Kok Wee Chong1, Derrick W S Chan2, Yin Bun Cheung3, Leng Kee Ching4, Szu Liang Hie5, Terrence Thomas1, Simon Ling1, Ene Choo Tan4. 1. Neurology Service, Department of Paediatric Medicine, KK Women's and Children's Hospital, Singapore, Singapore. 2. Neurology Service, Department of Paediatric Medicine, KK Women's and Children's Hospital, Singapore, Singapore Office of Clinical Sciences, Duke-NUS. 3. Office of Clinical Sciences, Duke-NUS. 4. KK Research Centre, KK Women's and Children's Hospital, Singapore, Singapore. 5. Pharmacy Department, KK Women's and Children's Hospital, Singapore, Singapore.
Abstract
OBJECTIVES: To determine the association between severe cutaneous drug reactions (SCDR), HLA-B*1502 allelism, carbamazepine dose and treatment duration in a Singapore paediatric population. METHOD: Case-control study of SCDR with carbamazepine and HLA-B*1502. We recruited 32 cases, 5 with Steven Johnson Syndrome/Toxic Epidermolytic Necrolysis (SJS/TEN) (2 Chinese, 3 Malay), 6 with hypersensitivity syndrome (HSS) (5 Chinese, 1 Indian), 11 with minor drug reactions (9 Chinese, 2 Malay) and 10 controls (7 Chinese, 2 Malay, 1 Indian). HLA-B*1502 allelism was assayed. HLA-B*1502 status and the type of drug reaction were compared using univariate analysis. The time-span from treatment onset to reaction and the dose-time to reaction association in the 3 groups were analysed. RESULTS: HLA-B*1502 was positive in: 5/5 (SJS/TEN), 0/6 (HSS), 1/11 (minor drug reactions) and 1/10 controls. OR for SJS/TEN in HLA-B*1502-positive patients relative to that in HLA-B*1502-negative patients was estimated by exact logistic regression to be 27.20 (95% CI 2.67 to ∞). Median treatment duration (days) until allergic reactions was 12 (range 11-13), 16 (range 10-37) and 11 (range 0-63) for SJS/TEN, HSS and minor drug reactions, respectively. Median dose at onset of reactions was 6.2 mg/kg/day (range 4.6-7.4), 9.8 mg/kg/day (range 7.7-12.2) and 6.7 mg/kg/day (range 3.6-20.0) for the 3 groups, respectively. CONCLUSIONS: HLA-B*1502 positivity increases the odds of carbamazepine-induced SCDR in Singapore children of Chinese and Malay ethnicity. Adverse drug reactions to carbamazepine occurred within 2 weeks and at low doses. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
OBJECTIVES: To determine the association between severe cutaneous drug reactions (SCDR), HLA-B*1502 allelism, carbamazepine dose and treatment duration in a Singapore paediatric population. METHOD: Case-control study of SCDR with carbamazepine and HLA-B*1502. We recruited 32 cases, 5 with Steven Johnson Syndrome/Toxic Epidermolytic Necrolysis (SJS/TEN) (2 Chinese, 3 Malay), 6 with hypersensitivity syndrome (HSS) (5 Chinese, 1 Indian), 11 with minor drug reactions (9 Chinese, 2 Malay) and 10 controls (7 Chinese, 2 Malay, 1 Indian). HLA-B*1502 allelism was assayed. HLA-B*1502 status and the type of drug reaction were compared using univariate analysis. The time-span from treatment onset to reaction and the dose-time to reaction association in the 3 groups were analysed. RESULTS:HLA-B*1502 was positive in: 5/5 (SJS/TEN), 0/6 (HSS), 1/11 (minor drug reactions) and 1/10 controls. OR for SJS/TEN in HLA-B*1502-positive patients relative to that in HLA-B*1502-negative patients was estimated by exact logistic regression to be 27.20 (95% CI 2.67 to ∞). Median treatment duration (days) until allergic reactions was 12 (range 11-13), 16 (range 10-37) and 11 (range 0-63) for SJS/TEN, HSS and minor drug reactions, respectively. Median dose at onset of reactions was 6.2 mg/kg/day (range 4.6-7.4), 9.8 mg/kg/day (range 7.7-12.2) and 6.7 mg/kg/day (range 3.6-20.0) for the 3 groups, respectively. CONCLUSIONS:HLA-B*1502 positivity increases the odds of carbamazepine-induced SCDR in Singapore children of Chinese and Malay ethnicity. Adverse drug reactions to carbamazepine occurred within 2 weeks and at low doses. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Authors: Ana Alfirevic; Munir Pirmohamed; Branka Marinovic; Linda Harcourt-Smith; Andrea L Jorgensen; Tess E Cooper Journal: Cochrane Database Syst Rev Date: 2019-07-17
Authors: Dinh Van Nguyen; Hieu Chi Chu; Doan Van Nguyen; Minh Hong Phan; Timothy Craig; Karl Baumgart; Sheryl van Nunen Journal: Asia Pac Allergy Date: 2015-04-29
Authors: Ju Sun Song; Eun-Suk Kang; Eun Yeon Joo; Seung Bong Hong; Dae-Won Seo; Soo-Youn Lee Journal: Ann Lab Med Date: 2014-08-21 Impact factor: 3.464