Background/Objectives: Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN) are rare but severe skin conditions, often triggered by medications, that can be life-threatening. These conditions frequently affect the eyes, causing ocular surface disease, which can result in visual impairment or blindness. Although the exact mechanisms behind SJS/TEN remain unclear, key inflammatory mediators such as IL-1β, IL-6, and RIPK3 are believed to play critical roles in inflammation, necroptosis, and regulatory processes. Investigating these factors offers new insights into the disease’s underlying mechanisms and potential targets for treatment. This study aims to determine the roles of IL-1β, IL-6, and RIPK3 in the pathogenesis of SJS/TEN. Methods: The study examined the expression levels of IL-1β, IL-6, and RIPK3 in skin biopsies from patients with biopsy-confirmed SJS/TEN, using lichen planus as a positive control and normal skin as a baseline control. Immunohistochemistry was employed for this analysis. Additionally, the impact of SJS/TEN patient plasma on mitochondrial function was assessed in platelets and human corneal epithelial (H-CET) cells. Using a fluorescent plate reader, mitochondrial activity and superoxide ion levels were measured, comparing plasma from SJS/TEN patients to normal human plasma. Results: Skin biopsies from SJS/TEN patients showed a significantly higher expression of IL-1β, IL-6, and RIPK3 compared to both lichen planus and normal controls. Furthermore, plasma from SJS/TEN patients significantly reduced platelet viability and increased mitochondrial and total cellular superoxide ions, as demonstrated by elevated levels of MitoSOX Red and CellROX Red. Conclusions: These findings suggest that IL-1β, IL-6, and RIPK3 may contribute to the pathogenesis of SJS/TEN and highlight their potential as targets for therapeutic intervention.

Necroptosis has been implicated in the pathogenesis of Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), with prior studies demonstrating tissue-level involvement of receptor-interacting protein kinases RIPK1 and RIPK3. However, their systemic expression in the circulatory compartment remains incompletely characterized. The objective of this study is to evaluate circulating levels of RIPK1 and RIPK3 in patients with SJS/TEN and explore their potential association with diseases. Serum samples from patients with SJS/TEN and control groups were analyzed for RIPK1 and RIPK3 levels using ELISA. Group differences were assessed using non-parametric statistical methods. Circulating levels of RIPK1 and RIPK3 were elevated in patients with SJS/TEN compared with controls. These findings were consistent across analyses; however, variability within groups and overlap between cohorts were observed. These results suggest an association between increased circulating RIPK1 and RIPK3 levels and SJS/TEN. Given the limited sample size, heterogeneous control populations, and lack of functional or phosphorylation-specific assays, these findings should be considered exploratory. Further studies incorporating larger cohorts and mechanistic validation are needed to clarify the role of necroptosis-related pathways in the systemic manifestations of SJS/TEN.

Aim: This preliminary study aims to evaluate the expression of high mobility group box 1 (HMGB-1) in keratoconic corneas, normal corneas, and corneas from donors with Fuchs’ corneal dystrophy using immunohistochemistry. Methods: Under a Loyola University Institutional Review Board (IRB) approved protocol (LU#219768), archived paraffin-embedded corneal tissues were obtained from the Loyola University Medical Center Department of Pathology. The study included three keratoconic corneas, three normal donor corneas, and three Fuchs’ dystrophy corneas. Tissue sections were deparaffinized in 100% xylene, rehydrated through a graded ethanol series, and subjected to antigen retrieval. Sections were stained with an HMGB-1 primary antibody, followed by a fluorescently conjugated anti-rabbit IgG secondary antibody and 4',6-diamidino-2-phenylindole (DAPI) nuclear counterstain. Immunofluorescence imaging and deconvolution analysis were performed using a Nikon Eclipse Ti2 microscope equipped with a digital camera. Two prespecified comparisons, keratoconus versus normal and Fuchs’ dystrophy versus normal, were evaluated using Welch’s independent-samples t tests with Holm adjustment for multiple testing. Statistical analyses were performed using IBM SPSS Statistics. Results: HMGB-1 expression was increased in corneal tissues from patients with keratoconus and Fuchs’ corneal dystrophy compared with normal controls. The increased levels of HMGB-1 suggest enhanced activation of pro-inflammatory and tissue-remodeling pathways. Increased HMGB-1 expression in keratoconus may be associated with cellular stress, inflammation, and extracellular matrix remodeling. Conclusions: These preliminary findings suggest that HMGB-1 expression may be increased in keratoconus; however, due to the small sample size of n = 3 per group, larger studies are needed to confirm this association and clarify its potential role in disease pathogenesis. These findings suggest that HMGB-1 may be associated with corneal cellular stress and inflammatory signaling present in keratoconic corneas and warrant further investigation and validation.