A study of drug eruptions by provocative tests

Sixty cases of drug eruptions were observed during the period of one year. The incidence of drug eruption was 0.47% amongst all Dermatology O.P.D. attendances. Male to female ratio was 7:3. The highest number of cases were seen in the age group of 21-30 years. Fixed drug eruptions were the most frequent (58.3%), followed by urticaria and angioedema (20%). The drug sulphonamides (including co-trimoxazole) accounted for the highest number of eruptions (35%). The other drugs which were responsible for the eruptions, in order of frequency, were oxyphenbutazone, ampicillin, analgin, penicillin, tetracycline, ibuprofen, paracetamol, phenylbutazone, acetaminophen and phenobarbitone. The causative drug (s) were confirmed by provocation tests in 42 (70%) cases.     

Drug‐induced bullous pemphigoid in diabetes mellitus patients receiving dipeptidyl peptidase‐IV inhibitors plus metformin

Background Preclinical data and reports of adverse skin reactions in patients treated with dipeptidyl peptidase‐IV inhibitors (gliptins) have increased awareness towards skin‐targeting side‐effects of these anti‐hyperglycaemic drugs. Bullous pemphigoid (BP), sometimes drug‐induced, is the most commonly acquired autoimmune blistering dermatosis in western countries, typically a disease of the elderly people with significant morbidity and excess mortality. Objective To report the development of BP in five diabetics under gliptin (4 vildagliptin, 1 sitagliptin) plus metformin in fixed‐dose drug combinations. Case reports From March to August 2010 six out of nine newly diagnosed BP patients in our Department were type 2 diabetics. Five of them were on gliptin plus metformin (three different trade preparations) for 2–13 months prior to BP onset. In all cases BP was controlled after withdrawal of the suspected medication and relatively mild therapeutic interventions. In two cases the eliciting role of the preceding treatment is supported by evidence at the level ‘probable/likely’ according to the WHO‐UMC algorithm. Conclusions This is the first report of drug‐induced BP as a group adverse event of the gliptins plus metformin combination therapy for glycaemia control in type 2 diabetes mellitus patients.     

Variability in the clinical pattern of cutaneous side‐effects of drugs with systemic symptoms: does a DRESS syndrome really exist?

OBJECTIVE: To improve the definition of the various clinical patterns of patients with drug-induced cutaneous side-effects with systemic symptoms, and their possible relationships with the triggering medication, with the ultimate goal of helping in the identification of the causal drug in difficult situations when the patient is taking several drugs. METHODS: Cases of drug-induced cutaneous side-effects associated with various systemic syndromes related to anticonvulsants (carbamazepine, phenytoin and phenobarbitone), minocycline, allopurinol, abacavir and nevirapine were collected retrospectively from the French Pharmacovigilance database (FPD) over a period of 15 years (1985-2000). The clinical patterns typical of the causative drugs were described and compared with data from the literature. RESULTS: Two hundred and sixteen patients with symptoms and signs consistent with cutaneous drug reactions with systemic symptoms were reported to the FPD during this period of time. Their pattern was similar to published data for these drugs, with fever, cutaneous eruption, hepatic abnormalities and eosinophilia being the most prominent but inconstant symptoms. There are clues suggesting that some particular lesional patterns may exist for some drugs. CONCLUSIONS: Although some trends emerge from these retrospective data, they suggest that no clear, unified outline can currently be defined for these multi-organ drug-induced reactions. Instead, a constellation of various symptoms and signs were recorded, that might be sorted in different patterns according to the causal drug, a finding that might indeed improve accurate identification of the causative drug in patients receiving several principal medications at a time. A national prospective study systematically collecting standardized data is required better to define the outlines of these severe adverse drug reactions and to evaluate prognostic data.     

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.     

Drug-induced linear IgA bullous dermatosis

We report the case of a 69-year-old Japanese woman with multiple blistering lesions covering almost her whole body. Linear IgA and C3 depositions were seen at the basement membrane zone on direct immunofluorescence (IF). Linear IgA bullous dermatosis (LABD) is one of the autoimmune diseases resulting in subepidermal blisters. It is clinically similar to bullous pemphigoid and IF is required to distinguish the two diseases. In this case, the blistering lesions appeared after vancomycin treatment. This drug was strongly suspected as a cause of LABD in light of the clinical course of the patient even though a drug-lymphocyte stimulating test was negative. Among the various implicated causative drugs, vancomycin is the most commonly associated with LABD.     

Eosinophilic spongiosis in association with bullous pemphigoid and chronic lymphocytic leukaemia

We report the onset of an unusual blistering eruption following a diagnosis of B-cell chronic lymphocytic leukaemia (CLL). The histology consistently showed eosinophilic spongiosis, but the diagnosis of bullous pemphigoid was only confirmed after 13 years by repeated immunofluorescence studies. The occurrence of subepidermal blistering diseases in association with B-cell lymphoproliferative disorders is rare; a recent study showed that the majority of these cases are epidermolysis bullosa acquisita, confirmed by immunological studies. Only two cases of immunofluorescence-proven bullous pemphigoid in association with CLL have been previously reported.     

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。     

药物诱发大疱性类天疱疮的研究进展

【摘要】 药物诱发大疱性类天疱疮（BP）是指由系统或局部用药后诱发的一种特殊类型BP。对所有新发或是突然加重的BP患者，应警惕药物诱发的可能性，特别是近年报道较多的疫苗接种及二肽基肽酶4抑制剂、肿瘤坏死因子α拮抗剂和程序性死亡受体1/程序性死亡配体1抑制剂等新型药物。本文综述近年来药物诱发BP的研究进展。     

Topical provocation in 31 cases of fixed drug eruption: change of causative drugs in 10 years

The pathomechanism of fixed drug eruption remains to be clarified, but patch testing has been used to determine the causative drug. 31 patients with fixed drug eruption were investigated to evaluate the diagnostic value of patch testing and to compare the causative drugs over the 10 years between the late 1980s and the late 1990s. 22 of them were given an oral provocation test to confirm the results of patch testing. A reaction showing definite infiltration, which occurred in 13 of 22 patients, reliably indicated the causative drug. In contrast, a patch test reaction without definite infiltration was not always correlated with systemic provocation. All except 1 patient found out their causative drug. The most frequent causative drug was sulfamethoxazole-trimethoprim in the late 1980s, but it had become chlormezanone 10 years later.     

Drugs associated with acute generalized exanthematic pustulosis

INTRODUCTION: Acute generalized exanthematous pustulosis is a severe eruption which is usually drug related. If the causative drug is discontinued, acute generalized exanthematous pustulosis resolves spontaneously in ten days. The aim of this study was to compare drugs suspected of causing acute generalized exanthematous pustulosis reported to French Pharmacovigilance centres and those reported in the literature. MATERIALS AND METHODS: All cases of "pustular eruption" qualified as "serious" reported to the French Pharmacovigilance Centers between January 1985 and December 2001 were analyzed. Cases for which the diagnosis of acute generalized exanthematous pustulosis was not clearly identified were reviewed by a dermatologist. The relationship between acute generalized exanthematous pustulosis and drug exposure was re-examined by one of us. An exhaustive review of the literature was also performed. RESULTS: Review of the data base revealed 207 cases of serious acute generalized exanthematous pustulosis leading to death in 4 cases (2%). Of these cases of acute generalized exanthematous pustulosis, only one drug was suspected in 107 cases (51.6%). The main drugs involved were: pristinamycin (18 cases), amoxicillin (+/- clavulanic acid) (16 cases), hydroxychloroquine (8 cases) and a combination of spiramycin + metronidazole (5 cases). DISCUSSION: The most frequent causal drugs in our study and in the literature are: amoxicillin +/- clavulanic acid, pristinamycin, hydroxychloroquine, ampicillin, diltiazem, co-trimoxazole, terbinafine, carbamazepine and spiramycin +/- metronidazole. Only pristinamycin and diltiazem have information in their summary of product characteristics regarding the risk of acute generalized exanthematous pustulosis. Because it is essential to discontinue the causative drug as soon as possible if a pustular eruption occurs, physicians must be informed of the risk, which should be added to the "adverse events", and "warnings" sections of the summary of product characteristics of the drugs concerned. CONCLUSION: Our results show the relevance of notification of side effects by physicians to pharmacovigilance centres, leading to the identification of a signal and public health dissemination of warnings.     

Cutaneous Reactions Induced by Calcium Channel Blocker: High Frequency of Psoriasiform Eruptions

Fifteen cases with cutaneous reactions to calcium channel blockers (Ca-antagonist), dihydropiridine (including nicardipine, nifedipine, nisoldipine), verapamil, and diltiazem are reported. The patients from Yokohama City University Hospital and affiliated hospitals included 4 males and 11 females with cardiovascular diseases. Their average age was 64.7 (54 to 82) years. They had been taking Ca-antagonists for an average of 95 days (7 days to 10 years) before they developed dermatitis. The frequency of reactions to Ca-antagonists was high with diltiazem (5/16: 31.25%) and dihydropyridine (7/16: 43.75%), including nifedipine (4/7), nisoldipine (1/7), and nicardipine (2/7). Stevens-Johnson syndrome (MCOS) was associated only with verapamil. A notable type of eruption was the psoriasiform type, including exacerbation of psoriasis, which was resolved or easily controlled after discontinuation of the drug. Provocation tests verified the Ca-antagonist as the cause in 7 cases of psoriasiform eruption. The frequency of positive patch tests to Ca-antagonists was low except for diltiazem. Patch tests with diltiazem showed positive reactions in 54% (7 of 13 patients), based on our experience and papers published in Japan. Ca-antagonists are occasional causes of a wide spectrum of cutaneous reactions and should also be considered as causative factors in patients who develop psoriasiform eruptions or in patients whose psoriasis is exacerbated while using these drugs.     

Linear IgA bullous dermatosis: a clinical study of 16 cases at National Taiwan University Hospital

BackgroundLinear immunoglobulin A bullous dermatosis (LABD) is a rare autoimmune subepidermal bullous disease. It is defined by continuous linear deposition of IgA in the basement membrane zone on direct immunofluorescence microscopy. The clinical presentations of LABD may mimic other diseases, and data in Taiwanese populations are still lacking. The current study aims to examine LABD status in Taiwan.MethodsWe reviewed the database at our institute from 1995 to 2008. The gold standard for the diagnosis of LABD is based on continuous linear depositions of IgA in the basement membrane zone on direct immunofluorescence.ResultsA total of 16 LABD patients were identified. Mean age at diagnosis was 55 years, and most (> 80%) occurred after the fourth decade. The trunk was most commonly involved (76%). However, in contrast to previous reports, the mucosal involvement was rare in our series (18%). Initial impressions were dermatitis herpetiformis in 8 patients (50%), bullous pemphigoid in 4 patients (25%), and vasculitis, varicella, and pemphigus vulgaris in the remaining 4 patients (25%). Four patients reported a history of drug ingestion shortly before the onset of the disease, and all recovered after discontinuing the offending drugs. One of them had griseofulvin-associated LABD, a case not reported previously. The other three drugs were rifampin, vancomycin and gemcitabine. Among the various regimens, dapsone (100 mg) twice a day achieved the best treatment response in the five treated patients.ConclusionThe rare and diverse presentations of LABD highlight the importance of our study results in aiding clinical diagnosis and planning treatment strategies.     

糖尿病患者服用二肽基肽酶Ⅳ抑制剂后发生大疱性类天疱疮32例临床特征分析

目的:探讨糖尿病患者服用二肽基肽酶Ⅳ抑制剂（DPP4i）后发生的大疱性类天疱疮（BP）的临床特征。方法:收集沈阳市第七人民医院2014年1月至2020年12月病房收治的合并糖尿病的BP患者116例,分为BP发病前应用DPP4i治疗糖尿病的DPP4i-BP组和未应用DPP4i治疗的普通BP组,分析和比较两组的一般临床资料...     

75例儿童重症药疹临床分析

目的：分析我院儿童重症药疹的临床特点。方法：对我院75例儿童重症药疹患者临床资料进行回顾性分析。结果：75例患儿发病年龄0~17岁，其中婴儿期13例（17.33%），1~3岁11例（14.67%），3~6岁13例（17.33%），6~12岁33例（44.00%），12~18岁5例（6.67%）；SJS 44例（58.60%），DHS 20例（26.60%），TEN 11例（14.60%）。常见致敏药物为抗生素类（33例，44.00%），解热镇痛类（14例，18.67%），抗癫痫类（13例，17.33%）。结论：我院儿童重症药疹主要致敏药物为抗生素类，好发年龄为6~12岁，最常见的类型为SJS。     

428例药疹临床分析

目的：了解药疹的主要临床特征及常见的致敏药物。方法：收集1998年10月～2003年10月确诊为药疹的病例428例，并对其发病年龄、主要致敏药物、皮疹类型等临床特征进行分析。结果：药疹的发病年龄有所提高，主要致敏药物以抗生素最常见，其次为解热镇痛抗炎药、生物制品、抗痛风药、抗癫痫药及中成药等。皮疹类型以麻疹样或猩红热样型最常见，其次为荨麻疹型、固定型、多形红斑型等，抗痛风药和抗癫痫病药多引起重症药疹。结论：引起药疹的主要致敏药物的种类已发生变化，抗生素已上升为药疹致病药物中的首位。     

138例药疹住院病例分析

目的 探讨药疹致敏药物与临床表现。方法 收集2005年1月至2007年6月，对住院治疗的138例药疹病例，进行回顾性分析。结果 主要的致敏药物为抗菌药，占31.46%；其中阿莫西林致病最常见，占11.23%；其次为非甾体抗炎药，占28.09%；中药类，占15.73%。口服给药是引起药疹的主要途径，占54.17%。主要的皮疹类型为多形红斑型，占33.71％，其次为固定型，占28.09％，发疹型占22.47％。重症药疹主要致敏药物为抗痛风药和中药类。结论 抗菌药和非甾体抗炎药引起药疹比较常见，尤其是阿莫西林。中成药引起药疹的发生率有所上升，临床应重视口服给药引起药疹的问题。     

Fixed eruptions: causative drugs and challenge tests

The drugs responsible for eighty-six cases of fixed drug eruption have been identified, and in all but two were confirmed by challenge. The series included sixteen cases of generalized bullous fixed eruption, which resembles Lyell's syndrome. The main causative drugs were phenazones and barbiturates, both in the series as a whole and in the group of the most severe cases. The same drugs were the most frequent causative agents in a report from Finland 10 years ago.     

2018-2020年皮肤科住院患者金黄色葡萄球菌感染状况及MRSA与MSSA耐药性分析

目的:研究我院住院患者中皮肤软组织感染者(SSTIs)金黄色葡萄球(SA)感染情况及MR-SA与MSSA耐药特点.方法:选取我院2018年1月1日至2020年12月31日入院时存在SSTIs且进行细菌培养及药敏试验的患者,分析SA及MRSA检出率、病种分布,以及MRSA与MSSA耐药性的差异.结果:共分析1455例患者...     

大疱性表皮坏死松解型药疹—43例回顾性研究

报告大疱性表皮坏死松解型药疹４３例。男２１例，女２２例，年龄２～８２岁。致病药物包括抗生素（头孢菌素、青霉素为主），解热镇痛药（安乃近为主），磺胺药（ＳＭＺｃｏ）及抗痛风药（别瞟呤醇）等。皮损累及全身者３６例（８３．７％），其中于２４小时内波及全身者１５例。３８例伴粘膜损害。病死１１例（２５．６％）。继发感染为主要死因。据分析，年龄、皮损范围、血尿素氮水平、皮质类固醇起用时间及继发感染等与本病预后有关。对本病的处理要点予以讨论。     

住院药疹239例致敏药物分析

目的:明确239例药疹的主要致敏药物种类。方法:对本院皮肤科2007年5月至2017年4月就诊的239例药疹患者临床资料进行回顾性分析。结果:239例药疹患者中可确定致敏药物有105例(非重症药疹患者88例,重症药疹患者17例)。非重症药疹致敏药物主要为抗生素类32例(36.4%),解热镇痛药17例(19.3%)、中药16例(18.2%)。重症药疹主要致敏药物为抗生素类5例(29.4%),解热镇痛药3例(17.6%)、卡马西平类3例(17.6%)、抗痛风类药物3例(17.6%)。结论:本组患者药疹最常见的致敏药物为抗生素类。