title: Severe bullous hypersensitivity reactions after exposure to carbamazepine in a Han-Chinese child with a positive HLA-B*1502 and negative in vitro toxicity assays: evidence for different pathophysiological mechanisms.
abstract: BACKGROUND
  Drug hypersensitivity syndrome (DHS) can present in several clinical forms ranging from simple maculopapular skin rash to severe bullous reactions and multi-system dysfunction. Genetic analysis of DHS patients has revealed a striking association between carbamazepine (CBZ)-induced severe bullous reactions, such as Steven-Johnson Syndrome, and toxic epidermal necrolysis in individuals from Southeast Asia who carry a specific HLA allele (HLA-B*1502). This ethnic-specific relationship with a disease phenotype has raised the question of the commonality of the pathogenesis mechanisms of these diseases. The aim of this study was to investigate the genetic and metabolic bases of DHS development to help predict patient susceptibility.
  
  
  METHODS
  A case of carbamazepine-induced Steven-Johnson Syndrome reaction in a HLA-B*1502 positive child of Han Chinese origin, a carbamazepine-induced DHS case in a Caucasian patient and 3 healthy controls were investigated. We performed two types of in vitro toxicity assay, the lymphocyte toxicity assay (LTA) and the novel in vitro platelet toxicity assay (iPTA) on cells taken from the Chinese child 3 and 9 months after recovery from the reaction and from two healthy volunteers. We also tested the Caucasian patient, who developed CBZ-induced DHS, 3 months after the reaction.
  
  
  RESULTS
  Both LTA and iPTA tests were negative 3 and 9 months after the reaction on samples from the Chinese child whereas the tests were positive in the Caucasian patient.
  
  
  CONCLUSIONS
  These results strongly suggest more than one mechanistic pathway for different CBZ-induced hypersensitivity reactions in patients with different ethnic backgrounds.
authors.affiliation: Ivey Chair in Molecular Toxicology, University of Western Ontario, London, Ontario, Canada. aelzagal@uwo.ca
authors.forename: Abdelbaset A
authors.initials: AA
authors.lastname: Elzagallaai
authors.forename: Facundo
authors.initials: F
authors.lastname: Garcia-Bournissen
authors.forename: Yaron
authors.initials: Y
authors.lastname: Finkelstein
authors.forename: John R
authors.initials: JR
authors.lastname: Bend
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rieder
authors.forename: Gideon
authors.initials: G
authors.lastname: Koren
mesh_terms: D000927:Anticonvulsants / Q000009:adverse effects; D044466:Asian People / Q000235:genetics; D001792:Blood Platelets / Q000187:drug effects; D002220:Carbamazepine / Q000009:adverse effects*; D016022:Case-Control Studies; D002648:Child; D002681:China; D004342:Drug Hypersensitivity / Q000235:genetics* / Q000503:physiopathology; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D012720:Severity of Illness Index; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced* / Q000503:physiopathology
chemical_list: D000927:Anticonvulsants; D015235:HLA-B Antigens; D002220:Carbamazepine