title: Severe Cutaneous Adverse Reactions: The Pharmacogenomics from Research to Clinical Implementation.
abstract: Severe cutaneous adverse reactions (SCARs), previously thought to be idiosyncratic or unpredictable, are a deadly form of adverse drug reactions with skin manifestations. Current pharmacogenomic studies of SCARs have made important strides, as the prevention of SCARs, to some extent, appears attainable with the identification of genetic variants for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs). Despite the improvement of incidence, a treatment guideline for this devastating condition is still unavailable, highlighting the inadequacy of contemporary accepted therapeutic interventions. As such, prompt withdrawal of causative drugs is believed to be a priority of patient management. In this review, we discuss recent cutting-edge findings concerning the discovery of biomarkers for SCARs and their clinical utilities in the better prediction and early diagnosis of this disease. The knowledge compiled herein provides clues for future investigations on deciphering additional genetic markers for SCARs and the design of clinical trials for the prospective identification of subjects at genetic risk for this condition, ultimately personalizing the medicine.
authors.affiliation: Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung 204, Taiwan. ssu1@cgmh.org.tw.|Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taipei, Linkou and Keelung 105, Taiwan. ssu1@cgmh.org.tw.
authors.forename: Shih-Chi
authors.initials: SC
authors.lastname: Su
authors.affiliation: Institute of Pharmacology, School of Medicine, Infection and Immunity Research Center, National Yang-Ming University, Taipei 112, Taiwan. sihung@ym.edu.tw.
authors.forename: Shuen-Iu
authors.initials: SI
authors.lastname: Hung
authors.affiliation: Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung 204, Taiwan. alangfan@gmail.com.
authors.forename: Wen-Lang
authors.initials: WL
authors.lastname: Fan
authors.affiliation: Institute of Pharmacology, School of Medicine, Infection and Immunity Research Center, National Yang-Ming University, Taipei 112, Taiwan. laura44@ms10.hinet.net.
authors.forename: Ro-Lan
authors.initials: RL
authors.lastname: Dao
authors.affiliation: Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung 204, Taiwan. chung1@cgmh.org.tw.|Institute of Pharmacology, School of Medicine, Infection and Immunity Research Center, National Yang-Ming University, Taipei 112, Taiwan. chung1@cgmh.org.tw.|College of Medicine, Chang Gung University, Taoyuan 333, Taiwan. chung1@cgmh.org.tw.
authors.forename: Wen-Hung
authors.initials: WH
authors.lastname: Chung
mesh_terms: D000493:Allopurinol / Q000009:adverse effects; D019380:Anti-HIV Agents / Q000009:adverse effects*; D000927:Anticonvulsants / Q000009:adverse effects*; D015415:Biomarkers / Q000378:metabolism; D002220:Carbamazepine / Q000009:adverse effects; D015224:Dideoxynucleosides / Q000009:adverse effects; D005819:Genetic Markers; D006074:Gout Suppressants / Q000009:adverse effects*; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics / Q000276:immunology; D010597:Pharmacogenetics; D057285:Precision Medicine; D011379:Prognosis; D056737:Safety-Based Drug Withdrawals; D013262:Stevens-Johnson Syndrome / Q000209:etiology / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D000099227:Abacavir
chemical_list: D000493:Allopurinol; D019380:Anti-HIV Agents; D000927:Anticonvulsants; D015415:Biomarkers; D002220:Carbamazepine; D015224:Dideoxynucleosides; D005819:Genetic Markers; D006074:Gout Suppressants; D015235:HLA-B Antigens; D000099227:Abacavir
keywords: clinical implementation; pharmacogenomics; severe cutaneous adverse reactions