Abstract
Purpose :
Drugs are associated with acute-onset of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We have reported that the main causative drugs for SJS/TEN with severe ocular complications (SOC) were cold medicines and within them, dipyrone was the most common cold medicine. This study examined HLA class I and II associations with dipyrone induced SJS/TEN with SOC to help identify possible molecular genetic mechanisms underlying the disease predisposition.
Methods :
We studied the histocompatibility antigen genes HLA-DRB1, and DQB1 in addition of HLA-A, B, C of 27 Brazilian dipyrone related SJS/TEN with SOC. We performed polymerase chain reaction amplification followed by hybridization with sequence-specific oligonucleotide probes (PCR-SSO) using commercial bead-based typing kits. We also used genotyped data of 123 healthy volunteers for HLA-DRB1, DQB1, and HLA-A, B, and C.
Results :
HLA-A*66:01 (carrier frequency: p=0.03; OR=23.8; 95%CI=1.1-526.7) ; gene frequency: p=0.03, OR=22.4; 95%CI=1.0-479.4), HLA-B*44:03 (carrier frequency: p=0.002; OR=8.8; 95%CI=2.3-33.9) ; gene frequency: p=0.001, OR=7.5; 95%CI=2.3-23.8), HLA-DRB1*04:02 (carrier frequency :p=0.03; OR23.8; 95%CI=1.1-526.7) ; gene frequency: p=0.03, OR=22.4; 95%CI=1.0-479.4) and HLA-DQB1*04:02 (carrier frequency :p=0.01; OR=11.4; 95%CI=1.8-70.8) ; gene frequency: p=0.003, OR=12.6; 95%CI=2.3-69) were associated with dypirone related SJS/TEN with SOC in the White Brazilian population. HLA-B*15:17 (carrier frequency: p=0.03; OR=28; 95%CI=1.3-622.8) ; gene frequency: p=0.03, OR=26.2; 95%CI=1.2-563.2 and HLA-B*18:01 (carrier frequency: p=0.03; OR=28; 95%CI=1.3-622.8) ; gene frequency: p=0.03, OR=26.2; 95%CI=1.2-563.2) were associated with dypirone related SJS/TEN with SOC in the Pardo Brazilian population.
Conclusions :
Dypirone related SJS/TEN with SOC was associated with HLA-A*66:01, HLA-B*44:03, HLA-DRB1*04:02 and HLA-DQB1*04:02 in the White Brazilian population and with HLA-B*15:17 and HLA-B*18:01 in the Pardo Brazilian population.
This is a 2020 ARVO Annual Meeting abstract.