207 - COSMECEUTICALS AND SKIN CARE IN DERMATOLOGY

Question 1

The focus on identifying facial skin issues is caring for the skin from a phenotypic approach, which is a simplified way to discuss the various issues that need to be considered when prescribing the proper skin-care regimen.

The phenotypic approach focuses on 4 main facial skin issues:

Answer 1

skin hydration, inflammation, pigmentation, and skin aging risk factors.

Question 2

characterized by dull color (usually gray white), rough texture, and an elevated number of ridges, and may be associated with a sensation of tightness or itching

Answer 2

.Xerosis, or “dry skin,”

Patients complain that their “skin is no longer radiant” because its rough surface is a poor reflector of light. Although the etiology of dry skin is multifactorial, the most significant factor in the development of xerosis is the role of the stratum corneum (SC) skin barrier and its capacity to retain water.

Question 3

Rawlings et al. showed that patients with dry skin have a perturbation in the lipid bilayer of the SC. 5 The SC skin barrier is composed of a bilayer lipid membrane formed from 3 primary groups of compounds:

Answer 3

(1) ceramides, (2) fatty acids, and (3) cholesterol.

When present in the proper amount and ratio (1:1:1), these components help to protect the skin and keep it watertight (Figs. 207-1 and 207-2).

Question 4

When the barrier is impaired, the skin develops an inability to retain water, which leads to dehydration if interventions to retard water evaporation are not implemented. Defects or deficiencies in this barrier layer of the skin cause a spike in water evaporation, known as _______

Answer 4

transepidermal water loss (TEWL)

TEWL leads to decreased water content in the SC and abnormal desquamation of corneocytes. Desmosomes remain intact at higher levels of the SC, and desmoglein I levels remain elevated in the superficial SC of individuals with dry skin as compared to controls. This occurs because the enzymes necessary for desmosome digestion are impaired when the water level is insufficient, which spurs abnormal desquamation resulting in visible “clumps” of keratinocytes that leave the skin appearing rough and dry. Recent studies suggest that both the initial cohesion and the ultimate desquamation of corneocytes from the SC surface may be orchestrated by localized changes in pH, which selectively activate different classes of extracellular proteases in a pH-dependent fashion. 9 For this reason, the pH of skin-care products should be taken into account when designing a skin-care regimen for a patient with dry skin. Impairment of the lipid bilayer of the SC can be engendered by various exogenous factors such as ultraviolet (UV) radiation, detergents, acetone, chlorine, and prolonged water immersion. Skin barrier impairment is often caused by an incorrect choice of skin cleansers and moisturizers or overzealous use of exfoliating methods. Although skin barrier function is the most important issue to consider when approaching dehydrated skin, there are other factors to take into account that affect the perception of skin hydration.

Question 5

How long does it take for sebaceous glands to generate enough sebum to be visualized and accurately measured on the skin’s surface?

Answer 5

20 minutes

Sebum production plays a role in dry skin because it provides an occlusive layer on the surface of the skin that retards TEWL. When assessing the face for the presence of sebum, it is important to wait 20 minutes after the patient washes because that is how long it takes the sebaceous glands to generate enough sebum to be visualized and accurately measured on the skin’s surface.

Question 6

What are the contents of the oily secretion of the sebaceous glands?

Answer 6

wax esters, sterol esters, cholesterol, di- and triglycerides, squalene, and the antioxidant vitamin E and is thought to confer protection to the skin from environmental insults such as free radicals.

Lipids from modified sebaceous glands in the eye, called meibomian glands, help prevent dry eyes by hindering tear evaporation. 12,13 It is important to note that sebaceous gland–impoverished skin, such as the lips and the skin in prepubertal children, may be at a higher risk for free radical and other environmental damage.

Question 7

Explain briefly the age-related change seen in sebaceous gland activity.

Answer 7

Sebum production changes at different stages of life. It is well understood that an age-related change is seen in sebaceous gland activity, with levels typically low during childhood, rising in the mid- to late teens, and generally remaining stable for decades until trailing off in the seventh and eighth decades as endogenous androgen production declines.

Children between 2 and 9 years of age commonly display eczematous patches (pityriasis alba) on the face and trunk that disappear with the onset of sebaceous gland activation.

Question 8

What are the factors that influence sebum production?

Answer 8

The level of sebum production is influenced by diet, stress, hormone production, exercise, and genetics.

In a study of 20 pairs each of identical and nonidentical like-sex twins, the identical twins exhibited essentially the same sebum excretion rates, with significantly divergent acne severity, whereas the nonidentical twins differed significantly according to both parameters, implying both the genetic influence of sebum and the mediation of exogenous factors in lesion development.

The presence of sebum on the face does not exclude a skin barrier defect but often compensates for it. In fact, an adequate or increased amount of sebum production can mask a deficient skin barrier. This is the reason that some patients state that they have combination skin that is oily in the t-zone and dry along the sides of the face. In the case of this t-zone type of combination skin, the patient should be treated as an oily facial skin type because the barrier repair moisturizers will feel too heavy and cosmetically displeasing to them. However, they need to be treated with a barrier repair moisturizer in areas with few sebaceous glands such as the arms and legs.

Question 9

NATURAL MOISTURIZING FACTOR

Answer 9

Natural moisturizing factor (NMF) provides intracellular hydration. It is derived from the breakdown of the protein filaggrin, which provides structural support and strength in the lower layers of the SC. It is broken down in the higher levels (stratum compactum) of the SC into free amino acids, including histidine, glutamine (glutamic acid), and arginine. 16 These osmotically active amino acids remain inside the keratinocyte and avidly bind to water. The pace at which filaggrin is broken down into NMF is thought to be regulated by aspartate protease (cathepsin), which initiates this cascade and determines the amount of NMF that is present. 17 Interestingly, this putative aspartate protease (cathepsin) is regulated by changes in external humidity. In other words, in low-humidity environments, the pace of NMF production increases. This acclimation process typically occurs over the course of several days, 18 and cannot yet be regulated artificially via products or procedures.

Question 10

GLYCOSAMINOGLYCANS

Answer 10

Glycosaminoglycans (GAGs), such as heparan sulfate and hyaluronic acid, bind and hold water, providing skin hydration and structural integrity. Although their role in skin hydration and aging is poorly understood, much research is ongoing to look at effects of aging on the characteristics of these and other important GAGs. 20 These GAGs are found in skin-care products that target dry and aged skin.

Question 11

Hyaluronic Acid (HA)

Answer 11

HA, which can bind

1000 times its weight in water, is a glycosaminoglycan found in the extracellular matrix and thought to give the skin its volume and plumpness. HA is produced mainly by fibroblasts and keratinocytes in the skin, and has an estimated turnover rate of 2 to 4.5 days in mammals. 21 HA is localized not only in the dermis but also in the epidermal intercellular spaces, especially the middle spinous layer, but not in the SC or stratum granulosum. 22 Aged skin, which is less plump than youthful skin, is characterized by decreased levels of HA. The exact contribution of HA in skin hydration is not clear. Studies have been conflicting about the penetration of HA into the skin on topical application,23 but the size of the molecule plays an important role.24 HA has been added to various drug formulations to increase drug delivery because it seems to play a role in enhancing penetration of other ingredients through a poorly understood mechanism. 25 Oral glucosamine supplements have been shown to increase production of HA in the skin and joints.

Question 12

Heparan Sulfate (HS)

Answer 12

HS and heparan sulfate

proteoglycans (HSPGs), such as syndecan, glypican, and perlecan, are the most common constituents of the cell surface and extracellular matrix, including the basement membrane. These glycans bind ligands at the cell surface and modulate key processes in the skin such as cell proliferation, migration, communication, and activation because of their capacity to bind, store, present, degrade, and amplify key secreted signaling molecules such as growth factors and cytokines. A decreased detection of endogenous HS and HSPGs in the skin has been linked to aging, resulting in deterioration of the mechanical properties of the dermis.28 Increasing the amount of HS in the skin may provide an important target for skin rejuvenation by not only increasing the skin’s ability to hold onto water but also restoring skin homeostasis. Endogenous HS is too large and highly polar to penetrate into skin when applied topically because it is rapidly degraded on the skin surface. Therefore, it serves primarily as a humectant, which brings water onto the surface of the skin. Studies are being conducted with an HS analog that has been shown to penetrate into skin to improve hydration and lower TEWL as well as improve wrinkles and even skin tone.29

Question 13

AQUAPORIN3

Answer 13

Aquaporin-3 (AQP3) is a member of a family of homologous aquaporin water channels that facilitate fluid transport. AQP3 is a member of a subclass of aquaporins called aquaglyceroporins, which transport not only water but also glycerol and possibly other small solutes. Researchers have found that AQP3 is expressed at the plasma membrane of epidermal keratinocytes in human skin. 30 There is evidence for a high concentration of solutes (Na, + K, + and Cl– ) and a low concentration of water (13%-35%) 31 in the superficial SC, producing in the steady-state gradients of both solutes and water from the skin surface to the viable epidermal keratinocytes. 32,33 It has been proposed that AQP3 might facilitate transepidermal water permeability to protect the SC against desiccation by evaporative water loss from the skin surface and/or to dissipate water gradients in the epidermal keratinocyte cell layer. 30 A study looking at skin phenotype in transgenic mice lacking AQP3 showed significantly reduced water and glycerol permeability in AQP3 null mice proving that AQP3 is functional as a plasma membrane water/glycerol transporter in the epidermis. Conductance measurements showed remarkably reduced SC water content in AQP3 null mice in most areas of the skin. However, epidermal cell water permeability is probably not a major determinant of SC hydration because water movement across AQP3 is markedly slow compared with other tissues. 35 Pharmacologic manipulation of AQP3 may be used in the future to treat skin disorders of excess and decreased hydration. At this time, the only cosmeceutical ingredients that have demonstrated a role in regulating AQP3 are Ajuga turkestanica 36 and glycerin.

Question 14

Charaterize an ideal skin

Answer 14

balanced sebum secretion, an intact SC with an unbroken barrier, sufficient levels of NMF and GAGs, and normal expression of AQP3.

Question 15

For those with oily skin, what is the better choice of cleanser?

Answer 15

The choice of cleanser is crucial because cleansers have a significant effect on the lipid contents of the skin, which affects skin barrier function. In the case of oily skin (excess sebum), a foaming cleanser that contains surfactants to remove the excess lipid is preferable. Oily skin types prefer the clean feeling that these give to the skin.

Oily skin types should be treated with a foaming cleanser and either a light moisturizer or no moisturizer at all.

Question 16

For dry skin type, what is the better choice of cleanser?

Answer 16

For dry skin types, a nonfoaming cleanser such as an oil, cream, or milk cleanser is preferable. Choose nonfoaming cleansers that deposit fatty acids on the skin, thereby repairing the skin barrier. Good choices include stearic acid (a component of shea butter), which has straight nonpolar hydrophobic tails that stack closely together in the cell membrane giving optimal barrier repair. Linoleic acid, found in safflower oil, argan oil, and others, is also a good choice because of its antiinflammatory capabilities; however, its barrier repair properties are not as strong as those of stearic acid. Avoid oleic acid, found in olive oil, which can cause membrane disruption because its fatty acid hydrophobic tails project at an angle that disrupts the bilayer membrane’s natural structure (Fig 207-3).

Dry skin types should be treated with lipid-sparing cleansers such as nonfoaming cleansers and barrier repair moisturizers.

Humectant-, occlusive-, and exfoliant-containing cleansers and moisturizers can be added to the basic skin-care regimen to treat other issues such as pigmentation and wrinkles and to increase compliance by demonstrating a more rapid visible result on the skin.

Question 17

Cleanser pH choice for oily or dry skin

Answer 17

The pH of the cleanser also plays a role in skin barrier function. Soap cleansers that exhibit a high pH have been consistently shown to perturb the skin barrier.

Dry skin types need a neutral or acidic cleanser while oily types that do not exhibit a propensity for inflammation can tolerate a higher-pH soap-type cleanser. Cleansers are the most commonly used skin-care product, so their impact on oily and dry skin cannot be overemphasized.

Question 18

Exfoliants

Answer 18

Exfoliants,

which are often found in exfoliating cleansers, aid in desquamation of the superficial layer of the SC, leading to a smoother surface and greater light-reflecting abilities. Exfoliants can be mechanical as in the case of crushed shells, sugar or rice grains, aluminum particles, rotating brushes, or rough fabrics. These promote an immediate visual improvement of the skin but overuse can lead to barrier impairment.

Hydroxy acids represent the family of chemical exfoliants.

α-Hydroxy acids such as lactic and glycolic acids have humectant properties, whereas β-hydroxy acids such as salicylic acid extract lipids from the skin and have drying properties. Exfoliants are often used by skin-care companies to show the immediate benefit of their product on the skin, but these benefits are short-lived and deceiving if the exfoliant products are not combined with barrier repair moisturizers.

Question 19

Moisturizers

Answer 19

Moisturizers play an import role in

treating dry and oily skin. Oily skin types make their own moisturizer because, by definition, they produce an adequate or excess amount of sebum to provide surface occlusion to help retard TEWL. The oily sensation that sebum causes on the skin may make people with oily skin types less likely to use sun protection because many sunscreen products are made with silicones and oil-soluble ingredients that render an oily feel. For this reason, very oily skin types should use a sunscreen in lieu of a moisturizer and slightly oily types should use a lighter lotion or serum-type moisturizer. The choice of cleanser will influence the need for a moisturizer. Oily types should avoid oils and heavy cream moisturizers and will likely prefer humectant-containing moisturizers such as those with hyaluronic acid and heparan sulfate analog. Dry skin types should all use a barrier repair moisturizer containing the proper ratio of ceramides, fatty acids, and cholesterol, which is 1:1:1. 40 Historically, ceramides have been derived from animals, but new technologies using a pseudoceramide formulated in a multilamellar emulsion (MLE) have been shown to mimic the skin’s natural 3-dimensional barrier structure. 41 Only barrier repair moisturizers will help correct underlying defects in the skin so that skin health can improve; however, there are other classes of ingredients that are included in moisturizers as a temporary solution. These ingredients are popular because their effects are more rapidly observable than barrier repair ingredients, which may take 4 or more days to yield noticeable results.42

Question 20

Emollients

Answer 20

Emollients are substances added to immediately soften and smooth the skin. They function by filling the spaces between desquamating corneocytes to create a smooth surface, which makes the skin reflect light better and impart immediate visible improvement. 43 Emollients provide increased cohesion that causes a flattening of the curled edges of the individual corneocytes. 4 This leads to a smoother surface with less friction and greater light refraction. Many emollients have barrier repair, humectant, and occlusive properties as well as smoothing emollient properties.

Question 21

Occlusives

Answer 21

Occlusives, such as naturally occurring sebum and exogenously applied ingredients, often contain lipids and coat the surface of the skin. Plastic wrap, patches, and masks are examples of occlusion technologies used in skin-care regimens. The occlusive coating provides an emollient effect, helps increase penetration of previously applied ingredients, and decreases TEWL. Ingredients with the highest occlusive properties are petrolatum and oils. Petrolatum, for example, has a water vapor loss resistance 170 times that of olive oil. However, petrolatum has a greasy feeling that may make agents containing it cosmetically unacceptable to many patients. Other commonly used occlusive ingredients include paraffin, squalene, dimethicone, soybean oil, grapeseed oil, propylene glycol, lanolin, and beeswax. These agents are only effective while present on the skin; once removed, the TEWL returns to the previous level. Decreasing TEWL by more than 40% can lead to maceration and increased levels of bacteria; therefore, there is a limit to the amount of occlusive ingredients that can be used.

Question 22

Humectants

Answer 22

Humectants are ingredients with high water absorption capabilities that are able to attract water from the atmosphere. They are most effective when the atmospheric humidity is greater than 80%. Although humectants may draw water from the environment to help hydrate the skin, in low-humidity conditions they may absorb water from the deeper epidermis and dermis, leading to increased skin dryness. For this reason, they are more effective when combined with occlusives. Humectants rapidly draw water into the skin, causing a slight swelling of the SC that gives the perception of smoother skin with fewer wrinkles. Examples of commonly used humectants include glycerin, sorbitol, sodium hyaluronate, urea, propylene glycol, α-hydroxy acids, and sugars. The effects of humectants are temporary, usually lasting less than 24 hours. However, the barrier repair properties of glycerin (also known as glycerol and glycerine) and its ability to traverse AQP3 channels give it longerlasting effects than other humectants.

Question 23

Types of Ingredients in Moisturizers for Topical Skin Care

Answer 23

Question 24

Give medications that decrease sebum production

Answer 24

Oral ketoconazole, oral spironolactone, oral contraceptives, oral retinoids, and injected botulinum toxin type A have been shown to decrease sebum secretion. Statins and other cholesterol-lowering medications may increase the risk of dry skin but studies are conflicting.

Question 25

Define resistant skin

Answer 25

skin that rarely exhibits signs of sensitivity, which include acne lesions, redness, itching, flushing, stinging, and urticaria

Question 26

Define sensitive skin

Answer 26

Characterized by frequent incidence of signs of sensitivity and inflamation, which include acne lesions, redness, itching, flushing, stinging, and urticaria

Question 27

What are the 4 distinct variations of sensitive skin that should be considered independently when customizing a skin-care regimen?

Answer 27

The 4 types of sensitive skin are

(1) acne type (prone to developing acne lesions such as papules, pustules, comedones, and cysts);
(2) rosacea type (featuring a tendency toward recurrent flushing, facial redness, and experiencing hot sensations);
(3) stinging type (predilection to stinging or burning sensations); and
(4) allergic type (more likely to exhibit erythema, pruritus, and skin flaking on contact with allergens and irritants).

A review of 27,485 patient results from the Baumann Skin Type Indicator (BSTI) Questionnaire 53 taken by patients in 30+ different dermatology offices showed that 73% of patients who presented to these offices reported having sensitive skin (unpublished data). See Table 207-2 for the breakdown of sensitive subtypes in these patients. Each of these subtypes of sensitive skin can occur alone or in combination with other types of sensitive skin. Although all 4 types benefit from the addition of antiinflammatory ingredients, 54 each subtype has unique skin-care needs.

Question 28

Describe sensitive skin ACNE TYPE

Answer 28

Sensitive skin acne subtypes are characterized by recurring papules, pustules, comedones, and cysts and exhibit an increased amount of fluorescence from the porphyrins produced by Propionibacterium acnes bacteria when seen under various types of light.

Question 29

3 Primary factors in the pathogenesis of acne

Answer 29

(1) inflammation,
(2) disordered keratinization, and
(3) the presence of the bacteria P. acnes.

In many acne cases, elevated sebum production is seen but this is not a requirement to develop acne. In fact, patients with dry skin and acne are more difficult to treat than those with oily skin and acne because many of the medications used to treat acne lead to dryness of the skin.

Question 30

Although acne has various causal pathways and contributing factors, the essential pathognomonic feature is

Answer 30

abnormal keratinization of the SC with adherence of desquamated skin cells in the hair follicles

These skin cells combine with sebum and clog the follicle, creating a comedone. The bacteria P. acnes migrates into the hair follicle, causing a cascade of events including activation of Toll-like receptor 2. This stimulates the release of cytokines and other inflammatory factors that trigger the inflammatory response.

Question 31

Goals of treatment for acne

Answer 31

• lowering P. acnes levels,
• blocking inflammatory pathways, and
• normalizing keratinization

Skin-care regimens for acne take about 8 to 12 weeks to yield results, so patients should be educated about the delay to improve compliance.

Question 32

This can be used to visualize the amount of P.acnes on the skin

Answer 32

Camera imaging such as the Canfield Visa CA

This helps determine the amount of bacteria at baseline, tracks improvement, and encourages the patient to return for followup visits to check progress. Decreased bacterial counts are often seen in the camera before the acne lesions clear, showing the patient that progress is occurring.

Question 33

Disuss the treatment and maintenance regimens for acne

Answer 33

The treatment regimen should be implemented for the first 12 weeks, which is geared to speed healing of active lesions in addition to preventing new lesions. Use acne medications such as benzoyl peroxide, clindamycin, salicylic acid, and retinoids but they should be combined with nonfoaming cleansers and noncomedogenic barrier repair ingredients in dry types. Acne treatment visits should be scheduled at weeks 4, 8, and 12 to improve compliance. Studies have shown that compliance improves around the time of the patient visit55 ; therefore, monthly visits are suggested until the acne medications are being tolerated and acne has significantly improved. After the acne has cleared, switch the patient to a retinoid-containing maintenance regimen geared to prevent recurrence (Table 207-3).

In summary, when treating sensitive skin with multiple subtypes, remove the allergens first, then add antiinflammatory ingredients, and finally proceed with acne medications. The more subtypes of sensitive skin the patient has, the more closely they should be monitored. Acne patients may feel frustrated by the delay in resolution so it is important to explain the process to them. Addition of oral medications or blue light can hasten the process of acne treatment without compromising this stepwise routine. As with other skin issues, once the skin type has reverted to a resistant type, the patient can be placed on a maintenance regimen to keep the symptoms of the sensitive subtypes at bay.

Question 34

Discuss the ROSACEA TYPE of sensitive skin

Answer 34

Rosacea is characterized by facial redness and flushing that may include inflammatory papules and telangiectasias. Topical skin care for rosacea is primarily geared toward vasoconstrictive, antimicrobial, and antiinflammatory ingredients to decrease redness and prevent progression. Many types of antiinflammatory ingredients are found in skin-care products (Table 207-4). These should be combined with prescription medications and vascular laser (595 nm) treatments for maximal results. However, special thought needs to be given to what these types of patients should not use. Vigorous exfoliation should be avoided. Triggers such as cold and heat could contribute to this pathology if the patient uses extreme temperatures of water or has frequent facials that often include facial steaming.

The choice of cleansers, moisturizers, and sunscreens should include some form of antiinflammatory ingredient. If retinoids are to be used, they should be started slowly to avoid exacerbation of rosacea. Decreasing the dose and frequency by applying a low-strength retinoid on top of an antiinflammatory moisturizer every third night is often tolerated by rosacea patients. The dose and frequency can be increased as they adjust.

Question 35

Discuss the STINGING TYPE of sensitive skin

Answer 35

Burning, stinging, or itching caused by application of a cosmetic or topical medicament without detectable visible or microscopic change is termed sensory irritation. The afferent limb of this reaction is carried by C nerve fibers that are present throughout the dermis and viable epidermis. The stinging occurs on the face within an hour of application in susceptible individuals. Patients with this subtype of sensitive skin do not have a higher incidence of atopy or dry skin, but do report frequent adverse reactions to cosmetics. Several tests such as the lactic acid stinging test have been devised to identify patients with the stinging propensity; however, there is no universally accepted test because different ingredients sting different people. Patients with rosacea and patients experiencing retinoid dermatitis often report stinging even with contact to only water. The stinging sensation is not necessarily associated with erythema as many patients feel stinging without experiencing redness or irritation.56 Most often patients with the stinging subtype of sensitive skin feel stinging upon application of the following ingredients: α-hydroxy acids (particularly glycolic acid), benzoic acid, bronopol, cinnamic acid compounds, Dowicel 200, formaldehyde, lactic acid, propylene glycol, quaternary ammonium compounds, sodium lauryl sulfate, sorbic acid, urea, ascorbic acid, and witch hazel. Use of antiinflammatory ingredients may help lessen stinging but the best therapy is avoidance of products with stinging ingredients.

Patients who have inflammation and redness from rosacea need to have antiinflammatory ingredients added to their regimen and should be given about 4 weeks for the inflammation to calm down before adding any acne treatment ingredients. If the patient has concurrent stinging with the redness, in many cases the stinging will clear with the same antiinflammatory ingredients used for the rosacea regimens. Once the redness and stinging have improved and allergens have been identified, then the patient can be placed on an acne regimen with less risk of side effects.

Question 36

Discuss theALLERGIC/IRRITANT TYPE of sensitive skin

Answer 36

The allergic/irritant subtype is more likely to develop a dermatitis upon exposure to various allergens and irritants. This subtype also has been called “status cosmeticus” by Fisher, 57 contact urticaria when a wheal and flare response occurs, 58 “cosmetic intolerance syndrome” when it occurs with cosmetics, and more commonly contact or irritant dermatitis. This subtype can be due to an increased immune response in the case of contact dermatitis or an impaired skin barrier that allows allergens and irritants to more easily enter the skin. 59 Various studies reveal that approximately 10% of patch-tested dermatologic patients are allergic to at least one ingredient common in cosmetic products. 60 Fragrances and preservatives are the most common allergens (Table 207-5). New emerging allergens include sorbitan, the preservatives methylisothiazolinone and sodium dehydroacetate, cetyl alcohol, bisabolol, peppermint, and the red pigment carmine.

The first step in treating these patients is to try and identify the allergen by patch testing or a detailed history. In some cases, a patient diary will reveal the culprit. The popularity of organic and natural ingredients has resulted in an increase in exposure to plantderived allergens. Skin care should aim for avoidance of the allergen and fortification of the skin barrier with barrier repair ingredients. There are also cosmeceutical products that coat the skin to protect against nickel and other allergen contact.

Treatment of sensitive skin depends upon the subtype. Many people have more than one type of sensitive skin. In that case, it is important to know which subtype is predominant. The allergic/irritant subtype is the most important because the treatment includes avoiding inciting factors. Use of a hypoallergenic skincare line is preferred in the case of this type of skin. Products should be added one at a time with a week in between each addition so that if the patient has a reaction, it is easier to identify the culprit.

Question 37

Cleansers for sensitive skin

Answer 37

Sensitive skin types are more prone to inflammation, so they should avoid extremes of temperature. Washing with tepid water is prudent. Avoiding exfoliants is particularly important including scrubs, facial cloths, and rotating brushes, which all can cause dermatographism, flushing, and other forms of inflammation in these susceptible types. In fact, friction has been associated with an increase in acne breakouts. Soothing cleansers that contain antiinflammatory ingredients are preferred. Hydroxy acid cleansers may irritate stinging and rosacea types but will help decrease P. acnes counts by lowering the pH and preventing and treating comedones in acne types. Salicylic acid is a good choice of hydroxy acids for acne skin types because it is lipophilic, able to enter the pilar unit, and exhibits the antiinflammatory properties of salicylates. Patients with the allergic/irritant subtype should avoid foaming cleansers that can disturb the skin barrier, facilitating entry of foreign substances into the skin.

Question 38

Moisturizers for sensitive skin

Answer 38

Patients with acne are often hesitant about moisturizer use but at least one study has demonstrated improvement of acne with moisturizer use alone.61 Moisturizers that do not contain comedogenic ingredients such as isopropyl myristate, isopropyl palmitate, and coconut oil (although not all forms of coconut extract are acnegenic) should be chosen. Patients with the rosacea type of sensitive skin do well with soothing antiinflammatory ingredients such as argan oil, chamomile, niacinamide, colloidal oatmeal, feverfew, licorice extract, green tea, and chamomile. These should be combined in the regimen with prescription rosacea medications such as azelaic acid, metronidazole, brimonidine, ivermectin, and oxymetazoline. Oxymetazoline and brimonidine have α-adrenoreceptor agonist activity that results in vasoconstriction, causing a rapid improvement in facial redness. Brimonidine has selective α 2 activity, 62 whereas oxymetazoline has effects on both α 1 and α 2 adrenergic receptors. Using these vasoconstrictive prescription products may improve compliance by showing rapid and noticeable results. Brimonidine has been associated with rebound redness, and therefore should be combined with other antiinflammatory ingredients. Oxymetazoline seems to confer some antiinflammatory benefits in addition to the vasoconstrictive effects. 63 If retinoids are used in rosacea-prone skin, they should be introduced slowly and in conjunction with antiinflammatory ingredients. Patients with stinging-type skin should avoid retinoids and ingredients with a low pH such as acids whereas patients with allergic- and irritant-prone skin should avoid known allergens and any harsh ingredients.

Question 39

Discuss skin pigmentation

Answer 39

The third primary skin characterization parameter is based on the presence or absence of uneven skin tone caused by hyperpigmentation or dyschromia on the face. The dyschromia may be in the form of melasma, solar lentigines, or postinflammatory hyperpigmentation.

Skin pigment (melanin) is produced by melanocytes, which transfer the pigment via melanosomes to keratinocytes. Melanin is derived from the enzymatic breakdown of tyrosine by tyrosinase into 3,4-dihydroxyphenylalanine, which yields 2 forms of melanin (eumelanin and pheomelanin).

Question 40

Four mechanisms employed to impede the devlopment of skin pigmentation

Answer 40

• sunscreen use and sun avoidance,
• inhibiting the tyrosinase enzyme,
• preventing melanosome transfer into keratinocytes by blocking the PAR-2 receptor, and
• increasing desquamation of the SC

Treatments work best if all of these 4 strategies are employed. Patient education is crucial because patient habits can greatly contribute to dyspigmentation, especially melasma. For example, stress, estrogen use, heat exposure, melatonin supplements, over exfoliation leading to skin inflammation, and lack of SPF use in cars and indoors can all contribute to melanocyte activation.

Question 41

SUNSCREEN

Answer 41

Sunscreen should be a routine part of the skin regimen every morning even if the patient stays indoors. There are many new SPF formulations that block infrared and other forms of light that can worsen melasma. If the patient has oily skin, then the SPF can be used in lieu of a moisturizer. Acne-prone patients should be treated with a noncomedogenic sunscreen. Oral sun-protective supplements such as polypodium leukotomes and pycnogenols offer extra protection but should not be used as a replacement for sunscreen.

Question 42

TYROSINASE INHIBITORS

Answer 42

Tyrosinase inhibitors block the production of melanin and include vitamin C, hydroquinone, kojic acid, arbutin, mulberry extract, and licorice extract (Table 207-6). Many authors recommend a “holiday” from tyrosinase inhibitors every 3 to 6 months to prevent tachyphylaxis although the need for this is anecdotal. 65,66 Ascorbic acid is a tyrosinase inhibitor that has a different structure than the others so it can be used during the holiday period. Hydroquinone is the most effective tyrosinase inhibitor but unfounded public concerns about hydroquinone safety 67 have popularized the use of similar derivatives such as kojic acid and arbutin. Hydroquinone has been found to be efficacious in combination with a retinoid and a steroid in the “Kligman formula” because retinoids and steroids such as fluocinolone inhibit tyrosinase. This triple combination agent combines hydroquinone with retinoids, which prevent the skin-thinning effects of steroids, and steroids that mitigate the inflammation from retinoids and hydroquinone.

Question 43

PAR2 BLOCKERS

Answer 43

Small proteins present in soy, such as soybean trypsin inhibitor and Bowman-Birk inhibitor, exhibit depigmenting activity and prevent UV-induced pigmentation both in vitro and in vivo. 68 These soy proteins inhibit the cleavage of the 7 transmembrane G-protein coupled receptor known as protease-activated receptor 2 (PAR-2). It is expressed in keratinocytes at intersection points with melanocytes and functions like a key opening a lock allowing the melanosomes to transfer from the melanocyte into the keratinocyte. Both soy and niacinamide, a derivative of vitamin B3 , have been shown to inhibit melanosome movement from melanocytes to keratinocytes.

Question 44

EXFOLIANTS

Answer 44

Removing the top layer of the SC induces the cell cycle to speed up, which hastens desquamation of melanosome-laden keratinocytes. The melanocytes cannot make the pigment fast enough to keep the keratinocytes full of melanosomes, so less pigmentation is seen at the cell surface. Exfoliants work much better when combined with tyrosinase inhibitors and PAR-2 blocking agents in addition to sunscreen. Exfoliants can be mechanical such as microdermabrasion, scrubs, rotating brushes, or rough fabrics, or chemical such as hydroxy acids. Retinoids also serve the purpose of accelerating desquamation. These ingredients can be added into the skin-care regimen or applied as an inoffice procedure to treat dyschromia. However, overuse or misuse can result in inflammation, which would stimulate the melanocytes to make more melanin and worsen the problem. For this reason, exfoliants should be used with extreme caution and patients should be educated about the harms of overexfoliating. Using exfoliating cleansers such as hydroxy acid cleansers is a low-risk way to add exfoliants into the skin-care regimen. In-office peels can be used but with caution and only by experienced users because peels can easily exacerbate melasma.

Question 45

LIGNIN PEROXIDASE

Answer 45

Lignin peroxidase is an enzyme synthesized by the white-rot tree fungus Phanerochaete chrysosporium that breaks down lignin in decaying trees. 70 It is used in the paper industry to whiten wood pulp and was found to break down eumelanin, which has a similar structure to lignin. 71 In topical preparations, lignin peroxidase has been found to be effective for the improvement of skin pigmentation due to an excess of eumelanin. Lignin peroxidase is commercially available as a glycoprotein known as ligninase (or Melanozyme), which functions best at a pH of 2 to 4.5. It has been found to be nonirritating and safe for use in all of the sensitive skin subtypes. It can be used during the holiday period when tyrosinase inhibitors are discontinued to help prevent rebound of melasma during the maintenance period.

Question 46

ANTIOXIDANTS

Answer 46

Antioxidants play multiple roles in the treatment and prevention of dyschromia. Their actions may include one or more of the following: chelating copper, neutralizing free radicals, and decreasing inflammation. Tyrosinase requires copper to function, and many antioxidants such as flavonoids chelate copper. Free radicals can incite inflammatory pathways leading to increased melanocyte activity. Many antioxidant ingredients such as argan oil and green tea have antiinflammatory activities independent of their antioxidant capabilities. Some antioxidants prevent UV-induced pigmentation by affecting the p53 pigmentation pathway through the rate-limiting step of p53 phosphorylation at site. This phosphorylation step is blocked by the plant-derived antioxidant phloretin. 73 Ascorbic acid (vitamin C) is a unique antioxidant in that it also has tyrosinase-inhibiting properties separate from its antioxidant properties. Antioxidants are formulated in serums, sunscreens, and moisturizers.

Question 47

Skin care for pigmented and non pigmented skin types

Answer 47

Nonpigmented types should use a daily sunscreen to preserve even skin tone. Pigmented skin types should be prescribed and educated on 2 forms of skin-care regimens: the treatment regimen and the maintenance regimen. Melasma studies show a 1- to 2-grade improvement at 12 to 16 weeks in most cases. For this reason, the treatment regimen should last 3 to 4 months and the patient should be warned that it may take several treatment cycles depending on (1) severity of melasma, (2) compliance with regimen, (3) sun avoidance, and (4) presence of other factors such as stress and estrogen use. Compliance is a major factor in achieving success. Monthly visits with photography and mexameter or other objective measurements at each visit can improve compliance. Patients should be counseled that changes in these measurements and in photos are not usually seen until 12 weeks to prevent discouragement, which usually occurs at the week 8 visit. The treatment cycle should consist of (1) daily broad-spectrum SPF;

(2) twice-daily tyrosinase inhibitor; (3) nightly retinoid;
(4) a PAR-2 blocking agent in either a sunscreen, serum, or moisturizer; and (5) an exfoliating cleanser. To save regimen steps and improve efficacy, the evening product can be a triple combination of retinoid, tyrosinase inhibitor, and a steroid such as the “Kligman formula.” After 4 months, or on clearance of the pigmentation disorder, the regimen should be changed to a maintenance regimen. The maintenance regimen should not have tyrosinase inhibitors (with the exception of ascorbic acid) but should include (1) daily broad-spectrum SPF; (2) an antioxidant such as ascorbic acid; (3) a PAR-2 blocking agent in either a sunscreen, serum, or moisturizer; (4) lignin peroxidase; and (5) an exfoliating cleanser. The maintenance regimen will be used for at least 1 month or until pigmentation begins to return, at which time the treatment regimen will be resumed for another 4 months. The back-and-forth cycle will continue until the dyspigmentation clears. This may take 1 to 6 treatment cycles but clearing will occur in almost all cases if the patient is compliant with the regimen and lifestyle advice.

Question 48

SKIN AGING

Answer 48

Aging of the skin is a complex chain of events reflecting natural intrinsic and extrinsic processes. Intrinsic aging is a function of individual heredity and results

from the passage of time. This process is, of course, inevitable and beyond voluntary control. However, the largest percentage of skin aging is due to lifestyle factors such as sun exposure, tanning bed use, smoking, increased cortisol levels, increased blood sugar levels, lack of exercise, excessive use of drugs and alcohol, and poor diet. Use of daily sunscreen, retinoids, and other antiaging technologies can mitigate the risk of skin aging. Wrinkle-prone skin is found in patients over the age of 20 who do not use antiaging technologies to prevent wrinkles while also engaging in several deleterious lifestyle behaviors. There are many exaggerated claims about antiaging ingredient efficacy, but only a few have stood the test of scientific evaluation. Although many studies are ongoing, it is much too early for any technologies to manipulate gene expression and affect skin aging with one notable exception—retinoids. Retinoids, by definition, bind the retinoic acid receptor, which turns on and off various genes including the procollagen gene. The only antiaging technologies that have been proven in vivo to improve skin appearance with long-term use are daily sunscreen, hydroxy acids, ascorbic acid, and retinoids. Many other antiaging technologies are being studied that aim to improve the appearance of skin or slow aging by lengthening telomeres; neutralizing free radicals; affecting production of matrix metalloproteinases, growth factors, and cytokines; preventing glycation; increasing skin levels of hyaluronic acid, heparan sulfate, collagen, and elastin; preserving or improving mitochondrial or lysosome function; and upregulating sirtuin expression. 74 The focus here is on the technologies that have demonstrated efficacy and are more widely used by dermatologists and omits the overhyped and unproven technologies.

The dermatologic focus of antiaging skin care should be to prevent the formation of rhytides in the first place, 75 and to improve wrinkles and a thinning dermis once this occurs. Prevention of aging is difficult to prove but the goal is to halt the degradation of the main structural components of the skin—collagen, elastin, heparan sulfate, and HA—all of which are known to be diminished in aged skin. The treatment of aging skin, usually judged by visual analysis of wrinkles, is much easier to prove but harder to achieve without using deceptive measures such as photography and use of humectants that immediately plump the skin. For this reason, placebo-controlled trials are vital to substantiate wrinkle improvement claims. Ingredients that have data to substantiate claims of wrinkle prevention include sunscreens and retinoids. Ingredients that have plausible claims that they prevent skin aging include ascorbic acid, through its collagenstimulating and antioxidant properties, and green tea because of its antioxidant and antiinflammatory properties. The only ingredients that have convincing peerreviewed data about their ability to improve wrinkles are hydroxy acids, ascorbic acid, and retinoids. Ingredients that have qualities that suggest they improve skin aging but need more proof include growth factors such as transforming growth factor-β, epidermal-derived growth factor, hyaluronic acid, and heparan sulfate.

Ingredients that have minimal to no published peerreviewed scientific data on photoaging include stem cells, collagen, products to prevent or reverse glycation, and ingredients that claim to upregulate sirtuin or lengthen telomeres. It is important to note that an antiaging claim can be made on any product that contains sunscreen.

Question 49

SUNSCREENS

Answer 49

UV exposure results in skin damage through several mechanisms including sunburn cell formation, creation of thymine dimers, collagenase production, and provoking an inflammatory response. Signaling through p53 following telomere disruption is also a common feature observed in aging as well as photodamage.76 Although much remains to be learned about the mechanisms through which UV irradiation unleashes a chain of cascading health effects, photoaging, photocarcinogenesis, and photo-immunosuppression are well-known results of UV exposure. 77 Every antiaging regimen should consist of a daily SPF. The most important factor to consider when choosing a sunscreen is patient compliance. Oily types will not wear a heavy oil-based product, whereas acne-prone types often suspect their SPF as the cause of breakouts. Chemical sunscreen agents often precipitate allergic dermatitis in susceptible sensitive skin subtypes. Patients should be educated on the major points of sunscreen use because many do not use enough SPF and do not reapply it.

Question 50

CLEANSERS

Answer 50

Cleansers prepare the skin by removing sweat, dirt, and debris that can decrease the penetration of skincare ingredients. Penetration of ingredients in their active form is a major issue for most antiaging products because the skin barrier prevents penetration of large and/or charged molecules. This barrier to penetration affects the efficacy of peptides, hyaluronic acid, growth factors, antioxidants, and many other ingredients. Cleansers can change the pH and other factors on the skin’s surface that affect both penetration and the chemical structure and efficacy of the compounds that are placed on the skin after cleansing. For example, a low-pH cleanser such as a hydroxy acid will lower the skin’s surface pH, increasing penetration of ascorbic acid, which penetrates more readily at a pH of 2 to 2.5. 78 A low pH would also improve the efficacy of lignin peroxide preparations and render the skin less hospitable for acne bacteria. Soap, on the other hand, increases the skin’s pH. 79 The choice of an antiaging cleanser depends directly on skin hydration, presence of a sensitive subtype, and choice of therapeutic products to be used on the skin after cleansing.

Question 51

MOISTURIZERS AND SERUMS

Answer 51

The main goal of antiaging skin care is to preserve and increase dermal levels of collagen, heparan sulfate, hyaluronic acid, and elastin. Of these, elastin is the most

elusive as no ingredients have been able to increase levels of mature functional elastin. To protect and/or encourage production of these components, antiaging serums and moisturizers should contain a retinoid at a minimum. Collagen synthesis has been shown to be increased through the use of retinoids. 80 Retinoids also have been demonstrated in animal models to increase production of HA 81 and have been shown in multiple studies to improve photoaged skin. 82-84 Not all patients, especially dry skin types and sensitive skin types with the rosacea subtype, can tolerate a retinoid. Retinoids penetrate easily into the skin and can incite a reaction known as retinoid dermatitis. Starting the patient accordingly on a regimen directed to barrier repair and/or decreasing inflammation for 4 weeks may increase patient tolerance of retinoids and prevent retinoid dermatitis. Retinoids should be started with a low dose and used sparingly. One suggested regimen is a pea-size amount of product applied over moisturizer every third night. The amount and frequency can be adjusted as the patient’s dryness and inflammation improve. Oily and resistant skin types usually have no trouble tolerating retinoids.

Antioxidants are commonly used in antiaging regimens to neutralize free radicals that damage DNA and cell membranes leading to increased aging, and induce glycation that causes damage to collagen strands. 85 Free radicals can act directly on growth factor and cytokine receptors in keratinocytes and dermal cells, leading to skin inflammation. The direct effects of free radicals on the aging process are beginning to be understood. In 1998, investigators demonstrated that free radical activation of the mitogen-activated protein kinase pathways resulted in production of collagenase, which led to degradation of collagen. 86 Another study by Kang and colleagues on human skin supported this concept. They showed that when human skin was pretreated with the antioxidants genistein and N-acetyl cysteine, the UV induction of the cJun-driven enzyme collagenase was blocked. 87 Antioxidants may block the process of glycation, but more data are needed before this hypothesis is proven. Many antioxidants are available in skin-care products, including argan oil, vitamins C and E, ferulic acid, coenzyme Q10 , green tea, phloretin, pycnogenol, resveratrol, silymarin, and idebenone. Vitamin C is a particularly interesting antioxidant because it has the added ability to induce fibroblasts to produce collagen.88

Hydroxy acids have been shown in multiple studies to improve fine lines and skin texture. 89 Present in cleansers, moisturizers, masks, in-office peels, and several other modalities, they function by increasing desquamation of the SC cells, which stimulates the stem cells in the skin to begin to produce various important cell components including collagen and hyaluronic acid. Hydroxy acids must be formulated at the proper pH to be effective, with the most acidic versions causing the most exfoliation but with increased side effects. Hydroxy acids can affect the efficacy of other ingredients applied at the same time, so their order in the regimen should be carefully considered.