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Epidermal programmed cell death‐ligand 1 expression in TEN associated with nivolumab therapy
Authors:Karina L. Vivar  Maria Deschaine  Jane Messina  Jennifer M. Divine  Alejandro Rabionet  Nishit Patel  Michael A. Harrington  Lucia Seminario‐Vidal
Affiliation:1. Department of Dermatology and Cutaneous Surgery, University of South Florida, Tampa, Florida;2. Anatomic Pathology, Moffitt Cancer Center, Tampa, Florida;3. Departments of Dermatology and Pathology and Cell Biology, University of South Florida, Tampa, Florida;4. Department of Surgery, Division of Plastic Surgery, University of South Florida, Tampa, Florida
Abstract:Nivolumab is a programmed cell death receptor‐1 (PD‐1) antibody used in the treatment of metastatic or unresectable melanoma. Cutaneous reactions are the most common adverse events reported with these agents and are rarely severe or life‐threatening. Here we present a case report describing the clinicopathological findings of a patient with a fatal toxic epidermal necrolysis (TEN) eruption associated with use of nivolumab for treatment of metastatic melanoma. The patient developed a pruritic, morbiliform eruption, which slowly progressed over 3 months to a tender, exfoliative dermatosis. Histology initially showed interface dermatitis and subsequently revealed full thickness epidermal necrosis. The diagnosis of TEN was made. From initial biopsy to TEN presentation, there was an increase in the number of CD8+ lymphocytes within the dermal–epidermal junction and an increase of programmed death ligand 1 (PD‐L1) expression in both lymphocytes and keratinocytes. Despite treatment with infliximab, high‐dose steroids and intravenous immunoglobulin, the patient expired. Herein we describe what we believe is the second case of TEN associated with anti‐PD1 therapy reported in the literature. Increased expression of PD‐L1 by immunohistochemistry was observed as the eruption progressed to TEN. Early diagnosis and treatment is necessary in these fatal TEN reactions secondary to the anti‐PD‐1 antibody therapies.
Keywords:nivolumab  programmed cell death receptor‐1 antibodies  adverse drug reaction  drug rash  toxic epidermal necrolysis
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