Skin manifestations associated with checkpoint inhibitors

Abstract Immune checkpoint inhibitors (ICIs) are a relatively novel class of drugs whose administration has been approved for several malignancies. Adverse events are quite common, and the skin is the most frequently involved organ. In fact, regardless of the neoplasm being treated, more than 50% of...

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Main Authors: Gianluca Nazzaro, Stefano Buffon, Serena Giacalone, Carlo Alberto Maronese, Angelo Valerio Marzano
Format: Article
Language:English
Published: Wiley 2022-06-01
Series:JEADV Clinical Practice
Subjects:
Online Access:https://doi.org/10.1002/jvc2.27
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author Gianluca Nazzaro
Stefano Buffon
Serena Giacalone
Carlo Alberto Maronese
Angelo Valerio Marzano
author_facet Gianluca Nazzaro
Stefano Buffon
Serena Giacalone
Carlo Alberto Maronese
Angelo Valerio Marzano
author_sort Gianluca Nazzaro
collection DOAJ
description Abstract Immune checkpoint inhibitors (ICIs) are a relatively novel class of drugs whose administration has been approved for several malignancies. Adverse events are quite common, and the skin is the most frequently involved organ. In fact, regardless of the neoplasm being treated, more than 50% of patients receiving ICIs develop cutaneous immune‐related adverse events (irAEs), with variable time to onset and severity. Potential pathogenetic mechanisms include drug‐induced formation of neoantigens, unmasking of hidden self‐antigens, and diffuse keratinocyte apoptosis induced by CD4+ and CD8+ T cell activation. Risk of cutaneous irAEs seems to be higher after anti‐CTLA‐4 rather than anti‐PD‐1/PD‐L1 agent administration and rises in case of combination therapy. Furthermore, incidence of skin toxicity increases in the presence of specific malignancies (i.e., advanced melanoma) and pre‐existing dermatoses or autoimmune diseases, while the possible role of ethnicity is still unclear. Aim of this review is to summarise the current knowledge of cutaneous irAEs and provide the clinician with a detailed clinical and histopathological description of the following types of skin toxicity: inflammatory dermatoses, immunobullous diseases, alterations of melanocytes, alterations of keratinocytes, hair abnormalities, oral and nail involvement. Particular attention is given to practical management of the different cutaneous irAEs, including detailed information about treatment regimens and necessity for ICI discontinuation. Patients should always receive multidisciplinary care, especially in severe or recalcitrant cases. The role of the dermatologists remains pivotal, particularly with regard to differential diagnosis and management of complex skin toxicity, as well as regular long‐term follow‐up of the patient's conditions.
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spelling doaj.art-6e3ab8d2eb434b929e76f1148e24e4772022-12-22T02:30:52ZengWileyJEADV Clinical Practice2768-65662022-06-0112738710.1002/jvc2.27Skin manifestations associated with checkpoint inhibitorsGianluca Nazzaro0Stefano Buffon1Serena Giacalone2Carlo Alberto Maronese3Angelo Valerio Marzano4Dermatology Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan ItalyDermatology Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan ItalyDermatology Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan ItalyDermatology Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan ItalyDermatology Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan ItalyAbstract Immune checkpoint inhibitors (ICIs) are a relatively novel class of drugs whose administration has been approved for several malignancies. Adverse events are quite common, and the skin is the most frequently involved organ. In fact, regardless of the neoplasm being treated, more than 50% of patients receiving ICIs develop cutaneous immune‐related adverse events (irAEs), with variable time to onset and severity. Potential pathogenetic mechanisms include drug‐induced formation of neoantigens, unmasking of hidden self‐antigens, and diffuse keratinocyte apoptosis induced by CD4+ and CD8+ T cell activation. Risk of cutaneous irAEs seems to be higher after anti‐CTLA‐4 rather than anti‐PD‐1/PD‐L1 agent administration and rises in case of combination therapy. Furthermore, incidence of skin toxicity increases in the presence of specific malignancies (i.e., advanced melanoma) and pre‐existing dermatoses or autoimmune diseases, while the possible role of ethnicity is still unclear. Aim of this review is to summarise the current knowledge of cutaneous irAEs and provide the clinician with a detailed clinical and histopathological description of the following types of skin toxicity: inflammatory dermatoses, immunobullous diseases, alterations of melanocytes, alterations of keratinocytes, hair abnormalities, oral and nail involvement. Particular attention is given to practical management of the different cutaneous irAEs, including detailed information about treatment regimens and necessity for ICI discontinuation. Patients should always receive multidisciplinary care, especially in severe or recalcitrant cases. The role of the dermatologists remains pivotal, particularly with regard to differential diagnosis and management of complex skin toxicity, as well as regular long‐term follow‐up of the patient's conditions.https://doi.org/10.1002/jvc2.27immune checkpoint inhibitorsimmunotherapyskin toxicity
spellingShingle Gianluca Nazzaro
Stefano Buffon
Serena Giacalone
Carlo Alberto Maronese
Angelo Valerio Marzano
Skin manifestations associated with checkpoint inhibitors
JEADV Clinical Practice
immune checkpoint inhibitors
immunotherapy
skin toxicity
title Skin manifestations associated with checkpoint inhibitors
title_full Skin manifestations associated with checkpoint inhibitors
title_fullStr Skin manifestations associated with checkpoint inhibitors
title_full_unstemmed Skin manifestations associated with checkpoint inhibitors
title_short Skin manifestations associated with checkpoint inhibitors
title_sort skin manifestations associated with checkpoint inhibitors
topic immune checkpoint inhibitors
immunotherapy
skin toxicity
url https://doi.org/10.1002/jvc2.27
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AT stefanobuffon skinmanifestationsassociatedwithcheckpointinhibitors
AT serenagiacalone skinmanifestationsassociatedwithcheckpointinhibitors
AT carloalbertomaronese skinmanifestationsassociatedwithcheckpointinhibitors
AT angelovaleriomarzano skinmanifestationsassociatedwithcheckpointinhibitors