INTRODUCTION
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and severe mucocutaneous reactions. SJS and TEN are most often provoked by medications such as allopurinol, sulfonamides, anticonvulsants, penicillins, non-steroidal anti-inflammatory drugs, and immune checkpoint inhibitors (ICIs).1 SJS and TEN are characterized by extensive necrosis and detachment of the epidermis and are considered on the same disease continuum with SJS characterized by detachment of <10 percent of the body surface (BSA), TEN involves detachment of >30 percent of the BSA, and SJS/TEN overlap describes patients with skin detachment of 10 to 30 percent of BSA. In this review, we will use SJS/TEN to refer collectively to this spectrum.2,3
The estimated incidence of SJS/TEN ranges from 1 to 7 cases per million per year.4 It has also been reported that the incidence of SJS/TEN is higher in patients with active cancer.3,5 The risk of progression to SJS/TEN from ICI use for various cancers has increased significantly. Zhu et al also report that there were proportionately more ICI-associated cases of SJS/TEN from Japan and suggest that this may be due to differences in the reporting structure since anti-PD-1 drugs were first approved in Japan.3
The estimated incidence of SJS/TEN ranges from 1 to 7 cases per million per year.4 It has also been reported that the incidence of SJS/TEN is higher in patients with active cancer.3,5 The risk of progression to SJS/TEN from ICI use for various cancers has increased significantly. Zhu et al also report that there were proportionately more ICI-associated cases of SJS/TEN from Japan and suggest that this may be due to differences in the reporting structure since anti-PD-1 drugs were first approved in Japan.3
Medications are the leading cause of SJS/TEN, but there is a lack of clarity regarding the presentations and treatments of typical SJS/TEN due to drugs such as anticonvulsants, lamotrigine, and atypical SJS/TEN due to ICIs in regards to malignancy. Mechanistically, in the normal response to cancer, there is a cross-talk between dendritic and T-cells. A tumor produces antigens that are delivered to antigen presenting cells (APCs) which then results in the activation of tumor-specific T-cells that ultimately lyse or kill cancer cells in the tumor. Tumors escape from the immune system by using T-cell anergy and recruiting regulatory cells (CD4+ Tregs, myeloid suppressor cells, M2 macrophages). Cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) is one immunologic checkpoint that maintains immunologic homeostasis.6 After T-cell activation, CTLA-4 is upregulated on the plasma membrane where it downregulates T-cell function through both T cell–extrinsic and T cell–intrinsic mechanisms. CTLA-4 binds and competes for the same ligands as CD28, but with greater affinity, thereby dampening costimulation. This molecule also functions in the recruitment of phosphatases, inhibition of transcription factors associated with T cell activity, such as NF-kappaB, NFAT, and AP-1, and activation of ubiquitin ligases.7 Downregulating CTLA-4 can lead to augmented CD28 induced anti-self response towards tumors
