004 Clinicopathological and molecular profile of Stevens–Johnson syndrome and toxic epidermal necrolysis-like acute graft-versus-host disease

Cutaneous manifestations of acute graft-versus-host disease (aGVHD) can mimic drug-induced-Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). We aimed to investigate clinicopathological characteristics, transcriptomic profiles, and prognosis of SJS/TEN-like aGVHD. We analyzed and compared a retrospective cohort of 15 SJS/TEN-like-aGVHD patients and 16 non-SJS/TEN-like-aGVHD patients between 2000 and 2021. SJS/TEN-like aGVHD was associated with significantly more extensive erythema and skin detachment, higher aGVHD grading, more bacteremia and multiorgan complications. Histopathology of skin samples from SJS/TEN-like aGVHD showed significantly severe dyskeratosis and interface change. Transcriptomic profile by NanoString technology showed upregulated IL-8, IL-1B, CCL20, THBS1, ITGB4, AXL, AMICA1, TNFRSF18, CMA1, CD207, CD1C and MS4A2 of SJS/TEN-like aGVHD compared with non-SJS/TEN-like aGVHD. Non-SJS/TEN-like aGVHD showed higher FOXP3 expression. Immunohistochemistry on skin biopsy samples of SJS/TEN-like aGVHD showed significantly lower CD45RO, CD103 as well as FoxP3 cells compared with non-SJS/TEN-like aGVHD. The total mortality rate of SJS/TEN-like aGVHD patients was 80% with higher 2-month early and 5-year late mortality rates compared with non-SJS/TEN-like aGVHD. T-regulatory (Treg) cells play a crucial role in maintaining immune tolerance after transplantation and reduced Treg cells are associated with GVHD development. Lower immune tolerance resulting from fewer Treg cells in SJS/TEN-like aGVHD may contribute to intense skin inflammation, severe extracutaneous complications, and poor prognosis. SJS/TEN-like aGVHD is associated with multiple systemic complications and high mortality. Hyperinflammation with decreased immune-regulation may contribute to the disease severity.