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Association between human leukocyte antigens and cutaneous adverse drug reactions to antiepileptics and antibiotics in the Iranian population

Mortazavi, H ; Sharif University of Technology | 2022

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  1. Type of Document: Article
  2. DOI: 10.1111/dth.15393
  3. Publisher: John Wiley and Sons Inc , 2022
  4. Abstract:
  5. In this case–control study, class І and ІІ human leukocyte antigen (HLA) alleles in Iranian patients with benign and severe cutaneous adverse drug reactions (CADRs) due to aromatic anticonvulsants and antibiotics were evaluated. Patients diagnosed with CADRs (based on clinical and laboratory findings) with a Naranjo score of ≥ 4 underwent blood sampling and HLA-DNA typing. The control group comprised 90 healthy Iranian adults. Alleles with a frequency of more than two were reported. Deviations from Hardy–Weinberg equilibrium were not observed. Eighty patients with CADRs including 54 females and 26 males with a mean age of 41.49 ± 16.08 years were enrolled in this study. The culprit drugs included anticonvulsants (lamotrigine, carbamazepine, and phenytoin) and antibiotics (ciprofloxacin and co-trimoxazole). The comparison of allele frequencies in the Iranian healthy control group and the group with benign CADRs revealed that HLA-Cw*04, and HLA-A*24 were significantly associated with lamotrigine-induced maculopapular CADRs. Furthermore, HLA-B*51 showed a significant correlation with carbamazepine-induced maculopapular CADRs. Significant associations were also detected between ciprofloxacin-induced urticarial CADRs with HLA-B*40, and HLA-DRB1*14. In the severe group, HLA-B*38 and HLA-DRB1*13 were significantly associated with lamotrigine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Moreover, HLA-A*31 and HLA-Cw*04 were significantly correlated with carbamazepine-induced drug reactions with eosinophilia and systemic symptoms (DRESS). HLA-B*08 also showed a significant correlation with ciprofloxacin-induced acute generalized exanthematous pustulosis (AGEP). In conclusion, Lamotrigine-induced MPE was significantly correlated with HLA-Cw*04, and HLA-A*24. Similarly, lamotrigine-induced SJS/TEN was significantly associated with HLA-B*38 and HLA-DRB1*13. Additionally, HLA-A*31 was associated with DRESS caused by carbamazepine. The most frequent CADR-inducing drugs were anticonvulsants. © 2022 Wiley Periodicals LLC
  6. Keywords:
  7. Antibiotics ; Antiepileptics ; Culprit drug ; Cutaneous adverse drug reaction ; Human leukocyte antigen ; Alanine aminotransferase ; Antibiotic agent ; Anticonvulsive agent ; Aspartate aminotransferase ; Cefalexin ; Cefixime ; Cotrimoxazole ; Creatinine ; HLA antigen class 1 ; HLA antigen class 2 ; HLA C antigen ; HLA DRB1 antigen ; Leukocyte antigen ; Ofloxacin ; Phenytoin ; Piperacillin ; Antiinfective agent ; HLA A antigen ; HLA antigen ; Acute generalized exanthematous pustulosis ; Blood sampling ; Case control study ; Controlled study ; DNA probe ; DRESS syndrome ; Eosinophilia ; Erythema multiforme ; Fixed drug eruption ; Genetic association ; Histopathology ; Human ; Human tissue ; Iranian people ; Maculopapular rash ; Major clinical study ; Phototoxicity ; Severe cutaneous adverse reaction ; Stevens Johnson/toxic epidermal necrolysis overlap syndrome ; Syndrome ; Toxic epidermal necrolysis ; Urticaria ; Genetics ; Stevens Johnson syndrome ; Adult ; Anti-Bacterial Agents ; Anticonvulsants ; Carbamazepine ; Case-Control Studies ; Ciprofloxacin ; Female ; Genotype ; HLA Antigens ; HLA-B Antigens ; HLA-DRB1 Chains ; Humans ; Iran ; Lamotrigine ; Male ; Middle Aged ; Stevens-Johnson Syndrome ; HLA B antigen ; HLA-A Antigens
  8. Source: Dermatologic Therapy ; Volume 35, Issue 5 , 2022 ; 13960296 (ISSN)
  9. URL: https://onlinelibrary.wiley.com/doi/abs/10.1111/dth.15393