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.
OBJECTIVE
To determine the association between severe cutaneous drug reactions (SCDR), HLA-B*1502 allelism, carbamazepine dose and treatment duration in a Singapore paediatric population.


METHODS
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.
Neurology Service, Department of Paediatric Medicine, KK Women's and Children's Hospital, Singapore, Singapore.
Kok Wee
KW
Chong
Neurology Service, Department of Paediatric Medicine, KK Women's and Children's Hospital, Singapore, Singapore Office of Clinical Sciences, Duke-NUS.
Derrick W S
DW
Chan
Office of Clinical Sciences, Duke-NUS.
Yin Bun
YB
Cheung
KK Research Centre, KK Women's and Children's Hospital, Singapore, Singapore.
Leng Kee
LK
Ching
Pharmacy Department, KK Women's and Children's Hospital, Singapore, Singapore.
Szu Liang
SL
Hie
Neurology Service, Department of Paediatric Medicine, KK Women's and Children's Hospital, Singapore, Singapore.
Terrence
T
Thomas
Neurology Service, Department of Paediatric Medicine, KK Women's and Children's Hospital, Singapore, Singapore.
Simon
S
Ling
KK Research Centre, KK Women's and Children's Hospital, Singapore, Singapore.
Ene Choo
EC
Tan
D000293:Adolescent; D000483:Alleles; D000927:Anticonvulsants / Q000009:adverse effects*; D002220:Carbamazepine / Q000009:adverse effects*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004342:Drug Hypersensitivity / Q000235:genetics*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D059910:HLA-B15 Antigen / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D012307:Risk Factors; D012846:Singapore; D013262:Stevens-Johnson Syndrome / Q000235:genetics*
D000927:Anticonvulsants; C483536:HLA-B*15:02 antigen; D059910:HLA-B15 Antigen; D002220:Carbamazepine
Adverse reactions; Carbamazepine; HLA-B*1502