{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:33:42Z","timestamp":1788532422463,"version":"build-2803163510"},"reference-count":60,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,3,5]],"date-time":"2014-03-05T00:00:00Z","timestamp":1393977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["FRN 114403"],"award-info":[{"award-number":["FRN 114403"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2014,4]]},"abstract":"Summary<\/jats:title>\n \n Objective<\/jats:title>\n \n To systematically review evidence on genetic risk factors for carbamazepine (\n CBZ<\/jats:styled-content>\n )\u2013induced hypersensitivity reactions (\n HSR<\/jats:styled-content>\n s) and provide practice recommendations addressing the key questions: (1) Should genetic testing for\n HLA<\/jats:styled-content>\n \u2010B*15:02 and\n HLA<\/jats:styled-content>\n \u2010A*31:01 be performed in patients with an indication for\n CBZ<\/jats:styled-content>\n therapy to reduce the occurrence of\n CBZ<\/jats:styled-content>\n \u2010induced\n HSR<\/jats:styled-content>\n s? (2) Are there subgroups of patients who may benefit more from genetic testing for\n HLA<\/jats:styled-content>\n \u2010B*15:02 or\n HLA<\/jats:styled-content>\n \u2010A*31:01 compared to others? (3) How should patients with an indication for\n CBZ<\/jats:styled-content>\n therapy be managed based on their genetic test results?\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n A systematic literature search was performed for\n HLA<\/jats:styled-content>\n \u2010B*15:02 and\n HLA<\/jats:styled-content>\n \u2010A*31:01 and their association with\n CBZ<\/jats:styled-content>\n \u2010induced\n HSR<\/jats:styled-content>\n s. Evidence was critically appraised and clinical practice recommendations were developed based on expert group consensus.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Patients carrying\n HLA<\/jats:styled-content>\n \u2010B*15:02 are at strongly increased risk for\n CBZ<\/jats:styled-content>\n \u2010induced Stevens\u2010Johnson syndrome\/toxic epidermal necrolysis (\n SJS<\/jats:styled-content>\n \/\n TEN<\/jats:styled-content>\n ) in populations where\n HLA<\/jats:styled-content>\n \u2010B*15:02 is common, but not\n CBZ<\/jats:styled-content>\n \u2010induced hypersensitivity syndrome (\n HSS<\/jats:styled-content>\n ) or maculopapular exanthema (\n MPE<\/jats:styled-content>\n ).\n HLA<\/jats:styled-content>\n \u2010B*15:02\u2013positive patients with\n CBZ<\/jats:styled-content>\n \u2010\n SJS<\/jats:styled-content>\n \/\n TEN<\/jats:styled-content>\n have been reported from Asian countries only, including China, Thailand, Malaysia, and India.\n HLA<\/jats:styled-content>\n \u2010B*15:02 is rare among Caucasians or Japanese; no\n HLA<\/jats:styled-content>\n \u2010B*15:02\u2010positive patients with\n CBZ<\/jats:styled-content>\n \u2010\n SJS<\/jats:styled-content>\n \/\n TEN<\/jats:styled-content>\n have been reported so far in these groups.\n HLA<\/jats:styled-content>\n \u2010A*31:01\u2013positive patients are at increased risk for\n CBZ<\/jats:styled-content>\n \u2010induced\n HSS<\/jats:styled-content>\n and\n MPE<\/jats:styled-content>\n , and possibly\n SJS<\/jats:styled-content>\n \/\n TEN<\/jats:styled-content>\n and acute generalized exanthematous pustulosis (\n AGEP<\/jats:styled-content>\n ). This association has been shown in Caucasian, Japanese, Korean, Chinese, and patients of mixed origin; however,\n HLA<\/jats:styled-content>\n \u2010A*31:01 is common in most ethnic groups. Not all patients carrying either risk variant develop an\n HSR<\/jats:styled-content>\n , resulting in a relatively low positive predictive value of the genetic tests.\n <\/jats:p>\n <\/jats:sec>\n \n Significance<\/jats:title>\n \n This review provides the latest update on genetic markers for\n CBZ HSR<\/jats:styled-content>\n s, clinical practice recommendations as a basis for informed decision making regarding the use of\n HLA<\/jats:styled-content>\n \u2010B*15:02 and\n HLA<\/jats:styled-content>\n \u2010A*31:01 genetic testing in patients with an indication for\n CBZ<\/jats:styled-content>\n therapy, and identifies knowledge gaps to guide future research.\n <\/jats:p>\n \n A PowerPoint slide summarizing this article is available for download in the Supporting Information section\n here<\/jats:ext-link>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/epi.12564","type":"journal-article","created":{"date-parts":[[2014,3,5]],"date-time":"2014-03-05T17:30:55Z","timestamp":1394040655000},"page":"496-506","source":"Crossref","is-referenced-by-count":204,"title":["Recommendations for\n HLA<\/scp>\n \u2010B*15:02 and\n HLA<\/scp>\n \u2010A*31:01 genetic testing to reduce the risk of carbamazepine\u2010induced hypersensitivity reactions"],"prefix":"10.1111","volume":"55","author":[{"given":"Ursula","family":"Amstutz","sequence":"first","affiliation":[{"name":"Division of Translational Therapeutics Department of Pediatrics University of British Columbia Vancouver British Columbia Canada"},{"name":"Pharmaceutical Outcomes Programme British Columbia Children's Hospital Vancouver British Columbia Canada"},{"name":"Child and Family Research Institute Vancouver British Columbia Canada"},{"name":"Department of Clinical Chemistry University of Bern and Inselspital University Hospital Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil H.","family":"Shear","sequence":"additional","affiliation":[{"name":"Dermatology, Clinical Pharmacology and Toxicology Department of Medicine Sunnybrook Health Sciences Centre University of Toronto Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Rieder","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Departments of Medicine, Physiology, Pharmacology and Pediatrics Schulich School of Medicine and Dentistry University of Western Ontario London ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soomi","family":"Hwang","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences University of British Columbia Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Fung","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences University of British Columbia Vancouver British Columbia Canada"},{"name":"Prohealth Clinical Research Centre Vancouver British Columbia Canada"},{"name":"Departments of Family Medicine and Pathology and Laboratory Medicine Faculty of Medicine University of British Columbia Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidefumi","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Division for Clinical Trials Clinical Research Center National Center for Child Health and Development Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary B.","family":"Connolly","sequence":"additional","affiliation":[{"name":"Child and Family Research Institute Vancouver British Columbia Canada"},{"name":"Division of Neurology Department of Pediatrics British Columbia Children's Hospital and University of British Columbia Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Ito","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and Toxicology Department of Pediatrics The Hospital for Sick Children University of Toronto Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce C.","family":"Carleton","sequence":"additional","affiliation":[{"name":"Division of Translational Therapeutics Department of Pediatrics University of British Columbia Vancouver British Columbia Canada"},{"name":"Pharmaceutical Outcomes Programme British Columbia Children's Hospital Vancouver British Columbia Canada"},{"name":"Child and Family Research Institute Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the CPNDS clinical recommendation group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,3,5]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"Novartis Pharmaceuticals Corporation.Tegretol\u00ae[prescribing information]. 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