分子靶向抗肿瘤药物皮肤不良反应研究进展

近年来靶向抗肿瘤药物的使用在恶性肿瘤治疗中逐渐广泛,显著提高了患者生存率,但其引起的皮肤不良反应十分常见.根据作用靶点的不同对靶向药物不良反应进行分类分析,可找出其中的共性与个性,为皮肤科及肿瘤科医生提供诊疗的新思路.本文将分别从细胞膜相关抑制剂、胞内信号通路抑制剂及免疫检测点抑制剂三个方面综述临床上较为常见的靶向药物...     

固定性药疹致敏药物特异检测研究

应用不同可疑致敏药物作为抗原，采用微量全血培养法对３４例ＦＤＥ患者和２０名健康人进行ＳＬＴＴ检测研究。在实验组得到６１．７６％阳性结果，而健康对照组中无１例阳性，两组比较有显著性差异（Ｐ＜０．００５），初复发患者阳性率一致（Ｐ＞０．０５）。实验结果表明，微量全血培养法ＳＬＴＴ是一个特异性较强、安全、简便易行的特异性体外诊断方法     

皮肤药物不良反应的研究进展北大核心CSCD

药物不良反应十分常见,而皮肤是其重要的靶器官之一。皮肤药物不良反应（cutaneousadversedrugreaction,CADR）的发病机制复杂,临床表现多样,病因诊断较为困难。现概述CADR的特殊临床表现、发生机制和诊断方法。     

新型药物的皮肤不良反应

近年来,新型药物如免疫检查点抑制剂、分子靶向药物和生物制剂得到了极大的开发和推广,使得多种肿瘤性和难治性炎性疾病有了新的治疗选择,但其导致的皮疹等药物不良反应也较常见,轻者如痤疮、甲周炎、脱发等,较重者可出现Stevens-Johnson综合征、中毒性表皮坏死松解症等,影响患者生活质量,甚至威胁生命.因此,临床皮肤科医...     

药物皮肤不良反应的现状

新的治疗药物引起的皮肤反应 :抗病毒药物 :ＨＩＶ - 1蛋白酶抑制剂引起向心性肥胖综合征 ,以高脂血症及胰岛素抵抗为其生物学特征 ;非核苷类逆转录酶抑制剂奈韦拉平为一严重药疹高危险性相关药物 ,红斑为常见的不良反应 ,其发生率约 30 % ,但可引起重症多形红斑 (ＳＪＳ)及中毒性表皮坏死松解症 (ＴＥＮ)。抗惊厥药 :拉莫三嗪最常见不良反应为红斑 ,发生率约为 5% ,既往 3年有 10例ＳＪＳ及ＴＥＮ和 2例超敏综合征病例报道 ,尤其和丙戊酸联用时。氟喹诺酮类药 :导致光毒副作用发生率约 0 4 %～2 4 % ,其发生率的高低依次为替诺沙星 (高危…     

皮肤假性淋巴瘤的研究进展

皮肤假性淋巴瘤系指临床表现或组织病理类似恶性淋巴瘤,但又不满足恶性淋巴瘤诊断标准的一组淋巴细胞增生性病变.根据皮损中浸润淋巴细胞的主要类型,可分为皮肤B细胞假性淋巴瘤和皮肤T细胞假性淋巴瘤.临床表现多样,通常为红色斑块、丘疹或结节,头颈部多见.部分皮损有自愈性和复发性.组织学上可见淋巴细胞浸润,一般呈多克隆增生,但易与其他恶性疾病混淆.皮肤假性淋巴瘤尚无特效治疗方法,目前的治疗包括手术切除、光动力疗法、干扰素等,但可能复发.本病预后良好,但有转变为恶性淋巴瘤的可能,需要长期随访.     

皮肤药物不良反应的临床新发现

近年来，陆续有关于某些新药(少数为老药)出现不同形态的皮肤反应的文献报道，也发现了一些皮肤反应的新类型尤其是提出了药物超敏综合征的概念，本文复习文献对这些皮肤不良反应作一介绍。     

常见分子靶向抗肿瘤药物皮肤不良反应及诊治的研究进展

近年来,分子靶向抗肿瘤药物在肿瘤内科领域中发挥着重要作用。根据药物作用靶点不同,具体可分为表皮生长因子受体抑制剂(epidermal growth factor receptor inhibitors, EGFRIs)、酪氨酸激酶抑制剂(tyrosine kinase inhibitors, TKIs)、BRAF抑制剂、免疫检查点抑制剂等。不同种类药物诱发的皮肤不良反应谱有重叠,也有各自特殊表现。治疗原则依据皮损的严重程度,轻中度皮损仅对症处理,重度皮损应减药或停药。本文对分子靶向抗肿瘤药物所引起临床常见的皮肤相关不良反应及治疗进展进行综述。     

淋巴细胞转化试验在药疹诊断中的应用

引起药疹的药物种类繁多,但对其检测目前尚无确切可靠的实验室方法.本文通过国内外学者对淋巴细胞转化试验在药疹诊断中的研究,综述了淋巴细胞在药疹发生中的作用机制及该试验在药疹诊断中的应用范围、影响因素、灵敏性及特异性.     

Severe cutaneous adverse drug reactions

The clinical manifestations of drug eruptions can range from mild maculopapular exanthema to severe cutaneous adverse drug reactions (SCAR), including drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms, Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) which are rare but occasionally fatal. Some pathogens may induce skin reactions mimicking SCAR. There are several models to explain the interaction of human leukocyte antigen (HLA), drug and T‐cell receptor (TCR): (i) the “hapten/prohapten” theory; (ii) the “p‐i concept”; (iii) the “altered peptide repertoire”; and (iv) the “altered TCR repertoire”. The checkpoints of molecular mechanisms of SCAR include specific drug antigens interacting with the specific HLA loci (e.g. HLA‐B*15:02 for carbamazepine‐induced SJS/TEN and HLA‐B*58:01 for allopurinol‐induced SCAR), involvement of specific TCR, induction of T‐cell‐mediated responses (e.g. granulysin, Fas ligand, perforin/granzyme B and T‐helper 1/2‐associated cytokines) and cell death mechanism (e.g. miR‐18a‐5p‐induced apoptosis; annexin A1 and formyl peptide receptor 1‐induced necroptosis in keratinocytes). In addition to immune mechanism, metabolism has been found to play a role in the pathogenesis of SCAR, such as recent findings of strong association of CYP2C9*3 with phenytoin‐induced SCAR and impaired renal function with allopurinol SCAR. With a better understanding of the mechanisms, effective therapeutics and prevention for SCAR can be improved.     

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.     

Pharmacogenetics of cutaneous adverse drug reactions

Drug-induced hypersensitivity reactions are of major medical concern because they are associated with high morbidity and high mortality. In addition, individual patients' reactions are impossible to predict in each patient. In the field of severe cutaneous adverse drug reactions (cutaneous ADR) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug-induced hypersensitivity syndrome (DHIS) or drug rash with eosinophilia and systemic symptoms (DRESS), major advances have recently been gained through studies of an association between HLA alleles and drug hypersensitivity induced by specific drugs. The results of these pharmacogenomic studies allow prediction of the risk of adverse reactions in patients treated with certain drugs, including carbamazepine and other aromatic antiepileptic drugs, allopurinol and abacavir. However, different ethnic populations show variations in the genetic associations. A strong association between carbamazepine-induced SJS/TEN and HLA-B*1502 has been found in Southeast Asian patients but not in Caucasian and Japanese patients. Moderate associations between aromatic amine anticonvulsants and other HLA alleles have been proposed in Japanese patients. In contrast, HLA-B*5801 was found to be associated with allopurinol-induced cutaneous ADR, including SJS/TEN and DIHS/DRESS, in Caucasian and Asian patients, including the Japanese. These differences may, at least in part, be due to the differences in allele frequency in different ethnic populations. This article reviews the progress in pharmacogenomics, associated mainly with carbamazepine and allopurinol in different ethnic populations. Pharmacogenetic screening based on associations between adverse reactions and specific HLA alleles helps to avoid serious conditions associated with drug hypersensitivity.     

Negative predictive value of drug skin tests in investigating cutaneous adverse drug reactions

Summary Background Drug skin tests are useful in aetiological analyses of cutaneous adverse drug reactions to determine if the drug can be rechallenged, or to avoid a cross‐reaction with a substitute drug. Objectives To evaluate the negative predictive value of drug skin tests. Methods We retrospectively analysed the files of patients referred for drug reactions. We have enrolled those having strictly determined drug reactions with clinical features, delayed onset after drug intake, drug causality assessment, and negative drug skin tests followed by drug administration. Oral provocation tests or substitution tests with a drug of the same class as that suspected of causing the drug reactions were performed. Results From 1957 files analysed, 200 patients were included. After 403 patch tests, 403 prick tests and 304 intradermal tests, which were all negative, 260 oral provocation tests and 143 substitution tests were done; 307 different drugs were rechallenged. There were 42 positive drug re‐administrations in 27 oral provocation tests and 15 substitution tests. The negative predictive value of our drug skin tests was 89·6%. The negative predictive value for beta‐lactams was 87% for oral provocation tests and 96% for substitution tests, and for corticosteroids it was 100% and 74%, respectively. Conclusions  Negative drug skin tests do not eliminate the responsibility of a drug in drug reactions, and must be followed by drug re‐administration under hospital surveillance.     

伊马替尼引起的皮肤不良反应

甲磺酸伊马替尼是治疗慢性髓性白血病和恶性胃肠道间质肿瘤的一线用药,其皮肤黏膜不良反应的发生率较高。作者通过复习国内外文献描述该药导致的各种皮肤黏膜症状,并总结其发病机制和治疗对策,旨在帮助皮肤科医生提高对该药皮肤黏膜不良反应的认识,给予及时诊治。     

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。