DAC - Barrera Cutánea - Biopatología
Deepen in the news of physio-pathology and alterations of the skin barrier in patients affected by CAD.
Canine atopic dermatitis (CAD) is a chronic allergic and inflammatory disease of genetic predisposition (ICADA 2015). It is estimated that it may affect 2% of the canine population and between 10 and 15% of those who suffer from skin diseases.
The pathogenesis for CAD has been associated most frequently with hypersensitivity reactions mediated by immunoglobulin E (IgE), but now the evidence is inclined to theories that include the integrity of the skin barrier as a key factor in the clinical expression of the disease (Olivry et al. 2010). CAD shares many immunological and clinical similarities with human atopic dermatitis (HAD) (Marsella, Olivry 2003), because it is similar in distribution of lesions and in the epicutaneous route of exposure to allergens (Marsella et al. 2011).
The stratum corneum (SC), as the surface layer of the epidermis, consists of the cornified keratinocytes or corneocytes surrounded by lamellar lipid complexes. In addition, SC is essential for the protection of the skin barrier, preventing transepidermal water loss (TEWL) and preventing the entry of exogenous substances. Also, lipids and proteins are very important components in cornification processes and differentiation of the epidermis (Marsella et al. 2011).
The stratum corneum (SC) is a highly specialized, essentially waterproof structure, except for a small influence, which serves to maintain hydration and flexibility. Hydration in the surface layers is critical to facilitate desquamation, the peeling process of the skin on the skin surface. In the course of its evolution through the different epidermal layers (stratum basale, stratum spinosum, stratum granulosum and stratum corneum) the keratinocyte follows a program of terminal differentiation. The protein synthesis stops in the interface between the stratum granulosum and the stratum corneum. The lamellar bodies are synthesized and the different lipid fractions are released into the extracellular space to be later organized in the stratum corneum. Postmortem keratinocytes modifications are essential for the proper functioning of the stratum corneum and to the existence of controlled desquamation process (Hardlig 2004).
The integrity of the epidermal barrier in humans can be measured non-invasively through the transepidermal water loss or TEWL (Oestmann 1993; Pinnagoda et al. 1990), that generally it is effected using open or closed chamber evaporimeters (Olivry 2011). The usefulness of measuring TEWL in dogs is not clear, because there is a very large variation between individuals and anatomical locations, which does not allow reliable comparisons between trials (Beco, Fontaine 2000; Lau-Guillard et al. 2010). There is another method to measure the skin barrier function and the levels of skin hydration, using a technique known as corneometry (Blichmann et al. 1988). Hydration levels appear to be similar between normal skin and skin uninjured in dogs with CAD. The injured skin shows lower hydration values (Shimada et al. 2009).
Stratum corneum lipids are composed mainly of free fatty acids, cholesterol and ceramides. Ceramide synthesis takes place in the stratum basale. These are converted into glucosylceramides and sphingomyelin which are then grouped into lamellar bodies. These cells migrate to the stratum granulosum and release their contents into the intercellular spaces.
The excreted lipids are organized in lipid bilayers. Ceramide levels in the stratum corneum are regulated by a balance between synthetic enzymes and ceramidases (Ohnishi et al. 1999).
A reduction in the total amount of ceramides and some subclasses of free and protein-bound ceramides in atopic canine patients with uninjured stratum corneum, is associated with an increase in transepidermal water loss (Popa et al. 2011).
The protein that has been most discussed in recent years in the pathogenesis of AD is filaggrin (Marsella et al. 2011), for being responsible of adding keratin and other proteins in the upper layers of the epidermis, to form the stratum corneum. The conversion process of profilaggrin into filaggrin is the one maintaining the integrity of the epidermis (Santoro et al. 2010).
Studies on the clinical efficacy of complex skin lipids, used topically in the treatment of CAD, tend to show significant changes in the stratum corneum, after 3 weeks of local application of an emulsion with ceramides, free fatty acids and cholesterol (Popa et al. 2012).
Shampoos containing sphingosine, antiseptics, fatty acids and complex sugars, have been used in dogs with CAD, showing decrease in the pruritus degree and the severity index and extent of the CAD (CADESI) (Bourdeau et al. 2007). Another study with topical products based on plant essential oils and unsaturated fatty acids (spot-on and spray) obtained similar results with evident reduction in the pruritus level (CADESI), but no evidence of improvement in values of transepidermic water loss TEWL (Tretter et al. 2011).
Recent treatment recommendations against CAD - 2015, published by the International Committee on Allergic Diseases of Animals (ICADA), refer potential benefits of the essential fatty acids in chronic cases of CAD. Oral delivery of essential fatty acids, especially Omega 6, as a supplement or included in balanced diets, can positively influence surface lipids, improving brightness and quality of the layer and reducing clinical signs of the CAD, but not as monotherapy. Simultaneous use of immunotherapy, emollient shampoos and essential fatty acid supplements, help decrease the dose and frequency of oral glucocorticoids, cyclosporine and oclacitinib, to maintain remission of clinical signs in chronic CAD (Olivry et al. 2015).
The biopathology of the CAD shows alterations in structure and function of the skin barrier, whether due to environmental factors, inborn metabolism errors or acquired diseases. It is broadly accepted the concept that a defective barrier is not simply a secondary result but the predisposing leading to inflammation in the cornification disorders. Therefore, understanding of the molecular basis of the perturbation of the skin barrier leads to the implementation of adequate therapeutic options to improve the barrier, both anatomically and functionally, to maintain and/or restore skin quality.
Skin homeostasis is altered in a myriad of skin diseases, if not in all, resulting in epidermal hyperproliferation and aberrant differentiation.
It is clear the concept that a healthy skin barrier equals healthy skin and therefore it is necessary an optimal care to maintain it (Olivry, Marsella 2012).
References
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2. Blichmann CW, Serup J. Assessment of skin moisture. Measurement of electrical conductance, capacitance and transepidermal water loss. Acta Dermato-venereologica. 1988;68:284–290.
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10. Popa I, Remoue N, Osta B, et al. The lipid alterations in the stratum corneum of dogs with atopic dermatitis are alleviated by topical application of a sphingolipid-containing emulsion. Clinical and Experimental Dermatology. 2012;37(6):665–671.
11. Santoro D, Marsella R, Bunick D, et al. Expression and distribution of canine filaggrin in the skin of healthy and atopic beagles (abstract). Veterinary Dermatology. 2010;21:323.