Studies for Pathogenesis of Fixed Drng Emptions Through the Change of Cytochrome p450 Isozymes / 대한피부과학회지

ABSTRACT

The reasons of same site recurrence in fixed drug eruptions (FDEs) remain to be clarified. Although the nature of antigen in FDE is unknown, drug metabolites could play a role for antigen formation. Cytochrome p450 isozymes (CYPs) are important enzymes for drug metabolism. This study was done to examine the role of CYPs in FDEs. Provoked lesion was compared with non-provoked lesion by the same drug on the same patient to overcome inter-individual variations of CYPs. The reverse transcriptase-polymerase chain reaction (RT-PCR) with primers for CYPs and the immunohistochemistry (IHC) with anti-CYPs, pancytokeratin, and leukocyte common antigen (LCA) antibodies were conducted. The causative drugs were different in 13 patients who conducted RT-PCR, and the result could not be analyzed by the cause. The levels of CYP2C8/19 and CYP2E1 mRNAs increased significantly in provoked lesions. The keratinocytes in cases of mefenamic acid-induced FDEs stained strongly with anti-CYP2C9 antibody not with the other three antibodies (CYP1A1, CYP2E1, and CYP3A4). The FDE cases from doxycycline, which is not metabolized by CYP2C9 enzyme, and those from chlormezanone did not react to anti-CYP2C9 antibody. The cells stained with CYP antibodies did not react with anti-LCA antibody but with anti-pancytokeratin antibody. The number of cells which reacted to anti-LCA antibody clearly increased in the provoked lesions, regardless of the cause. The above results suggest that CYPs may contribute the drug antigen formation and different levels of CYPs between provoked and non-provoked lesions can play a role for the same site recurrence of lesions in FDEs.