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Barrier function and immunology of the skin: skin health and skin disease

Barrier function and immunology of the skin: skin health and skin disease. Julia Schofield. Barrier function. Why does it matter?. Childhood eczema. Eczema is common Mild, moderate or severe 20% under one year olds Big impact on families

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Barrier function and immunology of the skin: skin health and skin disease

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  1. Barrier function and immunology of the skin: skin health and skin disease Julia Schofield

  2. Barrier function Why does it matter?

  3. Childhood eczema • Eczema is common • Mild, moderate or severe • 20% under one year olds • Big impact on families • Recent research shows importance of barrier function • Relevant to eczema of all types in all ages

  4. Barrier function and atopic eczema

  5. A Healthy Skin Barrier Swelled corneocytes Cornified envelope Intact Corneodesmosomes Lipid Lamellae pH 5.5 Degradatory Proteases Lipid processing NMF H2O NMF H2O NMF H2O Filaggrin Protease Inhibitors Lipid delivery Profilaggrin 1/2/2020 The Academic Unit of Dermatology Research, The University of Sheffield. 5

  6. A Healthy Skin Barrier Swelled corneocytes Cornified envelope Intact corneodesmosomes pH 5.5 NMF H2O NMF H2O NMF H2O Natural moisturizing factor Urocanic acid, Pyrrolidone carboxylic acid, lactic acid, urea Lipid Lamellae Ceramide: cholesterol: fatty acids Degradatory proteases Protease inhibitors Lipid delivery & processing Filaggrin Danby SG & Cork MJ, The Academic Unit of Dermatology Research, The University of Sheffield. 1/2/2020 6

  7. Allergens & Irritants pH 5.5 NMF H2O NMF H2O NMF H2O Water 1/2/2020 The Academic Unit of Dermatology Research, The University of Sheffield. 7

  8. Brick => Corneocyte Mortar => Lipid Lamellae 3/26/09 The Academic Unit of Dermatology Research, University of Sheffield 8

  9. Mortar => Lipid Lamellae Ceramides + Fatty acids + Cholesterol 3/26/09 The Academic Unit of Dermatology Research, University of Sheffield 9

  10. The Normal Skin Barrier 3/26/09 The Academic Unit of Dermatology Research, University of Sheffield Cork et al 2006 JACI 10

  11. Irritants & allergens 1/2/2020 Danby SG & Cork MJ, The Academic Unit of Dermatology Research, The University of Sheffield. 11

  12. What goes wrong in childhood eczema?

  13. Infant skin has a low epidermal barrier reserve(i) (i)Nikolovski J, Stamatas GN, Kollias N, Wiegand BC. J Invest Dermatol. 2008 Jul;128(7):1728-36 (picture:) Cork MJ, Danby SG, Vasilopoulos Y, Hadgraft J, Lane ME, Moustafa M, Guy RH, Macgowan AL, Tazi-Ahnini R, Ward SJ. Epidermal barrier dysfunction in atopic dermatitis. J Invest Dermatol. 2009 Aug;129(8):1892-908

  14. When is the skin barrier not optimum? Danby SG & Cork MJ, The Academic Unit of Dermatology Research, The University of Sheffield. 1/2/2020 14

  15. A Defective Skin Barrier in AD Defective lipid lamellae Degraded Corneodesmosomes Abnormal cornified envelope (Reduced levels of ceramides) pH 7.0 NMF H2O NMF H2O NMF H2O (Reduced levels of ceramides) Filaggrin Lipid processing Degradatory Proteases Profilaggrin Lipid delivery Protease Inhibitors 1/2/2020 The Academic Unit of Dermatology Research, The University of Sheffield. 15

  16. PAR = Proteinase-activated Receptor-2

  17. An allergic response is elicited Allergens NMF H2O NMF H2O NMF H2O Th2 Th1 ? Cork, Danby et al (2009) In Skin Moisturization. Academic Unit of Dermatology Research, The University of Sheffield

  18. Allergens & Irritants pH 7.0 NMF H2O NMF H2O NMF H2O Water 1/2/2020 The Academic Unit of Dermatology Research, The University of Sheffield. 18

  19. Irritants & allergens TEWL 1/2/2020 The Academic Unit of Dermatology Research, The University of Sheffield. 19

  20. What do we mean by irritants?

  21. Identifying irritants: ask about skin care regime • Bath or shower • How often, per day, per week • Products used for washing/showering, added to bath • Products used for laundry

  22. Common irritants

  23. Common cause of irritancy! TOO MUCH WASHING!!!!

  24. Itching: some simple tips STOP ALL IRRITANTS: • Shower gels • Soaps • Biological washing powders • Fabric conditioners • Leave on moisturiser • NOT AQUEOUS CREAM

  25. The effect of topical products/treatments on pH and protease activity

  26. A Healthy Skin Barrier Swelled corneocytes Cornified envelope Intact Corneodesmosomes Lipid Lamellae pH 5.5 Degradatory Proteases Lipid processing NMF H2O NMF H2O NMF H2O Filaggrin Protease Inhibitors Lipid delivery Profilaggrin 1/2/2020 The Academic Unit of Dermatology Research, The University of Sheffield. 26

  27. A Defective Skin Barrier in AD Defective lipid lamellae Degraded Corneodesmosomes Abnormal cornified envelope (Reduced levels of ceramides) pH 7.0 NMF H2O NMF H2O NMF H2O (Reduced levels of ceramides) Filaggrin Lipid processing Degradatory Proteases Profilaggrin Lipid delivery Protease Inhibitors 1/2/2020 The Academic Unit of Dermatology Research, The University of Sheffield. 27

  28. Protease activity in the skin barrier Protease Activity (in the stratum corneum - no red stain) Nucleated layers (nuclear material stained red) Dermis The Academic Unit of Dermatology Research, University of Sheffield

  29. The effect of pH on skin barrierprotease activity: clinical relevance pH 8.5 pH 7.0 pH 5.0 Acute AD pH 7.3 Current AD pH 5.7 Normal skin pH 5.0 The Academic Unit of Dermatology Research, University of Sheffield

  30. The Effect of Washing with Liquid Soap on Skin Surface pH *p = <0.05; ***p = <0.001; n = 3 Danby SG & Cork MJ, The Academic Unit of Dermatology Research, The University of Sheffield. 1/2/2020 30

  31. The Effect of Washing with Liquid Soap on Skin Surface pH Acute AD Current AD (non-lesional site) Clinical relevance* *p = <0.05; ***p = <0.001; n = 3 Danby SG & Cork MJ, The Academic Unit of Dermatology Research, The University of Sheffield. 1/2/2020 31

  32. Aqueous cream – first appeared in the BNF in 1958 Its formulation containing SLS remains largely unchanged today

  33. Aqueous Cream Leave-On compared with No Treatment for 4 weeks Skin Barrier Integrity: End Point 1/2/2020 The Academic Unit of Dermatology Research, The University of Sheffield 33

  34. Atopic eczema and domestic water hardness. McNally NJ, Williams HC, Phillips DR, Smallman-Raynor M, Lewis S, Venn A, Britton J. Lancet. 1998 Aug 15;352(9127):527-31. “Living in a hard water area is significantly associated with an increased lifetime prevalence of AD” Confirmed by 2 replicate studies (in Japan and Spain) Danby SG & Cork MJ, The Academic Unit of Dermatology Research, The University of Sheffield. 1/2/2020 34

  35. A Randomised Controlled Trial of Ion-Exchange Water Softeners for the Treatment of Eczema in Children Kim S. Thomas, Tara Dean, Caroline O'Leary, Tracey H. Sach, Karin Koller, Anthony Frost, Hywel C. Williams, and the SWET Trial TeamPLoS Med. 2011 February; 8(2): e1000395.

  36. To summarise

  37. Atopic eczema: pathophysiology BRICK WALL THEORY

  38. The Brick Wall theory Leads to dry skin Irritants penetrate and trigger inflammatory response

  39. Brick wall theory: correct barrier function Correcting barrier function reduces dry skin and penetration of irritants and inflammation

  40. EMOLLIENTSEMOLLIENTSEMOLLIENTS!

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