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Aesthetic, anti-aging, and regenerative medicine: an anti-aging approach for the treatment of hyperpigmentation.

Hyperpigmentation is a common condition in which areas of the skin become darker in color than the surrounding skin. These darker patches or spots occur when there is an increase of melanin that forms in the skin. Melanin is the substance that gives skin its color. Melanin is produced in the skin by the melanocytes through a series of oxidative reactions involving the amino acid tyrosine and the enzyme tyrosinase. The degree of discoloration is due to the location of the excess melanin. Hyperpigmentation that forms in the epidermal layer of the skin is brown, while hyperpigmentation forming in the dermal skin layer is blue-gray.

Hyperpigmentation can be caused by hormonal changes (e.g., pregnancy), acne, sun exposure, or medications, or may be inherited. Some common forms of hyperpigmentation include lentigines (sun spots), melasma, and postinflammatory hyperpigmentation (PIN).

Sun spots (or age spots) are characterized by small, darkened patches usually found on the hands, face, or other areas frequently exposed to the sun.

Melasma is a hyperpigmentation disorder that mainly affects women during their reproductive years. An estimated 6 million women in the US suffer from the condition and 45 to 50 million women are affected worldwide. The condition is characterized by a patchy brown, tan, or blue-gray facial skin discoloration. There are three main distribution patters of these patches: centrofacial (forehead, upper lip, nose, and chin); malar (cheeks and nose); and mandibular (along the jawline). There are three main types of pigmentation seen in melasma: epidermal, dermal, and mixed. Epidermal melasma is characterized by the presence of excess melanin in the superficial layers of the skin. Dermal melasma is characterized by the occurrence of melanophages (cells that ingest melanin) throughout the dermis. Mixed melasma exhibits a combination of both epidermal and dermal melasma characteristics.

While the cause of melasma is uncertain, it is triggered by sun exposure, hormonal changes, or heredity. Dark spots and hyperpigmentation become darker when exposed to the sun. This occurs because melanin absorbs the sun's rays to protect the skin from overexposure, making the dark patches and spots darker.

Postinflammatory hyperpigmentation usually occurs as a response to an inflammation of the skin, as is seen in acne, allergic reactions, dermatitis, psoriasis, medications, or trauma. The dark spots are characterized by feathered, nondistinctive borders, appearing only at the site of the inflammation.

These common pigmentation disorders have a major impact on a person's quality of life, affecting her psychological and social well-being.

The goal of hyperpigmentation treatment includes the degrading of melanosomes, blocking the formation of melanosomes, and slowing the growth of melanocytes. Simply put, the treatment should alleviate the triggers of the pigmentation, slow existing pigmentation, and prevent new pigmentation from forming.

No matter what treatment is used, sun avoidance is mandatory for people suffering from hyperpigmentation. As previously mentioned, ultraviolet rays encourage the production of melanin as a protective measure. This not only causes more dark spots to form, but makes the existing pigmentation worse. It is imperative that those suffering from hyperpigmentation avoid the sun as much as possible and wear sunscreen and protective clothing when outdoors. Daily use of a broad-spectrum, high-SPF sunscreen will assist in preventing more dark spots from forming. The sunscreen should block both UVA and UVB light and have a minimum SPF 30.

Topical agents used to treat hyperpigmentation are skin lighteners that act at various points during the production and degradation of melanin. Common topical agents include hydroquinone, retinoids, azelaic acid, kojic acid, lignin peroxidase, and various botanical agents.

Hydroquinone is considered the gold standard for the topical treatment of hyperpigmentation. Hydroquinone prevents the reaction that allows the conversion of tyrosine to melanin. It is available in over-the-counter products in strengths up to 2% and by prescription in strengths up to 4%. Hydroquinone is often combined in skin care products with glycolic acid, vitamin C, or retinol to enhance penetration into the skin. It is important to note that hydroquinone products only prevent the formation of new melanin. Hydroquinone products take 4 to 6 weeks to show an effect because the agent needs time to penetrate the skin and alter melanocyte metabolism. Side effects of hydroquinone use include skin irritation, dermatitis, and ochronosis, a blue-black skin discoloration. Ochronosis is usually seen in darker skin tones when hydroquinone is used in high concentrations (above 4%) or if a low concentration is used for extended time periods.

Hydroquinone has been proved effective for the treatment of hyperpigmentation in numerous clinical studies. A study by Salem et al. treated 45 patients with darker skin tones for melasma using either 4% topical hydroquinone, 30% TCA chemical peel, or Q-switched Nd:YAG laser. The results showed that the topical hydroquinone treatment scored significantly higher than the other treatments during improvement evaluations.

Retinoids, such as tretinoin, tazarotene, and adapalene, reduce pigmentation by normalizing the activation of the melanocytes in the skin. While these products are effective in reducing hyperpigmentation, it takes a minimum of 24 weeks to see an improvement. These products cause irritation, dryness, and scaling, which sometimes makes them unattractive for the purpose of treating hyperpigmentation.

Clinical studies substantiate the use of retinoids for the treatment of hyperpigmentation. A study by Grimes et al. treated acne and postinflammatory hyperpigmentation of 74 darker-skinned patients with 0.01% tazarotene cream versus a placebo. Results showed that the tazarotene cream reduced the appearance of hyperpigmentation within 18 weeks. Retinoids are available by prescription only.

Azelaic acid is a skin lightener derived from Pitryrosporum ovale, a yeast found in wheat, rye, and barley. It acts as a tyrosinase inhibitor and takes several months to show an effect. Azelaic acid is best used in combination with other ingredients, such as glycolic acid or a retinoid to enhance penetration. Side effects of azelaic acid include skin irritation, scaling, burning, and itching.

Clinical studies have shown azelaic acid to be effective in treating hyperpigmentation. A study by Balina and Graupe compared the efficacy of 20% azelaic acid versus 4% hydroquinone cream for the treatment of melasma. Azelaic acid was shown to be as effective as hydroquinone 4% but without its side effects. Azelaic acid is known commercially as Finacea or Intendis and is available by prescription.

Kojic acid is a skin lightener derived from the fungus of Aspergilline oryzae and is a tyrosinase inhibitor. Kojic acid is available in strengths of 1% to 4%, and best results are seen when it is combined with ingredients such as glycolic acid, vitamin C, or licorice extract to enhance penetration. It is generally equivalent to the other topical therapies, but is more irritating.

A double-blind study compared glycolic acid 5% with either hydroquinone 4% or kojic acid 4% for three months. Both combinations proved equally effective with reduction of pigmentation in 51% of patients.

One of the newer botanicals on the market is lignin peroxidase, a natural ingredient derived from a mushroom that grows on Phanerochaete chrysosporium trees. It lightens the skin by decomposing and fading melanin in its final structure after it is transported to the upper layer of the skin. This ingredient needs to be activated by hydrogen peroxide to be effective. It works in a short period of time and does not cause the side effects seen with many lightening agents.

When this ingredient was used twice daily for 28 days, 82% of subjects treated demonstrated a significant decrease in the appearance of pigmentation. Additionally, 91% of the subjects showed overall improvement in firmness and skin tone. Lignin peroxidase is found in the Elure skin care system, which can be obtained in cosmetic physicians' offices.

Hyperpigmentation can be successfully treated with the use of aesthetic lasers and light-based treatments. The goal of laser and light therapy is to target the melanin in the skin via selective photothermolysis, meaning that the beam has a specific target (pigment) and leaves the surrounding skin intact. Laser and light devices used to treat hyperpigmentation include Q-switched lasers, intense pulsed light, ablative and fractional lasers treatments, and combination laser/light therapy.

Q-switched lasers use photoacoustic waves of light to vibrate and eventually shatter the melanin target. This wavelength minimized epidermal damage and is safe for all skin tones, especially darker skin, because heat is not generated. Advantages of Q-switched laser treatment include no downtime, quick treatment time, minimal discomfort, and the ability to treat all skin types. Q-switched lasers treat both epidermal and dermal hyperpigmentation, as evidenced by clinical studies. Wavelengths used include the Nd:YAG, ruby, and pulsed dye.

Intense pulsed light can be used to reduce the intensity of melasma, but can only be used safely and successfully in lighter skin types. This treatment causes a thermal injury to the melanocytes, causing the destruction of the melanin in the areas of hyperpigmentation, resulting in the sloughing of the damaged lesion via exfoliation.

There are two types of laser resurfacing: full ablation and fractional ablation. Full laser ablation involves the removal of precise layers of skin. Full contact laser resurfacing can be easily controlled to provide superficial or deep resurfacing. Ablative resurfacing improves superficial melasma and solar lentigines (sun spots). Fractional resurfacing is a laser treatment wherein the device vaporizes columns of tissue. This results in microscopic areas of treated and nontreated tissue. The untreated tissue allows for more rapid healing and the reduction of tissue volume results in tissue tightening. Fractional ablative lasers can be used to treat refractory hyperpigmentation disorders. During this treatment, the goal is to ablate the superficial layers of skin, which includes the abnormal malanocytes. Multiple treatments are recommended for best results. Ablative fractional devices include Profractional by Sciton, Pearl by Cutera, Pixel by Alma, and SmartXide DOT by Deka Medical.

Nonablative fractional resurfacing works by coagulating microscopic columns of tissue to variable depths. It differs from ablative fractional resurfacing in that the stratum corneum (the most superficial skin layer) remains intact, allowing for potentially less downtime. The coagulated tissue sloughs off over one to two weeks and multiple treatments are needed for optimal results.

The best approach to hyperpigmentation is a combination of the aforementioned treatments. Physicians specializing in cosmetic procedures can formulate a personalized treatment plan that encompasses full spectrum sunscreen, topical skin preparations, and laser/ light treatments. Avoidance of the sun or any of the other triggers for hyperpigmentation is the best defense.

by Sharon McQuillan, MD

Dr. McQuillan is a board-certified physician who specializes in aesthetic, anti-aging, and regenerative medicine. She founded the Ageless Aesthetic Institute, a level 4 ACCME-accredited aesthetic training program for medical professionals in order to standardize and elevate the practice of aesthetic medicine. Dr. McQuillan has educated thousands of medical professionals in the art and science of aesthetic and anti-aging treatments for over a decade. Dr. McQuillan lectures internationally on aesthetic and regenerative medicine for many organizations and is the medical director of the Aesthetic Fellowship, hosted by the American Academy of Anti-Aging Medicine. Dr. McQuillan owns and operates the Ageless Institute in Aventura, Florida, offering anti-aging, aesthetic, regenerative, and weight-loss treatments. In 2009, Dr. McQuillan forms the Ageless Regenerative Institute in conjunction with a team of experts in stem cell therapies. This expert team has developed an approved method and protocol for the harvesting and isolation of adipose-derived stem cells for autologous transplantation.
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Author:McQuillan, Sharon
Publication:Townsend Letter
Article Type:Report
Geographic Code:1USA
Date:Dec 1, 2012
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