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The role of the stratum corneum (SC) and several associated epidermal barrier (EB) functions in both healthy and compromised skin have gained increased recognition over more recent years. This is most evident based on the work of research that has defined correlations between EB impairments and compromised skin, including those related to specific skin disorders.1-3 Although atopic skin and eczematous dermatitis have been the primary focus, the importance of SC impairments and EB dysfunction in other skin diseases has also gained increased recognition.3-7 In addition, the importance of developing topical vehicle formulations that are “barrier friendly” is well recognized.
The main goal of this supplement is to encourage clinicians to understand the importance of addressing EB function in maintaining healthy skin and to appreciate its role in the overall management of many skin disorders. Objectives to support this goal are to provide summaries of physiologic SC and EB barrier functions, outline SC self-repair mechanisms, define compromised skin and SC impairments, evaluate potential differences in the EB among different skin types and ethnicities, and review the roles of moisturization and barrier repair in the management of specific skin disorders.
It is important to recognize that the EB represents a collection of specific diverse functions, many of which occur primarily within the SC. These include maintenance of water content and balance (permeability barrier), prevention and responses to invasion by microbial organisms and antigens (antimicrobial barrier and immune response barrier), reduction of the effects of ultraviolet (UV) light exposure (photoprotection barrier), and mitigation of the effects of oxidative stresses (antioxidant barrier).3 Many of the activities of the EB occur within the SC, which is why the terms SC impairment and EB impairment are often used interchangeably. In fact, the entire epidermis contributes to the EB, although many of the major activities of barrier maintenance and repair occur within the SC. The major components of the SC and EB function are depicted in Table 1. These EB functions are dynamic and work collectively to maintain healthy skin, characterized by invisible desquamation, smooth texture, elasticity, and ability to respond to shearing forces without rigidity and microfissuring.3
The structural and functional activities of the SC have been well described in the literature and will only be summarized in this supplement in order to elucidate clinical relevance.1-3,7-9 Overall, the EB functions to physiologically maintain the integrity of the skin. By maintaining proper cutaneous water balance and mitigating exogenous environmental and microbial stresses, the SC sustains normal desquamation and skin elasticity.1,3,7-11
Sustaining an intact and noncompromised SC and maintenance of physiologic EB function are dependent on the continuous replenishment of specific structural components of the epidermis. As the lower epidermis gives rise to the SC at the transition zone of the granular layer, the formation of the intercellular lipid membrane between corneocytes, and its direct relationship to the establishment of a proper water gradient provide the foundation for optimal enzymatic functioning and establishment of the proper acidic pH within the SC. The end results of both optimal functioning of SC enzymes and a proper pH are the continuous building of stable epidermal structures via corneocyte envelopment and adhesion, formation of an intercellular lipid membrane that is specified in composition and lamellar structure, and the reparative ability to increase production of filaggrin, the precursor of natural moisturizing factors (NMF) which provide intracellular humectancy within the SC (Figures 1 and and22).1-3,7-14 Enzymatic activity also contributes to formation of the physiologic SC lipids, which comprise approximately 20 percent of the volume of the SC and are composed of ceramides (40-50%), cholesterols (25%), and free fatty acids (10-15%), most of which are present within the intercellular lipid membrane.1,3,8
Exogenous factors that can alter the integrity of the SC cause an increase in transepidermal water loss (TEWL) and alterations of SC proteins and lipids, progressively leading to compromised skin.1,3,15,16 Unless these factors are adequately countered by SC self-repair mechanisms and/or moisturization, the SC becomes overstressed, with continued increased TEWL leading to incomplete desquamation, loss of skin elasticity, increased skin rigidity, and epidermal proliferation.1,3 Exogenous factors that lead to increased TEWL and SC/EB dysfunctions include improper skin care, exposure to cutaneous irritants, occupational exposures, application of certain topical agents, and low ambient humidity (Figure 3).3,15,16
In some individuals, underlying skin status and disease states, such as atopic dermatitis, innate xerosis, ichthyosis, psoriasis, diabetes, and increased age, exhibit inherent SC impairments, which predispose to increased TEWL, and when adversely affected by the aforementioned exogenous factors, the magnitude of EB permeability barrier compromise is further compounded.1-3,6,17,18 ln such cases, it is more difficult for SC self-repair mechanisms to normalize SC functional integrity and EB function as both exogenous and endogenous factors are contributing to EB impairment. For example, indivuduals with atopic skin are unable to produce adequate amounts of certain ceramides, and many exhibit filaggrin gene mutations, thus leading to a baseline increase in TEWL within their normal-appearing skin that increases during eczematous flares.2,3
Figure 3 shows the exogenous and endogenous factors that contribute to compromised skin and depicts the physiologic adaptations of the SC in response to these factors. When compromise of the SC permeability barrier is allowed to persist without adequate repair, the underlying pathophysiologic aberrations lead to clinically apparent changes in the skin.1,3 Abnormal desquamation leads to clumping of corneocytes, which presents visibly as scaling and flaking; loss of elasticity and increased rigidity leads to microfissuring and macrofissuring; and epidermal proliferation can lead to hyperkeratosis.3 The stepwise progression of changes secondary to continued SC permeability barrier damage are demonstrated in Figure 4, depicting alterations induced by increased TEWL over time within visibly normal skin, xerotic skin, and eczematous skin.
As skin is exposed to multiple exogenous factors that may lead to EB impairments, the SC is continuously active in maintaining a functional physiologic state by utilizing a variety of self-repair mechanisms. Once TEWL is increased beyond the normal homeostatic level, multiple self-repair mechanisms are induced within the SC and at the granular zone transition layer of the epidermis.3,8,10,19,20-22 These self-mechanisms are:
On a daily basis, the SC is dynamic and utilizes self-repair mechanisms to maintain a normal physiologic balance within skin, and to contribute to overall homeostatic water balance. When exogeneous and/or exogenous factors create EB impairment that is not correctable by self-repair alone (overstressed SC), visible xerotic, eczematous, and specific disease state manifestations emerge.1,3,8
This underscores the need to incorporate proper daily skin care utilizing a gentle cleanser and well-formulated moisturizer to assist the SC in maintaining EB integrity. The use of gentle skin cleansing and moisturization/barrier repair becomes more evident clinically in patients with underlying disease states that are characterized by asteatotic skin changes and/or sensitive skin due to the disease state itself and/or topical therapies used for treatment.1,4,23-30
Although the structural and functional components of the SC and EB barrier have been reasonably defined, there is more recent interest in ethnic and racial differences that may translate to differences in clinical presentations of xerotic skin changes and skin sensitivity.31-34 Although conflicting evidence exists in some areas, some observations have been made that may assist in targeting certain groups with specific skin care formulations.31-37 The following observations have been gleaned from studies assessing potential differences in SC/EB barrier structure and functions among different races and ethnicities:
More data are needed on differences in SC/EB structure and function among individuals of different races, ethnicities, and different magnitudes of skin pigmentation (FST). A summary of findings gleaned to date depicts relative differences based on an overall consensus from available literature.31 Racial variability in physiological properties of the SC and EB can directly impact SC water content and sensitivity to exogenously applied agents. Given the large number of moisturizers presently available in the marketplace, several different moisturizer/barrier repair formulations with individual ingredients may be employed to promote skin hydration. More data are needed to determine if certain moisturizers/barrier repair formulations may be more or less effective than others to maintain SC/EB structure and function and to manage xerotic skin disorders.31
There is a body of evidence to show that optimal management of many skin diseases, including eczematous dermatitis, acne vulgaris, rosacea, psoriasis, and xerosis, includes appropriate skin care.33,23-30 Incorporation of a gentle (nonirritating) skin cleanser and a well-designed moisturizer/barrier repair formulation can contribute to improvement of disease-associated signs and symptoms and can mitigate cutaneous irritation caused by certain topical medications.3,23-27 The distinction between moisturizers and topical barrier repair products is not clearly defined. Conventional moisturizers, available over-the-counter (OTC), can be purely occlusive (i.e., petrolatum, lanolin), or can contain both occlusive agents (i.e., petrolatum, occlusive/protective emollients) and humectant ingredients (i.e., glycerin, hyaluronic acid), designed primarily to reduce TEWL and increase SC hydration.25,26,40 Barrier repair formulations, usually made available as prescription products, contain the fundamental ingredients of a conventional moisturizer along with specific “physiologic” ingredients (i.e., ceramides, essential fatty acids) and formulation design characteristics that directly target barrier repair (i.e., replenishment of the SC intercellular lipid membrane).26 However, there are also OTC moisturizer formulations that contain physiologic lipids (i.e., ceramides, ceramide precursors, fatty acids) and other special additives (i.e., niacinamide) that can assist in barrier repair.26 The following are examples of clinical use of moisturizers and barrier repair formulations, which contributed to favorable therapeutic outcomes:
Supplement disclosure:This supplement was supported by educational grants from Valeant and PuraCap. The content and preparation of this supplement was completed solely by the authors. No individuals from any company or agency was involved in content development, preparation, review, or submission of this manuscript.