AI Article Synopsis
- A lack or mutation in metabolic enzymes, specifically the CYP2C9 gene, may lead to cutaneous adverse drug reactions (CADRs) from diphenylhydantoin (DPH), and patch testing is often ineffective for these reactions.
- Three out of ten patients with DPH-induced CADRs exhibited a heterozygous CYP2C9*3 variant, which significantly increased their odds of adverse reactions compared to other groups.
- This variant appears to differentiate CADR patients with positive patch-test results from those without, highlighting its potential role in adverse drug reactions related to DPH.
Article Abstract
Background: Apart from allergic mechanisms, a lack or mutation of metabolic enzymes may cause adverse drug reactions. Patch testing has rarely been useful in cutaneous adverse drug reactions (CADRs) induced by diphenylhydantoin (DPH). Genetic polymorphisms leading to altered metabolic processes of cytochrome P(450) (CYP) 2C9, a main metabolic enzyme for DPH, may be the pathological mechanism for certain cases of DPH-induced CADRs.
Objective: To examine the effects of an altered CYP2C9 variant, CYP2C9*3, on DPH-induced CADRs.
Methods: Ten patients with DPH-induced CADRs were examined for CYP2C9 genetic polymorphisms. The results were compared with non-exposed controls and 39 neurological patients without DPH-induced CADRs despite exposure to DPH. The patients with DPH-induced CADRs were also patch tested with anti-epileptic drugs and the results were compared with 40 DPH-exposed and 58 non-exposed controls.
Results: A heterozygous CYP2C9*3 variant was found in three of the 10 DPH-induced CADR patients. The crude odds ratios (OR) of the patients compared with those of exposed and non-exposed controls were 167 and 71, respectively. Only one neurological patient, who had never taken DPH, showed the variant in both exposed (P=0.007) and non-exposed (P=0.001) controls. Positive patch-test results were displayed in three of the ten DPH-induced patients, but the patients with positive patch-test reactions to DPH differed from those with the CYP2C9*3 polymorphism. No patients and controls displayed a CYP2C9*2 variant.
Conclusion: A CYP2C9*3 variant could play a role in the proportion of patients with DPH-induced CADRs that differ from patients with DPH-induced CADRs showing positive patch-test results.
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Article Synopsis
- A lack or mutation in metabolic enzymes, specifically the CYP2C9 gene, may lead to cutaneous adverse drug reactions (CADRs) from diphenylhydantoin (DPH), and patch testing is often ineffective for these reactions.
- Three out of ten patients with DPH-induced CADRs exhibited a heterozygous CYP2C9*3 variant, which significantly increased their odds of adverse reactions compared to other groups.
- This variant appears to differentiate CADR patients with positive patch-test results from those without, highlighting its potential role in adverse drug reactions related to DPH.
Enhancement in number and function of antigen-presenting cells in the lymphatic tissue of rats after in vivo administration of diphenylhydantoin (DPH).
Clin Exp Immunol
October 1989
Department of Medicine, University of Essen, West Germany.
We present a monoclonal IgG1 antibody, KiMy1R, which is specific for macrophages and their derivatives in the lymphatic tissue of the rat, and evaluate the distribution of subsets of mononuclear cells in popliteal and para-aortal lymph nodes of Wistar rats after injection of 50 mg DPH into the hindpads. Compared with resting lymphatic tissue and lymph nodes of animals treated with phenobarbital, DPH induced a significant increase (P less than 0.01) of the proportion of phagocytic cells.
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