You are in: eMedicine Specialties > Dermatology > COSMETICS MoisturizersArticle Last Updated: Apr 29, 2008AUTHOR AND EDITOR INFORMATIONAuthor: Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Medicine, Professor of Pediatrics, Professor of Pathology, Professor of Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School Robert A Schwartz is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi Coauthor(s): Santiago A Centurion, MD, Staff Physician, Department of Dermatology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey; Isabelle Thomas, MD, Associate Professor, Department of Dermatology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School; Chief of Dermatology Service, Veterans Affairs Medical Center of East Orange Editors: Zoe Diana Draelos, MD, Clinical Associate Professor, Department of Dermatology, Wake Forest University School of Medicine; Primary Investigator, Dermatology Consulting Services; Private Practice; David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Director, Division of Dermatology, Scott and White Clinic; Director Dermatology Residency Training Program, Scott and White Clinic; Christen M Mowad, MD, Associate Professor, Department of Dermatology, Geisinger Medical Center; Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University; Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center Author and Editor Disclosure Synonyms and related keywords: lubricants, emollients, greases, barrier creams, protective creams, humectant INTRODUCTIONA moisturizer is an agent designed to make the stratum corneum softer and more pliant by increasing its hydration. A large number of preparations are available, many of which are marketed as cosmetic and therapeutic moisturizers. Two new anti-inflammatory moisturizers are on the market as prescription drugs, MimyX cream and Atopiclair cream, both of which have been approved by the US Food and Drug Administration (FDA) as medical devices rather than drugs.1, 2 With the realization that the stratum corneum is a dynamic and interactive tissue, new emphasis has been placed on agents that are used to moisturize the skin; these are suitably termed moisturizers. Their multiplicity and potential effects, including barrier functions, transepidermal water loss, and the exogenous or endogenous offenders that result in dry, scaly skin, parallel the increased understanding of the stratum corneum. Moisturizers are a group of cosmetic products designed for skin care and hygiene. Their claims are centered on the treatment of dry skin that results in smooth, more supple and healthier looking skin. Moisturizers have come under intense scrutiny in recent years regarding their therapeutic effects. They possibly are the most prescribed products in dermatology, and, until recently, dermatologists have received little or no training regarding these products, including their ingredients, pharmacokinetics, benefits, and toxicities. Naturally occurring skin lipids and sterols are often added to moisturizers. In the correct proportions, these agents can help promote repair of cutaneous barrier function. In the wrong proportions, they can delay repair. Moisturizers, at times, are referred to as humectants, emollients, lubricants, oils, and greases; however, these terms are not interchangeable. Each term has a specific definition. The Webster's Collegiate Dictionary of the English Language defines these terms as follows:
Moisturizers claim to heal and prevent dry skin; however, presently, no clear or simple definition of dry skin exists. Dry skin is dependent on several denominators, including the following:
Pierard3 attempted a universal definition of dry skin, "...dry skin is not a unique, well-defined condition but represents a medley of totally unrelated changes in the structure of the stratum corneum associated." Environmental and systemic conditions influence the properties of dry skin. Interaction of lipophilic moisturizers on stratum corneum lipid domains in vitro and in vivo have been analyzed.4 Many, if not most, lipophilic moisturizers do not drastically change the lamellar organization of the stratum corneum intracellular lipid matrix, but, rather, form separate domains in it. A near-infrared multispectral imaging method for measuring skin hydration was used in a clinical study for estimating skin hydration effects of skin moisturizers and cleansers.5 This new method was compared with the standard electrical methods for evaluating changes in skin hydration based on conductance and capacitance measurements. This imaging technique showed more sensitive discrimination between treatments and control, and the results correlated highly with the visual appearance of dryness. The correct use of moisturizers and cleansers is important for patients with dermatologic disease.6 Moisturizers containing certain ingredients, including occlusives and humectants, offer effective repair of damaged stratum corneum. EVALUATION OF DATA ON MOISTURIZERSData regarding moisture of the skin should be evaluated in a universal and absolute manner. This allows for reproduction and understanding of the subject matter. The different research techniques include the following:
Components of the skinLipids The nonpolar nature of lipids limits the passage of polar water molecules within cells, between cells, and from cells to the environment. In the 1950s, Kligman established trailblazing studies on epidermal barrier, "…the raison d'être of the viable epidermis is to make the horny layer." Since his early work, research on the stratum corneum has risen exponentially. Works by Downing, Gray, and Yardley have sketched a lucid portrait of the stratum corneum lipid composition in healthy and diseased skin. The extracellular membrane of the stratum corneum is composed of mainly ceramides, which constitute about 40% of lipid content, cholesterol (25%), and free fatty acids (10-15%), followed by smaller amounts of triglycerides, stearyl esters, and cholesterol sulfate. These lipids are synthesized throughout the epidermis where they are packaged in lamellar granules and subsequently undergo differentiation. In the lamellar granules, the lipids are stacked and flattened into lipid vesicles. After extrusion to the extracellular space, these flattened vesicles undergo rearrangement to form broad, multilamellar sheets. This process constitutes the water barrier. Ceramides become sphingolipids when glycosylated by the primary alcohol of sphingosine. A small number of ceramides are esterified with fatty acids, mainly linoleic acid. This composition results in acylceramides and is thought to serve an important function, that of maintaining the multi-bilayer organization of the barrier lipids. Cholesteryl sulfate is another important molecule, particularly in the desquamation process. It has been shown to be the intercellular cement. High amounts of cholesteryl sulfate have been shown to inhibit desquamation and the opposite in deficient disorders. Recent studies have shown that cholesteryl sulfate may inhibit transglutaminase-mediated involucrin cross-linking and its esterification to the omega-hydroxyceramides of the lipid envelope. Lipids play an important role in corneal barrier. They are first secreted from the lamellar bodies and subsequently undergo further differentiation. This transformation of probarrier lipids to the final ceramide-rich stratum corneum takes several steps. Any disruption of these steps consequently disturbs the process of barrier maturation and leads to water loss. Essential fatty acid deficiency, enzyme inhibitors, defective enzymes, enzyme deficiency, environmental constituents, topically applied agents, or water content of the stratum corneum can all cause perturbations of the barrier maturation process. Hou et al8 found major alterations in the lamella, being too thin, absent, or focally increased in essential fatty acid deficiency. Recessive X-linked ichthyosis shows a lack of the enzyme steroid sulfatase, which structurally leads to a lack of desmosomal disk disappearance and of lamellar bodies. In psoriasis, harlequin ichthyosis, atopic dermatitis, and congenital ichthyosiform erythroderma, lamellar bodies and the amount of lipids in the intercellular spaces are deficient. Ichthyosis vulgaris shows deficiency of keratohyalin granules, resulting in decreased natural moisturizing factor (NMF). Xerotic skin shows global deficiency in cholesterologenesis and other lipids. Other conditions are lamellar ichthyosis (see Ichthyosis, Lamellar) and epidermolytic hyperkeratosis (EHK) (see Epidermolytic Hyperkeratosis [Bullous Congenital Ichthyosiform Erythroderma]). A defect occurs on keratins 1 and 10 in EHK. A defect of transglutaminase is found in lamellar ichthyosis. Both conditions present at birth as collodium baby, but they differ in that lamellar ichthyosis can have ectropion, eclabium, or alopecia as opposed to EHK. The cornified envelope The protective barrier provided by stratified squamous epithelia relies on the cornified cell envelope (CE), a structure synthesized at late stages of keratinocyte differentiation. The CE is composed of structural proteins, including involucrin, loricrin, and the small proline-rich (SPRR) proteins. Genes localized at band 1q21 encode all the components of the CE. Sebum and dry skin Kligman9, 10 pointed out that children who are prepuberal produce almost no sebum, but most of these children did not have dry skin. Data have shown that sebum production is not correlated with the degree of xerosis. Squier et al11 found that sebum applied to rodent skin actually decreased the barrier function of the epidermis. Sebaceous glands produce squalene wax ester triglyceride and free fatty acids. The structures of the fatty acids esterified in the triglycerides are predominantly unique to sebum, indicating their endogenous synthesis in these glands. Water in the stratum corneum The pioneer work of Blank12 50 years ago shed light into the criticality of water and its effect on the plasticity of the skin. If a piece of cornified epithelium, such as cutting from a callus on the plantar surface of the foot, is dried out, it becomes very hard and brittle in spite of any natural oils it may contain. Any attempt to soften this cornified epithelium with petrolatum, anhydrous lanolin, or natural glycerides of fatty acids, such as olive oil, meets with complete failure, even though the oils remain in contact with the cornified epithelium for months at normal or elevated temperatures. If, on the other hand, similar pieces of cornified epithelium are allowed to absorb a little moisture, they become soft and pliable; therefore, it is apparent that the water content of the cornified epithelium is a more important factor in maintaining the flexibility of this layer than is its oil content. For this reason, a study of the factors that influence the moisture content of the stratum corneum has been undertaken. The stratum corneum possesses approximately 30% water, which is mainly associated with its elasticity. Ten percent of the water is bound to lipids, and, the remaining 20%, which is resistant to solvent and water extraction, may be secondary to keratin components. The innermost layers of the stratum corneum contain a high level of water, while the outermost layers of the stratum corneum contain a water level largely dependent on the ambient relative humidity. Plasticization of the stratum corneum is regarded to be a function dependent on its water content. Healthy stratum corneum must be able to maintain an adequate level of water against the evaporative diffusion gradient created by a low relative humidity. Any impairment of water binding because of adverse effects of exogenous toxins or endogenous components of the stratum corneum results in perturbation and pathological phenomena. A healthy stratum corneum contains about 10% tightly held water. The tightly bound water is closely dependent on the presence of NMF. NMF is a complex interaction of various substances, such as humectants, that are hygroscopic (ie, they attract water molecules from the environment). Data show that the water content of the stratum corneum increases with increasing relative humidity. The presence of NMF tends to increase the water content of the stratum corneum whenever the ambient relative humidity exceeds about 40-50%. The increased corneal thickness is about 10-15% when the stratum corneum is allowed to equilibrate in vitro from 0% relative humidity to 60%. Robbins and Fernee13 demonstrated that the presence of water does not fill voids or holes in the stratum corneum but, instead, causes swelling. Types of moisturizersMoisturizers Information on moisturizers has exponentially increased in recent years. Their structure and function are surprisingly complex and sophisticated; many are equidistant between cosmetics and drugs. Moisturizers of the new millennium include agents that mimic natural ingredients and function as botanicals, including vitamins, hydroxy acids, and retinoids. Other common ingredients are collagen, elastin, DNA, ribonucleic acid (RNA), lecithin, sodium hyaluronate, sodium passive cutaneous anaphylaxis (PCA), and ceramides. Disruption of intercellular lipid lamellae in the upper layers of the stratum corneum results in abnormal desquamation and an increase in TEWL. A simple explanation of a moisturizer's mechanism states that water, which otherwise would have been lost, is held by hygroscopic properties in the stratum corneum. Subsequently, this contributes to the smoothing of the skin surface due to swelling of the outer layers. Leveque14 showed that occlusion of the skin by products, such as petrolatum, paraffin, waxes, or greases, restores and enhances the natural diffusion of moisture from the dermal capillary beds. Downing and colleagues indicated that properly functioning intercellular lipids trapped and redistributed water effectively throughout the epithelium. Moisturizers impart a temporary barrier to damaged stratum corneum, which allows time for reparation of this layer. Two concepts have been proposed to explain water passage through the skin. First, the solubility-diffusion model postulates that water has a finite solubility in lipids; therefore, it can permeate through lipids in accordance with the accepted theory of P = KD/d. In this model, the water molecules are moving through the lipid barrier as individual entities, or 1 molecule at a time. This model is probably the best description of transepidermal water loss through the stratum corneum. The second model postulates that water passes through lipids through transient pores or water-filled channels. The evidence for the existence of such channels or pores is inconclusive in the case of most biomembranes and especially for the stratum corneum. Humectants Humectants are substances that attract water when applied to the skin. The source of the water is transepidermal, unless the relative humidity is very high (>80%). Humectants can also increase transepidermal water loss. At times, this can lead to a perception of skin tightness or dryness. Examples of humectants include glycerin, sorbitol, urea, alpha hydroxy acids (AHAs), and sugars. Lactic acid, particularly the salt form ammonium lactate, has demonstrated an ability to reduce the thickened stratum corneum of xerosis as well as to remove and clear the thick scales in ichthyosis and other hyperkeratotic conditions. Occlusion Lanolin was the first substance to be used in an occlusive system. Its use as a barrier has been known for thousands of years. Similar to other moisturizers, lanolin functionality was thought to be occlusive; therefore, lanolin prevents the loss of water. Today, other functions of lanolin are known as well. It has the reputation of being a contact sensitizer; however, this is controversial. Because of this reputation, petrolatum is now the principal ingredient used in occlusive formulations. Depending on the concentration, petrolatum physically blocks the surface of the stratum corneum and reduces transepidermal water loss. This increases the water content in the stratum corneum, thus producing a state of hydration. Two reasons exist as to why occlusion is one of the best treatments of dry skin. First, transepidermal water is the most effective source of water (water added to the skin evaporates in 10-20 min). Second, these occlusive agents have an emollient effect. Natural moisturizing factor NMF is a combination of several low molecular weight substances. These substances include amino acids, pyrrolidone carboxylic acid, lactate, urea, ammonia, uric acid, glucosamine, creatinine, citrate, sodium, potassium, calcium, magnesium, phosphate, chlorine, sugar, organic acids, peptides, and other unidentified substances. Many of these substances are added to moisturizers to help its hygroscopic properties. Too much of these substances cause irritation. For example, lactic acid and propylene glycol also act as exfoliants, and urea leads to dehiscence of corneocytes and contains broad-spectrum antibacterial properties. Thus, maintenance and hydration of the stratum corneum is the result of a multifaceted masterpiece. Emollients Emollients fill the spaces between the corneocytes, thus providing therapeutic improvement to defects in desquamation. Emollients function in smoothing the roughened skin, changing the skin's appearance, lubricating, replacing natural skin lipids, and providing occlusion. Emollients are composed of water in oil emulsions; thus, oil is the largest component, which ranges from 3-25%. The concentration of oil in emollients is important for easier spreading and for the degree of occlusion that is desired. Emollients with low spreading value are most often used for night and facial creams, around eye wrinkles, and in cosmetics. They include castor oil, almond oil, and oleyl oleate. Emollients with medium spreading value are most often used in day and sun protection creams and oils. They include octyl dodecanol, hexyl decanol, oleyl alcohol, and decyl oleate. Emollients with high spreading value are most often used in body lotions, hand creams and lotions, and bath additives. They include isopropyl stearate, isopropyl palmitate, isopropyl myristate, hexyl laureate, and dioctyl cyclohexane. The type of emollient and the water-to-oil ratio determines the classification of the moisturizer, which is important for different types of skin. Individuals with oily skin should choose an oil-free moisturizer. Two types of oil-free moisturizers are available. One group contains strictly oil-free products, such as propylene glycol and glycerin, which are drying and can cause stinging on irritated skin. The second group contains emollient esters, which have an oil-like behavior. Esters have been shown by the Rabbit Ear Assay to be possible comedogenics. Esters marketed for dry skin contain heavier oils (eg, petrolatum), and normal skin products usually contain mineral oil and propylene glycol as the main ingredients. MimyX cream and Atopiclair cream are anti-inflammatory nonsteroidal moisturizers on the market as prescription drugs, both approved by the FDA as medical devices rather than drugs in order to bypass the need to perform 3 phases of rigorous FDA-sanctioned studies.1, 2, 15, 16 MimyX cream represents a new class of topical therapy that contains a palmitoylethanolamide, an endogenous bioactive fat said to be deficient in atopic skin. It is said to be comparable to low-potency steroids in skin barrier function repair, although it lacks steroidal or calcineurin-inhibitor effects. Atopiclair (MAS063DP) is a hydrophilic cream that can be effective for dry skin and atopic dermatitis, as can MimyX cream. It contains glycyrrhetinic acid and other ingredients. Atopiclair also lacks steroidal or calcineurin-inhibitor effects. FUNCTIONAL INGREDIENTS IN MOISTURIZERSTwenty years ago, Kligman presented a controversial concept term, cosmeceutical, to represent formulation with ingredients that have cosmetic and druglike qualities. The Food and Drug Cosmetic Act of 1938 provided the definition of what is to be considered a cosmetic or a drug. It states that a cosmetic is, "an article intended to be rubbed, poured, sprinkled, sprayed on, introduced into, or otherwise applied to the human body or any part thereof for cleansing, beautifying, promoting attractiveness, or altering the appearance," and drugs are, "articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man." Ingredients that are documented as having a potential biological effect and reducing the severity of dry skin are AHAs and beta hydroxy acids (BHAs), including their salts, as well as retinoids. The hydroxy acids are classified according to the number of carboxylic acids on their configuration. Monocarboxylic acids are glycolic, lactic, and mandelic acids. Dicarboxylic acids include malic and tartaric acids. Tricarboxylic acids embody citric acid found in citrus fruits. The BHAs encompass mostly salicylic acid and its derivatives. AHAs have interesting effects on the stratum corneum. They have been shown to exfoliate; thus, they are useful in hyperkeratotic conditions. They act as humectants and have a normalizing effect on the stratum corneum, increasing its plasticity and flexibility. Retinoids are another class of botanicals with important physiologic implications. These compounds have been shown to be beneficial on photoaged skin. Clinically, they have been shown to reduce some of the stigmata of photodamaged skin. Histologically, Weiss et al have shown epidermal thickening with increased mitosis of keratinocytes. Compaction of the stratum corneum and reduction of pigmentation occur, with glucosaminoglycan accumulation in the dermis. Vitamins have become ordinary ingredients in moisturizers. Their role in protection from oxygen radicals produced by exogenous (eg, UV light) and endogenous (eg, inflammation) states has long been known. When topically applied, vitamins have shown to reduce cellular injury by these harmful insults. VEHICLE INGREDIENTSEmulsifiers Emulsifying agents are used to assist in the production of an emulsion. An emulsion is formed when 2 or more nonmixable liquids are shaken until the mixture continues to appear homogenized. Preservatives A preservative is essential in any lotion or cream formulation, especially one containing water. The system must be protected from microbiologic contamination during manufacture and after the user opens and potentially contaminates the system by using it.
Fragrances Fragrances are used to mask the odor of formulation ingredients and to impart a pleasant fresh aroma. Fragrance is added to 65% of moisturizers. Fragrances are the most common sensitizers. They are the most likely irritating agents, especially in individuals who already have a preexisting dermatosis. TOXICITYDermatitis is rarely observed in the application of moisturizers. When dermatitis occurs, the most frequent ingredients liable are fragrances, preservatives, lanolin, vehicles, and sunscreens. The most common offenders in fragrances are cinnamic alcohol, hydroxycitronella, and isoeugenol. Other ingredients capable of producing dermatitis include the following:
Among the plethora of ingredients capable of producing adverse effects, popular elements include the following:
Most of the above ingredients are rarely the causative agents of dermatitis; however, subjective irritation is common. Maibach17 coined the term subjective dermatitis. Subjective dermatitis occurs when the application of a cosmetic product, such as a moisturizer, causes burning, stinging, or itching without a detectable visible or microscopic change, which is a subjective irritation or an irritant in place of a true allergic contact dermatitis. EXAMPLES OF MARKETED MOISTURIZERS/LOTIONS
PROPER USE OF MOISTURIZERS IN COMMON INFLAMMATORY DERMATOSISAtopic dermatitis The therapy of atopic dermatitis remains a challenge. The success of any therapeutic concept is based on a broad and early diagnostic approach, which allows relevant provocation factors and allergens to be ruled out. During remission periods, the regular use of a topical basic therapy that consists of a drug-free, water-in-oil moisturizer has been shown to decrease relapses and severity. Psoriasis In psoriasis, the use of moisturizers has been shown to improve adjuvant therapy with corticosteroids. In phototherapy, moisturizers have been shown to improve efficacy and may a have protective component against damage by UV-A light. Ichthyosis Treatment with AHAs and/or lactate 12% lotion significantly improved vulgaris, lamellar, sex-linked, Netherton, and EHK forms of ichthyosis. This new therapeutic modality expands the scope and the extent of ichthyotic conditions that now may be treated successfully. Mild xerosis Almost any of the emollient or filler systems provide symptomatic relief. Moderate xerosis Humectant or occlusive systems may provide a more active mechanism to hydrate the stratum corneum. When pruritus is a factor, the occlusive lotion or cream may provide more relief than humectant systems. Severe xerosis For moderate-to-severe xerosis, treatment is similar to ichthyotic or hyperkeratotic conditions, again AHAs and/or lactate offer the superior therapy. Rosacea Rosacea, which often includes increased facial skin dryness and sensitivity, may benefit from moisturizer use as an adjuvant treatment.6 A randomized, investigator-blinded, controlled observational study found a niacinamide-containing facial moisturizer provided clinical benefit to subjects with rosacea. SUMMARYUsing basic therapeutics that have few adverse effects can reduce the need for corticosteroids and other specific medications. This means economical benefit as well. Thus far, adjuvant basic treatment is an essential part in the therapy of chronic inflammatory skin diseases. Moisturizers are evolving continuously to more sophisticated products. They attempt to reduce irritancy and to possess better delivery systems. They attempt to mimic the natural behavior of NMFs and to eliminate preservatives. Compounds, such as AHAs and retinoids, are routinely included, and, as the population becomes more diverse, the need and the preferences of different ethnic groups will be addressed. REFERENCES
Article Last Updated: Apr 29, 2008 |