重症药疹的研究进展

重症药疹主要包括中毒性表皮坏死松解型、重症多形红斑型、Stevens-Johnson综合征及剥脱性皮炎型。本文就有关重症药疹的历史、发病情况、病因、并发症和后遗症、鉴别诊断及治疗等方面研究进展现状作一简单综述。     

重症药疹58例临床分析

目的探讨重症药疹的致敏药物、发生规律、临床特征和治疗措施。方法对1990年12月-2013年4月本院收治的58例重症药疹患者的临床资料进行回顾性分析。结果 58例重症药疹患者中,以重症多形红斑(SJS,25例,43.10%))最多见。致敏药物以抗癫痫药(25.86%)和抗菌药物(25.86%)为主,其次是解热镇痛药(17.24%)。黏膜损害和肝功能损害是最常见的并发症。重症药疹均给予系统用糖皮质激素治疗,SJS组8例、TEN组4例以及DIHS组2例给予激素联合人免疫球蛋白治疗。结论重症药疹中以SJS居多。抗癫痫药物、抗菌药物以及解热镇痛药是引起重症药疹最常见的药物,系统应用糖皮质激素尤其是联合人免疫球蛋白治疗重症药疹有效。     

灰黄霉素致重症药疹1例

患者，女，44岁，主因面部、上肢大疱性皮损就诊于我院急诊科，后转入我科，详细询问病史，因治疗甲癣口服灰黄霉素（西安利君制药股份有限公司）5片／次，每日3次后第二天出现皮损。患者否认其他及药物过敏史。体检：一般情况良好。皮肤科情况：整个面部、双臂至手臂及背部可见大小不等、大的约鸡蛋大小松弛性水疱，部分疱已破损，疱液流出，后背呈鲜红色（图1、图2），用手触合成片状皮损，双眼及口腔黏膜未见糜烂渗出，查血常规：单核细胞11．4％，白细胞正常，嗜酸细胞未检出。尿常规：尿潜血（＋＋＋）。根据患者主诉，原因明确，诊断为重症药疹（光感型）。     

重症药疹68例临床分析

目的 :　探讨重症药疹的致病药物、临床特征及疗效相关因素。方法 :　回顾性分析 6 8例重症药疹患者临床资料 ,并与同期住院 16 5例非重症药疹患者进行比较。结果 :　 6 8例患者男女之比为1:1.1,平均发病年龄为 41.9± 2 1.2 ,皮质类固醇治疗剂量相当泼尼松 1.79± 1.0 1mg kg d ,痊愈率83.8%。与非重症药疹相比 6 0岁以上发病率、致病药物、高烧、并发症和粘膜损害的发生率、皮质类固醇治疗剂量、治愈率有明显差异 (P <0 .0 1)。诱发因素为误诊、再次服用致病药物及治疗不利。结论 :重症药疹老年人发病率高 ,致病药物最常见的是解热镇痛药 ,影响疗效的主要因素是并发症 ,重要的是早期足量短程皮质类固醇治疗以减少死亡率     

重症药疹72例临床分析

重症药疹临床上是指重症多形红斑型药疹、大疱性表皮松解型药疹和剥脱性皮炎型药疹 ,这些药疹是皮肤科重症 ,如诊疗不当 ,常导致严重后果 ,甚至死亡。近年来 ,随着新药不断出现 ,药疹患者有增多趋势 ,为探讨临床用药与重症药疹的关系 ,现将 1990年 1月～ 2 0 0 0年 5月我科所住 72例重症药疹患者情况进行分析如下。1　临床资料1.1　一般资料　 72例重症药疹患者均为本院住院病例 ,占同期住院药疹人数18.5 % ,其中男 39例、女 33例 ,年龄 6个月～ 6 9岁、平均 32岁。原发病多为感染性疾病、神经精神科疾病 (如癫痫病、神经痛等 )、外伤及其它…     

46例重症药疹临床分析

重症药疹包括大疱性表皮坏死松解型(BENL)、重症多形红斑型(SJS)、剥脱性皮炎型(ED)、药物超敏反应综合征(DIHS)及急性泛发性发疹性脓疱病(AGEP)等.重症药疹患者病情危重,易出现严重并发症,病死率较高,必须及时治疗[1].现就我院皮肤科2006年6月-2011年6月住院治疗的46例重症药疹患者的临床资料分析结果报告如下.     

重症药疹24例临床分析

目的了解重症药疹的临床特点及预后相关因素。方法对长海医院2002年8月~2005年8月收治的24例重症药疹的临床资料进行分析。结果24例重症药疹中剥脱性皮炎型药疹8例,大疱性表皮坏死松解型药疹2例,重症多形红斑型药疹14例。别嘌醇在致病药物中占首位,其他依次为头孢类、卡马西平、对乙酰氨基酚及其他类。结论预后与药疹类型、发病到足量激素治疗的时间、患者内脏累及的多少及伴随基础疾病有很大的关系;应用别嘌醇及抗生素等药物应慎重;早期足量应用糖皮质激素仍是治疗重症药疹的主要手段。     

甲氨蝶呤致重症药疹3例

报告3例甲氨蝶呤(MTX)导致的重症药疹.2例为女性患儿,年龄分别为6岁和9岁,1例为40岁男性患者,潜伏期分别为4、18、2 d,均先表现为手掌、足跖红色斑疹,2例后来发展为重症多形红斑型药疹,1例发展为中毒性表皮坏死松解症,均伴黏膜损害和骨髓抑制.给予糖皮质激素及对症治疗后,2例死亡,1例治愈.     

重症药疹45例临床分析

目的探讨重症药疹的发病特点、临床特征及预后的相关因素。方法对本科1996年7月-2010年3月收治的45例重症药疹患者的临床资料进行回顾性分析。结果致敏药物以抗生素最为常见,其次为解热镇痛药,中药过敏者数量多于以往文献报道;别嘌醇所致药疹潜伏期长,重症多形性红斑型为最常见的重症药疹。死亡3例,死因主要为感染和脏器衰竭。结论早期足量使用糖皮质激素有助于病情的控制,联用人免疫球蛋白对危重患者有效;预后与年龄、皮损范围、糖皮质激素的应用、有无继发感染和基础疾病及严重程度密切相关。     

重症药疹35例临床分析

目的：探讨重症药疹的临床特点及预后相关因素。方法：对临床收集35例重症药疹进行分析。结果：致敏药物以抗癫痫药为首位（占34．29％）；药疹类型以中毒性表皮坏死松解症（TEN）型最常见，各型药疹常伴系统损害；丙种球蛋白联合糖皮质激素治疗TEN型药疹疗效明显优于非丙种球蛋白治疗。结论：预后与药疹类型、基础疾病及治疗措施有很大关系，糖皮质激素治疗仍为首选，丙种球蛋白联合糖皮质激素治疗为重症药疹提供了更有效的方法。     

Oral manifestations of adverse drug reactions: guidelines

Background Adverse drug reactions are noxious and unintended responses to a medicinal product. Many drugs have the potential to induce adverse reactions in the mouth. The extent of such reactions is unknown; however, because a lot of them are asymptomatic, many are believed to go unnoticed. Adverse oral drug reactions are responsible for oral lesions and manifestations that can mime local or systemic disease. Their pathogenesis, especially of the mucosal reactions, is largely unknown and appears to involve complex interactions between the drug in question, other medications, the patient's underlying disease, genetics and lifestyle factors. Aim In this study, we have listed the principal signs and symptoms of oral and perioral adverse drug reactions and the responsible drugs. Diagnosis for adverse drug reaction is not easy given also the limited utility of laboratory tests. The association between a drug and an adverse drug reaction is mostly based on the disappearance of the reactions following discontinuance of the offending drug. Sometimes, it is useful to perform rechallenge tests reintroducing the drug to establish cause and effect. Conclusions Knowledge of adverse drug‐induced oral effects helps health professionals to better diagnose oral disease, administer drugs and improve patient compliance during drug therapy and may foster a more rational use of drugs.     

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.     

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.     

Patch testing in severe cutaneous adverse drug reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis

Patch testing may help to assess the culpability of a drug in an adverse reaction. Our aim was to study patch testing in severe cutaneous ad verse drug reactions [ADRs] (Stevens-Johnson syndromeitoxic epidermal necrolysis (SJS/TEN). acute genera exanthematous pustulosis (AGEP), and other cutaneous ADRs). 59 patients with cutaneous ADRs were included: 22 had SJS/TEN. 14 AGEP, and 23 other cutaneous ADRs. Patients were patch tested with the suspect drug and with H standard series of drugs. 2 patients among the 22 SJSTEN cases had a relevant positive test. 7 patients among the 14 AGEP cases had a relevant positive test. 6 patients among the 23 other cutaneous ADRs had a relevant positive test. Our results suggest that patch testing has a weak sensitivity in SJS'TEN and is not appropriate in these diseases. Patch testing seems more adapted to other cutaneous ADRs, such as AC it: P. in which the proportion of positive patch tests was significantly higher (P<0.02). Nevertheless, the difference of sensitivity of patch testing in SJS TEN, AGEP or other cutaneous ADRs could be linked not only to the clinical type of eruption, but also lo the different spectrum of culprit drugs in each type of eruption.     

Cutaneous adverse drug reactions during chemotherapy: consider non-antineoplastic drugs

Cutaneous adverse drug reactions (CADR) during chemotherapy are not rare, but difficult to manage. Case 1, a 49-year-old man was treated with 5-fluorouracil, irinotecan, and oxaliplatin for a pancreatic tumour. He developed a generalized urticaria during his seventh course of chemotherapy. 2 months later, skin tests determined a granisetron allergy with an ondansetron cross-reaction. Substituting the anti-emetic allowed continuation of the chemotherapy. Case 2, a 44-year-old woman, having recurring breast cancer that was treated with doxorubicin, and docetaxel developed a maculo-papular rash (MPR) the day after the first chemotherapy treatment. 2 weeks later, skin tests determined a corticosteroid class A allergy. Using a class C corticosteroid, no other reaction occurred. Case 3, a 44-year-old woman, having breast cancer treated with 5-fluorouracil, cyclophosphamide, and epirubicin developed an MPR after the second chemotherapy treatment. 12 days later, skin tests showed a granisetron allergy. Using alizapride, chemotherapy was continued with no further reaction. CADR necessitate a thorough investigation, modified according to the patient's chemotherapy treatment chronology and precautions while testing the molecules. Tests are rarely carried out, however, these tests allow for continuation of effective chemotherapy once the responsible agent has been determined. The 3 cases reported underline the role of complementary treatment and the necessity to test those molecules.