Human Leukocyte Antigen Gene Testing and Carbamazepine-Induced Toxic Epidermal Necrolysis: A Study of Pediatric Practice

2020 ◽  
pp. 120347542095242
Author(s):  
Jessica M.S. Asgarpour ◽  
Lauren M. Lam ◽  
Tina K. Vogel ◽  
Helly R. Goez ◽  
Loretta Fiorillo
Keyword(s):  
At Risk ◽  
High Risk ◽  
Toxic Epidermal Necrolysis ◽  
Therapeutic Interventions ◽  
Stevens Johnson Syndrome ◽  
Drug Induced ◽  
Realistic Potential ◽  
Gene Testing ◽  
Johnson Syndrome ◽  
Standard Of Practice

Background Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening drug-induced dermatologic conditions. SJS/TEN occurs in 1-10 per 10 000 patients taking carbamazepine (CBZ) (Pratt VM, McLeod HL, Rubinstein WS et al. Medical Genetics Summaries. National Center for Biotechnology Information US; 2018: 1-527). The development of SJS/TEN is associated with variable drug metabolism and presence of an at-risk HLA haplotype. HLA-B*15:02 and HLA-A*31:01 haplotypes can produce a hyperimmune response in the setting of CBZ use in patients of Asian and European descent, respectively (Schneider JA, Cohen PR. Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A concise review with a comprehensive summary of therapeutic interventions emphasizing supportive measures. Adv Ther. 2017; 34:1235-1244). Objective The US Food and Drug Administration (FDA) and the Canadian pharmacogenomics Network for Drug Safety (CPNDS) recommend that patients with high-risk ethnic backgrounds should be genetic tested before initiating CBZ (Sukasem C, Chaichan C, Nakkrut T et al. Association between HLA-B Alleles and Carbamazepine-induced maculopapular exanthema and severe cutaneous reactions in Thai patients. Journal of Immunology Research. 2018; 1-11).We sought out to assess the awareness of this in prescribing practitioners and their standard of practice. Materials and methods We created a 15-question survey and distributed to pediatric neurologists and pediatricians at the University of Alberta. We hypothesized that there was a discordance between the standard of practice and the recommendation by the FDA and CPNDS. Results The survey results indicated a lack of awareness of the at-risk ethnicities for CBZ-induced SJS/TEN. HLA gene testing was rarely done prior to initiation of CBZ in high-risk patients. In addition, there was a lack of awareness for standard of care for genetic testing in Canada and worldwide. Conclusions Our results demonstrate an evident gap between current prescriber practices and existing FDA and CPNDS recommendations to screen for HLA genotypes. We hope that this study captures the realistic potential to improve patient outcomes.

scholarly journals Stevens - Johnson Syndrome and Toxic Epidermal Necrolysis; Extensive Review of Reports of Drug-Induced Etiologies, and Possible Therapeutic Modalities

2018 ◽  
Vol 6 (4) ◽  
pp. 730-738 ◽  
Author(s):  
Adegbenro Omotuyi John Fakoya ◽  
Princess Omenyi ◽  
Precious Anthony ◽  
Favour Anthony ◽  
Precious Etti ◽  
...  
Keyword(s):  
Adverse Drug Reaction ◽  
Toxic Epidermal Necrolysis ◽  
Stevens Johnson Syndrome ◽  
Hypersensitivity Reactions ◽  
Extensive Review ◽  
Drug Induced ◽  
Therapeutic Modalities ◽  
Johnson Syndrome ◽  
Mucous Membranes ◽  
Degrees Of Severity

Stevens - Johnson Syndrome and Toxic Epidermal Necrolysis are adverse hypersensitivity reactions that affect the skin and mucous membranes. They are characterised by erythematous macules and hemorrhagic erosions of the mucous membranes. Epidermal detachments of varying degrees of severity also occur in these conditions. Various aetiologies are associated with these conditions, with adverse drug reaction being the most common. Though the worldwide incidence of these conditions is recorded as low, diverse types of medication are being observed to lead to these conditions. This review compiles information on the details of Stevens-Johnson syndrome and Toxic Epidermal Necrolysis, the pathophysiology, therapeutic management, and largely considers the drug-induced etiologies associated with these conditions.

scholarly journals Causative drugs and HLA-B polymorphism in drug-induced Stevens-Johnson syndrome - toxic epidermal necrolysis: A study in five hospitals in Jakarta

2019 ◽  
Author(s):  
Anesia Tania ◽  
Evita Halim Effendi ◽  
Inge Ade Krisanti ◽  
Yulia Ariani
Keyword(s):  
Toxic Epidermal Necrolysis ◽  
Drug Eruption ◽  
Stevens Johnson Syndrome ◽  
Allele Polymorphism ◽  
Exclusion Criteria ◽  
Drug Induced ◽  
Causative Drug ◽  
Johnson Syndrome ◽  
Luminex Technology ◽  
Referral Hospitals

Stevens-Johnson syndrome and toxic epidermal necrolysis is a very rare but lifethreatening form of cutaneous drug eruption. In recent years, several countries in Asia had succeded in preventing carbamazepine induced SJS/TEN by screening for HLA-B*15:02 before prescribing carbamazepine. This study aimed to acquire data regarding causative drugs and HLA-B allele polymorphism in SJS/TEN patient in Jakarta. We acquired data from 5 referral hospitals from March 2015 to March 2017. Subject fulfilling the inclusion and exclusion criteria was interviewed and blood sample was taken for DNA extraction. The DNA was examined with PCR SSOP and Luminex technology for high resolution HLA-B typing. We studied 22 subjects. The median age was 45,4 years old (14-74). The most common causative drug in this study is carbamazepine. HLA-B*15:02 and HLAB* 18:01 were the most common allele in all subjects. HLA-B*15:02 was found in five (72%) out of seven subjects whose condition was caused by carbamazepine. The most common causative drug of SJS/TEN in five hospitals in Jakarta is carbamazepine, with five (72%) out seven subjects had HLA-B*15:02 allele.

scholarly journals Drug-induced liver injury associated with stevens-Johnson syndrome/toxic epidermal necrolysis: Patient characteristics, causes, and outcome in 36 cases

Hepatology ◽  
2015 ◽  
Vol 63 (3) ◽  
pp. 993-999 ◽  
Author(s):  
Harshad Devarbhavi ◽  
Sujata Raj ◽  
Venu H. Aradya ◽  
Vijaykumar T. Rangegowda ◽  
Girish P. Veeranna ◽  
...  
Keyword(s):  
Liver Injury ◽  
Toxic Epidermal Necrolysis ◽  
Patient Characteristics ◽  
Stevens Johnson Syndrome ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Johnson Syndrome

Drug-Induced Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis Call for Optimum Patient Stratification and Theranostics via Pharmacogenomics

2018 ◽  
Vol 19 (1) ◽  
pp. 329-353 ◽  
Author(s):  
Chonlaphat Sukasem ◽  
Theodora Katsila ◽  
Therdpong Tempark ◽  
George P. Patrinos ◽  
Wasun Chantratita
Keyword(s):  
Toxic Epidermal Necrolysis ◽  
Clinical Care ◽  
Genomic Medicine ◽  
Stevens Johnson Syndrome ◽  
Future Research ◽  
Great Promise ◽  
Patient Stratification ◽  
Clinical Implementation ◽  
Drug Induced ◽  
Johnson Syndrome

The Global Genomic Medicine Collaborative, a multinational coalition of genomic and policy experts working to implement genomics in clinical care, considers pharmacogenomics to be among the first areas in genomic medicine that can provide guidance in routine clinical practice, by linking genetic variation and drug response. Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe life-threatening reactions to medications with a high incidence worldwide. Genomic screening prior to drug administration is a key opportunity and potential paradigm for using genomic medicine to reduce morbidity and mortality and ultimately eliminate one of the most devastating adverse drug reactions. This review focuses on the current understanding of the surveillance, pathogenesis, and treatment of SJS/TEN, including the role of genomics and pharmacogenomics in the etiology, treatment, and eradication of preventable causes of drug-induced SJS/TEN. Gaps, unmet needs, and priorities for future research have been identified for the optimal management of drug-induced SJS/TEN in various ethnic populations. Pharmacogenomics holds great promise for optimal patient stratification and theranostics, yet its clinical implementation needs to be cost-effective and sustainable.

Common risk allele in aromatic antiepileptic-drug induced Stevens–Johnson syndrome and toxic epidermal necrolysis in Han Chinese

2010 ◽  
Vol 11 (3) ◽  
pp. 349-356 ◽  
Author(s):  
Shuen-Iu Hung ◽  
Wen-Hung Chung ◽  
Zhi-Sheng Liu ◽  
Chien-Hsiun Chen ◽  
Mo-Song Hsih ◽  
...  
Keyword(s):  
Antiepileptic Drug ◽  
Toxic Epidermal Necrolysis ◽  
Risk Allele ◽  
Han Chinese ◽  
Stevens Johnson Syndrome ◽  
Drug Induced ◽  
Johnson Syndrome

scholarly journals DRUG-INDUCED STEVENS-JOHNSON SYNDROME AND TOXIC EPIDERMAL NECROLYSIS

2016 ◽  
Vol 65 (4) ◽  
pp. 377-381
Author(s):  
Dalia Dop ◽  
◽  
Desdemona Stepan ◽  
Cristian Gheonea ◽  
Elena Carmen Niculescu ◽  
...  
Keyword(s):  
Toxic Epidermal Necrolysis ◽  
Rare Diseases ◽  
Intravenous Immunoglobulins ◽  
Stevens Johnson Syndrome ◽  
Drug Induced ◽  
Johnson Syndrome ◽  
Medical Emergencies ◽  
Steven Johnson Syndrome ◽  
Restitutio Ad Integrum

Steven-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare diseases that appear following the administration of risk drugs. Both are severity grades of the same condition and are considered medical emergencies, because they are potentially lethal. They are characterized by mucocutaneous tenderness, erythema, necrosis and bullous detachment similar to extended burns. We report 3 cases of SJS/TEN in which the etiology was probably drug-related (Paracetamol, Atomoxetinum, Sulfamethoxazolum + trimethoprinum), with restitutio ad integrum following the administration of intravenous immunoglobulins.

Immunohistochemical Expression of Apoptotic Markers in Drug-Induced Erythema Multiforme, Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

2007 ◽  
Vol 20 (3) ◽  
pp. 557-566 ◽  
Author(s):  
A.V. Marzano ◽  
A. Frezzolini ◽  
M. Caproni ◽  
A. Parodi ◽  
D. Fanoni ◽  
...  
Keyword(s):  
Toxic Epidermal Necrolysis ◽  
Erythema Multiforme ◽  
Fas Ligand ◽  
Normal Skin ◽  
Basal Layer ◽  
Immunohistochemical Analysis ◽  
Stevens Johnson Syndrome ◽  
Drug Induced ◽  
Johnson Syndrome ◽  
Dermal Infiltrate

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 spectrum 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.

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