Toxic epidermal necrolysis associated with pembrolizumab

Abstract

<jats:sec><jats:title>Introduction</jats:title><jats:p> Stevens-Johnson syndrome and toxic epidermal necrolysis are severe cutaneous drug eruptions characterized by epidermal detachment. Pembrolizumab is a monoclonal antibody that binds to the programmed death-1 receptor, and it has been associated with numerous cutaneous adverse side-effects, including Stevens-Johnson syndrome. </jats:p></jats:sec><jats:sec><jats:title>Case report</jats:title><jats:p> We describe a 63-year-old male with metastatic lung adenocarcinoma who developed a rapidly progressing maculopapular rash three days after a first dose of pembrolizumab. On day 16, the rash affected more than 80% of body surface area with detachment of large sheets of necrolytic epidermis in 30–40% of body surface area. However, the patient only presented with mild mucosal involvement. Histopathologic examination of a skin biopsy showed a subepidermal blister with overlying prominent full thickness epidermal keratinocytic necrosis and a superficial perivascular infiltrate of lymphocytes. A toxic epidermal necrolysis secondary to pembrolizumab was then diagnosed. Management and outcome: In addition to supportive cares, the patient received corticosteroids and cyclosporine. The patient responded rapidly to the immunosuppressant therapy, and nearly complete re-epithelialization was achieved 24 days after the start of the reaction. </jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p> In our review of the literature, 15 other cases of Stevens-Johnson syndrome/toxic epidermal necrolysis were reported with programmed death-1/programmed cell death ligand-1 inhibitors. To our knowledge, this is the first case of toxic epidermal necrolysis secondary to pembrolizumab published in the literature. The American Society of Clinical Oncology guidelines suggest that cyclosporine, in addition to corticosteroids, be initiated when toxic epidermal necrolysis is suspected. Clinicians should be aware of this rare dermatological emergency with the increasing use of pembrolizumab in oncology. </jats:p></jats:sec>

Cemiplimab for Locally Advanced and Metastatic Cutaneous Squamous-Cell Carcinomas: Real-Life Experience from the French CAREPI Study Group

“…One cemiplimab-related death from toxic epidermal necrolysis occurred. About 20 Stevens–Johnson syndrome/toxic epidermal necrolysis cases have been reported with other inhibitors of PD-1 or its ligand [ 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. Toxic epidermal necrolysis is responsible for high mortality [ 56 ].…”

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

“…In Asian countries, traditional medicine can also be a causative drug of SJS/TEN [20]. Currently, SJS/TEN is reported to be associated with pembrolizumab [21], and itraconazole [22]. Patch test, lymphocyte transformation test, and enzyme-linked immunospot can be used to detect culprit drugs in SJS/TEN but none of them is considered as standard [1,23].…”

Oral manifestations of immune‐related adverse events in cancer patients treated with immune checkpoint inhibitors

“…Stevens‐Johnson Syndrome (SJS)‐like and Toxic Epidermal Necrolysis (TEN)‐like reactions have been reported in patients on pembrolizumab and nivolumab, as well as combination treatment with nivolumab and ipilimumab (Keerty et al, 2020; Logan et al, 2020). These reactions have presented 3 days to 7 months following initiation of ICI therapy (Cai et al, 2020; Goldinger et al, 2016; Hwang et al, 2019; Keerty et al, 2020; Maloney et al, 2020; Riano et al, 2020; Saw et al, 2017). In several cases, SJS‐like and TEN‐like reactions were preceded by prodromal skin rashes that subsequently evolved into mucosal and skin denudation more characteristic of the conditions (Cai et al, 2020; Goldinger et al, 2016; Keerty et al, 2020; Maloney et al, 2020).…”