Antituberculosis drug-induced hypersensitivity syndrome and its association with human leukocyte antigen

• Published in: Tuberculosis (Edinburgh, Scotland) Scotland), 2013-03, Vol.93 (2), p.270-274
• Main Authors: Kim, Sang-Heon, Lee, Soo-Keol, Kim, Sang-Hoon, Park, Heung-Woo, Chang, Yoon-Seok, Lee, Kyung Wha, Jee, Young-Koo
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Antitubercular Agents - adverse effects; Antituberculosis drugs; Case-Control Studies; Chemical and Drug Induced Liver Injury - etiology; Chemical and Drug Induced Liver Injury - genetics; Drug Eruptions - etiology; Drug Eruptions - genetics; Drug Hypersensitivity - etiology; Drug Hypersensitivity - genetics; Drugs; Female; Gene Frequency; Genetic association; Genetic Predisposition to Disease; Genotype; Histocompatibility Testing - methods; HLA Antigens - genetics; Human leukocyte antigen; Humans; Hypersensitivity syndrome; Infectious Disease; Male; Middle Aged; Mycobacterium; Pulmonary/Respiratory; Young Adult
• ISSN: 1472-9792; 1873-281X
• DOI: 10.1016/j.tube.2012.10.010

Summary 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.