title: Pharmacogenetic markers of severe cutaneous adverse drug reactions.
abstract: Different responses, in terms both of efficacy and toxicity, are commonly observed for any drug administered to apparently homogeneous groups of patients. It is estimated that adverse drug reactions (ADRs) cause 3-6% of all hospitalizations, accounting for 5% to 9% of hospital admission costs. The skin is often involved in ADRs and although most cutaneous ADRs have a favorable course, they may present as severe adverse cutaneous drug reactions (SCARs), such as Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (also referred to as drug-induced hypersensitivity syndrome), and acute generalized exanthematous pustulosis. SCARs are associated with significant mortality and require prompt diagnosis and adequate treatment. Pharmacogenetics studies individual variants in the DNA sequence associated with drug efficacy and toxicity, allowing prescription of a drug to patients expected to benefit from it, and excluding from treatment those who are at risk of developing ADRs. Pharmacogenetics already achieved several important results in the prevention of SCARs, and pharmacogenetic testing is now recommended by regulatory agencies before administration of abacavir and carbamazepine, leading to reduced incidence of SCARs. In this review, the pharmacogenetic associations of SCARs that have been validated in independent, case-control association studies will be presented. By familiarizing with principles of pharmacogenetics, dermatologists should be able to correlate specific cutaneous ADR phenotypes to the underlying genotype, thus contributing to better drug safety and facilitating drug discovery, development and approval.
authors.affiliation: Centre for Inherited Cardiovascular Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy - r.borroni@smatteo.pv.it.
authors.forename: R G
authors.initials: RG
authors.lastname: Borroni
mesh_terms: D000493:Allopurinol / Q000009:adverse effects; D019380:Anti-HIV Agents / Q000009:adverse effects; D000927:Anticonvulsants / Q000009:adverse effects; D015415:Biomarkers; D002220:Carbamazepine / Q000009:adverse effects; D015224:Dideoxynucleosides / Q000009:adverse effects; D003875:Drug Eruptions / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control; D063926:Drug Hypersensitivity Syndrome / Q000209:etiology / Q000235:genetics; D004791:Enzyme Inhibitors / Q000009:adverse effects; D005805:Genes, MHC Class I; D055106:Genome-Wide Association Study; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D019829:Nevirapine / Q000009:adverse effects; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D013262:Stevens-Johnson Syndrome / Q000209:etiology / Q000235:genetics; D000099227:Abacavir
chemical_list: D000493:Allopurinol; D019380:Anti-HIV Agents; D000927:Anticonvulsants; D015415:Biomarkers; D002220:Carbamazepine; D015224:Dideoxynucleosides; D004791:Enzyme Inhibitors; D006680:HLA Antigens; D019829:Nevirapine; D000099227:Abacavir