SEVERE BULLOUS HYPERSENSITIVITY REACTIONS AFTER EXPOSURE TO CARBAMAZEPINE IN A HAN-CHINESE CHILD WITH A POSITIVE HLAB* 1502 AND NEGATIVE IN VITRO TOXICITY ASSAYS: EVIDENCE FOR DIFFERENT PATHOPHYSIOLOGICAL MECHANISMS

Main Article Content

Abdelbaset A Elzagallaai
Facundo Garcia-Bournissen
Yaron Finkelstein
John R Bend
Michael J Rieder
Gideon Koren

Keywords

Adverse drug reactions, drug hypersensitivity syndrome, in vitro diagnosis, drug-induced Stevens-Johnson Syndrome, in vitro toxicity assay

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.


 


Method


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.


 


Conclusion


These results strongly suggest more than one mechanistic pathway for different CBZ-induced hypersensitivity reactions in patients with different ethnic backgrounds.

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