title: Antituberculosis drug-induced hypersensitivity syndrome and its association with human leukocyte antigen.
abstract: Antituberculosis drug (ATD)-induced hypersensitivity syndrome (HSS) is a serious adverse reaction to ATDs, but much remains to be determined regarding its characteristics and genetic risk factors. In this study, we have collected cases of ATD-induced HSS and their clinical features, and investigated the associations of ATD-induced HSS with human leukocyte antigen (HLA). Subjects with ATD-induced HSS and ATD-tolerant controls were recruited through analysis of a multicenter adverse drug reaction registry in Korea. HLA allele frequencies were compared between subjects with ATD-induced HSS (n = 14) and two control groups: ATD-tolerant controls (n = 166) and the general population (n = 485). The number of enrolled subjects with ATD-induced HSS (n = 14) was comparable to those of patients with HSS induced by other common drugs such as allopurinol during the recruitment period. The frequency of Cw*0401 was much higher in the cases (50.0%) compared with ATD-tolerant controls (12.7%, Pc = 0.0204, OR = 6.90) and the general population (12.8%, Pc = 0.0132, OR = 6.82). Our results suggest that ATD is an important causative agent inducing HSS with distinct clinical features. The strong association of Cw*0401 with the risk for ATD-induced HSS suggests immunological involvement in the development of this syndrome.
authors.affiliation: Department of Internal Medicine, Hanyang University College of Medicine, 17 Haengdang-dong, Seongdong-gu, Seoul 133-792, South Korea. sangheonkim@hanyang.ac.kr
authors.forename: Sang-Heon
authors.initials: SH
authors.lastname: Kim
authors.forename: Soo-Keol
authors.initials: SK
authors.lastname: Lee
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Heung-Woo
authors.initials: HW
authors.lastname: Park
authors.forename: Yoon-Seok
authors.initials: YS
authors.lastname: Chang
authors.forename: Kyung Wha
authors.initials: KW
authors.lastname: Lee
authors.forename: Young-Koo
authors.initials: YK
authors.lastname: Jee
mesh_terms: D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000235:genetics; D003875:Drug Eruptions / Q000209:etiology / Q000235:genetics; D004342:Drug Hypersensitivity / Q000209:etiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D006680:HLA Antigens