Cosmeceuticals for rosacea

    Cosmeceuticals for Rosacea Zoe Diana Draelos MD PII: DOI: Reference:

S0738-081X(16)30278-4 doi: 10.1016/j.clindermatol.2016.10.017 CID 7115

To appear in:

Clinics in Dermatology

Please cite this article as: Draelos Zoe Diana, Cosmeceuticals for Rosacea, Clinics in Dermatology (2016), doi: 10.1016/j.clindermatol.2016.10.017

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ACCEPTED MANUSCRIPT Cosmeceuticals for Rosacea

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Address for Correspondence Zoe Diana Draelos, MD Dermatology Consulting Services 2444 North Main Street High Point, NC, 27262 [email protected] 336-841-2040

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Zoe Diana Draelos, MD Consulting Professor Department of Dermatology Duke University School of Medicine Durham, North Carolina

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Abstract Rosacea patients present a challenge to the dermatologist as they typically possess sensitive skin, have a need for facial demodex and bacterial colonization control, exhibit vasomotor instability, require camouflaging of telangiectatic mats, and desire prescription treatment. Currently available pharmaceuticals are aimed at inflammation reduction primarily through the use of topical and oral antibiotics. Recently, vasoconstrictor formulations have emerged, but these drugs have a temporary effect improving appearance without addressing the underlying cause, which remains largely unknown. Cosmeceuticals, including cleansers, moisturizers, cosmetics, sunscreens, and antiinflammatory botanicals, can be used as adjuvant therapies in combination with traditional therapies. This article explores the effective use of cosmeceuticals in the treatment of rosacea to enhance pharmaceutical outcomes and more readily meet patient expectations.

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Facial Cleansers in Rosacea Facial cleansing is important in patients with rosacea, because rosacea represents a disease of the biofilm. Whether rosacea is due to demodex colonization, the presence of bacteria in the gut of the demodex mite, Pitysporon acnes on the skin surface, or over expression of cathelicidins on the skin, cleansing to maintain a healthy biofilm is important. The cleansing needs of a rosacea patient are to remove excess sebum, environmental debris, desquamating corneocytes, unwanted organisms, and old skin care and cosmetic products while preserving the skin barrier. Skin barrier preservation is essential because patients with rosacea form a subset of sensitive skin sufferers that experience adverse events when exposed to mild irritants or substances that produce noxious sensory stimuli.(1)

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Cleansers are adept at removing lipids from the skin surface, but surfactants cannot distinguish between sebum and intercellular lipids. The thorough removal of sebum, required for bacterial and fungal growth on the skin, may also damage the intercellular lipids resulting in barrier damage manifesting as increased facial redness, stinging, burning, and itching. It is counterproductive to use an anti-inflammatory treat rosacea when the skin cleanser is enhancing inflammation. Cleanser selection is very important in rosacea, but the cleanser chosen must match the sebum production and cleansing needs of the patient. Table 1 summarizes the cleanser type appropriate for rosacea patients with oily, normal, and dry skin. Remember that most patients in the rosacea age group possess combination skin. It is not unrealistic to recommend an oily skin cleanser for the sebum rich central face and a dry skin cleanser for the lateral sides of the face. Customizing cleanser application to each area followed by water rinsing may assist in normalizing the biofilm while maintaining the skin barrier.

Table 1: Cleansing Categories for Rosacea Patients

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Cleanser Type

Formulation

Oily skin

Soap

Normal skin

Syndet

Dry skin

Lipid free cleanser

Long chain fatty acid alkali salts with a pH between 910 Synthetic detergents, contain less than 10% soap, adjusted pH of 5.5-7 Liquids that clean without fats

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Rosacea Skin Type

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Morning and evening cleansing are recommended for rosacea patients. The hands and no other implement should be used to minimize facial trauma. The fingers coated with cleanser can get into the curves and folds around the nose where Pityrosporum organisms grow, resulting in the overlap of the condition between seborrheic dermatitis and rosacea. The fingers are also useful to cleanse the eyebrows and beard area also afflicted with seborrheic dermatitis. The water temperature should be lukewarm and not too hot or cold to prevent facial flushing from rapid temperature change. Abundant water should be splashed on the face to thoroughly remove the cleanser, which can cause irritation if not completely rinsed. The skin should be gently dabbed dry with a soft towel to minimize redness induced by rubbing.

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Facial Moisturizers in Rosacea Following cleansing, it may be helpful to normal to dry complected rosacea patients to apply a moisturizer. Moisturizers are important to provide an optimal environment for barrier repair. Facial moisturizers mimic the effect of sebum on the skin surface by preventing evaporation of water from the skin into the environment, but they do not or should not support bacterial growth. For this reason, it is not wise to use moisturizers containing oils from plant or animal materials that could promote bacterial growth. For example, coconut, olive, hemp, argan, and sunflower oils should be avoided. Silicone-based moisturizers are the best to use because they are aesthetically pleasing, do not make the skin feel warm, and do not support the growth of organisms. Moisturizers should also attempt to mimic the intercellular lipids, composed of sphingolipids, free sterols, and free fatty acids. Yet, the moisturizing substances must not occlude the sweat ducts, or miliaria will result, must not produce irritation at the follicular ostia, or an acneiform eruption will result, and must not initiate comedo formation. Furthermore, the facial moisturizer must not produce noxious sensory stimuli, which may also provoke a rosacea flare. Moisturizers are used to heal barrier-damaged skin by minimizing trans-epidermal water loss (TEWL) and creating an environment optimal for rosacea control. There are three categories of substances that can be combined to enhance the water content of the skin include occlusives, humectants, and hydrocolloids.

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Occlusives are oily substances that retard transepidermal water loss by placing an oil slick over the skin surface, while humectants are substances that attract water to the skin, not from the environment, unless the ambient humidity is 70%, but rather from the inner layers of the skin. Humectants draw water from the viable dermis into the viable epidermis and then from the nonviable epidermis into the stratum corneum. Hydrocolloids are physically large substances, which cover the skin thus retarding transepidermal water loss.

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The best moisturizers to prevent facial rosacea flares combine occlusive and humectant ingredients. For example, a well-formulated moisturizer might contain petrolatum, mineral oil, and dimethicone as occlusive agents.  Petrolatum is the synthetic substance most like intercellular lipids, but too high a concentration will yield a sticky greasy ointment. The aesthetics of petrolatum can be improved by adding dimethicone, also able to prevent water loss, but allowing a reduction in the petrolatum concentration and a thinner more acceptable formulation.  Mineral oil is not quite as greasy as petrolatum, but still an excellent barrier repair agent, that further improves the ability of the moisturizer to spread, yielding enhanced aesthetics.  The addition of glycerin to the formulation will attract water from the dermis speeding hydration. It is through the careful combination of these ingredients that facial moisturizers can be constructed to prevent a rosacea flare. All active cosmeceutical formulations for rosacea use a moisturizer as the vehicle to deliver the active agents. Moisturizers for rosacea patients can also be combined with sunscreen to provide long term improvement in rosacea, as photodamage is a known contributory factor. Patients with rosacea require broad spectrum protection with an SPF of 30+ to achieve UVB and UVA coverage. Many patients with rosacea do not like sunscreens because they are sticky and impart a warm feeling to the skin. This warmth may be due to the sunscreen active agent converting UV radiation into heat. This is the mechanism by which all organic sunscreens function. Because facial warmth is a flushing trigger for many rosacea sufferers, the temperature change should be avoided. Inorganic sunscreens, such as titanium dioxide and zinc oxide, do not release heat when struck by UV radiation, but rather largely reflect the energy. This means patients with rosacea should select sunscreen-containing moisturizers that contain dimethicone and zinc oxide for best results. Colored Cosmetics for Redness Reduction Following cleansing and moisturizing, the red skin appearance characteristic of rosaca should be optimized. Colored cosmetics are useful for camouflaging in women rosacea patients. The cosmetics camouflage the underlying redness by either blending colors or concealing the underlying skin to achieve a more desirable appearance. The art of blending colors to minimize facial redness utilizes the complementary color to red, which is green. Moisturizers with a slight green tint are applied after the prescription

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medication and well blended. Several currently marketed moisturizers for rosacea contain a slight green tint. Because the mixture of red and green produce brown, the sheer green tint will tone down bright red cheeks. A facial foundation should be applied over the green tint to achieve complete camouflage.

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Camouflaging can also be achieved with green facial powder. These powders contain a blend of pigments designed to tone down facial redness in persons who do not wish to wear a facial foundation. These tinted powders can be worn by men and women and are useful to assist in the absorption of oil, as well.

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Sometimes, the facial redness is too dramatic to cover with a traditional facial foundation or powder. In this case, it may be helpful to apply prescription vasoconstrictor brimonidine, prior to applying cosmetics. The brimonidine will remove the facial redness over 30 minutes while the patient is traveling to work. If brimonidine is not suitable, opaque facial foundations can be used in women. These facial foundations are creams wiped from a stick or stroked from a compact. The creams are thick accounting for the increased concentration of pigments and anhydrous to provide waterproof properties. These are the same cosmetics that are used for surgical camouflaging purposes.

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Facial Cosmeceuticals in Rosacea Many active cosmeceutical agents have been added to moisturizers to improve facial redness reduction. Most of these ingredients are botanical anti-inflammatories with the intent to reduce facial redness by interrupting the inflammatory cascade. Interrupting the inflammatory cascade in difficult, which is why all skin care products should be carefully selected for the rosacea patient. Table 2 contains a list of all the commonly used botanicals in rosacea moisturizing formulations. Each of these botanicals is briefly discussed.

Table 2 Facial Cosmeceuticals for Redness Reduction Botanical Ingredient

Active Agent

Skin Functional Effect

Ginkgo biloba

Terpenoids (ginkgolides, bilobalides), flavinoids, flavonol glycosides

Green tea

Polyphenols such as epicatechin, epicatechin-3gallate, epigallocatchin, epigallocatecin-3-gallate Aloin, aloe emodin, aletinic acid, choline, choline salicylate

Decrease circulation at the capillary level, reduce inflammation through antiradical and antilipoperoxidant effects Reduces UVB induced inflammation by functioning as an antioxidant Salicyate derivative inhibits cyclooxygenase pathway

Aloe vera

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Feverfew

Parthenolide, tanetin

Glycyrrhiza inflate

Licochalcone A

Enhances the water holding capacity of the extracellular matrix improving barrier function Inhibits the release of prostaglandins and serotonin Inhibits keratinocytes release of prostaglandins in response to UVB induced erythema

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Allantoin

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1. Ginkgo biloba Ginkgo biloba leaves contain unique polyphenols such as terpenoids (ginkgolides, bilobalides), flavinoids, and flavonol glycosides with anti-inflammatory effects.(2) These anti-inflammatory effects have been linked to antiradical and antilipoperoxidant effects in experimental fibroblast models. Ginkgo leaves are also purported to alter skin microcirculation by reducing blood flow at the capillary level and inducing a vasomotor change in the arterioles of the subpapillary skin plexus. Taken together, these changes may lead to decreased skin redness.

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2. Green Tea Green tea, also known as Camellia sinensis, is another anti-inflammatory botanical containing polyphenols, such as epicatechin, epicatechin-3-gallate, epigllocatechin, and eigallocatechin-3-gallate. The term "green tea" refers to the manufacture of the botanical extract from fresh leaves of the tea plant by steaming and drying at elevated temperatures avoiding oxidation and polymerization of the polyphenolic components. A study by Katiyar et al, demonstrated the anti-inflammatory effects of topical green tea application on C3H mice.(3) A second study by the same authors found topically applied green tea extract containing epigallocatechin-3-gallate reduced UVB-induced inflammation as measured by double skin-fold swelling.(4) Green tea extracts are the most commonly used cosmeceutical botanical anti-inflammatory at the time of this writing. 3. Aloe Vera The second most commonly used anti-inflammatory botanical is aloe vera. The mucilage is released from the plant leaves as a colorless gel and contains 99.5% water and a complex mixture of mucopolysaccharides, amino acids, hydroxy quinone glycosides, and minerals. Compounds isolated from aloe vera juice include aloin, aloe emodin, aletinic acid, choline, and choline salicylate.(5) The reported cutaneous effects of aloe vera relevant to rosacea include reduced inflammation, decreased skin bacterial colonization, and enhanced wound healing. The anti-inflammatory effects of aloe vera may result from its ability to inhibit cyclooxygenase as part of the arachidonic acid pathway through the choline salicylate component of the juice; however, the aloe vera

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4. Allantoin Allantoin is oldest anti-inflammatory ingredient added to many moisturizers labeled as appropriate for sensitive skin. It naturally found in the comfrey root, but usually synthesized by the alkaline oxidation of uric acid in a cold environment.(6) It is a white crystalline powder readily soluble in hot water, making it easy to formulate in cream and lotion moisturizers designed for sensitive skin. It is termed as a skin protectant, which may be helpful in redness reduction.

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5. Feverfew Feverfew is a small bush with citrus scented leaves used as a traditional medicinal herb. It has been used to treat headaches, arthritis, and digestive problems. The antiinflammatory benefits of this plant have been attributed to parthenolide and tanetin, which are thought to decrease the release of serotonin and prostaglandins.(7) It also induces vasoconstriction. These are the mechanisms that may allow feverfew to reduce redness in rosacea. A skin care line based on parthenolide free feverfew is currently marketed for rosacea, because parthenolide can induce allergic contact dermatitis.

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6. Glycyrrhiza inflata Glycyrrhiza inflata is a member of the licorice family, known for containing a variety of anti-inflammatory botanicals. One extract isolated by heating from the root of the Glycyrrhiza inflata licorice plant is licochalcone A. It possesses anti-inflammatory properties as evidenced its in vitro ability to inhibit the keratinocytes release of PGE2 in response to UVB-induced erythema and the lipopolysaccharide-induced release of PGE2 by adult dermal fibroblasts.(8) Licochalcone A is the active agent in one of the largest product lines currently sold internationally for redness reduction.

Cosmeceutical and Skin Care Selection in Rosacea On occasion, cosmeceuticals may appear to worsen the redness of rosacea. Despite excellent oral and/or topical medications, the symptoms of stinging, burning, and itching may worsen. It is important not to overlook the possibility that the cosmeceutical may the offending cause. In this case, it may be worthwhile to embark on a logical elimination scheme to determine which products can and cannot be tolerated. Table 3 introduces an algorithm for dealing with these difficult rosacea patients, based more on the art of medicine than the science.(9) Table 3 Skin Care Treatment Algorithm for Problematic Rosacea Patient 1. Discontinue all topical cosmetics, over-the-counter treatment products, cleansers, moisturizers, and fragrances. Use only a lipid-free cleanser and a bland moisturizing cream for 2 weeks.

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2. Discontinue all topical prescription rosacea medications for 2 weeks. Especially avoid medications containing retinoids, benzoyl peroxide, glycolic acid, and propylene glycol. Oral medications for rosacea may be continued. 3. Eliminate all sources of facial skin friction. 4. Discontinue any physical activities that involve facial skin friction, such as horse back riding, football, and cycling, where a helmet with a chin strap is required. 5. Evaluate the patient at 2 weeks to determine if any improvement has occurred or if any concommitant dermatoses are present. If an underlying dermatoses, such as seborrheic dermatitis, psoriasis, eczema, atopic dermatitis, or perioral dermatitis appear, treat as appropriate until 2 weeks after all visible signs of the newly diagnosed skin disease have disappeared. 6. Patch test patient to allergens with facial application relevance. Determine which of these allergens are clinically relevant and make avoidance recommendations. 7. Evaluate the patient’s mental status especially noting signs of depression, menopause, or psychiatric disease. 8. Allow the woman patient to add one facial cosmetic in the following order: lipstick, face powder, blush. 9. Use test all remaining cosmetics used by the patient by applying nightly to a 2 cm area lateral to the eye for at least 5 consecutive nights. Cosmetics should be tested in the following order: mascara, eye liner, eyebrow pencil, eye shadow, facial foundation, blush, facial powder, and any other colored facial cosmetic. 10. Lastly, use test all topical rosacea medications by applying nightly to a 2 cm area lateral to the eye for 5 consecutive nights. 11. Analyze all data and present the patient with a list of medications, skin care products, and cosmetics that are appropriate for use.

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This process may be time consuming, but it is a thorough approach to determining the topical products that are appropriate for the challenging rosacea patient who needs more in depth assessment. The first step is to discontinue all medications and skin care products except a mild cleanser and moisturizer. Remember that the vehicle for the rosacea medication may be causing irritation. Also, eliminate all physical facial skin irritation, such as turtle neck sweaters, face scarves, hats, and chin straps. Consider patch testing for facial relevant sources of allergic and irritant contact dermatitis. Try to control hormonal and mental issues, if possible, because both can contribute to uncontrollable flushing. Finally, add back skin care products, cosmeceuticals, and topical medications systematically to identify possible sources of worsening facial redness. Conclusions Cosmeceuticals can be helpful or a hindrance in the rosacea patient. Many antiaging cosmeceuticals function by producing exfoliation or slight skin irritation. Popular cosmeceutical ingredients that induce irritation include retinol, alpha hydroxy acids, and beta hydroxy acids. Devices for antiaging include mechanized brushes, particulate scrubs, and needling rollers. While the rosacea patient may wish to participate in the anti-aging market, use of these cosmeceuticals and devices will surely worsen facial redness.

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The key to using cosmeceuticals successfully in the rosacea patient is to customize a skin treatment regimen. Examine the patient's sebum production to pick an appropriate cleanser and moisturizer. Select the optimal prescription therapy, but also recommend camouflaging techniques where appropriate. Consider methods to enhance sunscreen compliance; however, problems may still occur. If this happens, use the skin care treatment algorithm presented to determine the cause of the increased facial redness and formulate a solution. Cosmeceuticals should become a useful adjuvant in rosacea therapy.

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References 1

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Basketter DA, Griffiths HA: A studyof the relationship between susceptibility to skin stinging and skin irritation. Contact Dermatitis 1993;29:185-188.

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Svobodova, Alena, Jitka Psotova, and Daniela Walterová. "Natural phenolics in the prevention of UVinduced skin damage. A review." Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2003; 147: 137-45. Katiyar SK, Elmets CA: Green tea and skin. Arch Dermatol 2000;136:989-994.

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Katiyar SK, Elmets CA, Agarwal R, et al: Protection against ultraviolet-B radiation-induced local and systemic suppression of contact hypersensitivity and edema responses in C3H/HeN mice by green tea polyphenols. Photochem Photobiol 1995;62:855-861 Surjushe, Amar, Resham Vasani, and D. G. Saple. "Aloe vera: a short review." Indian J Dermatol

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Draelos, Zoe Diana. "Botanicals as topical agents." Clin Dermatol 2001; 19: 474-477.

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Martin, Katharine, et al. "Parthenolide-depleted Feverfew (Tanacetum parthenium) protects skin from UV irradiation and external aggression." Arch Dermatol Research 2008; 300: 69-80.

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Weber TM, Ceilley RI, Bueger A, Kolbe L, Trookman NS, Rizer RL, Schoelermann A: Skin tolerance, efficacy, and quality of life of patients with red facial skin using a skin care regimen containing licochalcone A. J Cosmet Dermatol 2006: 227-232 Draelos ZD. Sensitive skin: perceptions, evaluation, and treatment. Contact Derm 1997;8:67-78