Moisturizer Types	Functions	Ingredients
Occlusive	Trap water on the skin surface and enhance lipid component of epidermal barrier.	Oils (petrolatum, mineral oil) Cholesterol, squalene Waxes (beeswax, carnauba wax, liquid wax) Silicones (dimethicone, cyclomethicone) Stearic acid, cetyl alcohol, stearyl alcohol Lanolin, lanolin alcohol
Humectant	Attract water from the dermis.	Glycerin Urea Hyaluronic acid Sorbitol Propylene glycol
Emollient	Smooth roughened epidermis.	C12-15 alkyl benzoate Cetyl stearate Glyceryl stearate Octyl octanoate Decyl oleate Isostearyl alcohol

Moisturizers are formulated in oil-in-water emulsions as creams or lotions, and their heaviness depends on the relative amounts of oil and water. Ointments contain nearly all oil, creams contain more oil relative to water, and lotions contain more water relative to oil. Creams and lotions tend to be less irritating and drying than gels and solutions. The following list shows product formulations from most to least hydrating:

• Ointment (most hydrating)

• Cream

• Lotion

• Gel

• Solution (least hydrating).

Barrier repair creams are a newer class of moisturizer that contain occlusive and humectant ingredients at ratios that closely mimic the content of normal, healthy stratum corneum: ceramides (50%), fatty acids (30%), and cholesterol (30%). They enhance barrier function, reduce transepidermal water loss, and increase the skin’s resistance to environmental irritants.⁹ These products may be used by patients with compromised barriers, such as those exposed to cleansers and chemicals, and conditions such as atopic dermatitis. Barrier repair products include nonprescription CeraVe^® and TriCeram^®, and prescription Mimyx^®, Atopiclair^®, and EpiCeram^®.

Dry skin may also be associated with hyperkeratosis as seen with ichthyosis, keratosis pilaris, and callouses. Topical hydroxy acids such as lactic acid 5% to 12% (e.g., generic ammonium lactate available in the brand names of Lac-Hydrin^® and AmLactin^®) and urea 10% to 40% (e.g., Carmol^® and Vanamide^®) are keratolytic and function to reduce stratum corneum thickness and increase hydration.¹⁰

Exfoliation treatments, which superficially resurface the skin by removing the topmost layers of the epidermis, can also be used to treat dry skin. Exfoliation stimulates the keratinocyte maturation process with regeneration of a healthier epidermis. This results in a compacted stratum corneum and increased production of ceramides, which improves epidermal barrier function and skin hydration.^11,¹² Exfoliation, where the outermost layers of skin are removed, can be achieved using mechanical methods (e.g., microdermabrasion) with gentle abrasion, or using chemical methods (e.g., chemical peels) with application of topical products such as acids (see Chapter 23, Microdermabrasion, and Chapter 22, Chemical Peels, respectively).

Photoaging

Most of the changes seen with skin aging are due to years of cumulative UV exposure, referred to as photoaging.^13,¹⁴ Skin is affected by ultraviolet A radiation (UVA, 320 to 400 nm), long-wavelength solar radiation that penetrates into the dermis, and ultraviolet B (UVB, 290 to 320 nm), shorter wavelength radiation that is absorbed by the epidermis.

Skin Rejuvenation Products

Skin rejuvenation products are aimed at preventing and treating cosmetic issues associated with photoaging, which include textural changes, dyschromia, and vascular ectasias. A simple three-part regime of topical products can be used to cleanse, treat, and protect the skin, whereby each product provides a specific benefit.

Products used for the treatment of photoaging must address several aspects of the aging process, including increasing skin exfoliation and stimulating epidermal renewal, increasing synthesis of collagen and other dermal matrix components, reducing hyperpigmentation, and increasing hydration. Products used for skin protection are aimed at preventing damage from UV exposure and free-radical oxidation. Skin care regimes usually consist of multiple topical products, including prescription medications and cosmeceuticals, to address these various aspects of skin aging. Table 24-2 lists topical products commonly used for skin rejuvenation and their functions.¹⁵

TABLE 24-2 Skin Rejuvenation Products and Their Functions ¹⁶^–¹⁹

CLEANSE
Cleanser selected based on skin oiliness/dryness
TREAT
Textural changes Fines lines Rough skin	Retinoids, hydroxy acids, N-acetyl glucosamine, growth factors, kinetin, peptides, moisturizers
Dyschromia Solar lentigines Postinflammatory hyperpigmentation	Retinoids, hydroquinone, kojic acid, azelaic acid, arbutin, and others (Tables 24-3 and 24-4)
Vascular ectasias Telangiectasias Rosacea	Bisoprolol, allantoin, aloe, algae extract, borage and evening primrose oil, vitamin C, chamomile, green tea extracts
PROTECT
Antioxidants	Vitamin C, vitamin E, ferulic acid, coffee berry, idebenone, gluconolactone, polyhydroxy acids, resveratrol, tea and red wine extracts
Sunscreens	Zinc oxide, titanium dioxide, and others (Figure 24-1)

Prevention of Photoaging

Antioxidants

UV light generates free radicals in skin which oxidize nucleic acids, proteins, and lipids, leading to the development of skin cancers and signs of photoaging.¹³ The skin protects itself by preventing free-radical damage with endogenous antioxidants consisting primarily of vitamin C in the aqueous compartment, and vitamin E in the lipid compartment such as cell membranes and stratum corneum. Vitamins C and E can be applied topically to enhance antioxidant protection.^16,¹⁷ These two antioxidants act synergistically. Ferulic acid is another antioxidant that can improve the protective effects of vitamins E and C.¹⁷ In addition to antioxidant properties, vitamin C also directly increases collagen synthesis and clinically reduces fine lines.²⁰ The greatest percutaneous absorption of topical vitamin C is obtained with L-ascorbic acid in acidic formulations at pH 3.5 or less, with concentrations of 10% to 20%.¹⁷

Sunscreens

Sunscreens protect the skin by reducing UV exposure. There are two main types of sunscreen ingredients each of which has a different mechanism of action. Physical sunscreens, composed of inorganic compounds, reflect and scatter UV light, whereas chemical sunscreens, composed of organic sunscreens, absorb UV light.¹⁸ To achieve broad-spectrum UVA and UVB coverage, multiple sunscreens are often combined. Figure 24-1 shows common sunscreen ingredients and their UV blocking capabilities. Certain sunscreen combinations offer greater photostability. For example, avobenzone alone has poor photostability; however, the addition of oxybenzone (HelioPlex^®) renders it highly photostable. Sunscreens with broad-spectrum UVA and UVB coverage with an SPF 30 are generally recommended for daily use. Because sunscreens do not block all UV radiation, maximal protection from UV damage is provided by using an antioxidant in addition to a sunscreen.¹⁷

FIGURE 24-1 Sunscreens and their ultraviolet light blocking capabilities.

SPF stands for sun protection factor (soon to be renamed as sunburn protection factor by the FDA) and represents the ability of a sunscreen to delay erythema on sun-exposed skin, primarily by blocking UVB. For example, if erythema develops after 10 minutes of sun exposure in a given individual with unprotected skin, after application of an SPF 30 sunscreen, the individual will develop the same degree of erythema in 10 × 30 or 300 minutes (5 hours) of sun exposure. The standard SPF testing dose for sunscreens on human skin, and the basis for a sunscreen product’s SPF designation, is 2 mg/cm², regardless of the formulation (cream, lotion, spray, powder, makeup, etc.), which equates to tsp for the face and 1 oz for the body of cream sunscreens.

Treatment of Photoaging

Retinoids

Topical retinoids are used to treat virtually all cosmetic aspects of photoaged skin, including: fine lines, dry and rough skin, hyperpigmentation, as well as acne.^19,^21,²² Retinoids are vitamin A derivatives, which range from potent prescription products such as tretinoin and synthetic tretinoin derivatives such as tazarotene, to less active cosmeceutical products such as retinol (Figure 24-2). Two topical retinoid products are FDA approved to treat photoaging: Renova^® (tretinoin) and Avage^® (tazarotene). Several other topical prescription retinoids approved to treat acne are also used off-label to treat photoaging such as Retin-A^® (tretinoin), Retin-A^® Micro (a less irritating formulation of tretinoin), Differin^® (adapalene), and other generic versions of these.

FIGURE 24-2 Topical retinoids.

Prescription retinoids have an associated local skin reaction of erythema, sensitivity, peeling, and flaking, called a retinoid dermatitis, which usually occurs within a week of initiating therapy. While this irritative response spontaneously resolves for most patients in 4 to 6 weeks, it can persist for the duration of use. The rejuvenating effects of prescription retinoids are more rapid than cosmeceuticals. Results are usually apparent by 1 month, with improved texture due to compaction of the stratum corneum, and by 3 months reduction of hyperpigmentation and fine lines are evident. Combining prescription retinoids with other aesthetic procedures such as lasers and chemical peels can be challenging, because retinoids must be discontinued 1 week prior to treatment and restarted 2 weeks after these treatments. This repeated initiation and termination of therapy can cyclically induce a retinoid dermatitis. For this reason, some providers use prescription retinoids as a stand-alone intervention for photoaged skin. Prescription retinoids are a particularly useful treatment option for skin rejuvenation in patients with darker Fitzpatrick skin types (IV through VI), where more aggressive procedures may be contraindicated.

Cosmeceutical retinoids include retinol (vitamin A), retinal (vitamin A aldehyde), and retinol storage forms (retinyl acetate and retinyl palmitate).²³ They are less irritating than prescription retinoids and, when used in recommended doses, do not cause a retinoid dermatitis. However, they are much less effective than prescription retinoids in reducing the signs of photoaging.

Matrix Metalloproteinase Inhibitors

Matrix metalloproteinases (MMPs) are naturally occurring enzymes that degrade the skin’s extracellular matrix to facilitate recycling of collagen, elastin, and glycoaminoglycans.²⁴ In young, healthy skin, production of matrix components exceeds destruction caused by MMPs. In photoaged skin, matrix degradation is accelerated because UV light upregulates MMPs. Enhanced matrix degradation combined with age-related decline in collagen synthesis, decreases the structural integrity of the skin’s matrix and contributes to the formation of wrinkles, skin laxity, and telangiectasias.²⁵ Products that inhibit MMPs, such as zinc, calcium, idebenone, and lactobionic acid (polyhydroxy acid) reduce destruction of dermal matrix, increase dermal collagen and elastin, and clinically improve textural changes in photoaged skin.^26,²⁷

Human-Derived Growth Factors

Endogenous growth factors are regulatory proteins that initiate wound healing by mediating signaling pathways within and between cells.²⁸ Multiple growth factors migrate to wounds and interact synergistically to promote wound healing and tissue regeneration including synthesis of new dermal matrix components. Topical application of growth factor products, such as Nouricel-MD^®, which is derived from human fibroblast cultures, twice daily for 3 months has been shown to improve skin hydration and reduce roughness, hyperpigmentation, and wrinkles in photoaged skin.^29,³⁰ Growth factors are large protein molecules and their size may limit penetration through an intact epidermis. Combining them with skin resurfacing procedures that thin or disrupt the skin’s barrier, such as laser resurfacing, chemical peels, and microdermabrasion, or topical exfoliants such as hydroxy acids, may improve penetration of these active proteins.³¹

Peptides

Peptides are short-chain amino acids that act as protein mimics to stimulate repair processes in photoaged skin.³² Peptides, rather than their parent proteins, are used topically because these smaller compounds have greater skin penetration. Palmitoyl pentapeptide-3 (e.g., Matrixyl^® by Sederma, StriVectin^® by Klein Becker) is a sequence from procollagen that has been found to stimulate the production of collagens. Palmitoyl oligopeptide (by Sederma) is derived from elastin and stimulates growth of fibroblasts and angiogenesis.³³

Another peptide, acetyl hexapeptide-8 (e.g., Argireline^® by Lipotec), is derived from the SNAP-25 protein, which is designed to reduce the effects of acetylcholine in producing muscle contraction and purported to have “botulinum toxin–like effects.” One report suggests that 10% acetyl hexapeptide-8 used for 30 days reduces wrinkle depth by 30%.³³ Additional studies are necessary to support this finding and its proposed mechanism of action. Novel peptide research is a growing area of cosmeceutical development. Significant effects with many peptides can be demonstrated in vitro, where target receptors are easily accessed, and the challenge for peptides, as with all topical products, is to demonstrate penetration through the skin barrier and good clinical efficacy in vivo, when the biologic target is less accessible.

Plant Hormones

Kinetin (N⁶-furfuryladenine) is a plant cytokinin that functions as a natural antioxidant and is used as an ingredient in rejuvenation skin care products.^34,³⁵ It has reported rejuvenation effects on cultured human fibroblast cells (in vitro),³⁶ but no studies are currently available in vivo to assess for clinical efficacy.

Hydroxy Acids

Alpha hydroxy acids (AHAs) are part of almost any skin rejuvenation topical product regime, and they include glycolic, lactic, citric, and mandelic acids. AHAs stimulate epidermal cell production, exfoliation, and even out the distribution of melanin in photodamaged skin.^10,^37,³⁸ AHA histologic effects include increased deposition of glycosaminoglycans, improved elastin fiber quality, and increased collagen synthesis.³⁷^–³⁹ When formulated in more acidic preparations with higher concentrations, AHAs are commonly used as chemical peel agents. Polyhydroxy acids (such as gluconolactone) and bionic acids (such as lactobionic acid and maltobionic acid) are second-generation hydroxyacids that have AHA-like effects but are less irritating. They also function as humectant moisturizers and antioxidants.⁴⁰^–⁴²

Amino Sugars

N-acetylglucosamine is a naturally occurring amino sugar compound that is a building block of hyaluronic acid (a glycosaminoglycan). Topical application stimulates synthesis of hyaluronic acid in fibroblasts and keratinocytes, increases skin thickness,^43,⁴⁴ and enhances exfoliation.⁴⁵ Clinically, N-acetylglucosamine has been found to reduce wrinkles, increase hydration, and improve hyperpigmentation.⁴⁶^–⁴⁸

In summary, prescription retinoid products can address many aspects of skin aging and offer significant improvements for photodamaged skin. For patients intolerant of prescription retinoids, alternative cosmeceutical therapies are available. These rejuvenation skin care regimes typically contain a combination of three to four cosmeceutical products that address fine lines and rough skin texture, improve skin brightness, and offer protection from UV damage. Box 24-1 lists topical products that can be used for a rejuvenation skin care regime (or as a preprocedure skin care regime).

Hyperpigmentation

Hyperpigmentation is a common aesthetic complaint and typically presents as solar lentigines, postinflammatory hyperpigmentaion or melasma. Solar lentigines are apparent in photoaged skin as small brown macules that increase in size and number with chronic sun exposure. Postinflammatory hyperpigmentation can be seen in susceptible individuals, especially darker Fitzpatrick skin types (IV through VI), as brown discoloration commonly arising at sites of previously inflamed acne lesions or sites of wound healing. Melasma presents as hyperpigmented reticular patches and brown macules, typically on the cheekbones, upper lip, forehead, and/or chin (Figure 24-3). Melasma is frequently observed following a change in female hormonal status such as during pregnancy (chloasma) or with use of oral contraceptives.⁴⁹

FIGURE 24-3 Melasma.

(Copyright Rebecca Small, MD.)

Hyperpigmentation results from increased melanin synthesis and deposition in the epidermis and dermis. An understanding of the melanin synthesis and distribution pathways is helpful in selecting treatments for hyperpigmentation. The key regulatory step in melanin synthesis is the enzymatic conversion of tyrosine to melanin by tyrosinase in melanocytes. Melanin is packaged into melanosomes in the melanocytes and then distributed to surrounding epidermal keratinocytes (Figure 24-4). One of the physiologic roles of melanin in the skin is to shield keratinocyte nuclei by absorbing harmful UV light. Upregulation of melanin synthesis is thus a physiologic protective mechanism against UV damage. Many other factors, however, can also upregulate melanin synthesis contributing to unwanted hyperpigmentation (see Figure 24-4).⁵⁰

FIGURE 24-4 Melanin synthesis and cellular distribution.

Treatment of Hyperpigmentation

Assessment pigmentation depth in the skin can be helpful prior to initiating treatment for hyperpigmentation, because epidermal pigment is more responsive to topical products compared to dermal pigment. Pigmentation depth can be evaluated using a Wood’s lamp. Illuminated epidermal pigment typically enhances under a Wood’s lamp, whereas dermal pigment does not.

Treatment of hyperpigmentation with topical products is aimed at suppressing melanin synthesis and deposition in the skin and at removing pigment that is already present. Topical products for hyperpigmentation, commonly called lightening, brightening, or bleaching agents, include prescription products and cosmeceuticals. Most topical lightening agents act by inhibiting tyrosinase, the key enzymatic step in melanin production (Figure 24-4).

Hydroquinone, a tyrosinase inhibitor, is the most potent topical lightening agent. It is available as an OTC drug in 2% formulations and may be prescribed as a 4% cream or formulated by compounding pharmacies in strengths of 6% to 8%. Combination products containing hydroquinone and retinoids are commonly used, and some of these often have steroids added to reduce the irritation associated with their use. Tri-Luma^® is one such combination product that is FDA approved for treatment of melasma. Other prescription topical products commonly used for hyperpigmentation are summarized in Table 24-3.⁵¹

TABLE 24-3 Prescription Topical Products for Hyperpigmentation ⁵¹

Cosmeceutical skin lightening agents, such as kojic acid and arbutin, are also tyrosinase inhibitors. Although not as effective as hydroquinone, their efficacy can be improved by combining them with products that enhance penetration into the skin such as hydroxy acid exfoliants or retinoids, such as retinol. Copper metal chelators can also be used to help reduce pigment production, because copper is an essential cofactor necessary for synthesis of melanin. Common cosmeceuticals used for treatment of hyperpigmentation are summarized in Table 24-4.

TABLE 24-4 Cosmeceutical Topical Products for Hyperpigmentation ^16,^37,⁵²^–⁵⁵

Product	Occurrence
Acetyl glucosamine	Chitin
Arbutin, methyl arbutin	Bearberry extract, certain herbs, pear trees
Decapeptide-12 (Lumixyl^®)	Synthetic
Emblica	Indian gooseberry
Glycolic acid	Sugar cane
Kojic acid	Fungi
Licorice extract (glabridin)	Licorice root
Mulberry extract	Roots of the broussonetia papyrifera tree
Niacinamide	Amide form of vitamin B₃
Retinoids (retinol, retinal, retinyl acetate, retinyl palmitate)	Vitamin A
Soy isoflavones	Soybean
Vitamin C	Citrus fruits

Reduction of hyperpigmentation with topical products typically requires 3 months of daily application. Figure 24-5 shows a patient with lentigines and mottled hyperpigmentation of the lower face (A) prior to treatment and (B) after 3 months with daily use of 0.05% tretinoin, 4% hydroquinone, hydroxy acid, 20% vitamin C, and broad spectrum sunscreen. Figure 24-6 shows a patient with melasma and postinflammatory hyperpigmentation (A) before and (B) after 3 months of twice daily use of four main products containing 0.5% retinol, an exfoliant (lactic acid), brightening agents (2% hydroquinone, 3% kojic acid and 5% azelaic acid, licorice extract, and arbutin), anti-inflammatory ingredients (borage and evening primrose oils), and a broad-spectrum sunscreen.

FIGURE 24-5 Hyperpigmentation (A) before and (B) after daily use for 3 months of 0.05% tretinoin, 4% hydroquinone, and lactic acid.

(Copyright Rebecca Small, MD.)

FIGURE 24-6 Melasma and postinflammatory hyperpigmentation (A) before and (B) after twice daily use for 3 months of 0.5% retinol, lactic acid, 2% hydroquinone, 3% kojic acid, and 5% azelaic acid.

(Courtesy of PCA Skin, Scottsdale, AZ.)

Reduction of hyperpigmentation can also be achieved with procedures that exfoliate and remove melanin-laden keratinocytes in the epidermis. Various methods of exfoliation can be used in combination with topical products, such as chemical peels, microdermabrasion, and superficial laser skin resurfacing. Certain lasers (e.g., Q-switched 1064 nm) treat hyperpigmentation by targeting and reducing melanosomes in the dermis. Combination therapy with minimally invasive aesthetic procedures such as these and topical products can achieve the most rapid and effective reduction in hyperpigmentation.

Preprocedure and Postprocedure Products

Proper selection and use of skin care products before and after aesthetic procedures, such as chemical peels and laser treatments, contributes to successful and sustainable clinical results and may reduce procedure risks such as hyperpigmentation.

Preprocedure topical regimens often contain the same products as rejuvenation skin care regimes and usually consist of retinoids, hydroxy acids, antioxidants, sunscreens, and skin lightening agents (see Box 24-1).⁵⁶ The goal for using these products is to condition the skin and create a healthier baseline epidermis and dermis. This allows for more even penetration of products, as with chemical peels, and promotes more rapid postprocedure healing. Preprocedure skin care regimens are ideally started 1 month prior to cosmetic procedures and discontinued 1 week prior to the procedure, to ensure a fully intact epidermis at the time of treatment. In persons prone to hyperpigmentation, a topical lightening agent is also used, such as hydroquinone 4% to 8%, which may reduce the risk of postinflammatory hyperpigmentation postprocedure.

Selection of postprocedure products depends on the type of cosmetic procedure performed. Ablative procedures, which disrupt the epidermis, require use of an occlusive ointment moisturizer without active ingredients immediately postprocedure. Common occlusive postprocedure products are shown in Table 24-5. This product is used for approximately 4 to 7 days postprocedure, until re-epithelialization occurs. There is some evidence that certain nonocclusive products, such as Biafine^® (see Table 24-6), may be used as alternatives to occlusive topical products during this phase of wound healing.⁵⁷ Because sunscreen is not used during this time, sun avoidance is critical.

TABLE 24-5 Occlusive Postprocedure Products ^58,⁵⁷

Product Brand Name (Manufacturer)	Hydrating Ingredients	Other Ingredients
Aquaphor^® (Beiersdorf)	Mineral oil Lanolin	Panthenol (vitamin B5) Bisoprolol (chamomile)
Catrix 10^® (Lescarden)	Petrolatum Beeswax Paraffin	10% Bovine mucopolysaccharide cartilage
Primacy^® (SkinCeuticals)	Petrolatum Squalene Oat kernel oil Rose oil	Bisoprolol (chamomile) Aloe Vitamin E
Protective Recovery Balm^® (BiO2 Cosmeceuticals)	Mineral oil Petrolatum Paraffin Dimethicone
Puralube^® (Nycomede)	Light mineral oil White petrolatum

TABLE 24-6 Nonocclusive Postprocedure Products ^57,^59,⁶⁰

Product Brand Name (manufacturer)	Reparative Ingredients (intended effect)
Epidermal Repair^® (SkinCeuticals)	Beta glucan Centella asiatica (collagen synthesis)
TNS Ceramide Treatment Cream^® (SkinMedica)	Hydroxypropyl bispalmitamide MEA (ceramide for barrier enhancement) NouriCel-MD^® (growth factors) Palmitoyl oligopeptide and palmitoyl tetrapeptide-7 (matrix synthesis)
Biafine^® (Ortho-McNeil)	Trolamine and sodium alginate (wound healing)

Once the skin has fully re-epithelialized, postprocedure occlusive products may be discontinued and products that are soothing and reparative used. Some common non-occlusive reparative products are listed in Table 24-6. A broad-spectrum sunscreen (SPF 30 or greater) containing zinc and/or titanium is used daily. At 1 month postprocedure, when skin is no longer sensitive, patients’ preprocedural rejuvenation products may be resumed. If postinflammatory hyperpigmentation is a concern or if the procedure is targeting pigment reduction, skin-lightening products are also resumed.

Procedures that leave the epidermis intact, such as nonablative laser treatments and superficial resurfacing treatments like chemical peels and microdermabrasion, require nonocclusive postprocedure products for 2 weeks with resumption of routine rejuvenation skin care products thereafter.