title: Phenobarbital-induced severe cutaneous adverse drug reactions are associated with CYP2C19*2 in Thai children.
abstract: BACKGROUND
  Aromatic anticonvulsant-induced severe cutaneous adverse drug reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrosis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS), are fatal immune-mediated adverse drug reactions. CYP2C19, a cytochrome P450 isoform, plays a role in metabolic rate of aromatic anticonvulsant. HLA-B*1502 has also been demonstrated to be associated with carbamazepine-induced SJS-TEN.
  
  
  METHODS
  Forty case patients who were diagnosed with SCARs after initiation of phenobarbital (PB), phenytoin (PHT), or carbamazepine (CBZ) for 1-8 wk and forty control patients who received PB, PHT, or CBZ at least 2 months with no adverse drug reactions were enrolled in the study. The genotypes of CYP2C19*1, CYP2C19*2, and HLA-B*1502 were analyzed using allele-specific polymerase chain reaction technique. Clinical characteristics of SCARs patients who used different drugs were also analyzed.
  
  
  RESULTS
  There was no significant difference in sex, onset of symptoms, laboratory results, treatment, and length of stay among patients with SCARs due to PB, PHT, or CBZ. The patients with CYP2C19*2 variant had a trend to have a likelihood to develop SCARs more than the patients with CYP2C19 wild type (OR = 2.5, 95% CI (0.96-67.3) p = 0.06). In subgroup analysis, the patients with CYP2C19*2 variant were at four times increased risk of SCARs from phenobarbital more than the patients with CYP2C19 wild type (OR = 4.5, 95% CI (1.17-17.37) p < 0.03). There was no association between the HLA-B*1502 and aromatic anticonvulsant-induced severe cutaneous adverse reactions (SCARs).
  
  
  CONCLUSIONS
  CYP2C19*2 variant may play a role in the genetic predisposition of SCARs from phenobarbital.
authors.affiliation: Division of Pediatrics Allergy, Immunology and Rheumatology, Mahidol University, Bangkok, Thailand.
authors.forename: Wiparat
authors.initials: W
authors.lastname: Manuyakorn
authors.forename: Khanitha
authors.initials: K
authors.lastname: Siripool
authors.forename: Wasu
authors.initials: W
authors.lastname: Kamchaisatian
authors.forename: Samart
authors.initials: S
authors.lastname: Pakakasama
authors.forename: Anannit
authors.initials: A
authors.lastname: Visudtibhan
authors.forename: Soamarat
authors.initials: S
authors.lastname: Vilaiyuk
authors.forename: Thidarat
authors.initials: T
authors.lastname: Rujirawat
authors.forename: Suwat
authors.initials: S
authors.lastname: Benjaponpitak
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D002220:Carbamazepine / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D065731:Cytochrome P-450 CYP2C19; D004252:DNA Mutational Analysis; D004342:Drug Hypersensitivity / Q000235:genetics*; D005260:Female; D005838:Genotype; D059910:HLA-B15 Antigen / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010634:Phenobarbital / Q000008:administration & dosage / Q000009:adverse effects*; D010672:Phenytoin / Q000008:administration & dosage / Q000009:adverse effects; D011110:Polymorphism, Genetic; D012867:Skin / Q000187:drug effects / Q000473:pathology; D013785:Thailand
chemical_list: D000927:Anticonvulsants; C483536:HLA-B*15:02 antigen; D059910:HLA-B15 Antigen; D002220:Carbamazepine; D010672:Phenytoin; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D010634:Phenobarbital