The epidermal barrier function and antimicrobial peptides in atopic dermatitis: the role of topical modulation

Introduction The epidermal barrier is a crucial component of the defensive function of the skin. The main skin protective functions are related to water loss modulation/prevention, UV-protection, anti-oxidant and antimicrobial actions. It is well established that epidermal barrier function is abnormal in subjects suffering from atopic dermatitis. Several evidences have shown that this alteration could be considered as the initial pathogenic factor starting the pathological process of atopic dermatitis. The aim of this review was to discuss the role of topical modulation in the epidermal barrier function and antimicrobial peptides in atopic dermatitis. Conclusion The use of emollients has shown to reduce the risk of atopic dermatitis flares and to reduce the need for topical corticosteroid. New emollient and moisturizing products seem promising not only in controlling symptoms and signs of atopic dermatitis but also in improving the skin barrier functions acting specifically in the ceramide component and in normalising antimicrobial peptides production of keratynocites. Introduction Atopic dermatitis (AD) is characterised by reduced skin hydration and an impaired skin barrier mainly due to a deficit in moisturizing property, alteration in lipid content and in the production of antimicrobial substances1–4. It is important to note that in AD subjects’ epidermal barrier dysfunction could be observed also in the skin not involved in active lesions5. Skin barrier defect in AD is mainly due to reduced lipid (i.e. ceramide) content of the epidermis; a reduced or genetically altered filaggrin synthesis and finally a reduced synthesis of antimicrobial peptides (AMPs)6. The deficit of the innate immunity could explain the increased risk of pathogenic bacterial colonisation and infection observed in AD subjects7. For these reasons, treatments with the aim to improve skin barrier properties of AD subjects could be a relevant approach in the strategic treatment of this skin condition. In view of the fact that AD is a chronic condition, caring for atopic skin must be a day-to-day task. Efficient skin care may reduce acute flares by improving the compromised skin barrier and reducing trans-epidermal water loss (TEWL)8. The mainstay of basic AD management, supported by several international guidelines, is the regular use of moisturisers together with good skin hydration and the avoidance of known triggers9. New moisturising products could contain additional compounds helping in the recovery of the normal skin barrier (i.e. ceramide topical supplementation) or showing anti-inflammatory action10. When used as mono-therapy, the use of moisturising creams is associated with a clinical improvement in AD. A particular interest could be found in the use of topical anti-inflammatory and moisturising products containing compounds, which could improve the innate immunological system of the skin such as isoleucine. Topical isoleucine has shown to increase production at the skin level of AMPs11. Therefore, the use of these kinds of products could have a strong rationale in AD coadiuvant treatment. In patients with mild to moderate AD chronic lesion, the use of non-steroidal cream containing Lisoleucine has shown to significantly reduce the eczema area and severity index (EASI) score of children with AD of the face with a clinical efficacy significantly greater than the control emollient cream12. These data, therefore, suggest that it could be possible to modulate and improve the defective skin barrier system in AD patients through topical specific compounds. This paper discusses topical modulation in the epidermal barrier function and AMPs in AD. Discussion Epidermal barrier alteration in AD: focus on filaggrin The superficial layer of the skin (epidermis) plays an important role in several physiologic critical functions such as control and modulation of water loss, antimicrobial defence, the hydration of skin, UV defence, antioxidant defence and the formation of a mechanical barrier13. The normal epidermal barrier is formed mainly by flattened keratinocytes, holding together by corneodesmosomes, a water resistant layer of lipid lamellae which prevent water loss, and finally by natural moisturizing factor, a mixture of aminoacids, urea and other substances, which are contained inside the keratinocyte cell. It is well known that atopic dermatitis is a clinical condition characterised by a deficit of the barrier function of the * Corresponding author Email: [email protected] Via A. Nota 18, 20126 Milan, Italy