Skin 101: Understanding the Fundamentals of Skin Barrier Physiology—Why is This Important for Clinicians?

J Clin Aesthet Dermatol. 2025;18(2):7–15.

by James Q. Del Rosso, DO, and Leon Kircik, MD
Dr. Del Rosso is Research Director at JDR Dermatology Research in Las Vegas, Nevada; Senior Vice President of Clinical Research and Strategic Development at Advanced Dermatology and Cosmetic Surgery in Maitland, Florida; and Adjunct Clinical Professor (Dermatology) at Touro University Nevada in Henderson, Nevada. Dr. Kircik is Medical Director at Skin Sciences, PLLC, in Louisville, Kentucky.

FUNDING: The authors received no compensation for preparation of this article. This article was written solely by the authors. 

DISCLOSURES: Dr. Del Rosso has served as a consultant, speaker and/or researcher for Arcutis, Bausch Health, Beiersdorf, Galderma, Unilever, L’Oreal, LaRoche-Posay, and Sente.

ABSTRACT: This article reviews epidermal barrier dysfunctions and more thoroughly discusses the stratum corneum (SC) permeability barrier, physiologic self-repair mechanisms in healthy skin, and the clinical and structural effects of an overstressed SC permeability barrier. Discussion includes epidermal barrier impairments induced by both exogenous exposures and endogenous factors such as specific dermatologic disorders. Due the plethora of skin care products on the market and the variability of their contents and vehicle formulations, this article addresses core concepts required to optimize skin care product selection, including for specific disease states such as atopic dermatitis, psoriasis, acne vulgaris, and rosacea. To summarize, the selection of skin care products is directed at maintaining SC hydration, including assisting the SC in self-repair when conditions are adverse. This approach optimizes the ability to sustain healthy skin structure, function and appearance.

KEYWORDS: Skin barrier, epidermal barrier, skin care, stratum corneum dysfunction, transepidermal water loss, corneometry

Introduction

In dermatology, there is an inherent tendency to focus on how to treat various skin conditions based on the most current scientific information, especially with newer therapeutic options. This is true especially in the clinical arena where patients are directly cared for. Publications and presentations usually emphasize pharmacologic and/or procedural therapies, however, the exponential increase in skin care options over time has created a center stage for including optimized skin care as an integral component of cutaneous disease management and post-procedural approaches. The primary objective of this article is based on the premise that to truly understand what we apply to patient care, we need to “learn how to walk before we run.” Once the core fundamentals are mastered, we are in a much better position to translate our knowledge into the clinical setting and more effectively manage many skin conditions, especially common disorders.

Over a decade ago, I (JDR) was fortunate enough to interact which scientists who were dedicated to researching the basic functions of the stratum corneum and epidermal barrier in normal and diseased skin. After a focused period of deep work in studying all the scientific information that could be found on epidermal structure and function, I (JDR) voluntarily served as lead author of a comprehensive article on the clinical relevance of maintaining the functional integrity of the stratum corneum in healthy and diseased skin.¹ This article was dedicated to providing dermatology with a core reference that pieces together a wide body of basic science and clinical research, including articles from several different authors that are published in journals that most dermatologists and staff are not likely encounter in their mainstream dermatology literature. Much of what is stated in the article from 2013 still applies today. This article serves to review and update the reader on the fundamentals of skin barrier function as a foundation to understanding and applying the integration of skin care into clinical management in their practice.

What does the term “skin barrier” actually refer to?

The term skin barrier, which is also commonly referred to as the epidermal barrier, is often incompletely misunderstood, as the epidermal barrier of the skin is actually a collection of multiple barrier functions. When the terms skin barrier or epidermal barrier are used in professional conversation, they are usually referring to the ability of the epidermis, especially the stratum corneum (SC), to provide selective permeability of exogenous and endogenous substances and to continually regulate and maintain homeostatic water content and balance in order to sustain healthy skin elasticity and physiologic desquamation; terms such as transepidermal water loss (TEWL) and corneometry (measure of water content in skin) are often mentioned.^1–3 These functions refer specifically to the epidermal permeability barrier.¹

In fact, these permeability barrier functions are components of a collective group of physiologic and homeostatic epidermal barrier responsibilities, carried out primarily within the SC. Additionally, these physiologic epidermal barrier responsibilities are continually responding dynamically to various exogenous exposures that are adversely affecting epidermal barrier integrity and function.^1–9 Hereafter, the term epidermal barrier will be used here to also synonymously encompass the term skin barrier.^1–3 Table 1 depicts the multiple barrier functions that collectively comprise the epidermal barrier; these individual barrier functions are reviewed in more detail elsewhere.^1-10

How does the epidermal barrier respond physiologically to protect healthy skin? 

Structural characteristics. Before reviewing how the epidermal barrier functions in self-repair to sustain healthy skin in response to endogenous exposures, a brief review of epidermal structure is relevant. Figure 1 depicts the classically described “bricks and mortar” structure of the SC. The structural integrity framework of the corneocytes (“bricks”) which are held together by corneodesmosomes, is maintained primarily by keratin macrofibrils and other structural proteins encased by a cornified envelope and covalently bound lipids.⁴ Within the corneocytes exists a relative concentration of natural moisturizing factor (NMF); NMF is highly hygroscopic and serves as the innate humectant that retains within the SC the necessary water content and balance to homeostatically maintain the hydrolytic activity needed for optimal desquamation, skin elasticity, and prevention of desiccation, rigidity, and fissuring of the skin.^1,4,9–11 When SC water content decreases below a critical threshold level due to factors increasing TEWL, the SC protein filaggrin is broken down to form NMF as a SC self-repair response; the multiple components of NMF are primarily free amino acids (40%), pyrrolidone carboxylic acid (12%), lactate (12%), simple sugars (9%), urea (7%) and multiple electrolytes.^1,4,5,9–18

Importantly, the spaces between the corneocytes are interconnected to form an intercellular lipid membrane, with SC lipids representing 20 percent of total SC volume^1,4,18,19 This membrane is vital to maintaining SC physiology, especially water flux and balance.^{1,4,9–11,18,19} For optimal function, the intercellular lipid membrane is purposely designed to predominantly contain relative concentrations of specific lipids that are strategically arranged in a lattice of ceramides (40–50%), cholesterols (25%), and free fatty acids (10–15%), exhibiting specific structural characteristics to provide physiologic epidermal barrier function.^1,4,18–20 Importantly, reductions in chain length of both free fatty acids and ceramides correlate directly with decreased density of SC lipid organization and greater impairment of epidermal barrier function in skin affected by atopic dermatitis.²⁰

Functional characteristics. The structural and functional integrity of the SC is highly dependent on an adequate water content and gradient; many of the enzymes that catalyze vital SC functions are hydrolytic and do not operate efficiently if water content is below a requisite threshold concentration.^1,3,4,9,10 With regard to maintaining physiologic epidermal water content, the SC is innately capable of multiple self-repair mechanisms when exposed to exogenous exposures that induce adverse changes that impair the SC permeability barrier.^1,4,5,9,11 Examples of relatively abrupt and/or repetitive exposures that can increase TEWL and promote skin desiccation include marked reduction in ambient humidity, adverse skin care practices, poorly formulated skin care, exposure to cutaneous irritants and/or allergens, occupational exposures, certain topical medications, and inadequately designed topical vehicles.¹ Importantly, SC water serves to plasticize the SC, thus enhancing elasticity and reducing epidermal rigidity that enhances fissuring, especially when skin encounters lateral shearing forces; proper water content directly affects other physical properties, such as flexibility, pliability, desquamation of individual corneocytes, skin pH, and cornified cell envelope formation.^{2–4,9,11–13,21–25}

Self-repair. Self-repair within the SC is quickly triggered by even modest increases in TEWL and decreased SC water content.^1–5 There is immediate release of stored lipids from lamellar bodies in the SC which partially reverses the increase in TEWL. This is followed within a few hours by markedly upregulated production of major SC lipids which serve to restore intercellular lipid membrane integrity and contribute to SC water binding capacity.^1,4,26–28 Another immediate response to increased TEWL is cytokine release that promotes epidermal thickening to physically reduce the magnitude of TEWL.^1–5,9 

A fundamental self-repair mechanism in response to increased TEWL and decreased SC water content is the upregulation in filaggrin production and its subsequent conversion into NMF. As NMF increases SC humectancy, more water is retained within the SC, thus reversing the adverse effects of decreased SC water content.^{1–5,17,21,29} Over time, SC self-repair can maintain healthy skin when effectively coupled with mitigation of the inciting exogenous factors discussed above that induce epidermal barrier damage and impair the permeability barrier. Repeated exposure to inciting triggers, especially when frequent and of high magnitude, can often override the ability of SC self-repair to maintain healthy skin. Common examples of this latter scenario are frequent hand washing and/or overwashing, repeated exposure to skin irritants, use of poorly formulated skin care products including harsh skin cleansers, and excessively hot showering.¹ As will be discussed below, certain skin diseases are associated with impairments in SC self-repair which further compounds the effects of exogenous exposures that damage the skin barrier.

What is the clinical relevance of skin pH?

Alterations in skin pH alone can result in clinically relevant changes in SC barrier function.^30–38 This is exemplified by the neutral to alkaline pH of the SC in the early neonatal period which facilitates the growth of opportunistic organisms such as Candida albicans, creating a regional environment that predisposes to diaper dermatitis. After approximately the first three months of life, the SC physiologically converts to an acidic pH for optimal epidermal barrier function; this “sweet spot” is commonly referred to as the acid mantle of the skin (skin pH 4–6).^1,23,30 

An elevated skin pH induces a multitude of direct and indirect effects that adversely alter several epidermal barrier functions, many secondary to the subsequent increase in SC protease activity. These adverse effects include disruption of skin barrier homeostasis (decreased SC lipid synthesis, degradation of lipid synthesis enzymes, augmented non-physiologic desquamation, inhibition of lamellar body lipid secretion), suppression of innate antimicrobial peptide (AMP) defense (altered AMP processing and activity), induction of inflammation (“jump start” cytokine activation [IL-1, TNF alpha]), and augmented pruritus (pruritogen release such as leukotriene B4 and prostaglandin E2); many of these effects can markedly alter the structure and function of the SC permeability barrier.^1,38

Another important observation is that an acidic SC pH favors growth of normal bacterial flora and a more diverse cutaneous microbiome, as opposed to an alkaline pH, which is more supportive of the growth of potential pathogens such as Staphylococcus aureus and Candida albicans.^4,30,36,38 Innate buffering capacity of the skin is decreased in neonatal skin, geriatric skin, with repeated washing using alkaline soaps/skin cleansers, and with regular use of alkaline moisturizers.³³ As an elevated (alkaline) skin pH is noted in both atopic dermatitis and acne vulgaris, use of cleansers and/or moisturizers that are not formulated to mitigate disturbance of skin pH may contribute to adverse effects such as irritation and/or deterioration of the underlying skin condition.^33,36,37

What is an overstressed epidermal barrier?

An overstressed epidermal barrier occurs when exogenous, endogenous, or a combination of both sources produce SC permeability barrier impairment that exceeds the ability of self-repair mechanisms to fully and visibly correct the induced epidermal barrier dysfunction.¹ The potential exogenous factors were discussed earlier. Endogenous factors include individual genetic, ethnic and/or racial predispositions, effects of increased age, or underlying disease states that are inherently associated with permeability barrier impairment.^1,4,39,40 These affected individuals are at an inherent disadvantage when stresses that are placed upon the epidermal barrier exceed the restorative self-repair abilities of the SC. In such cases, the self-repair functions of the SC are not able to keep up with the speed and/or magnitude of permeability barrier restoration needed to fully reverse the excess in TEWL. Unless corrected by proper therapeutic intervention, the clinical sequelae of skin desiccation is the progressive march starting with subclinical effects, then to visible signs and symptoms of xerosis (ie, dry skin) which often increase in severity over time, then to signs and symptoms of an acute or subacute flare of eczematous dermatitis, and finally to chronic eczematous dermatitis and progressive hyperkeratotic changes, especially on the hands and feet (Figure 2). 

Disease states the compromise the epidermal barrier and stratum corneum self-repair

Compromise of epidermal barrier function is commonly associated with several dermatologic disease states, with the SC permeability barrier frequently affected.^1,4 Xerosis, although not often thought of as a fundamental primary skin disease, is probably the most commonly encountered skin disorder that is primarily correlated with impairment of the epidermal permeability barrier.¹ Atopic dermatitis (AD), due to the plethora of data on overall pathophysiology and multiple epidermal barrier abnormalities, has served as the “poster skin disease” used to illustrate the multiple profound effects of epidermal barrier dysfunction.^{1,4,22,38,41–46} Epidermal barrier dysfunctions are identified in many dermatologic diseases, with specific barrier abnormalities varying among different disease states. In this article, we will discuss selected common skin diseases to illustrate different examples.

Xerosis. Xerosis, described as one of the most common human skin afflictions, is the initial clinical evidence of an impaired SC permeability barrier as described in Figure 2.^1,4,47,48  

Regardless of etiology, xerosis is the visible reaction pattern that occurs when TEWL becomes excessive and exceeds the ability of SC to adequately self-repair the permeability barrier.^1,47,48 Ultimately, xerosis is best defined clinically, presenting as skin that is dull in appearance, rough, scaly, flakey, and tight, often with associated pruritus, and in some cases discomfort especially in low ambient humidity.^1,4

Xerosis may be observed in individuals that do not have any apparent endogenous primary skin disease. Phenotypic xerosis is not uncommon among the general population and may reflect a range of variability in SC self-repair capacity among the general population. Development of xerosis is also affected by the extent of exposure to inciting exogenous factors. In many cases, xerosis can exist concurrently with other primary skin diseases, the most common being atopic dermatitis.^1,4,43,48 Avoidance of exacerbating exogenous factors along with proper use of well-formulated cleanser and moisturizer formulations are the foundation of management for xerotic skin.^{1,21,28,47,49–51} 

Atopic dermatitis. Atopic dermatitis is associated with multiple barrier impairments that are well described elsewhere.^{1,4,20,23,27,29,36,41–46,52,53} In this article, the primary emphasis is on SC permeability barrier dysfunction in AD. SC lipid abnormalities have been demonstrated in eczematous skin, in xerotic skin, and in uninvolved skin in patients with AD.^{1,4,20,22,27,28,42,43,54} 

Although the major lipid fraction affected in AD is ceramides, the free fatty acid subfraction is also affected.^{1,20,45,51,52} The upregulated Th2 cascade associated with increases in IL-4, IL-13, and IL-31 cytokines reduces the expression of major ceramide synthesizing enzymes, thus contributing to SC permeability barrier impairment.^52,55 Some studies have shown that the greatest ceramide subfraction decrease in AD patients was ceramide-1 in both lesional (eczematous) and nonlesional skin (visibly uninvolved without presence of eczema); however, ceramide-2 through ceramide-6 were also markedly decreased in both lesional and nonlesional skin.^{1,28,43,54,56} Additionally, correlation of SC ceramide composition with permeability barrier function in patients with AD showed marked decreases in both ceramide-1 and ceramide-3, with a direct correlation between reduction in ceramide-3 and an increase in TEWL.^41,54,56 

Collectively, SC permeability dysfunction in AD correlates with decreased total ceramide levels, altered ceramide chain lengths (increased short chain ceramides, decreased long chain,  ceramides), altered free fatty acid chain lengths (increased short chain free fatty acids, decreased long chain free fatty acids), and a decrease in hydroxy-fatty acids.⁵² From a clinical perspective, the importance of consistently addressing atopic skin with proper skin care (cleansing and moisturization) is strongly supported by a three- to five- fold increase in TEWL noted in lesional skin compared to nonlesional skin in AD, and a two-fold increase in TEWL in clinically normal and xerotic skin (without eczematous changes) in AD patients who present with active AD flares at other skin sites.^{41,54,56–58} 

A common genetic aberration that impairs the SC permeability barrier, affecting 30 to 50 percent of AD patients are filaggrin gene mutations, studied primarily in white patients but not limited to this population.^29,44,52 The resultant filaggrin deficiency impairs the physiologic self-repair response to increased TEWL due to the reduced ability to produce NMF through the usual route of filaggrin degradation.^1,29,44 Downstream consequences of filaggrin deficiency in AD patients affected by filaggrin gene mutations can include xerotic skin, decrease in skin lipids, and an altered skin microbiome with increased skin colonization by Staphylococcus aureus.⁵² The possible presence of filaggrin deficiency due to this genetic predisposition in many AD patients supports why some moisturizers formulated to specifically target xerotic and atopic skin contain components of NMF.^17,59

Psoriasis. The pathophysiology of psoriasis is complex, multifactorial, and has been progressively updated based on continued advances in basic science and clinical research.^60,61 An understanding of the SC abnormalities noted in psoriasis have been evaluated with considerations given to how they impact on the pathophysiology of the disease and its management.^62–68 SC abnormalities observed in plaque psoriasis lesions that can translate to impairment of SC permeability barrier functions include abnormal disposition of lamellar bodies in some phenotypes, genetically-associated changes in epidermal differentiation including aberrant expression of keratins, altered cornified cell envelope formation, decreased filaggrin expression, altered ceramide synthesis and subfractions in psoriatic skin lesions correlating directly with increased TEWL, reduced levels of short chain fatty acids and increased cholesterol in psoriatic lesions compared to healthy skin, altered expression of specific SC enzymes (eg, ceramidase, transglutaminases), decreased keratinocyte aquaporin-3 skin hydration channels, increased epidermal hyperproliferation, and disruption of SC intercellular connections (multiple affected proteins).^65,67,68 Upregulation of IL-17 and IL-22 are noted to play important roles in keratinocyte activity and inflammation in psoriasis.; abnormal keratinocyte differentiation is observed in psoriatic skin with markers of epidermal proliferation highly expressed in psoriatic lesions which are reduced with effective treatment.⁶⁷ 

The overall epidermal barrier dysfunction in plaque psoriasis, including marked impairments of SC permeability function, is multifactorial, encompassing abnormalities in both epidermal structure and function and also lipid content. Importantly, the total amount of ceramide content in keratinocytes and fibroblasts in psoriatic skin lesions is not reduced with SC permeability barrier dysregulation  likely correlating with abnormalities of ceramide subtype in psoriasis; changes in free fatty acids and the reported increase in SC cholesterol may also alter the relative balance within the intercellular lipid membrane.⁶⁷ This may impact on the choice of moisturizer formulation if there is also the logical desire to replenish the skin with specific ingredients in managing psoriasis.^68–71

Acne vulgaris. Data are limited on SC permeability barrier dysfunctions that are innately present in untreated acne vulgaris (AV); most of the emphasis on epidermal barrier impairment in AV focuses on topical therapeutic agents and vehicle formulations as many are associated with cutaneous inflammation.^1,72,73 One of the early studies completed in patients with AV (N=36) showed increased TEWL, reduced SC hydration based on conductance testing, reduction in total SC ceramides, and reduction in SC free sphingosine as compared to the study control group.⁷⁴ It is uncertain whether or not epidermal barrier impairment in AV is inherently a part of the AV disease state, is primarily secondary to inflammation occurring during a flare, and is also present in nonlesional skin during and AV flare or between flares.^37,73,74

Some topical acne medications and/or vehicle formulations are associated with adverse visible signs of cutaneous irritation, such as peeling, scaling, and erythema. As a result, the clinically apparent association of a topical AV formulation and/or a therapeutic AV ingredient with impairment of the SC permeability barrier or other SC functions is an important clinical consideration.¹ Cutaneous application of benzoyl peroxide has been demonstrated to increase TEWL, oxidize SC antioxidants (eg, alpha tocopherol [vitamin E]), and induce lipid peroxidation; supplementation with topical vitamin E did not correct the increase in TEWL, but did reduce markers of lipid peroxidation.⁷⁵ Topical retinoids commonly induce varying degrees of application site erythema, peeling, and flaking, usually within the first month of use, due to their inherent mechanism of action which alters epidermal differentiation and increases SC cellular dyscohesion.⁷⁶ This is referred to as the initial period of “retinization” and is commonly interpreted as cutaneous irritation; regardless, these changes represent alterations in SC structure and can influence the permeability barrier.¹ Additionally, some topical retinoid vehicle formulations are associated with a greater potential for cutaneous irritation. Several vehicle modifications and gentle skin care approaches have been recommended to reduce the adverse visible skin changes that are often associated with topical retinoid use and other topical acne therapies (such as benzoyl peroxide), especially in the first weeks of initiating therapy and/or when used in combination with other topical acne medications.^77,78 One study that supports using SC permeability barrier-enhancing moisturization before and during and after initiation of topical retinoid therapy showed that this approach facilitated adaptation to the initial period of “retinization and induced signs of cutaneous irritation, decreased TEWL, and improved cutaneous hydration as measured by conductance.⁷⁹ It is also important to regularly incorporate skin care with a gentle skin cleanser and moisturizer in patients treated with oral isotretinoin.⁸⁰ 

The importance of adjunctive skin care as an integral component of acne management is well established in medical literature.^{1,71,73,75,77–83} Skin care concepts and approaches that specifically discuss use in patients with AV are available in the literature, with selected references shown here.^77,81

Rosacea. Cutaneous rosacea, most often presenting clinically as central facial erythema with papules and pustules (papulopustular rosacea) and central facial erythema without papules and pustules (erythematotelangiectatic rosacea), is often associated with symptoms of stinging and burning, especially during periods of flaring. Several specific epidermal barrier impairments, including SC permeability barrier dysfunction, have been demonstrated in facial rosacea; multiple potential triggers have been frequently noted, resulting in “sensitive skin” commonly associated with facial rosacea, both during and between flares.^84,86–88 In untreated adult patients with papulopustular rosacea (N=915) pooled from multiple studies, dryness, scaling, and edema were reported by 65 to 69 percent, 51 to 58 percent, and 32 to 38 percent of subjects, respectively; facial skin burning, stinging, and pruritus were reported by 34 to 36 percent, 29 to 34 percent, and 49 to 52 percent of subjects, respectively.^1,89,90

Sensitive skin and SC permeability barrier dysfunction in cutaneous rosacea are evidenced by the above discussion, providing strong support for adjunctive gentle skin care using a well-selected cleanser and moisturizer.^84,90–96 There are data to support increased TEWL, decreased epidermal hydration, increase SC pH, increased stinging induced by lactic acid facial skin testing, associated symptoms of stinging, burning, tingling, and itching, and an increased risk of facial contact dermatitis; specific SC lipid abnormalities have not been identified in rosacea prone skin.^{86,87,97–99} Designated skin care approaches with cleansers and moisturizers, and formulation characteristics including specific ingredients to mitigate SC permeability barrier dysfunction and the associated diffuse facial erythema of rosacea, are discussed in selected references.^{92,94,96,97,100} Although rosacea is reported to most commonly affect white individuals with fair skin, it is well-recognized that rosacea can affect all racial and ethnic groups including those with darker skin types such as people of African descent, Asian, and Latino populations.^101,102,103

How can skin care be optimized to maintain the functional integrity of the epidermal barrier?

The above article outlines epidermal barrier dysfunctions and more thoroughly discusses the SC permeability barrier, physiologic self-repair mechanisms in healthy skin, and the effects of an overstressed SC permeability barrier including exogenous inducing factors, and endogenous factors such as specific dermatologic disorders. Due the plethora of skin care products on the market and the variability of their contents and vehicle formulations, a complete discussion of individual products is beyond the scope of this article. However, a few basic concepts deserve mention here. Ultimately, the selection of skin care products needs to focus on the maintenance of SC hydration, including assisting the SC in self-repair when conditions are adverse, in order to sustain healthy function and appearance of the skin. 

Skin cleansers. The use of a well-formulated gentle skin cleanser that effectively removes exogenous and exfoliated debris and excess sebum, that does not perturb skin pH, and  produces negligible damage to the SC is optimal for both healthy skin and disease-affected skin.^{95,96,101–106} Well-designed adjunctive skin care that is selected based on the needs of the individual patient, which includes a well-formulated gentle skin cleanser, augments therapeutic response to overall treatment in a variety of skin conditions, such as AD and rosacea, and/or can reduce adverse effects associated with therapies that can adversely affect the SC.¹

Moisturizers. Moisturizers are recommended, concurrently with an appropriate gentle cleanser, for use in people with healthy skin who encounter intermittent or continuous exogenous exposures that diminish or overstress SC permeability barrier function, in individuals with impairments of SC permeability function due to inherent phenotypic xerotic skin, elderly skin, in the management of underlying dermatologic disease (as described above), and/or in those utilizing therapies that induce SC permeability barrier dysfunction (as described above).^{1,4,11,21,26, 28,48–51,59,68–72,75,77–79,81,83,84,90–97,101–103} For example, a thorough evidenced-based review of studies evaluating consistent moisturizer use in patients with eczematous dermatitis demonstrated therapeutic contribution that decreased the frequency and severity of flares and reduced the amount of topical corticosteroid use needed over time.⁵⁰   

The three core fundamental components of a well-designed moisturizer are occlusive agents, humectants, and agents that provide an emollient effect.^47,49,59 Occlusive agents retard water evaporation by forming a hydrophobic barrier layer on the skin surface; these often include hydrocarbons/oils/waxes (eg, petrolatum, mineral oil, paraffin, Carnauba wax, silicone derivatives), fatty alcohols (cetyl alcohol, stearyl alcohol, lanolin alcohol), and other fatty acids, wax esters, and sterols.^47,59 Humectants attract water from the dermis and from high ambient humidity into the epidermis to maintain SC water content; these include glycerin (glycerol), hyaluronic acids, urea, panthenol, propylene glycol, sodium PCA, and certain lactates.^47,59 Emollients exhibit different physical properties, protective, fatting, astringent, or dry characteristics) and are included to impart a soft and smooth skin texture by “filling the crevices” and fissures characteristic of xerotic skin; these include castor oil, Jojoba oil, silicone derivatives, isopropyl myristate, isopropyl palmitate, and isostearyl alcohol.^47,59   

Ultimately, moisturizing agents that incorporate quality fundamental ingredients in appropriate concentrations and combinations, such as humectants, occlusive agents and emollients, and contain physiological lipids or ingredients that augment skin lipid synthesis, and/or include other agents such as components of NMF that facilitate permeability barrier restoration, may be an optimal choice as these formulations are designed to target specific SC abnormalities that lead to xerotic skin changes, at least in most cases.^1,47,49,59 Agents that are predominantly only occlusive and/or humectant may exhibit less substantivity, may produce less overall beneficial impact on physiological barrier restoration, and are often less likely to be preferred by patients for continued use due to a greasy or sticky texture.^1,47,49,59 Importantly, individual formulations must be evaluated based on their own performance in both research investigations and after careful observation during clinical use. correlated with the reasons why they were rationally selected. In the article above, several examples are given with references for further information that provide more detail on suggested formulations and ingredients for xerotic skin conditions and specific disease states.

Conclusion

The epidermal barrier is a collective entity comprised of multiple individual barrier functions as depicted in Table 1. This article primarily emphasizes the SC permeability barrier which is a major dynamic component of overall epidermal barrier function, and is involved in regulation of epidermal water content, flux, and balance. Understanding the physiology of the SC permeability barrier in healthy skin and self-repair mechanisms that counter the adverse effects of increased TEWL and decreased SC hydration are fundamental to comprehending accurate clinical evaluation of barrier-related impairments in healthy and disease-affected skin. Various disease states exhibit specific barrier impairments that frequently include structural and functional SC dysfunction and permeability barrier dysregulation. Adjunctive skin care is a vital integral component in dermatologic practice, with product selection tailored to the needs of the individual patient. Without proper skin care, it is far more difficult to maintain healthy skin and to optimally manage several skin diseases, as outlined in this article.     

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