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Cosmetic concerns and management strategies to combat aging
Maturitas 70 (2011) 256–260
Contents lists available at ScienceDirect
Maturitas journal homepage: www.elsevier.com/locate/maturitas
Review
Cosmetic concerns and management strategies to combat aging Deanne Mraz Robinson ∗ , Sumaira Z. Aasi 333 Cedar St., LCI 501 New Haven, CT 06520-8059, United States
a r t i c l e
i n f o
Article history: Received 15 July 2011 Accepted 22 July 2011
Keywords: Aging Photoprotection Botulinum toxins Soft tissue fillers Chemical peel Laser surgery
a b s t r a c t Multiple modalities with varying degrees of complexity and risks exist in the treatment of the aging face. Paramount to all treatment paradigms is photoprotection to prevent further damage. Intervetions should be geared towards addressing the intrinsic and extrinsic signs of aging and can include topical retinoid therapy, superficial chemical and laser resurfacing, botulinum toxin and soft tissue fillers. The combination of these primary, secondary, and tertiary therapies will address the underlying pathophysiologic changes of the aging face and thus will provide the optimal aesthetic outcome. © 2011 Elsevier Ireland Ltd. All rights reserved.
Contents 1. 2. 3. 4. 5.
6. 7.
Primary prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Secondary prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Tertiary prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1. Botulinum toxin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Superficial skin resurfacing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1. Chemical peeling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Soft tissue fillers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1. Temporary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2. Semipermanent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Laser surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Competing interests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Provenance and peer review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Aging is an inescapable reality of human existence. From the moment of our birth, our skin begins the intrinsic or natural process of aging, which inevitably leads to loss of elasticity, soft tissue and volume loss, as well as a reduction in bony and cartilaginous support of the face [1]. In contrast, extrinsic or photoaging, results from cumulative exposure to ultraviolet radiation and causes wrinkling, keratoses, loss of elasticity and translucency, telangiectasias, and cutaneous pre-cancers and malignancies [2]. As cumulative sun exposure mounts, the cutaneous signs of photoaging accrue and
∗ Corresponding author. Tel.: +1 203 785 4091, fax: +1 203 785 7637. E-mail address: [email protected] (D.M. Robinson). 0378-5122/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.maturitas.2011.07.020
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are additive to the ongoing process of intrinsic aging. Photoaging affects all races, but has more severe effects on lighter pigmented individuals in contrast to their darker pigmented counterparts. In 1975, Fitzpatrick developed a phototype classification of skin types that can be used as a measure of progressive extrinsic aging. Familiarity with this classification system is imperative when evaluating an aging face and contemplating different treatment algorithms since the risks as well as the outcomes of these procedures correlate with the skin phototype. The Fitzpatrick skin types [3] are listed in Table 1. Therapies for the treatment of photodamage can be subdivided into primary, secondary and tertiary prevention [4]. Primary prevention, in the form of photoprotection, will reduce development of extrinsic aging. Secondary prevention, in the form of topical
D.M. Robinson, S.Z. Aasi / Maturitas 70 (2011) 256–260 Table 1 Fitzpatrick skin type. Type I (White) – always burn and never tans Type II (White) – always burns and can tan minimally Type III (White) – burns moderately and then tans Type IV (Olive) – minimal burning and tans well Type V (Brown) – rarely burns and tans darkly Type VI (Black) – never burns and tans darkly
retinoid therapy, aids in attenuating the effects of photoaging. Lastly, tertiary prevention ameliorates the effects of photoaging as well as intrinsic aging via the use of botulinum toxin, soft tissue fillers, and superficial chemical and laser skin resurfacing. Each of these treatment modalities will be discussed separately. 1. Primary prevention As mentioned previously, treatment geared towards primary prevention of photodamage is paramount. A myriad of topical, injectable, and procedural treatments are available, but at the core of all treatment paradigms is sun protection via sun avoidance, broad spectrum ultraviolet (UV) A and B defense, and protective clothing. The SPF or sun protection factor is a standardized measure by which all sunscreens are rated. It correlates to the amount of UV B radiation a person can be exposed to before developing redness, compared to not using sunscreen at all [5]. The SPF does not measure protection for UV A defense, which is the portion of the spectrum accountable for photoaging. However, sunscreens with a higher concentration of UV A blocking ingredients, such as dioxybenzone, oxybenzone, titanium dioxide, zinc oxide, do confer protection against photoaging in vivo [6]. Application of sunscreen should be performed at 2 mg/cm2 ; however evidence has shown that only 25% of people actually properly apply sunscreen at this recommended dose. Unfortunately, lower dose applications make the SPF fall exponentially [7] leading to a reduced protection. In addition, patients should be counseled to avoid peak hours of UV exposure from 10 am to 4 pm, wear protective clothing, such as long sleeves, hats, sunglasses and/or UV protective factor clothing.
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damaged forearms, an improvement in texture, dyspigmentation, and wrinkling was noted. Further evaluation in 2004 [13] compared vehicle, tretinoin, and four different concentrations (0.01%, 0.025%, 0.05%, and 0.1%) of tazarotene gel. The results illustrated a significant improvement in photodamage parameters with both tazarotene, at all concentrations, and tretinoin treated patients as compared to vehicle. Of note, there was no statistical difference in patients treated with tretinoin versus tazarotene. However, the efficacy of tretinoin versus tazarotene in treating photodamage was retested in 2004 [14]. In this multicenter, double-blind, randomized, parallel-group study, subjects were randomly assigned to apply either tazarotene 0.1% cream or tretinoin 0.05% cream to their faces for 24 weeks. The results favored tazarotene cream for overall integrated assessment of photodamage, improvement in dyspigmentation, as well as in coarse wrinkling. The effects of tazorotene can be seen as early as in 2 weeks of usage and results continue to improve at 52 weeks of treatment [15]. Far less research has been conducted for the use of adapalene in photodamage. Kang et al. [16] examined the use of adapalene gel in treating actinic damage and solar lentigos in a randomized, controlled, parallel group study and found its efficacious in reducing the number of precancerous lesions and lightening of lentigos. In addition, a retrospective evaluation of paired clinical photographs (pre and post 9-month treatment) revealed a significant improvement in fine wrinkles. Interestingly, systemic retinoids have failed to show amelioration of features of extrinsic aging [17]. The adverse-effects of topical retinoid therapy are erythema, burning sensation with application, and mild to moderate symptoms of skin irritation. This can be mitigated by using an appropriate dose of topical retinoid for the treatment area and weaning to low dose retinoid cream, as needed, when stronger preparations are not tolerated. When treating women of childbearing age, it is essential to keep in mind that adapalene and tretinoin are pregnancy class C and tazarotene is class X, and thus, patients should be appropriately counseled.
3. Tertiary prevention 3.1. Botulinum toxin
2. Secondary prevention Topical retinoids are an essential component for combating the signs of aging skin and have been used as such for a multitude of years [8]. The topical retinoid class of tretinoin, adapalene, and tazarotene are naturally occurring and synthetic derivatives of Vitamin A that function by stimulating retinoid acid receptors (RARs) and retinoid X receptors (RXRs). The most heavily studied retinoid, tretinoin, (all-trans-retinoic acid) has been shown in numerous studies to statistically improve the signs of photoaging. Weinstein and colleagues illustrated marked reduction in fine wrinkling, dyspigmentation, and skin laxity with tretinoin usage, which was corroborated by histopathology [9]. Similar outcomes were observed in a double blind, vehicle-control study performed by Weiss et al. in which subjects treated with tretinoin demonstrated statistically significant improvement in photodamage in comparison to vehicle subjects [10]. Fewer trials have been conducted assessing the effect of tretinoin on the intrinsic aging process. Kligman et al. [11] applied tretinoin cream to the inner thigh of elderly females and vehicle cream to the contralateral thigh for a period of nine months. Marked histopathological findings resulted including thickening of the epidermis and uniformity of keratinocytes. However, objective assessment of the treated thigh was more modest and demonstrated a slightly less scaly and less wrinkled appearance. Sefton first investigated tazarotene, a synthetic retinoid, in 2000 [12] in a pilot study evaluating the efficacy of 0.1% tazarotene gel. After 12 weeks of use on moderately actinic
Clostridium botulinum produces seven different serotypes of botulinum toxin, A–G, with botulinum A being the most potent. Botulinum toxins function by inhibition of acetylcholine at the neuromuscular junction, and specifically for A class, by cleavage of the SNAP-25 proteins leading to chemodenervation of the neuromuscular junction [18]. Original work in the cosmetic realm with botulinum toxin A (BTX-A) was serendipitously conducted in the 1980s. Patients were treated with BTX-A for ocular strabismus and were coincidentally noted to have objective improvement in their glabellar rhytids [19]. Further work by the husband and wife team of Carruthers and Carruthers on the effects of BTX-A incited a great interest for additional research and clinical applications for BTX-A [20]. Two current formulations of BTX-A are approved for use in treating moderate to severe glabellar lines in patients 18–65 years of age in the United States, Botox® (Onabotulinumtoxin A) and Dysport® (Abobotulinumtoxin A). Botox® originally gained FDA approval for cosmetic purposes in 2002, while Dysport® recently gained approval in 2009. The targets of glabellar injections with BTX-A are procerus and the corrugator supercilli muscles. Evidence for reduction in dynamic rhytids with BTX-A injections was established by Carruthers and colleagues who noted a significant reduction with 20 units of BTX-A, in this case Botox® , injected into 5 glabellar sites after 120 days [21]. Similar results have been illustrated with Dysport® ; in the phase III studies of Abobotulinumtoxin A, 720 treated patients showed significantly improved moderate to
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severe glabellar lines as compared with placebo [22]. Dilution and subsequent dosing of Onabotulinumtoxin A and Abobotulinumtoxin A have been evaluated, and are felt not to be equivalent, with proposed dilution ratio of 1:2.33–1:5 units, respectively [23]. The effects of BTX-A typically last 3–6 months, however, some studies report effects lasting up to 12 months duration [24]. Adjuvant cosmetic use of BTX-A includes, but is not limited to, horizontal forehead creases, crow’s feet, eye shaping, mentalis cobblestoning, anterior necklines, and mandibular angle shaping [25]. Equally as important as clinical efficacy, patient satisfaction with BTX-A treatments is very high [26]. Contraindications to treatment with BTX-A include pregnancy or lactation, infection at proposed site of injection, history of neuromuscular disorder, or known hypersensitivity to any botulinum toxin preparation or to any of the components of the formulation [27]. Common side effects associated with BTX-A injections include localized ecchymosis, pain, and edema at the injection sites, in addition to headache and, rarely, flu-like symptoms [28]. Inexperienced injectors can encounter more serious complications such as eyelid and brow ptosis. In 2009, the FDA mandated a black box warning to appear on all toxins, including BTX-A products, which warns consumers against distant spread of toxin and subsequent severe effects that may occur including muscle weakness, diplopia, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, and dyspnea. Given the universal warning for all botulinum toxins, appropriate patient counseling should be provided.
4. Superficial skin resurfacing 4.1. Chemical peeling Chemical peels of the skin can be performed with a variety of different chemicals and are categorized by the level of injury they produce within the skin: superficial, medium, and deep [29]. Superficial chemical peels produce damage only to the epidermis and are suitable for patients with minimal photodamage [30]. Epidermal regrowth typically occurs within three to five days and superficial chemical resurfacing functions by decreasing keratinocyte adhesion and increasing dermal collagen [31]. Chemicals such as trichloroacetic acid 10–30%, glycolic acid 20–70%, and salicylic acid 20–30% are frequently utilized for superficial resurfacing of photodamaged skin. In contrast, medium (Jessner’s-35% TCA) and deep chemical peeling agents (Baker Gordon phenol) produce injury into the papillary dermis and the mid-reticular dermis, respectively, and concomitant with the deeper level of damage is a higher risk of postoperative complications. When assessing patients for superficial chemical resurfacing contraindications include active herpes simplex infection or active inflammation, and isotretinoin use within the last 6 months [32]. In addition, patients with prior history of radiation therapy should be assessed for adequate adnexal structure volume to allow for sufficient re-epithelialization. In contrast to medium or deep peels, in which herpes simplex prophylaxis is universally recommended, for superficial chemical peels, a personal history of prior herpes simplex virus infection should be obtained and the patient should be appropriately prophylaxed in the event of a positive history. Appropriate prophylaxis can be either valacyclovir 500 mg twice daily or acyclovir 400 mg three times daily beginning on the day of the peel and continued for 10–14 days, given normal renal function [33]. Lastly, the patient’s Fitzpatrick skin type must be determined. Superficial chemical resurfacing can safely be used in ethnic skin, but patients with skin types III–VI are at greater risk for postinflammatory hypo and hyperpigmentation and this risk must be seriously considered, especially with medium and deep chemical peels. [34]. Post-peel skin care for all patients includes aggressive
photoprotection for all skin types and gentle cleansing and moisturizing during the desquamation and re-epithelialization phases. 5. Soft tissue fillers Soft tissue augmentation with fillers can be used to combat soft tissue and volume loss and supplement the bony and cartilaginous support of the face, in addition to filling static rhytids. Fillers are derived from various compounds and can be categorized as temporary, semipermanent and permanent. Temporary dermal fillers include xenogenic porcine and bovine collagens, bioengineered human collagen, and hyaluronic acid (HA) fillers. Calcium hydroxylapatite and poly-l-lactic acid (PLLA) compromise the semipermanent fillers class and polymethylmethacrylate and liquid silicone are permanent fillers. The discussion of permanent fillers is beyond the scope of this review (Table 2). 5.1. Temporary Xenogenic bovine collagen was the “gold standard” of fillers and had been used since 1981 for the treatment of facial rhytids [35]. The duration of effect is dependent on the depth in which the collagen filler is placed within the skin, in addition to the site being treated. On average, the duration of effect is 3–6 months [36]. Optimal placement of collagen is within the superficial dermis as deeper placement results in reduced effectiveness. Prior to treatment with collagen, two separate and consecutive skin tests are required, as approximately 3% of patients will display a cutaneous allergy despite negative testing and 1.3% of patients will develop a delayed sensitivity [37]. Additional potential risks include granuloma and abscess formation, reactivation of herpes simplex, and local necrosis [38]. In contrast, hyaluronic acid (HA) fillers are associated with rare hypersensitivity reactions. Hyaluronic acid is a ubiquitous and naturally occurring hydrophilic acid mucopolysaccharide that provides dermal support via water retention [39]. Hyaluronic acid has no organ or tissue specificity, thus no pretesting is required. De novo collagen synthesis, as assessed with immunohistochemistry, PCR, and electron microscopy, has shown and been hypothesized to occur through stretching of dermal fibroblasts with subsequent activation [40]. Hyaluronic acid fillers can be used to augment the aging face by revolumizing the cheeks and lips and correcting nasolabial and marionette lines, as well as horizontal neck creases [41]. Depending on the concentration of the given HA filler, the depth of injection can range from the superficial to deep dermis. Side-effects of treatment with HA fillers can include pain, ecchymosis, and edema at the injection site. Rare cases of hypersensitivity reactions have been reported and are hypothesized to be result of contamination from the bacterial fermentation process [38]. In addition, rare cases of necrosis or embolization can occur with incident intra-arterial injection [42]. Hyaluronidase can be utilized to degrade improperly placed HA fillers but less evidence exists for its utility in correcting other adverse reactions [43]. 5.2. Semipermanent Poly-l-lactic acid (PLLA) and calcium hydroxylapatite are both utilized for adding volume to the aging face. Poly-l-lactic acid was originally FDA approved for HIV-associated lipodystrophy and in 2009 gained acceptance for cosmetic use in the non-HIV patient. Treatment with PLLA stimulates fibroblasts with resulting neocollagen production and gradual increase in facial volume [44]. PLLA is utilized in cases of advanced volume loss and can be injected into the dermis and supraperiosteally [45] and is most useful in contouring the nasolabial folds and cheeks [46]. The most common adverse reaction associated with PLLA therapy is nodule formation and this is most likely to occur in the periorbital and perioral areas
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Table 2 Review of soft tissue fillers. Filler
Duration of effect
Pretesting required
Collagen Zyderm, bovine collagen in phosphate-buffered saline with 0.3% lidocaine Zyplast, bovine collagen cross linked with glutaraldehyde in 3 mg/mL lidocaine Cosmoderm–Human derived collagen CosmoPlast–Human derived collagen cross linked with glutaraldehyde
3–6 months
Yes, two separate skin tests
Hyaluronic acid JUVÉDERM® Ultra, JUVÉDERM® Ultra Plus, JUVÉDERM® Ultra XC, and JUVÉDERM® Ultra Plus XC- bacterial derived cross-linked HA, with or without 0.3% lidocaine (XC) Restylane, Restylane-l, bacterial derived HA, with or without 0.3% lidocaine (L) Perlane, Perlane-l With or without 0.3% lidocaine (L)
3–6 months
No
1–2 years
No
1–2 years
No
Semipermanent Calcium Hydroxylapatite Radiesse PLLA Sculptra
[47]. As such, PLLA should be avoided in these sites. Volume correction with PLLA can last up to two years [48] and it is thus, a durable contouring agent. Hydroxylapatite is another semipermanent filler that is FDA approved to correct moderate-to-deep nasolabial folds and has been shown to increase dermal collagen, as well [49]. Similar to PLLA, hydroxylapatite is implanted into the deep dermis and has lasting effects for 1–2 years [50]. Adverse reactions include nodule formation, which is most common if utilized in lip volumization [51] and thus, hydroxylapatite should be avoided in this location. 6. Laser surgery A myriad of lasers are available currently for the treatment of the aging face. Lasers can be used to target telangiectasias, benign lentigos, in addition to textural improvement (Table 3). This review will briefly focus on the use of ablative versus fractional laser surgery and a few nonablative modalities, namely pulsed-dye and intense pulse light therapy. Pulse-dye laser (PDL) with wavelengths of 585 and 595 nm can be used to target the superficial telangiectasias and erythema of the aging face resulting in significant reduction of redness. In addition, a new combination 595/1064 nm laser has shown significant improvement in telangiectasias, diffuse erythema, dyspigmentation, and lentigines after five sequential treatments [52]. To further target pigment and telangiectasias within the skin, the intense pulse light (IPL) source can be utilized. IPL is a continuous spectrum of light ranging from 500 to 1200 nm. Depending on the clinical scenario, the range may be narrowed to target a specific entity, such as hemoglobin. IPL has shown efficacy in vascular and pigmented manifestations of photoaging, and can be used in conjunction with additional agents for the treatments pre-cancerous lesions [53]. Recent work has illustrated that IPL imparts stimulatory effects on skin fibroblasts in vitro thus, hypothesizing IPL’s photorejuvenating effect in vivo [54]. Ablative skin resurfacing is the gold standard for treating photo-aged skin and produces the most dramatic clinical results. However, parallel to these impressive responses are prolonged recovery times and the risk of severe post-operative Table 3 Review of laser and intense pulse light and targets. Telangiectasias and erythema
Pulsed dye, intense pulse light, and potassium titanyl phosphate
Solar lentigos
Intense pulse light Q-switched, Ruby and Alexandrite, Neodynium:YAG CO2 , Erbium YAG, fractional lasers
Textural improvement
consequences such as burning, prolonged erythema, milia, and dyspigmentation [55]. Ablative laser surgery is conducted with either the continuous wave carbon dioxide (CO2 ) [10,600 nm] or Erbium:Yttrium–Aluminum–Garnet Laser (2940 nm) and is a serious commitment by both the physician and the patient. As such, fractional resurfacing is a popular alterative as risk and recovery times are reduced. Without injuring the overlying epidermis, nonablative resurfacing creates dermal injury in columns to improve the aging face. In contrast, fractional ablative resurfacing creates damage in regularly spaced columns to the epidermis and dermis over the treated surface [56]. While neither of these modalities illicit results similar to that of traditional ablative laser surgery, the recovery time and risk profile are much improved and thus, are a favored means of treatment. Fractional laser therapy has been shown to be efficacious for dyschromia, photoaging on the face, chest, neck, and hands, telangiectasias, and improvement in texture and laxity [57]. 7. Conclusion In summary, multiple modalities with varying degrees of complexity and risks exist in the treatment of the aging face. Paramount to all treatment paradigms is photoprotection to prevent further damage. Therapies should be geared towards addressing the intrinsic and extrinsic signs of aging and include topical retinoid therapy, superficial chemical and laser resurfacing, botulinum toxin and fillers. The combination of these primary, secondary, and tertiary therapies will address the underlying pathophysiologic changes of aging and thus will provide the optimal aesthetic outcome. Contributors Deanne Mraz Robinson, M.D., Primary author, Yale Dermatology Chief Resident, Department of Dermatology, Yale New Haven Hospital. Sumaira Z. Aasi, M.D., Secondary author, Associate Chief, Section of Cutaneous Oncology and Dermatologic Surgery, Associate Professor, Department of Dermatology, Yale School of Medicine Competing interests No competing interests for either of the authors. Provenance and peer review Commissioned and externally peer reviewed.
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References [1] Miranda A Farage, Kenneth W Miller, Peter Elsner, Howard I Maibach. Cutaneous and ocular toxicology. structural characteristics of the aging skin: a review 2007;26(4):343–57. [2] Gilchrest BA. A review of skin ageing and its medical therapy. Br J Dermatol 1996;135(6):867–75. [3] James WD, Berger TG, Elston DM. Andrews’ diseases of the skin clinical dermatology. 11th ed. Elsevier; 2011. [4] Rabe JH, Mamelak AJ, McElgunn PJ, Morison WL, Sauder DN. Photoaging: mechanisms and repair. J Am Acad Dermatol 2006;55(1):1–19. [5] Sunburn Protection Factor (SPF) (2009-04-30). www.fda.gov/AboutFDA/ CentersOffices/CDER/ucm106351.htm; 2011 [accessed 01.06.11]. [6] Takeuchi T, Uitto J, Bernstein EF. A novel in vivo model for evaluating agents that protect against ultraviolet A-induced photoaging. J Invest Dermatol 1998;110(4):343–7. [7] Faurschou A, Wulf HC. The relation between sun protection factor and amount of sunscreen applied in vivo. Br J Derm VL 2007;156(4):716–9. [8] Kligman AM, Grove GL, Hirose R, Leyden JJ. Topical tretinoin for photoaged skin. J Am Acad Dermatol 1986;15(4 Pt 2):836–59. [9] Weinstein GD, Nigra TP, Pochi PE, et al. Topical tretinoin for treatment of photodamaged skin: a multicenter study. Arch Dermatol 1991;127: 659–65. [10] Weiss JS, Ellis CN, Headington JT, Tincoff T, Hamilton TA, Voorhees JJ. Topical tretinoin improves photoaged skin: a double-blind vehicle-controlled study. JAMA 1988;259:527–32. [11] Kligman AM, Dogadkina D, Lavker RM. Effects of topical tretinoin on nonsun-exposed protected skin of the elderly. J Am Acad Dermatol 1993;29(1): 25–33. [12] Sefton J, Kligman AM, Kopper SC, Lue JC, Gibson JR. Photodamage pilot study: a double-blind, vehicle-controlled study to assess the efficacy and safety of tazarotene 0.1% gel. J Am Acad Dermatol 2000;43(4):656–63. [13] Kang S, Leyden JJ, Lowe NJ, et al. Tazarotene cream for the treatment of facial photodamage: a multicenter, investigator-masked, randomized, vehicle controlled, parallel comparison of 0.01%, 0.025%, 0.05%, and 0.1% tazarotene creams with 0.05% tretinoin emollient cream applied once daily for 24 weeks. Arch Dermatol 2001;137(12):1597–604. [14] Lowe, Gifford M, Tanghetti E, et al. Tazarotene 0.1% cream versus tretinoin 0.05% emollient cream in the treatment of photodamaged facial skin: a multicenter, double-blind, randomized, parallel-group study. J Cosmet Laser Ther 2004;6(2):79–85. [15] Phillips TJ, Gottlieb AB, Leydon JJ, et al. Efficacy of 0.1% tazarotene cream for the treatment of photodamage: a 12 month multicenter, randomized trial. Arch Dermatol 2002;138(11):1486–93. [16] Kang S, Goldfarb MT, Weiss JS, Metz RD, Hamilton TA, Voorhees JJ, Griffiths CE. Assessment of adapalene gel for the treatment of actinic keratoses and lentigines: a randomized trial. J Am Acad Dermatol 2003;49(1):83–90. [17] Bagatin E, Parada MO, Miot HA, Hassun KM, Michalany N, Talarico S. A randomized and controlled trial about the use of oral isotretinoin for photoaging. Int J Dermatol 2010;49(2):207–14. [18] Montecucco C, Molgó J. Botulinal neurotoxins: revival of an old killer. Curr Opin Pharmacol 2005;5(3):274–9. [19] Scott AB. Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery. Ophthalmology 1980;87:1044–9. [20] Carruthers JDA, Carruthers JA. Treatment of glabellar frown lines with C. Botulinum A exotoxin. J Dermatol Surg Oncol 1992;18:17–21. [21] Carruthers JA, Lowe NJ, Menter MA, et al. A multicenter, double-blind, randomized, placebo-controlled study of the efficacy and safety of botulinum toxin type A in the treatment of glabellar lines. BOTOX Glabellar Lines I Study Group. J Am Acad Dermatol 2002;46:121–3. [22] Baumann L, Brandt FS, Kane MA, Donofrio LM. An analysis of efficacy data from four phase III studies of botulinum neurotoxin type A.-A.B.O. for the treatment of glabellar lines. Aesthetic Surg J 2009;29(Suppl. 6):S57–65. [23] Klein AW, Carruthers A, Fagien S, Lowe S. Plast Reconstr Surg 2008;121: 413–22. [24] Carruthers A, Carruthers J, Said S. Dose-ranging study of botulinum toxin type A in the treatment of glabellar rhytids in females. Dermatol Surg 2005;31(4):414–22, discussion 422. [25] Carruthers J, Carruthers A. Botulinum toxin in facial rejuvenation: an update. Obstet Gynecol Clin N Am 2010;37:571–82. [26] Fried RG, Philip Werschler W, Floirendo T. The botulinum toxin experience: results of a patient self-report questionnaire. J Clin Aesthet Dermatol 2009;2(11):37–40. [27] Allergan and medicis. Full Prescription Information 2011.
[28] Batra RS, Dover JS, Arndt KA. Adverse event reporting for botulinum toxin type. J Am Acad Dermatol 2005;53(6):1080–2. [29] Coleman 3rd WP, Brody HJ. Advances in chemical peeling. Dermatol Clin 1997;15(1):19–26. [30] Monheit GD, Chastain MA. Chemical and mechanical skin resurfacing. In: Bolognia JL, Jorizzo JL, Rapini RP, editors. Dermatology. Elsevier Limited; 2008. p. 2313–28. [31] Landau M. Chemical peels. Clin Dermatol 2008;26(2):200–8. [32] Clark E, Scerri L. Superficial medium-depth chemical peels. Clin Dermatol 2008;26(2):209–18. [33] Monheit GD. Facial resurfacing may trigger the herpes simplex virus. Cosmet Dermatol 1995;8:9–16. [34] Zakopoulou N, Kontochristopoulos G. Superficial chemical peels. J Cosmet Dermatol 2006;5(3):246–53. [35] Cockerham K, Hsu VJ. Collagen-based dermal fillers: past, present, future. Facial Plast Surg 2009;25(May (2)):106–13. [36] Cheng JT, Perkins SW, Hamilton MM. Collagen and injectable fillers. Otolaryngol Clin N Am 2002;35(1):73–85. [37] Cooperman LS, Mackinnon V, Bechler G, Pharriss BB. Injectable collagen:a sixyear clinical, investigation. Aesthetic Plast Surg 1985;9(2):145–51. [38] Requena L, Requena C, Christensen L, Zimmermann US, Kutzner H, Cerroni L. Adverse reactions to injectable soft tissue fillers. J Am Acad Dermatol 2011;64(1):1–34. [39] Matarasso SL, Sadick NS. Soft tissue augmentation. In: Bolognia JL, Jorizzo JL, Rapini RP, editors. Dermatology. Elsevier Limited; 2008. p. 2369–80. [40] Wang F, Garza LA, Kang S, Varani J, Orringer JS, Fisher GJ, Voorhees JJ. In vivo stimulation of de novo collagen production caused by cross-linked hyaluronic acid dermal filler injections in photodamaged human skin. Arch Dermatol 2007;143(2):155–63. [41] Han TY, Lee JW, Lee JH, Son SJ, Kim BJ, Mun SK, Kim MN, Lee CK. Subdermal minimal surgery with hyaluronic acid as an effective treatment for neck wrinkles. Dermatol Surg 2011, doi:10.1111/j.1524-4725.2011.02057 [Epub ahead of print]. [42] Lupo RJM, Cohen JL, Duffy D. Delayed presentation of impending necrosis following soft tissue augmentation with hyaluronic acid and successful management with hyaluronidase. J Drugs Dermatol 2007;6(3):325–8. [43] Hirsch RJ, Lupo M, Cohen JL, Duffy D. Hyaluronidase in the correction of hyaluronic acid-based fillers: a review and a recommendation for use. J Cosmet Dermatol 2009;8(4):317–23. [44] Rzany B, Becker-Wegerich P, Bachmann F, Erdmann R, Wollina U. Nonsurgical rejuvenation of the aging face with injectable poly-l-lactic acid for restoration of soft tissue volume. Aesthet Surg J 2011;31(1):95–109 [Schierle CF and Casas LA]. [45] Fitzgerald R, Vleggaar D. Using poly-l-lactic acid (PLLA) to mimic volume in multiple tissue layers. J Drugs Dermatol 2009;8(Suppl. 10):s5–14. [46] Lowe NJ. Appropriate use of Poly-l-lactic acid and clinical considerations. J Eur Acad Venerol 2006;20:2–6. [47] Schierle CF, Casas LA. Nonsurgical rejuvenation of the aging face with injectable poly-l-lactic acid for restoration of soft tissue volume. Aesthet Surg J 2011;31(1):95–109. [48] Lowe NJ, Maxwell CA, Lowe P, Shah A, Patnaik R. Injectable poly-l-lactic acid: 3 years of aesthetic experience. Dermatol Surg 2009;35(Suppl. 1):344–9. [49] Berlin A, Hussain M, Goldberg D. Calcium hydroxylapatite filler for facial rejuvenation: a histologic and immunohistochemical analysis. Dermatol Surg 2008;34:64–7. [50] Bass LS, Smith S, Busso M, McClaren M. Calcium hydroxylapatite (radiesse) for treatment of nasolabial folds: long-term safety and efficacy results. Aesthetic Surg J 2010;30(2):235–8. [51] Duffy DM. Complications of fillers. Overview. Dermatol Surg 2005;31:1626–33. [52] Berlin AL, Hussain M, Goldberg DJ. Cutaneous photoaging treated with a combined 595/1064 nm laser. J Cosmet Laser Ther 2007;9(4):214–7. [53] Goldman MP, Weiss RA, Weiss MA. Intense pulsed light as a nonablative approach to photoaging. Dermatol Surg 2005;31(9 Pt 2):1179–87, discussion 1187. [54] Cao Y, Huo R, Feng Y, Li Q, Wang F. Effects of intense pulsed light on the biological properties and ultrastructure of skin dermal fibroblasts: potential roles in photoaging. Photomed Laser Surg 2011;29(March (5)):327–32. [55] Tierney EP, Hanke CW. Review of the literature: treatment of dyspigmentation with fractionated resurfacing. Dermatol Surg 2010;36(10):1499–508. [56] Alexiades-Armenakas MR, Dover JS, Arndt KA. The spectrum of laser skin resurfacing: nonablative, fractional, and ablative laser resurfacing. J Am Acad Dermatol 2008;58(5):719–37, quiz 738–40. [57] Tierney EP, Kouba DJ, Hanke CW. Review of fractional photothermolysis: treatment indications and efficacy. Dermatol Surg 2009;35(July (10)):1445–61.
Contents lists available at ScienceDirect
Maturitas journal homepage: www.elsevier.com/locate/maturitas
Review
Cosmetic concerns and management strategies to combat aging Deanne Mraz Robinson ∗ , Sumaira Z. Aasi 333 Cedar St., LCI 501 New Haven, CT 06520-8059, United States
a r t i c l e
i n f o
Article history: Received 15 July 2011 Accepted 22 July 2011
Keywords: Aging Photoprotection Botulinum toxins Soft tissue fillers Chemical peel Laser surgery
a b s t r a c t Multiple modalities with varying degrees of complexity and risks exist in the treatment of the aging face. Paramount to all treatment paradigms is photoprotection to prevent further damage. Intervetions should be geared towards addressing the intrinsic and extrinsic signs of aging and can include topical retinoid therapy, superficial chemical and laser resurfacing, botulinum toxin and soft tissue fillers. The combination of these primary, secondary, and tertiary therapies will address the underlying pathophysiologic changes of the aging face and thus will provide the optimal aesthetic outcome. © 2011 Elsevier Ireland Ltd. All rights reserved.
Contents 1. 2. 3. 4. 5.
6. 7.
Primary prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Secondary prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Tertiary prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1. Botulinum toxin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Superficial skin resurfacing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1. Chemical peeling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Soft tissue fillers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1. Temporary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2. Semipermanent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Laser surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Competing interests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Provenance and peer review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Aging is an inescapable reality of human existence. From the moment of our birth, our skin begins the intrinsic or natural process of aging, which inevitably leads to loss of elasticity, soft tissue and volume loss, as well as a reduction in bony and cartilaginous support of the face [1]. In contrast, extrinsic or photoaging, results from cumulative exposure to ultraviolet radiation and causes wrinkling, keratoses, loss of elasticity and translucency, telangiectasias, and cutaneous pre-cancers and malignancies [2]. As cumulative sun exposure mounts, the cutaneous signs of photoaging accrue and
∗ Corresponding author. Tel.: +1 203 785 4091, fax: +1 203 785 7637. E-mail address: [email protected] (D.M. Robinson). 0378-5122/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.maturitas.2011.07.020
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are additive to the ongoing process of intrinsic aging. Photoaging affects all races, but has more severe effects on lighter pigmented individuals in contrast to their darker pigmented counterparts. In 1975, Fitzpatrick developed a phototype classification of skin types that can be used as a measure of progressive extrinsic aging. Familiarity with this classification system is imperative when evaluating an aging face and contemplating different treatment algorithms since the risks as well as the outcomes of these procedures correlate with the skin phototype. The Fitzpatrick skin types [3] are listed in Table 1. Therapies for the treatment of photodamage can be subdivided into primary, secondary and tertiary prevention [4]. Primary prevention, in the form of photoprotection, will reduce development of extrinsic aging. Secondary prevention, in the form of topical
D.M. Robinson, S.Z. Aasi / Maturitas 70 (2011) 256–260 Table 1 Fitzpatrick skin type. Type I (White) – always burn and never tans Type II (White) – always burns and can tan minimally Type III (White) – burns moderately and then tans Type IV (Olive) – minimal burning and tans well Type V (Brown) – rarely burns and tans darkly Type VI (Black) – never burns and tans darkly
retinoid therapy, aids in attenuating the effects of photoaging. Lastly, tertiary prevention ameliorates the effects of photoaging as well as intrinsic aging via the use of botulinum toxin, soft tissue fillers, and superficial chemical and laser skin resurfacing. Each of these treatment modalities will be discussed separately. 1. Primary prevention As mentioned previously, treatment geared towards primary prevention of photodamage is paramount. A myriad of topical, injectable, and procedural treatments are available, but at the core of all treatment paradigms is sun protection via sun avoidance, broad spectrum ultraviolet (UV) A and B defense, and protective clothing. The SPF or sun protection factor is a standardized measure by which all sunscreens are rated. It correlates to the amount of UV B radiation a person can be exposed to before developing redness, compared to not using sunscreen at all [5]. The SPF does not measure protection for UV A defense, which is the portion of the spectrum accountable for photoaging. However, sunscreens with a higher concentration of UV A blocking ingredients, such as dioxybenzone, oxybenzone, titanium dioxide, zinc oxide, do confer protection against photoaging in vivo [6]. Application of sunscreen should be performed at 2 mg/cm2 ; however evidence has shown that only 25% of people actually properly apply sunscreen at this recommended dose. Unfortunately, lower dose applications make the SPF fall exponentially [7] leading to a reduced protection. In addition, patients should be counseled to avoid peak hours of UV exposure from 10 am to 4 pm, wear protective clothing, such as long sleeves, hats, sunglasses and/or UV protective factor clothing.
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damaged forearms, an improvement in texture, dyspigmentation, and wrinkling was noted. Further evaluation in 2004 [13] compared vehicle, tretinoin, and four different concentrations (0.01%, 0.025%, 0.05%, and 0.1%) of tazarotene gel. The results illustrated a significant improvement in photodamage parameters with both tazarotene, at all concentrations, and tretinoin treated patients as compared to vehicle. Of note, there was no statistical difference in patients treated with tretinoin versus tazarotene. However, the efficacy of tretinoin versus tazarotene in treating photodamage was retested in 2004 [14]. In this multicenter, double-blind, randomized, parallel-group study, subjects were randomly assigned to apply either tazarotene 0.1% cream or tretinoin 0.05% cream to their faces for 24 weeks. The results favored tazarotene cream for overall integrated assessment of photodamage, improvement in dyspigmentation, as well as in coarse wrinkling. The effects of tazorotene can be seen as early as in 2 weeks of usage and results continue to improve at 52 weeks of treatment [15]. Far less research has been conducted for the use of adapalene in photodamage. Kang et al. [16] examined the use of adapalene gel in treating actinic damage and solar lentigos in a randomized, controlled, parallel group study and found its efficacious in reducing the number of precancerous lesions and lightening of lentigos. In addition, a retrospective evaluation of paired clinical photographs (pre and post 9-month treatment) revealed a significant improvement in fine wrinkles. Interestingly, systemic retinoids have failed to show amelioration of features of extrinsic aging [17]. The adverse-effects of topical retinoid therapy are erythema, burning sensation with application, and mild to moderate symptoms of skin irritation. This can be mitigated by using an appropriate dose of topical retinoid for the treatment area and weaning to low dose retinoid cream, as needed, when stronger preparations are not tolerated. When treating women of childbearing age, it is essential to keep in mind that adapalene and tretinoin are pregnancy class C and tazarotene is class X, and thus, patients should be appropriately counseled.
3. Tertiary prevention 3.1. Botulinum toxin
2. Secondary prevention Topical retinoids are an essential component for combating the signs of aging skin and have been used as such for a multitude of years [8]. The topical retinoid class of tretinoin, adapalene, and tazarotene are naturally occurring and synthetic derivatives of Vitamin A that function by stimulating retinoid acid receptors (RARs) and retinoid X receptors (RXRs). The most heavily studied retinoid, tretinoin, (all-trans-retinoic acid) has been shown in numerous studies to statistically improve the signs of photoaging. Weinstein and colleagues illustrated marked reduction in fine wrinkling, dyspigmentation, and skin laxity with tretinoin usage, which was corroborated by histopathology [9]. Similar outcomes were observed in a double blind, vehicle-control study performed by Weiss et al. in which subjects treated with tretinoin demonstrated statistically significant improvement in photodamage in comparison to vehicle subjects [10]. Fewer trials have been conducted assessing the effect of tretinoin on the intrinsic aging process. Kligman et al. [11] applied tretinoin cream to the inner thigh of elderly females and vehicle cream to the contralateral thigh for a period of nine months. Marked histopathological findings resulted including thickening of the epidermis and uniformity of keratinocytes. However, objective assessment of the treated thigh was more modest and demonstrated a slightly less scaly and less wrinkled appearance. Sefton first investigated tazarotene, a synthetic retinoid, in 2000 [12] in a pilot study evaluating the efficacy of 0.1% tazarotene gel. After 12 weeks of use on moderately actinic
Clostridium botulinum produces seven different serotypes of botulinum toxin, A–G, with botulinum A being the most potent. Botulinum toxins function by inhibition of acetylcholine at the neuromuscular junction, and specifically for A class, by cleavage of the SNAP-25 proteins leading to chemodenervation of the neuromuscular junction [18]. Original work in the cosmetic realm with botulinum toxin A (BTX-A) was serendipitously conducted in the 1980s. Patients were treated with BTX-A for ocular strabismus and were coincidentally noted to have objective improvement in their glabellar rhytids [19]. Further work by the husband and wife team of Carruthers and Carruthers on the effects of BTX-A incited a great interest for additional research and clinical applications for BTX-A [20]. Two current formulations of BTX-A are approved for use in treating moderate to severe glabellar lines in patients 18–65 years of age in the United States, Botox® (Onabotulinumtoxin A) and Dysport® (Abobotulinumtoxin A). Botox® originally gained FDA approval for cosmetic purposes in 2002, while Dysport® recently gained approval in 2009. The targets of glabellar injections with BTX-A are procerus and the corrugator supercilli muscles. Evidence for reduction in dynamic rhytids with BTX-A injections was established by Carruthers and colleagues who noted a significant reduction with 20 units of BTX-A, in this case Botox® , injected into 5 glabellar sites after 120 days [21]. Similar results have been illustrated with Dysport® ; in the phase III studies of Abobotulinumtoxin A, 720 treated patients showed significantly improved moderate to
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severe glabellar lines as compared with placebo [22]. Dilution and subsequent dosing of Onabotulinumtoxin A and Abobotulinumtoxin A have been evaluated, and are felt not to be equivalent, with proposed dilution ratio of 1:2.33–1:5 units, respectively [23]. The effects of BTX-A typically last 3–6 months, however, some studies report effects lasting up to 12 months duration [24]. Adjuvant cosmetic use of BTX-A includes, but is not limited to, horizontal forehead creases, crow’s feet, eye shaping, mentalis cobblestoning, anterior necklines, and mandibular angle shaping [25]. Equally as important as clinical efficacy, patient satisfaction with BTX-A treatments is very high [26]. Contraindications to treatment with BTX-A include pregnancy or lactation, infection at proposed site of injection, history of neuromuscular disorder, or known hypersensitivity to any botulinum toxin preparation or to any of the components of the formulation [27]. Common side effects associated with BTX-A injections include localized ecchymosis, pain, and edema at the injection sites, in addition to headache and, rarely, flu-like symptoms [28]. Inexperienced injectors can encounter more serious complications such as eyelid and brow ptosis. In 2009, the FDA mandated a black box warning to appear on all toxins, including BTX-A products, which warns consumers against distant spread of toxin and subsequent severe effects that may occur including muscle weakness, diplopia, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, and dyspnea. Given the universal warning for all botulinum toxins, appropriate patient counseling should be provided.
4. Superficial skin resurfacing 4.1. Chemical peeling Chemical peels of the skin can be performed with a variety of different chemicals and are categorized by the level of injury they produce within the skin: superficial, medium, and deep [29]. Superficial chemical peels produce damage only to the epidermis and are suitable for patients with minimal photodamage [30]. Epidermal regrowth typically occurs within three to five days and superficial chemical resurfacing functions by decreasing keratinocyte adhesion and increasing dermal collagen [31]. Chemicals such as trichloroacetic acid 10–30%, glycolic acid 20–70%, and salicylic acid 20–30% are frequently utilized for superficial resurfacing of photodamaged skin. In contrast, medium (Jessner’s-35% TCA) and deep chemical peeling agents (Baker Gordon phenol) produce injury into the papillary dermis and the mid-reticular dermis, respectively, and concomitant with the deeper level of damage is a higher risk of postoperative complications. When assessing patients for superficial chemical resurfacing contraindications include active herpes simplex infection or active inflammation, and isotretinoin use within the last 6 months [32]. In addition, patients with prior history of radiation therapy should be assessed for adequate adnexal structure volume to allow for sufficient re-epithelialization. In contrast to medium or deep peels, in which herpes simplex prophylaxis is universally recommended, for superficial chemical peels, a personal history of prior herpes simplex virus infection should be obtained and the patient should be appropriately prophylaxed in the event of a positive history. Appropriate prophylaxis can be either valacyclovir 500 mg twice daily or acyclovir 400 mg three times daily beginning on the day of the peel and continued for 10–14 days, given normal renal function [33]. Lastly, the patient’s Fitzpatrick skin type must be determined. Superficial chemical resurfacing can safely be used in ethnic skin, but patients with skin types III–VI are at greater risk for postinflammatory hypo and hyperpigmentation and this risk must be seriously considered, especially with medium and deep chemical peels. [34]. Post-peel skin care for all patients includes aggressive
photoprotection for all skin types and gentle cleansing and moisturizing during the desquamation and re-epithelialization phases. 5. Soft tissue fillers Soft tissue augmentation with fillers can be used to combat soft tissue and volume loss and supplement the bony and cartilaginous support of the face, in addition to filling static rhytids. Fillers are derived from various compounds and can be categorized as temporary, semipermanent and permanent. Temporary dermal fillers include xenogenic porcine and bovine collagens, bioengineered human collagen, and hyaluronic acid (HA) fillers. Calcium hydroxylapatite and poly-l-lactic acid (PLLA) compromise the semipermanent fillers class and polymethylmethacrylate and liquid silicone are permanent fillers. The discussion of permanent fillers is beyond the scope of this review (Table 2). 5.1. Temporary Xenogenic bovine collagen was the “gold standard” of fillers and had been used since 1981 for the treatment of facial rhytids [35]. The duration of effect is dependent on the depth in which the collagen filler is placed within the skin, in addition to the site being treated. On average, the duration of effect is 3–6 months [36]. Optimal placement of collagen is within the superficial dermis as deeper placement results in reduced effectiveness. Prior to treatment with collagen, two separate and consecutive skin tests are required, as approximately 3% of patients will display a cutaneous allergy despite negative testing and 1.3% of patients will develop a delayed sensitivity [37]. Additional potential risks include granuloma and abscess formation, reactivation of herpes simplex, and local necrosis [38]. In contrast, hyaluronic acid (HA) fillers are associated with rare hypersensitivity reactions. Hyaluronic acid is a ubiquitous and naturally occurring hydrophilic acid mucopolysaccharide that provides dermal support via water retention [39]. Hyaluronic acid has no organ or tissue specificity, thus no pretesting is required. De novo collagen synthesis, as assessed with immunohistochemistry, PCR, and electron microscopy, has shown and been hypothesized to occur through stretching of dermal fibroblasts with subsequent activation [40]. Hyaluronic acid fillers can be used to augment the aging face by revolumizing the cheeks and lips and correcting nasolabial and marionette lines, as well as horizontal neck creases [41]. Depending on the concentration of the given HA filler, the depth of injection can range from the superficial to deep dermis. Side-effects of treatment with HA fillers can include pain, ecchymosis, and edema at the injection site. Rare cases of hypersensitivity reactions have been reported and are hypothesized to be result of contamination from the bacterial fermentation process [38]. In addition, rare cases of necrosis or embolization can occur with incident intra-arterial injection [42]. Hyaluronidase can be utilized to degrade improperly placed HA fillers but less evidence exists for its utility in correcting other adverse reactions [43]. 5.2. Semipermanent Poly-l-lactic acid (PLLA) and calcium hydroxylapatite are both utilized for adding volume to the aging face. Poly-l-lactic acid was originally FDA approved for HIV-associated lipodystrophy and in 2009 gained acceptance for cosmetic use in the non-HIV patient. Treatment with PLLA stimulates fibroblasts with resulting neocollagen production and gradual increase in facial volume [44]. PLLA is utilized in cases of advanced volume loss and can be injected into the dermis and supraperiosteally [45] and is most useful in contouring the nasolabial folds and cheeks [46]. The most common adverse reaction associated with PLLA therapy is nodule formation and this is most likely to occur in the periorbital and perioral areas
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Table 2 Review of soft tissue fillers. Filler
Duration of effect
Pretesting required
Collagen Zyderm, bovine collagen in phosphate-buffered saline with 0.3% lidocaine Zyplast, bovine collagen cross linked with glutaraldehyde in 3 mg/mL lidocaine Cosmoderm–Human derived collagen CosmoPlast–Human derived collagen cross linked with glutaraldehyde
3–6 months
Yes, two separate skin tests
Hyaluronic acid JUVÉDERM® Ultra, JUVÉDERM® Ultra Plus, JUVÉDERM® Ultra XC, and JUVÉDERM® Ultra Plus XC- bacterial derived cross-linked HA, with or without 0.3% lidocaine (XC) Restylane, Restylane-l, bacterial derived HA, with or without 0.3% lidocaine (L) Perlane, Perlane-l With or without 0.3% lidocaine (L)
3–6 months
No
1–2 years
No
1–2 years
No
Semipermanent Calcium Hydroxylapatite Radiesse PLLA Sculptra
[47]. As such, PLLA should be avoided in these sites. Volume correction with PLLA can last up to two years [48] and it is thus, a durable contouring agent. Hydroxylapatite is another semipermanent filler that is FDA approved to correct moderate-to-deep nasolabial folds and has been shown to increase dermal collagen, as well [49]. Similar to PLLA, hydroxylapatite is implanted into the deep dermis and has lasting effects for 1–2 years [50]. Adverse reactions include nodule formation, which is most common if utilized in lip volumization [51] and thus, hydroxylapatite should be avoided in this location. 6. Laser surgery A myriad of lasers are available currently for the treatment of the aging face. Lasers can be used to target telangiectasias, benign lentigos, in addition to textural improvement (Table 3). This review will briefly focus on the use of ablative versus fractional laser surgery and a few nonablative modalities, namely pulsed-dye and intense pulse light therapy. Pulse-dye laser (PDL) with wavelengths of 585 and 595 nm can be used to target the superficial telangiectasias and erythema of the aging face resulting in significant reduction of redness. In addition, a new combination 595/1064 nm laser has shown significant improvement in telangiectasias, diffuse erythema, dyspigmentation, and lentigines after five sequential treatments [52]. To further target pigment and telangiectasias within the skin, the intense pulse light (IPL) source can be utilized. IPL is a continuous spectrum of light ranging from 500 to 1200 nm. Depending on the clinical scenario, the range may be narrowed to target a specific entity, such as hemoglobin. IPL has shown efficacy in vascular and pigmented manifestations of photoaging, and can be used in conjunction with additional agents for the treatments pre-cancerous lesions [53]. Recent work has illustrated that IPL imparts stimulatory effects on skin fibroblasts in vitro thus, hypothesizing IPL’s photorejuvenating effect in vivo [54]. Ablative skin resurfacing is the gold standard for treating photo-aged skin and produces the most dramatic clinical results. However, parallel to these impressive responses are prolonged recovery times and the risk of severe post-operative Table 3 Review of laser and intense pulse light and targets. Telangiectasias and erythema
Pulsed dye, intense pulse light, and potassium titanyl phosphate
Solar lentigos
Intense pulse light Q-switched, Ruby and Alexandrite, Neodynium:YAG CO2 , Erbium YAG, fractional lasers
Textural improvement
consequences such as burning, prolonged erythema, milia, and dyspigmentation [55]. Ablative laser surgery is conducted with either the continuous wave carbon dioxide (CO2 ) [10,600 nm] or Erbium:Yttrium–Aluminum–Garnet Laser (2940 nm) and is a serious commitment by both the physician and the patient. As such, fractional resurfacing is a popular alterative as risk and recovery times are reduced. Without injuring the overlying epidermis, nonablative resurfacing creates dermal injury in columns to improve the aging face. In contrast, fractional ablative resurfacing creates damage in regularly spaced columns to the epidermis and dermis over the treated surface [56]. While neither of these modalities illicit results similar to that of traditional ablative laser surgery, the recovery time and risk profile are much improved and thus, are a favored means of treatment. Fractional laser therapy has been shown to be efficacious for dyschromia, photoaging on the face, chest, neck, and hands, telangiectasias, and improvement in texture and laxity [57]. 7. Conclusion In summary, multiple modalities with varying degrees of complexity and risks exist in the treatment of the aging face. Paramount to all treatment paradigms is photoprotection to prevent further damage. Therapies should be geared towards addressing the intrinsic and extrinsic signs of aging and include topical retinoid therapy, superficial chemical and laser resurfacing, botulinum toxin and fillers. The combination of these primary, secondary, and tertiary therapies will address the underlying pathophysiologic changes of aging and thus will provide the optimal aesthetic outcome. Contributors Deanne Mraz Robinson, M.D., Primary author, Yale Dermatology Chief Resident, Department of Dermatology, Yale New Haven Hospital. Sumaira Z. Aasi, M.D., Secondary author, Associate Chief, Section of Cutaneous Oncology and Dermatologic Surgery, Associate Professor, Department of Dermatology, Yale School of Medicine Competing interests No competing interests for either of the authors. Provenance and peer review Commissioned and externally peer reviewed.
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