title: Do HLA-A markers predict skin-reactions from aromatic antiepileptic drugs in a Norwegian population? A case control study.
abstract: OBJECTIVE
  Cutaneous adverse reactions (cADRs) from carbamazepine (CBZ) have been associated with human leukocyte antigens (HLA). Our aims were to assess the clinical usefulness of HLA-A*31:01 as a predictor of CBZ-induced cADRs in the Norwegian population and to explore whether cADRs from aromatic antiepileptic drugs (AEDs) in general might be linked with a common HLA-A-marker.
  
  
  METHODS
  86 ethnic Norwegians with a history of non-bullous cADRs from aromatic AEDs were included. 114 subjects tolerant to at least one aromatic AED were used as drug-specific controls. Complete HLA-A genotyping was performed. 1026 blood donors were used as population controls.
  
  
  RESULTS
  Comparing all cADR subjects with controls and blood donors, there were no statistical differences for any HLA-A allele, except for HLA-A*24 (p=0.022 vs. controls and p=0.014 vs. blood donors). When comparing tolerant controls with patients having had a cADR to one of the two most used drugs, CBZ (n=48) and lamotrigine (n=28), we found no significant associations for CBZ to HLA-A*31:01 or HLA-A*24:02, but for lamotrigine there was an association with HLA-A*24:02 (p=0.027). In patients developing cross-reactivity (n=14) to aromatic AEDs, the presence of HLA-A*31:01 or HLA-A*24:02 was not different compared to patients with a single cARD tolerant to at least one other drug.
  
  
  CONCLUSIONS
  We question the clinical usefulness of HLA-A*31:01 as a marker for CBZ rash in the Norwegian population. A previously suggested protective effect of aromatic AED cross-reactivity from HLA-A*24:02 was not confirmed. The association between HLA-A*24:02 and lamotrigine-induced rash should be further investigated.
authors.affiliation: Department of Neurology and Clinical Neurophysiology, St Olav's Hospital, Trondheim, Norway; Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Maryam
authors.initials: M
authors.lastname: Shirzadi
authors.affiliation: Department of Medical Biochemistry, St Olav's Hospital, Trondheim, Norway.
authors.forename: Ketil
authors.initials: K
authors.lastname: Thorstensen
authors.affiliation: Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Grethe
authors.initials: G
authors.lastname: Helde
authors.affiliation: Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway; Department of Immunology and Transfusion Medicine, St Olav's Hospital, Trondheim, Norway.
authors.forename: Torolf
authors.initials: T
authors.lastname: Moen
authors.affiliation: Department of Neurology and Clinical Neurophysiology, St Olav's Hospital, Trondheim, Norway; Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway. Electronic address: eylert.brodtkorb@ntnu.no.
authors.forename: Eylert
authors.initials: E
authors.lastname: Brodtkorb
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects*; D002220:Carbamazepine / Q000009:adverse effects*; D016022:Case-Control Studies; D003429:Cross Reactions; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D059871:HLA-A24 Antigen / Q000235:genetics; D015791:HLA-A3 Antigen / Q000235:genetics*; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D009664:Norway; D014227:Triazines / Q000009:adverse effects; D018366:Vasculitis, Leukocytoclastic, Cutaneous / Q000139:chemically induced* / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D000927:Anticonvulsants; C442141:HLA-A*03:01 antigen; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen; D015791:HLA-A3 Antigen; D014227:Triazines; D002220:Carbamazepine; D000077213:Lamotrigine
keywords: Antiepileptic drug; Carbamazepine; Cross-reactivity; Cutaneous adverse reaction; HLA-A complex; Lamotrigine