12
Topicals in Skin Rejuvenation: Prescription Topicals Noëlle S. Sherber, MD, FAAD1
Facial Plast Surg 2014;30:12–15.
Abstract Keywords
► ► ► ► ►
skin care retinoids glycolic acid hydroquinone antiaging
Address for correspondence Noëlle S. Sherber, MD, FAAD, Sherber þ Rad, 1101 15th Street, NW, Washington, DC 20005 (e-mail: [email protected]).
With the recent proliferation of over the counter cosmeceuticals, prescription topical skin treatments have the cache of being evidence-based and not being available outside the setting of a patient–physician interaction. In the setting of facial rejuvenation, patient demand for prescription topical skin treatments falls into three main roles: (1) stimulation of collagen production; (2) improvement of dyspigmentation; and (3) amelioration of adult acne.
Stimulation of Collagen Production Many over-the-counter (OTC) antiaging topical treatments claim to stimulate collagen production, but most base this on in vitro data. Since cultured skin fibroblasts are so easily triggered to make collagen in vitro when agitated by drops of product being added to them, these data should not be extrapolated to actual in vivo use. The best studies for assessing realistic results from topical ingredients are randomized, double blind, vehicle-controlled trials in which each subject serves as an internal control with biopsies of the treatment and vehicle areas of each subject’s skin obtained and analyzed. These sorts of studies are rarely, if ever, conducted with cosmeceuticals, but can be found in the peer-reviewed literature on certain prescription topical skin treatments. The strength of these data is appealing to patients who want a more evidence-based approach to their antiaging concerns.
Glycolic Acid The understanding of the skin rejuvenating benefits of glycolic acid became further understood in 2001 with the publication of a randomized, double blind, vehicle-controlled trial examining the effects of 20% glycolic acid lotion (pH 3.9) as compared with a lotion vehicle when applied to the forearm twice daily for 3 months in 12 female subjects aged 51 to 68 years.1 One forearm was treated with the active ingredient, and the other received vehicle, and paired 4 mm punch biopsies were performed at the end of the study
Issue Theme Classical and State-of-theArt Skin Rejuvenation; Guest Editors, Lisa D. Grunebaum, MD, and Noëlle S. Sherber, MD, FAAD
period. While the sample size in this study was small, statistically significant differences (p < 0.05) in the primary endpoints could be ascertained at this power. In the treatment group, the epidermal thickness was 16.5% greater than in the control group, and there was a 180% increase in total epidermal hyaluronic acid and 9.4% epidermal hyaluronic acid staining in the treatment group as compared with the control. Notably, there was a 280% increase in collagen gene expression (dermal type I collagen mRNA) in the treatment group as compared with control samples. The clinical implications of these findings include a more plumped-up appearance to the skin, since even small increases in glycosaminoglycan (GAG) result in large increases in skin hydration given that they can bind up to 1,000 times their weight in water. Increased GAG production also precedes collagen formation. While a statistically significant 2.8fold increase in collagen gene expression was demonstrated in this study at the 3-month study endpoint, the increase in GAGs may be indicative that collagen production might be even greater in the longer term. Glycolic acid has become a very popular ingredient in OTC cosmeceuticals. However, the lack of regulation of these products has inherent risks. The guideline for cosmetic chemists to formulate OTC products is that the pH should be a minimum of 3.5, but one popular OTC glycolic acid serum has a pH of 2.3, which can cause problematic inflammation. The control over glycolic acid percentage and pH in prescription formulations, whether physician-administered or
Copyright © 2014 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662.
DOI http://dx.doi.org/ 10.1055/s-0033-1363763. ISSN 0736-6825.
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
1 Sherber þ Rad, Northwest, Washington, District of Columbia
Prescription Topicals in Skin Rejuvenation
Treatment of Dyspigmentation One of the hallmarks of older skin is uneven pigmentation, and improving this for a patient can make them look years younger as a 2010 study showed that using computer enhancement to remove discolorations on facial skin resulted in subjects thinking that the person in the photo was 1 to 5 years younger than her actual age.5 Smoothing lines and wrinkles resulted in a more significant decrease in perceived age than evening out pigmentation, but combing the two effects produced the greatest effect with a decrease in perceived age of 15 years. So, combining brightening treatments with revolumizing and treatment of dynamic rhytids is an optimal approach to rejuvenation. (Treatment of unwanted pigmentation is discussed more in depth in another chapter in this issue entitled “Treatment of Unwanted Pigment.”)
Tretinoin Retinoids have long been the gold standard ingredients for stimulating neocollagenesis, with a longstanding body of literature supporting their role in restoring dermal collagen in photoaged skin.2 Contrary to what some have believed, the degree of improvement seen with topical retinoid therapy does not correlate with the degree of irritation, or retinoid dermatitis, achieved through treatment. In a randomized vehicle-controlled trial of nearly 100 subjects, both tretinoin 0.1 and 0.025%, respectively, produced statistically significant improvement in photoaging as compared with vehicle, but despite 3-fold greater incidence of irritation in the tretinoin 0.1% group as compared with the 0.025% group, there are no statistically significant difference in efficacy between the two tretinoin treatment groups.3 Newer formulations of tretinoin are aimed at minimizing retinoid dermatitis resulting from treatment, which generally improved patient adherence to the treatment regimen. Atralin gel (Medicis; a division of Valeant Pharmaceuticals International., Inc., Bridgewater, NJ) has been the first prescription retinoid to combine tretinoin 0.05% with hydrating hyaluronic acid to minimize xerosis from treatment. The light gel texture of this product makes it ideal for patients to use as a serum underneath a rich occlusive moisturizer before bed. For those patients who prefer a cream formulation, ReFissa (Suneva Medical, San Diego, CA) offers a fragrance-free formulation of tretinoin 0.05% cream as an alternative to the heavily scented Renova form of tretinoin 0.02% cream or 0.05% emollient cream that peaked in popularity several years ago. For patients with sensitive skin who find that they cannot tolerate even the newer formulations of prescription retinoids for overnight use, short-contact therapy is an excellent option. The efficacy of short-contact therapy was first established in the setting of tazarotene treatment for acne.4 Since that time, dermatologists have been incorporating this technique into their practices for both acne treatment and the treatment of photoaging. Patients are instructed to apply a thin layer of the prescription retinoid to a clean dry face, and to let it remain in place an average of 5 minutes before cleansing thoroughly and moisturizing. This can work very well for mature skin types who develop treatment-limiting xerosis from having a retinoid in contact with their skin overnight.
13
Hydroquinone Dermatologists have long observed clinically that employing a synergistic approach to the treatment of solar dyschromia is superior to monotherapy with a tyrosinase inhibitor such as hydroquinone. This was substantiated in a 2007 study comparing 4% hydroquinone to combination therapy with 4% hydroquinone, 0.05% tretinoin, and 0.01% fluocinolone acetonide for the treatment of melasma.6 While the study was nonblinded, daily use of the triple-combination therapy resulted in 35% of subjects achieving melasma clearance by investigator rating, versus 5.1% of patients who were treated with 4% hydroquinone twice daily. Daily use is often a better schedule for patient treatment adherence than twice daily application, which is an additional rationale for triple-combination therapy. This triple-combination therapy for the treatment of dyspigmentation, 4% hydroquinone, 0.05% tretinoin, and 0.01% fluocinolone acetonide, has demonstrated superior results in addition studies. For instance, in a 2006 multicenter, investigator-blinded, randomized prospective trial, this combination was compared with nightly use of dual-combination creams containing either hydroquinone plus tretinoin, hydroquinone plus fluocinolone, or tretinoin plus fluocinolone.7 Based on the investigator assessments after 8 weeks of treatment, 26.1% of patients using the triple-combination treatment achieved complete clearance as compared with 9.5% for hydroquinone plus tretinoin, 1.9% for tretinoin plus fluocinolone, and 2.5% for hydroquinone plus fluocinolone. Notably, 77% of patients on the triple-combination therapy achieved complete or nearcomplete clearance, while only 46.8% of patients achieved this on the dual-combination regimens. With the help of a compounding pharmacist, additional improvements can be made to the combination therapy compounds. The addition of kojic acid has become popular with dermatologists, and, since hydroquinone formulations oxidize quickly, a compounding pharmacist can add an antioxidant, such as ascorbic acid, to the formulation to deter oxidation. Even with added antioxidant ingredients, patients should be cautioned that the product may begin to lose efficacy after 8 weeks and should be discarded if it starts to darken in color. Facial Plastic Surgery
Vol. 30
No. 1/2014
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
compounded through a pharmacist for at-home use, is a distinct advantage over OTC preparations. For patients with sensitive skin, short contact therapy with glycolic peels often works better than prolonged exposure to low pH exfoliants. (Chemical peels are discussed in greater detail in another article in this issue entitled “Chemical Peels.”) There have been recent innovations in in-office glycolic peel formulations with paired at-home skin care, such as the Vivité peel (Allergan, Inc., Irvine, CA), which pairs 70% glycolic acid with a potent antioxidant complex. The addition of antioxidants to the peel solution leads to diminished postpeel inflammation in the form of redness, sensitivity, and peeling, while preserving the exfoliating benefits of the peel, and the same approach is used in the at-home products that are physician dispensed.
Sherber
Prescription Topicals in Skin Rejuvenation
Sherber
Hydroquinone preparations should always be prescribed with limited refills and plans for follow-up care as there is a small but real risk of paradoxical pigmentation deposition, ochoronosis, from its use. Since patients prone to lengines and solar dyschromia may also be prone to postinflammatory hyperpigmentation, it is important to minimize treatmentrelated inflammation and dermatitis as is commonly seen with hydroquinone therapy. The triple-combination therapy outlined above incorporates a steroid to quell inflammation, but patients should also be cautioned to take a day off if they develop any treatment-related erythema. Of course, daytime broad-spectrum UV protection is a key element of treating dyspigmentation.
Azelaic Acid Azelaic acid is a reversible competitive inhibitor of tyrosinase derived from Pityrosporum ovale. It can be a helpful adjunct treatment for improving dyspigmentation, and, since it also has benefit against acne, is excellent to multitask and treat acne as well as unwanted pigmentation. It is a particularly excellent agent in the treatment of postinflammatory hyperpigmentation from acne, with one open-label study indicating improvement in acne and in postinflammatory hyperpigmentation in Fitzpatrick skin types IV–VI starting at 4 weeks of use.8 A new prescription formulation is Aza Clear (Epikinetics Pharma, llc., Los Angeles, CA), which combines azelaic acid and niacinamide. Niacinamide (vitamin B3) has demonstrated benefit when applied topically, and perhaps the best study of its effects to date is a double blind left-right randomized split-face study of 50 women with photoaging who applied 5% niacinamide to one half of the face, and vehicle control to the other half, twice daily for 12 weeks.9 One caveat to the study is that it is was sponsored by Proctor and Gamble, and all authors are employees of the company, but it was a well-designed clinical trial. The active treatment side demonstrated significant improvements as compared with control in the following clinical parameters: reductions in fine lines and wrinkles, hyperpigmented spots, red blotchiness, skin sallowness, and elasticity. In clinical practice, many dermatologists have not noted dramatic skin improvement as a result of niacinamide use, but, since niacinamide does not provoke skin irritation, it is a good addition to azelaic acid for potential for synergistic benefit without added inflammation.
Improvement in Adult Acne Many patients into their 30s, 40s, and even 50s develop comedonal and/or inflammatory acne, and clearing their skin is an important element of a skin rejuvenation program because a patient with smoother and more even-toned skin that still has active acne will be unlikely to be completely happy with the results from treatment. Acne treatments aimed at teenagers tend to be too drying for more mature skin, and trading acne for red peeling skin can create a problem that is even harder to conceal with makeup than the original acne would be. Facial Plastic Surgery
Vol. 30
No. 1/2014
Dapsone Gel A great new development in the treatment of adult acne has been topical anti-inflammatory treatments that do not cause the redness and xerosis typical of prescription topical acne treatments. Aczone gel (dapsone gel 5%; Allergan, Inc.) has an innovative makeup primer-like texture that makes it wear well under makeup, and does not cause a transient worsening of acne before the acne starts to improve.10 Since it has an anti-inflammatory effect, it does not cause peeling or redness, and this makes it an excellent choice for more mature patients whose skin is less oily than teenage skin would be. Although, the mechanism of action is not fully understood, it seems to be particularly effective in treating acne in women as compared with men after 12 weeks of therapy.11 As a result; many dermatologists are using this to treat hormonally related acne that may be occurring in the years in which patients are presenting for facial rejuvenation.
Benzoyl Peroxide Benzoyl peroxide is still a mainstay of acne treatment, but can be overly drying and irritating for mature skin. One formulation that has a more hydrating aqueous gel vehicle than others is Acanya gel (clindamycin phosphate (1.5%)/benzoyl peroxide (2.5%) gel; Medicis). This works very well as a spot treatment for inflammatory acne papules, and appears to work equally well for men and for women.12 Short contact therapy with cleansers can also be a good way to incorporate this ingredient into an acne treatment regimen without causing skin irritation or risking bleaching clothes, both of which can be very problematic for more mature patients.
Retinoids As mentioned previously, Atralin gel is a more hydrating form of tretinoin than others, and tretinoin remains a gold standard treatment for comedonal acne. While insurance will not cover Atralin gel outside the setting of teenage acne, in general, there has been a savings card available from the manufacturer that bring the cost within range of OTC retinoid options. In addition, in mature skin comedones may develop in areas of sun damage, such as the upper cheeks, termed Favre Rocouchot syndrome, and retinoids are an excellent approach to target both the comedones and the photoaging. For some adults with chronic acne that is recalcitrant to other treatment or is resulting in scarring, a 120 to 150 mg/kg course of isotretinoin may be the best course of treatment. Physicians must register with the iPledge program to prescribe this medication due to its teratogenicity, so referral to a dermatologist who is accustomed to the paperwork requirements and laboratory monitoring may be in order. For women with hormonal acne, particularly as characterized by inflammatory lesions along the jawline or on the chest, combination oral contraceptives and/or spironolactone may be the best strategy and so referral to a dermatologist familiar with the nuances of acne management through hormonal therapy may be advisable. For women in menopause or perimenopause with significant hormonally related acne, referral to an endocrinologist or a gynecologist with expertise in menopausal hormonal changes may be advantageous.
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
14
Acid-Based Treatments Glycolic acid is a wonderful anti-acne and anti-aging ingredient, and in-office peels can be an ideal adjunct to at-home skin care. For patients with active acne, peels incorporating a β-hydroxy acid, such as salicylic acid, are optimal since βhydroxy acids are lipophilic and dissolve in the oil that is congesting the pores. A modified Jessners peel includes both α- and β-hydroxy acids (lactic and salicylic) and can be a good choice to improve photoaging and acne. Alternatively, salicylic acid-only peels, such as Theraplex (The Theraplex Company, LLC, Memphis, TN) SA peels, can be alternated with α-hydroxy-only peels for optimal therapy. With the proliferation of OTC cosmeceuticals, a mastery of prescription-grade skin care products gives a physician an advantage in giving patients access to a privileged group of topical therapies that offer an effective and evidence-based approach to improve the health and beauty of the skin.
4
5
6
7 8
9
10
References 1 Bernstein EF, Lee J, Brown DB, Yu R, Van Scott E. Glycolic acid
treatment increases type I collagen mRNA and hyaluronic acid content of human skin. Dermatol Surg 2001;27(5):429–433 2 Griffiths CEM, Russman AN, Majmudar G, Singer RS, Hamilton TA, Voorhees JJ. Restoration of collagen formation in photodamaged human skin by tretinoin (retinoic acid). N Engl J Med 1993;329(8): 530–535 3 Griffiths CEM, Kang S, Ellis CN, et al. Two concentrations of topical tretinoin (retinoic acid) cause similar improvement of photoaging but different degrees of irritation. A double-blind, vehicle-con-
11
12
Sherber
trolled comparison of 0.1% and 0.025% tretinoin creams. Arch Dermatol 1995;131(9):1037–1044 Bershad S, Kranjac Singer G, Parente JE, et al. Successful treatment of acne vulgaris using a new method: results of a randomized vehicle-controlled trial of short-contact therapy with 0.1% tazarotene gel. Arch Dermatol 2002;138(4):481–489 Matts PJ, Fink B. Chronic sun damage and the perception of age, health and attractiveness. Photochem Photobiol Sci 2010;9(4): 421–431 Ferreira Cestari T, Hassun K, Sittart A, de Lourdes Viegas M. A comparison of triple combination cream and hydroquinone 4% cream for the treatment of moderate to severe facial melasma. J Cosmet Dermatol 2007;6(1):36–39 Nordlund JJ, Grimes PE, Ortonne JP. The safety of hydroquinone. J Eur Acad Dermatol Venereol 2006;20(7):781–787 Kircik LH. Efficacy and safety of azelaic acid (AzA) gel 15% in the treatment of post-inflammatory hyperpigmentation and acne: a 16-week, baseline-controlled study. J Drugs Dermatol 2011;10(6): 586–590 Bissett DL, Oblong JE, Berge CA. Niacinamide: A B vitamin that improves aging facial skin appearance. Dermatol Surg 2005;31(7 Pt 2):860–865, discussion 865 Draelos ZD, Carter E, Maloney JM, et al; United States/Canada Dapsone Gel Study Group. Two randomized studies demonstrate the efficacy and safety of dapsone gel, 5% for the treatment of acne vulgaris. J Am Acad Dermatol 2007;56(3):e1–e10 Tanghetti E, Harper JC, Oefelein MG. The efficacy and tolerability of dapsone 5% gel in female vs male patients with facial acne vulgaris: gender as a clinically relevant outcome variable. J Drugs Dermatol 2012;11(12):1417–1421 Harper JC. Gender as a clinically relevant outcome variable in acne: benefits of a fixed combination clindamycin phosphate (1.2%) and benzoyl peroxide (2.5%) aqueous gel. J Drugs Dermatol 2012; 11(12):1440–1445
Facial Plastic Surgery
Vol. 30
No. 1/2014
15
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Prescription Topicals in Skin Rejuvenation
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Topicals in Skin Rejuvenation: Prescription Topicals Noëlle S. Sherber, MD, FAAD1
Facial Plast Surg 2014;30:12–15.
Abstract Keywords
► ► ► ► ►
skin care retinoids glycolic acid hydroquinone antiaging
Address for correspondence Noëlle S. Sherber, MD, FAAD, Sherber þ Rad, 1101 15th Street, NW, Washington, DC 20005 (e-mail: [email protected]).
With the recent proliferation of over the counter cosmeceuticals, prescription topical skin treatments have the cache of being evidence-based and not being available outside the setting of a patient–physician interaction. In the setting of facial rejuvenation, patient demand for prescription topical skin treatments falls into three main roles: (1) stimulation of collagen production; (2) improvement of dyspigmentation; and (3) amelioration of adult acne.
Stimulation of Collagen Production Many over-the-counter (OTC) antiaging topical treatments claim to stimulate collagen production, but most base this on in vitro data. Since cultured skin fibroblasts are so easily triggered to make collagen in vitro when agitated by drops of product being added to them, these data should not be extrapolated to actual in vivo use. The best studies for assessing realistic results from topical ingredients are randomized, double blind, vehicle-controlled trials in which each subject serves as an internal control with biopsies of the treatment and vehicle areas of each subject’s skin obtained and analyzed. These sorts of studies are rarely, if ever, conducted with cosmeceuticals, but can be found in the peer-reviewed literature on certain prescription topical skin treatments. The strength of these data is appealing to patients who want a more evidence-based approach to their antiaging concerns.
Glycolic Acid The understanding of the skin rejuvenating benefits of glycolic acid became further understood in 2001 with the publication of a randomized, double blind, vehicle-controlled trial examining the effects of 20% glycolic acid lotion (pH 3.9) as compared with a lotion vehicle when applied to the forearm twice daily for 3 months in 12 female subjects aged 51 to 68 years.1 One forearm was treated with the active ingredient, and the other received vehicle, and paired 4 mm punch biopsies were performed at the end of the study
Issue Theme Classical and State-of-theArt Skin Rejuvenation; Guest Editors, Lisa D. Grunebaum, MD, and Noëlle S. Sherber, MD, FAAD
period. While the sample size in this study was small, statistically significant differences (p < 0.05) in the primary endpoints could be ascertained at this power. In the treatment group, the epidermal thickness was 16.5% greater than in the control group, and there was a 180% increase in total epidermal hyaluronic acid and 9.4% epidermal hyaluronic acid staining in the treatment group as compared with the control. Notably, there was a 280% increase in collagen gene expression (dermal type I collagen mRNA) in the treatment group as compared with control samples. The clinical implications of these findings include a more plumped-up appearance to the skin, since even small increases in glycosaminoglycan (GAG) result in large increases in skin hydration given that they can bind up to 1,000 times their weight in water. Increased GAG production also precedes collagen formation. While a statistically significant 2.8fold increase in collagen gene expression was demonstrated in this study at the 3-month study endpoint, the increase in GAGs may be indicative that collagen production might be even greater in the longer term. Glycolic acid has become a very popular ingredient in OTC cosmeceuticals. However, the lack of regulation of these products has inherent risks. The guideline for cosmetic chemists to formulate OTC products is that the pH should be a minimum of 3.5, but one popular OTC glycolic acid serum has a pH of 2.3, which can cause problematic inflammation. The control over glycolic acid percentage and pH in prescription formulations, whether physician-administered or
Copyright © 2014 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662.
DOI http://dx.doi.org/ 10.1055/s-0033-1363763. ISSN 0736-6825.
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
1 Sherber þ Rad, Northwest, Washington, District of Columbia
Prescription Topicals in Skin Rejuvenation
Treatment of Dyspigmentation One of the hallmarks of older skin is uneven pigmentation, and improving this for a patient can make them look years younger as a 2010 study showed that using computer enhancement to remove discolorations on facial skin resulted in subjects thinking that the person in the photo was 1 to 5 years younger than her actual age.5 Smoothing lines and wrinkles resulted in a more significant decrease in perceived age than evening out pigmentation, but combing the two effects produced the greatest effect with a decrease in perceived age of 15 years. So, combining brightening treatments with revolumizing and treatment of dynamic rhytids is an optimal approach to rejuvenation. (Treatment of unwanted pigmentation is discussed more in depth in another chapter in this issue entitled “Treatment of Unwanted Pigment.”)
Tretinoin Retinoids have long been the gold standard ingredients for stimulating neocollagenesis, with a longstanding body of literature supporting their role in restoring dermal collagen in photoaged skin.2 Contrary to what some have believed, the degree of improvement seen with topical retinoid therapy does not correlate with the degree of irritation, or retinoid dermatitis, achieved through treatment. In a randomized vehicle-controlled trial of nearly 100 subjects, both tretinoin 0.1 and 0.025%, respectively, produced statistically significant improvement in photoaging as compared with vehicle, but despite 3-fold greater incidence of irritation in the tretinoin 0.1% group as compared with the 0.025% group, there are no statistically significant difference in efficacy between the two tretinoin treatment groups.3 Newer formulations of tretinoin are aimed at minimizing retinoid dermatitis resulting from treatment, which generally improved patient adherence to the treatment regimen. Atralin gel (Medicis; a division of Valeant Pharmaceuticals International., Inc., Bridgewater, NJ) has been the first prescription retinoid to combine tretinoin 0.05% with hydrating hyaluronic acid to minimize xerosis from treatment. The light gel texture of this product makes it ideal for patients to use as a serum underneath a rich occlusive moisturizer before bed. For those patients who prefer a cream formulation, ReFissa (Suneva Medical, San Diego, CA) offers a fragrance-free formulation of tretinoin 0.05% cream as an alternative to the heavily scented Renova form of tretinoin 0.02% cream or 0.05% emollient cream that peaked in popularity several years ago. For patients with sensitive skin who find that they cannot tolerate even the newer formulations of prescription retinoids for overnight use, short-contact therapy is an excellent option. The efficacy of short-contact therapy was first established in the setting of tazarotene treatment for acne.4 Since that time, dermatologists have been incorporating this technique into their practices for both acne treatment and the treatment of photoaging. Patients are instructed to apply a thin layer of the prescription retinoid to a clean dry face, and to let it remain in place an average of 5 minutes before cleansing thoroughly and moisturizing. This can work very well for mature skin types who develop treatment-limiting xerosis from having a retinoid in contact with their skin overnight.
13
Hydroquinone Dermatologists have long observed clinically that employing a synergistic approach to the treatment of solar dyschromia is superior to monotherapy with a tyrosinase inhibitor such as hydroquinone. This was substantiated in a 2007 study comparing 4% hydroquinone to combination therapy with 4% hydroquinone, 0.05% tretinoin, and 0.01% fluocinolone acetonide for the treatment of melasma.6 While the study was nonblinded, daily use of the triple-combination therapy resulted in 35% of subjects achieving melasma clearance by investigator rating, versus 5.1% of patients who were treated with 4% hydroquinone twice daily. Daily use is often a better schedule for patient treatment adherence than twice daily application, which is an additional rationale for triple-combination therapy. This triple-combination therapy for the treatment of dyspigmentation, 4% hydroquinone, 0.05% tretinoin, and 0.01% fluocinolone acetonide, has demonstrated superior results in addition studies. For instance, in a 2006 multicenter, investigator-blinded, randomized prospective trial, this combination was compared with nightly use of dual-combination creams containing either hydroquinone plus tretinoin, hydroquinone plus fluocinolone, or tretinoin plus fluocinolone.7 Based on the investigator assessments after 8 weeks of treatment, 26.1% of patients using the triple-combination treatment achieved complete clearance as compared with 9.5% for hydroquinone plus tretinoin, 1.9% for tretinoin plus fluocinolone, and 2.5% for hydroquinone plus fluocinolone. Notably, 77% of patients on the triple-combination therapy achieved complete or nearcomplete clearance, while only 46.8% of patients achieved this on the dual-combination regimens. With the help of a compounding pharmacist, additional improvements can be made to the combination therapy compounds. The addition of kojic acid has become popular with dermatologists, and, since hydroquinone formulations oxidize quickly, a compounding pharmacist can add an antioxidant, such as ascorbic acid, to the formulation to deter oxidation. Even with added antioxidant ingredients, patients should be cautioned that the product may begin to lose efficacy after 8 weeks and should be discarded if it starts to darken in color. Facial Plastic Surgery
Vol. 30
No. 1/2014
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
compounded through a pharmacist for at-home use, is a distinct advantage over OTC preparations. For patients with sensitive skin, short contact therapy with glycolic peels often works better than prolonged exposure to low pH exfoliants. (Chemical peels are discussed in greater detail in another article in this issue entitled “Chemical Peels.”) There have been recent innovations in in-office glycolic peel formulations with paired at-home skin care, such as the Vivité peel (Allergan, Inc., Irvine, CA), which pairs 70% glycolic acid with a potent antioxidant complex. The addition of antioxidants to the peel solution leads to diminished postpeel inflammation in the form of redness, sensitivity, and peeling, while preserving the exfoliating benefits of the peel, and the same approach is used in the at-home products that are physician dispensed.
Sherber
Prescription Topicals in Skin Rejuvenation
Sherber
Hydroquinone preparations should always be prescribed with limited refills and plans for follow-up care as there is a small but real risk of paradoxical pigmentation deposition, ochoronosis, from its use. Since patients prone to lengines and solar dyschromia may also be prone to postinflammatory hyperpigmentation, it is important to minimize treatmentrelated inflammation and dermatitis as is commonly seen with hydroquinone therapy. The triple-combination therapy outlined above incorporates a steroid to quell inflammation, but patients should also be cautioned to take a day off if they develop any treatment-related erythema. Of course, daytime broad-spectrum UV protection is a key element of treating dyspigmentation.
Azelaic Acid Azelaic acid is a reversible competitive inhibitor of tyrosinase derived from Pityrosporum ovale. It can be a helpful adjunct treatment for improving dyspigmentation, and, since it also has benefit against acne, is excellent to multitask and treat acne as well as unwanted pigmentation. It is a particularly excellent agent in the treatment of postinflammatory hyperpigmentation from acne, with one open-label study indicating improvement in acne and in postinflammatory hyperpigmentation in Fitzpatrick skin types IV–VI starting at 4 weeks of use.8 A new prescription formulation is Aza Clear (Epikinetics Pharma, llc., Los Angeles, CA), which combines azelaic acid and niacinamide. Niacinamide (vitamin B3) has demonstrated benefit when applied topically, and perhaps the best study of its effects to date is a double blind left-right randomized split-face study of 50 women with photoaging who applied 5% niacinamide to one half of the face, and vehicle control to the other half, twice daily for 12 weeks.9 One caveat to the study is that it is was sponsored by Proctor and Gamble, and all authors are employees of the company, but it was a well-designed clinical trial. The active treatment side demonstrated significant improvements as compared with control in the following clinical parameters: reductions in fine lines and wrinkles, hyperpigmented spots, red blotchiness, skin sallowness, and elasticity. In clinical practice, many dermatologists have not noted dramatic skin improvement as a result of niacinamide use, but, since niacinamide does not provoke skin irritation, it is a good addition to azelaic acid for potential for synergistic benefit without added inflammation.
Improvement in Adult Acne Many patients into their 30s, 40s, and even 50s develop comedonal and/or inflammatory acne, and clearing their skin is an important element of a skin rejuvenation program because a patient with smoother and more even-toned skin that still has active acne will be unlikely to be completely happy with the results from treatment. Acne treatments aimed at teenagers tend to be too drying for more mature skin, and trading acne for red peeling skin can create a problem that is even harder to conceal with makeup than the original acne would be. Facial Plastic Surgery
Vol. 30
No. 1/2014
Dapsone Gel A great new development in the treatment of adult acne has been topical anti-inflammatory treatments that do not cause the redness and xerosis typical of prescription topical acne treatments. Aczone gel (dapsone gel 5%; Allergan, Inc.) has an innovative makeup primer-like texture that makes it wear well under makeup, and does not cause a transient worsening of acne before the acne starts to improve.10 Since it has an anti-inflammatory effect, it does not cause peeling or redness, and this makes it an excellent choice for more mature patients whose skin is less oily than teenage skin would be. Although, the mechanism of action is not fully understood, it seems to be particularly effective in treating acne in women as compared with men after 12 weeks of therapy.11 As a result; many dermatologists are using this to treat hormonally related acne that may be occurring in the years in which patients are presenting for facial rejuvenation.
Benzoyl Peroxide Benzoyl peroxide is still a mainstay of acne treatment, but can be overly drying and irritating for mature skin. One formulation that has a more hydrating aqueous gel vehicle than others is Acanya gel (clindamycin phosphate (1.5%)/benzoyl peroxide (2.5%) gel; Medicis). This works very well as a spot treatment for inflammatory acne papules, and appears to work equally well for men and for women.12 Short contact therapy with cleansers can also be a good way to incorporate this ingredient into an acne treatment regimen without causing skin irritation or risking bleaching clothes, both of which can be very problematic for more mature patients.
Retinoids As mentioned previously, Atralin gel is a more hydrating form of tretinoin than others, and tretinoin remains a gold standard treatment for comedonal acne. While insurance will not cover Atralin gel outside the setting of teenage acne, in general, there has been a savings card available from the manufacturer that bring the cost within range of OTC retinoid options. In addition, in mature skin comedones may develop in areas of sun damage, such as the upper cheeks, termed Favre Rocouchot syndrome, and retinoids are an excellent approach to target both the comedones and the photoaging. For some adults with chronic acne that is recalcitrant to other treatment or is resulting in scarring, a 120 to 150 mg/kg course of isotretinoin may be the best course of treatment. Physicians must register with the iPledge program to prescribe this medication due to its teratogenicity, so referral to a dermatologist who is accustomed to the paperwork requirements and laboratory monitoring may be in order. For women with hormonal acne, particularly as characterized by inflammatory lesions along the jawline or on the chest, combination oral contraceptives and/or spironolactone may be the best strategy and so referral to a dermatologist familiar with the nuances of acne management through hormonal therapy may be advisable. For women in menopause or perimenopause with significant hormonally related acne, referral to an endocrinologist or a gynecologist with expertise in menopausal hormonal changes may be advantageous.
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Acid-Based Treatments Glycolic acid is a wonderful anti-acne and anti-aging ingredient, and in-office peels can be an ideal adjunct to at-home skin care. For patients with active acne, peels incorporating a β-hydroxy acid, such as salicylic acid, are optimal since βhydroxy acids are lipophilic and dissolve in the oil that is congesting the pores. A modified Jessners peel includes both α- and β-hydroxy acids (lactic and salicylic) and can be a good choice to improve photoaging and acne. Alternatively, salicylic acid-only peels, such as Theraplex (The Theraplex Company, LLC, Memphis, TN) SA peels, can be alternated with α-hydroxy-only peels for optimal therapy. With the proliferation of OTC cosmeceuticals, a mastery of prescription-grade skin care products gives a physician an advantage in giving patients access to a privileged group of topical therapies that offer an effective and evidence-based approach to improve the health and beauty of the skin.
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References 1 Bernstein EF, Lee J, Brown DB, Yu R, Van Scott E. Glycolic acid
treatment increases type I collagen mRNA and hyaluronic acid content of human skin. Dermatol Surg 2001;27(5):429–433 2 Griffiths CEM, Russman AN, Majmudar G, Singer RS, Hamilton TA, Voorhees JJ. Restoration of collagen formation in photodamaged human skin by tretinoin (retinoic acid). N Engl J Med 1993;329(8): 530–535 3 Griffiths CEM, Kang S, Ellis CN, et al. Two concentrations of topical tretinoin (retinoic acid) cause similar improvement of photoaging but different degrees of irritation. A double-blind, vehicle-con-
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trolled comparison of 0.1% and 0.025% tretinoin creams. Arch Dermatol 1995;131(9):1037–1044 Bershad S, Kranjac Singer G, Parente JE, et al. Successful treatment of acne vulgaris using a new method: results of a randomized vehicle-controlled trial of short-contact therapy with 0.1% tazarotene gel. Arch Dermatol 2002;138(4):481–489 Matts PJ, Fink B. Chronic sun damage and the perception of age, health and attractiveness. Photochem Photobiol Sci 2010;9(4): 421–431 Ferreira Cestari T, Hassun K, Sittart A, de Lourdes Viegas M. A comparison of triple combination cream and hydroquinone 4% cream for the treatment of moderate to severe facial melasma. J Cosmet Dermatol 2007;6(1):36–39 Nordlund JJ, Grimes PE, Ortonne JP. The safety of hydroquinone. J Eur Acad Dermatol Venereol 2006;20(7):781–787 Kircik LH. Efficacy and safety of azelaic acid (AzA) gel 15% in the treatment of post-inflammatory hyperpigmentation and acne: a 16-week, baseline-controlled study. J Drugs Dermatol 2011;10(6): 586–590 Bissett DL, Oblong JE, Berge CA. Niacinamide: A B vitamin that improves aging facial skin appearance. Dermatol Surg 2005;31(7 Pt 2):860–865, discussion 865 Draelos ZD, Carter E, Maloney JM, et al; United States/Canada Dapsone Gel Study Group. Two randomized studies demonstrate the efficacy and safety of dapsone gel, 5% for the treatment of acne vulgaris. J Am Acad Dermatol 2007;56(3):e1–e10 Tanghetti E, Harper JC, Oefelein MG. The efficacy and tolerability of dapsone 5% gel in female vs male patients with facial acne vulgaris: gender as a clinically relevant outcome variable. J Drugs Dermatol 2012;11(12):1417–1421 Harper JC. Gender as a clinically relevant outcome variable in acne: benefits of a fixed combination clindamycin phosphate (1.2%) and benzoyl peroxide (2.5%) aqueous gel. J Drugs Dermatol 2012; 11(12):1440–1445
Facial Plastic Surgery
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Prescription Topicals in Skin Rejuvenation
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