Recommendations for HLA-B*15:02 and HLA-A*31:01 genetic testing to reduce the risk of carbamazepine-induced hypersensitivity reactions.
- Amstutz U Division of Translational Therapeutics, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada; Pharmaceutical Outcomes Programme, British Columbia Children's Hospital, Vancouver, British Columbia, Canada; Child and Family Research Institute, Vancouver, British Columbia, Canada; Department of Clinical Chemistry, University of Bern and Inselspital University Hospital, Bern, Switzerland.
- Shear NH
- Rieder MJ
- Hwang S
- Fung V
- Nakamura H
- Connolly MB
- Ito S
- Carleton BC
- 2014-03-07
Published in:
- Epilepsia. - 2014
Drug-induced hypersensitivity syndrome
Maculopapular exanthema
Pharmacogenetic testing
Rash
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Anticonvulsants
Carbamazepine
Drug Hypersensitivity
Genetic Markers
Genetic Testing
HLA-A Antigens
HLA-B15 Antigen
Humans
Risk Factors
English
OBJECTIVE
To systematically review evidence on genetic risk factors for carbamazepine (CBZ)-induced hypersensitivity reactions (HSRs) and provide practice recommendations addressing the key questions: (1) Should genetic testing for HLA-B*15:02 and HLA-A*31:01 be performed in patients with an indication for CBZ therapy to reduce the occurrence of CBZ-induced HSRs? (2) Are there subgroups of patients who may benefit more from genetic testing for HLA-B*15:02 or HLA-A*31:01 compared to others? (3) How should patients with an indication for CBZ therapy be managed based on their genetic test results?
METHODS
A systematic literature search was performed for HLA-B*15:02 and HLA-A*31:01 and their association with CBZ-induced HSRs. Evidence was critically appraised and clinical practice recommendations were developed based on expert group consensus.
RESULTS
Patients carrying HLA-B*15:02 are at strongly increased risk for CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in populations where HLA-B*15:02 is common, but not CBZ-induced hypersensitivity syndrome (HSS) or maculopapular exanthema (MPE). HLA-B*15:02-positive patients with CBZ-SJS/TEN have been reported from Asian countries only, including China, Thailand, Malaysia, and India. HLA-B*15:02 is rare among Caucasians or Japanese; no HLA-B*15:02-positive patients with CBZ-SJS/TEN have been reported so far in these groups. HLA-A*31:01-positive patients are at increased risk for CBZ-induced HSS and MPE, and possibly SJS/TEN and acute generalized exanthematous pustulosis (AGEP). This association has been shown in Caucasian, Japanese, Korean, Chinese, and patients of mixed origin; however, HLA-A*31:01 is common in most ethnic groups. Not all patients carrying either risk variant develop an HSR, resulting in a relatively low positive predictive value of the genetic tests.
SIGNIFICANCE
This review provides the latest update on genetic markers for CBZ HSRs, clinical practice recommendations as a basis for informed decision making regarding the use of HLA-B*15:02 and HLA-A*31:01 genetic testing in patients with an indication for CBZ therapy, and identifies knowledge gaps to guide future research. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
To systematically review evidence on genetic risk factors for carbamazepine (CBZ)-induced hypersensitivity reactions (HSRs) and provide practice recommendations addressing the key questions: (1) Should genetic testing for HLA-B*15:02 and HLA-A*31:01 be performed in patients with an indication for CBZ therapy to reduce the occurrence of CBZ-induced HSRs? (2) Are there subgroups of patients who may benefit more from genetic testing for HLA-B*15:02 or HLA-A*31:01 compared to others? (3) How should patients with an indication for CBZ therapy be managed based on their genetic test results?
METHODS
A systematic literature search was performed for HLA-B*15:02 and HLA-A*31:01 and their association with CBZ-induced HSRs. Evidence was critically appraised and clinical practice recommendations were developed based on expert group consensus.
RESULTS
Patients carrying HLA-B*15:02 are at strongly increased risk for CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in populations where HLA-B*15:02 is common, but not CBZ-induced hypersensitivity syndrome (HSS) or maculopapular exanthema (MPE). HLA-B*15:02-positive patients with CBZ-SJS/TEN have been reported from Asian countries only, including China, Thailand, Malaysia, and India. HLA-B*15:02 is rare among Caucasians or Japanese; no HLA-B*15:02-positive patients with CBZ-SJS/TEN have been reported so far in these groups. HLA-A*31:01-positive patients are at increased risk for CBZ-induced HSS and MPE, and possibly SJS/TEN and acute generalized exanthematous pustulosis (AGEP). This association has been shown in Caucasian, Japanese, Korean, Chinese, and patients of mixed origin; however, HLA-A*31:01 is common in most ethnic groups. Not all patients carrying either risk variant develop an HSR, resulting in a relatively low positive predictive value of the genetic tests.
SIGNIFICANCE
This review provides the latest update on genetic markers for CBZ HSRs, clinical practice recommendations as a basis for informed decision making regarding the use of HLA-B*15:02 and HLA-A*31:01 genetic testing in patients with an indication for CBZ therapy, and identifies knowledge gaps to guide future research. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
- Language
-
- English
- Open access status
- green
- Identifiers
-
- DOI 10.1111/epi.12564
- PMID 24597466
- Persistent URL
- https://sonar.ch/global/documents/193374
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