Aesthetic Dermatology

If stranded on a deserted island and he could have only one laser, cosmetic dermatologist E. Victor Ross says he would choose an intense pulse light. Separating the science from the marketing of lasers can be a challenge.

View Video Now.

If stranded on a deserted island and he could have only one laser, cosmetic dermatologist E. Victor Ross says he would choose an intense pulse light. Separating the science from the marketing of lasers can be a challenge.

View Video Now.

If stranded on a deserted island and he could have only one laser, cosmetic dermatologist E. Victor Ross says he would choose an intense pulse light. Separating the science from the marketing of lasers can be a challenge.

View Video Now.

Cosmetic dermatologists need to remain ethical in how they choose and promote a product or procedure, as well as how they market their practice to patients, Dr. Susan H. Weinkle says in an interview. Topics discussed include the need to explain off-label drug usage and potential conflicts of interest.

 View Video Now.

Cosmetic dermatologists need to remain ethical in how they choose and promote a product or procedure, as well as how they market their practice to patients, Dr. Susan H. Weinkle says in an interview. Topics discussed include the need to explain off-label drug usage and potential conflicts of interest.

 View Video Now.

Cosmetic dermatologists need to remain ethical in how they choose and promote a product or procedure, as well as how they market their practice to patients, Dr. Susan H. Weinkle says in an interview. Topics discussed include the need to explain off-label drug usage and potential conflicts of interest.

 View Video Now.

Many products that tout antioxidant activity include antioxidant ingredients that contain polyphenols. There are numerous classes of polyphenols, which are the largest group of phytochemicals and the most broadly disseminated among plants (J. Am. Diet. Assoc. 1999;99:213-8). They are secondary plant metabolites represented by more than 8,000 naturally occurring compounds.

These widely divergent substances, which exhibit various levels of antioxidant activity, share a common structural component: a phenol or an aromatic ring, usually two, with at least one hydroxyl group, that are linked via a three-carbon bond to form a six-unit heterocyclic ring (J. Nutr. 2003;133:3248S-54S).

Attention has been increasingly focused on polyphenols, as they are known to be an important part of, and the most abundant source of antioxidants in, the human diet. They are present in many vegetables, fruits, herbs, grains, teas, and beans, as well as coffee, propolis, and red wine (Biomed. Pap. Med. Fac. Univ. Palacky Olomouc. Czech Repub. 2003;147:137-45; J. Nutr. 2000;130:2073S-85S; Annu. Rev. Nutr. 2002;22:19-34; Pharmacol. Ther. 2001;90:157-77; Free Radic. Biol. Med. 2001;30:1213-22).

The most prevalent and frequently studied polyphenols are known as flavonoids. Based on the connection of an aromatic ring to the heterocyclic ring, as well as the oxidation state and functional groups of the heterocyclic ring, flavonoids are further divided into flavones (based on the 2-phenylchromen-4-one skeleton, e.g., apigenin and luteolin); flavonols (based on the 3-hydroxy-2-phenylchromen-4-one skeleton and functional group, e.g., quercetin, kaempferol, myricetin, and fisetin); flavanones (based on the 2,3-dihydro-2-phenylchromen-4-one skeleton and functional group, e.g., naringenin, hesperetin, and eriodictyol); isoflavones (based on the 3-phenylchromen-4-one skeleton, e.g., genistein and daidzein); flavanols or catechins (based on the 2-phenyl-3,4-dihydro-2H-chromen-3-ol skeleton and functional groups, e.g., epicatechin, epicatechin 3-gallate, epigallocatechin, epigallocatechin 3-gallate (EGCG), catechin, gallocatechin); anthocyanins (based on the 2-phenylchromenylium ion skeleton, e.g., cyanidin and pelargonidin); and proanthocyanidins or condensed tannins (which are polymer chains of flavanols, such as catechins, and include pycnogenol, leukocyanidin, and leucoanthocyanidin) (Annu. Rev. Nutr. 2002;22:19-34; Asia Pac. J. Clin. Nutr. 2004;13:S72; J. Nutr. 2000;130:2073S-85S; J. Nutr. 2003;133:3248S-54S).
Tannins, phenolic polymers of high molecular weight, are divided into three classes: hydrolyzable tannins (e.g., ellagic acid, found in pomegranates, raspberries, strawberries, cranberries, and walnuts), derived tannins (created during food handling and processing and present in black and oolong teas), and condensed tannins, described above (J. Am. Diet. Assoc. 1999;99:213-8; J. Nutr. 2003;133:3248S-54S).

Some specific flavonoids can be found in the following food sources: flavonols in apples with skin, broccoli, olives, onions, and green and black tea; flavones in celery and parsley; flavonones in grapefruit, oranges, and their juices; and catechins (flavanols) in apples with or without skin, dark chocolate, cocoa, red wine, and green and black tea (Asia Pac. J. Clin. Nutr. 2004;13:S72).

There are a plethora of other polyphenols, many of which confer health benefits, including stilbenes (e.g., resveratrol, found in red wine), lignans (e.g., enterodiol, found in flaxseed and flaxseed oil), and phenolic acids, such as hydroxybenzoic and hydroxycinnamic acids, among which caffeic and ferulic acids are often present in foods.

Broad health benefits have been associated with hundreds of polyphenolic substances. Notably, some of the best known research results on polyphenols have reported on the success of various topical applications of green tea catechins, ferulic acid, resveratrol, and other related compounds (many of which have been addressed in this column). The rest of this discussion focuses on new information regarding systemic efficacy, topical delivery, or applications of a representative from several subclasses of these compounds.

Flavonols: Quercetin
A water-in-oil microemulsion containing quercetin has been shown, in porcine skin in vitro and hairless mouse skin in vivo, to enhance the penetration of the flavonol into the stratum corneum, epidermis, and dermis. The preparation also was found to significantly inhibit ultraviolet B (UVB)-induced metalloproteinase activity and glutathione reduction (Eur. J. Pharm. Biopharm. 2008;69:948-57).

Flavones: Apigenin
The topical application of 4',5,7-trihydroxyflavone (apigenin) on mouse skin has been shown to decrease skin tumor size and incidence induced by UVB exposure (Cancer Res. 2008:68:3057-65). In a different study, the apigenin glycosides 7-O-glucuronide, 7-O-methylglucuronide, and pectolinarin also have been demonstrated to induce collagen type I synthesis in fibroblasts. The investigators found that all tested compounds promoted the activity of prolidase, which initiates the last stage of collagen degradation and is integral to collagen production (Int. J. Mol. Med. 2007;20:889-95).

Flavonones: Naringenin
The citrus flavonone naringenin shows promise as a preventive agent against cutaneous aging as well as carcinogenesis. Naringenin has been demonstrated to exert an antiapoptotic effect in UVB-damaged cells, significantly extending long-term cellular survival, and to facilitate the removal of cyclobutane pyrimidine dimers from the genome (Photochem. Photobiol. 2008;84:307-16).

Isoflavones: Red Clover, Genistein, and Daidzein
Recently, red clover, whose isoflavones had previously been shown to contribute to a low incidence of osteoporosis and menopausal symptoms in high dietary concentrations, was examined for anti-aging effects. Investigators orally administered red clover extract containing 11% isoflavones to ovariectomized rats for 14 weeks, and found that collagen levels increased significantly in the treatment group as compared to the control group. Epidermal thickness and keratinization were normal in the treated group, but were reduced in the control group. The authors concluded that the regular dietary consumption of red clover isoflavones can alleviate cutaneous aging brought on by declines in estrogen (Phytother. Res. 2006;20:1096-9).

In a recent study evaluating the feasibility of skin absorption of the soy isoflavones genistein, daidzein, and glycitein, both genistein and daidzein inhibited UVB-induced hydrogen peroxide synthesis in keratinocytes. Analysis of vehicle effects on in vitro topical delivery revealed that genistein showed better skin absorption than daidzein. The investigators concluded that the topical application of soy isoflavones shows promise as a treatment for photoaging and photodamage (Int. J. Pharm. 2008;364:36-44).

Indeed, the topical application of isoflavones, including genistein and daidzein, has been shown to protect pig skin from photodamage caused by solar-simulated ultraviolet irradiation. Notably, the isoflavone compounds tested were less effective than a topical antioxidant formulation containing vitamins C and E and the phenolic acid ferulic acid (Photodermatol. Photoimmunol. Photomed. 2008;24:61-6).

Catechins (Flavanols): Epigallocatechin 3-gallate
Already considered a potent antioxidant, EGCG continues to receive attention for conferring an expanding range of health benefits. This compound, the most abundant and potent catechin in green tea, has been shown to hinder UVB-induced collagen-degrading matrix metalloproteinases (Food Chem. Toxicol. 2008;46:1298-307).

A different study of EGCG indicated that it hampered the proliferation and migration of keloid fibroblasts in vitro, and also curbed in vivo signs of keloids, by interrupting the signal transducer and activator of the transcription-3 signaling pathway. As a result of these findings, the investigators proposed EGCG as a preventive and therapeutic agent for keloids (J. Invest. Dermatol. 2008;128:2429-41). EGCG also has been suggested as a potential therapeutic approach to atopic dermatitis, given its success against AD-like skin lesions in a murine model (Int. Immunopharmacol. 2008;8:1172-82).

Anthocyanins: Cyanidin
Clearly, all flavonoids are not equal. In a recent study, methanol extracts of black raspberries, strawberries, and blueberries were tested for their capacity to inhibit UV-induced activation of nuclear transcription factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) in mouse epidermal cells. The methanol fractions of black raspberries, which contain the anthocyanin cyanidin 3-rutinoside, were found to time- and dose-dependently inhibit the effects of UV on NF-kappaB and AP-1, unlike the other berries, which do not contain cyanidin 3-rutinoside (Nutr. Cancer 2007;58:205-12).

Another form of cyanidin has also been shown to impart cutaneous benefits. Specifically, pretreatment of human keratinocytes with the anthocyanin cyanidin 3-O-glucoside has been demonstrated to protect against a wide array of UVB-induced damage (J. Agric. Food Chem. 2006;54:4041-7).

Proanthocyanidins: Pycnogenol
Investigators studied pycnogenol in an antioxidant mixture that also included evening primrose and vitamins C and E. After 10 weeks of oral administration to female SKH-1 hairless mice exposed to UVB irradiation three times weekly, the mixture was found to significantly inhibit wrinkle formation by suppressing UVB-induced matrix metalloproteinase activity while promoting collagen production (Photodermatol. Photoimmunol. Photomed. 2007;23:155-62).

Tannins: Ellagic Acid
In a double-blind, placebo-controlled, 4-week trial, investigators assessed the effects of orally administered ellagic acid-rich pomegranate extract on the pigmentation of 13 women after UV exposure. Healthy volunteers were randomly assigned to high-dose, low-dose, and control groups. The results showed that luminance values decreased by 1.73% in the high-dose group and 1.35% in the low-dose group, compared with the control group, and stains and freckles also were diminished (J. Nutr. Sci. Vitaminol. (Tokyo) 2006;52:383-8).

Stilbenes: Resveratrol
The antioxidant potency of resveratrol has been cited for conferring a wide range of salutary effects, including antitumorigenic and antiaging activity. Recently, a resveratrol-based skin care formulation intended to combat photoaging was reported to exhibit 17-fold greater antioxidant activity than idebenone (J. Cosmet. Dermatol. 2008;7:2-7). In a different study, resveratrol, the primary active polyphenolic constituent in red wine, was assessed in terms of topical/transdermal delivery viability, given the previously established benefits shown via systemic administration. Several hydrogel systems used as resveratrol vehicles were shown to be safe and effective methods for cutaneously delivering the therapeutic effects of this antioxidant (Biol. Pharm. Bull. 2008;31:955-62).

Phenolic Acids: Ferulic Acid
In a small study, a stable formulation of 15% L-corbic acid, 1% alpha-tocopherol, and 0.5% ferulic acid was applied topically to normal-appearing human skin for 4 days, and was found to confer significant photoprotection against solar-simulated UV radiation. The preparation was especially effective at diminishing thymine dimer mutations, which are linked to skin cancer. The authors also noted that the mechanism of action of this antioxidant formulation differs from that of sunscreens and, therefore, may serve as a supplement to such products (J. Am. Acad. Dermatol. 2008;59:418-25). It is worth noting that ferulic acid has been approved as a sunscreen agent in Japan (J. Pharm. Biomed. Anal. 2008;46:645-52).

Conclusion
A brief survey of the polyphenolic landscape obviously cannot do the subject justice. That said, from the dermatologic perspective, it is simply worth noting how often this diverse family of compounds factors occur in to the skin care formulations that are becoming more prevalent in the established armamentarium as well as the direct-to-consumer market.

Given the increasing attention paid here and elsewhere to the impact of diet on the skin, the status of the diverse class of polyphenolic compounds found in a wide array of plants, which includes several antioxidants, appears to be well deserved and warrants much more research.

Many products that tout antioxidant activity include antioxidant ingredients that contain polyphenols. There are numerous classes of polyphenols, which are the largest group of phytochemicals and the most broadly disseminated among plants (J. Am. Diet. Assoc. 1999;99:213-8). They are secondary plant metabolites represented by more than 8,000 naturally occurring compounds.

These widely divergent substances, which exhibit various levels of antioxidant activity, share a common structural component: a phenol or an aromatic ring, usually two, with at least one hydroxyl group, that are linked via a three-carbon bond to form a six-unit heterocyclic ring (J. Nutr. 2003;133:3248S-54S).

Attention has been increasingly focused on polyphenols, as they are known to be an important part of, and the most abundant source of antioxidants in, the human diet. They are present in many vegetables, fruits, herbs, grains, teas, and beans, as well as coffee, propolis, and red wine (Biomed. Pap. Med. Fac. Univ. Palacky Olomouc. Czech Repub. 2003;147:137-45; J. Nutr. 2000;130:2073S-85S; Annu. Rev. Nutr. 2002;22:19-34; Pharmacol. Ther. 2001;90:157-77; Free Radic. Biol. Med. 2001;30:1213-22).

The most prevalent and frequently studied polyphenols are known as flavonoids. Based on the connection of an aromatic ring to the heterocyclic ring, as well as the oxidation state and functional groups of the heterocyclic ring, flavonoids are further divided into flavones (based on the 2-phenylchromen-4-one skeleton, e.g., apigenin and luteolin); flavonols (based on the 3-hydroxy-2-phenylchromen-4-one skeleton and functional group, e.g., quercetin, kaempferol, myricetin, and fisetin); flavanones (based on the 2,3-dihydro-2-phenylchromen-4-one skeleton and functional group, e.g., naringenin, hesperetin, and eriodictyol); isoflavones (based on the 3-phenylchromen-4-one skeleton, e.g., genistein and daidzein); flavanols or catechins (based on the 2-phenyl-3,4-dihydro-2H-chromen-3-ol skeleton and functional groups, e.g., epicatechin, epicatechin 3-gallate, epigallocatechin, epigallocatechin 3-gallate (EGCG), catechin, gallocatechin); anthocyanins (based on the 2-phenylchromenylium ion skeleton, e.g., cyanidin and pelargonidin); and proanthocyanidins or condensed tannins (which are polymer chains of flavanols, such as catechins, and include pycnogenol, leukocyanidin, and leucoanthocyanidin) (Annu. Rev. Nutr. 2002;22:19-34; Asia Pac. J. Clin. Nutr. 2004;13:S72; J. Nutr. 2000;130:2073S-85S; J. Nutr. 2003;133:3248S-54S).
Tannins, phenolic polymers of high molecular weight, are divided into three classes: hydrolyzable tannins (e.g., ellagic acid, found in pomegranates, raspberries, strawberries, cranberries, and walnuts), derived tannins (created during food handling and processing and present in black and oolong teas), and condensed tannins, described above (J. Am. Diet. Assoc. 1999;99:213-8; J. Nutr. 2003;133:3248S-54S).

Some specific flavonoids can be found in the following food sources: flavonols in apples with skin, broccoli, olives, onions, and green and black tea; flavones in celery and parsley; flavonones in grapefruit, oranges, and their juices; and catechins (flavanols) in apples with or without skin, dark chocolate, cocoa, red wine, and green and black tea (Asia Pac. J. Clin. Nutr. 2004;13:S72).

There are a plethora of other polyphenols, many of which confer health benefits, including stilbenes (e.g., resveratrol, found in red wine), lignans (e.g., enterodiol, found in flaxseed and flaxseed oil), and phenolic acids, such as hydroxybenzoic and hydroxycinnamic acids, among which caffeic and ferulic acids are often present in foods.

Broad health benefits have been associated with hundreds of polyphenolic substances. Notably, some of the best known research results on polyphenols have reported on the success of various topical applications of green tea catechins, ferulic acid, resveratrol, and other related compounds (many of which have been addressed in this column). The rest of this discussion focuses on new information regarding systemic efficacy, topical delivery, or applications of a representative from several subclasses of these compounds.

Flavonols: Quercetin
A water-in-oil microemulsion containing quercetin has been shown, in porcine skin in vitro and hairless mouse skin in vivo, to enhance the penetration of the flavonol into the stratum corneum, epidermis, and dermis. The preparation also was found to significantly inhibit ultraviolet B (UVB)-induced metalloproteinase activity and glutathione reduction (Eur. J. Pharm. Biopharm. 2008;69:948-57).

Flavones: Apigenin
The topical application of 4',5,7-trihydroxyflavone (apigenin) on mouse skin has been shown to decrease skin tumor size and incidence induced by UVB exposure (Cancer Res. 2008:68:3057-65). In a different study, the apigenin glycosides 7-O-glucuronide, 7-O-methylglucuronide, and pectolinarin also have been demonstrated to induce collagen type I synthesis in fibroblasts. The investigators found that all tested compounds promoted the activity of prolidase, which initiates the last stage of collagen degradation and is integral to collagen production (Int. J. Mol. Med. 2007;20:889-95).

Flavonones: Naringenin
The citrus flavonone naringenin shows promise as a preventive agent against cutaneous aging as well as carcinogenesis. Naringenin has been demonstrated to exert an antiapoptotic effect in UVB-damaged cells, significantly extending long-term cellular survival, and to facilitate the removal of cyclobutane pyrimidine dimers from the genome (Photochem. Photobiol. 2008;84:307-16).

Isoflavones: Red Clover, Genistein, and Daidzein
Recently, red clover, whose isoflavones had previously been shown to contribute to a low incidence of osteoporosis and menopausal symptoms in high dietary concentrations, was examined for anti-aging effects. Investigators orally administered red clover extract containing 11% isoflavones to ovariectomized rats for 14 weeks, and found that collagen levels increased significantly in the treatment group as compared to the control group. Epidermal thickness and keratinization were normal in the treated group, but were reduced in the control group. The authors concluded that the regular dietary consumption of red clover isoflavones can alleviate cutaneous aging brought on by declines in estrogen (Phytother. Res. 2006;20:1096-9).

In a recent study evaluating the feasibility of skin absorption of the soy isoflavones genistein, daidzein, and glycitein, both genistein and daidzein inhibited UVB-induced hydrogen peroxide synthesis in keratinocytes. Analysis of vehicle effects on in vitro topical delivery revealed that genistein showed better skin absorption than daidzein. The investigators concluded that the topical application of soy isoflavones shows promise as a treatment for photoaging and photodamage (Int. J. Pharm. 2008;364:36-44).

Indeed, the topical application of isoflavones, including genistein and daidzein, has been shown to protect pig skin from photodamage caused by solar-simulated ultraviolet irradiation. Notably, the isoflavone compounds tested were less effective than a topical antioxidant formulation containing vitamins C and E and the phenolic acid ferulic acid (Photodermatol. Photoimmunol. Photomed. 2008;24:61-6).

Catechins (Flavanols): Epigallocatechin 3-gallate
Already considered a potent antioxidant, EGCG continues to receive attention for conferring an expanding range of health benefits. This compound, the most abundant and potent catechin in green tea, has been shown to hinder UVB-induced collagen-degrading matrix metalloproteinases (Food Chem. Toxicol. 2008;46:1298-307).

A different study of EGCG indicated that it hampered the proliferation and migration of keloid fibroblasts in vitro, and also curbed in vivo signs of keloids, by interrupting the signal transducer and activator of the transcription-3 signaling pathway. As a result of these findings, the investigators proposed EGCG as a preventive and therapeutic agent for keloids (J. Invest. Dermatol. 2008;128:2429-41). EGCG also has been suggested as a potential therapeutic approach to atopic dermatitis, given its success against AD-like skin lesions in a murine model (Int. Immunopharmacol. 2008;8:1172-82).

Anthocyanins: Cyanidin
Clearly, all flavonoids are not equal. In a recent study, methanol extracts of black raspberries, strawberries, and blueberries were tested for their capacity to inhibit UV-induced activation of nuclear transcription factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) in mouse epidermal cells. The methanol fractions of black raspberries, which contain the anthocyanin cyanidin 3-rutinoside, were found to time- and dose-dependently inhibit the effects of UV on NF-kappaB and AP-1, unlike the other berries, which do not contain cyanidin 3-rutinoside (Nutr. Cancer 2007;58:205-12).

Another form of cyanidin has also been shown to impart cutaneous benefits. Specifically, pretreatment of human keratinocytes with the anthocyanin cyanidin 3-O-glucoside has been demonstrated to protect against a wide array of UVB-induced damage (J. Agric. Food Chem. 2006;54:4041-7).

Proanthocyanidins: Pycnogenol
Investigators studied pycnogenol in an antioxidant mixture that also included evening primrose and vitamins C and E. After 10 weeks of oral administration to female SKH-1 hairless mice exposed to UVB irradiation three times weekly, the mixture was found to significantly inhibit wrinkle formation by suppressing UVB-induced matrix metalloproteinase activity while promoting collagen production (Photodermatol. Photoimmunol. Photomed. 2007;23:155-62).

Tannins: Ellagic Acid
In a double-blind, placebo-controlled, 4-week trial, investigators assessed the effects of orally administered ellagic acid-rich pomegranate extract on the pigmentation of 13 women after UV exposure. Healthy volunteers were randomly assigned to high-dose, low-dose, and control groups. The results showed that luminance values decreased by 1.73% in the high-dose group and 1.35% in the low-dose group, compared with the control group, and stains and freckles also were diminished (J. Nutr. Sci. Vitaminol. (Tokyo) 2006;52:383-8).

Stilbenes: Resveratrol
The antioxidant potency of resveratrol has been cited for conferring a wide range of salutary effects, including antitumorigenic and antiaging activity. Recently, a resveratrol-based skin care formulation intended to combat photoaging was reported to exhibit 17-fold greater antioxidant activity than idebenone (J. Cosmet. Dermatol. 2008;7:2-7). In a different study, resveratrol, the primary active polyphenolic constituent in red wine, was assessed in terms of topical/transdermal delivery viability, given the previously established benefits shown via systemic administration. Several hydrogel systems used as resveratrol vehicles were shown to be safe and effective methods for cutaneously delivering the therapeutic effects of this antioxidant (Biol. Pharm. Bull. 2008;31:955-62).

Phenolic Acids: Ferulic Acid
In a small study, a stable formulation of 15% L-corbic acid, 1% alpha-tocopherol, and 0.5% ferulic acid was applied topically to normal-appearing human skin for 4 days, and was found to confer significant photoprotection against solar-simulated UV radiation. The preparation was especially effective at diminishing thymine dimer mutations, which are linked to skin cancer. The authors also noted that the mechanism of action of this antioxidant formulation differs from that of sunscreens and, therefore, may serve as a supplement to such products (J. Am. Acad. Dermatol. 2008;59:418-25). It is worth noting that ferulic acid has been approved as a sunscreen agent in Japan (J. Pharm. Biomed. Anal. 2008;46:645-52).

Conclusion
A brief survey of the polyphenolic landscape obviously cannot do the subject justice. That said, from the dermatologic perspective, it is simply worth noting how often this diverse family of compounds factors occur in to the skin care formulations that are becoming more prevalent in the established armamentarium as well as the direct-to-consumer market.

Given the increasing attention paid here and elsewhere to the impact of diet on the skin, the status of the diverse class of polyphenolic compounds found in a wide array of plants, which includes several antioxidants, appears to be well deserved and warrants much more research.

Many products that tout antioxidant activity include antioxidant ingredients that contain polyphenols. There are numerous classes of polyphenols, which are the largest group of phytochemicals and the most broadly disseminated among plants (J. Am. Diet. Assoc. 1999;99:213-8). They are secondary plant metabolites represented by more than 8,000 naturally occurring compounds.

These widely divergent substances, which exhibit various levels of antioxidant activity, share a common structural component: a phenol or an aromatic ring, usually two, with at least one hydroxyl group, that are linked via a three-carbon bond to form a six-unit heterocyclic ring (J. Nutr. 2003;133:3248S-54S).

Attention has been increasingly focused on polyphenols, as they are known to be an important part of, and the most abundant source of antioxidants in, the human diet. They are present in many vegetables, fruits, herbs, grains, teas, and beans, as well as coffee, propolis, and red wine (Biomed. Pap. Med. Fac. Univ. Palacky Olomouc. Czech Repub. 2003;147:137-45; J. Nutr. 2000;130:2073S-85S; Annu. Rev. Nutr. 2002;22:19-34; Pharmacol. Ther. 2001;90:157-77; Free Radic. Biol. Med. 2001;30:1213-22).

The most prevalent and frequently studied polyphenols are known as flavonoids. Based on the connection of an aromatic ring to the heterocyclic ring, as well as the oxidation state and functional groups of the heterocyclic ring, flavonoids are further divided into flavones (based on the 2-phenylchromen-4-one skeleton, e.g., apigenin and luteolin); flavonols (based on the 3-hydroxy-2-phenylchromen-4-one skeleton and functional group, e.g., quercetin, kaempferol, myricetin, and fisetin); flavanones (based on the 2,3-dihydro-2-phenylchromen-4-one skeleton and functional group, e.g., naringenin, hesperetin, and eriodictyol); isoflavones (based on the 3-phenylchromen-4-one skeleton, e.g., genistein and daidzein); flavanols or catechins (based on the 2-phenyl-3,4-dihydro-2H-chromen-3-ol skeleton and functional groups, e.g., epicatechin, epicatechin 3-gallate, epigallocatechin, epigallocatechin 3-gallate (EGCG), catechin, gallocatechin); anthocyanins (based on the 2-phenylchromenylium ion skeleton, e.g., cyanidin and pelargonidin); and proanthocyanidins or condensed tannins (which are polymer chains of flavanols, such as catechins, and include pycnogenol, leukocyanidin, and leucoanthocyanidin) (Annu. Rev. Nutr. 2002;22:19-34; Asia Pac. J. Clin. Nutr. 2004;13:S72; J. Nutr. 2000;130:2073S-85S; J. Nutr. 2003;133:3248S-54S).
Tannins, phenolic polymers of high molecular weight, are divided into three classes: hydrolyzable tannins (e.g., ellagic acid, found in pomegranates, raspberries, strawberries, cranberries, and walnuts), derived tannins (created during food handling and processing and present in black and oolong teas), and condensed tannins, described above (J. Am. Diet. Assoc. 1999;99:213-8; J. Nutr. 2003;133:3248S-54S).

Some specific flavonoids can be found in the following food sources: flavonols in apples with skin, broccoli, olives, onions, and green and black tea; flavones in celery and parsley; flavonones in grapefruit, oranges, and their juices; and catechins (flavanols) in apples with or without skin, dark chocolate, cocoa, red wine, and green and black tea (Asia Pac. J. Clin. Nutr. 2004;13:S72).

There are a plethora of other polyphenols, many of which confer health benefits, including stilbenes (e.g., resveratrol, found in red wine), lignans (e.g., enterodiol, found in flaxseed and flaxseed oil), and phenolic acids, such as hydroxybenzoic and hydroxycinnamic acids, among which caffeic and ferulic acids are often present in foods.

Broad health benefits have been associated with hundreds of polyphenolic substances. Notably, some of the best known research results on polyphenols have reported on the success of various topical applications of green tea catechins, ferulic acid, resveratrol, and other related compounds (many of which have been addressed in this column). The rest of this discussion focuses on new information regarding systemic efficacy, topical delivery, or applications of a representative from several subclasses of these compounds.

Flavonols: Quercetin
A water-in-oil microemulsion containing quercetin has been shown, in porcine skin in vitro and hairless mouse skin in vivo, to enhance the penetration of the flavonol into the stratum corneum, epidermis, and dermis. The preparation also was found to significantly inhibit ultraviolet B (UVB)-induced metalloproteinase activity and glutathione reduction (Eur. J. Pharm. Biopharm. 2008;69:948-57).

Flavones: Apigenin
The topical application of 4',5,7-trihydroxyflavone (apigenin) on mouse skin has been shown to decrease skin tumor size and incidence induced by UVB exposure (Cancer Res. 2008:68:3057-65). In a different study, the apigenin glycosides 7-O-glucuronide, 7-O-methylglucuronide, and pectolinarin also have been demonstrated to induce collagen type I synthesis in fibroblasts. The investigators found that all tested compounds promoted the activity of prolidase, which initiates the last stage of collagen degradation and is integral to collagen production (Int. J. Mol. Med. 2007;20:889-95).

Flavonones: Naringenin
The citrus flavonone naringenin shows promise as a preventive agent against cutaneous aging as well as carcinogenesis. Naringenin has been demonstrated to exert an antiapoptotic effect in UVB-damaged cells, significantly extending long-term cellular survival, and to facilitate the removal of cyclobutane pyrimidine dimers from the genome (Photochem. Photobiol. 2008;84:307-16).

Isoflavones: Red Clover, Genistein, and Daidzein
Recently, red clover, whose isoflavones had previously been shown to contribute to a low incidence of osteoporosis and menopausal symptoms in high dietary concentrations, was examined for anti-aging effects. Investigators orally administered red clover extract containing 11% isoflavones to ovariectomized rats for 14 weeks, and found that collagen levels increased significantly in the treatment group as compared to the control group. Epidermal thickness and keratinization were normal in the treated group, but were reduced in the control group. The authors concluded that the regular dietary consumption of red clover isoflavones can alleviate cutaneous aging brought on by declines in estrogen (Phytother. Res. 2006;20:1096-9).

In a recent study evaluating the feasibility of skin absorption of the soy isoflavones genistein, daidzein, and glycitein, both genistein and daidzein inhibited UVB-induced hydrogen peroxide synthesis in keratinocytes. Analysis of vehicle effects on in vitro topical delivery revealed that genistein showed better skin absorption than daidzein. The investigators concluded that the topical application of soy isoflavones shows promise as a treatment for photoaging and photodamage (Int. J. Pharm. 2008;364:36-44).

Indeed, the topical application of isoflavones, including genistein and daidzein, has been shown to protect pig skin from photodamage caused by solar-simulated ultraviolet irradiation. Notably, the isoflavone compounds tested were less effective than a topical antioxidant formulation containing vitamins C and E and the phenolic acid ferulic acid (Photodermatol. Photoimmunol. Photomed. 2008;24:61-6).

Catechins (Flavanols): Epigallocatechin 3-gallate
Already considered a potent antioxidant, EGCG continues to receive attention for conferring an expanding range of health benefits. This compound, the most abundant and potent catechin in green tea, has been shown to hinder UVB-induced collagen-degrading matrix metalloproteinases (Food Chem. Toxicol. 2008;46:1298-307).

A different study of EGCG indicated that it hampered the proliferation and migration of keloid fibroblasts in vitro, and also curbed in vivo signs of keloids, by interrupting the signal transducer and activator of the transcription-3 signaling pathway. As a result of these findings, the investigators proposed EGCG as a preventive and therapeutic agent for keloids (J. Invest. Dermatol. 2008;128:2429-41). EGCG also has been suggested as a potential therapeutic approach to atopic dermatitis, given its success against AD-like skin lesions in a murine model (Int. Immunopharmacol. 2008;8:1172-82).

Anthocyanins: Cyanidin
Clearly, all flavonoids are not equal. In a recent study, methanol extracts of black raspberries, strawberries, and blueberries were tested for their capacity to inhibit UV-induced activation of nuclear transcription factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) in mouse epidermal cells. The methanol fractions of black raspberries, which contain the anthocyanin cyanidin 3-rutinoside, were found to time- and dose-dependently inhibit the effects of UV on NF-kappaB and AP-1, unlike the other berries, which do not contain cyanidin 3-rutinoside (Nutr. Cancer 2007;58:205-12).

Another form of cyanidin has also been shown to impart cutaneous benefits. Specifically, pretreatment of human keratinocytes with the anthocyanin cyanidin 3-O-glucoside has been demonstrated to protect against a wide array of UVB-induced damage (J. Agric. Food Chem. 2006;54:4041-7).

Proanthocyanidins: Pycnogenol
Investigators studied pycnogenol in an antioxidant mixture that also included evening primrose and vitamins C and E. After 10 weeks of oral administration to female SKH-1 hairless mice exposed to UVB irradiation three times weekly, the mixture was found to significantly inhibit wrinkle formation by suppressing UVB-induced matrix metalloproteinase activity while promoting collagen production (Photodermatol. Photoimmunol. Photomed. 2007;23:155-62).

Tannins: Ellagic Acid
In a double-blind, placebo-controlled, 4-week trial, investigators assessed the effects of orally administered ellagic acid-rich pomegranate extract on the pigmentation of 13 women after UV exposure. Healthy volunteers were randomly assigned to high-dose, low-dose, and control groups. The results showed that luminance values decreased by 1.73% in the high-dose group and 1.35% in the low-dose group, compared with the control group, and stains and freckles also were diminished (J. Nutr. Sci. Vitaminol. (Tokyo) 2006;52:383-8).

Stilbenes: Resveratrol
The antioxidant potency of resveratrol has been cited for conferring a wide range of salutary effects, including antitumorigenic and antiaging activity. Recently, a resveratrol-based skin care formulation intended to combat photoaging was reported to exhibit 17-fold greater antioxidant activity than idebenone (J. Cosmet. Dermatol. 2008;7:2-7). In a different study, resveratrol, the primary active polyphenolic constituent in red wine, was assessed in terms of topical/transdermal delivery viability, given the previously established benefits shown via systemic administration. Several hydrogel systems used as resveratrol vehicles were shown to be safe and effective methods for cutaneously delivering the therapeutic effects of this antioxidant (Biol. Pharm. Bull. 2008;31:955-62).

Phenolic Acids: Ferulic Acid
In a small study, a stable formulation of 15% L-corbic acid, 1% alpha-tocopherol, and 0.5% ferulic acid was applied topically to normal-appearing human skin for 4 days, and was found to confer significant photoprotection against solar-simulated UV radiation. The preparation was especially effective at diminishing thymine dimer mutations, which are linked to skin cancer. The authors also noted that the mechanism of action of this antioxidant formulation differs from that of sunscreens and, therefore, may serve as a supplement to such products (J. Am. Acad. Dermatol. 2008;59:418-25). It is worth noting that ferulic acid has been approved as a sunscreen agent in Japan (J. Pharm. Biomed. Anal. 2008;46:645-52).

Conclusion
A brief survey of the polyphenolic landscape obviously cannot do the subject justice. That said, from the dermatologic perspective, it is simply worth noting how often this diverse family of compounds factors occur in to the skin care formulations that are becoming more prevalent in the established armamentarium as well as the direct-to-consumer market.

Given the increasing attention paid here and elsewhere to the impact of diet on the skin, the status of the diverse class of polyphenolic compounds found in a wide array of plants, which includes several antioxidants, appears to be well deserved and warrants much more research.

PHOENIX — Dermatologists may be under the clinical impression that botulinum toxin is better suited for the upper face, while fillers are the treatment of choice for the lower face.

However, as demonstrated in a previous upper-face study, the combined use of toxin and filler gave not only a superior aesthetic result but virtually doubled the duration of aesthetic response (Dermatol. Surg. 2003;29:802-9).

To elucidate these findings, Dr. Jean Carruthers and her husband Dr. Alastair Carruthers designed a lower-face study at three clinical sites. Along with Dr. Gary D. Monheit, they recruited 30 women from each site, for a total of 90, for the parallel group study.

They randomized 30 patients to receive onabotulinumtoxinA (Botox, Allergan), 30 to Juvéderm Ultra and/or Juvéderm Ultra Plus (hyaluronic acid, Allergen), and the remaining 30 patients to a combination of both treatments.

They first assessed the 35- to 55-year-old patients at baseline. Each patient was treated once and allowed one touch-up session of filler, but as many treatments with lower-face botulinum toxin as they felt they needed. A blinded rater and a principal investigator followed clinical outcomes over 6 months.

Lip fullness was rated superior in the combination group, Dr. Monheit said at the joint annual meeting of the American Society for Dermatologic Surgery and the American Society of Cosmetic Dermatology and Aesthetic Surgery. Juvéderm alone was found more effective than botulinum toxin alone at increasing ratings on the lip-fullness scale. Photographic analysis confirmed the investigator evaluation.

In terms of oral commissure improvements, the combination outperformed both of the single treatments, although the “filler almost matched it in most aspects,” said Dr. Monheit of the departments of dermatology and ophthalmology at the University of Alabama at Birmingham.

Dr. Jean Carruthers is clinical professor of ophthalmology at the University of British Columbia, Vancouver. Dr. Alastair Carruthers is clinical professor in the department of dermatology at the same university. Investigators asked participants to purse their lips at each assessment. “We took smooch-pose photos to look at perioral lines,” Dr. Monheit said. “We also took grimace photos to show the power of the [depressor anguli oris] muscle.” At maximal contraction, the combination yielded better results again.

The investigators and patients also completed satisfaction questionnaires. They rated multiple areas. “Botox alone pretty well lagged behind [on the] investigator's lip satisfaction questionnaire,” the investigators noted. “The patient questionnaire had pretty much the same results: The combination and filler did best, and the toxin lagged behind.”

At the conclusion of the study, the combination treatment group fared better than the filler or the toxin groups alone on most outcome measures, including lip fullness, oral commissure severity, and perioral line improvement. In addition, subjective patient satisfaction and objective investigator satisfaction rankings were highest in the combined group. Overall, the results in the combined group were better, and the longevity of response was longer. “This is a confirmation of what we do on an everyday basis,” Dr. Monheit said.

Swelling, bruising, asymmetry, and lumps were adverse events recorded in patient diaries and reported by investigators, but these “minor adverse events were rarely noted in subjects with combination treatment,” Dr. Monheit said.

Disclosures: This investigator-initiated study was funded by Allergan. The company had no input on study design or outcome, according to the investigators. Dr. Jean and Alastair Carruthers are both consultants and researchers for Allergan, Merz Pharmaceuticals, and BioForm Medical. Dr. Monheit is a researcher and consultant for Allergan, Genzyme, and Johnson & Johnson, as well as a researcher for Dermik Laboratories, Inamed Aesthetics, and ColBar LifeScience.

PHOENIX — Dermatologists may be under the clinical impression that botulinum toxin is better suited for the upper face, while fillers are the treatment of choice for the lower face.

However, as demonstrated in a previous upper-face study, the combined use of toxin and filler gave not only a superior aesthetic result but virtually doubled the duration of aesthetic response (Dermatol. Surg. 2003;29:802-9).

To elucidate these findings, Dr. Jean Carruthers and her husband Dr. Alastair Carruthers designed a lower-face study at three clinical sites. Along with Dr. Gary D. Monheit, they recruited 30 women from each site, for a total of 90, for the parallel group study.

They randomized 30 patients to receive onabotulinumtoxinA (Botox, Allergan), 30 to Juvéderm Ultra and/or Juvéderm Ultra Plus (hyaluronic acid, Allergen), and the remaining 30 patients to a combination of both treatments.

They first assessed the 35- to 55-year-old patients at baseline. Each patient was treated once and allowed one touch-up session of filler, but as many treatments with lower-face botulinum toxin as they felt they needed. A blinded rater and a principal investigator followed clinical outcomes over 6 months.

Lip fullness was rated superior in the combination group, Dr. Monheit said at the joint annual meeting of the American Society for Dermatologic Surgery and the American Society of Cosmetic Dermatology and Aesthetic Surgery. Juvéderm alone was found more effective than botulinum toxin alone at increasing ratings on the lip-fullness scale. Photographic analysis confirmed the investigator evaluation.

In terms of oral commissure improvements, the combination outperformed both of the single treatments, although the “filler almost matched it in most aspects,” said Dr. Monheit of the departments of dermatology and ophthalmology at the University of Alabama at Birmingham.

Dr. Jean Carruthers is clinical professor of ophthalmology at the University of British Columbia, Vancouver. Dr. Alastair Carruthers is clinical professor in the department of dermatology at the same university. Investigators asked participants to purse their lips at each assessment. “We took smooch-pose photos to look at perioral lines,” Dr. Monheit said. “We also took grimace photos to show the power of the [depressor anguli oris] muscle.” At maximal contraction, the combination yielded better results again.

The investigators and patients also completed satisfaction questionnaires. They rated multiple areas. “Botox alone pretty well lagged behind [on the] investigator's lip satisfaction questionnaire,” the investigators noted. “The patient questionnaire had pretty much the same results: The combination and filler did best, and the toxin lagged behind.”

At the conclusion of the study, the combination treatment group fared better than the filler or the toxin groups alone on most outcome measures, including lip fullness, oral commissure severity, and perioral line improvement. In addition, subjective patient satisfaction and objective investigator satisfaction rankings were highest in the combined group. Overall, the results in the combined group were better, and the longevity of response was longer. “This is a confirmation of what we do on an everyday basis,” Dr. Monheit said.

Swelling, bruising, asymmetry, and lumps were adverse events recorded in patient diaries and reported by investigators, but these “minor adverse events were rarely noted in subjects with combination treatment,” Dr. Monheit said.

Disclosures: This investigator-initiated study was funded by Allergan. The company had no input on study design or outcome, according to the investigators. Dr. Jean and Alastair Carruthers are both consultants and researchers for Allergan, Merz Pharmaceuticals, and BioForm Medical. Dr. Monheit is a researcher and consultant for Allergan, Genzyme, and Johnson & Johnson, as well as a researcher for Dermik Laboratories, Inamed Aesthetics, and ColBar LifeScience.

PHOENIX — Dermatologists may be under the clinical impression that botulinum toxin is better suited for the upper face, while fillers are the treatment of choice for the lower face.

However, as demonstrated in a previous upper-face study, the combined use of toxin and filler gave not only a superior aesthetic result but virtually doubled the duration of aesthetic response (Dermatol. Surg. 2003;29:802-9).

To elucidate these findings, Dr. Jean Carruthers and her husband Dr. Alastair Carruthers designed a lower-face study at three clinical sites. Along with Dr. Gary D. Monheit, they recruited 30 women from each site, for a total of 90, for the parallel group study.

They randomized 30 patients to receive onabotulinumtoxinA (Botox, Allergan), 30 to Juvéderm Ultra and/or Juvéderm Ultra Plus (hyaluronic acid, Allergen), and the remaining 30 patients to a combination of both treatments.

They first assessed the 35- to 55-year-old patients at baseline. Each patient was treated once and allowed one touch-up session of filler, but as many treatments with lower-face botulinum toxin as they felt they needed. A blinded rater and a principal investigator followed clinical outcomes over 6 months.

Lip fullness was rated superior in the combination group, Dr. Monheit said at the joint annual meeting of the American Society for Dermatologic Surgery and the American Society of Cosmetic Dermatology and Aesthetic Surgery. Juvéderm alone was found more effective than botulinum toxin alone at increasing ratings on the lip-fullness scale. Photographic analysis confirmed the investigator evaluation.

In terms of oral commissure improvements, the combination outperformed both of the single treatments, although the “filler almost matched it in most aspects,” said Dr. Monheit of the departments of dermatology and ophthalmology at the University of Alabama at Birmingham.

Dr. Jean Carruthers is clinical professor of ophthalmology at the University of British Columbia, Vancouver. Dr. Alastair Carruthers is clinical professor in the department of dermatology at the same university. Investigators asked participants to purse their lips at each assessment. “We took smooch-pose photos to look at perioral lines,” Dr. Monheit said. “We also took grimace photos to show the power of the [depressor anguli oris] muscle.” At maximal contraction, the combination yielded better results again.

The investigators and patients also completed satisfaction questionnaires. They rated multiple areas. “Botox alone pretty well lagged behind [on the] investigator's lip satisfaction questionnaire,” the investigators noted. “The patient questionnaire had pretty much the same results: The combination and filler did best, and the toxin lagged behind.”

At the conclusion of the study, the combination treatment group fared better than the filler or the toxin groups alone on most outcome measures, including lip fullness, oral commissure severity, and perioral line improvement. In addition, subjective patient satisfaction and objective investigator satisfaction rankings were highest in the combined group. Overall, the results in the combined group were better, and the longevity of response was longer. “This is a confirmation of what we do on an everyday basis,” Dr. Monheit said.

Swelling, bruising, asymmetry, and lumps were adverse events recorded in patient diaries and reported by investigators, but these “minor adverse events were rarely noted in subjects with combination treatment,” Dr. Monheit said.

Disclosures: This investigator-initiated study was funded by Allergan. The company had no input on study design or outcome, according to the investigators. Dr. Jean and Alastair Carruthers are both consultants and researchers for Allergan, Merz Pharmaceuticals, and BioForm Medical. Dr. Monheit is a researcher and consultant for Allergan, Genzyme, and Johnson & Johnson, as well as a researcher for Dermik Laboratories, Inamed Aesthetics, and ColBar LifeScience.

PHOENIX — Some devices commonly touted for skin tightening are supported by evidence-based medicine, although few have data at the randomized, controlled-trial level, according to Dr. E. Victor Ross.

“We have a lot of skin-tightening devices … and I applaud those companies who have spent money trying to do good, controlled studies,” Dr. Ross said at the joint annual meeting of the American Society for Dermatologic Surgery and the American Society of Cosmetic Dermatology and Aesthetic Surgery.

Thermage (Solta Medical Inc., Hayward, Calif.) leads in the literature in terms of strong evidence to support its use for skin tightening, Dr. Ross said. For example, 8 of 60 published studies are “good randomized, controlled trials,” meaning they provide level 1 evidence of clinical benefit. Level 2 evidence is a nonrandomized study, whereas level 3 evidence is anecdotal or case reports showing benefit of a device.

Thermage is included in the greatest number of published studies because it has been marketed the longest, said Dr. Ross, director of the Scripps Clinic Laser and Cosmetic Dermatology Center in Carmel Valley, Calif.

Other skin-tightening devices are supported by less evidence. For example, there are no published, peer-reviewed studies about the ultrasound-focusing Ulthera system (Ulthera, Mesa, Ariz.). “But at least … you can see changes on routine histology,” he said. The Food and Drug Administration cleared marketing of the Ulthera system in September for noninvasive eyebrow lifts.

Although many manufacturers promote the “real-time temperature rise” of their devices, this may not be a fair basis for comparison because different devices heat to different levels of the skin, he said.

Another option in the skin-tightening market is the UltraShape device (UltraShape, San Ramon, Calif.). “UltraShape does have some good papers—at least two of nine are level 1, prospective randomized studies,” Dr. Ross said.

In contrast, none of the six published studies on the Accent laser system (Alma Lasers, Buffalo Grove, Ill.) are designed to provide level 1 evidence. “My interpretation of the six studies so far … is they are level 2 or 3. Also, clinical photos were not blinded as to which ones were 'before' and 'after,'” Dr. Ross said.

A promising device not yet available in the United States is the high-intensity, focused, ultrasound LipoSonix system (Medicis Technologies, Bothell, Wash.), he said. It is approved for use in Europe and Canada. Foamy macrophages—suggesting lipid uptake—are seen on histology after use of the LipoSonix device, suggesting a true clinical effect.

Disclosures: Dr. Ross is a researcher and/or consultant for Palomar Medical Technologies Inc., Lumenis Ltd., Cutera Inc., Candela Corp., Alma Lasers Ltd., Iridex Corp., Laserscope, Ulthera Inc., and Sciton Inc.

PHOENIX — Some devices commonly touted for skin tightening are supported by evidence-based medicine, although few have data at the randomized, controlled-trial level, according to Dr. E. Victor Ross.

“We have a lot of skin-tightening devices … and I applaud those companies who have spent money trying to do good, controlled studies,” Dr. Ross said at the joint annual meeting of the American Society for Dermatologic Surgery and the American Society of Cosmetic Dermatology and Aesthetic Surgery.

Thermage (Solta Medical Inc., Hayward, Calif.) leads in the literature in terms of strong evidence to support its use for skin tightening, Dr. Ross said. For example, 8 of 60 published studies are “good randomized, controlled trials,” meaning they provide level 1 evidence of clinical benefit. Level 2 evidence is a nonrandomized study, whereas level 3 evidence is anecdotal or case reports showing benefit of a device.

Thermage is included in the greatest number of published studies because it has been marketed the longest, said Dr. Ross, director of the Scripps Clinic Laser and Cosmetic Dermatology Center in Carmel Valley, Calif.

Other skin-tightening devices are supported by less evidence. For example, there are no published, peer-reviewed studies about the ultrasound-focusing Ulthera system (Ulthera, Mesa, Ariz.). “But at least … you can see changes on routine histology,” he said. The Food and Drug Administration cleared marketing of the Ulthera system in September for noninvasive eyebrow lifts.

Although many manufacturers promote the “real-time temperature rise” of their devices, this may not be a fair basis for comparison because different devices heat to different levels of the skin, he said.

Another option in the skin-tightening market is the UltraShape device (UltraShape, San Ramon, Calif.). “UltraShape does have some good papers—at least two of nine are level 1, prospective randomized studies,” Dr. Ross said.

In contrast, none of the six published studies on the Accent laser system (Alma Lasers, Buffalo Grove, Ill.) are designed to provide level 1 evidence. “My interpretation of the six studies so far … is they are level 2 or 3. Also, clinical photos were not blinded as to which ones were 'before' and 'after,'” Dr. Ross said.

A promising device not yet available in the United States is the high-intensity, focused, ultrasound LipoSonix system (Medicis Technologies, Bothell, Wash.), he said. It is approved for use in Europe and Canada. Foamy macrophages—suggesting lipid uptake—are seen on histology after use of the LipoSonix device, suggesting a true clinical effect.

Disclosures: Dr. Ross is a researcher and/or consultant for Palomar Medical Technologies Inc., Lumenis Ltd., Cutera Inc., Candela Corp., Alma Lasers Ltd., Iridex Corp., Laserscope, Ulthera Inc., and Sciton Inc.

PHOENIX — Some devices commonly touted for skin tightening are supported by evidence-based medicine, although few have data at the randomized, controlled-trial level, according to Dr. E. Victor Ross.

“We have a lot of skin-tightening devices … and I applaud those companies who have spent money trying to do good, controlled studies,” Dr. Ross said at the joint annual meeting of the American Society for Dermatologic Surgery and the American Society of Cosmetic Dermatology and Aesthetic Surgery.

Thermage (Solta Medical Inc., Hayward, Calif.) leads in the literature in terms of strong evidence to support its use for skin tightening, Dr. Ross said. For example, 8 of 60 published studies are “good randomized, controlled trials,” meaning they provide level 1 evidence of clinical benefit. Level 2 evidence is a nonrandomized study, whereas level 3 evidence is anecdotal or case reports showing benefit of a device.

Thermage is included in the greatest number of published studies because it has been marketed the longest, said Dr. Ross, director of the Scripps Clinic Laser and Cosmetic Dermatology Center in Carmel Valley, Calif.

Other skin-tightening devices are supported by less evidence. For example, there are no published, peer-reviewed studies about the ultrasound-focusing Ulthera system (Ulthera, Mesa, Ariz.). “But at least … you can see changes on routine histology,” he said. The Food and Drug Administration cleared marketing of the Ulthera system in September for noninvasive eyebrow lifts.

Although many manufacturers promote the “real-time temperature rise” of their devices, this may not be a fair basis for comparison because different devices heat to different levels of the skin, he said.

Another option in the skin-tightening market is the UltraShape device (UltraShape, San Ramon, Calif.). “UltraShape does have some good papers—at least two of nine are level 1, prospective randomized studies,” Dr. Ross said.

In contrast, none of the six published studies on the Accent laser system (Alma Lasers, Buffalo Grove, Ill.) are designed to provide level 1 evidence. “My interpretation of the six studies so far … is they are level 2 or 3. Also, clinical photos were not blinded as to which ones were 'before' and 'after,'” Dr. Ross said.

A promising device not yet available in the United States is the high-intensity, focused, ultrasound LipoSonix system (Medicis Technologies, Bothell, Wash.), he said. It is approved for use in Europe and Canada. Foamy macrophages—suggesting lipid uptake—are seen on histology after use of the LipoSonix device, suggesting a true clinical effect.

Disclosures: Dr. Ross is a researcher and/or consultant for Palomar Medical Technologies Inc., Lumenis Ltd., Cutera Inc., Candela Corp., Alma Lasers Ltd., Iridex Corp., Laserscope, Ulthera Inc., and Sciton Inc.

DermaDoctor Body Guard SPF-30 sunscreen works to avert sun damage on the face and body. The formulation contains the antioxidant epigallocatechin gallate (EGCG), the active ingredient in green tea, to counter UV damage to the skin. It also contains sebum-sequestering microparticles, which reduce excess surface oils that are already present on the skin, as well as botanicals for soothing and sodium hyaluronate for moisturizing. The product is noncomedogenic and leaves a matte finish. A tube of the sunscreen retails for about $25.

DermaDoctor Inc.

www.dermadoctor.com

DermaDoctor Body Guard SPF-30 sunscreen works to avert sun damage on the face and body. The formulation contains the antioxidant epigallocatechin gallate (EGCG), the active ingredient in green tea, to counter UV damage to the skin. It also contains sebum-sequestering microparticles, which reduce excess surface oils that are already present on the skin, as well as botanicals for soothing and sodium hyaluronate for moisturizing. The product is noncomedogenic and leaves a matte finish. A tube of the sunscreen retails for about $25.

DermaDoctor Inc.

www.dermadoctor.com

DermaDoctor Body Guard SPF-30 sunscreen works to avert sun damage on the face and body. The formulation contains the antioxidant epigallocatechin gallate (EGCG), the active ingredient in green tea, to counter UV damage to the skin. It also contains sebum-sequestering microparticles, which reduce excess surface oils that are already present on the skin, as well as botanicals for soothing and sodium hyaluronate for moisturizing. The product is noncomedogenic and leaves a matte finish. A tube of the sunscreen retails for about $25.

DermaDoctor Inc.

www.dermadoctor.com

Perfect Reflection is an antiaging serum combining antioxidants (vitamins A, C, D, and CoQ10) with 17 plant-derived amino acids. The 17-amino acid formulation is unique to AminoGenesis products. This water-based formulation from the company is designed to moisturize and rejuventate facial skin and to protect from radical damage. Vitamin A improves skin elasticity and smoothness while vitamin C protects collegen from oxidation and reduces dark spots. Vitamin D is key in epidermal cell turnover. CoQ10 helps preserve vitamin E in the skin. Perfect Reflection should be used daily after cleansing and before moisturizer. The product comes in a 1.3-oz package, and the cost is $69.

AminoGenesis

www.photolagen.com

Perfect Reflection is an antiaging serum combining antioxidants (vitamins A, C, D, and CoQ10) with 17 plant-derived amino acids. The 17-amino acid formulation is unique to AminoGenesis products. This water-based formulation from the company is designed to moisturize and rejuventate facial skin and to protect from radical damage. Vitamin A improves skin elasticity and smoothness while vitamin C protects collegen from oxidation and reduces dark spots. Vitamin D is key in epidermal cell turnover. CoQ10 helps preserve vitamin E in the skin. Perfect Reflection should be used daily after cleansing and before moisturizer. The product comes in a 1.3-oz package, and the cost is $69.

AminoGenesis

www.photolagen.com

Perfect Reflection is an antiaging serum combining antioxidants (vitamins A, C, D, and CoQ10) with 17 plant-derived amino acids. The 17-amino acid formulation is unique to AminoGenesis products. This water-based formulation from the company is designed to moisturize and rejuventate facial skin and to protect from radical damage. Vitamin A improves skin elasticity and smoothness while vitamin C protects collegen from oxidation and reduces dark spots. Vitamin D is key in epidermal cell turnover. CoQ10 helps preserve vitamin E in the skin. Perfect Reflection should be used daily after cleansing and before moisturizer. The product comes in a 1.3-oz package, and the cost is $69.

AminoGenesis

www.photolagen.com

SEATTLE — Successful reconstruction of facial defects created by Mohs surgery requires knowledge not only of appropriate operative techniques, but also of patients and their cancers.

Assessing a patient's skin cancer risk factors is key before repairing any Mohs defect, according to Dr. Michael L. Bentz, professor and chairman of the division of plastic and reconstructive surgery at the University of Wisconsin, Madison' “It's important to know who is more likely to come back with other skin cancers because it may change the way you stage and think about the reconstruction,” he said.

A prerequisite for successful reconstruction is ensuring that the cancer has been adequately treated, Dr. Bentz said at the annual meeting of the American Society of Plastic Surgeons.

“The first thing you are going to throw at these patients reconstructively is your best option, so you want to make sure that you have not compromised that by inadequate primary tumor treatment.” He recommended a good working relationship between the Mohs and reconstructing surgeon (if applicable), a careful review of pathology reports, and, if necessary, a reassessment of margins.

“Knowing your tumor is important,” he said. It is prudent to avoid initial definitive reconstruction of defects from dermatofibrosarcoma protuberans because of its high recurrence rate. “My goal with these is to get them grafted, let them sit a year or two, and then come back and do the definitive reconstruction,” he explained.

Maximizing the likelihood of a successful and uneventful reconstruction also requires a thorough preoperative assessment of the patient, given that most patients with skin cancer are older, with comorbidities, and that many take medications, particularly anticoagulants, that may need to be tapered.

Dr. Bentz and Dr. Frederick J. Menick, a plastic surgeon in private practice in Tucson, Ariz., went on to discuss the best way to repair defects and the best flaps to use.

▸ Pericranial flaps. These flaps are often a good option for repairing Mohs defects of the forehead, especially if bone is exposed, noted Dr. Bentz. “For patients who particularly are at risk of other skin cancers, you want to use big flaps because if you use small flaps, you will have difficulty using them again,” he said.

▸ Cheek flaps. If they are elevated to reconstruct lateral forehead defects, cheek flaps should be suspended from bone. “They weigh a fair amount and there is some tension on them,” he said. “So taking a permanent suture and suspending them to the appropriate tension point in bone, with or without drilling holes, helps avoid postoperative complications.”

Reconstructing Mohs cheek defects poses several challenges, including the limited number of lines available for hiding donor sites and the potential for distorting the eyelid. “You want to be thoughtful about how you reallocate cheek tissue, trying to hide your donor site and yet minimize the associated complications,” he said.

▸ Lip defects. Principles of cleft lip repair are often helpful in reconstructing larger Mohs defects of the lip, according to Dr. Bentz. “Don't be afraid to take the whole lip down to full-thickness fashion and put it back together,” he advised.

▸ Ear defects. Small defects can be reconstructed with full-thickness grafts, ideally taken from somewhere other than the ipsilateral retroauricular area, given the possibility of subsequent cancers of that ear requiring a retroauricular flap. Large ear defects can be reconstructed with a variety of techniques, but they all require attention to avoid constricting or accentuating the ear.

▸ Nose defects. When reconstructing small, superficial Mohs defects of the nose, Dr. Menick said that he mainly uses secondary healing, small composite grafts (for minor rim defects), and one-stage nasolabial flaps (for alar sidewall defects), along with a lot of full-thickness forehead skin grafts.

When reconstructing Mohs defects of the nose that are large (over 1.5 cm in diameter), deep, or adversely located (affecting the tip or columella), he recommended a forehead flap over the two-stage nasolabial flap. The forehead flap does not distort the nasolabial fold, is less obvious during the maturation phase, and never dies or contracts excessively.

▸ Forehead grafts. The secret to getting good results with a forehead skin graft is to not apply it right after the Mohs excision or if a Bovie has been used in the area, noted Dr. Menick. “I send the patient home, have them put Vaseline on the defect, wash it with soap and water, [and] wait about 14 days till it starts to granulate and all that burn injury is spit out,” he explained.

As to the type of forehead flap, he expressed a preference for the vertical flap, which, compared with the oblique flap, is much less likely to distort the eyebrow and leaves more options if patients need a second flap. “The vertical forehead flap is reliable, efficient, more vascular, and more widely applicable—it works like a charm,” he said.

Dr. Menick also endorsed the three-stage forehead flap over the two-stage because the added intermediate operation provides the ability to sculpt and contour the nose. Other relative merits include its provision of a thin, supple cover; a maximal blood supply; and an ideal framework. Adding an intermediate operation lengthens reconstruction from a 1-month procedure to a 2-month procedure, he acknowledged, but patients generally tolerate it, especially given the aesthetic outcome.

Disclosures: Dr. Bentz and Dr. Menick had no relevant conflicts of interest.

This patient's defect from Mohs surgery was repaired with a modified folding line technique developed by Dr. Frederick J. Menick as part of his three-stage forehead flap approach.

Source Photos courtesy Dr. Frederick J. Menick

SEATTLE — Successful reconstruction of facial defects created by Mohs surgery requires knowledge not only of appropriate operative techniques, but also of patients and their cancers.

Assessing a patient's skin cancer risk factors is key before repairing any Mohs defect, according to Dr. Michael L. Bentz, professor and chairman of the division of plastic and reconstructive surgery at the University of Wisconsin, Madison' “It's important to know who is more likely to come back with other skin cancers because it may change the way you stage and think about the reconstruction,” he said.

A prerequisite for successful reconstruction is ensuring that the cancer has been adequately treated, Dr. Bentz said at the annual meeting of the American Society of Plastic Surgeons.

“The first thing you are going to throw at these patients reconstructively is your best option, so you want to make sure that you have not compromised that by inadequate primary tumor treatment.” He recommended a good working relationship between the Mohs and reconstructing surgeon (if applicable), a careful review of pathology reports, and, if necessary, a reassessment of margins.

“Knowing your tumor is important,” he said. It is prudent to avoid initial definitive reconstruction of defects from dermatofibrosarcoma protuberans because of its high recurrence rate. “My goal with these is to get them grafted, let them sit a year or two, and then come back and do the definitive reconstruction,” he explained.

Maximizing the likelihood of a successful and uneventful reconstruction also requires a thorough preoperative assessment of the patient, given that most patients with skin cancer are older, with comorbidities, and that many take medications, particularly anticoagulants, that may need to be tapered.

Dr. Bentz and Dr. Frederick J. Menick, a plastic surgeon in private practice in Tucson, Ariz., went on to discuss the best way to repair defects and the best flaps to use.

▸ Pericranial flaps. These flaps are often a good option for repairing Mohs defects of the forehead, especially if bone is exposed, noted Dr. Bentz. “For patients who particularly are at risk of other skin cancers, you want to use big flaps because if you use small flaps, you will have difficulty using them again,” he said.

▸ Cheek flaps. If they are elevated to reconstruct lateral forehead defects, cheek flaps should be suspended from bone. “They weigh a fair amount and there is some tension on them,” he said. “So taking a permanent suture and suspending them to the appropriate tension point in bone, with or without drilling holes, helps avoid postoperative complications.”

Reconstructing Mohs cheek defects poses several challenges, including the limited number of lines available for hiding donor sites and the potential for distorting the eyelid. “You want to be thoughtful about how you reallocate cheek tissue, trying to hide your donor site and yet minimize the associated complications,” he said.

▸ Lip defects. Principles of cleft lip repair are often helpful in reconstructing larger Mohs defects of the lip, according to Dr. Bentz. “Don't be afraid to take the whole lip down to full-thickness fashion and put it back together,” he advised.

▸ Ear defects. Small defects can be reconstructed with full-thickness grafts, ideally taken from somewhere other than the ipsilateral retroauricular area, given the possibility of subsequent cancers of that ear requiring a retroauricular flap. Large ear defects can be reconstructed with a variety of techniques, but they all require attention to avoid constricting or accentuating the ear.

▸ Nose defects. When reconstructing small, superficial Mohs defects of the nose, Dr. Menick said that he mainly uses secondary healing, small composite grafts (for minor rim defects), and one-stage nasolabial flaps (for alar sidewall defects), along with a lot of full-thickness forehead skin grafts.

When reconstructing Mohs defects of the nose that are large (over 1.5 cm in diameter), deep, or adversely located (affecting the tip or columella), he recommended a forehead flap over the two-stage nasolabial flap. The forehead flap does not distort the nasolabial fold, is less obvious during the maturation phase, and never dies or contracts excessively.

▸ Forehead grafts. The secret to getting good results with a forehead skin graft is to not apply it right after the Mohs excision or if a Bovie has been used in the area, noted Dr. Menick. “I send the patient home, have them put Vaseline on the defect, wash it with soap and water, [and] wait about 14 days till it starts to granulate and all that burn injury is spit out,” he explained.

As to the type of forehead flap, he expressed a preference for the vertical flap, which, compared with the oblique flap, is much less likely to distort the eyebrow and leaves more options if patients need a second flap. “The vertical forehead flap is reliable, efficient, more vascular, and more widely applicable—it works like a charm,” he said.

Dr. Menick also endorsed the three-stage forehead flap over the two-stage because the added intermediate operation provides the ability to sculpt and contour the nose. Other relative merits include its provision of a thin, supple cover; a maximal blood supply; and an ideal framework. Adding an intermediate operation lengthens reconstruction from a 1-month procedure to a 2-month procedure, he acknowledged, but patients generally tolerate it, especially given the aesthetic outcome.

Disclosures: Dr. Bentz and Dr. Menick had no relevant conflicts of interest.

This patient's defect from Mohs surgery was repaired with a modified folding line technique developed by Dr. Frederick J. Menick as part of his three-stage forehead flap approach.

Source Photos courtesy Dr. Frederick J. Menick

SEATTLE — Successful reconstruction of facial defects created by Mohs surgery requires knowledge not only of appropriate operative techniques, but also of patients and their cancers.

Assessing a patient's skin cancer risk factors is key before repairing any Mohs defect, according to Dr. Michael L. Bentz, professor and chairman of the division of plastic and reconstructive surgery at the University of Wisconsin, Madison' “It's important to know who is more likely to come back with other skin cancers because it may change the way you stage and think about the reconstruction,” he said.

A prerequisite for successful reconstruction is ensuring that the cancer has been adequately treated, Dr. Bentz said at the annual meeting of the American Society of Plastic Surgeons.

“The first thing you are going to throw at these patients reconstructively is your best option, so you want to make sure that you have not compromised that by inadequate primary tumor treatment.” He recommended a good working relationship between the Mohs and reconstructing surgeon (if applicable), a careful review of pathology reports, and, if necessary, a reassessment of margins.

“Knowing your tumor is important,” he said. It is prudent to avoid initial definitive reconstruction of defects from dermatofibrosarcoma protuberans because of its high recurrence rate. “My goal with these is to get them grafted, let them sit a year or two, and then come back and do the definitive reconstruction,” he explained.

Maximizing the likelihood of a successful and uneventful reconstruction also requires a thorough preoperative assessment of the patient, given that most patients with skin cancer are older, with comorbidities, and that many take medications, particularly anticoagulants, that may need to be tapered.

Dr. Bentz and Dr. Frederick J. Menick, a plastic surgeon in private practice in Tucson, Ariz., went on to discuss the best way to repair defects and the best flaps to use.

▸ Pericranial flaps. These flaps are often a good option for repairing Mohs defects of the forehead, especially if bone is exposed, noted Dr. Bentz. “For patients who particularly are at risk of other skin cancers, you want to use big flaps because if you use small flaps, you will have difficulty using them again,” he said.

▸ Cheek flaps. If they are elevated to reconstruct lateral forehead defects, cheek flaps should be suspended from bone. “They weigh a fair amount and there is some tension on them,” he said. “So taking a permanent suture and suspending them to the appropriate tension point in bone, with or without drilling holes, helps avoid postoperative complications.”

Reconstructing Mohs cheek defects poses several challenges, including the limited number of lines available for hiding donor sites and the potential for distorting the eyelid. “You want to be thoughtful about how you reallocate cheek tissue, trying to hide your donor site and yet minimize the associated complications,” he said.

▸ Lip defects. Principles of cleft lip repair are often helpful in reconstructing larger Mohs defects of the lip, according to Dr. Bentz. “Don't be afraid to take the whole lip down to full-thickness fashion and put it back together,” he advised.

▸ Ear defects. Small defects can be reconstructed with full-thickness grafts, ideally taken from somewhere other than the ipsilateral retroauricular area, given the possibility of subsequent cancers of that ear requiring a retroauricular flap. Large ear defects can be reconstructed with a variety of techniques, but they all require attention to avoid constricting or accentuating the ear.

▸ Nose defects. When reconstructing small, superficial Mohs defects of the nose, Dr. Menick said that he mainly uses secondary healing, small composite grafts (for minor rim defects), and one-stage nasolabial flaps (for alar sidewall defects), along with a lot of full-thickness forehead skin grafts.

When reconstructing Mohs defects of the nose that are large (over 1.5 cm in diameter), deep, or adversely located (affecting the tip or columella), he recommended a forehead flap over the two-stage nasolabial flap. The forehead flap does not distort the nasolabial fold, is less obvious during the maturation phase, and never dies or contracts excessively.

▸ Forehead grafts. The secret to getting good results with a forehead skin graft is to not apply it right after the Mohs excision or if a Bovie has been used in the area, noted Dr. Menick. “I send the patient home, have them put Vaseline on the defect, wash it with soap and water, [and] wait about 14 days till it starts to granulate and all that burn injury is spit out,” he explained.

As to the type of forehead flap, he expressed a preference for the vertical flap, which, compared with the oblique flap, is much less likely to distort the eyebrow and leaves more options if patients need a second flap. “The vertical forehead flap is reliable, efficient, more vascular, and more widely applicable—it works like a charm,” he said.

Dr. Menick also endorsed the three-stage forehead flap over the two-stage because the added intermediate operation provides the ability to sculpt and contour the nose. Other relative merits include its provision of a thin, supple cover; a maximal blood supply; and an ideal framework. Adding an intermediate operation lengthens reconstruction from a 1-month procedure to a 2-month procedure, he acknowledged, but patients generally tolerate it, especially given the aesthetic outcome.

Disclosures: Dr. Bentz and Dr. Menick had no relevant conflicts of interest.

This patient's defect from Mohs surgery was repaired with a modified folding line technique developed by Dr. Frederick J. Menick as part of his three-stage forehead flap approach.

Source Photos courtesy Dr. Frederick J. Menick