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

Abstract

LETTER TO THE EDITORDear 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 association of specific human leukocyte antigen (HLA) alleles with lamotrigine-induced SCAR in patients from different geographical and ethnic origins.In our study, data from patients at 2 tertiary hospitals in Singapore-Singapore General Hospital and National University Hospital-which are part of the ongoing pharmacogenetics study of adverse drug reactions (ADR) of serious skin rash, in collaboration with the Health Sciences Authority (HSA) were retrospectively analysed. A total of 6 patients with a diagnosis of lamotrigineinduced SCAR from January 2003 to September 2018 were recruited. Recruitment was based on physician identification of eligible patients, and written informed consent for blood collection for HLA testing and for medical records access.Clinical assessments and treatment were conducted by specialist dermatologists correlating the clinical presentation and morphology with temporal drug history, and histology specimens if performed. The percentage of body-surface-area involvement was used to differentiate between SJS (<10%), SJS/TEN overlap (10-30%) and TEN (>30%). Eligibility and identification of the causative drug was made based on "certain" or "probable" causality as per the World Health Organization Uppsala Monitoring Centre (WHO-UMC) criteria and Algorithm for Assessment of Drug Causality (ALDEN) scoring. 1 Patients with "possible" causality were excluded.HLA genotyping was performed by the Singapore Immunology Network, according to verified methods by Pozzi et al. 2 Data obtained by sequencing were interpreted by Sequencing Analysis Software (Applied Biosystems, Waltham, US) and checked against a library of HLA sequences and alleles according to the Immunogenetics (IMGT)/HLA Database. 3