Lamotrigine-induced Stevens-Johnson Syndrome Research Articles

Lamotrigine-induced Stevens-Johnson Syndrome Toxic Epidermal Necrolysis (SJS/TEN) overlap with transaminitis in an Asian female: a case report

Background: Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN) is a dermatologic emergency characterized by extensive epidermal detachments. The most frequent etiology is drug reaction within an interval of the last 8 weeks. SJS/TEN may occur in any age, race, and gender; however, there is an increased risk in patients over 65. SJS and TEN are differentiated based on the extent of epidermal detachments, which is <10% in SJS, 10-30% in SJS-TEN overlap, and >30% in TEN. This case study aims to evaluate the Lamotrigine-induced Stevens-Johnson Syndrome Toxic Epidermal Necrolysis (SJS/TEN) overlap with transaminitis in an Asian female. Case Presentation: A 34-year-old woman presented with a pruritic and burning rash on almost all body parts. The suspected causative drug was lamotrigine, which she consumed within the last 2 weeks. Mucosal involvement was also found on the lips and genital mucosal. The affected body surface area was approximately 20%, with a positive Nikolsky sign. Laboratory studies showed elevated liver function tests. Based on the history, physical examination, and biopsy, the patient was diagnosed with SJS/TEN overlap. The suspected causative drug was immediately stopped, and supportive and systemic corticosteroid treatments were provided. The SCORTEN was 2, with a mortality rate of 12.1%. After a few days, the patient's condition had improved, the liver function test was normal, and there was no significant complication. Conclusion: SJS-TEN is a part of epidermal necrolysis, characterized by an extensive epidermal detachment. The management of SJS/TEN includes early detection, immediately stopping the suspected drugs, administering systemic corticosteroids, and other supportive treatments.

Association of Human Leukocyte Antigen Alleles with Carbamazepine- or Lamotrigine-Induced Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in an Iranian Population: A Case-control Study.

Genetic diversity in human leukocyte antigen (HLA) alleles across populations is a significant risk factor for drug-induced severe cutaneous adverse reactions (SCARs), e.g., carbamazepine (CBZ)- and lamotrigine (LTG)-induced Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). The present study aimed to investigate the frequency of different HLA alleles in Iranian patients with CBZ- and LTG-induced SJS/TEN. A case-control study was conducted from 2011 to 2018 at various hospitals affiliated with Shiraz University of Medical Sciences (Shiraz, Iran). A total of 31 patients receiving anticonvulsant drugs (CZB or LTG) were recruited and divided into two groups. The drug-induced group (n=14) included hospitalized patients due to CBZ- or LTG-induced SJS/TEN. The drug-tolerant group (n=17) included individuals receiving CBZ or LTG for at least three months with no adverse effects. In addition, 46 healthy individuals (control group) were recruited. The frequency of HLA-A, -B, and -DRB1 alleles in patients with CZB- or LTG-induced SJS/TEN was investigated. HLA typing was performed using the allele-specific polymerase chain reaction method. The Chi square test and Fisher's exact test were used to determine a potential association between SJS/TEN and HLA alleles. P<0.05 was considered statistically significant. CBZ- or LTG-induced SJS/TEN was not significantly associated with HLA alleles. However, HLA-DRB1*01 showed a significantly higher frequency in patients with CBZ-induced SJS/TEN than the CBZ-tolerant patients (30% vs. 9%, P=0.07). Overall, no significant association was found between CBZ- or LTG-induced SJS/TEN and HLA alleles. Further large-scale studies are required to substantiate our findings.

Lamotrigine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Singapore: A case series

Dear Editor, With the advancements in pharmacogenetics, potential genetic associations with severe cutaneous adverse drug reactions (SCAR)—which include Stevens- Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)—have been proposed. Lamotrigine is one of the 2 anticonvulsants found to be highly associated with SJS/TEN from the 2008 EuroSCAR study. Several studies worldwide have looked at the

Lamotrigine-induced Stevens–Johnson Syndrome Coexisting with Seborrheic Dermatitis in a Dengue virus-infected Patient: A Case Report

Stevens-Johnson syndrome is a serious skin condition. Lamotrigine-induced Stevens-Johnson syndrome is strongly associated with HLA*B1502 in the Thai population. Stevens-Johnson syndrome has never been reported to coexist with other skin diseases. Here, the authors report a case of Stevens&ndash;Johnson syndrome with severe seborrheic dermatitis in a Dengue virusinfected patient. The patient was treated with a high-dose systemic corticosteroid and has shown an excellent response to therapy. Keywords: Dengue viral infection, Seborrheic dermatitis, Stevens&ndash;Johnson syndrome, Lamotrigine, IL-17, Cytokine

Current and Future Perspectives on Helicobacter pylori Antibiotic Resistant Mechanisms and Therapeutic Regimens

Stevens-Johnson syndrome is a serious skin condition. Lamotrigine-induced Stevens-Johnson syndrome is strongly associated with HLA*B1502 in the Thai population. Stevens-Johnson syndrome has never been reported to coexist with other skin diseases. Here, the authors report a case of Stevens&ndash;Johnson syndrome with severe seborrheic dermatitis in a Dengue virusinfected patient. The patient was treated with a high-dose systemic corticosteroid and has shown an excellent response to therapy. Keywords: Dengue viral infection, Seborrheic dermatitis, Stevens&ndash;Johnson syndrome, Lamotrigine, IL-17, Cytokine

Investigating the association of Lamotrigine and Phenytoin‐induced Stevens‐Johnson syndrome/Toxic Epidermal Necrolysis with HLA‐B*1502 in Iranian population

Previous studies have found an association between HLA-B*1502 allele and lamotrigine-induced Stevens-Johnson syndrome (SJS)/ toxic epidermal necrosis (TEN) spectrum in Han Chinese populations. This study aims to investigate the association between HLA-B*1502 and lamotrigine- or phenytoin- induced SJS/TEN in an Iranian population. The medical records of twenty-eight lamotrigine-induced SJS/TEN patients and twenty-five lamotrigine-tolerant controls as well as eight phenytoin-induced SJS/TEN and twelve phenytoin-tolerant controls were extracted between March 2013 and March 2019 from the university hospitals in Mashhad, Iran. The presence of HLA-B*1502 allele was determined using real-time polymerase chain reaction (PCR). Among lamotrigine-induced patients with SJS/TEN, 11 (39.3%) patients tested positive for the HLA-B*1502 while only 3 (12.0%) of the lamotrigine-tolerant controls tested positive for this allele. The risk of lamotrigine-induced SJS/TEN was significantly higher in patients with HLA-B*1502, with an odds ratio (OR) of 4.74 [95% confidence interval (CI) 1.14-19.73, p=0.032]. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of HLA-B*1502 for lamotrigine-induced SJS/TEN was 39.29%, 88.00%, 78.57% and 56.41%, respectively. The HLA-B*1502 allele was present in 2 (25.0%) of phenytoin-induced SJS/TEN cases and 5 (41.7%) of the phenytoin-tolerant controls tested positive for HLA-B*1502 allele. The risk of phenytoin-induced SJS/TEN was not higher in the patients with HLA-B*1502 (OR=0.467 [95% confidence interval (CI) 0.065-3.34, p=0.642]). Lamotrigine-induced SJS/TEN is associated with HLA-B*1502 allele in an Iranian population but this is not the case for phenytoin-induced SJS/TEN.

Lamotrigine-induced Stevens-Johnson syndrome in a 25 year old lady

Stevens-Johnson syndrome (SJS) is an immune-complex mediated hypersensitivity reaction and has been linked as an adverse side effect to many drugs. This case is about a 25 year old woman who had lamotrigine-induced Stevens-Johnson syndrome which is known to occur but is rare. Lamotrigine, an anticonvulsive medication and also a commonly used mood stabilizer was prescribed to the patient to treat symptoms of anxiety and depression. The patient developed Stevens-Johnson syndrome 5 weeks after start of therapy. This case is discussed for its relevance to the use of lamotrigine which is currently prescribed very commonly in psychiatric practices.

Association of HLA-B*1502 allele with lamotrigine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese subjects: a meta-analysis.

Despite several studies investigating the association between the human leukocyte antigen HLA-B*1502 allele and lamotrigine-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in Han Chinese subjects, the relationship remains unclear. We performed a systematic review and meta-analysis to ascertain the association between the HLA-B*1502 allele and lamotrigine-induced SJS and TEN in Han Chinese populations. We searched the biomedical literature archived in the MEDLINE, Cochrane Library, EMBASE, Chinese Biomedical, Chinese National Knowledge Infrastructure, and China Science and Technology Journal databases. Only studies investigating the association between HLA-B*1502 and lamotrigine-induced SJS/TEN were included. We then performed a meta-analysis of the data in these studies. Four studies including a total of 12 patients with SJS/TEN and 128 lamotrigine-tolerant control subjects were identified. The HLA-B*1502 allele was present in 33.3% (four of 12) of lamotrigine-induced SJS/TEN cases but in only 9.4% (12 of 128) of lamotrigine-tolerant controls. The occurrence of SJS/TEN was thus associated with the presence of the HLA-B*1502 allele (odds ratio: 4.98, 95% confidence interval 1.43-17.28; P<0.05). We found a statistical association between HLA-B*1502 and lamotrigine-induced SJS/TEN in Han Chinese subjects. Future studies with larger sample sizes are suggested to verify the results.

Lamotrigine-induced hypersensitivity syndrome in a Han Chinese patient with the HLA-B*5801 genotype

Antiepileptic drug (AED) therapy is the mainstay for treating epilepsy. Most of the adverse effects in AED therapy are mild, predictable, and dose-dependent. Cutaneous eruptions, which lead to drug withdrawal and hospitalization, are the most frequent idiosyncratic adverse reactions. Severe cutaneous adverse reactions (SCARs) with high morbidity and mortality, including Stevens– Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug-induced hypersensitivity syndrome, are not uncommon in AED therapy. A strong association between the allele of human leukocyte antigen HLA-B*1502 and carbamazepine-induced SJS has been found in Han Chinese [1]. The lower incidence of carbamazepine-induced SJS in Caucasians, in contrast to its higher incidence in Han Chinese, suggests that there is an ethnic difference in susceptibility. Lamotrigine, one of the newer AEDs, has been reported as a risk factor for skin rashes. We previously [2] identified the risk factors of skin rashes in the patients treated with an initially high dose and rapid escalation of the dose of lamotrigine, and co-medicated with valproic acid. The role of HLA B*1502 in lamotrigine-induced SJS has been investigated and no definite association was found in the studied Han Chinese population [3], which is the same as in Caucasians. In contrast, there seems to be a weak association between HLA B*5801 and lamotrigineinduced SCARs in Caucasians [4]. We report a female Han Chinese patient with epilepsy and lamotrigine-induced SCARs; a genetic study identified the HLA-B*5801 allele as a risk factor. A 32-year-old Han Chinese woman with epilepsy, treated in a special epilepsy clinic in National Cheng Kung University Hospital for years, had been given regular valproic acid therapy (400 mg/day) and had a seizure frequency of around once a month. As the frequency had increased to around once a week, lamotrigine (starting at 20 mg/day, with a 20 mg/week increase) was added. Four weeks later, with the lamotrigine dose at 100 mg/day, she was admitted because of a high fever, generalized erythema, and jaundice. The patient’s blood test revealed high levels of AST (413 U/L), GPT (496 U/L), total bilirubin (17.7 mg/dL), LDH (790 IU/L), alkaline phosphate (582 IU/L), and gamma-GT (821 U/L). Combined with the high fever and a generalized rash, the patient was diagnosed with drug hypersensitivity syndrome. A skin biopsy (Fig. 1) showed mild spongiosis and scattered necrotic keratinocytes in the spinous layer, and vacuolar interface alteration of the basal layers with an infiltration of small lymphocytes. She also showed a perivascular infiltrate of small lymphocytes with scattered neutrophils in the upper dermis. These findings are consistent with maculopapular drug eruption. Under the diagnosis of lamotrigine-induced SCARs, we performed genotyping for this patient and the results showed the J. C. Chow Y.-J. Wu J.-J. Tsai Department of Pediatrics, Chi-Mei Foundation Medical Center, Tainan, Taiwan

Disseminated eruption of ectopic sebaceous glands following Stevens-Johnson syndrome

To the Editor: An 18-year-old white woman presented with a 1-year history of numerous asymptomatic, yellowish and skin-colored papules and plaques diffusely involving her face and chest. She reported that these lesions had developed approximately 4 months after an episode of lamotrigine-induced Stevens-Johnson syndrome (SJS). She had received only supportive care during her hospitalization for SJS; she had not received skin grafts to the face or chest. The patient was otherwise healthy except for history of a mood disorder, which was well controlled with bupropion and aripiprazole.

Lamotrigine-induced Stevens-Johnson syndrome

Lamotrigine is a new antiepileptic drug which is effective for partial or generalized seizure. However, administration of lamotrigine alone or in combination with valproic acid may lead to fatal Stevens-Johnson Syndrome(SJS) or toxic epidermal necrolysis(TEN). Although there are many published case reports of lamotrigine-induced SJS or TEN in Western countries, there have been few cases in the Korean Iiterature until now. Herein, we present a case of SJS associated with LTG.

Lamotrigine-induced Stevens-Johnson syndrome

A case of lamotrigine-induced Stevens-Johnson syndrome (SJS) is reported. A 29-year-old woman with a medical history of schizoaffective disorder arrived at the emergency department with a severe generalized skin reaction. Three to four days prior she had noticed bumps on her lips that had spread to her oral mucosa. She had also developed a diffuse, erythematous, pruritic full-body rash involving the palms of her hands and the soles of her feet and began to feel feverish. Her medications at admission included aripiprazole 30 mg p.o. daily, escitalopram 10 mg p.o. daily, and lamotrigine 75 mg p.o. daily. Lamotrigine was the only new medication, initiated four weeks before this admission. The dermatology service confirmed the diagnosis of SJS using punch biopsy. Lamotrigine was suspected to be the culprit and was discontinued immediately. The patient was given oral prednisone 40 mg and intravenous fluids. Hydroxyzine was given for pruritus, and petroleum jelly and viscous lidocaine were applied to her lips. On hospital day 2, her symptoms and dermatological manifestations improved, but she continued to complain about irritation and slight pain of the mouth. She then received a mouthwash consisting of diphenhydramine, viscous lidocaine, and sodium bicarbonate. On hospital day 3, the patient had improved substantially and was discharged home. Reports of these dermatological reactions in patients receiving lamotrigine for the treatment of bipolar disorder are limited. Dosing, prompt recognition, and patient education are crucial for preventing morbidity and mortality associated with the development of serious cutaneous reactions. SJS was associated with lamotrigine use, despite appropriate dosing and dosage adjustment.