malaysia

Background Adverse drug reactions are most commonly cutaneous in nature. Patterns of cutaneous adverse drug reactions (ADRs) and their causative drugs vary among the different populations previously studied. Objective Our aim is to determine the clinical pattern of drug eruptions and the common drugs implicated, particularly in severe cutaneous ADRs in our population. Materials and Methods This study was done by analyzing the database established for all adverse cutaneous drug reactions seen from January 2001 until December 2008. Results A total of 281 cutaneous ADRs were seen in 280 patients. The most common reaction pattern was maculopapular eruption (111 cases, 39.5%) followed by Stevens‐Johnson Syndrome (SJS: 79 cases, 28.1%), drug reaction with eosinophilia and systemic symptoms (DRESS: 19 cases, 6.8%), toxic epidermal necrolysis (TEN: 16 cases, 5.7 %), urticaria/angioedema (15 cases, 5.3%) and fixed drug eruptions (15 cases, 5.3%). Antibiotics (38.8%) and anticonvulsants (23.8%) accounted for 62.6% of the 281 cutaneous ADRs seen. Allopurinol was implicated in 39 (13.9%), carbamazepine in 29 (10.3%), phenytoin in 27 (9.6%) and cotrimoxazole in 26 (9.3%) cases. Carbamazepine, allopurinol and cotrimoxazole were the three main causative drugs of SJS/TEN accounting for 24.0%, 18.8% and 12.5% respectively of the 96 cases seen whereas DRESS was mainly caused by allopurinol (10 cases, 52.6%) and phenytoin (3 cases, 15.8%). Discussion The reaction patterns and drugs causing cutaneous ADRs in our population are similar to those seen in other countries although we have a much higher proportion of severe cutaneous ADRs probably due to referral bias, different prescribing habit and a higher prevalence of HLA‐B*1502 and HLA‐B*5801 which are genetic markers for carbamazepine‐induced SJS/TEN and allopurinol‐induced SJS/TEN/DRESS respectively. Conclusion The most common reaction pattern seen in our study population was maculopapular eruptions. Antibiotics, anticonvulsants and NSAIDs were the most frequently implicated drug groups. Carbamazepine and allopurinol were the two main causative drugs of severe ADRs in our population.     

Patch testing with carbamazepine and its main metabolite carbamazepine epoxide in cutaneous adverse drug reactions to carbamazepine

The value of skin tests in the diagnosis of adverse drug reactions (ADRs) has been limited. Lack of knowledge as to the nature of drug allergens has contributed to these limitations. Several reports have addressed the roles of metabolites in cutaneous ADRs and skin testing. We evaluated the role of a carbamazepine (CBZ) metabolite on the results obtained from patch tests, using CBZ and its main metabolite 10, 11-epoxide of CBZ (CBZ-epoxide), on 13 patients with CBZ-induced drug eruptions and 39 controls with no CBZ-induced cutaneous ADRs. 10 of the 13 patients showed a positive reaction, and 2 of the 10 patients had a reaction to the CBZ-epoxide only and 1 to both CBZ and CBZ-epoxide. None of the 39 controls displayed any reactions to either CBZ or CBZ-epoxide. Patch testing of suspected drugs, as well as their available metabolites, would be helpful in improving the results.     

Do Women Have More Adverse Drug Reactions?

Up to 5% of all hospital admissions are the result of adverse drug reactions (ADRs). Identifying those factors which may predispose to ADRs is essential for risk management. Amongst the known risk factors for adverse reactions are increasing age, polypharmacy, liver and renal disease as well as being female. Female patients have a 1.5- to 1.7-fold greater risk of developing an ADR, including adverse skin reactions, compared with male patients. The reasons for this increased risk are not entirely clear but include gender-related differences in pharmacokinetic, immunological and hormonal factors as well as differences in the use of medications by women compared with men. Women generally have a lower lean body mass, a reduced hepatic clearance, have differences in activity of cytochrome P450 (CYP) enzymes (40% increase in CYP3A4, varied decrease in CYP2D6, CYP2C19 and CYP1A2), and metabolize drugs at different rates compared with men. Other important factors include conjugation, absorption, protein binding and renal elimination, which may all have some gender-based differences. However, how these differences result in an increased risk of ADRs is not clear. There are pharmacodynamic differences between men and women, seen particularly with cardiac and psychotropic medications. There is no doubt that chlorpromazine, fluspirilene and various antipsychotics appear more effective in women than men for the same dosage and plasma concentration. Similarly, women are at increased risk of QT prolongation with certain anti-arrhythmic drugs compared with men even at equivalent serum concentrations. The mechanisms are unknown. Increasingly the evidence is that idiosyncratic drug reactions, particularly cutaneous reactions, appear to have an immunological etiology. It is possible that gender difference in T cell activation and proliferation account for this as well as the increased prevalence of skin diseases such as systemic lupus erythematosus and photosensitivity. Whatever the mechanism(s), it is important to be aware that gender is a significant factor in ADRs.     

索利那新联合坦索罗辛治疗经尿道前列腺电切术后膀胱过度活动症临床效果观察

目的：探讨索利那新联合坦索罗辛治疗经尿道前列腺电切术后膀胱过度活动症的临床效果。方法：选取2011年1月～2012年6月来我院进行经尿道前列腺电切术后出现膀胱过度活动症的患者48例,随机分为对照组和观察组,观察组给予索利那新5mg、坦索罗辛O．2rag,口服,1次／d,连续1周。对照组仅于疼痛时给予吲哚美辛栓剂对症治疗。治疗前后对两组患者进行膀胱过度活动症评分、生活质量评分及前列腺症状评分,评价药物的疗效及副反应发生情况。结果：48例患者均在住院部完成治疗,观察组用药时间约为7—10d,平均8．5d,待患者尿失禁、尿频等症状消失后停药。治疗前两组的OABSS评分、QOL评分、IPSS评分间无显著性差异（P〉0．05）,治疗后观察组的OABSS评分、QOL评分、IPSS评分均明显低于对照组,且存在显著性差异（P〈0．05）。观察组与治疗前比较,存在显著性差异,对照组三项评分与治疗前比较,无显著差异。观察组患者中仅1例出现口干症状,未见头晕、便秘、头痛等不良反应,其余患者未出现不良反应。结论：索利那新联合坦索罗辛用于治疗经尿道前列腺电切术后膀胱过度症疗效显著,可显著改善膀胱过度症状,不良反应低,值得临床推广应用。