Management of hyperpigmentation—and prevention of recurrence—can be a challenge for both patients and dermatologists. The challenge becomes more significant when patients present with additional dermatologic concerns, such as acne or atopic dermatitis. One rather common concern of patients with melasma or hyperpigmentation centers on the cutaneous signs of aging. That is no surprise given that UV exposure directly contributes both to skin aging and activation of melanocytes.

Given the wide range of topical anti-aging therapies now available on the market, dermatologists can recommend appropriate interventions to help patients with a history of pigmentary alteration to combat the signs of aging. In fact, for the dermatologists with a knowledge of the range of suitable products on the market, this patient presentation quickly transforms from challenging to rewarding. Whether combined with prescription topical therapies for hyperpigmentation or used alone, various products can help patients achieve smooth, even-toned skin. Any product that is irritating may lead to further post-inflammatory hyperpigmentation and a worsening of symptoms. Importantly, the dermatologist must instruct patients on appropriate sun protection and guide them to effective, non-irritating cosmeceutical products.

BASICS OF HYPERPIGMENTATION
The most important fundamental advice that any dermatologist can give to any patient is particularly pertinent to both pigmentary alterations and cosmetic concerns: wear sunscreen every day, rain or shine, January through December. An appropriate sunscreen formulation will provide SPF protection of 30 or higher and must be reapplied every two hours in northern climates and once an hour in temperate/hot areas closer to the equator. Patients must understand the importance of wearing sunscreen regardless of skin type. When patients with dark skin tones tell me that they don't think they need to wear sunscreen, I remind them that Bob Marley died of melanoma. Marley's melanoma was originally misdiagnosed as a hematoma in his toenail, as he was an avid soccer player.

There is a misconception among patients that typical make-up provides sufficient sun protection. While some make-up products are SPF rated, many are not. Even for those products with SPF, few patients would ever apply enough product—even a foundation—with sufficient coverage to adequately protect from UV radiation. Therefore, it's best for patients to apply a moisturizing sunscreen to the face, ears, neck , and other exposed areas before applying make-up. Melasma can appear in some very sensitive individuals on their arms and hands.

Prior to initiation of any cosmetic regimen or provision of cosmetic services, existing hyperpigmentation should be evaluated and treated. Hydroquinone remains the gold standard of topical hyperpigmentation therapy. Over the past few years, there was some discussion of the safety and concern about the availability of hydroquinone, and many over the counter (OTC) products have become scarce. Ambi is my preferred OTC product because it has been clinically tested and is safe and effective for most individuals. Much of this controversy seems to have been fueled by parties interested in diminishing the stature of hydroquinone, as they stood to financially benefit. The cumulative evidence provided by published studies and many years of patient use show that FDA-approved formulations of hydroquinone, when used properly, are both safe and effective. The FDA no longer appears to be investigating hydroquinone safety and is not expected to issue any new mandates regarding the agent.

Legitimate concerns remain, however, regarding some imported hydroquinone products that are distributed illegally in certain parts of the country, usually in stores that cater to ethnic populations. These unapproved products may contain unsafe concentrations of hydroquinone or other ingredients, such as high concentration or high-potency corticosteroids and/or heavy metals such as mercury or arsenic. These should not be applied to the face for extended periods.

TriLuma (Galderma) cream, with the combination of hydroquinone 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01%, is now the mainstay of hyperpigmentation therapy in my practice because it is effective and non-irritating. It is the only hydroquinone with a new drug application (NDA) that is FDA-approved for melasma. Following successful initial treatment, I often have patients apply TriLuma up to three days a week as a maintenance therapy. In cooler months when UV exposure is typically lower, reducing application to once weekly may be sufficient in many cases. Other hydroquinone formulations to consider include EpiQuin Micro (hydroquinone 4%, SkinMedica), formulated with microsponge technology, for patients with very sensitive skin. Aclaro PD (hydroquinone 4%, JSJ Pharmaceuticals) incorporates sunscreens and vitamin C and may be a wise choice for patients who have trouble complying with regular sunscreen use or who seek the additional skin rejuvenating benefits of topical vitamin C application.

TOPICAL ANTIAGING OPTIONS
Two primary considerations guide the selection of rejuvenation products and procedures for patients with hyperpigmentation or a history of hyperpigmentation. The first is to offer interventions that do not irritate the skin; irritation can lead to worsening of hyperpigmentation or new-onset post-inflammatory hyperpigmentation. Secondly, ideal interventions are those that, in addition to providing cosmetic improvement, either directly improve pigmentary alterations or support pharmaceutical interventions. Luckily, a number of cosmeceutical products may fit the bill.

RevaleSkin Intense Recovery Treatment (Stiefel) is in my experience a good option for patients with hypersensitive skin. With regular application, the product seems to actually improve barrier function, and clinical studies reported by Stiefel suggest that use of the product shortened recovery time for patients who had undergone procedures. The product contains CoffeeBerry extract 1.5% and is intended for all skin types. I have found that my patients who have been using RevaleSkin Intense Recovery can tolerate other topical products better. As this is a powerful antioxidant clinical studies have also proven that it decreases redness, enhances tone, and decreases fine lines.

Another cosmeceutical option that I recommend to my patients is TNS Essential Serum (SkinMedica), formulated with growth factors (Human Fibroblast Conditioned Media), plant-derived amino acid Dipalmitoyl Hydroxyproline, hyaluronic acid filling spheres, and antioxidants, including Ergothioneine (EGT), ubiquinone, Tocopheryl Acetate, and green tea extract. This is well tolerated by patients of all skin types and provides notable rejuvenating effects. TNS Recovery Complex (SkinMedica) is a less expensive option. It features the manufacturer's proprietary NouriCel-MD complex of human growth factors. All of the cosmeceuticals containing TNS notably build collagen and decrease fine lines and wrinkles.

Prescription topical tretinoin cream (Renova, Ortho-Neutrogena) is the gold standard in topical wrinkle reduction and can be an appropriate option for many patients with hyperpigmenation. However, I generally instruct patients to apply Renova or any tretinoin product just twice per week to minimize irritation.

All of the above products should be patch tested on the inner arm twice a day for three to five days before using on the face.

Glycolic acid may be appropriate for patients with hyperpigmentation when delivered via facial washes rather than leave-on formulations. For example, MD Forte facial cleansers (Allergan) are acceptable options. These cleansers range from 12% and 15% to 20% glycolic acid.

The Vivite line (Allergan) features botanicals that even skin tone. I generally recommend this line, which also includes glycolic acid, superoxide dismutase, peptides, and exfoliators. Vivite Vibrance is a newer option that is effective for hyperpigmentation. Results of small, unpublished clinical studies suggest the product can provide results that are as good or better than those from hydroquinone but without the irritation. I recommend salicylic acid, which is a beta-hydroxy acid, in the form of Beta Lifts 20% and 30% chemical peels. These even skin tone and improve acne, texture, and fine lines.

FUTURE DIRECTIONS
Several chemical compounds, some of which are tyrosinase inhibitors, have gained interest for their possible beneficial effects in treating hyperpigmentation. Azelaic acid (Azelex, Allergan; Finacea, Intendis) is available in the US as a treatment for acne and rosacea and may also be used as a primary treatment for hyperpigmentation. This agent may be considered as a first line acne treatment in patients with a history of or at high risk for PIH.

Among botanical agents under investigation are the tyrosinase inhibitor arbutin or bearberry extract (found in Vivite products among others) and licorice extract, which contains glabridin. Some published data show promise for these agents, though any optimal "dosing/concentration" or application data are lacking.

Kojic acid (5-hydroxy-2-(hydroxy methyl)-4-pyrone), is a fungal derivative that has been investigated and widely used in Japan for some time, though no FDA approved formulations are marketed in the US.

Finally, a new molecule that has been developed and incorporated into cosmeceutical products has been shown to lighten dark spots and even skin tone. Lumixyl, a synthetic peptide that inhibits tyrosinase, was found to provide a 40 percent improvement in facial pigmentation after nine weeks of use and a 50 percent improvement after 16 weeks, in a small study reported by developer emed, Inc. Patch testing reportedly showed the peptide did not elicit allergic reactions; it is water soluble and non-toxic. Basis Medical Technologies is slated to begin distributing Lumixyl-containing products in the US.

LIGHTEN UP
Addressing a patient's desire to improve hyperpigmentation and achieve notable rejuvenation had in the past represented a true conundrum for dermatologists. Advances in both prescription therapies and cosmeceutical development have led to the availability of many treatment possibilities. Today, dermatologists may find that meeting patients' dual goals can be mutually rewarding. Key to success is an emphasis on prevention of new cutaneous insult and meaningful correction of existing damage.