Epidemiology of Severe Cutaneous Adverse Drug Reaction and Its HLA Association among Pediatrics

Iran J Pharm Res. 2019 Winter;18(1):506-522.

Abstract

Severe cutaneous adverse drug reaction (SCAR) is considered to be a multifactorial drug side effect. This study was designed to investigate the epidemiology and human leukocyte antigen (HLA)-A and -B gene polymorphisms in pediatric patients with SCAR admitted in tertiary referral center, southwestern of Iran from 2013 to 2017. Demographic data, past allergy and autoimmune history, clinical presentations, drugs confirmed to be the cause of SCAR as well as its therapy were reviewed for each patient. HLA-A and -B allele frequencies were determined in 40 of the patients using polymerase chain reaction based on sequence specific primers (PCR-SSP) and compared with 40 healthy individuals as control group. Sixty-one patients with mean age of 6 years old and boy to girl ratio was 1.2/1 in this study. The most common type of SCAR in our patients was Steven Johnson Syndrome (SJS)/Toxic Epidermal Necrosis (TEN) mainly caused by beta-lactam antibiotics. Carbamazepine was the second cause of drug-induced SCAR. Moreover, HLA-A*02:01 and A*51:01 were related to the increased risk of SCAR while A*11:01 seemed to be protective against SCAR. HLA-A*02:01, HLA-A*24:02, and HLA-B*51:01 showed associations to the increased risk of SJS. Based on our results, beta-lactam antibiotics and antiepileptic drugs are the most common causes of severe adverse drug reaction in southwestern Iranian pediatric patients. Moreover, some HLA-A alleles can influence risk of SCAR.

Keywords: AGEP; DHR; DRESS; HLA; SCAR; STS/TEN.