A European study of HLA-B in Stevens-Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs

BACKGROUND: Stevens-Johnson syndrome (SJS) and its severe form, toxic epidermal necrolysis (TEN), are rare but life-threatening cutaneous adverse reactions to drugs, especially to allopurinol, carbamazepine, lamotrigine, phenobarbital, phenytoine, sulfamethoxazole, oxicam and nevirapine. Recently, a strong association between carbamazepine and allopurinol induced SJS or TEN has been described with respectively, HLA-B*1502 and HLA-B*5801 in a Han Chinese population from Taiwan and other Asian countries. OBJECTIVE: The objective is to further investigate the relationship between SJS/TEN and HLA-B in a large number of patients in a European population. METHODS: HLA-B genotyping was performed on 150 patients included in a European study (RegiSCAR) of SJS and TEN. We focused on patients related to 'high-risk' drugs including: 31 cases related to allopurinol, 28 to sulfamethoxazole, 19 to lamotrigine and 14 to oxicam. RESULTS: Sixty-one percent of 31 allopurinol-induced SJS/TEN patients carried the HLA-B*5801 allele and the figure was 55% for 27 patients of European ancestry [odds ratio=80 (34-187)], (P<10(-6)) as previously observed in Han Chinese. For other drugs, two rare alleles showed a weaker association with SJS/TEN in a limited number of patients: B*38 for sulfamethoxazole or lamotrigine-related patients, and B*73 for oxicam. CONCLUSION: At variance with prior results in Asia, this study shows that even when HLA-B alleles behave as strong risk factors, as for allopurinol, they are neither sufficient nor necessary to explain the disease. Further investigations are necessary to delineate the exact role of the HLA region in SJS/TEN, and to look for other associations in other regions of the genome.     

Fatal Toxic Epidermal Necrolysis Associated with Minoxidil

Minoxidil is a direct-acting peripheral vasodilator for the treatment of symptomatic hypertension, or refractory hypertension associated with target organ damage, that is not manageable with a diuretic and two other antihypertensive drugs. The most frequent adverse events associated with minoxidil include hypertrichosis and cardiovascular events related to its powerful antihypertensive effect, and less frequently, rashes, bullous eruptions, and Stevens-Johnson syndrome (SJS). Evidence suggests that SJS and toxic epidermal necrolysis (TEN) are variants of a single disease with common causes and mechanisms, but differing severities. Epidermal detachment is mild in SJS, moderate in overlap SJS-TEN, and severe (> 30% of body surface area) in TEN. We describe a case of minoxidil-associated SJS that evolved into fatal TEN. A 69-year-old African-American woman with a history of chronic kidney disease was admitted to the hospital for a cerebrovascular accident and uncontrolled hypertension. On hospital day 12, oral minoxidil was added to her drug regimen. On day 23, she developed a maculopapular rash on her face that gradually diffused to her chest and back. Vesicles and papular lesions extended to her extremities and mucosal membranes; results of a skin biopsy revealed SJS. A positive Nikolsky's sign (blisters spread on application of pressure) was detected. On days 27–31, diffuse bullae developed with rash exacerbation. Skin detachment exceeded 30% and was consistent with TEN. The patient died on day 39. An evaluation of the causality and time course suggested that minoxidil was the most likely culpable drug, with a Naranjo adverse drug reaction probability scale score indicating that the likelihood of the association was possible (score of 3). The mechanism of this reaction has not been well elucidated. It may be related to an impaired clearance of the minoxidil metabolite, or an immune stimulation resulting in apoptosis and epidermis destruction. To our knowledge, this is the first case report of fatal TEN associated with minoxidil. This case report emphasizes the importance of monitoring for serious dermatologic reactions in patients receiving minoxidil therapy.     

Lamotrigine and Stevens-Johnson Syndrome Prevention

Stevens-Johnson Syndrome (SJS) is a rare life-threatening condition characterized by severe mucocutaneous epidermal necrolysis and detachment of the epidermis. The condition centers around a delayed-type hypersensitivity reaction with a complex etiology stemming from a variety of causes. The number one cause is medication-related—common ones including sulfonamides, antiepileptics, allopurinol, and nonsteroidal anti-inflammatory drugs. Genetics also play a role as several human leukocyte antigen (HLA) genotypes within certain ethnic groups have been implicated in adverse reactions to specific drugs. HLAB*15:02 has been identified in the Chinese and others of Southeast Asian origin to increase susceptibility to lamotrigine and carbamazepine-induced SJS. Furthermore, patients of Japanese origin with HLAB*31:01 and Koreans with HLA-B*44:03 are also at increased risk of SJS after receiving the same two drugs. Of the antiepileptics, one most commonly associated with SJS is lamotrigine, a pre-synaptic voltage-gated sodium channel inhibitor. Lamotrigine is an antiepileptic drug of the phenyltriazine class that is indicated for the prevention of focal and generalized seizures in epileptic patients as well as monotherapy or adjunctive maintenance treatment for Bipolar disorder. The occurrence of SJS is not a rigid contraindication to lamotrigine reintroduction in the same patient. To facilitate this, manufacturers have developed a strict re-challenge dosing regimen to facilitate successful reintroduction of lamotrigine. In order to prevent the recurrence of SJS during a re-challenge, timing of re-dose and initial rash severity must be considered. Therefore, to prevent SJS recurrence, prime lamotrigine re-challenge patients are those with mild initial rash that has not occurred within the previous 4 weeks. The Federal Food and Drug Administration recommends the testing HLA subtypes for those associated with SJS prior to starting lamotrigine.     

Lamotrigine-induced toxic epidermal necrolysis in three patients treated for bipolar disorder

Exfoliative dermatitis, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), is a mild-to-life-threatening process that has been described after exposure to many antiepileptic drugs. The increased use of antiepileptic drugs for treatment of bipolar disorder and neurologic disorders has extended the risk of exfoliative disorder to this population of patients, and these patients and their health care providers may not be familiar with the risks involved with these drugs. We describe the cases of a 28-year-old woman with bipolar 1 disorder initially treated with lamotrigine, and two adolescent girls with bipolar 2 disorder treated with lamotrigine after poor responses to other drug regimens. In all three patients, rashes progressed to toxic epidermal necrolysis in spite of treatment with corticosteroids at their local hospitals; thus, they were transferred to our burn treatment center. Response to early corticosteroid treatment in suppressing progression of exfoliation was variable in these patients. Ultimately, two of the three required ventilatory support; their conditions improved within 8-32 days of treatment, and they were discharged from the hospital. Case reports of lamotrigine-induced exfoliative disorder in patients with bipolar disorder have been published. However, these three patients were admitted to our burn treatment center within a 12-month period. Our institution admits approximately 10-12 patients with TEN/year, and the increased use of lamotrigine for treatment of bipolar disorder is likely to result in more patients with TEN. Therefore, health care professionals need to be aware of the early signs and symptoms of exfoliative dermatotoxicity when treating patients with lamotrigine.     

别嘌呤醇致Stevens-Johnson综合征及中毒性表皮坏死松解症的发病机制和治疗

别嘌呤醇是次黄嘌呤的同分异构体,在体内可抑制黄嘌呤氧化酶而抑制体内尿酸合成,是目前临床广泛使用的唯一一个抑制尿酸合成的抗痛风药,其可诱发Stevens-Johnson综合征和中毒性表皮坏死松解症。SJS/TEN虽较为少见,却是危及生命的严重皮肤不良反应。因此对于SJS/TEN发病机制的认识,可以有效预防SJS/TEN的发生,而正确治疗措施的采取将减少并发症的发生,降低病死率。本文就SJS/TEN的发病机制及治疗进行综述。     

Population pharmacokinetics of lamotrigine adjunctive therapy in adults with epilepsy

Plasma concentrations of lamotrigine, an antiepileptic drug obtained in three adult controlled clinical trials conducted in the United States were pooled and analyzed using NONMEM, a population pharmacokinetic computer program, to facilitate development of dosing guidelines. A total of 2,407 lamotrigine plasma concentrations from 527 patients with epilepsy were analyzed. Regression equations for oral clearance were developed as a function of body size, age (18-64 years), gender, race, and use of concomitant antiepileptic drugs. The population mean apparent oral clearance of lamotrigine in adult patients receiving one concomitant enzyme-inducing antiepileptic drug and not valproic acid was estimated to be 1 mL/min/kg. Gender and age did not affect clearance significantly. On average, clearance was reduced by 25% in non-whites and increased by 13% in patients receiving more than one concomitant enzyme-inducing antiepileptic agent. Lamotrigine did not influence the disposition of phenytoin or carbamazepine. Dosing adjustments for lamotrigine in patients receiving concomitant enzyme-inducing antiepileptic drugs and not valproic acid should not be necessary for age, gender, or the number of concomitant enzyme-inducing antiepileptic drugs. Lamotrigine does not influence the dosing requirements for phenytoin or carbamazepine.     

Immunohistochemical expression of apoptotic markers in drug-induced erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are considered to be severity variants of the same disease, which is almost always associated with drug intake. In contrast, erythema multiforme (EM) is a disorder regarded as only rarely caused by drugs. Keratinocyte apoptosis has been shown to play an important part in the pathogenesis of SJS and TEN, whilst its role in EM remains controversial. To determine the expression of apoptosis-associated molecules Fas, Fas ligand (FasL), Bcl-2 and Bax in the above disorders, an immunohistochemical analysis was performed. We studied both lesional skin from thirty patients having drug-induced EM and 5 cases classified within the SJS/TEN spec nottrum and normal skin samples. We found a keratinocyte overexpression of Fas antigen, an important molecule mediating apoptosis, not only in SJS and TEN but also in EM. Another noteworthy finding was the strong expression of Bcl-2, a protein known as blocking apoptosis, along the basal layer and in the dermal infiltrate both in SJS/TEN and in EM. Taken together, these findings suggest that Fas-dependent keratinocyte apoptosis may play a part in the pathogenesis of both SJS/TEN and EM. Fas-mediated cell death may be partially suppressed by the Bcl-2 protein.     

重症多形红斑型药疹25例和中毒性表皮坏死松解症17例回顾性分析

对1990年12月~2013年4月本院收治的25例重症多形红斑（SJS）和17例中毒性表皮坏死松解症（TEN）患者的临床资料进行回顾性分析。探讨SJS和TEN的致敏因素、发生规律、临床特征和治疗措施。药物是引起SJS和TEN的最主要病因。致敏药物以抗菌药物为主（52.38%）,其次是抗癫痫药（28.57%）。黏膜损害和肝功能损害是最常见的并发症。 SJS和TEN均系统应用糖皮质激素治疗,SJS组8例和TEN组4例给予激素联合人免疫球蛋白治疗。系统应用糖皮质激素尤其是联合人免疫球蛋白治疗SJS和TEN有效。     

Association between HLA and Stevens–Johnson Syndrome Induced by Carbamazepine in Southern Han Chinese: Genetic Markers besides B*1502?

Previous studies have demonstrated a strong association between carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (CBZ-induced SJS/TEN) and HLA-B*1502 in Chinese, and HLA-A*3101 but not HLA-B*1502 in Caucasians and Japanese. Cases with CBZ-induced SJS/TEN negative for HLA-B*1502 were reported recently in Southeast Asia. Negative correlations between CBZ-induced SJS/TEN and B*0702 or B*4001 have also been reported, suggesting a possible protective role. Here, we genotyped HLA-B and HLA-A in 18 cases with CBZ-induced SJS/TEN, in comparison with CBZ-tolerant and normal controls in Southern Han Chinese. A strong association between HLA-B*1502 and CBZ-induced SJS/TEN was found, with 72.2% sensitivity and 87.1% specificity. However, we also found five patients with SJS (5/18, 27.78%) who were negative for HLA-B*1502. HLA-A*2402 was present in nine of 16 cases with SJS (56.25%, including three of five cases negative for HLA-B*1502), which was significantly more frequent than that of CBZ-tolerant controls or the general southern population. Only one case with SJS carried HLA-A*3101. No statistical difference in the mean age, sex ratio and CBZ usage was found between the CBZ-induced SJS/TEN group and the CBZ-tolerant group. In search for possible protective genetic markers in HLA-B*1502-positive but CBZ-tolerant patients, we failed to find any significant factors in the HLA alleles observed. Given the association between HLA-B*1502 and CBZ-induced SJS/TEN, genetic testing before initiating CBZ therapy is suggested in Han Chinese population. However, physicians should also be vigilant about SJS/TEN in those negative for HLA-B*1502. Other factors for the development of CBZ-induced SJS/TEN in HLA-B*1502-negative patients and protective factors in CBZ-tolerant patients should be investigated further.     

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。     

HCP5 genetic variant (RS3099844) contributes to Nevirapine-induced Stevens Johnsons Syndrome/Toxic Epidermal Necrolysis susceptibility in a population from Mozambique

Purpose

Nevirapine (NVP) is an anti-retroviral drug used for the treatment of HIV infection, that may cause several severe adverse events, including Stevens Johnsons Syndrome/Toxic Epidermal Necrolysis (SJS/TEN). A recent whole genome association study highlighted a strong association with allopurinol-induced SJS/TEN within the HCP5 and PSORS1C1 genes in the Japanese population. Our aim was to verify the contribution of these two genes in the susceptibility to NVP-induced SJS/TEN in a population from Mozambique.

Methods

Genotyping of PSORS1C1 rs2233945 and HCP5 rs3099844 SNPs was performed in a sample of 27 patients with SJS/TEN and 76 controls. A case–control and a haplotype analysis were performed.

Results

The HCP5 rs3099844 variant allele was significantly associated with the SJS/TEN susceptibility (OR?=?2.03 and P?=?0.039). The TA haplotype, carrying both the variant alleles of the two genes, showed a higher risk for developing SJS/TEN (OR?=?3.44and P?=?0.003). The regression analysis confirmed the contribution of HCP5 rs3099844 SNP (OR?=?2.05, P?=?0.047). By a log-linear model, we also investigated for interaction between HCP5 rs309844 and PSORS1C1 rs2233945 SNPs with respect to SJS/TEN risk, and we observed a strong interaction between the two SNPs (P?=?0.005).

Conclusions

We confirmed the association of HCP5 with the SJS/TEN susceptibility in a population from Mozambique treated with NVP.     

Erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis in children: a review of 10 years' experience.

OBJECTIVE: To review 10 years' experience in a tertiary care paediatric hospital of erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). In addition, to apply a recently described classification system for EM, SJS and TEN in children. DESIGN: Retrospective study of all children with a discharge diagnosis of EM, SJS or TEN over a 10-year period. SETTING: A university tertiary care paediatric hospital. PATIENTS: Sixty-one paediatric patients with a discharge diagnosis of EM, SJS or TEN. MAIN OUTCOME MEASURES: Epidemiology, laboratory features, causative factors, treatment methods, complications and mortality of EM, SJS and TEN in this group of patients. Comparison of correlation with aetiology of old and new classification systems in a paediatric population. RESULTS: Mucous membrane involvement was documented in 61% of patients. Ocular involvement was seen in 39%. Complications occurred in 21% cases, all of whom had SJS or TEN. Only one patient died as a result of their skin condition. Corticosteroids were used in 18% of cases; 95% of whom had a discharge diagnosis of SJS or TEN. The drugs most commonly identified as aetiological agents were sulphonamides and penicillins (26% each). The most frequently implicated infectious agent was herpes simplex virus (19.7%). Classification of study cases according to Bastuji-Garin et al. indicates a strong trend toward bullous EM cases being attributable to infection and SJS/TEN cases to drugs. There was no such clear trend with respect to aetiology when diagnosis was done without the classification system. CONCLUSION: EM, SJS and TEN rarely cause mortality but significant morbidity is seen. Infectious agents, particularly herpes simplex virus, and drugs, especially the sulphonamides and penicillins, are the most common aetiological agents. The classification system proposed by Bastuji-Garin et al. correlates better with aetiology than the practice that preceded it.     

Stevens-Johnson syndrome caused by combined use of lamotrigine and fluoxetine and review of the literature

Stevens-Johnson syndrome (SJS) is a rare, life-threatening acute allergic drug reaction presenting with target lesions and blebs of epidermis. Although a variety of etiologies such as infections and underlying malignancies have been implicated as potential causes of SJS, drugs remain the predominant inciting agent. This report presents a SJS case due to combined use of lamotrigine and fluoxetine. A 41-year-old man was admitted to our clinic with fever, skin eruptions (especially on the face and trunk) and lesions around the mouth. The patient’s history revealed lamotrigine and fluoxetine use during the previous three weeks for major depression. Dermatological examination revealed a typical clinical picture of SJS; his psychotropic medications were all stopped. While topical and ocular prednisolone (1mg/kg/day) cares were initiated, steroid dosage was reduced within 15 days. The condition of patient rapidly improved through this treatment. Effective management of SJS begins with prompt recognition of the entity, combined with attention to each of the major organs that may be affected, potential comorbidities and withdrawal of all potentially causative drugs. Clinicians should bear in mind the possibility that drugs with potential risk in developing SJS must be used carefully.     

Pharmacogenetics of toxic epidermal necrolysis

Importance of the field: Toxic epidermal necrolysis (TEN) and Stevens–Johnson Syndrome (SJS) are two of the most severe drug-induced cutaneous reactions. Advances in genome technologies have allowed researchers to identify genetic markers associated with this drug-associated event and these have provided a potential tool for prevention.

Areas covered in this review: Current updates of genetic biomarkers that have been identified as being associated with TEN/SJS induced by several drugs, and the associations of these markers in different populations, are discussed.

What the reader will gain: The strong association of HLA-B*1502 and carbamazepine (CBZ)-induced TEN/SJS have been reported by several independent studies. This association was mostly observed in patients of Southeast Asian ancestry; it was not observed in populations with low HLA-B*1502 allele frequency. Studies also suggest that drugs with a similar chemical structure to CBZ might also induce TEN/SJS in patients with HLA-B*1502. In addition to CBZ, HLA-B*5801 was also found to associate with allopurinol-induced TEN/SJS. This strongly suggests that the associations of these markers with TEN/SJS are drug specific.

Take home message: The strong association between CBZ and HLA-B*1502 has prompted the US Food and Drug Administration to update the label for CBZ to include genetic information and to recommend genetic testing before prescribing CBZ. Patients with Asian ancestry or who are from regions prevalent in HLA-B*1502 should be screened before CBZ treatment.     

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...     

Spontaneous reports of drug-induced erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis in Denmark 1968-1991

Spontaneous reporting systems (SRS) have been established to monitor drug safety problems after marketing, especially rare, but serious adverse drug reactions (ADRs). Among these are the skin disorders erythema multiforme (EM), Stevens- Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The purpose of this study has been to evaluate the data on these serious skin disorders available in a SRS. All reports concerning these diseases submitted to the Danish Committee on ADRs during the period 1968 to 1991 were reviewed according to predefined criteria. Information was often scarce,and the diagnosis of the reporter had to be accepted at face value in 28% of cases. Two hundred cases of EM, 74 of SJS and 29 of TEN were identified. More than 60% of cases were hospitalized. The diseases had fatal outcome in six patients with TEN, three with SJS and a single patient suffering from EM. One hundred and twenty-eight different drugs were reported as causal agents. Major drug groups involved were antibiotics (sulphonamides and penicillins), non-steroidal anti-inflammatory drugs, anti-epileptics and analgesics. Incidence estimates based on spontaneous reports were compared to the incidence according to the literature and data from a nationwide hospital discharge diagnosis register. The reporting fraction for EM and SJS is estimated to 10-30%, and for TEN to 25-50%, but the validity of reports is in some cases difficult to assess owing to lack of detail.     

Topiramate therapeutic monitoring in patients with epilepsy: effect of concomitant antiepileptic drugs

The authors assessed the effect of concomitant antiepileptic therapy on steady-state plasma concentrations of the new antiepileptic drug (AED) topiramate and the potential relation between topiramate plasma levels and side effects in a cohort of 116 patients with epilepsy. On the basis of concomitant AEDs, patients were divided into two subgroups, otherwise comparable for age and weight-adjusted daily dose of topiramate. Group A (n = 73) received topiramate plus AED inducers of cytochrome P450 (CYP) metabolism, such as carbamazepine, phenobarbital, and phenytoin. Group B (n = 43) received topiramate plus AEDs without inducing properties of CYP metabolism (namely valproic acid and lamotrigine). Weight-normalized topiramate clearance values, calculated as dosing rate/steady-state plasma drug concentration, were about 1.5-fold in patients receiving AED inducers compared with patients receiving AED noninducers. Topiramate plasma concentrations were linearly related to daily drug doses, regardless of concomitant AED therapy, over a dose range from 25 to 800 mg/d, although, at a given daily dose, a large interpatient variability was observed in matched plasma drug concentrations within each group of patients. Thirty-nine patients (34%) reported side effects associated with topiramate, mostly central nervous system effects. No consistent relation was observed between topiramate plasma concentrations and adverse effects, either in the cohort of patients as a whole or within each subgroup. From a clinical point of view, patients receiving concurrent treatment with enzyme-inducing AEDs can show twofold lower topiramate plasma concentrations compared with patients receiving valproic acid or lamotrigine, and appropriate topiramate dosage adjustments may be required when concomitant AED inducers are either added or withdrawn. Due to the observed variability in topiramate metabolic variables and the complex spectrum of possible pharmacokinetic and pharmacodynamic interactions with the most commonly coprescribed AEDs, monitoring of plasma topiramate concentrations may help the physician in the pharmacokinetic optimization of the drug dosage schedule in individual patients.     

Stevens-Johnson syndrome/toxic epidermal necrolysis in a patient receiving concurrent radiation and gemcitabine

A patient with stage IV malignant melanoma treated with daily radiotherapy and low-dose (100 mg/m2) daily gemcitabine developed a blistering skin eruption, fever and neutropenia consistent with overlap Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). The diagnosis was confirmed by skin biopsy of an affected area. The case history is described, and the literature relating to the development of SJS/TEN in association with chemotherapy and radiotherapy administration is reviewed. This report describes a serious potential complication of concurrent gemcitabine and radiotherapy.     

Hla-B alleles and lamotrigine-induced cutaneous adverse drug reactions in the Han Chinese population

Abstract: Lamotrigine (LTG) is a commonly used antiepileptic drug. However, the use of LTG is limited because of its cutaneous adverse drug reactions (cADRs) ranging from mild maculopapular eruption (MPE) to severe Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). A strong association between HLA‐B*1502 and carbamazepine‐induced SJS/TEN has been identified in Chinese and Thai. Although three of seven cases with HLA‐B*1502 have been reported in LTG‐induced SJS/TEN so far, the relationship between HLA‐B*1502 and LTG‐induced SJS/TEN needs further investigation. It is also unclear whether there is a specific genetic marker associated with LTG‐induced MPE in Chinese. In this study, we genotyped 43 Han Chinese patients treated with LTG (14 cases with LTG‐induced cADRs and 29 LTG‐tolerant controls), using PCR‐SSP for HLA‐B*1502 testing and low‐resolution genotyping, as well as sequencing for four‐digit genotyping. The two cases with SJS were negative for HLA‐B*1502, with B1301/1301 and 4601/5610, respectively. Combining the data with previous studies, there was no significant difference in the frequency of subjects with HLA‐B*1502 between the LTG‐induced SJS/TEN group and the LTG‐tolerant group (p = 0.08, OR 4.23, 95% CI 0.94–18.97). In the MPE group, only one was positive for HLA‐B*1502. There was no significant difference in the frequency of a specific HLA‐B allele between the MPE group and the LTG‐tolerant group either. In this study, no significant association between HLA‐B*1502 and LTG‐induced SJS or MPE was found. Given the small sample size and only HLA‐B locus genotyping, further large‐scale studies are required to explore genetic associations with LTG‐induced cADRs.