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
Reads0
Chats0
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
More filters
Journal ArticleDOI
New Treatments for Atopic Dermatitis Targeting Skin Barrier Repair via the Regulation of FLG Expression
TL;DR: In this article, the authors discuss the innovations in the therapy of atopic dermatitis, including biologics, small molecule therapies, and other drugs by highlighting regulatory mechanisms of skin barrier-related molecules, such as filaggrin (FLG) as a crucial pathway implicated in AD pathogenesis.
Journal ArticleDOI
A new era of atopic eczema research: Advances and highlights.
Claudia Hülpüsch,Claudia Hülpüsch,Andreas B Weins,Claudia Traidl-Hoffmann,Matthias Reiger,Matthias Reiger +5 more
TL;DR: The current state of the art in AE research is summarized in a review of novel microbial and immunological biomarkers described recently for the prediction of disease development and treatment response.
Journal ArticleDOI
Environment-dependent alterations of immune mediators in urban and rural south African children with atopic dermatitis.
Nonhlanhla Lunjani,Nonhlanhla Lunjani,Nonhlanhla Lunjani,Ge Tan,Ge Tan,Anita Dreher,Milena Sokolowska,David Groeger,Marcin Warwyzniak,Can Altunbulakli,Patrick Westermann,Wisdom Basera,Lelani Hobane,Maresa Botha,Claudia L. Gray,Avumile Mankahla,Clive M. Gray,Kari C. Nadeau,Carol Hlela,Michael Levin,Liam O'Mahony,Cezmi A. Akdis +21 more
TL;DR: In this paper, the authors measured immunological, socioeconomic and environmental factors in healthy children (n=74) and children with AD in rural and urban settings from the same ethno-linguistic AmaXhosa background in South Africa.
Journal ArticleDOI
Atopic Dermatitis: Striving for Reliable Biomarkers
Styliani Mastraftsi,Georgia Vrioni,Michail Bakakis,Electra Nicolaidou,Dimitris Rigopoulos,Alexander J. Stratigos,Stamatis Gregoriou +6 more
TL;DR: Thymus and activation-regulated chemokine/C-C motif ligand 17 (TARC/CCL17) has the greatest evidence-based support for becoming a reliable biomarker in AD correlated with disease severity in both children and adults.
Journal ArticleDOI
Bifurcation analysis of a mathematical model of atopic dermatitis to determine patient-specific effects of treatments on dynamic phenotypes.
Gouhei Tanaka,Elisa Domínguez-Hüttinger,Panayiotis Christodoulides,Kazuyuki Aihara,Reiko J. Tanaka +4 more
TL;DR: The mathematical method developed in this study can be used to explore and improve patient-specific personalised treatment strategies to control AD symptoms and is suitable for mathematically modelling effects of topical application of antibiotics, emollients, corticosteroids, and their combinations with different application schedules and doses.
References
More filters
Journal ArticleDOI
Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework*
Arthur J. Atkinson,Wayne A. Colburn,Victor G. DeGruttola,David L. DeMets,Gregory J. Downing,Daniel F. Hoth,John A. Oates,Carl C. Peck,Robert T. Schooley,Bert A. Spilker,Janet Woodcock,Scott L. Zeger +11 more
TL;DR: Biomarker measurements provide an avenue for researchers to gain a mechanistic understanding of the differences in clinical response that may be influenced by uncontrolled variables (for example, drug metabolism).
Journal ArticleDOI
The Endophenotype Concept in Psychiatry: Etymology and Strategic Intentions
TL;DR: The authors discuss the etymology and strategy behind the use of endophenotypes in neuropsychiatric research and, more generally, in research on other diseases with complex genetics.
Journal ArticleDOI
Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis
Colin N. A. Palmer,Alan D. Irvine,Ana Terron-Kwiatkowski,Yiwei Zhao,Haihui Liao,Simon P. Lee,David Goudie,Aileen Sandilands,Linda E. Campbell,Frances J.D. Smith,Grainne M. O'Regan,Rosemarie Watson,Jo E Cecil,Sherri J. Bale,John G. Compton,John J. DiGiovanna,John J. DiGiovanna,Philip Fleckman,Sue Lewis-Jones,Gehan Arseculeratne,Ann Sergeant,Colin S. Munro,Brahim El Houate,Ken McElreavey,Liselotte Brydensholt Halkjaer,Hans Bisgaard,Somnath Mukhopadhyay,Somnath Mukhopadhyay,W.H. Irwin McLean +28 more
TL;DR: It is shown that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis.
Journal ArticleDOI
Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis
Eric L. Simpson,Thomas Bieber,Emma Guttman-Yassky,Lisa A. Beck,Andrew Blauvelt,Michael J. Cork,Jonathan I. Silverberg,Mette Deleuran,Yoko Kataoka,Jean-Philippe Lacour,Külli Kingo,Margitta Worm,Margitta Worm,Yves Poulin,Andreas Wollenberg,Yuhwen Soo,Neil M.H. Graham,Gianluca Pirozzi,Bolanle Akinlade,Heribert Staudinger,Vera Mastey,Laurent Eckert,Abhijit Gadkari,Neil Stahl,George D. Yancopoulos,Marius Ardeleanu +25 more
TL;DR: Dupilumab improved the signs and symptoms of atopic dermatitis, including pruritus, symptoms of anxiety and depression, and quality of life, as compared with placebo in two phase 3 trials of identical design.
Related Papers (5)
Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis
Eric L. Simpson,Thomas Bieber,Emma Guttman-Yassky,Lisa A. Beck,Andrew Blauvelt,Michael J. Cork,Jonathan I. Silverberg,Mette Deleuran,Yoko Kataoka,Jean-Philippe Lacour,Külli Kingo,Margitta Worm,Margitta Worm,Yves Poulin,Andreas Wollenberg,Yuhwen Soo,Neil M.H. Graham,Gianluca Pirozzi,Bolanle Akinlade,Heribert Staudinger,Vera Mastey,Laurent Eckert,Abhijit Gadkari,Neil Stahl,George D. Yancopoulos,Marius Ardeleanu +25 more
Dupilumab treatment in adults with moderate-to-severe atopic dermatitis.
Lisa A. Beck,Diamant Thaçi,Jennifer D. Hamilton,Neil M.H. Graham,Thomas Bieber,Ross E. Rocklin,Jeffrey Ming,Haobo Ren,Richard Kao,Eric L. Simpson,Marius Ardeleanu,Steven P. Weinstein,Gianluca Pirozzi,Emma Guttman-Yassky,Mayte Suárez-Fariñas,Melissa D. Hager,Neil Stahl,George D. Yancopoulos,Allen Radin +18 more
Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis
Colin N. A. Palmer,Alan D. Irvine,Ana Terron-Kwiatkowski,Yiwei Zhao,Haihui Liao,Simon P. Lee,David Goudie,Aileen Sandilands,Linda E. Campbell,Frances J.D. Smith,Grainne M. O'Regan,Rosemarie Watson,Jo E Cecil,Sherri J. Bale,John G. Compton,John J. DiGiovanna,John J. DiGiovanna,Philip Fleckman,Sue Lewis-Jones,Gehan Arseculeratne,Ann Sergeant,Colin S. Munro,Brahim El Houate,Ken McElreavey,Liselotte Brydensholt Halkjaer,Hans Bisgaard,Somnath Mukhopadhyay,Somnath Mukhopadhyay,W.H. Irwin McLean +28 more