The following is a summary of “TNF-α‒Mediated Keratinocyte Expression and Release of Matrix Metalloproteinase 9: Putative Mechanism of Pathogenesis in Stevens‒Johnson Syndrome/Toxic Epidermal Necrolysis” published in the June 2023 issue of Investigative Dermatology by Olsson-Brown et al.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are severe adverse drug reactions of the skin characterized by extensive keratinocyte cell death and epidermal detachment. Little is known about how the separation occurs or how the TNF-inhibitor etanercept, an efficacious SJS/TEN treatment, prevents it. Utilizing RNA sequencing, upregulated transcripts in formalin-fixed, paraffin-embedded SJS/TEN epidermis biopsies were identified. 

Immunohistochemistry was used to evaluate the expression of matrix metalloproteinase 9 (MMP9) in skin biopsies and cultured human skin explants exposed to serum from patients with cutaneous adverse drug reactions. Using the HaCaT immortalized keratinocyte cell line, the TNF-induced expression and activity of MMP9 and its inhibition by etanercept were analyzed. Expression of epidermal MMP9 was markedly higher in SJS/TEN skin (70.6%) than in healthy control skin (0%; P = 0.0098) and nonbullous skin reactions (10.7%; P = 0.0002). Etanercept inhibited the induction of MMP9 expression and collagenase activity by SJS/TEN serum in healthy skin explants. 

Etanercept also inhibited the MMP9 expression induced by TNF- in the HaCaT cell line. Evidence suggests elevated epidermal MMP9 expression and collagenase activity are potential pathogenic mechanisms in SJS/TEN, mitigated by etanercept. To our knowledge, modulation of MMP9 expression and activity is an unreported therapeutic target for treating SJS/TEN.

Source: sciencedirect.com/science/article/pii/S0022202X22028986