Overview of Treatment of Photoaging and Pigmentary Changes of the Skin

There are three categories of treatment types for photoaging and pigmentary changes:

• Therapeutic modalities to improve pigmentary changes induced by UV light, which can be divided into topical agents and procedural agents
• Topical agents, which include retinoids, hydroquinones, and combination therapies
• Procedural agents, which include chemical peels, microdermabrasion, lasers, intense pulse light, and cryotherapy

There are a myriad of therapeutic modalities that can improve the pigmentary components of photoaging. These modalities may be divided into topical agents and procedural agents. Topical agents include retinoids, hydroquinones, and combination therapies. Procedural agents for the treatment of pigmentary abnormalities include chemical peels, microdermabrasion, lasers, intense pulse light, and cryotherapy. Some of the therapeutic modalities are better suited for certain skin types (Table 3.3).A brief overview of these agents will be provided with an emphasis on published clinical trials that support the efficacy of the particular modality. A more exhaustive review of each modality appears throughout this book.

Table 3.3. Treatment of pigmentary characteristics of photoaging in Asian,African American, and Caucasian skin   Treatment modality Asian African American Caucasian   Sunscreen ++ ++ ++   Antioxidants ++ ++ ++   Retinoids ++ ++ ++   Hydroquinones ++ ++ ++   Chemical peels + + ++   Microdermabrasion ++ ++ ++   Cryotherapy + - ++   Laser + - ++   Intense pulse light + + +

The leading topical agents for the treatment of photoaged skin, including pigmentary abnormalities, are the retinoids. In double-blind controlled trials, it has been demonstrated that the three retinoids available in the United States, tretinoin, adapalene, and tazarotene, effectively lighten pigmentary abnormalities associated with photoaging.Weiss demonstrated lightening of lentigines and other hyperpigmented areas on the face and forearms of 30 subjects who applied 0.1% tretinoin cream daily compared with vehicle for 4 months [67]. As an extension of that trial, Ellis demonstrated further improvement in hyperpigmentation as well as the other parameters of photoaging over a 6-month period with topical tretinoin applied daily to the face and forearm [68]. Rafal evaluated the efficacy of topical tretinoin in the treatment of lentigines associated with photoaging [69]. Tretinoin in a 0.1% concentration was applied to the faces of 58 subjects in this 10- month study. Clinical lightening of solar lentigines was noted in 83% of the treated facial lesions compared with 29% of controls.Histological analysis revealed a 35% decrease in epidermal pigmentation in the treated group compared with a 34% increase in the vehicle-treated group. Griffiths examined the efficacy of 0.1% tretinoin cream for 4 weeks in 45 Asians with hyperpigmented lesions on the face and hands [70].Each subject had at least four lentigines on the face and/or hands.Hyperpigmented lesions were lighter or much lighter in 90% of the patients receiving tretinoin compared with 33% of controls. Histology demonstrated a 41% decrease in epidermal pigmentation in the treated group compared with a 37% increase in the control group. There was a statistically significant correlation between decrease in histologic epidermal pigment and clinical lightening of the pigmented lesions. In a primarily African American population,Bulengo-Ransby demonstrated improvement in pigmentation with 0.1% topical tretinoin cream. This improvement was not with photoaging-associated pigmentation but with that seen in postinflammatory hyperpigmentation. Fifty-four subjects were treated for 40 weeks with a daily application of 0.1% tretinoin cream [71]. Significant improvement was demonstrated in the tretinoin group,with 91% of that group demonstrating lighter or much lighter pigmentation compared with 57% of the vehicle group. Epidermal melanin content decreased 23% in the tretinoin group compared with 3% of vehicle group.


Adapalene gel in either a 0.1% or 0.3% concentration was used for 9 months in the treatment of both actinic keratoses and solar lentigines in 90 subjects [72]. One month of adapalene use resulted in significant lightening of solar lentigines compared with the control group. At 9 months, nearly 60% of subjects had lightening of the lentigines compared with 36% of the control group.

The efficacy of tazarotene cream at a concentration of 0.1% for the treatment of facial photodamage was evaluated in 563 subjects over an initial 24-week period followed by a 28- week extension [73]. Improvement in pigmentary appearance was the first change to be noted in the tazarotene group, with mottled hyperpigmentation showing a statistically significant improvement over vehicle after 2 weeks of therapy. Lentigines and irregular dyspigmentation improved over 4 weeks. Pigmentation continued to improve as treatment continued.

Hydroquinones are the mainstay of treatment for most disorders of hyperpigmentation. However, there is a paucity of trials examining the efficacy of hydroquinone in the treatment of photoaged skin, including solar lentigines, mottled hyperpigmentation, and diffuse hyperpigmentation. Clinical studies using hydroquinone for the treatment of various other pigmentary abnormalities have been published. These include studies of postinflammatory hyperpigmentation and melasma. Results applicable to photoaging may be inferred from these trials. Sanchez and Vasquez, among others, demonstrated significant improvement in melasma using 3% hydroquinone in the treatment of 46 women with melasma [74]. Ruiz-Maldonado recommended hydroquinone in the concentration of 2–4% for the treatment of postinflammatory hyperpigmentation for 3 to 6 months [75].Glenn demonstrated that 6% hydroquinone solution produced a statistically significant lightening in various pigmentary disorders compared with 3% hydroquinone [76]. The pigmentation associated with photoaging requires the application of the hydroquinone twice daily directly to the area of involvement for 3 months.

The efficacy of combination therapy in the treatment of solar lentigines and hyperpigmentation has been reported for the combination of tretinoin/hydroquinone and the combination of 4-hydroxyanisole/tretinoin. Experience with the combination of 5% hydroquinone and tretinoin (0.1–0.4%) was reported by Yoshimura in 136 Asian subjects who applied the combination to face, trunk, and lower extremities for treatment of hyperpigmentation, including lentigines [77].After 8 weeks, 82% of the patients had a good to excellent result. However, postinflammatory hyperpigmentation was observed in some patients. Fleischer reported the results of the combination of 2% 4-hydroxyanisole and 0.01% tretinoin in the treatment of solar lentigines and related hyperpigmented lesions in two double-blind multicenter trials of 24 weeks’ duration [78]. The combination product, a vehicle, and each of the active ingredients individually were applied to solar lentigines on the forearm, dorsum of the hands, and the face twice daily. The combination product was statistically superior in the lightening of lentigines to each of its active components or vehicle.

Cryotherapy is an often-used procedural modality for the treatment of pigmentation in photoaged skin, particularly for lentigines. The mechanism of action of cryotherapy is the destruction of melanocytes on exposure to cold temperatures. Cold temperatures may be obtained through the use of liquid nitrogen or, less commonly, carbon dioxide or nitrous oxide, which are applied to the skin via direct contact or with a spray device. Two studies support the efficacy of cryotherapy in the treatment of solar lentigines. Almond-Roesler reported the successful treatment of solar lentigines by brief, gentle cryosurgery using a Kryomed device in 20 patients [79]. Lentigines on the hands of 80–100% of the subjects demonstrated lightening. Zouboulis reported resolution of lentigines in 6 subjects treated with nitrous oxide [80]. In addition to the destruction of melanocytes comprising the lentigo, adjacent and subadjacent melanocytes may be destroyed or injured, resulting in lesional and/or perilesional depigmentation, hypopigmentation, or hyperpigmentation. In a study using liquid nitrogen cryotherapy to lentigines on the dorsum of the hands in ten subjects, 50% of the treatment group experienced hypopigmentation at 6 months posttreatment [81]. Therefore, given the unpredictability of the response with cryotherapy, this modality is limited to the treatment of solar lentigines in lightly pigmented individuals.

Laser selection and techniques and intense pulse light for treatment of photoaging is discussed extensively in Chap. 3. Briefly, many lasers have the capability of treating pigmentation associated with photoaging but not in all skin types. The superficially located melanin pigment in solar lentigines lends them to treatment with the rapid-firing Q-switched lasers, including the Q-switched ruby, alexandrite, and Nd:YAG. Inappropriate destruction of melanocytes remains a potential problem for darker skin types. Therefore, laser therapy is infrequently used in darker skin types. Kopera reported the fading of 196 solar lentigines in eight women after treatment with the Q-switched ruby laser [82]. One treatment resulted in lesion improvement without adverse results. Rosenbach treated 21 lentigines in 11 patients with the Q-switched alexandrite laser [83]. Sixteen lesions had a good, excellent, or complete response. In that study, patients with skin types IV were included, and no hypopigmentation or hyperpigmentation was reported. Chan reported treating 34 Asian patients with solar lentigines with three types of Nd:YAG 532 lasers: the Versapulse Q-switched Nd:YAG 532, the Versapulse longpulse Nd:YAG 532 nm, and a conventional Q-switched Nd:YAG 532 [84]. Improvement in the lentigines was graded on a 10-point scale and ranged from 4.50–4.78. A range of adverse events occurred with all three lasers, including hyperpigmentation, hypopigmentation, and erythema. However, the adverse events were most pronounced with the Versapulse Q-switched Nd:YAG 532. The resurfacing lasers, the CO₂ and Er:YAG, will treat both wrinkles and pigmentary changes associated with photoaging. Again, they are not appropriate for darker skin types given the risks of postinflammatory hyperpigmentation.

Intense pulse light has been utilized for the treatment of lentigines and vascular lesions associated with photoaging.The experience of intense pulse light in the treatment of photoaging in Asian skin has been reported by Negishi, who determined the effectiveness of photorejuvenation for Asian skin types IV-V using intense pulse light [85]. Ninety-seven patients received three to six treatments using 550 nm and 570 nm cutoff filters. A rating of good or excellent was given to more than 90% of patients for pigmentation. No long-term adverse events were reported. Kawada examined the efficacy of intense pulse light in the treatment of lentigines in Asian subjects [86]. Forty percent of those patients with lentigines demonstrated a 50% improvement with treatment.

Superficial exfoliation of the upper layer of the skin is a strategy used to treat pigmentary disorders of photoaging. This is achieved with either microdermabrasion or chemical peeling agents. Cotellessa examined the efficacy of treatment with microdermabrasion of lentigines on the faces of 20 subjects [87]. Forty percent had complete remission, 50% partial remission, and 10% no response after a total of eight treatments administered every 2 weeks. The addition of trichloroacetic acid to microdermabrasion did not substantially improve the results in that study.

Superficial, medium, and deep chemical peels may be employed for the treatment of pigmentary abnormalities associated with photoaging. The specific agents used include glycolic acid (35–70%), salicylic acid (20–30%), trichloroacetic acid (10–25%), and combination peels, including Jessner’s solution (14% salicylic acid, 14% lactic acid, 14% resorcinol in 95% alcohol) and trichloroacetic acid, glycolic acid and trichloroacetic acid, and CO₂ and trichloroacetic acid. Lugo-Janer treated lentigines on the hands of 25 subjects with 30% trichloroacetic acid [88]. An improvement of 50% or more was reported in 47% in the trichloroacetic acid treated group. Improved efficacy was noted with the addition of liquid nitrogen cryotherapy with 71% of subjects displaying 50% improvement. Improved efficacy was reported in lighter skin types than darker skin types. Similarly, a study by Li demonstrated improvement in lentigines after treatment with 35% trichloroacetic acid [89].