Pharmacogenetics and adverse drug reactions in the skin

Hereditary variations in the handling of a drug (pharmacogenetics) may result in adverse reactions in the skin. Such reactions could result from: (1) an inherited defect in enzymes responsible for drug metabolism (formation or detoxification of potentially toxic metabolites); (2) altered susceptibility of an endogenous metabolic pathway to inhibition by a drug. Increased alcohol-dehydrogenase activity or decreased aldehyde-dehydrogenase activity will predispose an individual to ethanol-induced flushing. Decreased uroporphyrinogen decarboxylase may result in porphyria cutanea tarda. Slow acetylators are more susceptible to developing drug-induced lupus erythematosus. A hypersensitivity syndrome may result if a patient is unable to detoxify the toxic metabolites of a drug such as phenytoin. A pharmacogenetic defect should alert the clinician to the possibility of cross-reactivity with other drugs or potential drug reactions in relatives of the patient.