Update on Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Diagnosis and Management

Abstract

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the most severe cutaneous adverse reactions that are typically drug-induced in adults. Both SJS and TEN have high morbidity and mortality rates. SJS/TEN imposes clinical challenges for physicians managing patients suffering from this condition, both because it is rare and because it is a rapidly progressing systemic disease with severe cutaneous, mucosal, and systemic manifestations. Although many cases of SJS/TEN have been reported in the literature, there is no consensus regarding diagnostic criteria or treatment. Significant progress has been made in understanding its genetic predisposition and pathogenesis. This review is intended to provide physicians with a comprehensive but practical SJS/TEN roadmap to guide diagnosis and management. We review data on pathogenesis, reported precipitating factors, presentation, diagnosis, and management SJS/TEN focusing on what is new over the last 5 years.

Fig. 1

This figure describes the various pathways that lead to keratinocyte apoptosis and necroptosis, including interactions between antigen-presenting cells (APC), T cells, natural killer cells, monocytes, and keratinocytes. Natural killer (NK) cells can trigger keratinocyte apoptosis through interaction of CD94/NKG2C with HLA-E on keratinocytes and are the likely source of granulysin. APC present a peptide on a major histocompatibility complex (MHC) to a T cell receptor (TCR) expressed on a CD8+ (cytotoxic) T cell. The activated CD8+ T cells then trigger downstream cytokine/chemokine production and epidermal keratinocyte apoptosis through the Fas/Fas ligand (FasL) and the TCR/human leukocyte antigen (HLA) pathways. Additionally, drug-activated monocytes may trigger necroptosis of keratinocytes via Annexin A1 binding to formyl peptide receptor 1 (FPR1). The figure also outlines targets of treatment options including intravenous immunoglobulin, etanercept, and tumor necrosis factor. Abbreviations: TNF = tumor necrosis factor, HMGB1 = high mobility group box 1, TRAIL = TNF-related apoptosis-inducing ligand, FasL = Fas ligand, IL = interleukin, HLA = human leukocyte antigen, CD = cluster of differentiation, NKG2C = natural killer gene 2C, TCR = T cell receptor, MHC = major histocompatibility complex, T_RM = skin-resident memory T cells, CYP450 = cytochrome P450. Created with biorender.com

Fig. 2

Images of SJS/TEN. SJS/TEN presents with desquamation (A) and bullae (B) over large areas of skin. Additionally, it can present with genital (C), oral (D), and ocular (E) involvement. The condition often heals with persistent dyspigmentation (F)