Paradoxical Skin Reactions to Biologics in Patients With Rheumatologic Disorders

Targeted immune-modulating treatment with biological agents has revolutionized the management of immune-mediated inflammatory diseases, including rheumatologic conditions. The efficacy and tolerability of biological agents, from the initial tumour necrosis factor (TNF)-α inhibitors to the new anti-c...

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Main Authors: Simone Garcovich, Clara De Simone, Giovanni Genovese, Emilio Berti, Massimo Cugno, Angelo Valerio Marzano
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-03-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fphar.2019.00282/full
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author Simone Garcovich
Clara De Simone
Giovanni Genovese
Giovanni Genovese
Emilio Berti
Emilio Berti
Massimo Cugno
Massimo Cugno
Angelo Valerio Marzano
Angelo Valerio Marzano
author_facet Simone Garcovich
Clara De Simone
Giovanni Genovese
Giovanni Genovese
Emilio Berti
Emilio Berti
Massimo Cugno
Massimo Cugno
Angelo Valerio Marzano
Angelo Valerio Marzano
author_sort Simone Garcovich
collection DOAJ
description Targeted immune-modulating treatment with biological agents has revolutionized the management of immune-mediated inflammatory diseases, including rheumatologic conditions. The efficacy and tolerability of biological agents, from the initial tumour necrosis factor (TNF)-α inhibitors to the new anti-cytokine monoclonal antibodies, have dramatically changed the natural history of debilitating conditions such as rheumatoid arthritis and seronegative spondyloarthropathies. The widening use of biologics across several rheumatologic diseases has been associated with a new class of adverse events, the so-called paradoxical reactions. These events are inflammatory immune-mediated tissue reactions, developing paradoxically during treatment of rheumatologic conditions with targeted biologics that are commonly used for treating the idiopathic counterparts of these drug-induced reactions. The skin is frequently involved, and, even if considered rare to uncommon, these cutaneous manifestations are an important cause of biologic agent discontinuation. TNF-α antagonist-induced psoriasis, which can manifest de novo or as exacerbation of a pre-existing form, is the prototypic and most frequent paradoxical skin reaction to biologics while other reactions, such as eczematous and lichenoid eruptions, hidradenitis suppurativa, pyoderma gangrenosum, Sweet’s syndrome and granulomatous skin diseases, occur much more rarely. Management of these reactions consists of topical or systemic skin-directed therapies, depending on the severity and extension of the cutaneous picture, and it is generally associated with switching over to other disease-modifying regimens for treating the underlying rheumatologic condition. Here, we review in detail the current concepts and controversies on classification, pathogenesis and clinical management of this new class of cutaneous adverse events induced by biologics in rheumatologic patients.
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spelling doaj.art-cdf9dea3fb34442f9bf33ddb81dc3d572022-12-22T03:34:11ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-03-011010.3389/fphar.2019.00282443078Paradoxical Skin Reactions to Biologics in Patients With Rheumatologic DisordersSimone Garcovich0Clara De Simone1Giovanni Genovese2Giovanni Genovese3Emilio Berti4Emilio Berti5Massimo Cugno6Massimo Cugno7Angelo Valerio Marzano8Angelo Valerio Marzano9Institute of Dermatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, ItalyInstitute of Dermatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, ItalyUOC Dermatologia, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyDipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, ItalyUOC Dermatologia, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyDipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, ItalyDipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, ItalyMedicina Interna, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyUOC Dermatologia, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyDipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, ItalyTargeted immune-modulating treatment with biological agents has revolutionized the management of immune-mediated inflammatory diseases, including rheumatologic conditions. The efficacy and tolerability of biological agents, from the initial tumour necrosis factor (TNF)-α inhibitors to the new anti-cytokine monoclonal antibodies, have dramatically changed the natural history of debilitating conditions such as rheumatoid arthritis and seronegative spondyloarthropathies. The widening use of biologics across several rheumatologic diseases has been associated with a new class of adverse events, the so-called paradoxical reactions. These events are inflammatory immune-mediated tissue reactions, developing paradoxically during treatment of rheumatologic conditions with targeted biologics that are commonly used for treating the idiopathic counterparts of these drug-induced reactions. The skin is frequently involved, and, even if considered rare to uncommon, these cutaneous manifestations are an important cause of biologic agent discontinuation. TNF-α antagonist-induced psoriasis, which can manifest de novo or as exacerbation of a pre-existing form, is the prototypic and most frequent paradoxical skin reaction to biologics while other reactions, such as eczematous and lichenoid eruptions, hidradenitis suppurativa, pyoderma gangrenosum, Sweet’s syndrome and granulomatous skin diseases, occur much more rarely. Management of these reactions consists of topical or systemic skin-directed therapies, depending on the severity and extension of the cutaneous picture, and it is generally associated with switching over to other disease-modifying regimens for treating the underlying rheumatologic condition. Here, we review in detail the current concepts and controversies on classification, pathogenesis and clinical management of this new class of cutaneous adverse events induced by biologics in rheumatologic patients.https://www.frontiersin.org/article/10.3389/fphar.2019.00282/fullparadoxical skin reactionsbiologicsrheumatological disorderspsoriasisTNFα-inhibitors
spellingShingle Simone Garcovich
Clara De Simone
Giovanni Genovese
Giovanni Genovese
Emilio Berti
Emilio Berti
Massimo Cugno
Massimo Cugno
Angelo Valerio Marzano
Angelo Valerio Marzano
Paradoxical Skin Reactions to Biologics in Patients With Rheumatologic Disorders
Frontiers in Pharmacology
paradoxical skin reactions
biologics
rheumatological disorders
psoriasis
TNFα-inhibitors
title Paradoxical Skin Reactions to Biologics in Patients With Rheumatologic Disorders
title_full Paradoxical Skin Reactions to Biologics in Patients With Rheumatologic Disorders
title_fullStr Paradoxical Skin Reactions to Biologics in Patients With Rheumatologic Disorders
title_full_unstemmed Paradoxical Skin Reactions to Biologics in Patients With Rheumatologic Disorders
title_short Paradoxical Skin Reactions to Biologics in Patients With Rheumatologic Disorders
title_sort paradoxical skin reactions to biologics in patients with rheumatologic disorders
topic paradoxical skin reactions
biologics
rheumatological disorders
psoriasis
TNFα-inhibitors
url https://www.frontiersin.org/article/10.3389/fphar.2019.00282/full
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