Pharmacogenetics and Adverse Drug Reactions in the Skin

Abstract: 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.