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.
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Abstract: The epidermis contains epithelial cells, immune cells, and microbes which provides a physical and functional barrier to the protection of human skin. It plays critical roles in preventing environmental allergen penetration into the human body and responsing to microbial pathogens. Atopic dermatitis (AD) is the most common, complex chronic inflammatory skin disease. Skin barrier dysfunction is the initial step in the development of AD. Multiple factors, including immune dysregulation, filaggrin mutations, deficiency of antimicrobial peptides, and skin dysbiosis contribute to skin barrier defects. In the initial phase of AD, treatment with moisturizers improves skin barrier function and prevents the development of AD. With the progression of AD, effective topical and systemic therapies are needed to reduce immune pathway activation and general inflammation. Targeted microbiome therapy is also being developed to correct skin dysbiosis associated with AD. Improved identification and characterization of AD phenotypes and endotypes are required to optimize the precision medicine approach to AD.
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Citations
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.
470
Pathophysiology of atopic dermatitis: Clinical implications.
TL;DR: Understanding of AD pathophysiology will allow us to achieve a more precision medicine approach to the prevention and the treatment of AD.
Regulation of Filaggrin, Loricrin, and Involucrin by IL-4, IL-13, IL-17A, IL-22, AHR, and NRF2: Pathogenic Implications in Atopic Dermatitis
TL;DR: The mechanisms by which FLG, LOR, and IVL expression is regulated by IL-4, IL-13,IL-22, and IL-17A are focused on and how AHR and NRF2 dual activators exert their beneficial effects in the treatment of AD is summarized.
269
The role of filaggrin in atopic dermatitis and allergic disease.
TL;DR: A PubMed literature review consisting mainly of studies relating to filaggrin in the last 5 years is performed, looking at recent studies that aid the understanding of this crucial epidermal protein.
251
Update on Atopic Dermatitis: Diagnosis, Severity Assessment, and Treatment Selection.
TL;DR: An overview of AD is provided, including strategies for differential diagnosis and assessment of disease severity to guide treatment selection, and key clinical trials for crisaborole and dupilumab are reviewed, and other targeted treatments now in development are summarized.
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References
Atopic Dermatitis: Global Epidemiology and Risk Factors
TL;DR: It is proposed that allergy is rather a consequence of AD in subjects with a concomitant underlying atopic constitution, and there is a strong need to identify alternatives for disease prevention.
Endogenous Antimicrobial Peptides and Skin Infections in Atopic Dermatitis
Peck Y. Ong,Takaaki Ohtake,Corinne Brandt,Ian Strickland,Mark Boguniewicz,Tomas Ganz,Richard L. Gallo,Donald Y.M. Leung +7 more
TL;DR: A deficiency in the expression of antimicrobial peptides may account for the susceptibility of patients with atopic dermatitis to skin infection with S. aureus.
2K
The skin: an indispensable barrier
TL;DR: Changes in epidermal differentiation and lipid composition lead to a disturbed skin barrier, which allows the entry of environmental allergens, immunological reaction and inflammation in atopic dermatitis.
The cornified envelope: a model of cell death in the skin
TL;DR: New insights into the molecular mechanisms and the physiological endpoints of cornification are increasing the understanding of the pathological defects of this unique form of programmed cell death, which is associated with barrier malfunctions and ichthyosis.
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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.
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