title: HLA-A*31:01 and different types of carbamazepine-induced severe cutaneous adverse reactions: an international study and meta-analysis.
abstract: HLA-A*31:01 was reported to be associated with carbamazepine (CBZ)-induced severe cutaneous adverse reactions (SCAR), including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We conducted an international study using consensus diagnosis criteria to enroll a total of 93 patients with CBZ-SCAR from Europe or Asia. We found that HLA-A*31:01 showed a significant association with CBZ-DRESS in Europeans (P<0.001; odds ratio (OR) (95% confidence interval (CI))=57.6 (11.0-340)), and the strong association was also found in Chinese (P<0.001; OR (95% CI)=23.0 (4.2-125)). However, HLA-A*31:01 had no association with CBZ-SJS/TEN in neither Chinese nor Europeans. By comparison, HLA-B*15:02 showed a strong association with CBZ-SJS/TEN in Chinese (P<0.001, OR (95% CI)=58.1 (17.6-192)). A meta-analysis of this and other published studies confirmed that in all populations, HLA-A*31:01 had an extremely strong association with CBZ-DRESS (P<0.001, a pooled OR (95% CI)=13.2 (8.4-20.8)), but a much weaker association with CBZ-SJS/TEN (P=0.01, OR (95% CI)=3.94 (1.4-11.5)). Our data revealed that HLA-A*31:01 is a specific predictor for CBZ-DRESS but not for CBZ-SJS/TEN. More studies are needed to investigate the genetic determinant of CBZ-SJS/TEN in Europeans. Considering the potential clinical utility, the cost-effectiveness of the combined HLA-A*31:01 and HLA-B*15:02 genetic test to prevent CBZ-SCAR in Chinese needs further investigation.
authors: Inserm U946, Saint Louis Hospital, Institut Universitaire d'Hématologie, Université Paris Diderot, Paris, France.
authors: E
authors: E
authors: Genin
authors: 1] Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan [2] Department of Medical Biotechnology and Laboratory Science, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors: D-P
authors: DP
authors: Chen
authors: Institute of Pharmacology, School of Medicine, Infection and Immunity Research Center, National Yang-Ming University, Taipei, Taiwan.
authors: S-I
authors: SI
authors: Hung
authors: Institute of Medical Biometry and Medical Informatics, Freiburg University-Medical Center, Freiburg, Germany.
authors: P
authors: P
authors: Sekula
authors: Institute of Medical Biometry and Medical Informatics, Freiburg University-Medical Center, Freiburg, Germany.
authors: M
authors: M
authors: Schumacher
authors: 1] Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan [2] Department of Medical Biotechnology and Laboratory Science, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors: P-Y
authors: PY
authors: Chang
authors: 1] Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan [2] Department of Medical Biotechnology and Laboratory Science, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors: S-H
authors: SH
authors: Tsai
authors: 1] Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan [2] Department of Medical Biotechnology and Laboratory Science, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors: T-L
authors: TL
authors: Wu
authors: Research Unit, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.
authors: T
authors: T
authors: Bellón
authors: 1] Jean Dausset Laboratory, Saint Louis Hospital, Paris, France [2] Inserm UMRS 940, Saint Louis Hospital, Institut Universitaire d'Hématologie, Université Paris Diderot, Paris, France.
authors: R
authors: R
authors: Tamouza
authors: 1] Jean Dausset Laboratory, Saint Louis Hospital, Paris, France [2] Inserm UMRS 940, Saint Louis Hospital, Institut Universitaire d'Hématologie, Université Paris Diderot, Paris, France.
authors: C
authors: C
authors: Fortier
authors: 1] Jean Dausset Laboratory, Saint Louis Hospital, Paris, France [2] Inserm UMRS 940, Saint Louis Hospital, Institut Universitaire d'Hématologie, Université Paris Diderot, Paris, France.
authors: A
authors: A
authors: Toubert
authors: 1] Jean Dausset Laboratory, Saint Louis Hospital, Paris, France [2] Inserm UMRS 940, Saint Louis Hospital, Institut Universitaire d'Hématologie, Université Paris Diderot, Paris, France.
authors: D
authors: D
authors: Charron
authors: Inserm UMRS 940, Saint Louis Hospital, Institut Universitaire d'Hématologie, Université Paris Diderot, Paris, France.
authors: A
authors: A
authors: Hovnanian
authors: Inserm UMRS 940, Saint Louis Hospital, Institut Universitaire d'Hématologie, Université Paris Diderot, Paris, France.
authors: P
authors: P
authors: Wolkenstein
authors: Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospitals, Keelung, Linko, Chang Gung University College of Medicine, Taipei, Taiwan.
authors: W-H
authors: WH
authors: Chung
authors: Dokumentationszentrum schwerer Hautreaktionen (dZh), Department of Dermatology, Freiburg University-Medical Center, Freiburg, Germany.
authors: M
authors: M
authors: Mockenhaupt
authors: Service Dermatologie, Hôpital Henri-Mondor, Université Paris-Est, Créteil, France.
authors: J-C
authors: JC
authors: Roujeau
mesh_terms: D002220:Carbamazepine / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D015234:HLA-A Antigens / Q000235:genetics*; D006801:Humans; D012867:Skin / Q000187:drug effects*
chemical_list: D015234:HLA-A Antigens; D002220:Carbamazepine