title: Epidermal programmed cell death-ligand 1 expression in TEN associated with nivolumab therapy.
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.
authors.affiliation: Department of Dermatology and Cutaneous Surgery, University of South Florida, Tampa, Florida.
authors.forename: Karina L
authors.identifier: http://orcid.org/0000-0003-1434-6638
authors.initials: KL
authors.lastname: Vivar
authors.affiliation: Anatomic Pathology, Moffitt Cancer Center, Tampa, Florida.
authors.forename: Maria
authors.initials: M
authors.lastname: Deschaine
authors.affiliation: Anatomic Pathology, Moffitt Cancer Center, Tampa, Florida.|Departments of Dermatology and Pathology and Cell Biology, University of South Florida, Tampa, Florida.
authors.forename: Jane
authors.initials: J
authors.lastname: Messina
authors.affiliation: Department of Dermatology and Cutaneous Surgery, University of South Florida, Tampa, Florida.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Divine
authors.affiliation: Department of Dermatology and Cutaneous Surgery, University of South Florida, Tampa, Florida.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Rabionet
authors.affiliation: Department of Dermatology and Cutaneous Surgery, University of South Florida, Tampa, Florida.
authors.forename: Nishit
authors.initials: N
authors.lastname: Patel
authors.affiliation: Department of Surgery, Division of Plastic Surgery, University of South Florida, Tampa, Florida.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Harrington
authors.affiliation: Department of Dermatology and Cutaneous Surgery, University of South Florida, Tampa, Florida.
authors.forename: Lucia
authors.identifier: http://orcid.org/0000-0002-6004-2451
authors.initials: L
authors.lastname: Seminario-Vidal
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D000077594:Nivolumab; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D012878:Skin Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D013262:Stevens-Johnson Syndrome / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D009363:Neoplasm Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab
keywords: adverse drug reaction; drug rash; nivolumab; programmed cell death receptor-1 antibodies; toxic epidermal necrolysis