title: Lichenoid Dermatologic Toxicity From Immune Checkpoint Blockade Therapy: A Detailed Examination of the Clinicopathologic Features.
abstract: Immunotherapy targeting the programmed cell death 1 (PD-1) receptor has demonstrated tremendous promise in the treatment of advanced solid tumors. Dermatologic toxicities, however, are an emerging consequence of this therapy and have been clearly associated with immune checkpoint blockade antibodies. Distinctive clinical and histologic subtypes of dermatologic toxicity secondary to immunotherapy are emerging and include rare autoimmune bullous reactions (eg, bullous pemphigoid) and lichenoid eruptions. We report three patients who developed lichenoid dermatitis while receiving anti-PD-1 antibody therapy. The mean time to onset of lichenoid dermatologic toxicity was 42 days (range: 1-75 days) from initiation of anti-PD-1 antibody therapy. Lesions most frequently presented on the extremities and trunk as pustules, papules, and plaques. The face was not commonly involved. Of the five skin biopsies examined, all demonstrated dense band-like lymphocytic infiltrate, hyperkeratosis, hypergranulosis, saw-tooth rete ridge pattern, and dyskeratosis. Acanthosis was a feature in all of the skin biopsies, and in one, epidermal hyperplasia was prominent. In several skin biopsies, histologic features supporting a lichenoid drug eruption were present, including parakeratosis, spongiosis, periadnexal/perivascular inflammation, and eosinophils. Furthermore, the histologic features varied in skin biopsy specimens taken from the same patient at different sites, supporting a drug reaction. All patients' skin lesions improved with use of steroids: two were treated with topical steroids and one with systemic steroids. Recognition of the histopathologic patterns of dermatologic toxicities resulting from immune checkpoint blockade therapy will become increasingly important for ensuring appropriate management of dermatologic toxicities and optimal patient care.
authors.affiliation: *Department of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, TX; Departments of †Dermatology, and ‡Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Tetzlaff
authors.forename: Priyadharsini
authors.initials: P
authors.lastname: Nagarajan
authors.forename: Susan
authors.initials: S
authors.lastname: Chon
authors.forename: Auris
authors.initials: A
authors.lastname: Huen
authors.forename: Adi
authors.initials: A
authors.lastname: Diab
authors.forename: Pacha
authors.initials: P
authors.lastname: Omar
authors.forename: Phyu P
authors.initials: PP
authors.lastname: Aung
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Torres-Cabala
authors.forename: Steven R
authors.initials: SR
authors.lastname: Mays
authors.forename: Victor G
authors.initials: VG
authors.lastname: Prieto
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; D017512:Lichenoid Eruptions / Q000139:chemically induced* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D000077594:Nivolumab; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors
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