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Background: Drug-induced hypersensitivity such as anaphylaxis is an important cause of drug-related morbidity and mortality. Cefaclor is a leading cause of drug induced type I hypersensitivity in Korea, but little is yet known about genetic biomarkers to predict this hypersensitivity reaction. We aimed to evaluate the possible involvement of genes in cefaclor induced type I hypersensitivity. Methods: Whole exome sequencing (WES) and HLA genotyping were performed in 43 patients with cefaclor induced type I hypersensitivity. In addition, homology modeling was performed to identify the binding forms of cefaclor to HLA site. Results: Anaphylaxis was the most common phenotype of cefaclor hypersensitivity (90.69%). WES results show that rs62242177 and rs62242178 located in LIMD1 region were genome-wide significant at the 5 × 10−8 significance level. Cefaclor induced type I hypersensitivity was significantly associated with HLA-DRB1∗04:03 (OR 4.61 [95% CI 1.51–14.09], P

Background: Although beta-lactams are 1 of the major causative agents of severe cutaneous adverse reactions (SCAR), their epidemiology and clinical aspects have been poorly studied. This study aimed to investigate the characteristics of SCAR caused by beta-lactams in the Korean SCAR registry. Methods: We retrospectively analyzed beta-lactam-induced SCAR cases collected from 28 tertiary university hospitals in Korea between 2010 and 2015. The SCAR phenotypes included Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap, and drug reaction with eosinophilia and systemic symptoms (DRESS). Beta-lactams were classified according to their chemical structures: penicillins, cephalosporins, and carbapenems. The causative beta-lactams, clinical and laboratory features, treatments, and outcomes were evaluated. Results: Among the 275 antibiotic-induced SCAR cases, 170 patients developed SCAR induced by beta-lactams. Beta-lactam antibiotic-induced SCAR showed more frequent SJS/TEN compared to SCAR induced by non-beta-lactam antibiotics (SJS/TEN/SJS-TEN overlap/DRESS: 36.5/11.2/5.9/46.5% vs. 23.8/10.5/2.9/62.9%, P = 0.049). Cephalosporin was the most common culprit drug. Particularly, 91 and 79 patients presented with SJS/TEN and DRESS, respectively. The odds ratio (OR) for poor prognosis, such as sequelae and death, was significantly increased in subjects with SJS-TEN overlap and TEN and carbapenem as culprit drug in the multivariate analysis (OR, 35.61; P = 0.016, OR, 28.07; P = 0.006, OR 30.46; P = 0.027). Conclusion: Among antibiotic-induced SCAR, clinical features were different depending on whether the culprit drug was a beta-lactam antibiotic or SCAR type. The poor prognosis was related to SJS-TEN overlap, TEN type, and carbapenem as the culprit drug.