Moisturizer and Barrier Repair Formulations

Introduction

Over the past decade, the subject of epidermal barrier function and its relationship to both healthy and diseased skin has become very prominent in the dermatology literature. Coupled with this is the expectation that a dermatologist should have a very good understanding of the importance of maintaining the structure and function of the epidermal barrier and that they are facile in educating patients about proper skin care and rational product selection based on the clinical situation with each patient. Importantly, clinicians are most comfortable recommending a specific product, whether it is over-the-counter (OTC) or by prescription (Rx), if they understand why a given product makes sense for a patient who presents with a specific disorder.

With regard to selection of skin care products, many clinicians provide an array of samples, or become familiar with a few specific products through personal familiarity or the anecdotal experiences of individual patients. In the past, how clinicians chose individual skin care products was often arbitrary. However, there has been a marked increase in skin care formulations that contain more specialized ingredients, sometimes targeting specific skin disease states based on the ingredients used (i.e. ceramides and atopic skin). This is especially true with OTC moisturizers and Rx barrier repair products that contain more than the basic occlusive and humectant agents and also incorporate specific ingredients designed to repair and maintain stratum corneum (SC) permeability barrier integrity and function. In order to demonstrate evidence-based support for a given formulation, there has been a considerable increase in more rigorous scientific evaluation of OTC products and Rx-based barrier repair formulations. The scientific evaluations that are being used include a variety of laboratory assays that assess SC structure (i.e. quantitative assays) and/or function (i.e. transepidermal water loss (TEWL), SC hydration (corneometry), the incorporation of physiologic lipids in the epidermis (i.e. Raman spectroscopy), and clinical studies primarily in subjects with xerotic skin or with specific underlying skin disorders (i.e. atopic dermatitis (AD), acne vulgaris (AV), rosacea). With greater knowledge of how dysfunctions of the epidermal barrier contribute to the pathophysiology of specific skin conditions, and with more scientific data emerging to support individual Rx and OTC skin care formulations, clinicians are progressively basing their recommendations on a better appreciation and understanding of the science behind the formulations they recommend to their patients. This chapter specifically covers moisturizers and barrier repair formulations, including the rationale for how they are designed (i.e. ingredients) and their practical application in clinical practice.

General principles of fundamental skin care

Why are proper fundamental skin care and maintenance of physiologic skin hydration important as integral components of the management of both healthy and diseased skin? To appreciate the answer to this question from a dermatologic perspective, one must consciously recognize that the SC is a dynamic structure that is continuously responding to a variety of daily exogenous factors that diminish its integrity and function as a major physiologic responsibility of the epidermal barrier. It is equally important to recognize that the ‘epidermal barrier’ is actually a collection of physiologic and homeostatic barrier functions, most of which correlate physiologically with normal SC structural and functional integrity. These SC barrier functions include the permeability barrier, which controls water flux and content; the antimicrobial barrier, which comprises several widely distributed antimicrobial peptides (AMPS) that provide immediate innate protection against invasion by bacteria, viruses, and fungi: the antioxidant barrier, which counteracts the effects of reactive oxygen species (ROS) induced by a variety of exogenous exposures (i.e. ultraviolet [UV] light, pollutants); the immunologic barrier, which detects a variety of signals that trigger specific immunologic and/or inflammatory responses; and the photoprotection barrier, which serves to mitigate cellular damage produced by exogenous light exposures (i.e. UV light). A dominant barrier function, which is somewhat central to overall epidermal barrier integrity and activity, interacts with other SC barrier properties, and affects overall SC structural integrity and function, is the SC permeability barrier. This is because SC permeability barrier impairment leads to insufficient and poorly balanced SC water content. Lack of proper quantity and distribution of water within the SC leads to diminished function of several enzyme systems that are needed to physiologically maintain basic epidermal/SC structure, physiologic desquamation, and normal skin elasticity and resiliency. When SC water content is too low, the impaired function of major SC enzymes leads to skin roughness with visible scaling and flaking due to clumped corneocytes that have not been individually desquamated; increased skin rigidity, microfissuring and macrofissuring caused by desiccation and shearing forces that are not counteracted due to diminished skin elasticity and resiliency; and localized areas of hyperkeratosis, especially on the hands, feet, and elbows.

Three fundamental active skin care processes are integral to the maintenance of overall skin health and normal physiologic function of the SC, especially the permeability barrier: cleansing, moisturizing, and photoprotecing. Cleansing allows for removal of external debris, natural cutaneous secretions, and microorganisms. The degree of SC permeability barrier damage induced by a given cleanser correlates directly with characteristics of the formulation, such as alkaline pH, inclusion of harsh surfactants or emulsifying agents, and other excipients that can induce cutaneous irritation or allergy. Moisturizers are an important component of basic skin care as they serve to counteract a variety of exogenous and endogenous factors that damage the SC resulting in an increase in TEWL and a decrease in SC water content. Hence, use of a well-formulated moisturizer aids the inherent self-repair mechanisms of the SC and expedites permeability barrier repair by sustaining SC water content above the levels needed to maintain physiologic SC enzyme function. This ultimately preserves the structural and functional integrity of the SC permeability barrier. Although a discussion of photoprotection is beyond the scope of this chapter, suffice it is to say that rational measures to limit both acute and chronic photodamage, and the appropriate use of broad spectrum sunscreens are vital to the maintenance of skin health.

Exogenous factors that promote SC permeability barrier impairment include the use of poorly formulated skin cleansers (i.e. true soaps), desiccating astringents, topically applied irritants, certain topical medications (i.e. retinoids, benzoyl peroxide, corticosteroids, some vehicles) and low ambient humidity, which enhances evaporative water loss and SC desiccation. Endogenous factors include older age, chronic photodamage, and several disease states that are inherently associated with clinical or subclinical alteration of the epidermal barrier and/or reduced SC water content. Such disease states include inherited forms of xerosis; atopic dermatitis; atopic skin; ichthyosis vulgaris; and underlying disease states associated with a predilection for dry skin. Thus, individuals affected by any of the above endogenous factors exhibit inherent impairment of the SC permeability barrier, which can be compromised even further when exposed to exogenous factors that induce SC damage. When SC permeability barrier impairment exceeds barrier repair through insufficient self-repair and/or inadequate moisturization, the SC becomes ‘overstressed’ due to the prolonged increase in TEWL and decrease in skin hydration that remain unchecked. This scenario progressively leads to visible xerotic skin changes, asteatotic dermatitis (i.e. eczema craquele), and localized hyperkeratosis.

The use of moisturizers and barrier repair formulations is commonly recommended in dermatology practice, as clinicians appreciate the therapeutic contribution of adjunctive skin care. The myriad of moisturizer products available often confounds rational product selection. The bottom line is to maintain a ‘simplest is best approach’, especially as many product claims, special additives, and carefully marketed ‘prestige products’ are backed by little or no scientific evidence supporting their benefit or extraordinary expense.

Maintenance of normal skin integrity and water content

Cutaneous water balance, homeostasis, and normal appearance of skin require the presence of an epidermis, and importantly, a SC that is structurally and functionally intact. The epidermal permeability barrier is composed of two functioning components: 1) a cellular protein matrix composed of an intertwined and layered lattice of keratinocytes (‘bricks’) with an uppermost layer of thin SC cells (corneocytes); and 2) an intercellular lipid bilayer matrix (‘mortar’). Proper function and maintenance of both components assures skin integrity, water balance, hydration, and orderly corneocyte desquamation. Disturbance of either or both of the SC functional components increases TEWL, resulting eventually in xerotic skin changes if not corrected. The ideal range of SC water content is 20% to 35%; reduction to <10% water content results in visibly evident xerotic skin changes, although lesser changes in SC water content can trigger ‘self-repair’ mechanisms, such as immediate release of preformed physiologic lipid precursors stored in the granular layer and increase in filaggrin production, the predominant precursor of natural moisturizing factors (NMF).

Physiologic epidermal barrier repair

The homeostatic signal which correlates with maintenance and repair of epidermal barrier function is TEWL. When TEWL increases by as little as 1%, a physiologic signal initiates barrier repair by upregulating lipid synthesis. Disturbances in epidermal barrier permeability induce a physiologic response to restore barrier function, with normalization occurring within hours to days; the time course of restoration of barrier function is dependent on the extent of the insult, the age of the patient, and the patient's overall health status. Recovery (self-repair) of the epidermal barrier occurs as extracellular lipids are secreted into the SC interstitium by keratinocytes underlying the site of insult and are organized into lamellar membrane unit structures. Within 30 minutes, lamellar bodies are deposited from the outer granular layer which release pre-formed stored lipids as an immediate self-repair response, followed within the next 4 hours by synthesis of fatty acids and cholesterol, and over the next 6 to 9 hours by increased ceramide production.

Clinical impact of moisturizers

In the presence of intrinsic or extrinsic factors that promote SC permeability barrier disruption and reduced SC water content, moisturizers, especially those with optimized components, simulate the role of epidermal lipids in promoting and restoring permeability barrier function. Externally applied lipids have been shown to intercalate between corneocytes and can mitigate surfactant-induced skin irritation. Application of non-physiologic occlusive lipids, such as petrolatum, creates a diffuse hydrophobic phase that rapidly diminishes TEWL by permeating within the upper interstitium of the SC.

Some studies evaluating the application of physiologic lipids in moisturizers and barrier repair formulations have shown that certain ceramides can be incorporated into the SC, including at different depth levels, and do not appear to downregulate physiologic lipid production in skin. Based on in vitro murine models, the use of physiologic lipids in moisturizers appears to be optimized by inclusion of all three lipid components (ceramide, cholesterol, free fatty acids) in an optimized concentration ratio, otherwise barrier recovery may be impaired.

Significance of moisturizer application frequency

Due to the loss of applied product imposed by the continuous natural process of epidermal desquamation and limitations of product substantivity, persistent efficacy provided by moisturizer use requires repeated application on a daily basis.

Evaluation of moisturizing properties after discontinuation of treatment with moisturizers (regression phase analysis) has demonstrated long-lasting effects for several days in studies completed with some moisturizers, including lanolin-based and cetyl alcohol/petrolatum/polyglycerylmethacrylate-based moisturizer preparations. However, it is best that patients are educated to follow a reasonably regular routine with skin care including moisturizer use in order to encourage consistency, especially those with chronic eczematous skin disorders and xerosis-prone skin.