Clinical phenotypes and endophenotypes of atopic dermatitis: Where are we, and where should we go?
Thomas Bieber,Thomas Bieber,Angelo Massimiliano D'Erme,Cezmi A. Akdis,Claudia Traidl-Hoffmann,Roger Lauener,Georg Schäppi,Peter Schmid-Grendelmeier +7 more
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TLDR
A systems biology approach merging the numerous clinical phenotypes with robust biomarkers will be needed to best exploit their potential significance for the future molecular taxonomy of AD.Abstract:
Atopic dermatitis (AD) is a paradigmatic chronic inflammatory skin disease characterized by a complex pathophysiology and a wide spectrum of the clinical phenotype. Despite this high degree of heterogeneity, AD is still considered a single disease and usually treated according to the "one-size-fits-all" approach. Thus more tailored prevention and therapeutic strategies are still lacking. As for other disciplines, such as oncology or rheumatology, we have to approach AD in a more differentiated way (ie, to dissect and stratify the complex clinical phenotype into more homogeneous subgroups based on the endophenotype [panel of biomarkers]) with the aim to refine the management of this condition. Because we are now entering the era of personalized medicine, a systems biology approach merging the numerous clinical phenotypes with robust (ie, relevant and validated) biomarkers will be needed to best exploit their potential significance for the future molecular taxonomy of AD. This approach will not only allow an optimized prevention and treatment with the available drugs but also hopefully help assign newly developed medicinal products to those patients who will have the best benefit/risk ratio.read more
Citations
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Journal ArticleDOI
Atopic dermatitis endotypes and implications for targeted therapeutics.
TL;DR: Therapies targeting different cytokine axes and other mechanisms involved in disease pathogenesis, which are currently being tested for patients with AD across the disease spectrum, will expand the ability to dissect the relative contribution of each of these pathways to disease perpetuation.
Journal ArticleDOI
Efficacy and safety of fezakinumab (an IL-22 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by conventional treatments: A randomized, double-blind, phase 2a trial.
Emma Guttman-Yassky,Emma Guttman-Yassky,Patrick M. Brunner,Avidan U. Neumann,Avidan U. Neumann,Avidan U. Neumann,Saakshi Khattri,Ana B. Pavel,Kunal Malik,Giselle Singer,Danielle Baum,Patricia Gilleaudeau,Mary Sullivan-Whalen,Sharon Rose,Shelbi Jim On,Xuan Li,Judilyn Fuentes-Duculan,Yeriel Estrada,Sandra Garcet,Claudia Traidl-Hoffmann,James G. Krueger,Mark Lebwohl +21 more
TL;DR: Fezakinumab was well‐tolerated, with sustained clinical improvements after last drug dosing, andSignificance was primarily obtained in severe AD.
Journal ArticleDOI
Significance of Skin Barrier Dysfunction in Atopic Dermatitis
Byung Eui Kim,Donald Y.M. Leung +1 more
TL;DR: Improved identification and characterization of AD phenotypes and endotypes are required to optimize the precision medicine approach to AD.
Journal ArticleDOI
Interleukin-13: Targeting an underestimated cytokine in atopic dermatitis.
TL;DR: An update on the role of IL‐13 in AD is provided and the different strategies aimed at interfering with its biologic activity as well as their potential in a precision medicine approach in the management of AD are discussed.
Journal ArticleDOI
Lipid abnormalities in atopic skin are driven by type 2 cytokines
Evgeny V. Berdyshev,Elena Goleva,Irina Bronova,Nathan Dyjack,Cydney Rios,John Jung,Patricia A. Taylor,Mingeum Jeong,Clifton F. Hall,Brittany N. Richers,Kathryn A. Norquest,Tao Zheng,Max A. Seibold,Donald Y.M. Leung +13 more
TL;DR: The data support the pathogenic role of type 2 immune activation in AD skin lipid metabolism and downregulation of ELOVL3/ELOVL6 expression in keratinocytes by siRNA decreased the proportion of long-chain fatty acids globally and in sphingolipids.
References
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Journal ArticleDOI
Spontaneous atopic dermatitis is mediated by innate immunity, with the secondary lung inflammation of the atopic march requiring adaptive immunity
Sean P. Saunders,Tara Moran,Tara Moran,Achilleas Floudas,Achilleas Floudas,Felicity A. Wurlod,Felicity A. Wurlod,Agnieszka Kaszlikowska,Agnieszka Kaszlikowska,Maryam Salimi,Emma M. Quinn,Christopher J. Oliphant,Gabriel Núñez,Ross McManus,Emily Hams,Emily Hams,Alan D. Irvine,Andrew N. J. McKenzie,Graham S. Ogg,Padraic G. Fallon,Padraic G. Fallon +20 more
TL;DR: In conclusion, this study provides new insights into the understanding of the atopic march, with innate immunity initiating dermatitis and the adaptive immunity required for subsequent development of compromised lung function.
Journal ArticleDOI
Development of atopic dermatitis according to age of onset and association with early-life exposures
Caroline Roduit,Remo Frei,Georg Loss,Gisela Büchele,Juliane Weber,Martin Depner,Susanne Loeliger,Marie-Laure Dalphin,Marjut Roponen,Anne Hyvärinen,Josef Riedler,Jean-Charles Dalphin,Juha Pekkanen,Erika von Mutius,Charlotte Braun-Fahrländer,Charlotte Braun-Fahrländer,Roger Lauener +16 more
TL;DR: In this paper, the authors investigated whether early postnatal exposures, such as the introduction to complementary food in the first year of life, are associated with the development of atopic dermatitis, taking into account the reverse causality.
Journal ArticleDOI
Immune Pathways in Atopic Dermatitis, and Definition of Biomarkers through Broad and Targeted Therapeutics.
TL;DR: Biomarkers of lesional, nonlesional skin, and blood have been developed for baseline as well as after treatment with broad and specific treatments (i.e., cyclosporine A and dupilumab) to help with the development of novel targeted therapeutics and assessment of disease reversal.
Journal ArticleDOI
The burden of atopic dermatitis in US adults: results from the 2013 National Health and Wellness Survey
TL;DR: The significant burden associated with AD relative to those without AD suggests an unmet need for more effective management strategies and there appears to be a need for further characterization of disease severity and its impact on HRQoL.
Journal ArticleDOI
Clinical differences between atopic and atopiform dermatitis
Elian E. A. Brenninkmeijer,Phyllis I. Spuls,Catharina M. Legierse,Robert Lindeboom,J. Henk Sillevis Smitt,Jan D. Bos +5 more
TL;DR: The findings support that AFD is an entity distinct from AD, and with a distinction shown between AFD and AD, patient groups will be better defined and more homogeneous.
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