Photoaging

INTRODUCTION — Photoaging, also called extrinsic aging, is premature skin aging resulting from prolonged and repeated exposure to solar radiation [1]. The changes of photodamage are superimposed on the changes caused by chronologic aging (the so-called intrinsic or programmed aging) and are responsible for most of the age-associated features of skin appearance. Salient clinical features of photoaging include fine and coarse wrinkles, dyspigmentation, and loss of elasticity. (See "Normal aging", section on 'Skin'.)

Photodamage can be partially prevented and reversed with proper sun protection and various prescription medications. However, concerns about photoaging are primarily cosmetic and are influenced by geographic differences, culture, and personal values.

The pathogenesis, clinical features, and medical treatment of photoaging will be discussed here. Procedural techniques for the treatment of photoaging, including laser therapy, injection of soft tissue fillers, and botulinum toxin, are discussed separately. (See "Nonablative skin resurfacing for skin rejuvenation" and "Ablative laser resurfacing for skin rejuvenation" and "Injectable soft tissue fillers: Overview of clinical use" and "Overview of botulinum toxin for cosmetic indications".)

EPIDEMIOLOGY AND RISK FACTORS — Photoaging is responsible for the majority of age-associated cosmetic skin problems in fair-skinned populations. In European and North American adult populations with skin phototypes I, II, and III (table 1), the prevalence of clinically detectable photoaging may be as high as 80 to 90 percent [2].

Risk factors for photoaging include older age, male sex, skin phototypes I to III, high occupational or recreational sun exposure, and living in geographic locations with high sun irradiation [3]. Individuals with fair and less pigmented skin are at increased risk for photodamage and sun-induced skin cancer. The amount of time spent in the sunlight over a lifetime is a key risk factor for photoaging. (See "Epidemiology, pathogenesis, clinical features, and diagnosis of basal cell carcinoma", section on 'Risk factors' and "Cutaneous squamous cell carcinoma: Epidemiology and risk factors", section on 'Risk factors' and "Melanoma: Epidemiology and risk factors", section on 'Geographic and ethnic variation'.)

In an Australian study, skin texture changes of moderate to severe photoaging were observed in 72 percent of men and 47 percent of women under the age of 30 [4]. The severity of photoaging increases rapidly after the age of 30 and is associated with medium or light skin color, burning and never tanning after exposure to strong sunlight, and prolonged occupational or recreational sun exposure [3].

In populations with darker skin, wrinkling is not readily apparent until the age of approximately 50 years, and the severity is not as marked as in light-skinned populations of similar age [5]. One study found that the onset of wrinkles in Chinese women occurred on average 10 years later than in French women [6]. However, in Chinese women, the appearance of hyperpigmented spots was an earlier and more prominent sign of photoaging than in French women.

PATHOGENESIS — The loss of the structural integrity of the dermal extracellular matrix caused by chronic ultraviolet (UV) exposure is believed to be primarily responsible for the wrinkled appearance of photodamaged skin [7]. The dermal extracellular matrix is a complex meshwork of several macromolecules, including collagen and elastic fibers, glycoproteins, and glycosaminoglycans, which provide strength and resilience to the skin. Type I and III collagens are the most abundant proteins in the dermis and the main target of sun-induced damage.

Ultraviolet radiation — Both ultraviolet A (UVA) and ultraviolet B (UVB) appear to be implicated in the photoaging process, although UVA is emerging as the major contributor to photodamage [8]. UVA (320 to 400 nm) is thought to have a larger role than UVB in photoaging because it is able to penetrate deeper into the dermis than UVB and is at least 10-fold more abundant than UVB in the terrestrial sunlight [9].

Short wave UVB (290 to 320 nm) are mainly absorbed in the epidermis by cellular DNA. They induce direct DNA damage with formation of cyclobutane pyrimidine dimers and 6,4-photoproducts and are responsible for sunburn, inflammation, photocarcinogenesis, and immunosuppression [10,11]. UV radiation also indirectly damages DNA. The absorption of UVA photons transfers electrons and energy from cellular chromophores, such as porphyrins, bilirubin, melanin, and pterins, to oxygen molecules, resulting in the formation of singlet oxygen. Long wavelength radiations in the infrared (IR) range, which represent 50 percent of the total solar energy, may also contribute to photoaging of human skin [12-14].

The mechanisms underlying the UV-mediated damage to the skin connective tissue involve the formation of reactive oxygen species (ROS), cell surface receptor-initiated signaling, protein oxidation, and mitochondrial damage [9,15]. ROS, including superoxide anion, hydrogen peroxide, and singlet oxygen, activate cell surface receptors for cytokines and growth factors, including epidermal growth factor (EGF), interleukin (IL)-1, and tumor necrosis factor (TNF)-alpha. ROS also induce the transcription factor activator protein-1 (AP-1) and the nuclear transcription factor NF-kappa-B (figure 1).

AP-1 upregulates matrix metalloproteinases (MMPs), including interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), and 92kDa gelatinase (MMP-9) [15,16]. The combined actions of MMP-1, MMP-3, and MMP-9 degrade most of type I and III dermal collagen. With repeated sun exposure, the degraded collagen accumulates over time, resulting in the clinical and histologic features of photoaging [17-19]. AP-1 also inhibits type I and type III procollagen gene expression in the dermis by binding to the transcriptional complex responsible for procollagen transcription or blocking the activity of transforming growth factor (TGF)-beta [20,21].

The activation of the nuclear transcription factor NF-kappa-B upregulates the expression of proinflammatory cytokines, such as IL-1-beta, TNF-alpha, IL-6, IL-8, and various adhesion molecules [22,23]. These cytokines in turn upregulate AP-1 and further activate the NF-kappa-B pathway, enhancing the response to UV irradiation.

Mitochondria are the main endogenous source of ROS, which are produced during the conversion of adenosine diphosphate (ADP) to adenosine triphosphate (ATP) [9]. Endogenous ROS, particularly singlet oxygen, may induce deletions and rearrangements of mitochondrial DNA (tDNA). The most common mitochondrial mutation is a 4977 base-pair deletion termed "common deletion," which is found with high frequency in degenerative diseases and cancer [24,25]. This mutation is increased in photodamaged skin and may be induced in dermal fibroblasts by repetitive exposure to UVA radiation. [26,27]. Furthermore, it has also been observed that large blocks of genomic hypomethylation occur in photoaged skin similar to those seen in cutaneous carcinogenesis [28].

Visible light — More recent data suggest that visible light (400 to 760 nm) also plays a role in photoaging. Visible light comprises at least 40 percent of solar irradiation and has deeper penetration into the skin, given its longer wavelength, than UV radiation. Similar to UV radiation, visible light has been shown to lead to the production of ROS, proinflammatory cytokines, and MMPs in the dermal matrix [29,30].

Interestingly, melanin has a peak absorption spanning part of the visible light spectrum. While increased melanin protects patients against UV radiation, it may enhance the deleterious effects of visible light, especially in individuals with skin of color [31]. One study demonstrated that visible light produced a more intense and sustained pigmentary response in more highly pigmented skin (skin phototypes IV to VI) compared with UVA radiation [32]. Furthermore, the authors found that visible light had minimal effects in less pigmented skin.

Pigmentation caused by visible light is believed to be mediated by the activation of opsin, a G protein-coupled receptor. Shorter wavelengths of visible light (ie, blue light) can activate opsin, which leads to an influx of calcium and induction of melanogenesis in melanocytes [33]. Additionally, in individuals with highly pigmented skin, persistent pigmentation after exposure to visible light is attributed to continued tyrosinase activation as a downstream effect of this pathway.

Other environmental factors — In addition to sun exposure, several environmental factors may contribute to premature aging of the skin [34]:

●Air pollution – There is growing evidence that exposure to indoor and outdoor air pollutants, including lead, particulate matter (soot, exhaust, industry), nitrogen oxide (car exhaust), sulphur oxide (industrial plants), and ozone (ground level), may contribute to skin aging [34-40]. The association between air pollution and premature skin aging is supported by several epidemiologic studies [36,40]. In vitro studies suggest that the ozone-induced activation of aryl hydrocarbon receptor (AhR) and cytochrome P450 may lead to the production of metabolites of air pollutants that are toxic to the skin [34,41].

●Tobacco smoke – The role of smoking in accelerating skin aging is corroborated by observational and epidemiologic studies [3,42-44]. The so-called "smoker's face" is characterized by prominent perioral and periocular wrinkles and uneven complexion with a grayish hue [44]. The mechanism of tobacco smoke leading to facial wrinkling is poorly understood but is thought to involve impaired collagen biosynthesis and collagen degradation through induction of MMPs [45].

HISTOPATHOLOGY — Microscopic changes in the photodamaged skin include epidermal atrophy with thinning of the spinous layer, flattened dermoepidermal junction with loss of rete ridges, decreased collagen content, and deposition of amorphous masses of abnormally thickened, curled, and disintegrated elastic fibers and collagen breakdown products (solar elastosis) (picture 1). Increased number of atypical melanocytes and atypical epidermal cells may also be seen.

CLINICAL FEATURES — Sun-induced cutaneous changes vary among individuals, reflecting intrinsic differences in vulnerability and repair capacity. Age, sex, geographic location, and skin type (table 1) are factors influencing the severity and clinical appearance of photoaging [46]. (See 'Epidemiology and risk factors' above.)

Photoaging in individuals with phototypes I to IV — In individuals with light phototypes (table 1), sun-induced changes include fine and coarse wrinkles, solar elastosis, lentigines, mottled pigmentation, actinic keratoses, telangiectasias, loss of translucency and elasticity, xerotic texture, and sallow color (table 2 and picture 2A-F) [47,48]. In particular:

●In populations with skin types I or II, atrophic and dysplastic changes (eg, actinic keratoses) with fine wrinkling are common signs of photoaging.

●In contrast, in individuals with skin types III or IV, predominant features include increased skin thickness, deep wrinkles, and leathery appearance [9].

●Hyperpigmented macules and mottled hyperpigmentation are also common features of photodamaged skin (picture 2A) in phototypes I to IV [49].

In a study comparing age-matched Chinese women with White French women with similar lifelong sun exposure, although wrinkle onset occurred 10 years later in Chinese women, they had a higher prevalence and earlier appearance of hyperpigmented spots compared with French women [6]. Similar results were found in another study comparing skin aging features in German, Japanese, and Chinese women [50].

Other signs of severe photodamage include:

●Actinic purpura – Actinic purpura, also called senile purpura or Bateman purpura (picture 3), is a relatively common finding in older individuals with a history of excessive sun exposure. It presents as ecchymotic macules predominantly located on the photodamaged skin of forearms and dorsa of the hands.

●Actinic elastosis and cutis rhomboidalis nuchae – Actinic elastosis presents as a diffuse thickening and yellowish discoloration of the skin resulting from disorganized and damaged collagen and elastic tissue. It is typically seen in older individuals with fair complexion and a history of chronic sun exposure. On the posterior aspect of the neck, the formation of deep furrows results in a typical, irregular, rhomboidal pattern (cutis rhomboidalis nuchae) (picture 4).

●Poikiloderma of Civatte – Poikiloderma of Civatte presents as mottled pigmentation and telangiectasias involving the lateral aspects of the neck and the upper anterior chest in fair-skinned individuals with a history of high cumulative sun exposure (picture 5). The submental area is typically spared. (See "Acquired hyperpigmentation disorders", section on 'Poikiloderma of Civatte'.)

●Favre-Racouchot syndrome – Favre-Racouchot syndrome is characterized by the development of multiple comedones on the periorbital area on a background of severely photodamaged skin (picture 6) [51]. It is most commonly seen in older males with light complexion and a history of chronic sun exposure.

●Idiopathic guttate hypomelanosis – Idiopathic guttate hypomelanosis presents as multiple small, white macules that are typically located on the extensor surfaces of the upper and lower extremities (picture 7A-B). (See "Acquired hypopigmentation disorders other than vitiligo", section on 'Idiopathic guttate hypomelanosis'.)

Photoaging in individuals with phototypes V to VI — In individuals with skin types V or VI, the effects of photodamage generally occur 10 to 20 years later and are less severe than those observed in individuals with lighter skin, due to a lower susceptibility to sun damage [52]. In individuals with heavily pigmented skin, melanosomes are increased in number and size, contain more melanin, are more widely distributed in the epidermis, and are more slowly degraded, compared with lightly pigmented skin, leading to greater photoprotection [53].

In darker skin, premature aging typically manifests in the midface with prominent nasolabial folds, due to increased skin laxity, but fewer wrinkles (picture 8) [53]. Dyschromias can also be a prominent feature in these patients. Other signs may include mottled pigmentation, rough skin, dermatosis papulosa nigra, seborrheic keratoses, and solar lentigines.

While ultraviolet (UV) exposure is a major determinant of skin aging in individuals with light skin tones, its role is limited in those with highly pigmented skin. One study evaluated the correlation between photoaging scores and clinical, demographic, and lifestyle characteristics in 75 African American participants using a 9-point photonumeric scale designed to assess the degree of photodamage in highly pigmented skin [53]. In this study, only age was significantly correlated with skin aging; in a multiple regression model, sun exposure and male sex were contributor factors to skin aging.

DIAGNOSIS — The diagnosis of photoaging is clinical. Typical skin changes include fine and coarse wrinkles, lentigines, mottled pigmentation, loss of translucency and elasticity, and sallow color (picture 2A-F). In clinical practice, photographic scales of photoaging severity may be used for patient evaluation and management decisions (picture 9) [54,55]. A photonumeric scale for dark skin types has also been developed [56].

In research settings, several invasive and noninvasive methods have been used to quantify photodamage, including histopathology and immunohistochemistry, skin surface topography, ultrasound, or reflectance confocal microscopy [57].

PREVENTION

Photoprotection — Protection from the sun, including sun avoidance and use of sunscreens and protective clothing, is the first line of defense against photoaging for all skin types [58]. Ultraviolet (UV) irradiation tends to be the strongest at peak hours (10 AM to 4 PM) during summer months and at high altitudes [59,60]. Water, snow, and concrete can reflect up to 90 percent of the UV rays, whereas shade decreases the amount of UV by 50 to 90 percent [61,62]. Staying away from the sun in the peak hours or seeking shade may considerably reduce sun exposure.

We suggest daily use of broad-spectrum sunscreens, which provide protection against ultraviolet A (UVA) and ultraviolet B (UVB) radiation (table 3), to prevent premature aging of the skin. Sunscreen use is especially important for individuals with light skin (phototypes I, II, and III) who live in areas with high levels of solar irradiation. It is important to note that most people do not apply an adequate amount of sunscreen. Using a broad-spectrum sunscreen with a sun protection factor (SPF) of 30 or greater or applying a lower SPF sunscreen twice may ensure proper protection (see "Selection of sunscreen and sun-protective measures", section on 'Proper use of sunscreens'):

●In a randomized, community-based trial in Nambour, Australia, participants <55 years were randomly assigned to daily use of broad-spectrum sunscreen with SPF of 15+ and 30 mg of beta-carotene, daily use of sunscreen and placebo, discretionary use of sunscreen and 30 mg of beta-carotene, and discretionary use of sunscreen and placebo [63]. Participants in the daily sunscreen group were instructed to apply sunscreen to their head, neck, arms, and hands every morning, with reapplication after heavy sweating, bathing, or spending more than a few hours outdoors. To assess photoaging, silicone impressions of the skin surface markings were obtained from the back of the left hand at baseline and at the end of the study and graded on a scale ranging from 0 to 6. After 4.5 years, participants in the daily sunscreen group, with or without supplementation with beta-carotene, were less likely to have an increase in photoaging grade than participants in the discretionary sunscreen group (odds ratio 0.76, 95% CI 0.50-0.98). Although this trial suggests that daily use of sunscreen slows photoaging in young or middle-aged individuals, its results may not be generalizable to populations different from the one in which it was conducted or living in other geographic areas.

●In a prospective study, 32 women aged 40 to 55 years with Fitzpatrick phototype I to III applied a broad-spectrum, photostable sunscreen with SPF 30 daily for 52 weeks [64]. The comparison of paired digital photographs taken at baseline and at one year showed improvement in all parameters of photodamage, including overall facial photodamage score, crow's feet coarse wrinkles, and mottled pigmentation.

In addition to sunscreens, clothes, hats, and sunglasses provide uniform and reliable protection against UVB and UVA and are easy to use [65,66]. Factors that increase the ultraviolet protection factor (UPF) in clothing include synthetic (eg, polyester), tightly woven, thicker fabric, darker colors, and washing with optical whitening agents or UV-absorbing chemicals [66-69]. (See "Selection of sunscreen and sun-protective measures".)

It is important to emphasize the importance of photoprotection for all skin types [58]. It is well established that individuals with skin type V to VI exhibit clinical and histologic evidence of photodamage, making photoprotection also a priority in this group. However, a common misconception is that persons with highly pigmented skin are not at risk for sun-related damage [70]. Thus, clinicians may be less likely to provide this form of education to this patient population. In a survey of dermatologists, 89 percent of participants reported discussing photoprotection with skin type I patients but only 28 percent reported the same counseling for skin type VI patients [71]. Furthermore, a population-based study found that only 31 percent of African Americans engaged in sun-protective behavior and up to 63 percent had never used sunscreen [72].

Strict sun protection may increase the risk for vitamin D deficiency [73], but most individuals do not apply sufficient amounts of sunscreen for this to be a significant problem [74]. However, oral vitamin D supplementation is a safe, well-tolerated, and inexpensive alternative to achieve adequate vitamin D levels [75]. (See "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment" and "Vitamin D insufficiency and deficiency in children and adolescents".)

TREATMENT

Overview — Photoaging can be partially prevented and improved through a number of modalities, such as sun protection, topical prescription medications, cosmeceuticals, and cosmetic procedures. Factors to consider in the management of a patient with photoaging include the severity of skin changes and the patient's concern, expectations, and willingness to accept the costs of treatment:

●The first step in the management of photoaging involves educating the patient to adopt appropriate year-round sun protection measures, including sun avoidance, regular use of sunscreen and protective clothing, seeking shade, and avoiding peak sun hours. (See 'Photoprotection' above.)

●Topical retinoids are the mainstay of medical therapy for patients with mild to severe photoaging. The use of a topical retinoid should be tailored to the patient's skin type and ability to tolerate the medication. (See 'First-line therapy' below.)

●In patients with actinic keratoses, photoaging may improve in response to treatment with topical fluorouracil. (See 'Topical fluorouracil' below.)

●If the patient is interested in pursuing additional therapies, options such as chemical peels, injectables, lasers, and photodynamic therapy and their potential adverse effects should be fully discussed with the patient. (See 'Other therapeutic options' below.)

A variety of other substances called cosmeceuticals, which include antioxidants, vitamins, or plant extracts, are incorporated in cosmetic preparations and have been used in conjunction with topical retinoids (table 4). However, there is limited evidence from clinical studies to suggest that they are beneficial or that one particular preparation is better than another. (See 'Cosmeceuticals' below.)

First-line therapy

Topical retinoids — Topical retinoids are the first-line therapy for photoaging. Retinoids are a class of naturally occurring or synthetic compounds related to retinol (vitamin A). Retinoids exert their effects by binding and activating two groups of receptors belonging to the nuclear hormone receptor superfamily: the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs), which are ligand-dependent nuclear transcription factors [76]. In human skin, topical retinoids increase collagen production, induce epidermal hyperplasia, and decrease keratinocyte and melanocyte atypia [77-81].

Topical retinoids used for the treatment of photoaging include tretinoin (all-trans retinoic acid), tazarotene (a synthetic retinoid), and adapalene (a third-generation synthetic retinoid) (table 5). Tretinoin is the most extensively investigated therapy for photoaging [82].

Pretreatment counseling — It is important to counsel patients before initiating treatment with topical retinoids. Patients should be informed that local skin irritation can be expected as part of the treatment. Skin irritation, redness, scaling, dryness, burning, stinging, and peeling are common side effects of topical retinoids and often result in patient nonadherence [83]. Adverse effects peak during the first two weeks, are more frequent with higher concentrations, and decrease with time. Regular application of moisturizers is helpful in reducing irritation from topical retinoids.

Treatment with topical retinoids should not be started or continued during pregnancy because retinoids are known teratogens. However, there is no direct evidence that topical retinoids cause congenital malformations [84,85].

Tretinoin — We suggest topical tretinoin (table 5) as the initial treatment for photoaging. We prefer topical tretinoin to tazarotene because multiple available concentrations make titration easier, and in clinical experience (although not in clinical trials), tretinoin is less irritating than tazarotene.

Topical tretinoin can be used for mild to severe photoaging in patients of all skin prototypes. Several weeks or months of treatment typically are required before clinical improvement is appreciated [77,86].

The use of topical tretinoin for the treatment of photoaging is supported by several randomized trials and one meta-analysis [77,83,86-88]:

●A meta-analysis of 12 randomized trials demonstrated that in individuals with mild to severe photoaging of the face or forearms, tretinoin cream in concentrations of 0.02% to 0.1% applied once daily for 16 to 48 weeks was more effective than placebo in the physician-assessed overall improvement of photodamage [83]. As an example, the relative risk of overall improvement for tretinoin 0.05% cream versus placebo after 24 weeks was 1.73 (95% CI 1.39-2.14).

●A subsequent trial evaluated the long-term efficacy and safety of daily application of tretinoin 0.05% cream for two years in 204 subjects with moderate to severe photoaging [88]. The improvement in all signs of photodamage, overall photodamage severity, and global assessment of clinical response was greater in the active treatment group than in the placebo group (picture 10). Treatment with tretinoin was not associated with increased keratinocytic or melanocytic atypia.

Instructions for application — The concentration and frequency of application of topical tretinoin is titrated based upon the observed skin reaction in individual patients:

●Topical tretinoin should be applied sparingly (eg, thin layer or pea-sized amount).

●Topical tretinoin is initiated at the lowest active dose to minimize adverse effects and increase patient adherence. Topical tretinoin 0.02% or 0.025% cream or gel applied every other day, preferably at nighttime, is a common starting regimen. Patients with particularly sensitive skin may start with a twice-a-week regimen for the first few weeks and increase the frequency of application gradually.

●Topical tretinoin concentration and frequency of application may be gradually increased over several weeks as tolerated by the patient, up to a daily application of topical tretinoin 0.1%. However, higher concentrations may not correlate with increased clinical efficacy. As an example, 0.1% topical tretinoin is considerably more irritating than 0.025% topical tretinoin but may not offer additional benefit [87].

●Topical tretinoin should be tried for a minimum of four months because benefits may not be appreciated before then [83].

●The benefits of topical tretinoin are lost upon discontinuation. Although it has only been studied for a duration of two years [88], it may be continued indefinitely. A long-term maintenance regimen with a lower concentration or less frequent application may be an alternative to continued use.

Other topical retinoids

●Tazarotene – Tazarotene is an alternative to tretinoin for patients with mild to severe photoaging who desire treatment (table 5). Tazarotene is reserved for patients who have tolerated the highest concentration of tretinoin. It is also useful in patients who present with overactive sebaceous activity and oily skin complexion.

The efficacy of topical tazarotene is supported by several randomized trials and a meta-analysis [83,86,89]. In individuals with mild to severe photoaging of the face, tazarotene 0.05% or 0.1% cream applied daily for 24 weeks was more effective than placebo in the physician-assessed overall improvement of photodamage [83]. In one small study, tazarotene 0.05% and 0.1% were as effective as tretinoin 0.05% [86].

●Adapalene – Adapalene is a third-generation, synthetic topical retinoid that shows selectivity for the nuclear RAR beta-gamma. Due to its receptor selectivity, it causes less skin irritation and can be used off-label for the treatment of photoaging in individuals with more sensitive skin. The efficacy of adapalene gel 0.1% or 0.3% for cutaneous photoaging has been evaluated in one randomized trial and in a few uncontrolled studies [90,91]:

•In a randomized trial designed to evaluate the efficacy of adapalene 0.1% or 0.3% gel for the treatment of actinic keratoses and solar lentigines in 90 participants (mean age 63 years), a blind examination of paired clinical photographs (before and after nine-month treatment) of 42 patients revealed an improvement in fine wrinkles and mottled pigmentation with adapalene in comparison with vehicle treatment [90].

•In a six-month open-label study, 40 Latin American women with signs of facial photoaging were treated with adapalene 0.3% gel for 24 weeks [91]. Compared with baseline, improvements were noted in clinical grading of forehead, periorbital, and perioral wrinkles. Skin hydration and general skin tone were also improved.

Adapalene is US Food and Drug Administration (FDA) approved for the treatment of acne. In the United States, adapalene 0.1% gel is available without a prescription.

Complementary therapies

Cosmeceuticals — The term "cosmeceuticals" refers to a heterogeneous category of nonprescription topical products, including antioxidants, vitamins, retinoids, hydroxyacids, and plant extracts, that may have some activity in the treatment of photoaging (table 4) [92]. However, since cosmeceuticals are not classified as drugs, they are not subject to rigorous testing or regulation by local regulatory agencies, such as the FDA in the United States or the European Medicines Agency.

Cosmeceuticals are popular ingredients of a wide range of cosmetic products and are sometimes used in conjunction with topical retinoids to potentially enhance the antiaging benefits. However, there is limited evidence from clinical studies to suggest that they are beneficial or that one particular preparation is better than another. In a small randomized study, nonprescription 1% topical retinol was as effective as 0.02% tretinoin in improving photoaging [93].

Other therapeutic options — Other treatments that have been used to improve the signs of photoaging are briefly discussed below. The decision to use these therapies in the treatment of photoaging depends upon individual patient values and preferences.

Chemical peels — Chemical peels involve the application of caustic chemical substances to ablate definite skin layers; the subsequent cutaneous regeneration tightens the skin and evens the color. The decision to use chemical peels in the treatment of photoaging depends upon individual patient values and preferences.

Peels are classified by their intended depth of injury or ablation (table 6). Chemical peels result in a thinner, more compact stratum corneum, thicker epidermis, and uniform distribution of melanin [94]. Superficial and medium-depth peels may improve mild or moderate photoaging. Deep peels may be used for severe photodamage. Adverse effects are more common with medium-depth and deep peels and include hypo- or hyperpigmentation, infection, and scarring. (See "Chemical peels: Procedures and complications".)

Topical fluorouracil — Photoaging in patients with actinic keratoses may improve in response to treatment with topical fluorouracil [95]. Fluorouracil's mechanism of action involves epidermal injury, wound healing, and remodeling of the dermal matrix, resulting in improved appearance. (See "Treatment of actinic keratosis", section on 'Topical fluorouracil'.)

A beneficial effect of fluorouracil on the clinical signs of photoaging has been noted in several observational studies [95,96]. In one study, 21 patients aged 56 to 85 years who had multiple facial actinic keratoses and moderate to severe photoaging were treated with fluorouracil 5% for two weeks [95]. In addition to the expected clearance of actinic keratoses, improving of wrinkling, tactile roughness, lentigines, hyperpigmentation, and sallowness was noted starting four to six weeks after the completion of treatment and continuing through week 24.

However, a secondary analysis of data from a randomized trial including 932 veterans treated with a standard course of topical fluorouracil for the chemoprevention of basal and squamous cell carcinoma of the skin did not find a difference in photodamage (measured with four photonumeric scales) between baseline and 6, 12, and 18 months post-treatment [97].

Photodynamic photorejuvenation — Multiple studies have reported improvement in fine wrinkles, mottled hyperpigmentation, roughness, and sallowness following photodynamic therapy (PDT), a common treatment modality for actinic keratosis and field cancerization [98-101]. The mechanism of PDT in correcting the photodamage may include the upregulation of collagen production and increased epidermal proliferation [102].

PDT can be used alone or in combination with other treatment modalities for photoaging [103]. Pain during illumination is the main side effect of PDT. Daylight PDT, which is associated with little or no pain, may be an alternative and better accepted treatment modality [104]. (See "Photodynamic therapy".)

Invasive treatments — Other treatments that are commonly used to improve the signs of photoaging include:

●Injectable botulinum toxin (see "Overview of botulinum toxin for cosmetic indications" and "Botulinum toxin for cosmetic indications: Treatment of specific sites")

●Injectable soft tissue fillers (see "Injectable soft tissue fillers: Overview of clinical use")

●Laser resurfacing (see "Ablative laser resurfacing for skin rejuvenation" and "Nonablative skin resurfacing for skin rejuvenation")

SUMMARY AND RECOMMENDATIONS

●Risk factors and pathogenesis – Photoaging is premature skin aging that is responsible for most of the age-associated changes of the skin, especially in individuals with a history of prolonged and repeated exposure to solar radiation and in those with fair and less pigmented skin. Photoaging results from the loss of the structural integrity of the dermal extracellular matrix. While ultraviolet (UV) radiation, and in particular ultraviolet A (UVA) radiation, has a major pathogenetic role, wavelengths beyond the UV spectrum (infrared and visible light) also contribute to skin damage. (See 'Epidemiology and risk factors' above and 'Pathogenesis' above.)

●Clinical features – Clinical signs of photoaging include wrinkles, lentigines, mottled hyperpigmentation, actinic keratoses, loss of translucency and elasticity, xerotic texture, and sallow color (picture 2A-F). (See 'Clinical features' above.)

●Treatment:

•Sun protection – Protection from the sun, including sun avoidance and use of sunscreens and protective clothing, is the first line of defense against photoaging. We suggest regular use of broad-spectrum sunscreens, which provide protection against ultraviolet A (UVA) and ultraviolet B (UVB) radiation (table 3), for patients who desire to prevent premature aging of the skin (Grade 2B). Sunscreen use is advisable for individuals with all skin types and especially for those with light complexion (phototypes I, II, and III) who live in areas with high levels of solar irradiation. (See 'Photoprotection' above.)

•Topical retinoids – We suggest topical retinoids (table 5) as the first-line therapy for patients who desire treatment for photoaging (Grade 2A). We prefer topical tretinoin to other retinoids because it is the most extensively studied agent, is available in multiple concentrations, and is thus easier to titrate. Topical tretinoin can be used for mild to severe photoaging in patients of all skin prototypes. Topical tretinoin 0.02% or 0.025% cream or gel applied every other day, preferably at nighttime, is a common starting regimen. Tretinoin concentration and frequency of application may be gradually increased over several weeks as tolerated, up to a daily application of tretinoin 0.1%. (See 'Tretinoin' above.)

Skin irritation, redness, and peeling are common adverse effects of topical tretinoin and may be managed by dose titration and regular use of moisturizers. (See 'Pretreatment counseling' above.)

•Complementary therapies – Moisturizers containing cosmeceuticals, such as antioxidants, vitamins, or plant extracts, can be used in conjunction with topical retinoids for the treatment of photoaging (table 4). However, there is limited evidence of efficacy from clinical studies to suggest these preparations. (See 'Cosmeceuticals' above.)

•Procedural therapies – Procedural therapies used to improve the signs of photoaging, including chemical peels, injectable botulinum toxin, injectable soft tissue fillers, and laser resurfacing, are reviewed separately. (See "Overview of botulinum toxin for cosmetic indications" and "Injectable soft tissue fillers: Overview of clinical use" and "Ablative laser resurfacing for skin rejuvenation" and "Nonablative skin resurfacing for skin rejuvenation".)