title: Autoimmune dermatologic toxicities from immune checkpoint blockade with anti-PD-1 antibody therapy: a report on bullous skin eruptions.
abstract: Monoclonal antibodies against the immune checkpoint programmed cell death receptor 1 (PD-1) improve the hosts' antitumor immune response and have showed tremendous promise in the treatment of advanced solid tumors and hematologic malignancies. Reports of serious autoimmune dermatologic toxicities from immune checkpoint blockade therapy, however, are emerging. We report our experience with five patients who presented with pruritic vesicles and blisters on the skin while treated with anti-PD-1 antibody immunotherapy with either nivolumab or pembrolizumab. Four of the patients' skin biopsies revealed subepidermal bullae with immunohistochemical study for type IV collagen labeling the floor of the blister cavity and direct immunofluorescence studies (in three of the four patients tested) decorated linear IgG and C3 immune deposits on the blister roof, diagnostic of bullous pemphigoid. One patient developed bullous erythema multiforme. All patients had partial or complete resolution of skin lesions following treatment with systemic corticosteroid and cessation of checkpoint blockade. Recognition and treatment of rare immune-related bullous dermatologic toxicities will become increasingly important as more patients are treated with effective and newer immune checkpoint blockade therapy.
authors.affiliation: Department of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: George
authors.initials: G
authors.lastname: Jour
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Isabella C
authors.initials: IC
authors.lastname: Glitza
authors.affiliation: Department of Dermatology, University of Texas Medical School, Houston, TX, USA.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Ellis
authors.affiliation: Department of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Torres-Cabala
authors.affiliation: Department of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Tetzlaff
authors.affiliation: Department of Dermatology, University of Texas Medical School, Houston, TX, USA.
authors.forename: Janet Y
authors.initials: JY
authors.lastname: Li
authors.affiliation: Department of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Priyadharsini
authors.initials: P
authors.lastname: Nagarajan
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Auris
authors.initials: A
authors.lastname: Huen
authors.affiliation: Department of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Phyu P
authors.initials: PP
authors.lastname: Aung
authors.affiliation: Department of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Doina
authors.initials: D
authors.lastname: Ivan
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Carol R
authors.initials: CR
authors.lastname: Drucker
authors.affiliation: Department of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Victor G
authors.initials: VG
authors.lastname: Prieto
authors.affiliation: Department of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of Dermatology, University of Texas Medical School, Houston, TX, USA.|Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Rapini
authors.affiliation: Department of Dermatology, University of Texas Medical School, Houston, TX, USA.|Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Anisha
authors.initials: A
authors.lastname: Patel
authors.affiliation: Department of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Curry
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D003875:Drug Eruptions / Q000209:etiology* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D000077594:Nivolumab; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D012872:Skin Diseases, Vesiculobullous / Q000139:chemically induced* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab; C582435:pembrolizumab
keywords: anti-PD-1 antibody; autoimmune dermatologic toxicities; bullous erythema multiforme; bullous pemphigoid