An evidence-based, peer-reviewed journal for practicing clinicians in the field of dermatology
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S4 SUPPLEMENT TO THE JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY [APRIL 2016 • VOLUME 9 • NUMBER 4 • SUPPLEMENT 1] 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 2). 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 What is "Compromised Skin?" 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 Figure 1. This figure depicts the "bricks and mortar" structure of the stratum corneum. The corneocytes represent the bricks and the intercellular lamellar lipid membrane represents the mortar. Corneocytes comprise primarily keratin macrofibrils, are pro- tected externally by a cornified cell envelope, and are held together by corneodesmosomes. The intercellular lamellar lipid membrane is primarily composed of ceramides, cholesterol, and fatty acids. A mixture of multiple small hygroscopic com- pounds present within corneocytes, referred to collectively as natural moisturizing factor (NMF), plays a vital role in the physio- logical maintenance of stratum corneum hydration. (Reprinted with permission from Harding CR. Dermatol Ther. 2004;17:6–15.) Figure 2. The "Epidermal Factory": Progressive layers and corresponding production steps. Reprinted with permission from: Del Rosso JQ, Levin J. J Clin Aesthet Dermatol. 2011;4(9): 22–42. © 2011 Matrix Medical Communications.