Skin Barrier Repair

Introduction

Moisturizers are the key to skin barrier regulation and repair and the mainstay of treatment for atopic dermatitis (AD) along with topical medications ( ). Moisturizers have been shown to reduce transepidermal water loss and improve barrier function, preventing flares and the need for topical corticosteroid use in patients with AD ( ). Daily use of moisturizer improves xerosis, resolves pruritus quicker, and lengthens the time to flare compared to no treatment ( ). Thus daily use of moisturizers to preserve barrier function is fundamental to preventing flares and maintaining quiescent periods in AD.

The skin barrier

Skin is the largest organ of the body and functions as an interface between the internal and external environment. The skin is an essential factor to human survival as a physical barrier against harmful external agents and in protecting against dehydration. The stratum corneum is a major component of the skin barrier, which plays a key role in these important functions. In the stratum corneum, keratinocytes terminally differentiate into corneocytes, which are embedded into a lipid-rich extracellular matrix ( ). Corneocytes are characterized by cornified envelopes that contain densely packed keratin filaments cemented by several proteins, particularly filaggrin molecules. Filaggrin degradation produces natural moisturizing factor, which is responsible for hydration of the stratum corneum, as well as regulation of its pH ( ). As a result, acidification by filaggrin metabolites helps to retain the skin barrier ( ). The filaggrin metabolites, which make up natural moisturizing factor, include amino acids, lactic acids, salts, and urea ( ). Natural moisturizing factors in the extracellular matrix attract and bind water to maintain moisturization and lipids. The lipids are made from breakdown products of keratinocytes and corneocyte membranes, called lamellar granules ( ). Lamellar lipids are composed of cholesterol, free fatty acids, ceramides, and other sphingolipids ( ). Disruptions and disorders of these biochemical pathways can impair the skin barrier and increase its vulnerability to environmental insults and transepidermal water loss ( ). Additional details of the skin barrier are discussed in Chapter 5, Chapter 11, Chapter 15 .

AD is a common chronic inflammatory skin disease attributed to both epidermal barrier dysfunction and chronic T helper type 2 (Th2) inflammation ( ). The impaired barrier function in AD impacts allergic sensitization to protein antigens and microbes, including staphylococcal superantigens, which further exacerbates barrier dysfunction due to altered epidermal differentiation from underlying epidermal inflammation ( ). Th2-related cytokines, such as interleukin-4 (IL4), further intensify skin barrier impairment by altering keratinocyte differentiation and lipid synthesis in the stratum corneum ( ). Elevated transepidermal water loss correlates with AD severity. Thus, for patients with AD, restoring hydration and reducing transepidermal water loss with appropriate use of moisturizers plays a key role in repairing epidermal barrier dysfunction ( ).

Moisturizers

While there is no consensus regarding the definition of moisturizer , the term was initially coined by marketers to promote its function to moisten the skin ( ). Moisturizers address the epidermal repair dysfunction by acting as an occlusive barrier, slowing transepidermal water loss, retaining hydration, and protecting the skin from external irritants ( ). The terms moisturizer and emollient are often used interchangeably; however, moisturizers encompass emollients, occlusives, and humectants. Emollient is more specific to a moisturizer that is mostly made up of lipids and their components ( ). Emollients fill in the space between desquamating corneocytes to create a smooth surface and are used to soften, hydrate, and smooth the skin ( ). Examples of emollients include soy sterols, collagen, elastin, shea butter, glycol, and glyceryl stearate ( ). Occlusive topical agents are mostly oil based and are similar to intercellular matrix lipids like ceramide, cholesterol, and free fatty acids ( ). Occlusives form a thin hydrophobic film on the stratum corneum to slow the transepidermal water loss and thus prevent drying ( ). Examples of occlusive agents include petrolatum, dimethicone, mineral oil, silicone, olive oil, and lanolins ( ). Lastly, humectants are agents that attract and hold water from the dermis and the environment to moisturize the skin ( ). Humectants include glycerin, sorbitol, and α-hydroxyl acids ( ). The efficacy of moisturizers depends not only on the ingredients of the moisturizer but also on the proper delivery system to encourage adherence.

Moisturizer delivery systems

Choosing an ideal delivery system for a patient is critical to delivering the most efficacious treatment while also encouraging adherence to treatment. Various delivery systems include ointments, creams, lotions, gels, and oils. A summary of these moisturizer vehicles can be found in Table 22.1 .