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
Atopic dermatitis in the elderly: a review of clinical and pathophysiological hallmarks
TL;DR: Although the elderly are described as having a distinct presentation of AD and important comorbidities, most investigations and clinical care guidelines pertaining to AD do not include patients aged 60 years and older as a separate group from younger adults.
Journal ArticleDOI
How does parental history of atopic disease predict the risk of atopic dermatitis in a child? A systematic review and meta-analysis.
Nina Haarup Ravn,Anne-Sofie Halling,Aviva G. Berkowitz,Maria Rasmussen Rinnov,Jonathan I. Silverberg,Alexander Egeberg,Jacob P. Thyssen,Jacob P. Thyssen +7 more
TL;DR: This study provides evidence-based risk estimates that may guide physicians, who counsel parents with a history of atopic disease about their children's risk of AD, and future efforts towards establishing prophylactic interventions for AD on a general population level.
Journal ArticleDOI
IL-17E (IL-25) Enhances Innate Immune Responses during Skin Inflammation
Luisa Senra,Alessio Mylonas,Ruairi D. Kavanagh,Padraic G. Fallon,Curdin Conrad,J. Borowczyk-Michalowska,Ludovic Jean Wrobel,Guerkan Kaya,Nikhil Yawalkar,Wolf-Henning Boehncke,Wolf-Henning Boehncke,Nicolò Costantino Brembilla +11 more
TL;DR: It is proposed that IL-17E is an important common denominator of chronic skin inflammation, promoting innate immune cell recruitment and activation, as well as neutrophils in neutrophil-rich inflammatory skin diseases.
Journal ArticleDOI
Eosinophils Determine Dermal Thickening and Water Loss in an MC903 Model of Atopic Dermatitis
Karmella Naidoo,Ferdinand Jagot,Lieke W J van den Elsen,Christophe Pellefigues,Angela Jones,Huijun Luo,Karen A. Johnston,Gavin F. Painter,Ben Roediger,James J. Lee,Wolfgang Weninger,Wolfgang Weninger,Wolfgang Weninger,Graham Le Gros,Elizabeth Forbes-Blom +14 more
TL;DR: Eosinophil depletion significantly ameliorated AD pathology, most notably barrier dysfunction, to a similar extent as blocking of the IL-4/IL-13 axis by genetic deletion of STAT6.
Journal ArticleDOI
Predicting Skin Barrier Dysfunction and Atopic Dermatitis in Early Infancy
Eva Maria Rehbinder,Eva Maria Rehbinder,Kim M Advocaat Endre,Karin C. Lødrup Carlsen,Anna Asarnoj,Karen Eline Stensby Bains,Teresa Løvold Berents,Kai-Håkon Carlsen,Hrefna Katrín Gudmundsdóttir,Guttorm Haugen,Gunilla Hedlin,Ina Kreyberg,Live Solveig Nordhagen,Björn Nordlund,Carina Madelen Saunders,Leiv Sandvik,Håvard Ove Skjerven,Cilla Söderhäll,Anne Cathrine Staff,Riyas Vettukattil,Magdalena R. Værnesbranden,Linn Landrø,Monica Hauger Carlsen,Oda C Lødrup Carlsen,Peder Annæus Granlund,Berit Granum,Sandra Götberg,Katarina Hilde,Christine M. Jonassen,Unni Cecilie Nygaard,Knut Rudi,Ingebjørg Skrindo,Katrine Dønvold Sjøborg,Sandra G Tedner,Johanna Wiik,Angelica Johansen Winger +35 more
TL;DR: In early infancy, distinct parental and pregnancy-related factors were predictive for dry skin, high TEWL and AD in early infancy.
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