Transcript The Epidermal Barrier

The Epidermal Barrier
Catriona Curtis BVM&S MRCVS
Field Technical Advisor Virbac UK
Programme
• Introduction
• Structure
• Function
• Therapy
General Skin Functions
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Enclosing barrier
Environmental protection
Temperature regulation
Reservoir of fats, minerals, electrolytes, water, vitamins, fat,
carbohydrates, proteins, and other materials
Immunoregulation
Pigmentation
Antimicrobial action through the superficial lipid film
Vitamin D production
Adnexa production
Motion and shape (through pliability and flexibility)
Scott, Miller & Griffin - Muller & Kirk ’s Small Animal Dermatology 6th edition - 2001
Structure
The Epidermal Barrier
Emulsion ‘percolates’ between columns of squames,
providing ‘mortar’ to strengthen the epidermis as well as
providing the all important barrier effect
The Skin Barrier
Squames = “bricks
Intercellular lipid = “mortar”
Key Barrier Features
• Barrier to allergen, microbial and pathogen penetration
• Prevents trans-epidermal water loss (TEWL)
 A healthy stratum corneum has a high water content
 Ensures elasticity and pliability of the skin
• Impaired in specific skin disease proceses
 ATOPY
 KERATOSEBBORHEAIC DISORDERS
• Inflammatory responses can further impair epidermal differentiation
and hence barrier function
• Area of on going research in human and veterinary dermatology
 Marked similarities between human stratum corneum and canine
stratum corneum
 Human dermatologists using dogs as models for research
Lamellar Lipid Composition
• Composition
 ~50 % Ceramides 1,3 and 6
 ~25 % Cholesterol
 ~10-20 % Essential fatty acids
• They are produced by lamellar bodies in the stratum granulosum
and spinosum
• The lipids are then extruded from the lamellar bodies into the intercorneocyte space
• Concurrent enzymatic release transforms the polar lipids into
nonpolar lipids (hydrophobic)
 Ensuring that they are organised into multi-lamellar bilayers
Ceramide Composition
• Ceramides are complex sphingolipids
• They are formed from the amide linkage of a sphingoid base with a
variety of non hydroxylated, α-hydroxylated and ώ-hydroxylated
fatty acids
• 9 ceramides have been identified in the human stratum corneum
• Ceramides 1, 3 and 6 are now known to be present in the canine
lipid surface emulsion
• Canine stratum corneum ceramide composition similar to the human
stratum corneum
 Same sphingoid base
 Coupled to non hydroxylated and hydroxylated fatty acids
Ceramide Structure
Amide Bond
• The hydrophobic chain is formed when the ceramide joins with cholesterol and
free fatty acids
• These hydrophobic chains construct lipid bilayers
• This dramatically reduces the permeability to water and solutes
Ceramide 1 Composition
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Fatty acids attached to ceramides predominatly saturated
An exception is Linoleic acid, which is an essential component of ceramide 1
Ceramide 1 is critical to barrier function
Cholesterol is recognised important to cell to cell cohesion and hence alterations in
metabolism can affect desquamation.
What Happens When Things Go Wrong??
• Disruption of barrier function can allow;
 Allergen and pathogen penetration
 Trans epidermal water loss
 Increased permeability
• Now recognised as a primary disorder with some skin disease’s
 Defective lipid lamellae present (Inman et al 2003; Piekutowska et al
2008)
 Exhibit an irregular alignment and structure in comparison to normal
• Abormal lipid expression within the stratum corneum
 Reduced free lipid protein bound fatty acids and ceramides with atopic
dogs
 Larger amounts of glucosylceramides in atopic dogs
Defects
Electron microscopic observations of the stratum corneum intercellular lipids in normal and atopic dogs (1)
Courtesy of: T. Olivry, NC State University, USA.
Courtesy of: T. Olivry, NC State University, USA.
Cytokine Cascade
• It has been recognised that the compromised epidermal barrier will
facilitate penetration of antigens, pathogens and non specific
irritants
• This is turn can stimulate a cytokine cascade which is initiated in the
stratum granulosum
• The ensuing immunological cascade can further compromise the
barrier
Repairing The Barrier
• Combination of systemic and topical treatment
• Options
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Direct repair (Allerderm® spot –on)
Oral fatty acid supplementation
Therapy aiming at stopping the cytokine cascade
Therapy aimed at normalising epidermal turnover
• Management of primary and secondary skin disease
Conclusion
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Extensively studied in human and veterinary dermatology
Epidermal barrier is the main defence barrier of the skin
It is critical in reducing allergen penetration
Marked similarities between human epidermal barrier structure and
canine epidermal barrier
• Deficits and abnormalities in ceramides and fatty acids contribute to
the alterations in barrier function
• Skin disease further compromises barrier function
Please email any questions to
[email protected]
References
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irritant contact dermatitis, allergic contact dermatitis or atopic dermatitis: a multi-center study. Contact Dermatitis
2001;45:280-285.
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Di Nardo A, Sugino K, Wertz P et al. Sodium lauryl sulfate (SLS) induced irritant contact dermatitis: a correlation study
between ceramides and in vivo parameters of irritation. Contact Dermatitis 1996;35:86-91.
Di Nardo A, Wertz P, Giannetti A, Seidenari S. Ceramide and cholesterol composition of the skin of patients with atopic
dermatitis. Acta Derm Venereol 1998;78:27-30.
Downing DT. Lipid and protein structures in the permeability barrier of mammalian epidermis. J Lipid Res
1992;33:301-313.
References
Elias PM, Feingold KR. Does the tail wag the dog? Role of the barrier in the pathogenesis of inflammatory dermatoses
and therapeutic implications. Arch Dermatol 2001;137:1079-1081.
Elias PM, Hatano Y, Williams ML. Basis for the barrier abnormality in atopic dermatitis: outside-inside-outside
pathogenic mechanisms. J Allergy Clin Immunol 2008;121:1337-1343.
Fartasch M. Epidermal barrier in disorders of the skin. Microsc Res Tech 1997;38:361-372.
Hightower K, Marsella R, Creary E, Dutcher P. Evaluation of trans-epidermal water loss in canine atopic dermatitis: a
pilot study in beagle dogs sensitized to houst dust mites. 23rd Proceedings of the NAVDF Congress 2008, Denver,
Colorado, p183.
Inman AO, Olivry T, Dunston SM, Monteiro-Riviere NA, Gatto H. Electron Microscopic observations of stratum corneum
intercellular lipids in normal and atopic dogs. Vet Pathol 2001;38:720-723.
Jungersted JM, Hellgren LI, Jemec GB, Agner T. Lipids and skin barrier function--a clinical perspective. Contact
Dermatitis 2008;58:255-62.
Kwochka KW. The structure and function of epidermal lipids. Vet Dermatol 1993;4: 151-159
Lavrijsen APM, Bouwstra JA, Gooris GS et al. Reduced skin barrier function parallels abnormal stratum corneum lipid
organisation in patients with lamellar ichthyosis. J Invest Dermatol 1995;105:619-624.
References
Macheleidt O, Kaiser HW, Sandhoff K. Deficiency of epidermal protein-bound omega-hydroxyceramides in atopic
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Dermatol 1996;106:1096-1101.
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Piekutowska A, Pin D, Rème CA, Gatto H, Haftek M. Effects of a topically applied preparation of epidermal lipids on the
stratum corneum barrier of atopic dogs. J Comp Path 2008;138: 197-203.
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References
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stripping of stratum corneum from dogs. Arch Dermatol Res. 2010 Nov;302(9):639-644.
Popa I, Remoue N, Hoang LT, Pin D, Gatto H, Haftek M et al. Atopic dermatitis in dogs is associated with a high
heterogeneity in the distribution of protein-bound lipids within the stratum corneum. Arch Dermatol Res. (2011, in
press).
Scott DW, Miller WH, Griffin CE (Eds.). Structure and function of the skin. In: Small Animal Dermatology, 6th Edition.
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Virbac UK. Allerderm Product Profile 2010