METHODS: DNA was extracted from eighty-six patients. The patients were genotyped by AS-PCR. Computational modeling of the HLA-B*15:02 followed by docking studies were performed to screen 26 AEDs that may induce ADR among HLA-B*15:02 carriers.
RESULTS: Odd ratio for CBZ induced SJS/TEN and HLA-B*15:02 was 609.0 (95% CI: 23-15873; p=0.0002). Molecular modeling studies showed that acetazolamide, ethosuxiamide, lamotrigine, oxcarbazepine, phenobarbital, phenytoin, primidone and sodium-valproate may induce ADR in HLA-B*15:02 carriers alike CBZ. Conclusion. We confirmed HLA-B*15:02 as a predictor of SJS/TEN and recommend pre-screening. Computational prediction of DIHR is useful in personalized medicine.
METHODS: A retrospective study of all hospitalized cases of EM, SJS, and TEN was conducted covering an 8-year period from 1987 to 1994.
RESULTS: There were four cases (13.8%) of EM, 22 cases (75.9%) of SJS, and three cases (10.3%) of TEN. Drugs as a definitive cause was observed in one case (25%) of EM, 12 cases (54.5%) of SJS, and two cases (66.7%) of TEN. Drugs as a probable cause was observed in seven cases (31.8%) of SJS and one case (33.3%) of TEN. The male to female ratio was equal in EM and SJS. Antiepileptics were the commonest culprits, followed by antibiotics. One patient died of SJS and one patient died of TEN, giving mortality rates of 4.5% and 33.5% respectively. Fever was noted in 18 patients (62.1%). Leukocytosis was noted in 10 patients (34.5%), and nine patients (31.0%) had elevated liver transaminase enzymes. No significant correlation was noted between these biochemical changes and cutaneous eruption. Secondary infections were observed in 11 patients (37.9%): Staphylococcus aureus was the commonest isolated organism.
CONCLUSIONS: This study shows that drugs remain the commonest culprit in SJS and TEN. Despite adequate treatment, the mortality rate remains high, especially in TEN. These findings are similar to those of other reported studies.
METHODS: A case-control study was performed to detect HLA loci involved in aromatic antiepileptic drug-induced Stevens-Johnson syndrome in a southern Han Chinese population. Between January 1, 2006, and December 31, 2015, 91 cases of Stevens-Johnson syndrome induced by aromatic antiepileptic drugs and 322 matched drug-tolerant controls were enrolled from 8 centers. Important genotypes were replicated in cases with maculopapular eruption and in the meta-analyses of data from other populations. Sequence-based typing determined the HLA-A, HLA-B, HLA-C, and HLA-DRB1 genotypes.
RESULTS: HLA-B*15:02 was confirmed as strongly associated with carbamazepine-induced Stevens-Johnson syndrome (p = 5.63 × 10(-15)). In addition, HLA-A*24:02 was associated significantly with Stevens-Johnson syndrome induced by the aromatic antiepileptic drugs as a group (p = 1.02 × 10(-5)) and by individual drugs (carbamazepine p = 0.015, lamotrigine p = 0.005, phenytoin p = 0.027). Logistic regression analysis revealed a multiplicative interaction between HLA-B*15:02 and HLA-A*24:02. Positivity for HLA-A*24:02 and/or HLA-B*15:02 showed a sensitivity of 72.5% and a specificity of 69.0%. The presence of HLA-A*24:02 in cases with maculopapular exanthema was also significantly higher than in controls (p = 0.023). Meta-analysis of data from Japan, Korea, Malaysia, Mexico, Norway, and China revealed a similar association.
CONCLUSIONS: HLA-A*24:02 is a common genetic risk factor for cutaneous adverse reactions induced by aromatic antiepileptic drugs in the southern Han Chinese and possibly other ethnic populations. Pretreatment screening is recommended for people in southern China.