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- Presentation
The Epidermal Barrier and its Role in Atopic Dermatitis
Description
The presentation discusses the epidermal barrier's critical role in atopic dermatitis (AD), contrasting two primary theories: the "inside-out" hypothesis, which links AD to type 2 inflammation, and the "outside-in" hypothesis, which emphasizes skin barrier dysfunction that allows allergens and irritants to penetrate the skin. The speaker highlights the complexity of the skin's epithelial structure and the significance of intact stratum corneum and tight junctions in preventing inflammation and maintaining barrier function. Abnormalities in lipid composition, particularly ceramides, and tight junction proteins can disrupt this barrier, leading to increased inflammation through the activation of innate immune responses. The talk also outlines the role of filaggrin mutations in AD and their associations with food allergies and asthma. Additionally, advancements in therapies like dupilumab and their effects on improving skin barrier function and reducing Staphylococcus aureus colonization are emphasized. The conclusion asserts the need for better functional assays for assessing barrier integrity and highlights how various treatments may enhance skin barrier function, particularly treatments that target type 2 inflammation.
View moreConclusions
- Atopic dermatitis (AD) is influenced by both immune system dysfunction and skin barrier defects.
- There exists a dual mechanism of disease development in AD, characterized by both 'inside-out' (inflammation-driven) and 'outside-in' (barrier impairment-driven) hypotheses.
- Skin barrier dysfunction leads to increased susceptibility to allergens and infections, contributing to the severity of AD symptoms.
- The skin of individuals with AD shows altered lipid composition, specifically reduced long chain ceramides which decrease hydrophobicity, impacting barrier integrity.
- Filaggrin mutations are highly associated with atopic dermatitis and can lead to early onset, increased severity, and persistence of the disease.
- Type 2 inflammation is closely linked to defective barrier function and promotes pro-inflammatory mediators that exacerbate AD symptoms.
- Therapies for AD, particularly those targeting type 2 inflammation, improve skin barrier function and may reduce Staphylococcus aureus colonization, which is common in AD patients.
- Functional assessments of skin barrier integrity can predict who might develop atopic dermatitis, making early intervention possible.
- Further research is needed to refine barrier function measurements to effectively assess and treat atopic dermatitis.
- Thyssen JP. and Kezic S. J Allergy Clin Immunol 2014;134:792-9
- J Clin Invest. 2012;122(2):440-447
- J Invest Dermatol. 2013 Apr;133(4):988-98
- Scientific Reports. 2019 9:8625: 1-15
- Semin Cutan Med Surg. 2008 Jun;27(2):144
- Berdyshev, G Allergy Asthma Immunol Res. 2024;16:445
- Chermprapai et al. J. Lipid Res. 2012. 53: 2755
- Elias et al. Experimental Dermatology. 2018;27:847
- Janssens, Michelle et al. Journal of Investigative Dermatology. 2011. 131, 2136
- Kubo A et al. JEM (2009) 206: 2937-2946
- Yokouchi M et al. eLIFE (2016) 5: e19593
- De Benedetto A et al. J Allergy Clin Immunol (2011);127:773
- Nat Genet. 2006;38:337
- J Allergy Clin Immunol. 2014;134:82
- J Allergy Clin Immunol. 2012;129:1031
- J Allergy Clin Immunol. 2009;124:507
- Exp Dermatol. 2011;20:149
- J Invest Dermatol 2021;141:2611
- J Invest Dermatol 2023; doi:10.1016/j.jid.2022.10.019
- Callewaert ... Gallo. JID. 2020;140:191
- Kim J et al ., Allergy. 2023;78:1292
- Paller A et al ., JACI. 2019;143:26
- Sander N et al ., Br J Dermatol 2024; 191:344
- Horimukai et al. Cureus 2023; 15: e51196
- Montero-Vilchez T et al ., J. Clin. Med. 2022, 11, 3341
- Bissonnette R et al ., J Am Acad Dermatol. 2025:S0190-9622(25)00113-6