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
Persistence of Mild to Moderate Atopic Dermatitis
TL;DR: Based on this large longitudinal cohort study, symptoms associated with AD seem to persist well into the second decade of a child's life and likely longer.
Journal ArticleDOI
What the Eczema Area and Severity Index score tells us about the severity of atopic dermatitis: an interpretability study.
TL;DR: The Eczema Area and Severity Index (EASI) is an investigator‐assessed instrument measuring the severity of clinical signs in atopic dermatitis (AD).
Journal ArticleDOI
Biomarkers for atopic dermatitis: a systematic review and meta-analysis.
Judith L. Thijs,Todor K. Krastev,Stephan Weidinger,Constantinus F. Buckens,Marjolein S. de Bruin-Weller,Carla A.F.M. Bruijnzeel-Koomen,Carsten Flohr,DirkJan Hijnen +7 more
TL;DR: Serum thymus and activation-regulated chemokine (TARC) was found to be the most reliable biomarker studied, showing pooled correlation coefficients of 0.60 (95% CI 0.48–0.70) and 0.64 in longitudinal and cross-sectional studies, respectively.
Journal ArticleDOI
Intraindividual genome expression analysis reveals a specific molecular signature of psoriasis and eczema
Maria Quaranta,Bettina Knapp,Natalie Garzorz,M. Mattii,Venu Pullabhatla,Davide Pennino,Christian Andres,Claudia Traidl-Hoffmann,Andrea Cavani,Fabian J. Theis,Johannes Ring,Carsten B. Schmidt-Weber,Stefanie Eyerich,Kilian Eyerich +13 more
TL;DR: It is found that psoriasis-specific genes involved not only immune mediators but also regulators of metabolism and eczema-related genes included those related to the epidermal barrier and inflammasome activation.
Journal ArticleDOI
Atopic dermatitis 2.0: from the clinical phenotype to the molecular taxonomy and stratified medicine
TL;DR: This review suggests to exploit the recent knowledge about AD for a novel approach proposing a tentative first molecular taxonomy of this disease based on the genotype and endophenotype, with consequences in terms of personalized prevention and management.
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