Association of human antigen class I and class II genes with Stevens-Johnson syndrome/toxic epidermal necrolysis in a United States population

Abstract

Purpose : To investigate the association between class I and II human leukocyte antigen (HLA) genes and Stevens-Johnson syndrome (SJS)/ toxic epidermal necrolysis (TEN) with or without severe ocular complications (SOC) in an American population.

Methods : A prospective multicenter case-control study enrolled SJS/TEN patients and healthy controls from the families of the SJS/TEN patients between January 2017 and August 2020. HLA genotyping (HLA-A, HLA-B, HLA-C, and HLA-D) was performed using polymerase chain reaction followed by hybridization with sequence-specific oligonucleotide probes.

Results : The current study included 74 SJS/TEN patients and 49 healthy controls. The mean age of SJS/TEN patients at the onset of disease was 38.5± 20.0 years compared to 44.2±25.2 years in the healthy controls (P=0.76). In the SJS/TEN cohort, 60 patients had drug-induced SJS/TEN with lamotrigine and trimethoprim/ sulfamethoxazole being the most common inciting agents.
Age, sex, or race had no effect on the development of SOCs in patients with SJS/TEN. HLA-DQB1*03:01 was more prevalent in the SJS/TEN without SOC group (P=0.04). When looking at drug-specific SJS/TEN, HLA-A*68:01 was positively associated with lamotrigine-induced SJS/TEN (P=0.024). In allopurinol-induced SJS/TEN, HLA-B*58:01 was positively associated with disease (P<0.001). In trimethoprim-sulfamethoxazole, ibuprofen, and penicillin-induced SJS/TEN, no HLA genes were found to be associated with disease.

Conclusions : In the SJS/TEN cohort, HLA-DQB1*03:01 was shown to be protective against SOC development. HLA-A*68:01 and HLA-B*58:01 were positively associated with lamotrigine and allopurinol-induced SJS/TEN, respectively.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.