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Association of carbamazepine-induced severe cutaneous drug reactions and HLA-B*1502 allele status, and dose and treatment duration in paediatric neurology patients in Singapore
  1. Kok Wee Chong1,
  2. Derrick W S Chan1,2,
  3. Yin Bun Cheung2,
  4. Leng Kee Ching3,
  5. Szu Liang Hie4,
  6. Terrence Thomas1,
  7. Simon Ling1,
  8. Ene Choo Tan3
  1. 1Neurology Service, Department of Paediatric Medicine, KK Women's and Children's Hospital, Singapore, Singapore
  2. 2Office of Clinical Sciences, Duke-NUS
  3. 3KK Research Centre, KK Women's and Children's Hospital, Singapore, Singapore
  4. 4Pharmacy Department, KK Women's and Children's Hospital, Singapore, Singapore
  1. Correspondence to Dr Derrick W S Chan, Department of Paediatric Medicine, KK Women's & Children's Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore; derrick.chan.ws{at}kkh.com.sg

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.

  • Carbamazepine
  • HLA-B*1502
  • Adverse reactions

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